Waltham, MA, United States


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Rathmann W.,Heinrich Heine University Düsseldorf | Kostev K.,Epidemiology
Journal of Diabetes and its Complications | Year: 2017

Aims: Experimental and animal studies have supported the hypothesis that dipeptidyl peptidase-4 inhibitors (DPP-4i) may accelerate tumor metastasis. The aim was to analyze the relationships between DPP-4i therapy with risk of metastases in type 2 diabetes patients with breast, prostate and digestive organ cancers. Methods: Type 2 diabetes patients with first diagnoses of breast, prostate or digestive organ cancer were selected in general and internal medicine practices (Disease Analyzer Germany: 01/2008-12/2014). Propensity score matching between DPP-4i users and non-users was carried out for age, sex, diabetes duration, and metformin use. Time-dependent Cox regression models were used to estimate hazard ratios (HR) for metastases further adjusting for HbA1c, body mass index, comorbidity and co-therapy with glucose-lowering drugs (3-4. years follow-up). Results: 668 patients with newly diagnosed breast cancer, 906 with prostate cancer and 908 with digestive organ cancer were analyzed. In Cox regression, use of DPP-4i was not associated with an increased risk of metastases in patients with breast (adjusted HR, 95%CI: 1.00, 0.49-2.02), prostate (0.98, 0.54-1.77) or digestive organ cancers (0.97, 0.57-1.66). Conclusions: This first observational study in patients with type 2 diabetes and breast, prostate or digestive organ cancer found no increased risk of metastases in DPP-4i users. © 2017 Elsevier Inc.

Ley S.H.,Harvard University | Sun Q.,Harvard University | Sun Q.,Brigham and Women's Hospital | Willett W.C.,Harvard University | And 9 more authors.
American Journal of Clinical Nutrition | Year: 2014

Background: Greater red meat intake is associated with an increased type 2 diabetes and cardiovascular disease risk. However, the relation of red meat intake to biomarkers of inflammation and glucose metabolism has not been investigated thoroughly. Objective: We hypothesized that greater red meat intake would be associated with biomarkers of inflammation and glucose metabolism, which would be partly explained by body mass index (BMI). Design: We analyzed cross-sectional data from diabetes-free female participants in the Nurses' Health Study (n = 3690). Multiple linear regression was conducted to assess the associations of total, unprocessed, and processed red meat intakes (quartile categories) with plasma C-reactive protein (CRP), ferritin, adiponectin, fasting insulin, and hemoglobin A1c (Hb A1c). Results: Greater total, unprocessed, and processed red meat intakes were associated with higher plasma CRP, ferritin, fasting insulin, and Hb A1c and lower adiponectin after adjustment for demographic information (P-trend # 0.03 for all). Adiponectin was not associated with any type of red meat intake when further adjusted for medical and lifestyle factors. After adjustment for BMI, most of these associations with inflammatory and glucose metabolic biomarkers were substantially attenuated and no longer significant. BMI accounted for a statistically significant proportion of associations with CRP, Hb A1c, and fasting insulin (P-contribution # 0.02 for all) but not with ferritin. Substituting a serving of total red meat intake with alternative protein food in a combination of poultry, fish, legumes, and nuts was associated with significantly lower CRP (b 6 SE: 20.106 6 0.043), ferritin (20.212 6 0.075), Hb A1c (20.052 6 0.015), and fasting insulin (20.119 6 0.036) (all P # 0.02 for comparison of extreme quartiles for all). Conclusions: Greater red meat intake is associated with unfavorable plasma concentrations of inflammatory and glucose metabolic biomarkers in diabetes-free women. BMI accounts for a significant proportion of the associations with these biomarkers, except for ferritin. Substituting red meat with another protein food is associated with a healthier biomarker profile of inflammatory and glucose metabolism. © 2014 American Society for Nutrition.

