Rita Schinnar

Weight Gain in the First Week of Life and Overweight in Adulthood A Cohort Study of European American Subjects Fed Infant Formula

Background—Successful prevention of obesity and related cardiovascular risk factors requires a clear understanding of its determinants over the life course. Rapid infancy weight gain is associated with childhood obesity, whereas low infancy weight is associated with coronary heart disease. Our aim was to identify during which periods in infancy weight gain is associated with adult obesity. Methods and Results—A cohort of European American formula-fed subjects, measured on 7 occasions during infancy as part of several infant formula studies, were contacted at age 20 to 32 years, when they reported usual adult weight and height. A life-course plot was used to identify critical periods of weight gain associated with adulthood overweight (body mass index ≥25 kg/m2). These associations were tested with logistic regressions. Data were available for 653 subjects (72% of eligible subjects). Approximately 32% of them were overweight adults. The period between birth and age 8 days was identified as potentially critical. After adjustment for important confounding factors, weight gain during the first week of life was associated with adulthood overweight status (OR for each 100-g increase 1.28, 95% CI 1.08 to 1.52), as was weight gain during the first 112 days of life (OR 1.04, 95% CI 1.01 to 1.08). Similar results were obtained after standardization with z scores from a reference population. Conclusions—In formula-fed infants, weight gain during the first week of life may be a critical determinant for the development of obesity several decades later. These results contribute to the understanding of chronic disease programming and suggest new approaches to obesity prevention.

Association between asthma mortality and isoproterenol aerosols: A review

Abstract Alternative hypotheses explaining a worldwide epidemic of asthma deaths during the 1960s are reviewed and their comparative strengths are evaluated, not only according to how they fit the experimental, clinical, and pharmacologic evidence available, but also according to how consistently they explain both the international variations and the secular changes that were observed. Using data from six countries during 1962 through 1974, a multivariate regression analysis is applied to test hypotheses about the average relation of sales of aerosols containing sympathomimetics to the mortality attributed to asthma. Results point to an association between mortality and the per capita sales of a particularly strong dose preparation of isoproterenol aerosol in conjunction with misuse of the drug by patients in the period when the aerosols were first introduced.

A retrospective case-control study of the use of hormone-related supplements and association with breast cancer.

Hormone‐related supplements (HRS), many of which contain phytoestrogens, are widely used to manage menopausal symptoms, yet their relationship with breast cancer risk has generally not been evaluated. We evaluated whether use of HRS was associated with breast cancer risk, using a population‐based case–control study in 3 counties of the Philadelphia metropolitan area consisting of 949 breast cancer cases and 1,524 controls. Use of HRS varied significantly by race, with African American women being more likely than European American women to use any herbal preparation (19.2% vs. 14.7%, p = 0.003) as well as specific preparations including black cohosh (5.4% vs. 2.0%, p = 0.003), ginseng (12.5% vs. 7.9%, p < 0.001) and red clover (4.7% vs. 0.6%, p < 0.001). Use of black cohosh had a significant breast cancer protective effect (adjusted odds ratio 0.39, 95% CI: 0.22–0.70). This association was similar among women who reported use of either black cohosh or Remifemin (an herbal preparation derived from black cohosh; adjusted odds ratio 0.47, 95% CI: 0.27–0.82). The literature reports that black cohosh may be effective in treating menopausal symptoms, and has antiestrogenic, antiproliferative and antioxidant properties. Additional confirmatory studies are required to determine whether black cohosh could be used to prevent breast cancer.

Cancer incidence in The Health Improvement Network.

The utility of electronic medical record databases for clinical research relies on the validity and completeness of the recorded medical diagnoses. This study assessed whether the recorded incidence of cancer among patients in The Health Improvement Network (THIN) database is comparable to that expected in the UK based on national cancer registry data.

Validity of The Health Improvement Network (THIN) for epidemiologic studies of hepatitis C virus infection.

