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Statistical methods in epidemiology: Karl Pearson, Ronald Ross, Major Greenwood and Austin Bradford Hill, 1900-1945.

The tradition of epidemiological study through observation and the use of vital statistics dates back to the 18th century in Britain. At the close of the 19th century, however, a new and more sophisticated statistical approach emerged, from a base in the discipline of mathematics, which was eventually to transform the practice of epidemiology. This paper traces the evolution of that new analytical approach within English epidemiology through the work of four key contributors to its inception and establishment within the wider discipline.

Epidemiology↗

New considerations in analyzing stroke and heart disease mortality trends: the Year 2000 Age Standard and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision.

BACKGROUND: Monitoring of trends and patterns of stroke mortality will be of utmost importance in the coming decade. Two innovations in vital statistics may complicate this task and must be brought to the attention of both researchers and readers of research reports: the new Year 2000 Age Standard and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). SUMMARY OF REVIEW: For cerebrovascular diseases, the age-adjusted death rate is 2.4 times higher with the use of the year 2000 standard than with the use of the old 1940 standard. However, if rates for all years are computed with the use of the same age standard, the percent change from 1979 to 1995 is similar according to the 1940 standard (-35.8%) or the year 2000 standard (-34.3%). Another important effect of the change to the year 2000 standard is to reduce black/white differentials in age-adjusted death rates. Major discontinuities are not observed for mortality trends in cerebrovascular disease or heart disease between International Classification of Diseases, Ninth Revision (ICD-9) (1979-1998) and ICD-10 (1999 and following years) classifications. CONCLUSIONS: All data users must exercise caution to specify the age standard used when assessing or presenting age-adjusted rates over time or between groups. The comparability of ICD codes chosen for years before 1999 versus 1999 or following years must be checked to distinguish changes due to coding from true changes in mortality levels.

Epidemiologic Measurements↗

Global and regional cause-of-death patterns in 1990.

Demographic estimation techniques suggest that worldwide about 50 million deaths occur each year, of which about 39 million are in the developing countries. In countries with adequate registration of vital statistics, the age at death and the cause can be reliably determined. Only about 30-35% of all deaths are captured by vital registration (excluding sample registration schemes); for the remainder, cause-of-death estimation procedures are required. Indirect methods which model the cause-of-death structure as a function of the level of mortality can provide reasonable estimates for broad cause-of-death groups. Such methods are generally unreliable for more specific causes. In this case, estimates can be constructed from community-level mortality surveillance systems or from epidemiological evidence on specific diseases. Some check on the plausibility of the estimates is possible in view of the hierarchical structure of cause-of-death lists and the well-known age-specific patterns of diseases and injuries. The results of applying these methods to estimate the cause of death for over 120 diseases or injuries, by age, sex and region, are described. The estimates have been derived in order to calculate the years of life lost due to premature death, one of the two components of overall disability-adjusted life years (DALYs) calculated for the 1993 World development report. Previous attempts at cause-of-death estimation have been limited to a few diseases only, with little age-specific detail. The estimates reported in detail here should serve as a useful reference for further public health research to support the determination of health sector priorities.

Adolescent↗

Life expectancy in Down syndrome.

This study is part of a collaborative effort between the Division of Vital Statistics, Ministry of Health, Province of British Columbia and the Department of Medical Genetics, University of British Columbia. Permission to use the provincial vital and health records was conditional on the strict observance of the oath of secrecy regarding the nonstatistical information contained in the records. To develop life expectancy data for Down syndrome, we studied 1341 patients with Down syndrome identified by the British Columbia Health Surveillance Registry from more than one million consecutive live births from 1952-1981 inclusive. Our results indicate that life expectancy is much better than generally believed. For patients with Down syndrome with congenital heart anomalies, survival to age 1 year is 76.3%; to age 5, 61.8%; to age 10, 57.1%; to age 20, 53.1%; and to age 30, 49.9%. For patients with Down syndrome without congenital heart anomalies, survival to the same ages is 90.7%; 87.2%, 84.9%, 81.9%, and 79.2%, respectively. Survival for these patients without congenital heart defects is still significantly lower than that for a comparison group of mentally retarded persons without congenital heart defects.

Actuarial Analysis↗

The Canadian Birth Data Base: a new research tool to study reproductive outcomes.