Cruz Jr. A.I.,Epidemiology | Milewski M.D.,Epidemiology | Shapiro E.D.,Yale University
Journal of the American Academy of Orthopaedic Surgeons | Year: 2011

Lyme disease is the most common tick-borne disease in the United States and Europe. Increased awareness of the clinical manifestations of the disease is needed to improve detection and treatment. In the acute and late stages, Lyme disease may be difficult to distinguish from other disease processes. The epidemiology and pathophysiology of Lyme disease are directly related to the Borrelia burgdorferi spirochete and its effects on the integumentary, neurologic, cardiac, and musculoskeletal systems. Lyme arthritis is a common clinical manifestation of Lyme disease and should be considered in the evaluation of patients with monoarticular or pauciarticular joint complaints in a geographic area in which Lyme disease is endemic. Management of Lyme arthritis involves eradication of the spirochete with antibiotics. Generally, the prognosis is excellent. Arthroscopic synovectomy is reserved for refractory cases that do not respond to antibiotics. Copyright 2011 by the American Academy of Orthopaedic Surgeons.

Baral S.D.,Center for Public Health and Human Rights | Friedman M.R.,University of Pittsburgh | Geibel S.,Population Council | Rebe K.,Anova Health Institute | And 6 more authors.
The Lancet | Year: 2015

Male sex workers who sell or exchange sex for money or goods encompass a very diverse population across and within countries worldwide. Information characterising their practices, contexts where they live, and their needs is limited, because these individuals are generally included as a subset of larger studies focused on gay men and other men who have sex with men (MSM) or even female sex workers. Male sex workers, irrespective of their sexual orientation, mostly offer sex to men and rarely identify as sex workers, using local or international terms instead. Growing evidence indicates a sustained or increasing burden of HIV among some male sex workers within the context of the slowing global HIV pandemic. Several synergistic facilitators could be potentiating HIV acquisition and transmission among male sex workers, including biological, behavioural, and structural determinants. Criminalisation and intersectional stigmas of same-sex practices, commercial sex, and HIV all augment risk for HIV and sexually transmitted infections among male sex workers and reduce the likelihood of these people accessing essential services. These contexts, taken together with complex sexual networks among male sex workers, define this group as a key population underserved by current HIV prevention, treatment, and care services. Dedicated efforts are needed to make those services available for the sake of both public health and human rights. Evidence-based and human rights-affirming services dedicated specifically to male sex workers are needed to improve health outcomes for these men and the people within their sexual networks. © 2015 Elsevier Ltd.

Cantor R.M.,University of California at Los Angeles | Wilcox M.,Epidemiology
Genetic Epidemiology | Year: 2011

We summarize the work done by the contributors to Group 13 at Genetic Analysis Workshop 17 (GAW17) and provide a synthesis of their data analyses. The Group 13 contributors used a variety of approaches to test associations of both rare variants and common single-nucleotide polymorphisms (SNPs) with the GAW17 simulated traits, implementing analytic methods that incorporate multiallelic genotypes and haplotypes. In addition to using a wide variety of statistical methods and approaches, the contributors exhibited a remarkable amount of flexibility and creativity in coding the variants and their genes and in evaluating their proposed approaches and methods. We describe and contrast their methods along three dimensions: (1) selection and coding of genetic entities for analysis, (2) method of analysis, and (3) evaluation of the results. The contributors consistently presented a strong rationale for using multiallelic analytic approaches. They indicated that power was likely to be increased by capturing the signals of multiple markers within genetic entities defined by sliding windows, haplotypes, genes, functional pathways, and the entire set of SNPs and rare variants taken in aggregate. Despite this variability, the methods were fairly consistent in their ability to identify two associated genes for each simulated trait. The first gene was selected for the largest number of causal alleles and the second for a high-frequency causal SNP. The presumed model of inheritance and choice of genetic entities are likely to have a strong effect on the outcomes of the analyses. © 2011 Wiley Periodicals, Inc.

