Background: Whereas diet and lifestyle are strongly implicated in the etiology of colorectal cancer, single exposures generally are weakly and inconsistently associated with the disease. Exposure patterns may be more helpful for investigating diet and lifestyle-colorectal cancer associations. Evolutionary-concordance diet and Mediterranean diet pattern scores were previously found to be inversely associated with colorectal adenoma.
Methods: To investigate associations of these diet scores and an evolutionary-concordance lifestyle score (comprising smoking status, physical activity, and body mass index) with incident colorectal cancer, we analyzed data from the prospective Iowa Women's Health Study. Diet and lifestyle scores were calculated for each participant and categorized into quintiles, and associations estimated using Cox proportional hazards models.
Results: Of the 35,221 55- to 69-year-old cancer-free women at baseline, 1,731 developed colorectal cancer during follow-up. The multivariable-adjusted HR comparing persons in the highest relative to the lowest quintile of the lifestyle score was 0.66 (95% confidence interval, 0.56-0.78; Ptrend < 0.01). Although the estimated associations of the evolutionary-concordance diet and Mediterranean diet scores alone with colorectal cancer were null, relative to those in the lowest tertiles of both the evolutionary-concordance diet and lifestyle scores, those in the highest tertiles of both scores were at the lowest risk (Pinteraction < 0.01).
Conclusions: Our findings suggest that a more evolutionary-concordant lifestyle, alone and in interaction with a more evolutionary-concordant diet pattern, may be inversely associated with colorectal cancer risk. Impact: These results support further investigation of colorectal cancer etiology using evolutionary-concordance dietary and lifestyle pattern scores.
by
Poonum S. Korpe;
Rashidul Haque;
Carol Gilchrist;
Cristian Valencia;
Feiyang Niu;
Miao Lu;
Jennie Z. Ma;
Sarah E. Petri;
Daniel Reichman;
Mamun Kabir;
Priya Duggal;
William A. Petri
Background: Cryptosporidiosis is a common cause of infectious diarrhea in young children worldwide, and is a significant contributor to under-five mortality. Current treatment options are limited in young children. In this study, we describe the natural history of Cryptosporidium spp. infection in a birth cohort of children in Bangladesh and evaluate for association with malnutrition.
Methodology/Principal Findings: This is a longitudinal birth cohort study of 392 slum-dwelling Bangladeshi children followed over the first two years of life from 2008 to 2014. Children were monitored for diarrheal disease, and stool was tested for intestinal protozoa. Anthropometric measurements were taken at 3-month intervals. A subset of Cryptosporidium positive stools were genotyped for species and revealed that C. hominis was isolated from over 90% of samples. In the first two years of life, 77% of children experienced at least one infection with Cryptosporidium spp. Non-diarrheal infection (67%) was more common than diarrheal infection (6.3%) although 27% of children had both types of infection. Extreme poverty was associated with higher rates of infection (chi-square, 49.7% vs 33.3%, p = 0.006). Malnutrition was common in this cohort, 56% of children had stunted growth by age two. Children with Cryptosporidium spp. infection had a greater than 2-fold increased risk of severe stunting at age two compared to uninfected children (odds ratio 2.69, 95% CI 1.17, 6.15, p = 0.019) independent of sex, income, maternal body-mass index, maternal education and weight for age adjusted z (WAZ) score at birth.
Conclusions/Significance: Cryptosporidium infection is common (77%) in this cohort of slum-dwelling Bangladeshi children, and both non-diarrheal and diarrheal infections are significantly associated with a child’s growth at 2 years of age.
Background
Statistics indicate that Ethiopia has made remarkable progress in reducing child mortality. It is however estimated that there is high rate of perinatal mortality although there is scarcity of data due to a lack of vital registration in the country. This study was conducted with the purpose of assessing the determinants and causes of perinatal mortality among babies born from cohorts of pregnant women in three selected districts of North Showa Zone, Oromia Region, Ethiopia. The study used community based data, which is believed to provide more representative and reliable information and also aimed to narrow the data gap on perinatal mortality.
