Searched for: Department/Unit:Population Health
Gene-arsenic interaction in longitudinal changes of blood pressure: Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh
Farzan, Shohreh F; Karagas, Margaret R; Jiang, Jieying; Wu, Fen; Liu, Mengling; Newman, Jonathan D; Jasmine, Farzana; Kibriya, Muhammad G; Paul-Brutus, Rachelle; Parvez, Faruque; Argos, Maria; Bryan, Molly Scannell; Eunus, Mahbub; Ahmed, Alauddin; Islam, Tariqul; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Slavkovich, Vesna; Graziano, Joseph; Ahsan, Habibul; Chen, Yu
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide and mounting evidence indicates that toxicant exposures can profoundly impact on CVD risk. Epidemiologic studies have suggested that arsenic (As) exposure is positively related to increases in blood pressure (BP), a primary CVD risk factor. However, evidence of whether genetic susceptibility can modify the association between As and BP are lacking. In this study, we used mixed effects models adjusted for potential confounders to examine the interaction between As exposure from well water and potential genetic modifiers on longitudinal change in BP over approximately 7years of follow-up in 1137 subjects selected from the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in Bangladesh. Genotyping was conducted for 235 SNPs in 18 genes related to As metabolism, oxidative stress and endothelial function. We observed interactions between 44 SNPs with well water As for one or more BP outcome measures (systolic, diastolic, or pulse pressure (PP)) over the course of follow-up. The interaction between CYBA rs3794624 and well water As on annual PP remained statistically significant after correction for multiple comparisons (FDR-adjusted p for interaction=0.05). Among individuals with the rs3794624 variant genotype, well water As was associated with a 2.23mmHg (95% CI: 1.14-3.32) greater annual increase in PP, while among those with the wild type, well water As was associated with a 0.13mmHg (95% CI: 0.02-0.23) greater annual increase in PP. Our results suggest that genetic variability may contribute to As-associated increases in BP over time.
PMCID:4606937
PMID: 26220686
ISSN: 1096-0333
CID: 1698492
Incidence and prevalence of hepatitis c virus infection among persons who inject drugs in New York City: 2006-2013
Jordan, Ashly E; Des Jarlais, Don C; Arasteh, Kamyar; McKnight, Courtney; Nash, Denis; Perlman, David C
BACKGROUND: Hepatitis C virus infection is a source of significant preventable morbidity and mortality among persons who inject drugs (PWID). We sought to assess trends in hepatitis C virus (HCV) infection among PWID from 2006 to 2013 in New York City (NYC). METHODS: Annual cross-sectional surveys of PWID entering a large drug abuse treatment program were performed. Risk behavior questionnaires were administered, and HIV and HCV testing were conducted. Comparisons were made with prior prevalence and incidence estimates in 1990-1991 and 2000-2001 reflecting different periods of combined prevention and treatment efforts. RESULTS: HCV prevalence among PWID (N: 1535) was 67% (95% CI: 66-70%) during the study period, and was not significantly different from that observed in 2000-2001. The estimated HCV incidence among new injectors (persons injecting for =6 years) during 2006-2013 was 19.5/100 PYO (95% CI: 17-23) and did not differ from that observed in 2000-2001 (18/100 PYO, 95% CI: 14-23/100). CONCLUSIONS: Despite the expansion of combined prevention programming between 2000-2001 and 2006-2013, HCV prevalence remained high. Estimated HCV incidence among new injectors also remained high, and not significantly lower than in 2000-2001, indicating that expanded combined prevention efforts are needed to control the HCV epidemic among PWID in NYC.