A new tool for epidemiological, demographic, and genetic research--the Canadian Birth Data Base-is being developed at Statistics Canada. Over a million live birth and stillbirth records for the period 1987-89 received from all provincial and territorial offices of vital statistics are being processed in a form suitable for linkage with other files. Maternal, child health, occupational, and environmental concerns, as well as some of the consequences and possible risks involved in new reproductive technologies, could be investigated. Associations between socio-economic indicators (e.g., parental income, education, and occupation) and unfavourable birth outcomes could also be studied in the future. Approved statistical studies can be carried out within Statistics Canada on a cost-recovery basis. It is planned to update the data base annually.

Birth Certificates↗

Long-term trends in cancer mortality in the United States, 1930-1998.

BACKGROUND: Progress against cancer can be examined by analyzing long-term trends in cancer incidence and mortality. The recent directive from the U.S. Department of Health and Human Services to adopt the 2000 U.S. standard population for the age adjustment of death rates prompted the American Cancer Society to update historical cancer mortality statistics using the new standard. METHODS: Mortality data were abstracted by race, gender, year, and age at death for 1930 through 1959 from annual volumes of Vital Statistics of the United States. For 1960 through 1998, these data were obtained from data tapes provided by the National Center for Health Statistics. Two U.S. standard million populations (1970 and 2000) were used to calculate age-adjusted rates. Average annual percent change was estimated for each decade by site, gender, and age, and the statistical significance of the change was assessed at p < 0.05. RESULTS: After long-term increases or mostly level trends that date from the 1930s for some sites, death rates for cancers of the lung (in males), prostate, female breast, colon-rectum, pancreas, leukemia, and ovary were decreasing in the 1990s. Liver cancer death rates were increasing in the 1990s. Throughout the study period, death rates for female lung cancer increased, while death rates for stomach and uterine cancers declined. CONCLUSIONS: The trends of decreasing cancer death rates for the leading cancer sites in the 1990s are encouraging. However, surveillance researchers must continue to monitor these declines to assess whether the progress seen in this decade persists. Efforts also must be made to study the sites with increasing trends and identify potential underlying causes.

Adolescent↗

Uniform basic data sets for health statistical systems.

The United States approach to coordinating health statistics involves introduction of multipurpose basic data sets describing health status and the health care system. Standard reporting procedures have been used for many years for vital statistics. Recently designated data sets cover health manpower, inpatient facilities, short-stay hospital discharges, and use of ambulatory care services. A data set for long-term health care is in the design stage. Advantages of this approach in the United States and internationally are: basic comparisons can be made between health care settings are geographic areas while maintaining the variety and flexibility of existing public and private information systems; shared local, regional, and national data systems can be set up; and better coordination can be achieved between government-sponsored general-purpose and administrative data systems. Problem areas are: avoiding undue proliferation, e.g. of disease-specific data sets; adhering to the principle of minimal requirements; linking data sets and coordinating them with census and other social indicators; promoting widespread use; assuring data quality; establishing mechanisms for review and revision; and extending the concept internationally.

Data Display↗

Estimating hospital service areas using mortality statistics.

This article reports research testing an alternative methodology for patient origin studies that uses hospital deaths as a proxy measure for all discharges from a selected group of urban tertiary hospitals. Results indicated that mortality data from vital statistics records provide a reasonable approximation of patient travel patterns to acute care hospitals. Hospital service area indexes constructed from mortality statistics accurately predicted, on an aggregate regional basis, the results of a conventional patient origin study based on all hospital discharges. Hospital service areas, an important element of locational analysis in health planning, can be identified with the suggested methodology for states and areas lacking statewide uniform hospital discharge systems. A number of caveats are suggested for applying this methodology and interpreting its results.

Catchment Area, Health↗

Quantifying the iceberg effect for injury: using comprehensive community health data.

BACKGROUND: Injury is the leading cause of preventable morbidity and mortality in Canada. The "ice berg" effect in injuries was proposed to address the injury statistics that are often poorly documented. The aim of this investigation was to quantify the severity and magnitude of iceberg effect in Ontario, Canada. METHODS: Data from Vital Statistics (1999, mortality), Canadian Institute for Health Information (2001, hospitalizations), Census (2001, demographic information), National Ambulatory Care Reporting System (2001, emergency department visits), and the Canadian Community Health Survey (2000/01, other injuries) were used to construct the Ontario injury iceberg for ages 12 years and older. RESULTS: There were 79,577 fatalities in Ontario in 1999; 2,645 were attributable to injuries (crude rate: 2.3 per 10,000). Of the 913,540 hospitalizations (2001), 67,301 were caused by injuries. There were 3,520,253 emergency department (ED) visits (2001) and 959,278 were attributable to injuries. For injuries treated elsewhere, the most common treatment site was the physician's office (23.3%). The most common cause of injuries (CCHS) was falls (37.4%) and exertion/movement (20.5%). There were 1,928,000 injuries causing functional impairment (one injury to five individuals in the population). INTERPRETATION The high ratio of injury-related ED visits to deaths illustrated the high volume of injuries that present to the ED. The ratio of injuries resulting in functional impairment to the population demonstrates.that such injuries can be problematic, even if not resulting in hospitalization. Constructing the injury iceberg using valid data should assist researchers and decision-makers in priority setting.

