Biomedical subjects

D Spiegelman

Publications and source records attributed to D Spiegelman.

At least 19 recordsLinked to original sources

PubMed2006

Alcohol intake and ovarian cancer risk: a pooled analysis of 10 cohort studies.

Alcohol has been hypothesized to promote ovarian carcinogenesis by its potential to increase circulating levels of estrogen and other hormones; through its oxidation byproduct, acetaldehyde, which may act as a cocarcinogen; and by depletion of folate and other nutrients. Case-control and cohort studies have reported conflicting results relating alcohol intake to ovarian cancer risk. We conducted a pooled analysis of the primary data from ten prospective cohort studies. The analysis included 529 638 women among whom 2001 incident epithelial ovarian cases were documented. After study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then were pooled using a random effects model; no associations were observed for intakes of total alcohol (pooled multivariate RR=1.12, 95% CI 0.86-1.44 comparing > or =30 to 0 g day(-1) of alcohol) or alcohol from wine, beer or spirits and ovarian cancer risk. The association with alcohol consumption was not modified by oral contraceptive use, hormone replacement therapy, parity, menopausal status, folate intake, body mass index, or smoking. Associations for endometrioid, mucinous, and serous ovarian cancer were similar to the overall findings. This pooled analysis does not support an association between moderate alcohol intake and ovarian cancer risk.

Adult↗

PubMed2006

Socio-economic and demographic factors associated with prevalence of HIV infection among pregnant women in Dar es Salaam, Tanzania.

BACKGROUND: HIV/AIDS epidemic has become generalised in low resource settings in sub-Saharan Africa where 90% of all maternal-foetal transmission of HIV infection occurs. Global effort to scale-up pMTCT is underway, however, mechanisms to maximise screening of HIV- 1 positive women for Nevirapine treatment and other interventions, are not clear. OBJECTIVE: To identify socioeconomic and demographic characteristics associated with the prevalence of HIV- 1 infection among Tanzanian women. DESIGN: Cross-sectional study. SETTING: Four antenatal clinics in Dar es Salaam. RESULTS: HIV prevalence rate was 13.1 (95% confidence interval (CI): 12.7% - 13.5%) and it increased with increasing maternal age. Older age than 25, mid-arm circumference less than 25cm, geographic location, working in a public house, and partner's occupation were independently associated with higher prevalence of infection. Women in monogamous marriages were 77% less likely to be HIV infected compared to women with no regular partner. Similarly, women with more than five persons per household, and those who spent less on food had a significantly lower HIV prevalence. CONCLUSION: HIV infection is sufficiently widespread among women in Dar es Salaam suggesting that screening based on socioeconomic and demographic characteristics would miss a large proportion of the positives. There is need to increase facilities for counselling and testing using an opt-out approach for testing in all antenatal clinics in the city.

Adolescent↗

PubMed2005

Correlated errors in biased surrogates: study designs and methods for measurement error correction.

A measurement error model proposed previously allows for correlations between subject-specific biases and between random within-subject errors in the surrogates obtained from two modes of measurement. However, most of these model parameters are not identifiable from the standard validation study design, including, importantly, the attenuation factor needed to correct for bias in relative risk estimates due to measurement error. We propose validation study designs that permit estimation and inference for the attenuation factor and other parameters of interest when these correlations are present. We use an estimating equations framework to develop semi-parametric estimators for these parameters, exploiting instrumental variables techniques. The methods are illustrated through application to data from the Nurses' Health Study and Health Professionals' Follow-up Study, and comparisons are made to more restrictive models.

Bias↗

PubMed2005

Selenium levels in relation to morbidity and mortality among children born to HIV-infected mothers.

OBJECTIVE: To examine the relation between selenium status and child mortality and morbidity among children born to HIV-infected mothers. DESIGN: Prospective cohort study. METHODS: Study participants were originally part of a trial to study the effect of maternal vitamin supplements on maternal and child health outcomes. Morbidity information was collected during monthly clinic visits until the child reached 24 months of age. Out of 984 livebirths, 806 had morbidity information, and 610 also had data on plasma selenium levels available. SETTING: A study clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania, a tertiary-care hospital. RESULTS: The median age at baseline was 10.5 weeks. A total of 117 (19%) of the 610 study children died during follow-up. In a multivariate model, child plasma selenium levels were inversely associated with risk of all-cause mortality (P-value, test for trend=0.05). Plasma selenium levels were not significantly associated with risk of diarrhea or respiratory outcomes. CONCLUSIONS: Among infants born to HIV-infected women in sub-Saharan Africa, selenium status may be important to prevent child mortality. These preliminary findings warrant future reexamination.

