Standardized Morbidity Ratio Research Articles

Early gastric cancer: unrecognized indicator of multiple malignancies.

The aim of this study was to evaluate the postoperative outcome and occurrence of second primary malignancies in patients who underwent radical resection for early gastric cancer. Altogether 105 patients with early gastric cancer underwent radical resection and were followed up for a median period of 71 months. Overall lethality was analyzed with regard to mortality due to gastric cancer or other causes. Standardized mortality and morbidity ratios were calculated using data from the Tumor Registry of Lombardy. The 5-year survival rate was 82.8% (operative mortality excluded), which was not different from that expected from an age- and sex-matched Italian population. Ten second primary malignancies were identified, giving a standardized mortality ratio of 1.12 and a standardized morbidity ratio of 1.50. Patients undergoing surgery for early gastric cancer (especially the intestinal type) may have a circa 50% higher risk of a second tumor and should be periodically checked for other tumors, mainly in the supramesocolic area.

Incidence of acute myocardial infarction and cause-specific mortality after transurethral treatments of prostatic hypertrophy

Objectives. Transurethral resection of the prostate (TURP) is associated with a higher long-term mortality than open prostatectomy which has been ascribed to a higher incidence of acute myocardial infarction (AMI). To assess the possible excess risk associated with TURP, we studied the incidence of AMI and the cause-specific mortality in patients treated with TURP and transurethral microwave thermotherapy (TUMT). Methods. Patients treated for benign prostatic hypertrophy at a university hospital (888 patients with TURP and 478 with TUMT) were monitored during an average follow-up period of 3.9 years. The incidence of AMI and the causes of death were compared with those in the general population. Results. Both treatments were followed by a higher incidence of AMI than in the general population, in particular from 2 years or more after treatment (standardized morbidity ratio 1.50, 95% confidence interval [CI] 1.14 to 1.93). The long-term mortality from all causes was increased in patients younger than 75 years of age when undergoing any of the treatments (standardized mortality ratio [SMR] 1.16, 95% CI 0.97 to 1.39), in particular, death from cardiovascular diseases (SMR 1.25, 95% CI 0.95 to 1.60) and tumors (SMR 1.54, 95% CI 1.14 to 2.03). Conclusions. The similarity of the results for TURP and TUMT suggests that the prostatic enlargement rather than the treatment is associated with cardiovascular disease.

The effect on morbidity of variability in deprivation and population stability in England and Wales: an investigation at small-area level

We seek to determine whether variability in deprivation at small area level, and population stability, influence standardised morbidity ratios in England and Wales. A regression analysis was conducted with data from the 1991 British Census, in order to explain variation in morbidity. Both an area deprivation score (for electoral wards) and the within-area variability of deprivation scores were examined as possible determinants of morbidity (self-reported, limiting, long-term illness). Particular attention was focused on a spatially-sensitive measure of the variability of deprivation scores within a wider ‘locality’. There was a significant, positive relationship between age-standardised limiting, long-term illness and deprivation. The variation in area deprivation scores within the small areas themselves was also significant and positive. However, the variation in deprivation scores calculated for both an electoral ward and its contiguous neighbours (the locality) was slightly more significant. Areas with higher relative levels of in-migration also had significantly lower standardised morbidity ratios. Multivariate models showed that the deprivation score, the variation in deprivation scores for the broader locality, and the measure of migration, were all significant in combination. Residual analysis showed that many areas in London had lower levels of morbidity than expected, while electoral wards in the coal mining valleys of South Wales had higher levels than expected. We conclude that, for small areas (wards) in England and Wales, morbidity is related to deprivation, variation in deprivation within and surrounding each area, and the proportion of the population that are migrants. Variations in deprivation influence standardised morbidity rates, and policies which widen inequalities will influence health outcomes. Resource allocation based simply on measures of deprivation, which ignore population change within the area and variations in deprivation in the locality, may be inefficient.

Spatial and temporal analysis of Ross River virus disease patterns at Maroochy Shire, Australia: association between human morbidity and mosquito (Diptera: Culicidae) abundance.