Before using computerized databases to study hepatitis C virus (HCV) epidemiology, the validity of the diagnosis must be assessed. We determined the accuracy of HCV diagnostic codes within The Health Improvement Network (THIN), an electronic database containing medical record data from general medical practices in the United Kingdom.

Breast silicone implants and risk of systemic lupus erythematosus

The uncertain safety of breast implants has been a major controversy of late, both in the lay press and in the scientific literature. A case-control study had been performed in the Philadelphia metropolitan area during 1985-1987 to investigate potential risk factors for systemic lupus erythematosus (SLE). A total of 219 eligible cases who met the American Rheumatism Association criteria for SLE were identified from the medical practices of cooperating rheumatologists in the area; 195 (89%) of these were enrolled in the study. Friends of the cases, matched to the cases on sex and age (+/- 5 years) served as controls. For the current investigation, conducted during June 1992 through September 1992, we attempted to re-contact each of these individuals. Using a short telephone interview, we asked each subject to provide information on any surgery that they may have had prior to the index date, i.e. the year of diagnosis of SLE in the cases and the same year for the age-matched friend controls. Specific questions were asked about plastic surgery in general and breast implants in particular. 148 (75.9%) of the 195 SLE cases being sought and 111 (77.6%) of the 143 controls being sought agreed to be re-interviewed for this study. Only 1 (0.8%) out of 133 female SLE cases reported having had a breast implant, 8 years prior to the diagnosis of SLE. This compared to 0 out of the 100 female friend controls (Fisher exact one-tailed p-value = 0.57).(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of Raloxifene or Tamoxifen Use on Endometrial Cancer Risk: A Population-Based Case-Control Study

PURPOSE Raloxifene reduces breast cancer risk in women with osteoporosis, and both tamoxifen and raloxifene prevent breast cancer in high-risk women. However, in vitro, raloxifene does not share the pro-estrogenic effects of tamoxifen on the endometrium. Randomized trials of these agents have provided limited information about endometrial cancer risk in the general population. We sought to compare endometrial cancer risks associated with raloxifene, tamoxifen, and nonusers of a selective estrogen receptor modulator (SERM) in the general population and characterize the endometrial tumors occurring in these groups. METHODS We performed a case-control study of white and African American women age 50 to 79 years in the Philadelphia area. Patients were diagnosed with endometrial cancer between July 1999 and June 2002. Controls were identified through random-digit dialing. RESULTS We analyzed 547 cases and 1,410 controls. Among cases, 3.3% had taken raloxifene; 6.2% had taken tamoxifen. Among controls, 6.6% had taken raloxifene; 2.4% had taken tamoxifen. After adjustment for other risk factors, the odds of endometrial cancer among raloxifene users was 50% that of nonusers (odds ratio [OR] = 0.50; 95% CI, 0.29 to 0.85), whereas tamoxifen users had three times the odds of developing endometrial cancer compared with raloxifene users (OR = 3.0; 95% CI, 1.3 to 6.9). Endometrial tumors in raloxifene users had a more favorable histologic profile and were predominantly International Federation of Gynecology and Obstetrics stage I and low grade. CONCLUSION Raloxifene users had significantly lower odds of endometrial cancer compared with both tamoxifen users and SERM nonusers, suggesting a role for raloxifene in endometrial cancer prevention and individualization of SERM therapy.

Randomized clinical trial of a customized electronic alert requiring an affirmative response compared to a control group receiving a commercial passive CPOE alert: NSAID—warfarin co-prescribing as a test case