Child Mortality↗

PubMed2005

Bidi and cigarette smoking and risk of acute myocardial infarction among males in urban India.

Death from myocardial infarction (MI) in India is exacerbated by smoking of bidis or cigarettes. Smoking among 309 men with incident MI was compared to 618 age matched controls; 56% of the individuals with MI and 26% of controls were current smokers. Current smokers had a relative risk of 4.7 (95% confidence interval (CI) 3.2 to 6.9) compared to never smokers. Relative risks for smoking more than 10 cigarettes or 10 bidis daily were 9.1 (95% CI 4.7 to 17.7) and 8.1 (95% CI 4.3 to 15.3), respectively. It is estimated that smoking may cause 53% (95% CI 47% to 64%) of MIs among urban males in India.

Adult↗

PubMed2003

Role of acquired immune deficiency syndrome-defining conditions in human immunodeficiency virus-associated wasting.

To evaluate the contribution of acquired immune deficiency syndrome-defining conditions (ADCs) in human immunodeficiency virus (HIV)-associated wasting, we analyzed longitudinal data from 671 participants in a nutrition and HIV cohort study. Data on ADCs, height, and weight were collected at baseline and during 6 monthly study visits. The frequency of ADCs decreased over time, but the relative risk (RR) of wasting (decrease in body mass index [BMI] to <20 kg/m(2)) increased with a history of >1 ADC; the RR of wasting increased 1.3-fold with each additional historical ADC. Any ADC during the 6 months prior to a study visit was associated with a decrease in BMI to <20 kg/m(2). The risk of wasting increased 2.7-fold with each additional recent ADC. These risks were not altered when adjusted for socioeconomic status, CD4 cell count, energy intake, or baseline BMI. Although ADCs contribute to the development of wasting, their contribution is relatively small.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Intakes of vitamins E and C, carotenoids, vitamin supplements, and PD risk.

BACKGROUND: Oxidative damage has been implicated in the pathogenesis of PD. Limited and mostly retrospective epidemiologic data suggest a reduction or no change in risk of PD associated with high vitamin E intake. OBJECTIVE: To examine prospectively the associations between intakes of vitamins E and C, carotenoids, vitamin supplements, and risk of PD. METHODS: The authors documented the occurrence of PD within two large cohorts of men and women who completed detailed and validated semiquantitative food frequency questionnaires. A total of 371 incident PD cases were ascertained in the Nurses' Health Study, which comprised 76,890 women who were followed for 14 years, and the Health Professionals Follow-Up Study, which comprised 47,331 men who were followed for 12 years. RESULTS: Neither intake of total vitamins E or C or use of vitamin E or vitamin C supplements or multivitamins was significantly associated with risk of PD. The risk of PD, however, was significantly reduced among men and women with high intake of dietary vitamin E (from foods only). The pooled multivariate relative risk (RR) comparing individuals in the highest quintile with those in the lowest quintile was 0.68 (95% CI, 0.49 to 0.93). Consumption of nuts was also significantly associated with a reduced risk of PD (for >or=5/week vs <1/month, pooled RR, 0.57; 95% CI, 0.34 to 0.95). Intakes of dietary vitamin C and carotenoids were not significantly associated with risk of PD. CONCLUSIONS: Use of vitamin supplements and high intake of carotenoids do not appear to reduce the risk of PD. The reduction in risk of PD associated with high dietary vitamin E intake suggests that other constituents of foods rich in vitamin E may be protective. Alternatively, moderate amounts of vitamin E may reduce risk of PD, but this benefit may be lost with higher intakes.

Adult↗

PubMed2002

Demographic, family, and occupational characteristics associated with major depression: the Harvard study of moods and cycles.