Methods
A community based nested case control study was conducted among 4438 (cohorts of) pregnant women. The cohort was followed up between March 2011 to December 2012 in three districts of Oromia region, Ethiopia, until delivery. The World Health Organization verbal autopsy questionnaire for neonatal death was used to collect data. A binary logistic regression model was used to identify determinants of perinatal mortality. Causes of deaths were assigned by a pediatrician and neonatologist. Cases are stillbirths and early neonatal death. Control are live births surviving of the perinatal period’
Result
A total of 219 newborns (73 cases and 146 controls) were included in the analysis. Perinatal mortality rate was 16.5 per 1000 births. Mothers aged 35 years and above had a higher risk of losing their newborn babies to perinatal deaths than younger mothers [AOR 7.59, (95% CI, 1.91-30.10)]. Babies born to mothers who had a history of neonatal deaths were also more likely to die during the perinatal period than their counterparts [AOR 5.42, (95% CI, 2.27-12.96)]. Preterm births had a higher risk of perinatal death than term babies [AOR 8.58, (95% CI, 2.27-32.38)]. Similarly, male babies were at higher risk than female babies [AOR 5.47, (95% CI, 2.50-11.99)]. Multiple birth babies had a higher chance of dying within the perinatal period than single births [AOR 3.59, (95% CI, 1.20-10.79)]. Home delivery [AOR 0.23, (95% CI, 0.08-0.67)] was found to reduce perinatal deaths. Asphyxia, sepsis and chorioamnionitis were among the leading causes of perinatal deaths.
Conclusion
This study reported a lower perinatal mortality rate. The main causes of perinatal death identified were often related to maternal factors. There is still a need for greater focus on these interrelated issues for further intervention.
Purpose: To identify risk factors for a severe uveitis course among children with non-infectious uveitis.
Design: Retrospective cohort study
Method: This was a retrospective analysis of a prospectively collected database. Records of 94 children with uveitis were reviewed at enrollment and every 3-6 months (2011-2015). Severe uveitis was defined as a history of ocular complications or a visual acuity (VA) of ≤20/200. Children were compared by disease, VA, complications and race. Regression models were used to model risk factors for severe disease. When examining race, we focused on non-Hispanic African American and non-Hispanic White children only.
Results: Of 85 children with uveitis and complete ocular examinations, 27 (32%) had a history of a VA of ≤20/200. A subanalysis of non-Hispanic African American and White children showed an increased prevalence of VA ≤20/200 in non-Hispanic African Americans (18/25 (72%) vs. 4/43 (9%)). Non-Hispanic African Americans were more likely to be diagnosed at an older age (p=0.030), have intermediate uveitis (p=0.026), bilateral disease (p=0.032), a history of VA ≤20/50 (p=0.002), VA ≤20/200 (p<0.001), and a higher rate of complications (p<0.001). On multivariable analysis, non-Hispanic African American race was a significant predictor of blindness (OR=31.6, 95% CI (5.9– 168.5), p<0.001), after controlling for uveitis duration. Non-Hispanic African Americans also developed 2.2 times more unique complications per year of disease than non-Hispanic Whites when controlling for uveitis type and duration.
Conclusions: There appear to be racial differences in the outcomes of children with uveitis. Non-Hispanic African American children with non-juvenile idiopathic arthritis associated uveitis may have worse visual outcomes with increased vision loss and ocular complications. These findings highlight the need for future studies in minority populations.
The current health care climate mandates the delivery of high-value care for patients considering active surveillance for newly-diagnosed prostate cancer. Value is defined by increasing benefits (e.g., quality) for acceptable costs. This review discusses quality of care considerations for men contemplating active surveillance, and highlights cost implications at the patient, health-system, and societal level related to pursuit of non-interventional management of men diagnosed with localized prostate cancer. In general, most quality measures are focused on prostate cancer care in general, rather that active surveillance patients specifically. However, most prostate cancer quality measures are pertinent to men seeking close observation of their prostate tumors with active surveillance. These include accurate documentation of clinical stage, informed discussion of all treatment options, and appropriate use of imaging for less-aggressive prostate cancer. Furthermore, interventions that may help improve the quality of care for active surveillance patients are reviewed (e.g., quality collaboratives, judicious antibiotic use, etc.). Finally, the potential economic impact and benefits of broad acceptance of active surveillance strategies are highlighted.
by
Lameck Chinula;
Julie A.E. Nelson;
Jeffrey Wiener;
Jennifer H. Tang;
Stacey Hurst;
Gerald Tegha;
Albans Msika;
Sascha Ellington;
Mina C. Hosseinipour;
Ronald Mataya;
Lisa Haddad;
Athena Kourtis
Objectives: To assess the effect of the depot medroxyprogesterone acetate injectable (DMPA) and of the levonorgestrel (LNG) implant on genital HIV shedding among women receiving antiretroviral therapy (ART). Methods: We randomized HIV-infected Malawian women to either DMPA or LNG implant from May 2014 to April 2015. HIV RNA was measured in cervicovaginal lavage (CVL) fluid and TearFlo Strips (TFS), and HIV DNA was measured in cells collected by CVL. We compared the frequency and magnitude of HIV genital shedding before and for 6 months after initiation of contraception and between arms among women receiving ART. We also compared genital HIV RNA levels obtained by sample type (TFS versus CVL). Results: We analyzed data for 68 HIV-infected women receiving ART: 33 randomized to DMPA and 35 randomized to the LNG implant. Overall, HIV RNA was more often detectable and the quantity was higher on TFS compared with CVL. HIV DNA was detected very rarely in CVL cell samples (4 of 360 samples). The frequency of genital shedding and the genital HIV quantity did not increase after contraceptive initiation with either DMPA or LNG implant among women receiving ART. Conclusions: HIV-infected women receiving ART initiating contraception with either DMPA or LNG implant did not have any increase in genital HIV shedding during the first 6 months of contraceptive use. These findings are consistent with growing evidence that progestin contraception is not associated with increased HIV transmission risk from such women to their male partners. Consistent with other studies, genital HIV RNA detection was higher in TFS than in CVL fluid. Implications: In this randomized trial, neither DMPA nor the LNG implant, two of the most commonly used hormonal contraceptives among African women with HIV, was associated with increased genital HIV shedding in HIV-infected women receiving ART. These findings are reassuring and add to the currently limited information available for the highly effective contraceptive, LNG implant.