PMCID:4458155
PMID: 25891230
ISSN: 1879-0046
CID: 1690502
Use of Preoperative Testing and Physicians' Response to Professional Society Guidance
Sigmund, Alana E; Stevens, Elizabeth R; Blitz, Jeanna D; Ladapo, Joseph A
Importance: The value of routine preoperative testing before most surgical procedures is widely considered to be low. To improve the quality of preoperative care and reduce waste, 2 professional societies released guidance on use of routine preoperative testing in 2002, but researchers and policymakers remain concerned about the health and cost burden of low-value care in the preoperative setting. Objective: To examine the long-term national effect of the 2002 professional guidance from the American College of Cardiology/American Heart Association and the American Society of Anesthesiologists on physicians' use of routine preoperative testing. Design, Setting, and Participants: Retrospective analysis of nationally representative data from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey to examine adults in the United States who were evaluated during preoperative visits from January 1, 1997, through December 31, 2010. A quasiexperimental, difference-in-difference (DID) approach evaluated whether the publication of professional guidance in 2002 was associated with changes in preoperative testing patterns, adjusting for temporal trends in routine testing, as captured by testing patterns in general medical examinations. Main Outcomes and Measures: Physician orders for outpatient plain radiography, hematocrit, urinalysis, electrocardiogram, and cardiac stress testing. Results: During the 14-year period, the average annual number of preoperative visits in the United States increased from 6.8 million in 1997-1999 to 9.8 million in 2002-2004 and 14.3 million in 2008-2010. After accounting for temporal trends in routine testing, we found no statistically significant overall changes in the use of plain radiography (11.3% in 1997-2002 to 9.9% in 2003-2010; DID, -1.0 per 100 visits; 95% CI, -4.1 to 2.2), hematocrit (9.4% in 1997-2002 to 4.1% in 2003-2010; DID, 1.2 per 100 visits; 95% CI, -2.2 to 4.7), urinalysis (12.2% in 1997-2002 to 8.9% in 2003-2010; DID, 2.7 per 100 visits; 95% CI, -1.7 to 7.1), or cardiac stress testing (1.0% in 1997-2002 to 2.0% in 2003-2010; DID, 0.7 per 100 visits; 95% CI, -0.1 to 1.5) after the publication of professional guidance. However, the rate of electrocardiogram testing fell (19.4% in 1997-2002 to 14.3% in 2003-2010; DID, -6.7 per 100 visits; 95% CI, -10.6 to -2.7) in the period after the publication of guidance. Conclusions and Relevance: The release of the 2002 guidance on routine preoperative testing was associated with a reduced the incidence of routine electrocardiogram testing but not of plain radiography, hematocrit, urinalysis, or cardiac stress testing. Because routine preoperative testing is generally considered to provide low incremental value, more concerted efforts to understand physician behavior and remove barriers to guideline adherence may improve health care quality and reduce costs.
PMCID:4526021
PMID: 26053956
ISSN: 2168-6114
CID: 1688372
Optical coherence tomography reflects brain atrophy in MS: A four year study
Saidha, Shiv; Al-Louzi, Omar; Ratchford, John N; Bhargava, Pavan; Oh, Jiwon; Newsome, Scott D; Prince, Jerry L; Pham, Dzung; Roy, Snehashis; van Zijl, Peter; Balcer, Laura J; Frohman, Elliot M; Reich, Daniel S; Crainiceanu, Ciprian; Calabresi, Peter A
OBJECTIVE: To determine whether atrophy of specific retinal layers and brain substructures are associated over time, in order to further validate the utility of optical coherence tomography (OCT) as an indicator of neuronal tissue damage in patients with multiple sclerosis (MS). METHODS: Cirrus high definition OCT (including automated macular segmentation) was performed in 107 MS patients biannually (median follow-up: 46-months). Three-tesla magnetic resonance imaging brain scans (including brain-substructure volumetrics) were performed annually. Individual-specific rates of change in retinal and brain measures (estimated with linear regression) were correlated, adjusting for age, sex, disease duration, and optic neuritis (ON) history. RESULTS: Rates of ganglion cell + inner plexiform layer (GCIP) and whole-brain (r=0.45,p<0.001), gray matter (GM; r=0.37,p<0.001), white matter (WM; r=0.28,p=0.007) and thalamic (r=0.38,p<0.001) atrophy were associated. GCIP and whole-brain (as well as GM and WM) atrophy rates were more strongly associated in progressive MS (r=0.67,p<0.001) than relapsing-remitting MS (RRMS; r=0.33,p=0.007). However, correlation between rates of GCIP and whole-brain (and additionally GM and WM) atrophy in RRMS increased incrementally with step-wise refinement to exclude ON effects; excluding eyes and then patients (to account for a phenotype effect) the correlation increased to 0.45 and 0.60 respectively, consistent with effect modification. In RRMS, lesion accumulation rate was associated with GCIP (r=-0.30,p=0.02) and inner nuclear layer (r=-0.25,p=0.04) atrophy rates. INTERPRETATION: Over time GCIP atrophy appears to mirror whole-brain, and particularly GM atrophy, especially in progressive MS, thereby reflecting underlying disease progression. Our findings support OCT for clinical monitoring and as an outcome in investigative trials
