Clinical events in a large prospective cohort of children with sickle cell disease in Nagpur, India: evidence against a milder clinical phenotype in India.

BACKGROUND: The clinical phenotype of sickle cell disease (SCD) has been reported to be milder in India than in the United States. The objective of this large single-center study was to examine the rate of complications to define the phenotype of SCD in India. METHODS: The rate of complications per 100 person-years in 833 pediatric SCD patients for 1954 person-years in Nagpur, India including those diagnosed on newborn screen (NBS) and those presenting later in childhood (non-NBS) was compared to those reported in the cooperative study of sickle cell disease (CSSCD). Event rates were also compared between patients belonging to scheduled castes (SCs), scheduled tribes (STs), and other backward classes (OBC). RESULTS: Comparison of CSSCD versus Nagpur NBS versus Nagpur non-NBS for rates of pain (32.4 vs. 85.2 vs. 62.4), severe anemia (7.1 vs. 27 vs. 6.6), stroke (0.7 vs. 0.8 vs. 1.4), splenic sequestration (3.4 vs. 6.7 vs. 1.6), acute chest syndrome (24.5 vs. 23.6 vs. 1.0), and meningitis (0.8 vs. 0 vs. 0.1) revealed more frequent complications in Nagpur compared to CSSCD. Comparison of ST, SC, and OBC for rates of pain (84.6 vs. 71.9 vs. 63.5), acute chest syndrome (3.6 vs. 2.8 vs. 2.2), severe anemia (5.4 vs. 9.5 vs. 11.4), stroke (1.2 vs. 0.4 vs. 0.3), splenic sequestration (0.6 vs. 2.4 vs. 1.9), and meningitis (0.8 vs. 0 vs. 0.1) revealed significantly more frequent complications among ST. CONCLUSIONS: SCD-related complications are more frequent in Indian children than that observed in CSSCD. Further study is indicated to define SCD phenotype in India.

Factors related to age at natural menopause: longitudinal analyses from SWAN.

Early age at the natural final menstrual period (FMP) or menopause has been associated with numerous health outcomes and might be a marker of future ill health. However, potentially modifiable factors affecting age at menopause have not been examined longitudinally in large, diverse populations. The Study of Women's Health Across the Nation (SWAN) followed 3,302 initially premenopausal and early perimenopausal women from 7 US sites and 5 racial/ethnic groups, using annual data (1996-2007) and Cox proportional hazards models to assess the relation of time-invariant and time-varying sociodemographic, lifestyle, and health factors to age at natural FMP. Median age at the FMP was 52.54 years (n = 1,483 observed natural FMPs). Controlling for sociodemographic, lifestyle, and health factors, we found that racial/ethnic groups did not differ in age at the FMP. Higher educational level, prior oral contraceptive use, and higher weight at baseline, as well as being employed, not smoking, consuming alcohol, having less physical activity, and having better self-rated health over follow-up, were significantly associated with later age at the FMP. These results suggest that age at the natural FMP reflects a complex interrelation of health and socioeconomic factors, which could partially explain the relation of late age at FMP to reduced morbidity and mortality.

Elevated gastrin-releasing peptide receptor mRNA expression in buccal mucosa: association with head and neck squamous cell carcinoma.

BACKGROUND: Expression of gastrin-releasing peptide receptor (GRPR) is elevated in mucosa adjacent to head and neck squamous cell carcinoma (HNSCC) compared with mucosa from cancer-free controls, suggesting elevated GRPR expression may indicate presence of HNSCC. METHODS: We measured GRPR mRNA levels in histologically normal buccal mucosa from 65 surgical patients with HNSCC and 75 cancer-free control subjects using quantitative polymerase chain reaction (PCR). We tested for association between GRPR expression and HNSCC and evaluated differences in patient progression-free survival (PFS). RESULTS: Buccal GRPR expression was higher in cases but not controls who were active smokers (p = .04). High GRPR expression was associated with HNSCC (odds ratio [OR] = 3.55; 95% confidence interval [CI] = 1.15-10.93), even after adjustment for age, sex, tobacco use, and sample storage time. PFS did not differ between patients with HNSCC with high versus low GRPR expression (p = .22). CONCLUSION: Elevated buccal GRPR expression was significantly associated with HNSCC independent of known risk factors but was not an indicator of disease prognosis.

Ethnic variability in bone geometry as assessed by hip structure analysis: findings from the hip strength across the menopausal transition study.