OBJECTIVE: This study assesses the extent to which women with and without major depression differ by demographic, familial, and occupational characteristics. METHOD: From a community-based sample, the authors identified 332 women with and 644 women without current or past major depression based on Structured Clinical Interviews for DSM-IV. Demographic and background interviews were conducted in-person. RESULTS: Depressed women were more likely to have gained >or =35 lbs between age 18 and study enrollment (OR=1.6, 95% CI 1.1-2.5), experienced divorce (OR=2.0, 95% CI 1.4-2.8), or changed occupations (OR=1.5, 95% CI 1.1-2.1) compared with non-depressed women. Compared with women with no brothers, those with > or =1 brothers were less likely to have a history of depression (OR=0.8, 95% CI 0.6-1.1), whereas compared with women with no sisters, those with > or =1 sisters were more likely to have current or past depression (OR=1.4, 95% CI 1.0-1.9). These findings were not influenced by family sibship size. CONCLUSION: These results illustrate demographic differences between women with and without major depression and that sibship gender rather than size may also influence risk.

Adult↗

PubMed2002

HIV status and sociodemographic correlates of maternal body size and wasting during pregnancy.

OBJECTIVE: To examine HIV status and sociodemographic variables as correlates of body size (height, body mass index (BMI), and mid-upper-arm circumference (MUAC)) and wasting (MUAC <22 cm) in pregnant women. DESIGN: Cross-sectional study. SETTING: Four antenatal clinics in Dar es Salaam, Tanzania. SUBJECTS: Women presenting for first prenatal visit before the 23rd week of gestation, between April 1995 and July 1997 (n=13 760). RESULTS: Mean MUAC, BMI and height were 25.5 cm, 23.5 kg/m(2) and 155.1 cm, respectively. The prevalence of HIV infection was 13.1% and the overall prevalence of wasting was 4.7%. Wasting was 34% (95% CI=3%, 73%) more prevalent among HIV-infected than in uninfected mothers, after adjusting for week of gestation, height and sociodemographic indicators. The risk of wasting associated with HIV infection was highest among women with low level of education or unable to contribute to the household income. From a multiple linear regression model, BMI was positively associated with mother's age, level of education and money spent on food, but not with HIV infection, after adjusting for week of gestation. In multivariate analysis, height increased monotonically by categories of maternal age and level of education, and was also positively correlated with the ability to contribute to household income, the amount of money spent on food per person per day, and having a professional partner. CONCLUSION: HIV infection is a significant risk factor for wasting among pregnant women, particularly in groups of low socioeconomic status (SES). SES indicators are strongly correlated with maternal height and with BMI during the first and second trimesters of pregnancy independently of HIV status. SPONSORSHIP: The National Institute of Child Health and Human Development (NICHD R01 32257), and the Fogarty International Center (NIH D43 TW00004).

Adolescent↗

PubMed2002

Changes in lean body mass and total body weight are weakly associated with physical functioning in patients with HIV infection.

CONTEXT: For clinicians managing weight loss in patients with HIV, it would be useful to understand how changes in lean body mass (LBM) effect physical functioning, and whether LBM is more strongly related to physical functioning than total body weight (TBW). OBJECTIVE: To determine the relationship of changes in LBM and changes in total body weight (TBW) to changes in self-reported physical functioning in men and women with HIV infection. METHODS: Study design was longitudinal analysis of 1474 patient-intervals (each interval was approximately 6 months long) in 486 persons. Patients were participants in Nutrition for Healthy Living, a cohort study of HIV positive persons in Massachusetts and Rhode Island. The main outcome measure was change in self-reported physical functioning. RESULTS: Of the 1,474 intervals, 1,165 were contributed by men and 309 by women. The mean CD4 count for the 1,474 intervals was 383 cells/ micro L. In men, 5 kg changes in LBM and TBW were associated with 2.2 (95% confidence interval, 0.9, 3.4, P= 0.001) and 2.6 (95% confidence interval, 1.3, 3.9, P= 0.0002) point changes in physical functioning (on a 100-point scale), respectively, after adjusting for covariates. The relationships of changes in LBM and TBW to changes in physical functioning were linear. In women, there were no significant relationships between changes in LBM or TBW to changes in physical functioning. CONCLUSIONS: In this longitudinal analysis of relatively healthy persons with HIV infection, changes in LBM and TBW were significantly related to changes in physical functioning in men, but the magnitude of the relationship was small. In women, changes in LBM and TBW were not related to changes in physical functioning. Our data suggest that it is not necessary to measure body composition (lean and fat compartments) to understand the impact of changes in weight on physical functioning - it is sufficient to follow total body weight.