Notifications of Ross River (RR) virus disease in Maroochy Shire were mapped according to the patient's place of residence, and standardized morbidity ratios were calculated for each of 11 census districts, with 4 areas having higher than average overall rates of RR virus disease notification. Temporal analysis of RR virus disease notifications from each of the 11 areas indicated that epidemics of RR virus disease either were widespread, resulting in higher than average numbers of cases from the majority of areas, or limited to only certain areas. Mosquitoes were collected in CO2 light traps, and the numbers analyzed to determine whether there was any association between mosquito abundance and disease incidence. Seasonal light trap indices for the fresh water-breeding Culex annulirostris Skuse and brackish water-breeding Aedes funereus (Theobald) were correlated positively with disease incidence. There was no apparent association between Aedes vigilax (Skuse) or Aedes procax (Skuse) light trap indices and disease incidence. Identification of human subpopulations with higher than average rates of RR virus disease, and the mosquito vectors associated with virus transmission, should provide a framework for the development of focused and therefore more effective control programs.

Barbiturates and lung cancer: a re-evaluation.

Barbiturates, particularly phenobarbital, have been shown to be a tumour promoter in animal experiments and were found to be associated with increased risk of lung cancer in our cohort follow-up study to screen pharmaceuticals for possible carcinogenic effects. Sixteen more years of follow-up have accumulated permitting a more detailed evaluation of this association. In all, 10,213 subscribers of the Kaiser Permanente Medical Care Program who received barbiturates between 1969 and 1973 from its San Francisco pharmacy were followed up through 1992 and their incidence of lung cancer at biennial intervals was compared with what was expected based on the experience of the entire pharmacy cohort (143,594). Smoking-habit data were available on about half of the barbiturate users and were used to adjust for cigarette smoking in both the observed/expected analysis and in Cox proportional hazards analysis. The initially elevated standard morbidity ratio of 1.55 (95% CI: 1.25-1.91) with 3-7 years of follow-up gradually decreased and stabilized at about 1.3 after 11-15 years of follow-up. This trend for diminishing relative risk over time was more pronounced among the never smokers but their initial excess risk was not statistically significant due to small numbers. A dose-response trend was observed, based on the number of prescriptions dispensed. Analytical control for cigarette smoking reduced but did not eliminate either the association or the dose-response trend. Most of the barbiturate-associated cases in never smokers were women and the predominant histological type was adenocarcinoma. These findings from up to 23 years of follow-up are not conclusive because of the continuing small number of never smokers who developed lung cancer. However, they strengthen and refine previous observations of a barbiturate-lung cancer association, which is probably not fully explained by confounding by cigarette smoking. The diminution of excess risk over time is consistent with a tumour promoter effect. Findings among the never smokers suggest that this possible effect may be greatest on adenocarcinomas in women.

Risk of second malignancies after surgical treatment for early gastric cancer.

We evaluated the follow-up of 105 patients who received surgical treatment at our Institute for early gastric cancer (EGC). Median follow-up was 71 months. Operative mortality was 5.7% and the 5-year survival rate was 82.8%, approximately that of an age- and sex- matched Italian population. Overall mortality was assessed with regard to mortality from gastric cancer or other causes. Ten second primary malignancies were identified, and the standardized mortality ratio (1.12; 90% confidence interval [CI] 0.77-1.64) and standardized morbidity ratio (1.50; 90% CI 0.89-2.50) were determined using data from the Tumor Registry of Lombardy. To our knowledge, this is the biggest Western series to measure the risk EGC patients face of developing a second primary tumor. In conclusion, oncologists who follow-up patients surgically treated for EGC, a disease that is much less frequent in Western countries than in Eastern ones, should be aware of the possible occurrence of extragastric primary tumors so that they may plan the appropriate diagnostic investigation when necessary.

Increased risk of cancer in ulcerative colitis: a population-based cohort study.

There is an increased risk of colorectal cancer among patients with ulcerative colitis (UC). However, the overall and site specific cancer risks in these patients have been investigated to a limited extent. To study the association between UC and cancer, a population-based study of 1547 patients with UC in Stockholm diagnosed between 1955 and 1984 was carried out. The patients were followed in both the National Cancer Register and the National Cause of Death Register until 1989. For comparisons, regional cancer incidence rates in Stockholm County were used together with individually computed person-years at risk in the UC disease cohort. A total of 121 malignancies occurred among 97 individuals as compared with 89.8 expected (standardized morbidity ratio [SMR] = 1.4; 95% confidence interval (CI), 1.1-1.6). Overall, an excess number of colorectal cancers (SMR, 4.1; 95% CI, 2.7-5.8), and hepatobiliary cancers in men (SMR = 6.0; 95% CI, 2.8-11.1) associated with primary sclerosing cholangitis, was observed. The risk of pulmonary cancer was decreased (SMR = 0.3; 95% CI, 0.1-0.9). In all, 91 extracolonic malignancies were observed, compared with the 82.3 expected (SMR = 1.11; 95% CI, 0.9-1.3). In UC patients, the overall cancer incidence is increased mainly because of an increased incidence of colorectal and hepatobiliary cancer. This increase is partly counterbalanced by a decreased risk of pulmonary cancer compared with that in the general population.