Racial/ethnic origin plays an important role in fracture risk. Racial/ethnic differences in fracture rates cannot be fully explained by bone mineral density (BMD). Studies examining the influence of bone geometry and strength on fracture risk have focused primarily on older adults and have not included people from diverse racial/ethnic backgrounds. Our goal was to explore racial/ethnic differences in hip geometry and strength in a large sample of midlife women. We performed hip structure analysis (HSA) on hip dual-energy X-ray absorptiometry (DXA) scans from 1942 premenopausal and early perimenopausal women. The sample included white (50%), African American (27%), Chinese (11%), and Japanese (12%) women aged 42 to 52 years. HSA was performed using software developed at Johns Hopkins University. African American women had higher conventional (8.4% to 9.7%) and HSA BMD (5.4% to 19.8%) than other groups with the exception being Japanese women, who had the highest HSA BMD (9.7% to 31.4%). HSA indices associated with more favorable geometry and greater strength and resistance to fracture were more prevalent in African American and Japanese women. Femurs of African American women had a smaller outer diameter, a larger cross-sectional area and section modulus, and a lower buckling ratio. Japanese women presented a different pattern with a higher section modulus and lower buckling ratio, similar to African American women, but a wider outer diameter; this was offset by a greater cross-sectional area and a more centrally located centroid. Chinese women had similar conventional BMD as white women but a smaller neck region area and HSA BMD at both regions. They also had a smaller cross-sectional area and section modulus, a more medially located centroid, and a higher buckling ratio than white women. The observed biomechanical differences may help explain racial/ethnic variability in fracture rates. Future research should explore the contribution of hip geometry to fracture risk across all race/ethnicities.

A method to estimate off-schedule observations in a longitudinal study.

PURPOSE: Data in epidemiological studies sometimes are collected off-schedule from planned study visits. In an ancillary study to the Study of Women's Health Across the Nation (SWAN), longitudinal breast density data were collected retrospectively from mammograms that were not acquired at the study visits. We propose a method to estimate the off-schedule breast density measurements at the time of study visits. METHODS: This method uses local linear interpolation, with multiply imputed error terms drawn from assumed subject-specific normal distributions based on the within-subject standard deviations of mammographic density measurements. We evaluate the validity and implications of this approach. RESULTS: Coefficients of random intercept models used to assess the association between annual changes in body mass index and dense breast area estimated with this approach (ß = -0.17, p = .46) differed from those obtained when each mammogram was matched to the nearest study visit (ß = -0.30, p = .04). The proposed estimation approach had a small average prediction error (0.11 cm2). CONCLUSIONS: Because matching does not incorporate breast density changes over time, our local linear interpolation with multiple imputation approach may provide more accurate results. The proposed approach is applicable to other epidemiologic studies with off-schedule data in which the missing variable changes linearly over relatively short periods of time.

Change in follicle-stimulating hormone and estradiol across the menopausal transition: effect of age at the final menstrual period.

BACKGROUND AND OBJECTIVE: To determine whether patterns of change in serum estradiol (E2) and FSH across the menopausal transition were associated with age at the final menstrual period (FMP). DESIGN AND SETTING: The Study of Women's Health Across the Nation (SWAN) is a seven-site, multiethnic, longitudinal study of the menopausal transition being conducted in 3302 menstruating women who were aged 42-52 yr at the 1996 study baseline. MEASUREMENTS: Annually collected serum was assayed for E2 and FSH levels. Patterns of hormone change were evaluated in the 1215 women with a documented natural FMP by follow-up visit 9 (2006) using semiparametric stochastic and piecewise linear mixed modeling. RESULTS: The FSH pattern across the menopausal transition began with an increase 6.10 yr before the FMP, an acceleration 2.05 yr before the FMP, deceleration beginning 0.20 yr before the FMP, and attainment of stable levels 2.00 yr after the FMP, independent of age at the FMP, race/ethnicity, or smoking status. Obesity attenuated the FSH rise and delayed the initial increase to 5.45 yr before the FMP. The mean E2 concentration did not change until 2.03 yr before the FMP when it began decreasing, achieving maximal rate of change at the FMP, then decelerating to achieve stability 2.17 yr after the FMP. Obesity, smoking behavior, and being Chinese or Japanese were associated with some variation in E2 levels but not the pattern of E2 change. CONCLUSIONS: Time spans and overall patterns of change in serum FSH and E2 across the menopausal transition were not related to age at FMP or smoking, whereas time spans but not overall patterns were related to obesity and race/ethnicity.

Circulating dehydroepiandrosterone sulfate levels in women who underwent bilateral salpingo-oophorectomy during the menopausal transition.

