TOP MEDICAL JOURNALS

Medical Journal, Information and Resources

Archive for the ‘epidemiology UPDATE’ Category

American Journal of Epidemiology update july, 18, 2008

Written by admin on Jul 25th, 2008 | Filed under: epidemiology UPDATE

The Incidence of Esophageal Cancer and High-Grade Dysplasia in Barrett’s Esophagus: A Systematic Review and Meta-Analysis

Barrett’s esophagus is a well-recognized precursor of esophageal adenocarcinoma. Surveillance of Barrett’s esophagus patients is recommended to detect high-grade dysplasia (HGD) or early cancer. Because of wide variation in the published cancer incidence in Barrett’s esophagus, the authors undertook a systematic review and meta-analysis of cancer and HGD incidence in Barrett’s esophagus. Ovid Medline (Ovid Technologies, Inc., New York, New York) and EMBASE (Elsevier, Amsterdam, the Netherlands) databases were searched for papers published between 1950 and 2006 that reported the cancer/HGD risk in Barrett’s esophagus. Where possible, early incident cancers/HGD were excluded, as were patients with HGD at baseline. Forty-seven studies were included in the main analysis, and the pooled estimate for cancer incidence in Barrett’s esophagus was 6.1/1,000 person-years, 5.3/1,000 person-years when early incident cancers were excluded, and 4.1/1,000 person-years when both early incident cancer and HGD at baseline were excluded. Corresponding figures for combined HGD/cancer incidence were 10.0 person-years, 9.3 person-years, and 9.1/1,000 person-years. Compared with women, men progressed to cancer at twice the rate. Cancer or HGD/cancer incidences were lower when only high-quality studies were analyzed (3.9/1,000 person-years and 7.7/1,000 person-years, respectively). The pooled estimates of cancer and HGD incidence were low, suggesting that the cost-effectiveness of surveillance is questionable unless it can be targeted to those with the highest cancer risk.

Statin Use and Risk of Prostate Cancer: Results from a Population-based Epidemiologic Study

Epidemiologic studies of statin use in relation to prostate cancer risk have been inconclusive. Recent evidence, however, suggests that longer-term use may reduce risk of more advanced disease. The authors conducted a population-based study of 1,001 incident prostate cancer cases diagnosed in 2002–2005 and 942 age-matched controls from King County, Washington, to evaluate risk associated with statin use. Logistic regression was used to generate odds ratios for ever use, current use, and duration of use. No overall association was found between statin use and prostate cancer risk (odds ratio (OR) = 1.0, 95% confidence interval (CI): 0.8, 1.2 for current use; OR = 1.1, 95% CI: 0.7, 1.8 for >10 years’ use), even for cases with more advanced disease. Risk related to statin use, however, was modified by body mass index (interaction p = 0.04). Obese men (BMI ?30 kg/m2) who used statins had an increased risk (OR = 1.5, 95% CI: 1.0, 2.2) relative to obese nonusers, with a stronger association for longer-term use (OR = 1.8, 95% CI: 1.1, 3.0 for ?5 years’ use). Although statin use was not associated with overall prostate cancer risk, the finding of an increased risk associated with statin use among obese men, particularly use for extended durations, warrants further investigation.

Benign Breast Disease among First-Degree Relatives of Young Breast Cancer Patients

Benign breast disease is associated with increased risk of breast cancer. To further clarify whether there is a genetic link between benign and malignant breast lesions, the authors identified 14,648 first-degree female relatives of 8,807 patients in whom breast cancer was diagnosed at <50 years of age by using Danish nationwide cancer and population registers. Hospital register data were used to follow the relatives for occurrence of benign breast disease from 1977 to 2003 and to calculate rates of benign breast disease in the general population of Danish women for comparison. Risk for relatives was increased for benign breast diseases (observed/expected ratio = 1.54, 95% confidence interval: 1.42, 1.66), particularly for relatives aged <40 years. Higher risks were observed after breast cancer had been diagnosed in the family; however, an increased risk for relatives aged <50 years (observed/expected ratio = 1.24, 95% confidence interval: 1.02, 1.51) was present before breast cancer was diagnosed in the family. Enhanced surveillance of close relatives of breast cancer patients seems to be an important factor to address when investigating the association between benign breast disease and familial breast cancer. A genetic link between benign breast disease and breast cancer was indicated by our data but needs to be confirmed in future studies.

Body Size and Renal Cell Cancer Incidence in a Large US Cohort Study

Renal cell cancer (RCC) incidence has increased in the United States over the past three decades. The authors analyzed the association between body mass index (BMI) and invasive RCC in the National Institutes of Health (NIH)–AARP Diet and Health Study, a large, prospective cohort aged 50–71 years at baseline initiated in 1995–1996, with follow-up through December 2003. Detailed analyses were conducted in a subcohort responding to a second questionnaire, including BMI at younger ages (18, 35, and 50 years); weight change across three consecutive age intervals; waist, hip, and waist-to-hip ratio; and height at age 18 years. Incident RCC was diagnosed in 1,022 men and 344 women. RCC was positively and strongly related to BMI at study baseline. Among subjects analyzed in the subcohort, RCC associations were strongest for baseline BMI and BMI recalled at age 50 years and were successively attenuated for BMI recalled at ages 35 and 18 years. Weight gain in early (18–35 years of age) and mid- (35–50 years of age) adulthood was strongly associated with RCC, whereas weight gain after midlife (age 50 years to baseline) was unrelated. Waist-to hip ratio was positively associated with RCC in women and with height at age 18 years in both men and women.