Adult↗

PubMed2001

Epstein-Barr virus antibodies and risk of multiple sclerosis: a prospective study.

CONTEXT: Epidemiological studies suggest an association between infection with Epstein-Barr virus (EBV) and risk of multiple sclerosis (MS). OBJECTIVE: To determine whether elevation in serum antibody titers to EBV viral capsid antigen (VCA), nuclear antigens (EBNA, EBNA-1, and EBNA-2), and diffuse and restricted early antigen (EA-D and EA-R) as well as to cytomegalovirus (CMV) precede the occurrence of MS. DESIGN, SETTING, AND SUBJECTS: Prospective, nested case-control study. Of 62 439 women participating in the Nurses' Health Study (aged 30-55 years in 1976) and Nurses' Health Study II (aged 25-42 years in 1989) who gave blood samples in 1989-1990 and 1996-1999, respectively, and were followed up through 1999, 144 women with definite or probable MS and 288 healthy age-matched controls were included in the analysis. MAIN OUTCOME MEASURE: Serum antibody titers to the specific EBV and CMV antigens, compared between cases and controls. RESULTS: We documented 18 cases of MS with blood collected before disease onset. Compared with their matched controls, these women had higher serum geometric mean titers (GMTs) of antibodies to EBV but not CMV. Elevations were significant for antibodies to EBNA-1 (GMT, 515 vs 203; P =.03), EBNA-2 (GMT, 91 vs 40; P =.01), and EA-D (15.9 vs 5.9; P =.04). The strongest association was found for antibodies to EBNA-2; a 4-fold difference in titers was associated with a relative risk (RR) of MS of 3.9 (95% confidence interval [CI], 1.1-13.7). The corresponding RRs were 1.6 (95% CI, 0.7-3.7) for VCA, 2.5 (95% CI, 1.0-6.3) for EBNA, 1.8 (95% CI, 1.0-3.1) for EA-D, and 1.0 (95% CI, 0.6-1.7) for CMV. Significant but generally weaker elevations in anti-EBV antibodies were also found in analyses of 126 cases of MS with blood collected after disease onset and their matched controls. CONCLUSIONS: Our results support a role of EBV in the etiology of MS.

Adult↗

PubMed2001

Assessment of questionnaire validity for measuring total fat intake using plasma lipid levels as criteria.

The validation of dietary total fat measurements has been elusive because no specific biomarker exists. In metabolic studies with controlled diets, plasma fasting triglyceride levels are reduced with higher fat intake and can thus serve as an "alloyed gold" standard. Participants in this cross-sectional analysis were 269 men aged 47-83 years from the Health Professionals Follow-up Study who completed a semiquantitative food frequency questionnaire and provided fasting blood specimens in 1994. In a multiple regression analysis adjusted for age; smoking; alcohol consumption; physical activity; body mass index; and intakes of protein, dietary fiber, and total energy, total fat intake was inversely associated with fasting triglycerides (for a fat increase of 1% of energy, triglyceride levels were lower by 2.5% (95% confidence interval: -3.7 to -1.3%, p = 0.0002)). For reported fat intakes of 20% or less of energy, the geometric mean fasting triglyceride level was 179, and for more than 40% of energy, it was 102 mg/dl. In addition, as predicted by metabolic studies, the inverse association between dietary fat and fasting triglyceride level was much stronger among overweight men than among men with a BMI of less than 25. These data provide additional evidence that informative measurements of dietary fat can be obtained by carefully constructed food frequency questionnaires.

Adult↗

PubMed2001

Application of the method of triads to evaluate the performance of food frequency questionnaires and biomarkers as indicators of long-term dietary intake.

