Bio

Academic Appointments


Administrative Appointments


  • Director of Quantitiative Sciences Unit (QSU), Stanford University (2009 - Present)
  • Associate Professor, Stanford University (2012 - Present)
  • Clinical Associate Professor, Stanford University (2009 - 2012)
  • Associate Professor of Clinical Biostatistics, Columbia University (2009 - 2009)
  • Assistant Professor of Clinical Biostatistics, Columbia University (2000 - 2009)

Honors & Awards


  • Calderon Prize for Junior Faculty Achievement, Columbia University (2000-2003)
  • Phi Beta Kappa National Honor Society, Boston University (1993)
  • Distinction in Statistics, Boston University (1993)
  • Magna Cum Laude, Boston University (1993)

Professional Education


  • Ph.D., University of Washington, Biostatistics (2000)
  • M.S., University of Washington, Biostatistics (1997)
  • M.A., Boston University, Mathematics (1993)
  • B.A., Boston University, Mathematics (1993)

Community and International Work


  • Tutor and Mentor, Grosvenor House

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

Research & Scholarship

Current Research and Scholarly Interests


Dr. Desai is the Director of the Quantitative Sciences Unit. She is interested in the application of biostatistical methods to all areas of medicine including oncology, nephrology, and endocrinology. She works on methods for the analysis of epidemiologic studies, clinical trials, and studies with missing observations.

Teaching

2013-14 Courses


Publications

Journal Articles


  • Alcohol consumption and risk of melanoma and non-melanoma skin cancer in the Women's Health Initiative CANCER CAUSES & CONTROL Kubo, J. T., Henderson, M. T., Desai, M., Wactawski-Wende, J., Stefanick, M. L., Tang, J. Y. 2014; 25 (1): 1-10

    Abstract

    The relationship between alcohol consumption and preference of alcohol type with hazard of melanoma (MM) and risk of non-melanoma skin cancer (NMSC) was examined in the Women's Health Initiative (WHI) Observational Study (OS).A prospective cohort of 59,575 White postmenopausal women in the WHI OS (mean age 63.6) was analyzed. Cox proportional hazards models and logistic regression techniques were used to assess the hazard and risk of physician-adjudicated MM and self-reported NMSC, respectively, after adjusting for potential confounders including measures of sun exposure and skin type.Over 10.2 mean years of follow-up, 532 MM cases and 9,593 NMSC cases occurred. A significant relationship between amount of alcohol consumed and both MM and NMSC was observed, with those who consume 7+ drinks per week having a higher hazard of MM (HR 1.64 (1.09, 2.49), p global = 0.0013) and higher risk of NMSC (OR 1.23 (1.11, 1.36), p global < 0.0001) compared to non-drinkers. Lifetime alcohol consumption was also positively associated with hazard of MM (p = 0.0011) and risk of NMSC (p < 0.0001). Further, compared to non-drinkers, a preference for either white wine or liquor was associated with an increased hazard of MM (HR 1.52 (1.02, 2.27) for white wine; HR 1.65 (1.07, 2.55) for liquor) and risk of NMSC (OR 1.16 (1.05, 1.28) for white wine; OR 1.26 (1.13, 1.41) for liquor).Higher current alcohol consumption, higher lifetime alcohol consumption, and a preference for white wine or liquor were associated with increased hazard of MM and risk of NMSC.

    View details for DOI 10.1007/s10552-013-0280-3

    View details for Web of Science ID 000329351700001

    View details for PubMedID 24173533

  • Optical biopsy of sessile serrated adenomas: do these lesions resemble hyperplastic polyps under narrow-band imaging? Gastrointestinal endoscopy Kumar, S., Fioritto, A., Mitani, A., Desai, M., Gunaratnam, N., Ladabaum, U. 2013; 78 (6): 902-909

    Abstract

    Serrated colorectal lesions include hyperplastic polyps (HPs) and sessile serrated adenomas (SSAs). Optical biopsy could misclassify SSAs as unimportant if they resemble HPs.To explore the narrow-band imaging (NBI) features of SSAs. We hypothesized that SSAs resemble HPs under NBI.Retrospective analysis of data from our prospective study of NBI in routine practice.Single specialty group.Patients undergoing colonoscopy.Colonoscopy.Polyp histology prediction by community gastroenterologists. Features of SSAs versus HPs and adenomas by using the Narrow-Band Imaging International Colorectal Endoscopic (NICE) Classification.Among 2388 lesions, 141 were diagnosed on pathology as SSAs, 465 as HPs, and 1546 as adenomas. Each individual NICE feature of HPs was found in 38% to 42% of SSAs, 66% to 67% of HPs, and 15% to 20% of adenomas (P < .001 for each). Each individual NICE feature of adenomas was found in 57% to 62% of SSAs, 33% to 34% of HPs, and 80% to 84% of adenomas (P < .001 for each). Compared with HPs, SSAs were less likely (odds ratio [OR] 0.74; 95% confidence interval [CI], 0.69-0.79) and adenomas were even less likely (OR 0.62; 95% CI, 0.59-0.64) to have all 3 NICE features of HPs. SSAs >5 mm were more likely than smaller SSAs to have all 3 NICE features of adenomas. SSA location did not predict NBI features. Analyses restricted to high-confidence lesions showed similar results.The endoscopists were not NBI experts.Community gastroenterologists observed a profile of NICE features among SSAs that was intermediate to the profiles observed for HPs and adenomas. These results require confirmation by NBI experts.