Non-Hodgkin Lymphoma in Women: Reproductive Factors and Exogenous Hormone Use

Few studies of reproductive hormone exposures and non-Hodgkin lymphoma (NHL) have examined NHL subtypes. Associations between reproductive hormonal factors and risk of all NHL and of two predominant subtypes, diffuse large-cell lymphoma (DLCL) (n = 233) and follicular lymphoma (n = 173), were investigated among women (n = 581) in a large, population-based, case-control study (1,591 cases, 2,515 controls). Controls (n = 836) identified by random digit dialing were frequency matched by age and county to incident NHL cases ascertained in the San Francisco Bay Area of California in 1988–1993. Adjusted unconditional logistic regression was used to obtain odds ratios. More than four pregnancies indicated a possible lower risk of all NHL (odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.55, 1.2; p-trend = 0.06) and of DLCL (OR = 0.53, 95% CI: 0.31, 0.90; p-trend = 0.01). Exclusive use of menopausal hormone therapy for ?5 years was associated with a reduced risk of all NHL (OR = 0.68, 95% CI: 0.48, 0.98) and of DLCL (OR = 0.50, 95% CI: 0.30, 0.85). Oral contraceptive use indicated a lower risk of all NHL (OR = 0.68, 95% CI: 0.49, 0.94), and perhaps DLCL (OR = 0.79, 95% CI: 0.51, 1.2), and of follicular lymphoma (OR = 0.75, 95% CI: 0.46, 1.2). Results suggest that endogenous and exogenous reproductive hormones confer different risks by NHL subtype and are associated with a reduced risk of DLCL in women.

Consumption of trans-Fatty Acid and Its Association with Colorectal Adenomas

trans-Fatty acid consumption is known to have detrimental effects on cardiovascular health, but little is known about its role in digestive tract neoplasia. To investigate the association between colorectal adenomas and trans-fatty acid consumption, the authors utilized data from a cross-sectional study of 622 individuals who underwent complete colonoscopy between 2001 and 2002 at the University of North Carolina Hospitals. Participants were interviewed about demographic, lifestyle, and dietary factors thought to be related to colorectal cancer. trans-Fatty acid consumption, energy adjusted by the residual method, was categorized into quartiles based on its distribution in controls. Compared with participants in the lowest quartile of consumption, those in the highest quartile had an increased prevalence of colorectal adenomas, with an adjusted prevalence odds ratio of 1.86 (95% confidence interval: 1.04, 3.33). The authors further investigated the relation between trans-fatty acid consumption and colorectal neoplasia by examining the adenoma characteristics, with the adjusted prevalence odds ratios showing little or no difference by adenoma location, size, or number. These results suggest that consumption of high amounts of trans-fatty acid may increase the risk of colorectal neoplasia, and they provide additional support to recommendations to limit trans-fatty acid consumption.

Effects of Exposure to Polychlorinated Biphenyls and Organochlorine Pesticides on Thyroid Function during Pregnancy

In this study, the authors’ objective was to determine whether serum concentrations of polychlorinated biphenyls (PCBs), hexachlorobenzene, p,p‘-dichlorodiphenyl trichloroethane (DDT), o,p‘-DDT, and p,p‘-dichlorodiphenyl dichloroethylene (DDE) are associated with thyroid function during pregnancy. These compounds, as well as thyroid-stimulating hormone, total thyroxine, and free thyroxine, were measured in serum samples collected between October 1999 and October 2000 from 334 pregnant women living in the Salinas Valley, California. Data were analyzed by multivariate linear regression. After adjustment for covariates, seven of the 19 PCB congeners detected in more than 75% of participants and the sum of those congeners were negatively associated with free thyroxine concentrations. PCBs 44, 52, and 183 remained significant after the exclusion of two outliers. Hexachlorobenzene concentrations were negatively associated with both free thyroxine and total thyroxine. PCB and hexachlorobenzene concentrations were strongly correlated, which hampered the authors’ ability to identify their independent associations with thyroid function. None of the exposures under study were associated with thyroid-stimulating hormone. Results suggest that exposure to PCBs and/or hexachlorobenzene at background levels may affect thyroid function during pregnancy. These findings are of particular significance, since thyroid hormones of maternal origin may play an essential role in fetal neurodevelopment.

Early Childhood Infection by Human Herpesvirus 8 in Zambia and the Role of Human Immunodeficiency Virus Type 1 Coinfection in a Highly Endemic Area

Kaposi’s sarcoma occurs at high incidence among Zambian adults and children, but there is a paucity of data on human herpesvirus 8 (HHV-8) incidence and routes of infection, especially in children. Between 1998 and 2004, the authors conducted a prospective study of viral transmission in a cohort of 684 children in Lusaka, Zambia, to estimate the annual incidence of HHV-8 from birth through 48 months of age. Maternal and pediatric human immunodeficiency virus type 1 (HIV-1) infection status was also determined. The results, based on 1,532 child-years of follow-up, showed that HHV-8 seroconversion occurs early in life. The incidence rate of HHV-8 seroconversion was 13.8 infections per 100 child-years by 48 months of age. HIV-1-infected children were at substantially higher risk for HHV-8 seroconversion (adjusted hazard ratio = 4.60, 95% confidence interval: 2.93, 7.22). Maternal HIV-1 and HHV-8 infection status were not independently associated with risk of HHV-8 seroconversion in the child. HHV-8 antibody titers in children followed at all consecutive time points revealed seroreversion of HHV-8 antibodies, with undetectable titers in some children at one or more time points after seroconversion. These results demonstrate that cross-sectional serologic screening probably underestimates true HHV-8 seroprevalence in young Zambian children because of fluctuations in detectable antibody titers.

