Healthy Eating and Risks of Total and Cause-Specific Death among Low-Income Populations of African-Americans and Other Adults in the Southeastern United States: A Prospective Cohort Study.

BACKGROUND: A healthy diet, as defined by the US Dietary Guidelines for Americans (DGA), has been associated with lower morbidity and mortality from major chronic diseases in studies conducted in predominantly non-Hispanic white individuals. It is unknown whether this association can be extrapolated to African-Americans and low-income populations. METHODS AND FINDINGS: We examined the associations of adherence to the DGA with total and cause-specific mortality in the Southern Community Cohort Study, a prospective study that recruited 84,735 American adults, aged 40-79 y, from 12 southeastern US states during 2002-2009, mostly through community health centers that serve low-income populations. The present analysis included 50,434 African-Americans, 24,054 white individuals, and 3,084 individuals of other racial/ethnic groups, among whom 42,759 participants had an annual household income less than US$15,000. Usual dietary intakes were assessed using a validated food frequency questionnaire at baseline. Adherence to the DGA was measured by the Healthy Eating Index (HEI), 2010 and 2005 editions (HEI-2010 and HEI-2005, respectively). During a mean follow-up of 6.2 y, 6,906 deaths were identified, including 2,244 from cardiovascular disease, 1,794 from cancer, and 2,550 from other diseases. A higher HEI-2010 score was associated with lower risks of disease death, with adjusted hazard ratios (HRs) of 0.80 (95% CI, 0.73-0.86) for all-disease mortality, 0.81 (95% CI, 0.70-0.94) for cardiovascular disease mortality, 0.81 (95% CI, 0.69-0.95) for cancer mortality, and 0.77 (95% CI, 0.67-0.88) for other disease mortality, when comparing the highest quintile with the lowest (all p-values for trend < 0.05). Similar inverse associations between HEI-2010 score and mortality were observed regardless of sex, race, and income (all p-values for interaction > 0.50). Several component scores in the HEI-2010, including whole grains, dairy, seafood and plant proteins, and ratio of unsaturated to saturated fatty acids, showed significant inverse associations with total mortality. HEI-2005 score was also associated with lower disease mortality, with a HR of 0.86 (95% CI, 0.79-0.93) when comparing extreme quintiles. Given the observational study design, however, residual confounding cannot be completely ruled out. In addition, future studies are needed to evaluate the generalizability of these findings to African-Americans of other socioeconomic status. CONCLUSIONS: Our results showed, to our knowledge for the first time, that adherence to the DGA was associated with lower total and cause-specific mortality in a low-income population, including a large proportion of African-Americans, living in the southeastern US.

Obesity and all-cause mortality among black adults and white adults.

In recent pooled analyses among whites and Asians, mortality was shown to rise markedly with increasing body mass index (BMI; weight (kg)/height (m)(2)), but much less is known about this association among blacks. This study prospectively examined all-cause mortality in relation to BMI among 22,014 black males, 9,343 white males, 30,810 black females, and 14,447 white females, aged 40-79 years, from the Southern Community Cohort Study, an epidemiologic cohort of largely low-income participants in 12 southeastern US states. Participants enrolled in the cohort from 2002 to 2009 and were followed up to 8.9 years. Hazard ratios and 95% confidence intervals for mortality were obtained from sex- and race-stratified Cox proportional hazards models in association with BMI at cohort entry, adjusting for age, education, income, cigarette smoking, and alcohol consumption. Elevated BMI was associated with increased mortality among whites (hazard ratios for BMI >40 vs. 20-24.9 = 1.37 (95% confidence interval (CI): 1.02, 1.84) and 1.47 (95% CI: 1.15, 1.89) for white males and white females, respectively) but not significantly among blacks (hazard ratios = 1.13 (95% CI: 0.89, 1.43) and 0.87 (95% CI: 0.72, 1.04) for black males and black females, respectively). In this large cohort, obesity in mid-to-late adulthood among blacks was not associated with the same excess mortality risk seen among whites.

