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.

Risk factors for intrapair birth weight discordance in twins.

OBJECTIVES: To determine the risk factors for birth weight discordance in twins. METHODS: We used the United States (1995-97) Matched Multiple Birth File (n = 294 568) to assess the association between birth weight discordance and maternal sociodemographic, pregnancy and infant characteristics. RESULTS: Eighty-four per cent of the twins were 0-19% discordant, 11.1% were 20-29% discordant, 3.4% were 30-39% discordant, and 1.8% were > or = 2 40% discordant. The risk factors for birth weight discordance for same-sex twins were eclampsia (odds ratio (OR) 1.39,95% confidence interval (CI) 1.20, 1.61), pre-eclampsia (OR 1.31, 95% CI 1.24, 1.38), pre-existing hypertension (OR 1.32, 95% CI 1.12, 1.56), diabetes (OR 1.13, 95% CI 1.04, 1.24) and certain congenital anomalies. For opposite-sex twins, the risk factors for birth weight discordance were pre-eclampsia (OR 1.17, 95% CI 1.09, 1.27), pre-existing hypertension (OR 1.59,95% CI 1.32, 1.91), and certain congenital anomalies. Also, smoking and increased maternal age were associated with birth weight discordance in both same-sex and opposite-sex twins. CONCLUSIONS: Maternal hypertensive disorders, smoking and delayed childbearing were associated with intrapair birth weight discordance. The mechanisms of these associations deserve further investigation.

Level of aggregation for optimal epidemiological analysis: the case of time to surgery and unnecessary removal of the normal appendix.

STUDY OBJECTIVE: To illustrate the concept of "individualised fallacy", the result of improper interpretation and inference about aggregate level associations on the basis of associations at the individual level, in epidemiology. DESIGN: Cohort study. SETTING: Canadian province of Ontario. PATIENTS: All patients who underwent primary appendicectomy in 175 Ontario hospitals from 1989 to 1992. The association between rate of normal appendix removal and time to surgery was analysed at two levels: (1) at individual patient level, in which, for each patient, the exact number of days to surgery was derived, and (2) at hospital level, in which hospital specific proportions of time to surgery was calculated. MAIN RESULTS: Measured at individual level, compared with patients who had an operation on the same day of admission, the odds ratio was 2.41 (95% confidence intervals 2.28, 2.56) for patients who had an operation > 1 day after admission. Measured at hospital level, each 10% increase in the proportion of patients who had an operation > 1 day after admission resulted in a 15% reduction in the odds of normal appendix removal (odds ratio 0.85, 95% confidence intervals 0.82, 0.88) CONCLUSIONS: In this case study, hospital level measure correctly predicted a reduction in the rate of normal appendix removal by delaying surgery, whereas individual level measure biased the direction of the relation to the opposite. This example illustrates that bias in across level inference can occur either at individual or ecological level. The preferred level of analysis is the one that minimises confounding; often, it must be selected on the basis of a priori knowledge of the subject area.

Ethnic and racial differences in prostate cancer incidence and mortality.

Prostate cancer (CaP) incidence and mortality vary strikingly among ethnic, racial, and national groups. There is evidence that genetic, environmental, and social factors jointly-and often in combination-contribute to the observed differences in various populations. Noteworthy is the high rate of both CaP incidence and mortality among African Americans. Changes in the epidemiology of CaP since the advent of prostate specific antigen testing suggest that improved access to screening and treatment may serve to reduce somewhat the differences between the white and African-American populations. However, because the causes of these differences are likely to be multifactorial, a variety of strategies addressing the range of causes will be necessary to reduce the excess African-American mortality from this disease.

Impact of geographic proximity to cardiac revascularization services on service utilization.