Adolescent↗

Cancer associated with obstetric delivery: results of linkage with the California cancer registry.

OBJECTIVE: This study provides revised population-based measurements for the occurrence rates of cancer associated with obstetric delivery and examines perinatal and cancer-related outcomes within the group of women with 4,846,505 obstetric deliveries in California, inclusive of the years 1991 through 1999. STUDY DESIGN: This observational study used a population-based retrospective review of cases identified as a result of computer linkage of maternal/neonatal hospital discharge and birth/death records with case files in the California Cancer Registry (CCR). The effect of timing of cancer diagnosis on clinical outcomes was studied by dividing the cases into three groups as follows: "prenatal" for cancer diagnosis within 9 months before delivery, "at delivery" for cancer diagnosis during delivery hospitalization, and "post partum" for cancer diagnosis within 12 months after delivery. Computerized records for 4,846,505 obstetric patients and 4,906,920 newborn infants comprising the linked vital statistics birth/patient discharge database (VS/PDD) were used to identity-match cases within the CCR case files. Cases of malignant disease were categorized into 22 anatomic or histologic subgroups. Perinatal clinical outcomes including preterm delivery, prolonged neonatal hospital stay, stillbirth, neonatal death, frequency of first trimester prenatal care, and cesarean delivery were analyzed by use of International Classification of Diseases, 9th Revision, Clinical Modification codes from the VS/PDD. Clinical cancer outcomes including cancer stage and vital status on follow-up were drawn from CCR records. Statistical comparisons for trends were performed with the Cochran-Armitage test, outcomes comparisons with the Fisher exact test, and survival comparisons were performed with the Cox proportional hazard model. RESULTS: Among 4,846,505 obstetric deliveries, 4,539 cases of invasive malignancy were identified for an observed occurrence rate of 0.94 per 1000 births. Sixty-four percent of the cases occurred post partum; cancers of the breast, thyroid, cervix, along with malignant melanoma, and Hodgkin's disease accounted for 64% of the cases. The timing of cancer diagnosis affected clinical outcomes: for all cancer cases as a group, the most favorable perinatal and cancer outcomes occurred in women whose cancer diagnosis was made 6 to 9 months before delivery (6% of cases). The most unfavorable perinatal and cancer outcomes were associated with cancer diagnosis made 0 to 3 months before delivery (14% of cases). For women whose cancer was diagnosed post partum, perinatal outcomes were minimally affected by the presumed existence of occult cancer at the time of obstetric delivery. CONCLUSION: The use of computer-linkage to the CCR files enhanced identification of cases of maternal malignancy associated with obstetric delivery. Cancer diagnosis was associated with approximately 1 in 1000 deliveries. Most cases were diagnosed after delivery and were comprised predominantly of cancers of the breast, thyroid, cervix, malignant melanoma, and Hodgkin's disease. A small group of women (approximately 1 per 5000 deliveries) are seen within a few months before delivery or at delivery with malignant disease, many of whom have rapidly progressing disease and may require high-risk perinatal and oncology services.

Breast Neoplasms↗

The reporting of HIV/AIDS deaths in women.

OBJECTIVE: This study was undertaken to assess the completeness of vital statistics and case reports of acquired immunodeficiency syndrome (AIDS) in measuring human immunodeficiency virus (HIV)-related mortality in women 15 through 44 years of age. METHODS: We used vital records to determine the number of deaths attributed to HIV infection and excess deaths due to causes that have increased in tandem with the HIV epidemic. RESULTS: In 1988, among women 15 through 44 years of age, there were 1365 deaths with HIV infection listed as the underlying cause, 202 deaths with HIV infection listed as an associated cause, and 149 excess deaths due to conditions highly associated with HIV infection (subtotal = 1716). In addition, there were 780 excess deaths due to causes that may be related to HIV infection or illicit drug use (maximum estimate of HIV-related deaths = 2496). Of the deaths that occurred in 1988, 1532 were reported through AIDS surveillance (1668 deaths when adjusted for reporting delays). CONCLUSIONS: Underlying-cause-of-death vital records and AIDS surveillance identified 55% to 80% and 67% to 97%, respectively, of HIV-related deaths in women 15 through 44 years of age in 1988. The wide ranges of these estimates reflect the potential role of both HIV infection and drug use in contributing to excess mortality.