Banelli B.,Tumor Genetics and Epigenetics | Merlo D.F.,Epidemiology | Allemanni G.,Tumor Genetics and Epigenetics | Forlani A.,Tumor Genetics and Epigenetics | Romani M.,Tumor Genetics and Epigenetics
PLoS ONE | Year: 2013

Approximately 20% of stage 4 high-risk neuroblastoma patients are alive and disease-free 5 years after disease onset while the remaining experience rapid and fatal progression. Numerous findings underline the prognostic role of methylation of defined target genes in neuroblastoma without taking into account the clinical and biological heterogeneity of this disease. In this report we have investigated the methylation of the PCDHB cluster, the most informative member of the "Methylator Phenotype" in neuroblastoma, hypothesizing that if this epigenetic mark can predict overall and progression free survival in high-risk stage 4 neuroblastoma, it could be utilized to improve the risk stratification of the patients, alone or in conjunction with the previously identified methylation of the SFN gene (14.3.3sigma) that can accurately predict outcome in these patients. We have utilized univariate and multivariate models to compare the prognostic power of PCDHB methylation in terms of overall and progression free survival, quantitatively determined by pyrosequencing, with that of other markers utilized for the patients' stratification utilizing methylation thresholds calculated on neuroblastoma at stage 1-4 and only on stage 4, high-risk patients. Our results indicate that PCDHB accurately distinguishes between high- and intermediate/low risk stage 4 neuroblastoma in agreement with the established risk stratification criteria. However PCDHB cannot predict outcome in the subgroup of stage 4 patients at high-risk whereas methylation levels of SFN are suggestive of a "methylation gradient" associated with tumor aggressiveness as suggested by the finding of a higher threshold that defines a subset of patients with an extremely severe disease (OS <24 months). Because of the heterogeneity of neuroblastoma we believe that clinically relevant methylation markers should be selected and tested on homogeneous groups of patients rather than on patients at all stages. © 2013 Banelli et al.

De Ceglie A.,National Cancer Center Giovanni Paolo | Filiberti R.,Epidemiology | Baron T.H.,Mayo Medical School | Ceppi M.,Epidemiology | Conio M.,General Hospital
Critical Reviews in Oncology/Hematology | Year: 2013

The best approach to resolve colonic obstruction in patients with left-sided colon cancer is not established.In this meta-analysis the efficacy of stenting as bridge-to-surgery was compared to emergency surgery for the management of left-sided colonic obstruction. Fourteen studies (randomized and non controlled studies) were identified, including 405 patients in the stent group and 471 in the emergency group. The difference between proportions was evaluated as effect size (ESi). There was large heterogeneity among the studies.Stenting offered advantages over emergency surgery in terms of increase in primary anastomosis (ES. = 25.1%, p<. 0.001), successful primary anastomosis (ES = 23.7%, p<. 0.001), reduction of stoma creation (ES = -27.1%, p= 0.03), infections (ES = -7.9%, p= 0.006) and other morbidities (ES = -13.4%, p<. 0.001). The interventions were similar in regards to length of hospitalization, preoperative mortality and long-term survival. © 2013 Elsevier Ireland Ltd.

Coulm B.,Epidemiology | Lelong N.,French Institute of Health and Medical Research | Lelong N.,University Pierre and Marie Curie | Drewniak N.,French Institute of Health and Medical Research | Drewniak N.,University Pierre and Marie Curie
Birth | Year: 2012