Increased risk of cancer in ulcerative colitis: a population-based cohort study

OBJECTIVE: There is an increased risk of colorectal cancer among patients with ulcerative colitis (UC). However, the overall and site specific cancer risks in these patients have been investigated to a limited extent. To study the association between UC and cancer, a population-based study of 1547 patients with UC in Stockholm diagnosed between 1955 and 1984 was carried out. METHODS: The patients were followed in both the National Cancer Register and the National Cause of Death Register until 1989. For comparisons, regional cancer incidence rates in Stockholm County were used together with individually computed person-years at risk in the UC disease cohort. RESULTS: A total of 121 malignancies occurred among 97 individuals as compared with 89.8 expected (standardized morbidity ratio [SMR] = 1.4; 95% confidence interval (CI), 1.1–1.6). Overall, an excess number of colorectal cancers (SMR, 4.1; 95% CI, 2.7–5.8), and hepatobiliary cancers in men (SMR = 6.0; 95% CI, 2.8–11.1) associated with primary sclerosing cholangitis, was observed. The risk of pulmonary cancer was decreased (SMR = 0.3; 95% CI, 0.1–0.9). In all, 91 extracolonic malignancies were observed, compared with the 82.3 expected (SMR = 1.11; 95% CI, 0.9–1.3). CONCLUSIONS: In UC patients, the overall cancer incidence is increased mainly because of an increased incidence of colorectal and hepatobiliary cancer. This increase is partly counterbalanced by a decreased risk of pulmonary cancer compared with that in the general population.

Forearm fractures in Malmö, Sweden. Changes in the incidence occurring during the 1950s, 1980s and 1990s.

Between the 1950s and the 1980s, the incidence of forearm fractures increased in the city of Malmö. We have now collected data on all forearm fractures during 1991 and 1992 and compared them with previously published data from 1953-1957 and 1980-1981. During the 1990s, 1314 individuals with wrist fractures and 125 with shaft fractures were recorded. In men, we found a twofold increase in the standardized morbidity ratio (SMR) in the 1990s, compared with the 1950s. The 1990s, compared with the 1980s, showed a reduction in SMR to 0.85. In women, a comparison between the 1990s and the 1950s revealed a slight reduction in SMR, 0.9 during the 1990s. Comparison of the 1990s with the 1980s revealed a reduction in SMR to 0.7 after the age of 70 years. In individuals 60 years and older, we found a fivefold increase in the incidence of fractures of the shaft of the forearm, when comparing the 1990s with the 1980s. In women, the increase in incidence of wrist fractures appears to have been interrupted, when comparing the years 1991-1992 and 1980-1981. Among men, the incidence of wrist fractures appears to be increasing, even after the 1980s. The reduction in incidence among women may partly be explained by warmer winters during 1991-1992.

Echocardiographic Assessment of Patients Receiving Long-Term Treatment With Anorexiant Medications

To describe the prevalence and evaluate the risk of echocardiogram-determined valvulopathy in patients who received fenfluramine and phentermine in an effort to lose weight, in comparison with normal control subjects. A historical cohort study was conducted in a clinical obesity-management practice. A total of 164 patients (88% women) who were treated with fenfluramine-phentermine for weight loss had echocardiographic evaluations. A subsample was cross-validated. The prevalence of mild or greater aortic regurgitation was 18.3%, and the prevalence of moderate or greater mitral regurgitation was 3.7%. The prevalences of mild or greater tricuspid and pulmonary valve regurgitation, valve thickening, and pulmonary hypertension were 23.2%, 5.5%, 10.4%, and 6.7%, respectively. No significant increases in risk were found for moderate or greater regurgitation of any valve. Patients had at least a 3-fold risk for mild or greater aortic regurgitation (standardized morbidity ratio [SMR] = 3.03; 95% confidence interval [CI] = 2.05 to 4.33) and a 2-fold risk for tricuspid regurgitation (SMR = 2.24; 95% CI = 1.58 to 3.06) in comparison with normal healthy adults. Age and duration of drug therapy predicted increased risk for aortic regurgitation. Four patients who had moderate or greater aortic regurgitation had taken the fenfluramine-phentermine combination continuously for 454, 615, 645, and 984 days. Use of serotonergic anorexiant medications may increase risk for mild or greater aortic and tricuspid regurgitation, although selection bias and obesity as causes of the association cannot be ruled out. Age and duration of drug therapy were predictors of aortic valvulopathy. Population-based studies are needed to confirm these preliminary findings.