The false-positive to false-negative ratio in epidemiologic studies.

The ratio of false-positive to false-negative findings (FP:FN ratio) is an informative metric that warrants further evaluation. The FP:FN ratio varies greatly across different epidemiologic areas. In genetic epidemiology, it has varied from very high values (possibly even >100:1) for associations reported in candidate-gene studies to very low values (1:100 or lower) for associations with genome-wide significance. The substantial reduction over time in the FP:FN ratio in human genome epidemiology has corresponded to the routine adoption of stringent inferential criteria and comprehensive, agnostic reporting of all analyses. Most traditional fields of epidemiologic research more closely follow the practices of past candidate gene epidemiology, and thus have high FP:FN ratios. Further, FP and FN results do not necessarily entail the same consequences, and their relative importance may vary in different settings. This ultimately has implications for what is the acceptable FP:FN ratio and for how the results of published epidemiologic studies should be presented and interpreted.

Diabetes mellitus, other medical conditions and pancreatic cancer: a case-control study.

BACKGROUND: Diabetes and other medical conditions have been related to pancreatic cancer, but time risk quantification is unsettled. METHODS: We combined data from two case-control studies conducted in Italy, including 688 pancreatic cancer cases and 2204 controls. All subjects were interviewed by trained interviewers during their hospital stay. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression. RESULTS: Overall, 103 cases (15%) and 125 controls (5.7%) reported a history of diabetes. The OR for pancreatic cancer was more pronounced among those diagnosed with diabetes in the previous 2 years (OR = 5.17; 95% CI = 2.71-9.87) than among those with diabetes diagnosed more than 2 years ago (OR = 2.35; 95% CI = 1.70-3.26). The ORs remained significantly elevated 2-4 years (OR = 3.81; 95% CI = 2.07-7.04) and 5-9 years (OR = 3.75; 95% CI = 2.13-6.59) since diagnosis of diabetes, after which a non-significant 20% increased risk for pancreatic cancer was observed. As compared to non-diabetic non-smokers, the OR was 1.85 among non-diabetic current smokers, 2.17 among diabetic never/former smokers, and rose to 4.67 among diabetic current smokers, indicating a multiplicative effect between these two risk factors. Pancreatic cancer was significantly associated with pancreatitis, primarily among those diagnosed within 2 years (OR = 7.16; 95% CI = 2.25-22.78). In addition, the ORs were elevated for cholelithiasis (3.53; 95% CI = 1.67-7.45) and gastroduodenal ulcer (3.16; 95% CI = 1.14-8.73) only among those diagnosed within the past 2 years. CONCLUSIONS: Diabetes is associated with heightened risk of pancreatic cancer. The association is significant for diabetes diagnosed up to 10 years before pancreatic cancer.

Renal cell cancer among African Americans: an epidemiologic review.

Incidence rates for renal cell cancer, which accounts for 85% of kidney cancers, have been rising more rapidly among blacks than whites, almost entirely accounted for by an excess of localized disease. This excess dates back to the 1970s, despite less access among blacks to imaging procedures in the past. In contrast, mortality rates for this cancer have been virtually identical among blacks and whites since the early 1990s, despite the fact that nephrectomy rates, regardless of stage, are lower among blacks than among whites. These observations suggest that renal cell cancer may be a less aggressive tumor in blacks. We have reviewed the epidemiology of renal cell cancer, with emphasis on factors which may potentially play a role in the observed differences in incidence and mortality patterns of renal cell cancer among blacks and whites. To date, the factors most consistently, albeit modestly, associated with increased renal cell cancer risk in epidemiologic studies among whites--obesity, hypertension, cigarette smoking--likely account for less than half of these cancers, and there is virtually no epidemiologic evidence in the literature pertaining to their association with renal cell cancer among blacks. There is a long overdue need for detailed etiologic cohort and case-control studies of renal cell cancer among blacks, as they now represent the population at highest risk in the United States. In particular, investigation of the influence on renal cell cancer development of hypertension and chronic kidney disease, both of which occur substantially more frequently among blacks, is warranted, as well as investigations into the biology and natural history of this cancer among blacks.