A Simple Screening Approach for Assessing Community Prevalence and Phenotype of Polycystic Ovary Syndrome in a Semiurban Population in Sri Lanka

In most of South Asia, prevalences and phenotypes of polycystic ovary syndrome (PCOS) among women in the community are unknown. The authors aimed to estimate prevalence and phenotype in a community setting in Sri Lanka and to test a valid, feasible screening approach to early diagnosis. A community-based, cross-sectional study was carried out in 2005–2006. A random sample of 3,030 women aged 15–39 years was selected by cluster sampling proportionate to population size. An interviewer-administered questionnaire was utilized to screen for “probable cases” of PCOS based on menstrual history and clinical manifestations of hyperandrogenism. Selected “probable cases” underwent clinical, biochemical, and ovarian ultrasound assessment. The response rate was 96.2% (n = 2,915). A total of 220 (7.5%) “probable cases” were identified: 209 women with oligo/amenorrhea (95%) and 11 women with hirsutism (5%). Further evaluation of the 220 probable cases confirmed 164 newly diagnosed cases of PCOS based on the 2003 Rotterdam diagnostic criteria. With 19 previously diagnosed cases already present, total prevalence was 6.3% (95% confidence interval: 5.9, 6.8). Of the women with “oligo/amenorrhea and/or hirsutism,” 91.1% were confirmed to have PCOS; 99.4% of women with “regular cycles in the absence of clinical hyperandrogenism” were confirmed as normal. The most common phenotypes of PCOS were oligo/amenorrhea and polycystic ovaries (91.4%) and oligo/amenorrhea and hirsutism (48.3%).

Immeasurable Time Bias in Observational Studies of Drug Effects on Mortality

Observational studies suggesting that some drugs are effective at reducing mortality may have been subject to “immeasurable time bias” arising from the unidentified presence of hospitalizations when defining drug exposure with computerized health databases. The author illustrates the bias using a case-control study of 1,313 deaths and 1,313 controls selected from a cohort of 2,049 patients with chronic obstructive pulmonary disease from Saskatchewan, Canada, identified from 1990 and followed up through 1999. Different approaches were used to estimate the rate ratio of death associated with inhaled corticosteroid exposure, defined by a prescription dispensed in the 30-day period prior to the index date. More cases had been hospitalized during the 30-day exposure period (72%) than controls (26%), with lower durations of stay for cases who received an inhaled corticosteroid prescription (9.9 vs.16.2 days), thus introducing variations in measurable exposure times. The raw analysis that did not consider hospitalization found a rate ratio of 0.60 (95% confidence interval (CI): 0.50, 0.73). Alternatively, analyses accounting for variations in measurable times resulted in a rate ratio of 0.93 (95% CI: 0.76, 1.14) when weighted by measurable time, while use of the Kaplan-Meier estimator of the 30-day cumulative incidence of exposure found a rate ratio of 1.35 (95% CI: 1.14, 1.60). In conclusion, immeasurable time bias may be present in several observational database studies suggesting that certain drugs are effective at reducing mortality.

The Public-Use National Health Interview Survey Linked Mortality Files: Methods of Reidentification Risk Avoidance and Comparative Analysis

The National Center for Health Statistics (NCHS) conducts mortality follow-up for its major population-based surveys. In 2004, NCHS updated the mortality follow-up for the 1986–2000 National Health Interview Survey (NHIS) years, which because of confidentiality protections was made available only through the NCHS Research Data Center. In 2007, NCHS released a public-use version of the NHIS Linked Mortality Files that includes a limited amount of perturbed information for decedents. The modification of the public-use version included conducting a reidentification risk scenario to determine records at risk for reidentification and then imputing values for either date or cause of death for a select sample of records. To demonstrate the comparability between the public-use and restricted-use versions of the linked mortality files, the authors estimated relative hazards for all-cause and cause-specific mortality risk using a Cox proportional hazards model. The pooled 1986–2000 NHIS Linked Mortality Files contain 1,576,171 records and 120,765 deaths. The sample for the comparative analyses included 897,232 records and 114,264 deaths. The comparative analyses show that the two data files yield very similar results for both all-cause and cause-specific mortality. Analytical considerations when examining cause-specific analyses of numerically small demographic subgroups are addressed.

Testing Language Effects in Psychiatric Epidemiology Surveys with Randomized Experiments: Results from the National Latino and Asian American Study

To evaluate the prevalence of mental disorders for persons of non-English-language origin, it is essential to use translated diagnostic interviews. The equivalence of translated surveys is rarely tested formally. In the National Latino and Asian American Study (NLAAS), the authors tested whether a carefully translated mental health survey administered in Spanish produced results equivalent to those obtained by the original English version, using a randomized survey experiment. The NLAAS is a nationally representative survey carried out in the United States in 2002–2003. Bilingual respondents from the Latino section of the NLAAS (n = 332) were randomly assigned to receive either a Spanish- or English-language version of the World Mental Health Survey Composite International Diagnostic Interview. In tests of differences in lifetime and 12-month prevalences of 11 diagnoses and four higher-order aggregate disorder categories, in only one case was there an apparent difference between randomized language groups: Lifetime reports of generalized anxiety disorder were more prevalent in the bilingual group assigned to English than in the group interviewed in Spanish. Detailed follow-up analyses did not implicate any specific question in the generalized anxiety disorder protocol. Translation and back-translation of surveys does not guarantee that response probabilities are exactly equivalent. Randomized survey experiments should be incorporated into cross-cultural psychiatric surveys when possible.