Cutaneous melanoma risk and phenotypic changes in large congenital nevi: A follow-up study of 46 patients

Background: Large congenital melanocytic nevi may undergo malignant transformation. Few prospective studies have evaluated the incidence of melanoma in large congenital nevi or have described how their phenotypic characteristics change over time. Objective: We attempted to ascertain the incidence of cutaneous melanoma in a cohort of patients with large congenital nevi and to evaluate the frequency and nature of several morphologic changes over time. Methods: Forty-six patients with large congenital nevi were prospectively followed up in our Pigmented Lesion Group. Large congenital nevi were defined as those occurring at birth and comprising 5% body surface area or greater in infants, children, and preadolescents and more than 20 cm in adolescents and adults. Information was obtained on location, satellitosis, changes in color and nodularity, and incidence of melanoma. The most atypical histologic findings from those who underwent biopsy were also noted. Standardized morbidity ratios (SMR) and 5-year cumulative risk were calculated and presented with corresponding 95% confidence intervals (CI). Results: Twenty-four male and 22 female patients (age range, 7 days to 36.7 years; mean, 8.4 years) with large congenital nevi were followed up prospectively for a total of 335 person-years (range, 0.17 to 17.5 person-years; mean, 7.3 person-years). Two patients (4.3%) experienced 3 cutaneous melanomas that originated in their primary congenital nevi. We found one case of neurocutaneous melanosis. No satellite, extremity, or extracutaneous melanomas were detected. The majority of nevi in our cohort were located on the posterior trunk, were accompanied by multiple satellite congenital nevi, and became lighter over time. In the 27 patients who underwent biopsies, the most atypical histologic findings included melanoma, atypical melanocytic dysplasia, neurocristic dysplasia, atypical neural crest hamartomas, atypical spindle cell tumors, and congenital nevi with dysplasia. The SMR comparing observed-to-expected melanoma incidence was 148 (95% CI 18, 535; P = .0002) indicating a substantially increased risk of melanoma in patients with large congenital nevi. The cumulative 5-year risk of cutaneous melanoma was 5.7% (95% CI 0%, 13.5%). Conclusion: Our findings are consistent with the previously observed increased risk for the occurrence of cutaneous melanoma in patients with large congenital nevi. Although the number of patients with melanoma in this study is small, our observations and those of previous studies suggest that location and age correlates with melanoma risk. The majority of large congenital nevi are located on the trunk and may undergo several clinical changes as these patients age. Additional prospective studies are needed to gain more insight into the natural history and optimal management of large congenital nevi. (J Am Acad Dermatol 1998;39:923-32.)

Secondary leukemia following high cumulative doses of etoposide in patients treated for advanced germ cell tumors.

High cumulative epipodophyllotoxin dosages are reported to be associated with an elevated risk for secondary acute myeloid leukemia (s-AML). This study examined the risk of s-AML following cumulative etoposide doses greater than 2 g/m2 in patients with metastatic germ cell tumors (GCT). The incidence of s-AML was retrospectively assessed in patients treated within clinical trials between January 1986 and February 1996 at four university centers. All patients received high-dose chemotherapy (HDCT) plus autologous stem-cell support for metastatic GCT, including high cumulative etoposide doses (> 2 g/m2). Minimum patient follow-up was 12 months. Standardized morbidity ratio (SMR) was calculated to estimate the risk associated with high cumulative etoposide doses, as compared with the general population. A total of 302 patients with a median age of 29 years (range, 15 to 55) received a median cumulative etoposide dose of 5 g/m2 (range, 2.4 to 14 g/m2). Four cases of s-AML were observed, which resulted in a cumulative incidence of 1.3% (95% confidence interval [CI], 0.38% to 3.59%) at 52 months of median follow-up (range, 12 to 198). Two cases of secondary myelodysplasia (s-MDS) developed in patients with primary mediastinal GCT. Based on the observed four cases of AML, which are most likely etoposide-related, the risk for developing s-AML (SMR, 160 [95% CI, 43.7 to 411.2]) is significantly increased in comparison to the age-matched general population. Due to the low incidence of AML in the general population, the significantly elevated risk for developing s-AML affects only 1.3% of all patients who receive etoposide doses greater than 2 g/m2. HDCT, including etoposide doses greater than 2 g/m2, is associated with an acceptably low incidence of s-AML in patients with advanced GCT.