The clinical course of immediate breast implant reconstruction after breast cancer.

BACKGROUND: The number of women suitable for breast conserving treatment as well as immediate reconstruction after breast cancer has been increasing, and studies of complications hereafter are needed. MATERIAL AND METHODS: The cohort was identified in the prospective database of the Danish Registry for Plastic Surgery of the Breast during the period 1999 to 2006; 167 women with 189 immediate breast reconstructions (40 one-stage and 149 two-stage procedures) after breast cancer without a history of radiation therapy. The women were followed for complications until November 2009. Cumulative incidence risks were computed for infection, hematoma, seroma, severe capsular contracture (modified Baker III and IV), extrusion of the implant, implant rupture, asymmetry/displacement of the implant, any complication, and reoperation. In addition, we compared the postoperative course of immediate two-stage procedures with delayed two-stage procedures. RESULTS: The overall eight-year risk estimates for the immediate procedures were 76.4% for any complication, 5.3% for severe capsular contracture, 29.5% for displacement/asymmetry of the implant and 40.6% for reoperation. Significantly higher risk for reoperation was observed after immediate one-stage than after two-stage procedures. For immediate two-stage procedures acute complications such as infection, seroma and hematoma were higher in the expansion period than after the second planned surgery. Higher risks for acute complications were observed after immediate than after delayed two-stage procedures. CONCLUSION: Immediate breast implant reconstruction was found to have substantial risks of complications in non-radiated women, which should be considered in the guidance of breast cancer patients before choosing reconstructive procedure.

Determinants of plasma PFOA and PFOS levels among 652 Danish men.

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are used in a variety of industrial and consumer products and have been detected worldwide in human blood. The sources for human exposure are not well described, but dietary intake is suggested as an important source. In this study of 652 Danish men from the Diet, Cancer and Health cohort, we examined intake of 10 major dietary groups, tap water drinks, alcohol consumption, cooking method, geographical area, age, smoking status, and BMI as potential determinants of PFOA and PFOS plasma levels. Living in the Aarhus area was associated with higher PFOA and PFOS plasma levels compared with living in the Copenhagen area, and never smokers had higher levels than current smokers. Frying as compared with other cooking methods was a determinant of PFOA and PFOS levels. BMI and alcohol consumption were inversely associated with both compounds. Among the dietary groups, only intake of eggs was significantly positively associated with PFOS plasma levels. In future studies, PFOA and PFOS levels in air, dust and water samples should be measured to elucidate further the sources of exposure; exposure through diet needs to be studied in greater detail. Our finding of a higher body burden of PFOA and PFOS among never smokers also warrants further evaluation.

Integrated solution to purification challenges in the manufacture of a soluble recombinant protein in E. coli.

Apolipoprotein A 1 Milano (ApoA-1M), the protein component of a high-density lipoprotein (HDL) mimic with promising potential for reduction of atherosclerotic plaque, is produced at large scale by expression in E. coli. Significant difficulty with clearance of host cell proteins (HCPs) was experienced in the original manufacturing process despite a lengthy downstream purification train. Analysis of purified protein solutions and intermediate process samples led to identification of several major HCPs co-purifying with the product and a bacterial protease potentially causing a specific truncation of ApoA-1M found in the final product. Deletion of these genes from the original host strain succeeded in substantially reducing the levels of HCPs and the truncated species without adversely affecting the overall fermentation productivity, contributing to a much more efficient and robust new manufacturing process.

Excess suicide risk and other external causes of death among women with cosmetic breast implants: a neglected research priority.