AIDS-Related Opportunistic Infections↗

Trends in elderly mortality in the Nordic countries.

This study describes the development of elderly mortality in the Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) during this century. Long-term trends in total mortality are examined on the basis of life table statistics. More recent trends (from the 1950s onwards) are described by means of annual mortality rates according to a rough classification of causes of death. The series of vital statistics have been utilized as the data source for the long-term trends, and the original data for annual trends have been obtained from the mortality data bank files of the WHO. Marked improvements were observed in survival at advanced ages in the Nordic countries. However, the development has not been stable as in recent decades the elderly mortality rate has fluctuated, roughly comparable to the fluctuations in mortality among the younger age groups. The fact that the rate of recent improvement has been greatest in Finland where there, traditionally, is a high mortality level, and low in Norway and Sweden, where mortality levels are low, is in accordance with the idea of approaching a certain biological lower limit to mortality. However, certain characteristics seem to suggest that further advances are possible. Marked improvements have taken place recently in Iceland even though its mortality level at the end of the 1960s was already low. In addition, a large proportion of the differences in mortality rates between the Nordic countries may be due to external factors related to living conditions or life-style. Recent trends in mortality from several causes of death may also be primarily linked to such factors. Further research focusing particularly on a more detailed classification of causes of death and sociodemographic differentials within the national elderly populations is suggested.

Aged↗

Apolipoprotein E genotype and mortality: findings from the Cache County Study.

OBJECTIVES: To evaluate the association between apolipoprotein E (apo E) epsilon4 and mortality, the population attributable risk for mortality with epsilon4, and relative contributions of cardiovascular disease (CVD) and Alzheimer's disease (AD). DESIGN: Population-based cohort study. SETTING: Community-based. PARTICIPANTS: Permanent residents of Cache County, Utah, aged 65 and older as of January 1, 1995. MEASUREMENTS: Participants were genotyped at the apo E locus using buccal-swab deoxyribonucleic acid. Cardiovascular health was ascertained using self- or proxy-report interviews at participants' residences. AD was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders criteria. Utah Department of Vital Statistics quarterly reports were reviewed to identify participants who died. RESULTS: Crude evaluations showed nonsignificantly greater risk of death for epsilon2/2 (hazard ratio (HR)=1.66, 95% confidence interval (CI)=0.92-2.76) and epsilon3/4 (HR=1.11, 95% CI=0.97-1.26) genotypes and significantly greater risk for epsilon4/4 (HR=1.48, 95% CI=1.09-1.96). After adjustment for age, age(2), sex, and education, risks increased to 1.98 (95% CI=1.08-3.35), 1.28 (95% CI=1.12-1.46), and 2.02 (95% CI=1.47-2.71), respectively, compared with epsilon3/3 genotypes. Adjustment for presence of any CVD did not change the risk of death for epsilon3/4 and epsilon4/4. Adjustment for AD reduced the risk of death for epsilon3/4 (HR=1.13, 95% CI=0.99-1.30) and epsilon4/4 (HR=1.59, 95% CI=1.15-2.14). The population attributable risk of death for epsilon3/4 and epsilon4/4 genotypes combined is estimated at 9.6%. CONCLUSION: These findings suggested that the epsilon2/2, epsilon3/4, and epsilon4/4 genotypes have greater early mortality risks. Further analyses showed that AD partially mediates the association between epsilon3/4, epsilon4/4, and death.

Age Distribution↗

Changing trends in melanoma incidence and mortality.

OBJECTIVES: This article analyzes trends in melanoma incidence and mortality rates. Information on sun exposure supplements these statistics. DATA SOURCES: Melanoma incidence data were obtained from the National Cancer Incidence Reporting System and from the Canadian Cancer Registry. Cancer mortality data were extracted from the Canadian Vital Statistics Data Base. Information on sun exposure is from the 1996 Sun Exposure Survey. ANALYTICAL TECHNIQUES: Incidence and mortality rates were age-standardized to the 1991 Canadian population to account for changes in the age structure of the population over time. The average annual percentage changes in age-specific rates were calculated for selected time periods. MAIN RESULTS: After years of steady increases, melanoma incidence and mortality rates have levelled off as a result of declining rates in younger age groups, and for melanoma of the trunk among men and of the leg among women. Incidence rates for men are now higher than those for women; mortality rates for men are twice as high as for women.

Adolescent↗