Relapse rate, renal survival, and cancer morbidity in patients with Wegener's granulomatosis or microscopic polyangiitis with renal involvement.

Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are both frequently associated with antineutrophil cytoplasmic autoantibodies (ANCA). Immunosuppressive treatment has dramatically improved outcome for these patients, but today we have to deal with the problems of relapses, cases refractory to treatment, and long-term side effects of therapy. This study comprises a consecutive series of 123 patients with WG (n=56) or MPA (n=67) with biopsy-confirmed renal involvement, followed up for a median of 55 mo (range, 0.1 to 273.2 mo). ANCA was detected by enzyme-linked immunosorbent assay in 97% of patients. Nearly half of the patients (46%) relapsed. There was no statistically significant difference in overall relapse rate according to type of ANCA. Renal survival was 78% in patients alive at the end of follow-up. Three variables seemed important for renal survival: serum creatinine, the titer of proteinase 3-ANCA measured by capture enzyme-linked immunosorbent assay, and B thrombocyte count, at time of referral. Cancer incidence data were obtained from the population-based South Swedish Regional Tumor Registry. Standardized morbidity ratio was calculated using expected values from the health care region. We found an 11-fold increase in risk for bladder cancer in patients treated with cyclophosphamide for at least 12 mo. Skin carcinoma had the strongest relationship with azathioprine use for at least 12 mo and with corticosteroid therapy for at least 48 mo. In addition, four patients developed myelodysplastic syndrome and five had carcinoma in situ of the skin. Because the therapeutic regimen used today is not efficient enough to prevent relapses and is associated with a host of side effects, of which the risk for cancer is by far the most important, improved therapy and medical care are needed for patients with WG and MPA.

Fracture risk among patients with urolithiasis: A population-based cohort study

In a population-based retrospective cohort study, 624 Rochester, Minnesota residents with an initial symptomatic episode of urolithiasis in 1950 to 1974 were followed for 11,909 person-years for subsequent age-related fractures. During this period of observation, the number of patients with a first vertebral fracture was over four times the number expected on the basis of vertebral fracture incidence rates in the general population of Rochester [standardized morbidity ratio (SMR), 4.3; 95% confidence interval, 3.4 to 5.3]. The risk of vertebral fracture was elevated among men as well as women, and was associated with increasing age and with the use of corticosteroids for more than six months. However, vertebral fracture risk was increased nearly fourfold (SMR 3.9; 95% confidence interval, 3.0 to 4.9) among the urolithiasis patients without such exposure, which suggests that corticosteroids do not completely account for the association with vertebral fractures. There was no increase in the risk of hip, pelvis, proximal humerus or distal forearm fractures in this cohort of patients, and their survival was not impaired. Additional studies are needed to define the pathophysiology of vertebral fractures among patients with urolithiasis.

Meta-analysis and occupational epidemiology.

Meta-analysis is increasingly appearing in the epidemiologic literature. Although originally performed in the context of experimental or randomized controlled study designs and with regard to problems that are amenable to these designs, the method has also been applied to studies in observational epidemiologic settings. This movement has generated considerable debate about the validity of meta-analysis in observational studies, which can be said to be rather shaky. Meta-analysis is also appearing in occupational epidemiology, and a recent application to studies of industrial cohorts exposed to organic solvents has illustrated many of the arguments against meta-analysis of observational study. The propensity of meta-analysis for disarming critical approaches to individual study methods such as the standardized morbidity or mortality ratio (SMR) as effect measure, and to application of commonly used biostatistical techniques is illustrated. A cautionary note is sounded.

Associations between different forms of gastro-oesophageal reflux disease

Aims—To study the epidemiology and natural history of gastro-oesophageal reflux disease (GORD).Methods—Retrospective cohort study involving all 172 hospitals of the Department of Veterans Affairs. A total of 194 527 patients...