American Journal of Epidemiology update - june 7

Written by admin on Jun 14th, 2008 | Filed under: epidemiology UPDATE

Alcohol Drinking and Colorectal Cancer in Japanese: A Pooled Analysis of Results from Five Cohort Studies

Colorectal cancer is an alcohol-related malignancy; however, the association appears to be stronger among Asian populations with a relatively high prevalence of the slow-metabolizing aldehyde dehydrogenase variant. To examine the association between alcohol consumption and colorectal cancer in Japanese, the authors analyzed original data from five cohort studies that measured alcohol intake using validated questionnaires at baseline. Hazard ratios were calculated in the individual studies, with adjustment for a common set of variables, and then combined using a random-effects model. During 2,231,010 person-years of follow-up (ranging variously from 1988 to 2004), 2,802 colorectal cancer cases were identified. In men, multivariate-adjusted pooled hazard ratios for alcohol intakes of 23–45.9 g/day, 46–68.9 g/day, 69–91.9 g/day, and ?92 g/day, compared with nondrinking, were 1.42 (95% confidence interval (CI): 1.21, 1.66), 1.95 (95% CI: 1.53, 2.49), 2.15 (95% CI: 1.74, 2.64), and 2.96 (95% CI: 2.27, 3.86), respectively (p for trend < 0.001). The association was evident for both the colon and the rectum. A significant positive association was also observed in women. One fourth of colorectal cancer cases in men were attributable to an alcohol intake of ?23 g/day. An alcohol-colorectal cancer association seems to be more apparent in Japanese than in Western populations. Whether this difference can be ascribed to genetic or environmental factors needs to be clarified.

Conjugated Equine Estrogens and Breast Cancer Risk in the Women’s Health Initiative Clinical Trial and Observational Study

The Women’s Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogen-alone preparations. In 1993–2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women’s Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index.

Invited Commentary: Postmenopausal Unopposed Estrogen and Breast Cancer Risk in the Women’s Health Initiative–Before and Beyond

Three large clinical trials provoked major debate when hormone replacement therapy (HRT) did not reduce coronary heart disease in postmenopausal women as expected from observational epidemiologic studies. Less discussion has ensued about breast cancer or other adverse events. In this issue of the Journal, investigators from the Women’s Health Initiative (WHI) compare breast cancer findings from the randomized trial of unopposed estrogen with those from the large WHI observational study. This commentary briefly summarizes historical highlights of menopausal hormone use; risk-versus-benefit evaluations; scientific, clinical, and policy influences immediately before and during the WHI trial; breast cancer incidence trends; and the posttrial response in US clinical practice. Factors complicating interpretation of the results include differences in breast cancer risk profiles between women in the trial and those in the observational study cohort as well as heterogeneity in the definitions of menopause and prior use of HRT as applied by the WHI investigators to the two populations. Because millions of women use HRT, it is important to consider how the WHI and other research investigations might contribute to reducing gaps in understanding the relation between HRT and breast cancer risk.

Are Patients with Skin Cancer at Lower Risk of Developing Colorectal or Breast Cancer?

Ultraviolet exposure may reduce the risk of colorectal and breast cancer as the result of rising vitamin D levels. Because skin cancer is positively related to sun exposure, the authors hypothesized a lower incidence of breast and colorectal cancer after skin cancer diagnosis. They analyzed the incidence of colorectal and breast cancer diagnosed from 1972 to 2002 among 26,916 Netherlands skin cancer patients (4,089 squamous cell carcinoma (SCC), 19,319 basal cell carcinoma (BCC), and 3,508 cutaneous malignant melanoma (CMM)). Standardized incidence ratios were calculated. A markedly decreased risk of colorectal cancer was found for subgroups supposedly associated with the highest accumulated sun exposure: men (standardized incidence ratio (SIR) = 0.83, 95% confidence interval (CI): 0.71, 0.97); patients with SCC (SIR = 0.64, 95% CI: 0.43, 0.93); older patients at SCC diagnosis (SIR = 0.59, 95% CI: 0.37, 0.88); and patients with a SCC or BCC lesion on the head and neck area (SIR = 0.59, 95% CI: 0.36, 0.92 for SCC and SIR = 0.78, 95% CI: 0.63, 0.97 for BCC). Patients with CMM exhibited an increased risk of breast cancer, especially advanced breast cancer (SIR = 2.20, 95% CI: 1.10, 3.94) and older patients at CMM diagnosis (SIR = 1.87, 95% CI: 1.14, 2.89). Study results suggest a beneficial effect of continuous sun exposure against colorectal cancer. The higher risk of breast cancer among CMM patients may be related to socioeconomic class, both being more common in the affluent group.

Analgesic Drug Use and Risk of Epithelial Ovarian Cancer

Analgesic use may reduce ovarian cancer risk, possibly through antiinflammatory or antigonadotropic effects. The authors conducted a population-based, case-control study in Washington State that included 812 women aged 35–74 years who were diagnosed with epithelial ovarian cancer between 2002 and 2005 and 1,313 controls. Use of analgesics, excluding use within the previous year, was assessed via in-person interviews. Logistic regression was used to calculate odds ratios and 95% confidence intervals. Overall, acetaminophen and aspirin were associated with weakly increased risks of ovarian cancer. These associations were stronger after more than 10 years of use (acetaminophen: odds ratio (OR) = 1.8, 95% confidence interval (CI): 1.3, 2.6; aspirin: OR = 1.6, 95% CI: 1.1, 2.2) and were present for indications of headache, menstrual pain, and other pain/injury. Reduced risk was observed among aspirin users who began regular use within the previous 5 years (OR = 0.6, 95% CI: 0.4, 1.0) or used this drug for prevention of heart disease (OR = 0.7, 95% CI: 0.5, 1.0). These results, in the context of prior findings, do not provide compelling evidence of a true increase in risk of ovarian cancer among women who use these drugs. However, they add to the weight of evidence that, in the aggregate, provides little support for the use of analgesic drugs as chemoprevention for this disease.

