Matthew W. Gillman

Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement

IMPORTANCE Colorectal cancer is the second leading cause of cancer death in the United States. In 2016, an estimated 134,000 persons will be diagnosed with the disease, and about 49,000 will die from it. Colorectal cancer is most frequently diagnosed among adults aged 65 to 74 years; the median age at death from colorectal cancer is 68 years. OBJECTIVE To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on screening for colorectal cancer. EVIDENCE REVIEW The USPSTF reviewed the evidence on the effectiveness of screening with colonoscopy, flexible sigmoidoscopy, computed tomography colonography, the guaiac-based fecal occult blood test, the fecal immunochemical test, the multitargeted stool DNA test, and the methylated SEPT9 DNA test in reducing the incidence of and mortality from colorectal cancer or all-cause mortality; the harms of these screening tests; and the test performance characteristics of these tests for detecting adenomatous polyps, advanced adenomas based on size, or both, as well as colorectal cancer. The USPSTF also commissioned a comparative modeling study to provide information on optimal starting and stopping ages and screening intervals across the different available screening methods. FINDINGS The USPSTF concludes with high certainty that screening for colorectal cancer in average-risk, asymptomatic adults aged 50 to 75 years is of substantial net benefit. Multiple screening strategies are available to choose from, with different levels of evidence to support their effectiveness, as well as unique advantages and limitations, although there are no empirical data to demonstrate that any of the reviewed strategies provide a greater net benefit. Screening for colorectal cancer is a substantially underused preventive health strategy in the United States. CONCLUSIONS AND RECOMMENDATIONS The USPSTF recommends screening for colorectal cancer starting at age 50 years and continuing until age 75 years (A recommendation). The decision to screen for colorectal cancer in adults aged 76 to 85 years should be an individual one, taking into account the patients overall health and prior screening history (C recommendation).

A Nearly Continuous Measure of Birth Weight for Gestational Age Using a United States National Reference

BackgroundFully understanding the determinants and sequelae of fetal growth requires a continuous measure of birth weight adjusted for gestational age. Published United States reference data, however, provide estimates only of the median and lowest and highest 5th and 10th percentiles for birth weight at each gestational age. The purpose of our analysis was to create more continuous reference measures of birth weight for gestational age for use in epidemiologic analyses.MethodsWe used data from the most recent nationwide United States Natality datasets to generate multiple reference percentiles of birth weight at each completed week of gestation from 22 through 44 weeks. Gestational age was determined from last menstrual period. We analyzed data from 6,690,717 singleton infants with recorded birth weight and sex born to United States resident mothers in 1999 and 2000.ResultsBirth weight rose with greater gestational age, with increasing slopes during the third trimester and a leveling off beyond 40 weeks. Boys had higher birth weights than girls, later born children higher weights than firstborns, and infants born to non-Hispanic white mothers higher birth weights than those born to non-Hispanic black mothers. These results correspond well with previously published estimates reporting limited percentiles.ConclusionsOur method provides comprehensive reference values of birth weight at 22 through 44 completed weeks of gestation, derived from broadly based nationwide data. Other approaches require assumptions of normality or of a functional relationship between gestational age and birth weight, which may not be appropriate. These data should prove useful for researchers investigating the predictors and outcomes of altered fetal growth.

Activity, Dietary Intake, and Weight Changes in a Longitudinal Study of Preadolescent and Adolescent Boys and Girls

Objective. To examine the role of physical activity, inactivity, and dietary patterns on annual weight changes among preadolescents and adolescents, taking growth and development into account. Study Design. We studied a cohort of 6149 girls and 4620 boys from all over the United States who were 9 to 14 years old in 1996. All returned questionnaires in the fall of 1996 and a year later in 1997. Each child provided his or her current height and weight and a detailed assessment of typical past-year dietary intakes, physical activities, and recreational inactivities (TV, videos/VCR, and video/computer games). Methods. Our hypotheses were that physical activity and dietary fiber intake are negatively correlated with annual changes in adiposity and that recreational inactivity (TV/videos/games), caloric intake, and dietary fat intake are positively correlated with annual changes in adiposity. Separately for boys and girls, we performed regression analysis of 1-year change in body mass index (BMI; kg/m2). All hypothesized factors were in the model simultaneously with several adjustment factors. Results. Larger increases in BMI from 1996 to 1997 were among girls who reported higher caloric intakes (.0061 ± .0026 kg/m2 per 100 kcal/day; β ± standard error), less physical activity (−.0284 ± .0142 kg/m2/hour/day) and more time with TV/videos/games (.0372 ± .0106 kg/m2/hour/day) during the year between the 2 BMI assessments. Larger BMI increases were among boys who reported more time with TV/videos/games (.0384 ± .0101) during the year. For both boys and girls, a larger rise in caloric intake from 1996 to 1997 predicted larger BMI increases (girls: .0059 ± .0027 kg/m2 per increase of 100 kcal/day; boys: .0082 ± .0030). No significant associations were noted for energy-adjusted dietary fat or fiber. Conclusions. For both boys and girls, a 1-year increase in BMI was larger in those who reported more time with TV/videos/games during the year between the 2 BMI measurements, and in those who reported that their caloric intakes increased more from 1 year to the next. Larger year-to-year increases in BMI were also seen among girls who reported higher caloric intakes and less physical activity during the year between the 2 BMI measurements. Although the magnitudes of these estimated effects were small, their cumulative effects, year after year during adolescence, would produce substantial gains in body weight. Strategies to prevent excessive caloric intakes, to decrease time with TV/videos/games, and to increase physical activity would be promising as a means to prevent obesity.