by
Brianna Miller;
Noah C. Peeri;
L. Burt Nabors;
Jordan H. Creed;
Zachary J. Thompson;
Carrie M. Rozmeski;
Renato V. LaRocca;
Sajeel Chowdhary;
Jeffrey James Olson;
Reid C. Thompson;
Kathleen M. Egan
Gliomas are the most common type of malignant primary brain tumor and few risk factors have been linked to their development. Handedness has been associated with several pathologic neurological conditions such as schizophrenia, autism, and epilepsy, but few studies have evaluated a connection between handedness and risk of glioma. In this study, we examined the relationship between handedness and glioma risk in a large case–control study (1849 glioma cases and 1354 healthy controls) and a prospective cohort study (326,475 subjects with 375 incident gliomas). In the case–control study, we found a significant inverse association between left handedness and glioma risk, with left-handed persons exhibiting a 35% reduction in the risk of developing glioma [odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.51–0.83] after adjustment for age, gender, race, education, and state of residence; similar inverse associations were observed for GBM (OR = 0.69, 95% CI 0.52–0.91), and non-GBM (OR = 0.59, 95% CI 0.42–0.82) subgroups. The association was consistent in both males and females, and across age strata, and was observed in both glioblastoma and in lower grade tumors. In the prospective cohort study, we found no association between handedness and glioma risk (hazards ratio = 0.92, 95% CI 0.67–1.28) adjusting for age, gender, and race. Further studies on this association may help to elucidate mechanisms of pathogenesis in glioma.
by
Thomas Helland;
Nina Henne;
Ersilia Bifulco;
Bjorn Naume;
ELin Borgen;
Vessela N. Kristensen;
Jan T. Kvaloy;
Timothy Lash;
Grethe I. G. Alns;
Ron H. van Schaik;
Emiel A. M. Janssen;
Steinar Hustad;
Ernst A. Lien;
Gunnar Mellgren;
Havard Soiland
Background: Controversies exist as to whether the genetic polymorphisms of the enzymes responsible for the metabolism of tamoxifen can predict breast cancer outcome in patients using adjuvant tamoxifen. Direct measurement of concentrations of active tamoxifen metabolites in serum may be a more biological plausible and robust approach. We have investigated the association between CYP2D6 genotypes, serum concentrations of active tamoxifen metabolites, and long-term outcome in tamoxifen treated breast cancer patients. Methods: From an original observational study comprising 817 breast cancer patients, 99 women with operable breast cancer were retrospectively included in the present study. This cohort of patients were adjuvantly treated with tamoxifen, had provided serum samples suitable for measuring tamoxifen metabolites, and were relapse-free at 3 years after the primary treatment commenced. The median follow-up time from this entry point to breast cancer death was 13.9 years. Patients were CYP2D6 genotyped and grouped into four CYP2D6 phenotype groups (Ultra rapid, extensive, intermediate, and poor metabolizers). Tamoxifen and nine metabolites were quantified in serum (n = 86) and compared with CYP2D6 phenotype groups and outcome. Results: Breast cancer patients with low concentrations of Z-4-hydroxy-tamoxifen (Z-4OHtam; ≤ 3.26 nM) had a breast cancer-specific survival (BCSS) of 60% compared to 84% in patients with Z-4OHtam concentrations > 3.26 nM (p = 0.020, log-rank hazard ratio (HR) = 3.56, 95% confidence interval (CI) = 1.14-11.07). For patients with Z-4-hydroxy-N-desmethyl-tamoxifen (Z-endoxifen) levels ≤ 9.00 nM BCSS was 57% compared to 84% for patients with concentrations > 9.00 nM (p = 0.029, HR = 3.73, 95% CI = 1.05-13.22). Low concentrations of Z-4OHtam and Z-endoxifen were associated with poorer survival also after adjusting for clinically relevant variables (HR = 4.27, 95% CI = 1.35-13.58, and HR = 3.70, 95% CI = 1.03-13.25, respectively). Overall survival analysis showed similar survival differences for both active metabolites. The Antiestrogen Activity Score showed comparable effects, but did not improve the prognostic information. Conclusions: Patients with Z-4OHtam and Z-endoxifen concentrations lower than 3.26 nM or 9.00 nM, respectively, showed an adverse outcome. Our results suggest that direct measurement of active tamoxifen metabolite concentrations could be of clinical value. Validation in larger study cohorts is warranted.