Insulin-like Growth Factor 1, Insulin-like Growth Factor-Binding Protein 3, and Testicular Germ-Cell Tumor Risk

Studies have consistently shown that taller men are at increased risk of testicular germ-cell tumors. Thus, it is plausible that factors associated with height may also influence risk of these tumors. The authors examined associations between testicular germ-cell tumor risk and circulating concentrations of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) among 517 cases and 790 controls from the US Servicemen’s Testicular Tumor Environmental and Endocrine Determinants (STEED) Study (2002–2005). Odds ratios and 95% confidence intervals were estimated using logistic regression models, adjusting for age, race/ethnicity, height, and body mass index. All tests of significance were two-sided. Overall, there were no associations between IGF-1 or IGFBP-3 concentrations and risk of testicular germ-cell tumors (p > 0.05). However, when cases were separated by histologic type, there was a suggestion of a reduction in seminoma risk associated with the highest concentrations of IGF-1 as compared with the lowest concentrations (odds ratio = 0.66, 95% confidence interval: 0.40, 1.09). Although there were no overall associations with insulin-like growth factor, contrary to expectation, there was a suggestion that IGF-1 concentrations may be inversely associated with risk of seminoma.

Understanding Sequelae of Injury Mechanisms and Mild Traumatic Brain Injury Incurred during the Conflicts in Iraq and Afghanistan: Persistent Postconcussive Symptoms and Posttraumatic Stress Disorder

A cross-sectional study of military personnel following deployment to conflicts in Iraq or Afghanistan ascertained histories of combat theater injury mechanisms and mild traumatic brain injury (TBI) and current prevalence of posttraumatic stress disorder (PTSD) and postconcussive symptoms. Associations among injuries, PTSD, and postconcussive symptoms were explored. In February 2005, a postal survey was sent to Iraq/Afghanistan veterans who had left combat theaters by September 2004 and lived in Maryland; Washington, DC; northern Virginia; and eastern West Virginia. Immediate neurologic symptoms postinjury were used to identify mild TBI. Adjusted prevalence ratios and 95% confidence intervals were computed by using Poisson regression. About 12% of 2,235 respondents reported a history consistent with mild TBI, and 11% screened positive for PTSD. Mild TBI history was common among veterans injured by bullets/shrapnel, blasts, motor vehicle crashes, air/water transport, and falls. Factors associated with PTSD included reporting multiple injury mechanisms (prevalence ratio = 3.71 for three or more mechanisms, 95% confidence interval: 2.23, 6.19) and combat mild TBI (prevalence ratio = 2.37, 95% confidence interval: 1.72, 3.28). The strongest factor associated with postconcussive symptoms was PTSD, even after overlapping symptoms were removed from the PTSD score (prevalence ratio = 3.79, 95% confidence interval: 2.57, 5.59).

Familial Aggregation of Cryptorchidism–A Nationwide Cohort Study

Although cryptorchidism is the most common birth defect in boys affecting 4–9 percent of newborns and 1–2 percent of boys 1 year of age, the etiology remains largely unknown. The authors investigated the contribution of genetic and environmental factors to familial aggregation of cryptorchidism. Using Danish health registers, they identified 25,395 boys diagnosed with cryptorchidism in a cohort of 1,022,713 boys born in 1977–2005. Using binomial log-linear regression, they estimated recurrence risk ratios (RRRs) of cryptorchidism for male twin pairs and first-, second-, and third-degree relatives of a cryptorchidism case. The RRR in same-sex twins was 10.1 (95% confidence interval (CI): 7.78, 13.1). The RRR among first-degree relatives was significantly higher among brothers (RRR = 3.52, 95% CI: 3.26, 3.79) than for offspring of a cryptorchidism case (RRR = 2.31, 95% CI: 2.09, 2.54). The RRR was also found to be significantly higher in maternal (RRR = 2.12, 95% CI: 1.74, 2.60) than paternal (RRR = 1.28, 95% CI: 1.01, 1.61) half brothers. In conclusion, inherited factors were found to have a moderate influence on the risk of cryptorchidism. The data are compatible with the hypothesis that maternal factors operating in utero are important for the risk of cryptorchidism.

Parental Subfecundity and Risk of Decreased Semen Quality in the Male Offspring: A Follow-up Study

A few studies have found poor semen quality in sons whose mothers have received fertility treatment, but it is unknown whether the poor semen quality is related to the infertility treatment or to infertility per se, for example, whether it is caused by hereditable factors. Using data from a population-based, Danish follow-up study conducted in 2005–2006, the authors of the present study examined whether sons of subfertile couples who had not received fertility treatment had poorer semen quality than sons of fertile couples. Among the 311 participants, an inverse association between parental waiting time to pregnancy and both semen volume and total sperm count was observed (p trend = 0.04 and p trend = 0.046, respectively). Semen volume in sons of subfertile parents (pregnant after ?1 years) was 19% lower in comparison with that in sons of parents whose waiting time to pregnancy was 0–6 months (p = 0.02). Additionally, sperm concentration and percentage of morphologically normal sperm were, respectively, 22% (p = 0.15) and 23% (p = 0.13) lower in sons of subfertile parents. Results suggest a small-to-moderate effect of parental subfecundity on semen quality in sons, comparable with the hypothesis that low fecundity has at least partly hereditable causes.

Waist Circumference and Mortality

The authors examined the association between waist circumference and mortality among 154,776 men and 90,757 women aged 51–72 years at baseline (1996–1997) in the NIH-AARP Diet and Health Study. Additionally, the combined effects of waist circumference and body mass index (BMI; weight (kg)/height (m)2) were examined. All-cause mortality was assessed over 9 years of follow-up (1996–2005). After adjustment for BMI and other covariates, a large waist circumference (fifth quintile vs. second) was associated with an approximately 25% increased mortality risk (men: hazard ratio (HR) = 1.22, 95% confidence interval (CI): 1.15, 1.29; women: HR = 1.28, 95% CI: 1.16, 1.41). The waist circumference-mortality association was found in persons with and without prevalent disease, in smokers and nonsmokers, and across different racial/ethnic groups (non-Hispanic Whites, non-Hispanic Blacks, Hispanics, and Asians). Compared with subjects with a combination of normal BMI (18.5–<25) and normal waist circumference, those in the normal-BMI group with a large waist circumference (men: ?102 cm; women: ?88 cm) had an approximately 20% higher mortality risk (men: HR = 1.23, 95% CI: 1.08, 1.39; women: HR = 1.22, 95% CI: 1.09, 1.36). The finding that persons with a normal BMI but a large waist circumference had a higher mortality risk in this study suggests that increased waist circumference should be considered a risk factor for mortality, in addition to BMI.