PMCID:4703093
PMID: 26190464
ISSN: 1531-8249
CID: 1683692
Response to Dr. Fernandez-Viadero and Colleagues and Drs. Flaschner and Katz [Letter]
Rhodes, Ramona; Shega, Joseph; Vitale, Caroline; Malone, Michael; Unroe, Kathleen; Blaum, Caroline; Wald, Heidi
PMID: 26189866
ISSN: 1532-5415
CID: 1684772
Upper limit of cancer extent on biopsy defining very low-risk prostate cancer
Bratt, Ola; Folkvaljon, Yasin; Loeb, Stacy; Klotz, Laurence; Egevad, Lars; Stattin, Par
OBJECTIVE: To investigate how much Gleason pattern 3 cancer prostate biopsy specimens may contain without an increased risk of undetected more aggressive cancer, compared with the risk for cancers fulfilling the National Comprehensive Cancer Network (NCCN) criteria for very low-risk prostate cancer. PATIENTS AND METHODS: We identified 1286 men aged <70 years in the National Prostate Cancer Register of Sweden who underwent primary radical prostatectomy (RP) for stage T1c or T2 prostate cancer with Gleason pattern =3 only, prostate-specific antigen (PSA) level of <10 ng/mL and a PSA density of <0.15 ng/mL/mL. The association between the extent of cancer in the biopsies (the number and proportion of positive cores and the total cancer length in the cores in millimetres) and the likelihood of Gleason pattern 4-5 in the RP specimen was analysed with logistic regression. RESULTS: In all, 438 (34%) of the 1286 men had Gleason pattern 4-5 in the RP specimen. Increasing number and proportion of positive biopsy cores, as well as increasing biopsy cancer length were both significantly associated with increased risk of upgrading at RP in univariable analysis, but in multivariable analysis only biopsy cancer length remained significant. The 684 men with stage T1c and <8 mm cancer had similar risk of upgrading regardless of whether the number of positive biopsy cores was 1-2 or 3-4 (28% vs 27% risk); upgrading was more common among the remaining men (40%, P < 0.01). CONCLUSIONS: Men aged <70 years with stage T1c prostate cancer and 3-4 biopsy cores with Gleason pattern 3 are not more likely to have undetected Gleason pattern 4-5 cancer than men with 1-2 cores with cancer, provided that the total biopsy cancer length is <8 mm. We propose that the definition of very low-risk prostate cancer is widened accordingly.
PMID: 25053197
ISSN: 1464-410x
CID: 1684252
DWI for Renal Mass Characterization: Systematic Review and Meta-Analysis of Diagnostic Test Performance
Kang, Stella K; Zhang, Angela; Pandharipande, Pari V; Chandarana, Hersh; Braithwaite, R Scott; Littenberg, Benjamin
OBJECTIVE: The objective of our study was to perform a systematic review and meta-analysis of the test performance of DWI in the characterization of renal masses. MATERIALS AND METHODS: We performed searches of three electronic databases for studies on renal mass characterization using DWI. Methodologic quality was assessed for each study. We quantitatively analyzed test performance for three clinical problems: first, benign versus malignant lesions; second, clear cell renal cell carcinoma (RCC) versus other malignancies; and, third, high-versus low-grade clear cell RCCs. We summarized performance as a single pair of sensitivity and specificity values or a summary ROC curve. RESULTS: The studies in the literature were limited in both quantity and quality. For classification of benign versus malignant lesions, four studies with 279 lesions yielded a single summary estimate of 86% sensitivity and 78% specificity. For differentiation of clear cell RCC from other malignancies, five studies showed marked heterogeneity not conducive to meta-analysis. For differentiation of high-from low-grade clear cell RCCs, three studies with 110 lesions showed a threshold effect appropriate for summary ROC construction: The AUC was 0.83. CONCLUSION: Evidence suggests moderate accuracy of DWI for the prediction of malignancy and high-grade clear cell cancers, whereas DWI performance for ascertaining clear cell histologic grade remains unclear. To develop DWI as a noninvasive approach for the evaluation of solid renal masses, prospective studies with standardized test parameters are needed to better establish DWI performance and its impact on patient outcomes.
