Initial metformin or sulphonylurea exposure and cancer occurrence among patients with type 2 diabetes mellitus.

AIM: This was a retrospective cohort study of type 2 diabetes patients, to evaluate the association between initial metformin or sulphonylurea treatment and cancer incidence. METHODS: Patients identified in the UK Clinical Practice Research Datalink (CPRD), previously General Practice Research Database, during 1995-2008 who were initially stabilized on OHA monotherapy, including metformin, sulphonylurea, thiazolidinediones (TZDs) or meglitinides, were included in the cohort. New diagnoses of cancer, including malignant solid tumours and haematological malignancies, occurring during the follow-up were identified from the cohort. Age-standardized incidence rates were estimated and compared between metformin and sulphonylurea exposure groups. RESULTS: The age standardized incidences of cancer were 7.5 and 8.5 per 1000 person-years for the metformin and sulphonylurea exposure groups, respectively. After adjusting for potential confounders, the hazard ratios (HR) for malignant solid tumours and haematological malignancies were 1.06 (95% CI: 0.98, 1.15) and 0.98 (95% CI: 0.67, 1.43) for sulphonylurea group as compared to the metformin group, respectively. For individual cancers, the HRs were 1.17 (95% CI: 0.95, 1.44), 1.04 (95% CI: 0.83, 1.31) and 0.88 (95% CI: 0.71, 1.11) for colorectal cancer, breast cancer and prostate cancer, respectively. CONCLUSION: This study provides evidence that cancer incidence in the first few years after starting metformin or sulphonylurea therapy in type 2 diabetes patients is not much affected by choice of hypoglycaemic drug class.

Two-year glycaemic control and healthcare expenditures following initiation of insulin glargine versus neutral protamine Hagedorn insulin in type 2 diabetes.

AIMS: To compare 2-year glycaemic control, hypoglycaemia and healthcare expenditures following insulin glargine (glargine, n = 2105) or neutral protamine Hagedorn (NPH) insulin (NPH, n = 734) initiation in patients with type 2 diabetes (T2D). METHODS: Retrospective cohort study using an integrated US health insurance administrative database was conducted. Individuals with a diabetes diagnostic claim and initiated basal insulin therapy with glargine or NPH from 2001 to 2005 dispensed at least one oral antidiabetic drug prescription during 6 months prior to basal insulin initiation and enrolled in the same health insurance plan from 6 months before to 12 months or more after insulin initiation were identified. Repeated measures mixed-effects models evaluated glycaemic and financial outcomes to account for factors potentially contributing to selection of insulin therapy, that is, age, gender, baseline HbA1c level, health expenditures, co-morbidities, healthcare utilization, pharmacy co-payment and follow-up antidiabetic medications. RESULTS: Adjusted mean HbA1c value in the first year following insulin initiation was significantly lower for glargine versus NPH initiators (Δ = -0.43, p = 0.006); this difference diminished in the second year (Δ = -0.16, p = 0.375). First-year adjusted quarterly hypoglycaemia incidence rates were lower for glargine (2.1%) versus NPH (2.4%) (p = 0.02) as was the second-year quarterly rate (1.8 vs. 2.2%; p = 0.01). Both the first- and second-year adjusted total healthcare expenditures were lower in the glargine versus NPH group (year 1: $18,720 vs. $19,996, p = 0.005; year 2: $15,008 vs. $17,336; p < 0.001). CONCLUSIONS: Glargine therapy may be an effective long-term option for improving glycaemic control, with lower rates of hypoglycaemia and healthcare costs in patients with T2D.

Dietary patterns among men of Japanese ancestry in Hawaii.