Little is documented about the performance of the food frequency questionnaire (FFQ) in US minority groups and in populations in developing countries. The authors applied a novel technique, the method of triads, to assess the validity and reproducibility of the FFQ among Hispanics. The subjects were men (n = 78) and women (n = 42) living in Costa Rica. Seven 24-hour dietary recalls and two FFQ interviews (12 months apart) were conducted between 1995 and 1998 to estimate dietary intake during the past year. Plasma and adipose tissue samples were collected from all subjects. Validity coefficients, which measure the correlation between observed and "true" dietary intake, were also estimated. The median validity coefficients for tocopherols and carotenoids estimated by dietary recall, the average of the two FFQs, and plasma were 0.71, 0.60, and 0.52, respectively. Compared with adipose tissue, plasma was a superior biomarker for carotenoids and tocopherols. Adipose tissue was a poor biomarker for saturated and monounsaturated fatty acids but performed well for polyunsaturated fatty acids (validity coefficients, 0.45-1.01) and lycopene (validity coefficient, 0.51). This study also showed that biomarkers did not perform better than the FFQ and that they should be used to complement the FFQ rather than substitute for it.

Adipose Tissue↗

PubMed2001

Patterns of adherence with antiretroviral medications: an examination of between-medication differences.

OBJECTIVE: To determine whether adherence with one antiretroviral medication reliably predicts adherence with other antiretroviral medications. DESIGN: Cross-sectional repeated-measurement analysis. SETTING: Cohort study enrolling patients from Massachusetts and Rhode Island. PATIENTS: Total of 454 patients using antiretroviral medications for HIV infection. METHODS: For each antiretroviral medication, we asked patients to report how many days in the last week they had 1) missed a dose of the medication and 2) been off schedule with a dose of the medication. The reliability coefficient was used to compare between-person variance in adherence rates with total variance, which is the sum of between-person and within-person variance. RESULTS: The mean age of patients was 42 years; 28% were women and 37% were nonwhite. Sixty-six percent of patients were on three or more antiretroviral medications. Perfect adherence was reported by 42% of patients, and patients reported missing a dose on a mean of 1.5 days per week for each antiretroviral medication currently being taken. The reliability coefficient for days in the last week that the medication was missed was 0.85 (95% confidence interval [CI]: 0.83-0.87), and for days off-schedule in the last week, it was 0.88 (CI: 0.86-0.89). CONCLUSIONS: Most of the variability in antiretroviral adherence in this study was accounted for by between-patient differences in overall adherence rather than by within-patient differences in adherence patterns across medications. These data support the theory that when patients skip or are off schedule with doses, they skip or are off schedule with all the antiretroviral medications taken at that time. In the course of exploring patients' adherence issues, clinicians may find it useful to inquire about problematic dosing times. Researchers assessing adherence may not need to separately monitor adherence with each antiretroviral medication in a regimen.

Adult↗

PubMed2001

Assessment of markers of hepatitis C virus infection in a Japanese adult population.

Latent-class analysis was used to evaluate the usefulness of markers of hepatitis C virus (HCV) infection in characterizing the true, underlying infection in a community-based Japanese population. Antibodies to HCV were detected in 24%, HCV RNA in 22%, and HCV core protein in 19% of stored serum samples from 372 adults. A 2-class model suggested that positive results for any 2 virus markers defined the current HCV infection class, with an estimated prevalence of 22% (95% confidence interval, 18%-26%). The sensitivity for detection of current HCV infection was highest for anti-HCV (97%) and was more moderate for HCV RNA (91%) and HCV core protein (85%). The specificity for each marker was > or =96%. In general, the association between demographic factors and current HCV infection status was strengthened by use of latent-class analysis that combined data for markers of HCV infection, when compared with results of logistic regression analysis for each marker separately.

Agglutination Tests↗

PubMed2001

HIV-1 LTR subtype and perinatal transmission.

Multiple subtypes of HIV-1 have been identified; however, there is little data on the relative transmissibility of viruses belonging to different subtypes. A matched case-control study addressed whether viruses with different long terminal repeat (LTR) subtypes were transmitted equally from mother to infant. The LTR subtype was determined for 45 matched cases and controls who participated in a clinical trial in Tanzania. HIV-1 subtypes A, C, and D and intersubtype recombinant sequences were identified. Exact matched logistic regression analysis showed that viruses containing subtype A or intersubtype recombinant LTRs were 3.2 and 4.8 times more likely to be transmitted from mother to infant than viruses with subtype D LTRs. Viruses containing subtype C LTRs were 6.1 times more likely to be transmitted than those with subtype D LTRs. These differences in transmission were independent of maternal CD4 at enrollment. Thus, it appears that HIV-1 subtype may be associated with differing rates of perinatal transmission in Tanzania.