OBJECTIVE: A rise in circulating dehydroepiandrosterone sulfate (DHEAS) concentration occurs during the menopausal transition (MT) that is ovarian stage related but not age related. The objective of this study was to determine the source of the rise in circulating DHEAS. METHODS: Circulating DHEAS concentrations in women who had undergone bilateral salpingo-oophorectomy (BSO) were compared with the pattern of circulating DHEAS in women who progressed through the MT naturally. Annual serum samples from the Study of Women's Health Across the Nation (SWAN) over a 10-year study period were used. From 1,272 women in the SWAN cohort who were eligible for longitudinal evaluation of DHEAS annual samples, 81 underwent BSO during the premenopausal or early perimenopausal stage of the MT and were potentially available for study. Of these 81 BSO participants, 20 had sufficient annual samples for evaluation of the post-BSO trajectory of circulating DHEAS. SWAN women not having used hormone therapy previously and those with intact ovaries were compared with women who underwent a BSO immediately after a premenopausal or early perimenopausal annual visit. There were no interventions, and circulating concentration of DHEAS was the main outcome. RESULTS: A detectable rise in DHEAS was observed in 14 (70%) of the 20 BSO women, which is similar to the proportion (85%) of women with intact ovaries who had a detectable DHEAS rise. The mean rise in DHEAS (5%-8%) was similar in both BSO and non-BSO women. CONCLUSIONS: The MT rise in DHEAS (5%-8%) occurring in the absence of ovaries is largely of adrenal origin.

Circulating dehydroepiandrosterone sulfate concentrations during the menopausal transition.

CONTEXT: A previous report from the Study of Women Across the Nation indicated a rise in dehydroepiandrosterone sulfate (DHEAS) during the menopausal transition using data from three annual visits. OBJECTIVE: Our objective was to examine changes in DHEAS with chronological and ovarian aging, expanding the original analyses to include 10 yr of annual data. DESIGN: A longitudinal observational study and cross-sectional analyses of baseline data were conducted. OUTCOME MEASURES AND SUBJECTS: DHEAS, age, menopause status, ethnicity, smoking, weight, and height were assessed in 2886 women from five ethnic groups aged 42-52 yr at entry. Hysterectomy, bilateral oophorectomy, and hormone use were excluded. RESULTS: Cross-sectional analysis at baseline showed a linear decline in circulating log-transformed DHEAS with increasing age for either the entire cohort (2.81% per year) or for individual ethnicities. A similar negative association with baseline age (2.44% decline per year) was seen in longitudinal linear mixed modeling including observations from premenopause through late postmenopause, an additional 0.33% decline/year. In contradistinction, a late-transition rise in DHEAS was detected when the same women were analyzed by ovarian status. The average increase in mean circulating DHEAS level between early and late menopause transition, beyond changes predicted by aging, was 3.95%, followed by an average decline of 3.96% during the late postmenopause. Approximately 84.5% of the women had an estimated within-woman increase in DHEAS from premenopause/early perimenopause to late perimenopause/early postmenopause. CONCLUSION: These observations underscore differences between cross-sectional and longitudinal studies and the importance of considering ovarian status. Additional investigations regarding adrenal contribution to sex steroids in mid-aged women are warranted.

Long-term stability of electroencephalographic asymmetry and power in 3 to 9 year-old children.

We investigated the test-retest stability of resting EEG asymmetry and power in the alpha frequency range across a 0.6- to 3-year interval in 125 children (57 girls and 68 boys) for two age groups, 87 preschool children (3 to 5 year-olds) and 38 school-age children (6 to 9 year-olds). Children were from families with a parent's history of unipolar or bipolar depression (36 girls and 43 boys) or control families with no parent history of depression nor any other psychiatric disorder (21 girls and 25 boys). Frontal EEG asymmetry stability was low to moderate; intraclass correlations ranged from zero to 0.48 in the eyes-open condition, and from 0.19 to 0.45 in the eyes-closed condition. Also, parietal EEG asymmetry was low to moderate; intraclass correlations ranged from 0.21 to 0.52 in the eyes-open condition and from 0.27 to 0.72 in the eyes-closed condition. Stability of EEG asymmetry was not related to age, sex of the child, or parent's history of mood disorder. Frontal and parietal EEG power appeared moderately to highly stable. Intraclass correlations were between 0.65 and 0.86 in the eyes-open condition and between 0.52 and 0.90 in the eyes-closed condition. Although stability of EEG power was not statistical significantly different between preschool and school-age children, it consistently showed higher stability values in school-age children than in preschool children. Stability in school-age children approached values as has been reported for adults. The findings provide partial support to the concept of frontal EEG asymmetry as a trait marker in childhood.

Long-term stability of frontal electroencephalographic asymmetry in adults with a history of depression and controls.

We investigated the stability in resting EEG across a 1- to 3-year interval in 49 adults (33 female and 16 male) with a history of unipolar depression (first onset prior to the age of 14) and 50 controls (33 female and 17 male) with no history of major psychopathology. Current depressive symptoms were quantified by self-report at both assessments. For the entire sample, EEG asymmetry in the alpha range was moderately stable (intraclass correlations between 0.39 and 0.61). Sex, history of depression, depressive symptom severity at Time 2, and change in symptom severity between Time 1 and Time 2 were unrelated to stability of EEG asymmetry. These findings support the view that resting frontal EEG asymmetry reflects a moderately stable individual difference in adults, irrespective of sex and history of depression.