The dietary patters of 6663 men of Japanese ancestry, living in Hawaii and participating in the Honolulu Heart and Japan-Hawaii Cancer Studies, were analyzed according to country of birth and boyhood education. Approximately 80% of the men were born and educated in Hawaii (Nisei); the others were either born in Japan (Issei) or traveled to Japan for 5 or more years of boyhood education (Kibei). Twenty-four-hr diet recalls, obtained at the first cycle of examinations (1965 to 1968), revealed that the Nisei consumed significantly greater intakes of total and animal protein, total and saturated fat, and cholesterol than the Issei and Kibei. Values for weight, height, skinfold thickness, and serum cholesterol were in the same direction, and the differences were statistically significant. Food frequency questionnaires at the 1st and 3rd examinations covered a 6-year interval. At both time periods, the Issei and Kibei ate Japanese foods more frequently and in greater quantities than the Nisei. In general, the Nisei consumed more Western foods. Both food frequency questionnaires included 6 identical items; coffee, milk, green tea, rice, tofu (soybean curd), and tsukudani (preserved seaweed paste). The frequent and infrequent consumers were similarly characterized over the 6-year period. The findings suggest that the country of birth and education has lasting effects on adult eating patterns. The observed heterogeneity for specific food items and nutrients between the Nisei and Issei-Kibei men augers well for attempts to relate such items to chronic diseases such as cancer.

The reproducibility of dietary intake data in a prospective study of gastrointestinal cancer.

To test the reproducibility of the dietary questionnaire used in the Japan-Hawaii Cancer Study and to measure the consistency of dietary patterns over time, 109 men were reinterviewed with the same questionnaire after a 6-month interval and 111 men were reinterviewed after a 2-year interval. The responses for intake of the 33 food items in the questionnaire were fairly reproducible. Food items with substantial correlation coefficients in both groups of men tended to be consumed on a more habitual basis. This finding suggests that if habitually consumed foods are linked to specific cancers, it is less likely that such associations occur by chance. This is of particular importance because when many food items are considered in a dietary study, chance association between a specific food and cancer is not an infrequent event.

Dietary intake and the risk of coronary heart disease in Japanese men living in Hawaii.

The relationship of dietary intakes to subsequent development of coronary heart disease (CHD) during a 6-year follow-up period was investigated in 7705 men of Japanese ancestry, ages 45 to 68 and living in Hawaii. Data on the intakes of calories and nutrients were obtained by 24-hr diet recall interviews at the base-line examination. An index for ingestion of traditional Japanese diet (Japanese diet score) was also calculated for each man. The men who subsequently developed myocardial infarction or died of CHD generally ate less than those who remained free of CHD, with statistically significant differences for total calories, total carbohydrate, complex carbohydrate or starch, simple carbohydrate other than sucrose, vegetable protein, alcohol, and Japanese diet score. However, when other major risk factors for CHD were taken into account, the negative association with CHD remained statistically significant only for alcohol and, to a lesser extent, total carbohydrate intakes. The lower total caloric intakes in CHD cases, largely due to decreased alcohol and carbohydrate intakes, could not be accounted for by either under-reporting of food consumption among obese men or diminished physical activity in CHD cases.

A dietary method for an epidemiologic study of gastrointestinal cancer.

The validity of a dietary recall questionnaire was tested among 50 men of Japanese ancestry, participating in a prospective epidemiologic study of gastrointestinal cancer in Honolulu. The questionnaire included 33 food items consumed in Hawaii and suggested as possibly carcinogenic or possibly protective. Estimated intakes of frequencies and amounts during the previous day and previous 7 days were obtained. The validity study consisted of a comparison of a 7 day diary of the frequencies and amounts of the 33 items with a subsequent recall of the same items. The sensitivity (proportion of men recording an item who subsequently recalled it) was better for 24 of the 33 items during the 7-day period than the 1-day period. The overall agreement between the two methods on whether the item was eaten or not was only marginally less for the 7 days than for the 1 day. Estimated intakes tended to be higher for the diary than the recall method. The Spearman rank correlation coefficients among persons recording the items generally were good (greater than 0.7) for items eaten habitually and for those associated with specific events. Further, rank order correlations for quantitative recell of particular food items has considerable validity and is a reasonable choice of method for studies of large groups concerning the role of particular food items in the etiology of cancer.