Lindane and cancer in humans: a false alarm?

In up to 21 years of follow-up in a study to periodically screen pharmaceuticals for possible carcinogenic effects, 1146 persons who received lindane, an established carcinogen in animal experiments, showed for the first time a statistically significant increase in incidence of cancer (43 cases observed, 30.2 expected, standardized morbidity ratio 1.42, 95% confidence interval 1.03-1.92). The computer-stored data on drug dispensing and cancer occurrence also showed some evidence of a dose-response relationship. Review of the complete medical records suggested that at least part of the association was due to confounding by indication. Four of the cancer patients had Kaposi's sarcoma due to AIDS and the acquisition of pediculosis pubis or scabies, commonly treated with lindane, is associated with behaviour that also predisposes to AIDS. Four other patients also had strong risk factors that could readily be blamed for their cancer and one had not used the drug. Also, the location of the skin lesions or infestations treated with lindane seemed to bear no relation to the cancer sites. It is concluded that this study provides no convincing evidence of carcinogenicity of lindane; nor does it rule it out. In pharmacoepidemiology, it is advisable to supplement analyses of routinely collected data on drugs and clinical events with review of medical records when interesting associations are noted.

Risk of dementia among persons with diabetes mellitus: a population-based cohort study.

It is unclear whether persons with diabetes are at increased risk for dementia, including Alzheimer's disease. Existing studies are limited by small sample size, selection bias, and case-control designs. This population-based historical cohort study provides estimates of the risk of dementia and Alzheimer's disease associated with adult onset diabetes mellitus (AODM). The sample included all persons with AODM residing in Rochester, Minnesota, on January 1, 1970, plus all persons diagnosed in Rochester or who moved to Rochester with the diagnosis between January 1, 1970, and December 31, 1984. Individuals were followed through review of their complete medical records from AODM diagnosis until dementia onset, emigration, death, or January 1, 1985. Standardized morbidity ratios for dementia and Alzheimer's disease were calculated, using an expected incidence based on age- and sex-specific rates for the Rochester population. Poisson regression was used to estimate risks for persons with AODM relative to those without. Of the 1,455 cases of AODM followed for 9,981 person-years, 101 developed dementia, including 77 who met criteria for Alzheimer's disease. Persons with AODM exhibited significantly increased risk of all dementia (Poisson regression relative risk (RR) = 1.66, 95% confidence interval (CI) 1.34-2.05). Risk of Alzheimer's disease was also elevated (for men, R = 2.27, 95% CI 1.55-3.31; for women, RR = 1.37, 95% CI 0.94-2.01). These findings emphasize the importance of AODM prevention and prompt additional investigation of the relation between AODM and dementia.

Is Mycoplasma Pneumonia associated with childhood acute lymphoblastic leukemia?

Acute lymphoblastic leukemia (ALL) in the childhood peak may be a rare response to delayed first exposure to one or more common infectious agent(s). Mycoplasma Pneumonia has the appropriate socioeconomic correlates and clinical symptoms and the hypothesis that delayed first exposure to it may contribute to ALL is considered. Counts of positive reports of M Pneumonia from disease surveillance data for England and Wales (United Kindom) for 1975-92 have been taken as proxies for community burden of infection. Variation by months of birth (cohort) and diagnosis (period) of incidence of ALL in children born and diagnosed 1975-92 are compared with predictions. When periods were classified by mean M Pneumonia count rate in the nine preceding months, standardized morbidity ratios (SMR) for the highest and lowest 20 percent were 108 and 89 (rate ratio [RR] = 1.2, 95 percent confidence interval [CI] = 1.1-1.4). SMRs for cohorts with highest and lowest predicted risk (i.e., lowest and highest M Pneumonia count rate around birth and during infancy) were 110 and 97 (RR = 1.1, CI = 1.0-1.3). The trend for period was most marked in the cohorts with low opportunity for exposure when young. This ecologic analysis provides preliminary support for the hypothesis.

An efficient SAS program for exact stratification of person-years

An efficient Statistical Analysis System computer program for the exact stratification of person-years is described, in order to determine the expected number of deaths or cases of diseases in a cohort for the calculation of standardized mortality ratios or standardized morbidity ratios. A comparison of this program with Macaluso's “Method B” program shows that the speed of the former is considerably faster than that of the latter, when the widths of the categories defined by all of the time factors are identical.