BACKGROUND: In a highly competitive health care environment, even microgeographic differences in availability of tertiary services might affect access to care. OBJECTIVES: To study the impact of (1) geographic distance from patient's residence to cardiac revascularization services and (2) the availability of cardiac revascularization services at the hospital nearest the patient's residence on utilization of these services in a geographically small, densely populated area. METHODS: Historical cohort study of 55,659 New Jersey residents hospitalized between 1992 and 1996 with primary diagnosis of acute myocardial infarction (AMI). MAIN STUDY OUTCOMES: Use of percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft surgery (CABG) within 90 days of initial hospitalization for AMI and in-hospital mortality. Distance from patient's residence to nearest hospital with cardiac revascularization services (PTCA and CABG) was a straight-line distance in miles, categorized as 0 to <2, 2 to <5, 5 to <10, 10 to <15, 15 to <20, 20 to <25, > or =25 miles. Adjusted odds of PTCA or CABG use at each distance category were compared with odds at > or =25 miles. RESULTS: A strong linear decline in adjusted odds ratios for PTCA use was found with increasing distance of this service from the patient's residence (p <0.05). Adjusted odds of PTCA use were 2.4, 2.1, 1.8, 1.5, 1.3, and 1.0 times higher for each increasing distance category in comparison with > or =25 for patients aged <65 and 3.1, 2.7, 2.2, 1.9, 1.7, and 1.1 for patients aged > or =65. Use of CABG was also higher for patients residing closer to cardiac revascularization services. The availability of these services at the hospital nearest to the patient's residence also increased utilization. In-hospital mortality was not associated with distance from services. CONCLUSION: Even across a relatively small geographic area, shorter distance to services and availability of services at the nearest hospital were strongly related to increased utilization of cardiac revascularization services.

Impact of availability of hospital-based invasive cardiac services on racial differences in the use of these services.

BACKGROUND: Reports indicate that black patients are less likely than white patients to receive invasive cardiac services after hospitalization for acute myocardial infarction (AMI). There is still uncertainty as to why racial differences exist and how they affect patient outcomes. This is the first study to focus on the availability of invasive cardiac services and racial differences in procedure use. Study objectives were to (1) document whether racial differences existed in the use of invasive cardiac procedures, (2) study whether these racial differences were related to availability of hospital-based invasive cardiac services at first admission for AMI, and (3) determine whether there were racial differences in long-term mortality rates. METHODS: A historical cohort study was conducted with discharge records from all acute care hospitals in New Jersey for 1993 linked to death certificate records for 1993 and 1994. There were 13,690 black and white New Jersey residents hospitalized with primary diagnosis of AMI. Use of cardiac catheterization within 90 days, revascularization within 90 days (percutaneous transluminal coronary angioplasty [PTCA] or coronary artery bypass graft surgery [CABG]), and death within 1 year after admission for AMI were the main outcome measures. Patterns for PTCA and CABG as separate outcomes were also studied. Hospital-based cardiac services available were described as no invasive cardiac services, catheterization only, or PTCA/CABG. To account for payer status and comorbidity differences, patients 65 years and older with Medicare coverage were analyzed separately from those younger than 65 years. RESULTS: Black patients aged 65 and older were generally less likely to receive catheterization and revascularization than white patients, regardless of facilities available at first admission. For patients younger than 65 years, the greatest differences between black and white patients in catheterization and PTCA/CABG use within 90 days after AMI occurred when no hospital-based invasive cardiac services were available. However, use of invasive cardiac procedures within 90 days after AMI was substantially increased if the first hospital offered catheterization only or PTCA/CABG services, among all patients, especially among blacks younger than age 65. No significant racial differences or interactions with available services were found in 1-year mortality rates. CONCLUSIONS: Availability of invasive cardiac services at first hospitalization for AMI was associated with increased procedure use for both races. However, use of invasive cardiac procedures was generally lower for black patients than for white patients, regardless of services available. Long-term mortality rates after hospitalization for AMI did not differ between blacks and whites.

No difference in iron status between children with low and moderate lead exposure.

We compared the iron status between children 11 to 33 months old with confirmed blood lead levels of 20 to 44 microg/dL and demographically similar children with blood lead levels of <10 microg/dL. There were no differences. Laboratory investigation or empirical treatment for iron deficiency is not justified on the basis of moderately elevated blood lead levels alone.

Placenta previa: preponderance of male sex at birth.

To determine the relation between placenta previa and male sex at birth, the authors conducted two types of analysis: 1) a historical cohort analysis of singleton live births in New Jersey hospitals during 1989-1992 (N = 447,963); and 2) a meta-analysis of previously published studies on the subject. For the cohort analysis, subject mother-infant dyads were identified from linked birth certificate and maternal and infant hospital claims data. The infant's sex for mothers with an International Classification of Diseases, Ninth Revision, Clinical Modification, code of 641.0-641.1 for placenta previa (n = 2,685) was compared with infant's sex for mothers without placenta previa (n = 445,270). For the meta-analysis, seven published articles were located and summary effects were calculated using both fixed-effect and random-effects models. In the present cohort study, the male:female ratio at birth was significantly higher in women with placenta previa (1.19) than in those without placenta previa (1.05) (p<0.001). The association of placenta previa with male sex persisted when the analysis was either stratified or adjusted for the effects of maternal age, maternal parity, maternal smoking during the index pregnancy, race/ethnicity, the infant's gestational age, and the infant's birth weight. The meta-analytic results from the fixed-effect and random-effects models showed a 14% excess of placenta previa when women were carrying a viable male fetus as compared with a viable female fetus during pregnancy. The results were the same regardless of whether the present cohort study was included in the meta-analysis. In conclusion, the evidence obtained from these analyses strongly argues for an association between placenta previa and male sex at birth. The mechanism for this association remains to be determined.