Glucose intolerance and nine-year mortality in Japanese men in Hawaii.

The relationship between glucose intolerance and nine-year mortality was examined in a cohort of approximately 8,000 men of Japanese ancestry living in Hawaii who were 45 to 68 years of age at baseline examination. Age-adjusted mortality for death from all causes, cardiovascular disease, coronary heart disease and causes other than cardiovascular disease and cancer were significantly higher in men with glucose intolerance, defined by either medication for diabetes or 1-hour post-load serum glucose levels above the 90th percentile cut-point (225 mg/dl) at baseline examination, than in normoglycemic men. Although many cardiovascular risk factors were found to be associated with glucose intolerance, both post-load serum glucose level and medication for diabetes remained significant as risk factors for overall, cardiovascular and coronary death in multivariate logistic analysis in which confounding effects of age, blood pressure, serum cholesterol, body mass index and other important risk factors were taken into account.

Alcohol and mortality: the Honolulu Heart Study.

It has been shown previously that coronary heart disease was less likely to develop in Japanese men in Honolulu who drank alcoholic beverages than in those who abstained, and that the more they drank (up to about 60 ml/day of ethanol) the lower the risk. In this report on the same men, it is shown that the same sort of relation holds for mortality from coronary heart disease but that the reverse is true for death from cancer and from stroke. Men who drank were more likely to die from these causes than those who abstained, and the more they drank the greater the risk of death. Men who drank relatively large amounts were more likely to die from cirrhosis of the liver than other men. The resultant curve for total mortality is u-shaped, the lowest risk being for men who consumed from 1 to 10 ml/day of ethanol. Even at that low level of consumption, however, the risk of death from cancer or stroke was greater than it was for nondrinkers. In short, for this population of Japanese men, alcohol consumption appears to have some benefits and some hazards with regard to mortality, and the benefit or hazard depends on which cause of death is being considered.

Breast-feeding incidence and duration in black and white women.

The influence of sociodemographic factors on the incidence and duration of breast-feeding was evaluated in 668 black and 511 white women delivering their first child in the metropolitan Washington, DC, area. Breast-feeding rates were 84% among white and 49% among black women. Maternal educational level was strongly associated with breast-feeding, whereas the effect of ethnicity was moderate. Women with some college or some graduate school education had adjusted odds of breast-feeding that were 2.6 (95% confidence limit 1.9 to 3.7) and 5.2 (95% confidence limit 2.7 to 10.2) times higher than women with a high school education or less. In contrast, the adjusted odds of breast-feeding were 2.0 (95% confidence limit 1.4 to 3.1) times higher for white women compared with black women. The odds of breast-feeding increased among black women if they attended childbirth classes, were married, or were older. Among black women, the frequency of breast-feeding decreased sharply by 1 month postpartum. Breast-feeding duration for black v white women was 74% v 90% at 1 month, 44% v 72% at 4 months, and 26% v 50% at 7 months postpartum. The majority of black women (53%) used formula supplements in the hospital, which was the only factor significantly related to a shortened duration in this group (P less than .01). The high rate of formula supplementation among black women and its strong association with shortened duration of breast-feeding point to a need for more advice and support and less reliance on formula during the hospital stay.

Maternal asthma and transient tachypnea of the newborn.