Female↗

PubMed2001

Do HIV type 1 RNA levels provide additional prognostic value to CD4(+) T lymphocyte counts in patients with advanced HIV type 1 infection?

Our objective was to assess whether HIV-1 RNA levels provide additional prognostic information beyond CD4(+) T lymphocyte counts in the prediction of subsequent HIV-1 disease progression among patients with advanced HIV-1 disease. In a nested case-control study conducted in patients with baseline CD4(+) T lymphocyte counts < 300 cells/mm(3) and receiving nucleoside reverse transcriptase inhibitors, 102 patients who progressed to an AIDS-defining event or death were matched within 10 CD4(+) T lymphocyte cells/mm(3) to patients who did not progress. The relationship between plasma HIV-1 RNA levels and HIV-1 disease progression was studied using conditional logistic regression analysis, which adjusts for the matching by baseline CD4(+) T lymphocytes. We observed a 0.10 log(10) copies/ml difference in baseline HIV-1 RNA levels between cases and their matched controls (p = 0.027). The relative risk for HIV-1 disease progression increased with increasing baseline HIV-1 RNA levels (odds ratio [OR] for a 3-fold higher HIV-1 RNA level, 1.42; 95% confidence interval [CI], 1.08--1.86), and remained important when also controlling for clinical status at baseline and CD4(+) T lymphocytes at 2 months (p = 0.038). Higher baseline HIV-1 RNA levels were associated with HIV-1 disease progression among patients with a baseline CD4(+) T lymphocyte count of 100 cells/mm(3) or greater (OR, 1.80; 95% CI, 1.15--2.81), but not among patients with a baseline CD4(+) T lymphocyte count < 100 cells/mm(3) (OR, 1.09; 95% CI, 0.73--1.63). We concluded that HIV-1 RNA levels predict subsequent HIV-1 disease progression independent of CD4(+) T lymphocyte counts. The magnitude and importance of the prognostic information contained in the HIV-1 RNA levels appear to depend on the CD4(+) T lymphocyte counts.

Adult↗

PubMed2001

Intakes of carotenoids, vitamin C, and vitamin E and MS risk among two large cohorts of women.

BACKGROUND: Antioxidant nutrients may reduce the risk of MS. In a recent case-control study, vitamin C intake was significantly inversely associated with MS risk among women. However, no prospective data are available. OBJECTIVE: To examine prospectively the associations of intakes of carotenoids, vitamin C, and vitamin E with the risk of MS among women. METHODS: The authors documented the occurrence of definite and probable MS within two large cohorts of women who completed detailed and validated semiquantitative food frequency questionnaires. One cohort (Nurses' Health Study) comprised 81,683 women aged 38 to 63 years in 1984, who were followed for 12 years; the other (Nurses' Health Study II) comprised 95,056 women aged 27 to 44 years in 1991, who were followed for 6 years. RESULTS: The authors documented a total of 214 cases of MS. After adjustments for age, latitude of birthplace, pack-years of smoking, and total energy intake, the pooled multivariate relative risks (95% CIs) comparing women in the highest quintile with those in the lowest quintile were 1.1 (0.7 to 1.7) for alpha-carotene, 1.1 (0.7 to 1.6) for beta-carotene, 1.4 (0.8 to 2.2) for beta-cryptoxanthin, 1.0 (0.6 to 1.5) for lycopene, 1.0 (0.7 to 1.6) for lutein/zeaxanthin, 1.4 (0.9 to 2.1) for total vitamin C, 1.3 (0.9 to 2.0) for dietary vitamin C, 0.8 (0.6 to 1.3) for total vitamin E, and 0.9 (0.6 to 1.4) for dietary vitamin E. The authors found no associations between intakes of fruits and vegetables and risk of MS. Use of vitamin C, vitamin E, and multivitamin supplements was also unrelated to risk of MS. CONCLUSIONS: These findings do not support hypotheses relating higher intakes of dietary carotenoids, vitamin C, and vitamin E to reduced risk of MS in women.

Adult↗