Childhood lead screening knowledge and practice. Results of a New Jersey physician survey.

CONTEXT: As the nation moves toward targeted childhood lead screening, CDC continues to recommend universal screening in states with no childhood lead poisoning prevalence data. OBJECTIVE: The study was conducted, prior to the new universal screening state law, to determine physician screening practices and their consistency with key CDC recommendations as a basis for future education activities. DESIGN/SETTING/PARTICIPANTS: A statewide cross-sectional self-administered multiple choice survey of 541 randomly selected New Jersey pediatricians and family practitioners. OUTCOME MEASURES: Risk assessment, screening and case management practices and their consistency with CDC recommendations. RESULTS: We obtained 333 usable responses (69.4%). Most respondents reported confirming blood lead level, initiating case management, and identifying medical emergencies at blood lead levels lower than recommended by CDC. More than half reported not assessing the risk of the majority of their patients. At least one third were not screening infants, children between 1 and 2 years, or children between 2 and 6 years of age. Physicians who assessed risk tended to screen high-risk children in all age groups. Only 42% of pediatricians and 24% of family practitioners said they screened the majority of the children in their practice by age 2 years. About 60% of all respondents reported not providing lead exposure education to half their patients. CONCLUSIONS: Passing a universal screening law, as New Jersey has done, is one way to obtain baseline childhood lead poisoning prevalence data. Private practice-targeted physician education led by preventive medicine specialists may also be helpful.

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.

Vitamin A and birth defects.

OBJECTIVE: Our objective was to determine whether moderate doses of vitamin A are teratogenic. STUDY DESIGN: This was a geographically based case-control study. Women whose pregnancies produced offspring with neural tube defects (n = 548) or major malformations other than neural tube defects (n = 387) and normal control subjects (n = 573) were interviewed to determine periconceptional vitamin A supplement exposure levels. RESULTS: The proportion of women consuming doses of vitamin A between 8000 and 25,000 IU was no greater in the major malformations group or the group with neural tube defects than in the normal control group. For exposure from supplements and fortified cereals combined, women consuming >8000 and >10,000 IU daily had odds ratios for major malformations of 0.79 (95% confidence interval 0.40 to 1.53) and 0.73 (95% confidence interval 0.27 to 1.96), respectively, compared with women consuming <5000 IU. The results for neural tube defects were similar. For cranial neural crest defects the odds ratios were 0.76 (0.22 to 2.56) and 1.09 (0.24 to 4.98) for exposure to >8000 and >10,000 IU, respectively, versus exposure to <5000 IU. CONCLUSIONS: This study found no association between periconceptional vitamin A exposure at doses >8000 IU or >10,000 IU per day and malformations in general, cranial neural crest defects, or neural tube defects. If vitamin A is a teratogen, the minimum teratogenic dose appears to be well above the level consumed by most women during organogenesis.

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.

Sonographic assessment of endometrial pattern and thickness in patients treated with human menopausal gonadotropins.

OBJECTIVE: To analyze sonographically the endometrium in patients undergoing controlled ovarian stimulation with menotropins in order to determine the significance of endometrial pattern and thickness on pregnancy rate. DESIGN: This is a prospective, nonrandomized study comparing pregnancy rates in patients with hyperechoic homogeneous patterns with those in patients with isoechoic or hypoechoic trilaminar patterns. SETTING: Tertiary infertility center. PATIENTS: All patients receiving menotropin therapy at a tertiary infertility center. INTERVENTIONS: All patients received individualized dosing of hMG starting on cycle day 3. Transvaginal sonography was performed 15 hours before hCG administration and the endometrium was assessed. MAIN OUTCOME MEASURE: Occurrence of pregnancy as determined by serially rising beta-hCG titers and sonographic confirmation. RESULTS: During the study period, 175 patients were evaluated. Thirty-four (19%) patients had a homogeneous endometrium, whereas 141 (81%) patients had a trilaminar pattern. There was 1 pregnancy (2.9%) among women with a homogeneous endometrial pattern and 33 pregnancies (23%) among those with a trilaminar pattern. No significant differences were found in mean E2 level, follicle numbers, parity, and diagnosis between the two groups. CONCLUSION: In patients receiving menotropins, a homogeneous pattern is a bad prognostic sign, regardless of endometrial thickness.