OBJECTIVE: To examine the relationship between transient tachypnea of the newborn and asthma complicating pregnancy. DESIGN: Historical cohort analysis. Setting. Singleton live deliveries in New Jersey hospitals during 1989 to 1992 (n = 447 963). PATIENTS: Mother-infant dyads were identified from linked birth certificate and maternal and infant hospital claims data. Women with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code (493) for asthma (n = 2289) were compared with a four-fold larger randomly selected control sample (n = 9156) from the remaining pool of women. MAIN OUTCOME MEASURE: Transient tachypnea of the newborn. RESULTS: In the overall sample, after controlling for the confounding effects of important variables, infants of asthmatic mothers were more likely [odds ratio (OR), 1. 79; 95% confidence interval (CI), 1.35-2.37] than infants of control mothers to exhibit transient tachypnea of the newborn. A stratified analysis by gestational age and sex revealed larger and statistically significant associations in term infants (OR, 2.02; 95% CI, 1.42-2.87) as opposed to preterm infants (OR, 1.51; 95% CI, 0.94-2.43) and in male infants (OR, 1.91; 95% CI, 1.35-2.71) as opposed to female infants (OR, 1.51; 95% CI, 0.92-2.47). On the other hand, after adjusting for important confounding variables, respiratory distress syndrome and maternal asthma were not found to be associated (OR, 1.14; 95% CI, 0.79-1.64). CONCLUSION: The results of this study provide evidence that maternal asthma is a risk factor for transient tachypnea of the newborn and differences in gestational age and sex were apparent in this association. The mechanism for this association remains to be determined.

Hypochloremic metabolic alkalosis from ingestion of a chloride-deficient infant formula: outcome 9 and 10 years later.

In 1978 and 1979 two infant formulas, Neo-Mull-Soy and Cho-Free, were found to be deficient in chloride. The Centers for Disease Control received reports that hypochloremic metabolic alkalosis (HMA) had developed in 141 children as a result of exposure to these formulas. Thirty-five of these children were examined at 9 and 10 years of age and compared with a group of 32 children who were exposed to the chloride-deficient formulas but were not reported to experience HMA and a group of 61 children who received chloride-sufficient soy formulas in infancy. The control children were matched to the HMA children on sex, race, age, and maternal education. Growth characteristics, performance on the Wechsler Intelligence Scale for Children-Revised (WISC-R), the Boston Naming Test, the Rey-Osterrieth Test, the Clinical Evaluation of Language Fundamentals-Revised (CELF-R), and subtests from several other speech and language tests were compared across the groups. After adjustment for family income and the level of the father's education, significantly lower scores were observed in the HMA children on the WISC-R Arithmetic subtest (mean = 10.5) compared with the soy control children (mean = 12.0, P less than .05) and on the WISC-R Coding subtest (mean = 9.0) compared with the soy control children (mean = 10.8, P less than .01). All the WISC-R subtest scores were, however, within the normal range. Although no significant differences occurred on the CELF-R between groups, the risk of an HMA child falling below the range expected for a standard population was increased on the CELF-R Composite Total, Receptive, and Expressive Language scores: risk ratios = 2.14, 2.14, and 3.03 respectively. Significant differences were observed between the children exposed, both HMA and non-HMA children, and the soy control children for behavioral problems as determined by the Achenbach Childhood Behavioral Checklist. It is concluded that as a group, children with documented HMA appear to have recovered from their growth failure and have normal cognitive development. They may, however, be at risk for deficits in language skills that require expressive language abilities.

Left axis deviation and left anterior hemiblock among 8,000 Japanese-American men.

Electrocardiographic patterns of left axis deviation and left anterior hemiblock, defined by a frontal plane QRS axis of minus 30 degrees to minus 44 degrees and minus 45 degrees to minus 90 degrees, respectively, with normal QRS duration, were found to be fairly common (2.6 and 1.5 percent, respectively) in a community population of 8,000 Japanese-American men aged 45 to 69 years. More than 60 percent of men with these electrocardiographic patterns had no other cardiovascular abnormalities, and the incidence of fatal or nonfatal coronary heart disease and stroke in this group during observation periods of 3 to 6 years was not significantly different from that of control normal men. A significant association was found between these electrocardiographic patterns and the prevalence of hypertension, myocardial infarction and stroke. However, the association of myocardial infarction with left anterior hemiblock appeared to be coincidental and was attributed largely to the similarity of the electrocardiographic manifestations of left anterior hemiblock and inferior wall myocardial infarction. Men with left axis deviation were fatter and had higher blood pressure than the control population. No such difference could be demonstrated for men with left anterior hemiblock although this group was significantly older than control subjects and men with left axis deviation. The results of our study suggest that there are qualitative differences between the causative mechanisms and clinical features of left axis deviation and those of left anterior hemiblock.

Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California. Coronary heart disease risk factors in Japan and Hawaii.

Various risk factors were evaluated to explain a significantly greater incidence of coronary heart disease in men of Japanese ancestry resident in Hawaii compared with men resident in Japan. The independent predictors of incidence of coronary heart disease in both Japan and Hawaii were systolic blood pressure, serum cholesterol, relative weight and age. These factors appeared to influence incidence similarly in both areas because in each case the correlation coefficients for Japan and Hawaii did not differ significantly. The hypothesis that the greater incidence in Hawaii could be attributed to differences in levels of these risk factors was tested with the Walker-Duncan method. The four variable multiple logistic function describing the probability of coronary heart disease in Japan was applied to the cohort characteristics observed in Hawaii. The estimated incidence thus obtained was not significantly different from that actually observed in the men resident in Hawaii. Therefore the increased coronary risk profile in Hawaii compared with Japan can account for the greater incidence of coronary heart disease in the former. Current cigarette smoking was significantly related to the risk of coronary heart disease in Hawaii but not in Japan. This difference requires further investigation.

Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California. Incidence of myocardial infarction and death from coronary heart disease.

The incidence of myocardial infarction and death from coronary heart disease was studied in defined samples of 45 to 68 year old Japanese men in Japan, Hawaii and California. The incidence rate was lowest in Japan where it was half that observed in Hawaii (P less than 0.01). The youngest men in the sample in Japan were at particularly low risk. The incidence among Japanese men in California was nearly 50 percent greater than that of Japanese in Hawaii (P less than 0.05). A striking increase in the incidence of myocardial infarction appears to have occurred in the Japanese who migrated to the United States; this increase is more pronounced in California than in Hawaii.

Seasonal influences on childhood lead exposure.

We conducted a study to examine seasonal changes in residential dust lead content and its relationship to blood lead in preschool children. We collected blood and dust samples (floors, windowsills, and carpets) to assess lead exposure. The geometric mean blood lead concentrations are 10.77 and 7.66 microg/dL for the defined hot and cold periods, respectively (p < 0.05). Lead loading (milligrams per square meter) is the measure derived from floor and windowsill wipe samples that is most correlated with blood lead concentration, whereas lead concentration (micrograms per gram) is the best variable derived from carpet vacuum samples. The variation of dust lead levels for these three dust variables (floor lead loading, windowsill lead loading, and carpet lead concentration) are consistent with the variation of blood lead levels, showing the highest levels in the hottest months of the year, June, July, and August. The regression analysis, including the three representative dust variables in the equations to predict blood lead concentration, suggests that the seasonality of blood lead levels in children is related to the seasonal distributions of dust lead in the home. In addition, the outdoor activity patterns indicate that children are likely to contact high leaded street dust or soil during longer outdoor play periods in summer. Consequently, our results show that children appear to receive the highest dust lead exposure indoors and outdoors during the summer, when they have the highest blood lead levels. We conclude that at least some of the seasonal variation in blood lead levels in children is probably due to increased exposure to lead in dust and soil.

The contribution of the case-control approach to vaccine evaluation: Pneumococcal and Haemophilus influenzae type B PRP vaccines.

Case-control studies have had an increasing role in the postlicensure evaluation of vaccine efficacy. We review the contribution of case-control studies to the evaluation of vaccines for Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib) and compare these studies with clinical trials of these vaccines. We located one clinical trial and eight case-control studies of Hib PRP vaccine efficacy and three clinical trials and four case-control studies of pneumococcal vaccine efficacy. The pooled estimate of Hib PRP vaccine efficacy based on the case-control studies (0.38, 95% CL = 0.15-0.55) was lower than the efficacy of the clinical trial conducted in Finland (0.8, 95% CL = 0.57-0.98). The pooled estimate of pneumococcal vaccine efficacy based on the case-control studies (0.56, 95% CL = 0.44-0.66) was also lower than the pooled efficacy of the South African clinical trials (0.79, 95% CL = 0.69-0.86). Although the clinical trials provided crucial evidence that these vaccines worked in selected international settings, the direct evidence of efficacy in the United States rests largely on the case-control results. The utility of the case-control approach is supported.