BACKGROUND Studies that have looked at the effectiveness of computerized decision support systems to prevent drug-drug interactions have reported modest results because of low response by the providers to the automated alerts. OBJECTIVE To evaluate, within an inpatient computerized physician order entry (CPOE) system, the incremental effectiveness of an alert that required a response from the provider, intended as a stronger intervention to prevent concurrent orders of warfarin and non-steroidal anti-inflammatory drugs (NSAIDs). DESIGN Randomized clinical trial of 1963 clinicians assigned to either an intervention group receiving a customized electronic alert requiring affirmative response or a control group receiving a commercially available passive alert as part of the CPOE. The study duration was 2 August 2006 to 15 December 2007. MEASUREMENTS Alert adherence was compared between study groups. RESULTS The proportion of desired ordering responses (ie, not reordering the alert-triggering drug after firing) was lower in the intervention group (114/464 (25%) customized alerts issued) than in the control group (154/560 (28%) passive alerts firing). The adjusted OR of inappropriate ordering was 1.22 (95% CI 0.69 to 2.16). CONCLUSION A customized CPOE alert that required a provider response had no effect in reducing concomitant prescribing of NSAIDs and warfarin beyond that of the commercially available passive alert received by the control group. New CPOE alerts cannot be assumed to be effective in improving prescribing, and need evaluation.

Pairwise Combinations of Estrogen Metabolism Genotypes in Postmenopausal Breast Cancer Etiology

Estrogen exposures have been associated with breast cancer risk, and genes involved in estrogen metabolism have been reported to mediate that risk. Our goal was to better understand whether combinations of candidate estrogen metabolism genotypes are associated with breast cancer etiology. A population-based case-control study in three counties of the Philadelphia Metropolitan area was undertaken. We evaluated seven main effects and 21 first-order interactions in African Americans and European Americans for genotypes at COMT, CYP1A1, CYP1A2, CYP1B1, CYP3A4, SULT1A1, and SULT1E1 in 878 breast cancer cases and 1,409 matched random digit–dialed controls. In European Americans, we observed main effect associations of genotypes containing any CYP1A1*2C (odds ratio, 1.71; 95% confidence interval, 1.09-2.67) and breast cancer. No significant main effects were observed in African Americans. Three significant first-order interactions were observed. In European Americans, interactions between SULT1A1*2 and CYP1A1*2C genotypes (Pinteraction < 0.001) and between SULT1E1 and CYP1A2*1F genotypes were observed (Pinteraction = 0.006). In African Americans, an interaction between SULT1A1*2 and CYP1B1*4 was observed (Pinteraction = 0.041). We applied the false-positive report probability approach, which suggested that these associations were noteworthy; however, we cannot rule out the possibility that chance led to these associations. Pending future confirmation of these results, our data suggest that breast cancer etiology in both European American and African American postmenopausal women may involve the interaction of a gene responsible for the generation of catecholestrogens with a gene involved in estrogen and catecholestrogen sulfation. (Cancer Epidemiol Biomarkers Prev 2007;16(3):444–50)

Statin Therapy and Risk of Acute Memory Impairment

IMPORTANCE Reports on the association between statins and memory impairment are inconsistent. OBJECTIVE To assess whether statin users show acute decline in memory compared with nonusers and with users of nonstatin lipid-lowering drugs (LLDs). DESIGN, SETTING, AND PARTICIPANTS Using The Health Improvement Network database during January 13, 1987, through December 16, 2013, a retrospective cohort study compared 482,543 statin users with 2 control groups: 482,543 matched nonusers of any LLDs and all 26,484 users of nonstatin LLDs. A case-crossover study of 68,028 patients with incident acute memory loss evaluated exposure to statins during the period immediately before the outcome vs 3 earlier periods. Analysis was conducted from July 7, 2013, through January 15, 2015. RESULTS When compared with matched nonusers of any LLDs (using odds ratio [95% CI]), a strong association was present between first exposure to statins and incident acute memory loss diagnosed within 30 days immediately following exposure (fully adjusted, 4.40; 3.01-6.41). This association was not reproduced in the comparison of statins vs nonstatin LLDs (fully adjusted, 1.03; 0.63-1.66) but was also present when comparing nonstatin LLDs with matched nonuser controls (adjusted, 3.60; 1.34-9.70). The case-crossover analysis showed little association. CONCLUSIONS AND RELEVANCE Both statin and nonstatin LLDs were strongly associated with acute memory loss in the first 30 days following exposure in users compared with nonusers but not when compared with each other. Thus, either all LLDs cause acute memory loss regardless of drug class or the association is the result of detection bias rather than a causal association.