Does Temperature Modify the Association between Air Pollution and Mortality? A Multicity Case-Crossover Analysis in Italy

Adverse health effects of particulate matter <10 µm in aerodynamic diameter (PM10) and high temperatures are well known, but the extent of their interaction on mortality is less clear. This paper describes effect modification of temperature in the PM10–mortality association and tests the hypothesis that higher PM10 effects in summer are due to enhanced exposure to particles. All deaths of residents of nine Italian cities between 1997 and 2004 were selected. The case-crossover approach was adopted to estimate the effect of PM10 on mortality by season and temperature level. Three strata of temperature corresponding to low, medium, and high “ventilation” were identified, and the interaction between PM10 and temperature within each stratum was examined. Season and temperature levels strongly modified the PM10–mortality association: for a 10-µg/m3 variation in PM10, a 2.54% increase in risk of death in summer (95% confidence interval: 1.31, 3.78) compared with 0.20% (95% confidence interval: –0.08, 0.49) in winter. Analysis of the interaction between PM10 and temperature within temperature strata resulted in positive but, in most cases, nonstatistically significant coefficients. The authors found much higher PM10 effects on mortality during warmer days. The hypothesis that such an effect is attributable to enhanced exposure to particles in summer could not be rejected.

Diabetic Control and Risk of Tuberculosis: A Cohort Study

Diabetes mellitus is associated with tuberculosis. A cohort of 42,116 clients aged 65 years or more, enrolled at 18 Elderly Health Service centers in Hong Kong in 2000, were followed up prospectively through the territory-wide tuberculosis registry for development of tuberculosis from 3 months after enrollment to December 31, 2005, by use of their identity card numbers as unique identifier. The effects of diabetes mellitus and diabetic control on tuberculosis risk were assessed with adjustment for sociodemographic and other background variables. Diabetes mellitus was associated with a modest increase in the risk of active, culture-confirmed, and pulmonary (with or without extrapulmonary involvement) but not extrapulmonary (with or without pulmonary involvement) tuberculosis, with adjusted hazard ratios of 1.77 (95% confidence interval: 1.41, 2.24), 1.91 (95% confidence interval: 1.45, 2.52), 1.89 (95% confidence interval: 1.48, 2.42), and 1.00 (95% confidence interval: 0.54, 1.86), respectively. Diabetic subjects with hemoglobin A1c <7% at enrollment were not at increased risk. Among diabetic subjects, higher risks of active, culture-confirmed, and pulmonary but not extrapulmonary tuberculosis were observed with baseline hemoglobin A1c ?7% (vs. <7%), with adjusted hazard ratios of 3.11 (95% confidence interval: 1.63, 5.92), 3.08 (95% confidence interval: 1.44, 6.57), 3.63 (95% confidence interval: 1.79, 7.33), and 0.77 (95% confidence interval: 0.18, 3.35), respectively.

Geographic Prevalence and Multilevel Determination of Community-level Factors Associated with Herpes Simplex Virus Type 2 Infection in Chennai, India

Herpes simplex virus type 2 (HSV-2) is one of the most prevalent sexually transmitted infections, and it increases the risk of transmission of human immunodeficiency virus type 1 at least twofold. Individual-level factors are insufficient to explain geographic and population variation in HSV-2, suggesting the need to identify ecologic factors. The authors sought to determine the geographic prevalence and community-level factors associated with HSV-2 after controlling for individual-level factors among slums in Chennai, India. From March to June 2001, participants aged 18–40 years voluntarily completed a survey and were tested for HSV-2. Community characteristics were assessed through interviews with key informants and other secondary data sources. Multilevel nonlinear analysis was conducted. Eighty-five percent of eligible persons completed the survey; of these, 98% underwent HSV-2 testing, producing a final sample of 1,275. Participants were of Tamil ethnicity, were predominantly female and married, and were on average 30 years old. Fifteen percent were infected with HSV-2, and there was significant variation in HSV-2 prevalence among communities. After controlling for individual-level factors, the authors identified community-level factors, including socioeconomic status and the presence of injection drug users, that were independently associated with HSV-2 and explained 11% of the variance in prevalence. Future studies are needed to test mechanisms through which these community-level factors may be operating.

Assessment of Selection Bias in the Canadian Case-Control Study of Residential Magnetic Field Exposure and Childhood Leukemia

The authors evaluated the role of selection bias in the 1999 Canadian case-control study of residential magnetic field exposure and childhood leukemia. They included cases, participating controls, and first-choice nonparticipating controls in their analyses. Exposure was assessed by wire coding, a classification system based on the distribution line characteristics near homes. Although an imperfect measure of magnetic field exposure, wire coding is the only method applicable to nonparticipating subjects. First-choice nonparticipant controls tended to be of lower socioeconomic status than their replacements (non-first-choice participant controls), and lower socioeconomic status was related to higher wire code categories. The odds ratios for developing childhood leukemia in the highest exposure category were 1.6 (95% confidence interval: 1.0, 2.6) when the actual participating controls were used and 1.3 (95% confidence interval: 0.8, 2.1) when the first-choice ideal controls were used, regardless of their participation. Overall, the authors conclude that, although there is some evidence for control selection or participation bias in the Canadian study, it is unlikely to explain entirely the observed association between magnetic field exposure and childhood leukemia. Inherent problems in exposure assessment for nonparticipating subjects, however, limit the interpretations of these results, and the role of selection bias cannot entirely be dismissed on the basis of these results alone.