PMID: 26204281
ISSN: 1546-3141
CID: 1684042
Relation of quantitative visual and neurologic outcomes to fatigue in multiple sclerosis
Chahin, Salim; Miller, Deborah; Sakai, Reiko E; Wilson, James A; Frohman, Teresa; Markowitz, Clyde; Jacobs, Dina; Green, Ari; Calabresi, Peter A; Frohman, Elliot M; Galetta, Steven L; Balcer, Laura J
BACKGROUND: The relation of fatigue in multiple sclerosis (MS) to the visual system, an emerging structural and functional surrogate in MS, has not been well established. OBJECTIVE: We examined how physical and cognitive fatigue could be associated with visual dysfunction and neurologic impairment. METHODS: At a single time-point, we assessed 143 patients with: Low-contrast letter acuity (LCLA) and high-contrast visual acuity (VA) testing, the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and Neuro-Ophthalmic Supplement, the Modified Fatigue Impact Scale (MFIS), the MS Functional Composite (MSFC), and the Expanded Disability Status Scale (EDSS). RESULTS: Worse binocular LCLA scores were associated with increased levels of total and physical fatigue (p=0.026). Greater levels of fatigue were also associated with reduced vision-specific QOL (p<0.001). Patients with more physical, but not cognitive, fatigue had greater levels of impairment by the Timed 25-Foot Walk (T25W, r=0.39, p<0.001), 9-Hole Peg Test (9HP r=0.22, p=0.011) and EDSS (r=0.45, p<0.001). CONCLUSIONS: Reduced vision in MS is highly associated with physical fatigue and could be used to capture more global, difficult to describe, symptoms. The potential differences in physical vs. cognitive fatigue and their correlates may begin to provide insight into their underlying mechanisms.
PMID: 26195047
ISSN: 2211-0356
CID: 1683802
Quantitative Immunoblotting of Endogenous Hedgehog Pathway Components
Farzan, Shohreh F; Robbins, David J
Quantitative analysis and modeling of signaling pathway components can reveal important information about the dynamics of that system, including the relative stoichiometries and affinities between the individual signaling components, as well as rate-limiting steps in the signaling pathway. In this chapter, we present a method that we developed to quantify the steady-state ratio of core Hedgehog (Hh) signaling components in both cultured cells and the Drosophila embryo, a physiologically relevant tissue.
PMID: 26179042
ISSN: 1940-6029
CID: 1675342
Correlates of Adherence to Varenicline Among HIV+ Smokers
Shelley, Donna; Tseng, Tuo-Yen; Gonzalez, Mirelis; Krebs, Paul; Wong, Selena; Furberg, Robert; Sherman, Scott; Schoenthaler, Antoinette; Urbina, Anthony; Cleland, Charles M
INTRODUCTION: Low rates of adherence to smoking cessation pharmacotherapy may limit the effectiveness of treatment. However, few studies have examined adherence in smoking cessation trials thus, there is a limited understanding of factors that influence adherence behaviors. This brief report analyzes correlates of adherence to varenicline among people living with HIV/AIDS. METHODS: Study participants were recruited from three HIV care centers in New York City and enrolled in a three-arm randomized controlled pilot study in which all subjects received varenicline. At the 1-month study visit, there were no significant differences in adherence by study condition, therefore we combined treatment arms to examine correlates of adherence (n = 127). We used pill counts to assess varenicline adherence, defined as taking at least 80% of the prescribed dose. We conducted a multivariate path analysis to assess factors proposed by the information-motivation-behavioral skills model to predict adherence. RESULTS: Only 56% of smokers were at least 80% adherent to varenicline at 1 month. Adherence-related information, self-efficacy, a college degree, and non-Hispanic white race/ethnicity were associated with increased varenicline adherence. In path analysis, information and motivation were associated with increased adherence self-efficacy, and adherence self-efficacy was associated with increased adherence, but with marginal significance. These associations with adherence were no longer significant after controlling for race/ethnicity and education. CONCLUSIONS: Further exploration of the role of a modifiable correlates of adherence, such as adherence-related information, motivation and self-efficacy is warranted. Interventions are needed that can address disparities in these and other psychosocial factors that may mediate poor medication adherence.
PMCID:4580547
PMID: 26180221
ISSN: 1469-994x
CID: 1668962