Background: In many countries the closure of small maternity units has raised concerns about how the concentration of low-risk pregnancies in large specialized units might affect the management of childbirth. We aimed to assess the role of maternity unit characteristics on obstetric intervention rates among low-risk women in France. Methods: Data on low-risk deliveries came from the 2010 French National Perinatal Survey of a representative sample of births (n = 9,530). The maternity unit characteristics studied were size, level of care, and private or public status; the interventions included induction of labor; cesarean section; operative vaginal delivery (forceps, spatulas or vacuum); and episiotomy. Multilevel logistic regression analyses were adjusted for maternal confounding factors, gestational age, and infant birthweight. Results: The rates of induction, cesarean section, operative delivery, and episiotomy in this low-risk population were 23.9 percent, 10.1 percent, 15.2 percent, and 19.6 percent, respectively, and 52.0 percent of deliveries included at least one of them. Unit size was unrelated to any intervention except operative delivery (adjusted odds ratio [aOR] = 1.47 (95% CI, 1.10-1.96) for units with >3,000 deliveries per year vs units with <1,000). The rate of every intervention was higher in private units, and the aOR for any intervention was 1.82 (95% CI, 1.59-2.08). After adjustment for maternal characteristics and facility size and status, significant variations in the use of interventions remained between units, especially for episiotomies. Results for level of care were similar to those for unit size. Conclusions: The concentration of births in large maternity units in France is not associated with higher rates of interventions for low-risk births. The situation in private units could be explained by differences in the organization of care. Additional research should explore the differences in practices between maternity units with similar characteristics. © 2012, The Authors Journal compilation © 2012, Wiley Periodicals, Inc.

Loughlin J.,Epidemiology | Mast T.C.,Merck And Co. | Doherty M.C.,Harvard University | Wang F.T.,Epidemiology | And 3 more authors.
Pediatric Infectious Disease Journal | Year: 2012

BACKGROUND: A pentavalent rotavirus vaccine (RV5) demonstrated efficacy and safety in a large clinical trial before US licensure in 2006. The primary objective of this observational study was to assess the occurrence of intussusception (IS) among infants who received RV5 in routine use. Secondary objectives assessed the occurrence of Kawasaki disease (KD) and general safety. METHODS: We identified and followed infants with a health insurance claim for RV5 during the first 2 years of RV5 availability. Concurrent and historical cohorts receiving diphtheria-tetanus-acellular pertussis (DTaP) vaccine were used as comparators; the historical DTaP cohort informed sequential monitoring boundaries for IS and KD. Medical records from potential IS and KD cases were reviewed to confirm outcomes. General safety was evaluated across a wide range of outcomes using prespecified criteria. Incidence rates for outcomes along with relative risks and 95% confidence intervals (CIs) were estimated. RESULTS: The 85,397 RV5 and 62,820 DTaP recipients contributed 17,433 and 12,339 person-years, resulting in 6 and 5 confirmed cases of IS, respectively, within 30 days following any dose. The relative risk of IS was 0.8 (95% confidence interval: 0.22-3.52). The number of IS or KD cases did not cross the monitoring boundaries. The general safety evaluation did not identify any specific diagnoses or patterns of diagnoses that might suggest other safety concerns. CONCLUSION: RV5 was not associated with an increased risk of IS, KD, or any other recognized health outcome. Copyright © 2012 by Lippincott Williams & Wilkins.

Koopman J.S.,Epidemiology
American Journal of Epidemiology | Year: 2013

Polio eradication is on the cusp of success, with only a few regions still maintaining transmission. Improving our understanding of why some regions have been successful and others have not will help with both global eradication of polio and development of more effective vaccination strategies for other pathogens. To examine the past 25 years of eradication efforts, we constructed a transmission model for wild poliovirus that incorporates waning immunity (which affects both infection risk and transmissibility of any resulting infection), age-mediated vaccination rates, and transmission of oral polio vaccine. The model produces results consistent with the 4 country categories defined by the Global Polio Eradication Program: elimination with no subsequent outbreaks; elimination with subsequent transient outbreaks; elimination with subsequent outbreaks and transmission detected for more than 12 months; and endemic polio transmission. Analysis of waning immunity rates and oral polio vaccine transmissibility reveals that higher waning immunity rates make eradication more difficult because of increasing numbers of infectious adults, and that higher oral polio vaccine transmission rates make eradication easier as adults become reimmunized. Given these dynamic properties, attention should be given to intervention strategies that complement childhood vaccination. For example, improvement in sanitation can reduce the reproduction number in problematic regions, and adult vaccination can lower adult transmission. © 2013 © The Author 2013. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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