A Regression Approach for Estimating Multiday Adverse Health Effects of PM10 When Daily PM10 Data Are Unavailable

The authors propose a regression-based approach for obtaining multiday estimates of the adverse health effects of ambient particulate matter less than 10 µm in diameter (PM10) when daily PM10 time-series data are unavailable. This situation is common in the United States, because most US cities take PM10 measurements every 6 days. Current evidence suggests that adverse effects of PM10 are not concentrated on a single day but rather are spread out over multiple days, so the unavailability of daily PM10 data presents a problem for the estimation of these effects. The proposed model estimates weights that are used to construct a linear combination of single-lag PM10 effect estimates obtained from the available PM10 data. It is shown that this new approach provides estimates of the effect of PM10 on mortality that have less bias and mean squared error than currently available methods. Application of this method to the US cities contained in the National Morbidity, Mortality, and Air Pollution Study database produces an estimated national average effect of PM10 on nonaccidental mortality in persons over age 65 years, corresponding to a 0.32% increase per 10-µg/m3 increment in PM10. The estimated effects for cardiorespiratory mortality and other mortality are 0.34% and 0.22%, respectively.



American Journal of Epidemiology update, may 24

Written by admin on Jun 6th, 2008 | Filed under: epidemiology UPDATE

Psychiatric Diagnoses in Historic and Contemporary Military Cohorts: Combat Deployment and the Healthy Warrior Effect

Research studies have identified heightened psychiatric problems among veterans of Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF). However, these studies have not compared incidence rates of psychiatric disorders across robust cohorts, nor have they documented psychiatric problems prior to combat exposure. The authors’ objectives in this study were to determine incidence rates of diagnosed mental disorders in a cohort of Marines deployed to combat during OIF or OEF in 2001–2005 and to compare these with mental disorder rates in two historical and two contemporary military control groups. After exclusion of persons who had been deployed to a combat zone with a preexisting psychiatric diagnosis, the cumulative rate of post-OIF/-OEF mental disorders was 6.4%. All psychiatric conditions except post-traumatic stress disorder occurred at a lower rate in combat-deployed personnel than in personnel who were not deployed to a combat zone. The findings suggest that psychiatric disorders in Marines are diagnosed most frequently during the initial months of recruit training rather than after combat deployment. The disproportionate loss of psychologically unfit personnel early in training creates a “healthy warrior effect,” because only those persons who have proven their resilience during training remain eligible for combat.

Invited Commentary: How Healthy is the “Healthy Warrior”?

In this issue of the Journal, Larson et al. (Am J Epidemiol 2008;167:1269–1276) report incidence rates of 11.8% for any mental disorder and 1.6% for post-traumatic stress disorder among US Marines deployed during Operation Iraqi Freedom and Operation Enduring Freedom. Various methodological reasons can help explain why these rates are lower than those found in previous wars. One primary reason is varying methods of diagnosis. Other reasons include differences in percentages of active-duty personnel, windows of observation, and methods of calculating rates. In addition, comorbidity for some mental disorders and specific risks for developing certain disorders complicate interpretation of rates. Nevertheless, Larson et al. document evidence for the “healthy warrior” effect—namely that deployed Marines have fewer mental disorders than nondeployed Navy and Marine Corps personnel, with the exception of stress disorders. Suggestions are made for directions of future research into this effect.

Maternal Age, Exposure to Siblings, and Risk of Amyotrophic Lateral Sclerosis

Between 1987 and 2005, the authors conducted a nested case-control study based on the Swedish Multi-Generation Register to investigate whether early life exposures, namely, maternal age at delivery and exposure to siblings, are associated with an increased risk of amyotrophic lateral sclerosis (ALS). The study comprised 768 ALS cases and five controls per case matched by birth year and gender. Odds ratios and their corresponding 95% confidence intervals for ALS were estimated by conditional logistic regression modeling. Low maternal age (?20 years) and high maternal age (?41 years) were both associated with higher risk of ALS (odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.1, 2.0 and OR = 1.7, 95% CI: 1.1, 2.4, respectively). The relative risk of ALS increased slightly with increasing number of younger siblings (OR = 1.1, 95% CI: 1.0, 1.1; p = 0.02). Children whose first younger sibling was born after the age of 6 years had the greatest relative risk (OR = 1.8, 95% CI: 1.2, 2.7). Exposure to older siblings was not associated with the risk of ALS. Although the strength of the observed associations was modest, these results provided further support for the theory that early life exposures might contribute to the disease pathogenesis.

Predictors of the Timing of Natural Menopause in the Multiethnic Cohort Study

The timing of natural menopause has implications for several health endpoints; in particular, it is a risk factor for breast cancer. The authors investigated factors influencing the timing of natural menopause among 95,704 women with a mean age of 59.7 years (10th–90th percentile range, 47.0–71.0) in five racial/ethnic groups in the Multiethnic Cohort Study, including non-Latina Whites, Japanese Americans, African Americans, Native Hawai’ians, and Latinas. The authors investigated whether race/ethnicity and several lifestyle and reproductive characteristics were associated with the timing of natural menopause. Race/ethnicity was a significant independent predictor of the timing of natural menopause. Other factors, including smoking, age at menarche, parity, and body mass index, did not significantly alter the race/ethnicity-specific hazard ratios. Relative to non-Latina Whites, natural menopause occurred earlier among Latinas (US-born Latinas: hazard ratio (HR) = 1.10, 95% confidence interval (CI): 1.07, 1.14; non-US-born Latinas: HR = 1.25, 95% CI: 1.21, 1.30) and later among Japanese Americans (HR = 0.93, 95% CI: 0.90, 0.95). These results support the hypothesis that the timing of natural menopause is driven by a combination of genetic, reproductive, and lifestyle factors.

Are Racial Disparities in Preterm Birth Larger in Hypersegregated Areas?