Five large epidemiologic mortality studies of women with cosmetic breast implants have consistently reported a two- to threefold higher rate of suicide compared with the general female population. Overall, 135 suicides have been observed, compared with 66.9 expected, yielding a significantly elevated standardized mortality ratio of 2.0 (95% CI, 1.5-2.6). In addition to suicides, excesses from other external causes of death related to drug and alcohol abuse/dependence, atypical motor vehicle accidents, and other self-harm causes have been consistently reported. These observations, together with limited but direct epidemiologic evidence of preimplant psychiatric hospitalization, as well as self-reports of preimplant psychiatric disorders, including depression, eating disorders, and body image dissatisfaction, among implant women raise the possibility of significant underlying psychiatric morbidity for a subgroup of implant patients. Research into the psychiatric profiles and history of the women who have committed suicide in the investigated cohorts appears warranted.

Prenatal exposure to PFOA and PFOS and risk of hospitalization for infectious diseases in early childhood.

OBJECTIVES: To examine whether prenatal exposure to perfluorooctanesulfonate (PFOS) or perfluorooctanoate (PFOA) is associated with the occurrence of hospitalization for infectious diseases during early childhood. METHODS: We randomly selected 1400 pregnant women and their offspring from the Danish National Birth Cohort (1996-2002) and measured PFOS and PFOA levels in maternal blood during early pregnancy. Hospitalizations for infection of the offspring were identified by the linkage to the National Hospital Discharge Register through 2008. RESULTS: Hospitalizations due to infections were not associated with prenatal exposure to PFOA and PFOS. On the contrary, the relative risks of hospitalizations ranged from 0.71 to 0.84 for the three higher quartiles of maternal PFOA levels compared with the lowest, but no dose-response pattern was found. No clear pattern was observed when results were stratified by child's age at infection, with the exception of an inverse association between maternal PFC levels and risk of hospitalization during the child's first year of life. CONCLUSIONS: These findings suggest that prenatal exposure to PFOA or PFOS is not associated with increased risk of infectious diseases leading to hospitalization in early childhood.

Local complications after cosmetic breast augmentation: results from the Danish Registry for Plastic Surgery of the Breast.

BACKGROUND: Prospective long-term data on the occurrence of complications following breast augmentation are sparse and the reported frequencies differ substantially. METHODS: The Danish Registry for Plastic Surgery of the Breast has prospectively registered preoperative, perioperative, and postoperative data for women undergoing breast augmentation in Denmark since 1999. From the Registry, the authors identified 5373 women with a primary cosmetic breast augmentation between 1999 and 2007. The authors calculated incidence proportions of adverse clinical outcomes within three time intervals (0 to 30 days, 0 to 3 years, and 0 to 5 years) after primary implantation. Outcomes of primary interest were capsular contracture, asymmetry/ displacement of the implant, hematoma, and infection. RESULTS: During the entire follow-up period (mean, 3.8 years; range, 0.1 to 8.7 years), 16.7 percent of the women were registered with an adverse event and 4.8 percent of the women were registered with a surgery-requiring complication. The most common adverse events within 30 days were hematoma (1.1 percent) and infections (1.2 percent), whereas the most common adverse events within 5 years were change of tactile sense (8.7 percent) and asymmetry/ displacement of implant (5.2 percent). Within 5 years, 1.7 percent of the women had a record of severe capsular contracture. Displacement/asymmetry and capsular contracture were the most frequent indications for reoperation with removal or exchange of the implant. CONCLUSIONS: Population-based complication frequencies among women with cosmetic breast augmentation in a Danish nationwide implant registry were generally lower than those reported in other studies, although frequencies of complications increased with length of follow-up.

Cancer among Scandinavian women with cosmetic breast implants: a pooled long-term follow-up study.