Influence of heart rate on mortality among persons with hypertension: the Framingham Study.

Previous studies have shown positive associations between heart rate and both all-cause and cardiovascular mortality. These relationships, however, have not been investigated in persons with hypertension. Using 36-year follow-up data from the Framingham Study, we evaluated from 4530 subjects, aged 35 to 74, whose blood pressures were > or = 140 mm Hg systolic or > or = 90 mm Hg diastolic and who were not treated with antihypertensive medication. We used pooled logistic regression to calculate biennial mortality rates. Odds ratios and 95% confidence intervals for each increment in heart rate of 40 beats/min, adjusted for age and systolic blood pressure level, were: for all-cause mortality, 2.18 (1.68, 2.83) for men and 2.14 (1.59, 2.88) for women; and for cardiovascular mortality, 1.68 (1.19, 2.37) for men and 1.70 (1.08, 2.67) for women. Exclusion of outcomes in the first 2 or 4 years after measurement of heart rate did not materially change the results, which suggests that rapid heart is not merely an indicator of preexisting illness. Therefore heart rate may be an independent risk factor for cardiovascular death in persons with hypertension.

Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility

Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10−8 in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10−6 overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27–positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.

Maternal smoking during pregnancy and child overweight: systematic review and meta-analysis

Objective:Perform a systematic review of studies reporting on the association between maternal prenatal cigarette smoking and child overweight.Design:Meta-analysis of observational studies.Data sources:Medline search and review of reference lists among studies published through June 2006.Review methods:Included studies reported an association between maternal smoking during pregnancy and risk of overweight among children at least 2 years of age. We did not include in the meta-analysis studies that provided only a continuous measure of adiposity, although those studies are discussed separately.Results:Based on results of 84 563 children reported in 14 observational studies, children whose mothers smoked during pregnancy were at elevated risk for overweight (pooled adjusted odds ratio (OR) 1.50, 95% CI: 1.36, 1.65) at ages 3–33 years, compared with children whose mothers did not smoke during pregnancy. The pooled estimate from unadjusted odds ratios (OR 1.52, 95% CI: 1.36, 1.69) was similar to the adjusted estimate, suggesting that sociodemographic and behavioral differences between smokers and nonsmokers did not explain the observed association. Although we observed evidence for publication bias, simulating a symmetric set of studies yielded a similar estimate (OR 1.40, 95% CI: 1.26, 1.55).Conclusions:Prenatal smoking exposure appears to increase rates of overweight in childhood. In parts of the world undergoing the epidemiologic transition, the continuing increase in smoking among young women could contribute to spiraling increases in rates of obesity-related health outcomes in the 21st century.

Maternal Fish Consumption, Hair Mercury, and Infant Cognition in a U.S. Cohort.

Fish and other seafood may contain organic mercury but also beneficial nutrients such as n-3 polyunsaturated fatty acids. We endeavored to study whether maternal fish consumption during pregnancy harms or benefits fetal brain development. We examined associations of maternal fish intake during pregnancy and maternal hair mercury at delivery with infant cognition among 135 mother–infant pairs in Project Viva, a prospective U.S. pregnancy and child cohort study. We assessed infant cognition by the percent novelty preference on visual recognition memory (VRM) testing at 6 months of age. Mothers consumed an average of 1.2 fish servings per week during the second trimester. Mean maternal hair mercury was 0.55 ppm, with 10% of samples > 1.2 ppm. Mean VRM score was 59.8 (range, 10.9–92.5). After adjusting for participant characteristics using linear regression, higher fish intake was associated with higher infant cognition. This association strengthened after adjustment for hair mercury level: For each additional weekly fish serving, offspring VRM score was 4.0 points higher [95% confidence interval (CI), 1.3 to 6.7]. However, an increase of 1 ppm in mercury was associated with a decrement in VRM score of 7.5 (95% CI, –13.7 to –1.2) points. VRM scores were highest among infants of women who consumed > 2 weekly fish servings but had mercury levels ≤1.2 ppm. Higher fish consumption in pregnancy was associated with better infant cognition, but higher mercury levels were associated with lower cognition. Women should continue to eat fish during pregnancy but choose varieties with lower mercury contamination.