The causes of the racial/ethnic disparity in preterm birth (PTB) remain largely unknown; traditional risk factors such as smoking and prenatal care fail to account for it. The authors examined whether living in metropolitan areas (MAs) with high levels of residential racial segregation along multiple dimensions (hypersegregation) was associated with higher rates of PTB or larger racial disparities in PTB and whether segregation modified the established race-age association in PTB. The authors merged 2000 natality data (n = 1,944,703) with US Census measures of Black-White hypersegregation. They executed two-level hierarchical logistic regression analyses among White and Black mothers in 237 MAs to estimate the odds of PTB by hypersegregation, race, and age, after controlling for covariates. In unadjusted and adjusted models, Black infants in hypersegregated MAs were more likely to be preterm than Black infants in nonhypersegregated MAs (p < 0.001). Black-White PTB disparities were larger in hypersegregated areas than in nonhypersegregated areas (p < 0.001), and the age-race association with PTB was modified by hypersegregation (p < 0.001). Living in a hypersegregated MA had a more pronounced association with PTB among older Black women, and racial disparities in PTB were larger in hypersegregated areas among older mothers (p < 0.001). Since over 40% of Black childbearing women live in hypersegregated areas, residential segregation may be an important social determinant of racial birth disparities.

Risk of Oral Clefts in Relation to Prepregnancy Weight Change and Interpregnancy Interval

Epidemiologic evidence regarding the influence of maternal obesity on the risk of oral clefts is inconsistent. It is unknown whether increases in maternal weight before pregnancy are related to the risk of these malformations. The authors conducted a population-based cohort study in Sweden among 220,328 women who had their first two pregnancies between 1992 and 2004. The risk of oral clefts during the second pregnancy was estimated in relation to maternal change in body mass index (BMI; weight (kg)/height (m)2) from the beginning of the first pregnancy to the beginning of the second pregnancy. Among women whose second-pregnancy BMI was ?3 units higher than their first-pregnancy BMI, the adjusted risk of isolated cleft palate was 2.3 times higher (95% confidence interval: 1.4, 4.0) as compared with women whose BMI did not change substantially. BMI change was not related to the risk of cleft lip. Unexpectedly, the birth prevalence of isolated cleft palate per 1,000 livebirths increased linearly with the length of the interpregnancy interval, from 0.3 in women with intervals of <12 months to 0.9 in women with intervals of ?48 months (adjusted p for trend = 0.002). High prepregnancy maternal weight gain and long interpregnancy intervals appear to be associated with increased risk of cleft palate.

Association between Serum trans-Monounsaturated Fatty Acids and Breast Cancer Risk in the E3N-EPIC Study

The authors assessed the association between serum phospholipid fatty acids as biomarkers of fatty acid intake and breast cancer risk among women in the E3N Study (1989–2002), the French component of the European Prospective Investigation into Cancer and Nutrition. During an average of 7 years of follow-up, 363 cases of incident invasive breast cancer were documented among 19,934 women who, at baseline (1995–1998), had completed a diet history questionnaire and provided serum samples. Controls were randomly matched to cases by age, menopausal status at blood collection, fasting status at blood collection, date, and collection center. Serum phospholipid fatty acid composition was assessed by gas chromatography. Adjusted odds ratios for risk of breast cancer with increasing levels of fatty acids were calculated using conditional logistic regression. An increased risk of breast cancer was associated with increasing levels of the trans-monounsaturated fatty acids palmitoleic acid and elaidic acid (highest quintile vs. lowest: odds ratio = 1.75, 95% confidence interval: 1.08, 2.83; p-trend = 0.018). cis-Monounsaturated fatty acids were unrelated to breast cancer risk. A high serum level of trans-monounsaturated fatty acids, presumably reflecting a high intake of industrially processed foods, is probably one factor contributing to increased risk of invasive breast cancer in women.

Personal Use of Hair Dye and the Risk of Certain Subtypes of Non-Hodgkin Lymphoma

Personal use of hair dye has been inconsistently linked to risk of non-Hodgkin lymphoma (NHL), perhaps because of small samples or a lack of detailed information on personal hair-dye use in previous studies. This study included 4,461 NHL cases and 5,799 controls from the International Lymphoma Epidemiology Consortium 1988–2003. Increased risk of NHL (odds ratio (OR) = 1.3, 95% confidence interval (CI): 1.1, 1.4) associated with hair-dye use was observed among women who began using hair dye before 1980. Analyses by NHL subtype showed increased risk for follicular lymphoma (FL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) but not for other NHL subtypes. The increased risks of FL (OR = 1.4, 95% CI: 1.1, 1.9) and CLL/SLL (OR = 1.5, 95% CI: 1.1, 2.0) were mainly observed among women who started using hair dyes before 1980. For women who began using hair dye in 1980 or afterward, increased FL risk was limited to users of dark-colored dyes (OR = 1.5, 95% CI: 1.1, 2.0). These results indicate that personal hair-dye use may play a role in risks of FL and CLL/SLL in women who started use before 1980 and that increased risk of FL among women who started use during or after 1980 cannot be excluded.


International Journal of Epidemiology update, apr 3

Written by admin on Apr 3rd, 2008 | Filed under: epidemiology UPDATE
Body mass index, weight change and mortality risk in a prospective study in India
Catherine Sauvaget, Kunnambath Ramadas, Gigi Thomas, Jissa Vinoda, Somanathan Thara, and Rengaswamy Sankaranarayanan
Int. J. Epidemiol. 2008 published 3 April 2008, 10.1093/ije/dyn059
http://ije.oxfordjournals.org/
Commentary: Personality and health inequality: inconclusive evidence for an indirect hypothesis
John Gallacher
Int. J. Epidemiol. 2008 published 3 April 2008, 10.1093/ije/dyn062
http://ije.oxfordjournals.org/