No increased risks of specific types of cancer following breast implantation have been consistently reported, but data on risk beyond 15 years are limited. We have pooled the results of 2 nationwide cohort studies of 3,486 Swedish and 2,736 Danish women who underwent cosmetic breast implantation between 1965 and 1993. Cancer incidence through 2002 was ascertained through nationwide cancer registries. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated to compare cancer incidence among women with implants with women in the general population. Mean duration of follow up was 16.6 years (range 0.1-37.8 years). Over 50% of women were followed for 15 years or more after breast implantation and 13.3% for at least 25 years. There was a reduced incidence of breast cancer (SIR=0.73; 95% CI 0.58-0.90), whereas lung cancer was above expectation (SIR=1.64; 95% CI 1.10-2.36). The increased risk of lung cancer is expected due to the high prevalence of smoking among the women with implants in our study. With respect to other site-specific cancers, no significantly increased or decreased SIR was observed. This study, which includes women followed for almost 4 decades, represents the longest follow up of women with cosmetic breast implants to date. The results provide no evidence of an association between breast implants and any type of cancer.

Aspirin and other non-steroidal anti-inflammatory drugs and risk of colorectal cancer: a Danish cohort study.

OBJECTIVE: The optimal duration and dose of aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) in the potential prevention of colorectal cancer (CRC) have not been established. We examined this issue in the Danish Diet, Cancer, and Health Study. METHODS: Self-reported NSAID use at entry (January 1995-May 1997) was updated through June 2006, using a nationwide prescription database. CRC incidence was ascertained from nationwide registers. Cox proportional hazards regression was used to compute confounder-adjusted incidence rate ratios (RRs) and 95% confidence intervals (CIs). RESULTS: From 51,053 cohort subjects, we identified 615 CRC cases during 1995-2006. Daily aspirin use at entry was associated with a decreased risk of CRC (RR, 0.73; 95% CI, 0.49-1.10). A similar risk reduction was seen among subjects with 10 or more prescriptions for aspirin or non-aspirin NSAIDs and five or more years of follow-up. Most aspirin prescriptions were for 75-150 mg aspirin tablets. Among non-aspirin NSAID users, only those with body mass index (BMI) above 25 showed risk reductions [RR, 0.69 (0.47-1.03) for 10 or more prescriptions]. CONCLUSIONS: Long-term consistent use of aspirin or non-aspirin NSAIDs appears necessary to achieve a protective effect against CRC. Further studies of the effective dose of aspirin and the potential interaction between NSAID use and BMI are warranted.

The prognostic impact of comorbidities on renal cancer, 1995 to 2006: a Danish population based study.

PURPOSE: Comorbid disease in patients with renal cancer may affect renal cancer prognosis. We estimated the risk of 1 and 5-year mortality in patients with renal cancer in northern Denmark by comorbidity status. MATERIALS AND METHODS: We performed a cohort study tracking mortality in all patients with an incident diagnosis of renal cancer between 1995 and 2006 in a population of 1.6 million residents in northern Denmark. Using hospital discharge data before cancer diagnosis we calculated Charlson comorbidity index scores (0, 1-2 or 3+) in patients with renal cancer as well as absolute survival and relative mortality estimates according to comorbidity level. RESULTS: We identified 2,315 patients with renal cancer, of whom 950 (41%) had comorbidity. The prevalence of comorbidity tended to increase during the study period with the rate in patients with a score of 3+ increasing from 9% to 13%. The 5-year relative mortality rate was lower in patients with a positive Charlson index score with mortality almost twice as high in those with a score of 3+ and 1.2-fold higher in those with a score of 1-2 compared to mortality in those with no comorbidity. Generally similar patterns were observed for 1-year relative mortality. CONCLUSIONS: Comorbidity is common in patients with renal cancer and it is a negative prognostic factor.

Maternal levels of perfluorinated chemicals and subfecundity.