Empirical comparison of the results of randomized controlled trials and case-control studies in evaluating the effectiveness of screening mammography.

The gold standard for evaluating screening programs is the randomized controlled trial (RCT). Case-control studies are easier to perform but their role in this area is controversial. The purpose of this article is to compare empirically the results of RCTs and case-control studies conducted to evaluate the efficacy and effectiveness of screening mammography and examine possible explanations for differences in their results. We located eight RCTs and five case-control studies of screening mammography. For women aged 40-74 years at screening, comparison of the summary risk estimates of the RCTs (0.76, 95% CI: 0.69-0.83) with that of the case-control studies (0.44, 95%, CI: 0.38-0.50) showed RCTs to have a significantly higher summary risk estimate than case-control studies (ratio = 1.74, 95% CI: 1.48-2.04). It is notable that the RCTs were compromised in most instances by low compliance rates (50-80%) in the treatment groups and by significant use of screening in the control groups (20-30%). Adjustment of the RCT results for these cross-overs yields results that are in reasonable agreement with the summary estimate for the case-control studies. These findings support the use of case-control studies to estimate the efficacy of mammographic screening where RCTs are not feasible. They suggest that the efficacy of mammography in women aged 50 years and above is somewhat greater than the effectiveness measured by the intent-to-treat analysis of RCTs.

The importance of histologic type on breast cancer survival.

Breast cancer is a morphologically and genetically heterogeneous disease. The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute provides the large number of cases necessary to study individual histologic types of female invasive breast cancer that for practical reasons are otherwise unattainable. Attention was specifically focused on 4082 cases of mucinous adenocarcinoma and 139,154 cases of infiltrating duct carcinoma identified for the years 1973-1990. Life table analyses were conducted to compare survival by histologic type using death due to breast cancer as the outcome; Cox proportional hazards analysis was used to adjust for important covariates. Findings were that women diagnosed with mucinous adenocarcinoma have a rate of mortality due to breast cancer that is 0.38 that of the rate of women diagnosed with infiltrating duct carcinoma (95% confidence interval 0.34-0.42). We conclude that histologic type is important to consider in the prognosis and treatment of women diagnosed with breast cancer.

Antitrypsin and chronic obstructive pulmonary disease among Japanese-American men.

A total of 161 patients with chronic obstructive pulmonary disease (COPD) plus 100 control subjects (identified during a study of heart disease in 6,860 Japanese-American men aged 52 to 75 years who were residing in Hawaii) were analyzed for phenotype in search of the antitrypsin gene Z, which has been shown to be associated with pulmonary emphysema in other racial groups. No carriers of the Z gene were found, and the question of whether the rarity or absence of this gene relates to a low frequency of COPD among Japanese-Americans is reviewed.

Usefulness of community surveillance for the ascertainment of coronary heart disease and stroke.

In a prospective study of coronary heart disease (CHD) and stroke in Honolulu Japanese men, two methods of case ascertainment were used. The first consisted of cyclic re-examination of the cohort, and the second was based on periodic review of hospital discharge rosters, death certificates, and obituary columns (community surveillance). When a suspected case of CHD or stroke was located by either method, pertinent medical records were sought to verify it. Re-examination resulted in more complete ascertainment of CHD because it included silent myocardial infarction and angina pectoris. Community surveillance ascertained 83 per cent of all myocardial infarctions and CHD deaths combined; it was cheaper to operate and gave estimates of disease experience both in examined and unexamined men. In the first two years of this study, CHD incidence was 12 per cent lower in the examined men than in the total community.