by
Jonathan P. Troost;
Anne Waldo;
Noelle E. Carlozzi;
Shannon Murphy;
Frank Modersitzki;
Howard Trachtman;
Patrick H. Nachman;
Larry Greenbaum;
Chia-shi Wang
Background. Understanding the relationship between clinical and patient-reported outcomes (PROs) will help support clinical care and future clinical trial design of novel therapies for focal segmental glomerulosclerosis (FSGS). Methods. FSGS patients ≥8 years of age enrolled in the Nephrotic Syndrome Study Network completed Patient-Reported Outcomes Measurement Information System PRO measures of health-related quality of life (HRQoL) (children: global health, mobility, fatigue, pain interference, depression, anxiety, stress and peer relationships; adults: physical functioning, fatigue, pain interference, sleep impairment, mental health, depression, anxiety and social satisfaction) at baseline and during longitudinal follow-up for a maximum of 5 years. Linear mixed-effects models were used to determine which demographic, clinical and laboratory features were associated with PROs for each of the eight children and eight adults studied. Results. There were 45 children and 114 adult FSGS patients enrolled that had at least one PRO assessment and 519 patient visits. Multivariable analyses among children found that edema was associated with global health (-7.6 points, P ¼ 0.02) and mobility (-4.2, P ¼ 0.02), the number of reported symptoms was associated with worse depression (-2.7 per symptom, P ¼ 0.009) and anxiety (-2.3, P ¼ 0.02) and the number of emergency room (ER) visits in the prior 6 months was associated with worse mobility (-2.8 per visit, P < 0.001) and fatigue (-2.4, P ¼ 0.03). Multivariable analyses among adults found the number of reported symptoms was associated with worse function in all eight PROMIS measures and the number of ER visits was associated with worse fatigue, pain interference, sleep impairment, depression, anxiety and social satisfaction. Laboratory markers of disease severity (i.e. proteinuria, estimated glomerular filtration rate and serum albumin) did not predict PRO in multivariable analyses, with the single exception of complete remission and better pain interference scores among children (þ9.3, P ¼ 0.03). Conclusions. PROs provide important information about HRQoL for persons with FSGS that is not captured solely by the examination of laboratory-based markers of disease. However, it is critical that instruments capture the patient experience and FSGS clinical trials may benefit from a disease-specific instrument more sensitive to within-patient changes.
by
Joe M. Braun;
Julie L. Daniels;
Charles Poole;
Andrew F. Olshan;
Richard Hornung;
John T. Bernert;
Jane Khoury;
Larry L. Needham;
Dana Barr;
Bruce P. Lanphear
Maternal smoking during pregnancy is associated with increased risk of childhood overweight body mass index (BMI). Less is known about the association between prenatal secondhand tobacco smoke (SHS) exposure and childhood BMI. We followed 292 mother-child dyads from early pregnancy to 3 years of age. Prenatal tobacco smoke exposure during pregnancy was quantified using self-report and serum cotinine biomarkers. We used linear mixed models to estimate the association between tobacco smoke exposure and BMI at birth, 4 weeks, and 1, 2 and 3 years. During pregnancy, 15% of women reported SHS exposure and 12% reported active smoking, but 51% of women had cotinine levels consistent with SHS exposure and 10% had cotinine concentrations indicative of active smoking. After adjustment for confounders, children born to active smokers (self-report or serum cotinine) had higher BMI at 2 and 3 years of age, compared with unexposed children. Children born to women with prenatal serum cotinine concentrations indicative of SHS exposure had higher BMI at 2 (mean difference [MD] 0.3 [95% confidence interval -0.1, 0.7]) and 3 (MD 0.4 [0, 0.8]) years compared with unexposed children. Using self-reported prenatal exposure resulted in non-differential exposure misclassification of SHS exposures that attenuated the association between SHS exposure and BMI compared with serum cotinine concentrations. These findings suggest active and secondhand prenatal tobacco smoke exposure may be related to an important public health problem in childhood and later life. In addition, accurate quantification of prenatal secondhand tobacco smoke exposures is essential to obtaining valid estimates.