Are obese women at higher risk for producing malformed offspring?

OBJECTIVE: Our purpose was to determine whether obese women and underweight women have an increased risk of birth defects in their offspring. STUDY DESIGN: A geographically based case-control study of women living in California and Illinois was performed. There were 499 mothers of offspring with neural tube defects, 337 mothers of offspring with other major birth defects, and 534 mothers of offspring without birth defects who participated. RESULTS: Compared with women of normal weight, women who were extremely obese before pregnancy (body mass index > or = 31 kg/m2) showed a significantly increased risk of having an infant with a neural tube defect (odds ratio 1.8, 95% confidence interval 1.1 to 3.0), especially spina bifida (odds ratio 2.6, 95% confidence interval 1.5 to 4.5), after adjustments for age, race, education, and family income. Obese women also had significantly increased risks (p < 0.05) of having an infant with other defects of the central nervous system, great vessel defects, ventral wall defects, or other intestinal defects. CONCLUSION: Our data suggest that offspring of obese women (but not underweight women) are at an increased risk of neural tube defects and several other malformations. If these findings are confirmed, further research will be necessary before it can be concluded that weight reduction before pregnancy will lower the risk of birth defects among obese women. Until then, obese women can address their risk of birth defects with the same measures that are recommended for all women, such as adequate daily intake of folic acid and alpha-fetoprotein screening to identify malformed fetuses.

Maternal vitamin levels during pregnancies producing infants with neural tube defects.

Women at very high risk for having a child with a neural tube defect (NTD) because they had previously delivered affected children significantly reduced their recurrence rate by taking folate supplements before conception. To clarify how these results might apply to a lower-risk general obstetric population, we measured folate, vitamin B12, and retinol levels in maternal serum drawn early in 89 pregnancies resulting in NTD offspring and 178 control pregnancies identified from the Finnish Registry of Congenital Malformations. In 86.5% of the subjects, specimens were collected within 8 weeks after neural tube closure. In the NTD case mothers the mean (+/- SD) levels were not significantly lower than in control mothers: folate, 4.13 +/- 2.36 versus 4.28 +/- 2.52 ng/ml; vitamin B12, 482.8 +/- 161.1 versus 520.3 +/- 191.9 pg/ml; and retinol, 51.2 +/- 17.0 versus 50.5 +/- 16.9 micrograms/dl. After adjustment for age of the specimen, gestational age at which the specimen was drawn, maternal age, and maternal employment status, the odds ratios for being a case mother were 1.00 (95% confidence interval (CI) 0.91 to 1.10) for folate, 1.05 (95% CI 0.92 to 1.19) for vitamin B12, and 0.99 (95% CI 0.88 to 1.10) for retinol. Excluding NTD cases with known or suspected causes unrelated to vitamins, restricting the analyses to interviewed subjects, and excluding subjects whose specimens were collected after 15 gestational weeks confirmed that NTD case and control vitamin levels did not differ significantly. This population-based investigation in a low rate area demonstrated no relationship between maternal serum folate, vitamin B12, or retinol levels during pregnancy and the risk of NTDs.

A review of some tumors of interest for demographic study in Hawaii.1974.

Because of its multiracial character, Hawaii presents a unique opportunity to carry out demographic investigations of the etiology of certain common cancers. Tumors with substantially different incidence rates among the major ethnic groups in the Islands, or between a given immigrant group and its country of origin, are of particular interest for such studies. Among the cancer sites meeting these criteria, nasopharynx, stomach, prostate, large bowel, liver, female breast, uterine corpus, ovary, bladder, and thyroid are particularly prominent.

Vitamins, folic acid and neural tube defects: comments on investigations in the United States.

No clear answer concerning whether multivitamin/folate supplementation prevents neural tube defects (NTDs) is provided by three studies in the United States. All these studies are occurrence in nature, no recurrence studies having been conducted. The Atlanta Birth Defects Study is subject to pronounced memory and recall biases, the length between event and interview being as long as 16 years. In a second study (Boston University), objections can be raised to certain aspects of the experimental design, and the claim that 22 per cent of women started vitamins sufficiently early after pregnancy diagnosis to influence NTD formation is suspicious. Our NICHD case control study of 541 women in California and Illinois revealed no evidence for multivitamins or folic acid preventing NTDs. U.S. public policy-makers face difficulties in applying results of recurrence or occurrence studies in high-risk areas to low-risk areas in the U.S.