Sociodemographic predictors of antenatal and postpartum depressive symptoms among women in a medical group practice

Objective: Data are scarce regarding the sociodemographic predictors of antenatal and postpartum depression. This study investigated whether race/ethnicity, age, finances, and partnership status were associated with antenatal and postpartum depressive symptoms. Setting: 1662 participants in Project Viva, a US cohort study. Design: Mothers indicated mid-pregnancy and six month postpartum depressive symptoms on the Edinburgh postpartum depression scale (EPDS). Associations of sociodemographic factors with odds of scoring >12 on the EPDS were estimated. Main results: The prevalence of depressive symptoms was 9% at mid-pregnancy and 8% postpartum. Black and Hispanic mothers had a higher prevalence of depressive symptoms compared with non-Hispanic white mothers. These associations were explained by lower income, financial hardship, and higher incidence of poor pregnancy outcome among minority women. Young maternal age was associated with greater risk of antenatal and postpartum depressive symptoms, largely attributable to the prevalence of financial hardship, unwanted pregnancy, and lack of a partner. The strongest risk factor for antenatal depressive symptoms was a history of depression (OR = 4.07; 95% CI 3.76, 4.40), and the strongest risk for postpartum depressive symptoms was depressive symptoms during pregnancy (6.78; 4.07, 11.31) or a history of depression before pregnancy (3.82; 2.31, 6.31). Conclusions: Financial hardship and unwanted pregnancy are associated with antenatal and postpartum depressive symptoms. Women with a history of depression and those with poor pregnancy outcomes are especially vulnerable to depressive symptoms during the childbearing year. Once these factors are taken in account, minority mothers have the same risk of antenatal and postpartum depressive symptoms as white mothers.

Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region

Ulcerative colitis is a common form of inflammatory bowel disease with a complex etiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome-wide association scan for ulcerative colitis in 2,361 cases and 5,417 controls. Loci showing evidence of association at P < 1 × 10−5 were followed up by genotyping in an independent set of 2,321 cases and 4,818 controls. We find genome-wide significant evidence of association at three new loci, each containing at least one biologically relevant candidate gene, on chromosomes 20q13 (HNF4A; P = 3.2 × 10−17), 16q22 (CDH1 and CDH3; P = 2.8 × 10−8) and 7q31 (LAMB1; P = 3.0 × 10−8). Of note, CDH1 has recently been associated with susceptibility to colorectal cancer, an established complication of longstanding ulcerative colitis. The new associations suggest that changes in the integrity of the intestinal epithelial barrier may contribute to the pathogenesis of ulcerative colitis.

Longitudinal study of skipping breakfast and weight change in adolescents

BACKGROUND: Several cross-sectional studies reported that heavier children eat breakfast less often. However, no longitudinal studies have addressed whether skipping breakfast leads to excessive weight gain.OBJECTIVE: To investigate whether skipping breakfast was prospectively associated with changes in body fatness.METHODS: A cohort of >14 000 boys and girls from all over the US, 9- to 14-y-old in 1996, returned annual mailed questionnaires (1996–1999) for the Growing Up Today Study. We analyzed change in body mass index (BMI; kg/m2) over three 1-y periods among children who reported breakfast frequency.RESULTS: Children who reported that they never eat breakfast had lower energy intakes than those who eat breakfast nearly every day. Children who were more physically active reported higher energy intakes, as did those who reported more time watching television/videos and playing videogames. Like previous studies, skipping breakfast was associated with overweight, cross-sectionally. However, overweight children who never ate breakfast lost BMI over the following year compared to overweight children who ate breakfast nearly every day (boys: −0.66 kg/m2 (s.e.=0.22); girls: −0.50 kg/m2 (s.e.=0.14)). But normal weight children who never ate breakfast gained weight relative to peers who ate breakfast nearly every day (boys: +0.21 kg/m2 (s.e.=0.13); girls: +0.08 kg/m2 (s.e.=0.05)). Breakfast frequency was positively correlated with self-reported quality of schoolwork.CONCLUSIONS: Overweight children who never eat breakfast may lose body fat, but normal weight children do not. Since numerous studies link skipping breakfast to poorer academics, children should be encouraged to eat breakfast.