BACKGROUND: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are ubiquitous man-made compounds that are possible hormonal disruptors. We examined whether exposure to these compounds may decrease fecundity in humans. METHODS: Plasma levels of PFOS and PFOA were measured at weeks 4-14 of pregnancy among 1240 women from the Danish National Birth Cohort recruited from 1996 to 2002. For this pregnancy, women reported time to pregnancy (TTP) in five categories (<1, 1-2, 3-5, 6-12 and >12 months). Infertility was defined as having a TTP of >12 months or received infertility treatment to establish this pregnancy. RESULTS: Longer TTP was associated with higher maternal levels of PFOA and PFOS (P < 0.001). Compared with women in the lowest exposure quartile, the adjusted odds of infertility increased by 70-134 and 60-154% among women in the higher three quartiles of PFOS and PFOA, respectively. Fecundity odds ratios (FORs) were also estimated using Cox discrete-time models. The adjusted FORs were virtually identical for women in the three highest exposure groups of PFOS (FOR = 0.70, 0.67 and 0.74, respectively) compared with the lowest quartile. A linear-like trend was observed for PFOA (FOR = 0.72, 0.73 and 0.60 for three highest quartiles versus lowest quartile). When all quartiles were included in a likelihood ratio test, the trends were significant for PFOS and PFOA (P = 0.002 and P < 0.001, respectively). CONCLUSIONS: These findings suggest that PFOA and PFOS exposure at plasma levels seen in the general population may reduce fecundity; such exposure levels are common in developed countries.

Dietary vitamin D intake and cancers of the colon and rectum: a case-control study in Italy.

Epidemiologic evidence indicates that vitamin D is inversely associated with risk of colon or rectal cancer or both. Using data from a case-control study conducted in Italy between 1992 and 1996, we examined the relation between dietary intake of vitamin D and colon and rectal cancer risk. The study population comprised patients with incident colon cancer (n = 1,225) or rectal cancer (n = 728) and 4,154 hospital controls. Odds ratios (OR) and 95% confidence intervals (CI) according to deciles of vitamin D intake were estimated by multiple logistic regression. In addition, we adjusted for intensity of sunlight exposure through stratification by geographic region of residence, and we computed ORs separately by anatomic subsite within the colon. Adjusted ORs for colon cancer were seen to decrease after the 5th decile of vitamin D intake and reached 0.69 (95% CI = 0.50-0.96) for the 9th and 10th deciles, reflecting a statistically significant inverse trend. The inverse association appeared to be somewhat more pronounced for the proximal than the distal colon and was similar among strata of geographic region and calcium intake. Rectal cancer was unrelated to vitamin D intake in this population. In conclusion, we observed an inverse association between dietary vitamin D intake and colon cancer risk among those with the highest intake levels, which was somewhat unexpected given that these levels were still substantially below the levels considered optimal for colon cancer prevention.

Acetaminophen, aspirin and progression of advanced chronic kidney disease.

BACKGROUND: Although many studies have investigated the possible association between analgesic use (acetaminophen and aspirin) and the development of chronic kidney disease (CKD), the effect of analgesics on the progression of established CKD of any cause has not yet been investigated. METHODS: In this population-based Swedish cohort study, we investigated the decline over 5-7 years in estimated glomerular filtration rate (eGFR) among 801 patients with incident, advanced CKD (serum creatinine >3.4 mg/dL for men, >2.8 mg/dL for women for the first time) and with different analgesic exposures. Lifetime analgesic use and current regular use were ascertained through in-person interviews at inclusion while data on analgesic use during the follow-up was abstracted from the medical records at the end of the study period. A linear regression slope, based on their eGFR values during the follow-up, provided a summary of within-individual change. In the final multivariate analyses, a linear mixed effects model was implemented to assess the relation of analgesic use and change in eGFR over time. RESULTS: The progression rate for regular users of acetaminophen was slower than that for non-regular users (regular users progressed 0.93 mL/min/1.73 m(2) per year slower than non-regular users; 95% CI 0.03, 1.8). For regular users of aspirin, the progression rate was significantly slower than that for non-regular users (regular users progressed 0.80 mL/min/1.73 m(2) per year slower than non-regular users; 95% CI 0.1, 1.5). Different levels of lifetime cumulative dose of acetaminophen and aspirin did not significantly affect the progression rate. CONCLUSION: We suggest that single substance acetaminophen and aspirin may be safe to use by patients with diagnosed advanced CKD stage 4-5 without an adverse effect on the progression rate of the disease.