    View details for DOI 10.1016/j.gie.2013.06.004

    View details for PubMedID 23849819

  • Lower Skin Cancer Risk in Women with Higher Body Mass Index: The Women's Health Initiative Observational Study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Tang, J. Y., Henderson, M. T., Hernandez-Boussard, T., Kubo, J., Desai, M., Sims, S. T., Aroda, V., Thomas, F., McTiernan, A., Stefanick, M. L. 2013; 22 (12): 2412-2415

    Abstract

    The unclear relationship of obesity to incident melanoma and nonmelanoma skin cancer (NMSC) risks was evaluated in the large, geographically diverse longitudinal, prospective Women's Health Initiative (WHI) observational study. Risks of melanoma and NMSC in normal weight women were compared with risks in overweight [body mass index (BMI) = 25-29.0 kg/m(2)] and obese (BMI ≥ 30 kg/m(2)) women, using Cox proportional hazards models for melanoma and logistic regression for NMSC. Over a mean 9.4 years of follow-up, there were 386 melanoma and 9,870 NSMC cases. Risk of melanoma did not differ across weight categories (P = 0.86), whereas in fully adjusted models, NMSC risk was lower in overweight [OR, 0.93; 95% confidence interval (CI), 0.89-0.99] and obese (OR, 0.85; 95% CI, 0.80-0.91) women (P < 0.001). Excess body weight was not associated with melanoma risk in postmenopausal women but was inversely associated with NMSC risk, possibly due to lower sun exposure in overweight and obese women. This supports previous work demonstrating the relationship between excess body weight and skin cancer risk. Cancer Epidemiol Biomarkers Prev; 22(12); 2412-5. ©2013 AACR.

    View details for DOI 10.1158/1055-9965.EPI-13-0647

    View details for PubMedID 24042260

  • Associations between employee and manager gender: impacts on gender-specific risk of acute occupational injury in metal manufacturing BMC PUBLIC HEALTH Kubo, J. T., Cullen, M. R., Desai, M., Modrek, S. 2013; 13

    Abstract

    Prior research has shown increased risk of injury for female employees compared to male employees after controlling for job and tasks, but have not explored whether this increased risk might be moderated by manager gender. The gender of one's manager could in theory affect injury rates among male and female employees through their managers' response to an employee's psychosocial stress or through how employees differentially report injuries. Other explanations for the gender disparity in injury experience, such as ergonomic factors or differential training, are unlikely to be impacted by supervisor gender. This study seeks to explore whether an employee's manager's gender modifies the effect of employee gender with regards to risk of acute injury.A cohort of employees and managers were identified using human resources and injury management data between January 1, 2002 and December 31, 2007 for six facilities of a large US aluminum manufacturing company. Cox proportional hazards models were employed to examine the interaction between employee gender and whether the employee had female only manager(s), male only manager(s), or both male and female managers on injury risk. Manager gender category was included as a time varying covariate and reassessed for each employee at the midpoint of each year.The percentage of departments with both female and male managers increased dramatically during the study period due to corporate efforts to increase female representation in management. After adjustment for fixed effects at the facility level and shared frailty by department, manager gender category does not appear to moderate the effect of employee gender (p = 0.717). Manager category was not a significant predictor (p = 0.093) of time to first acute injury. Similarly, having at least one female manager did not modify the hazard of injury for female employees compared to males (p = 0.899) and was not a significant predictor of time to first acute injury (p = 0.601).Prior findings suggest that female manufacturing employees are at higher risk for acute injury compared to males; this analysis suggests that this relationship is not affected by the gender of the employee's manager(s).

    View details for DOI 10.1186/1471-2458-13-1053

    View details for Web of Science ID 000329295600001

    View details for PubMedID 24207014

  • Reply to Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women: the Women's Health Initiative. Cancer Tang, J. Y., Kubo, J., Desai, M. 2013; 119 (20): 3737-3738

    View details for DOI 10.1002/cncr.28247

    View details for PubMedID 23921712

  • Preference for wine is associated with lower hip fracture incidence in post-menopausal women BMC WOMENS HEALTH Kubo, J. T., Stefanick, M. L., Robbins, J., Wactawski-Wende, J., Cullen, M. R., Freiberg, M., Desai, M. 2013; 13
  • Changes in physical activity and body composition in postmenopausal women over time. Medicine and science in sports and exercise Sims, S. T., Kubo, J., Desai, M., Bea, J., Beasley, J. M., Manson, J. E., Allison, M., Seguin, R. A., Chen, Z., Michael, Y. L., Sullivan, S. D., Beresford, S., Stefanick, M. L. 2013; 45 (8): 1486-1492

    Abstract

    PURPOSE: Higher physical activity (PA) has been associated with greater attenuation of body-fat gain and preservation of lean mass across the lifespan. These analyses aimed to determine relationships of change in PA to changes in fat and lean body mass in a longitudinal prospective study of postmenopausal women. METHODS: Among 11,491 women enrolled at three Women's Health Initiative (WHI) clinical centers were selected to undergo dual-energy x-ray absorptiometry (DXA), 8,352 had baseline body composition measurements, with at least one repeated measure at yr 1, 3, and 6. PA data were obtained by self-report at baseline, 3 and 6 yr of follow-up. Time-varying PA impact on change in lean and fat mass during the six-yr study period for age groups (50-59y, 60-69y, 70- 79y) was estimated using mixed effects linear regression. RESULTS: Baseline PA and body composition differed significantly among the three age groups. The association of change in fat mass from baseline and time-varying PA differed across the three age groups (p=0.0006). In women aged 50-59, gain in fat mass from baseline was attenuated with higher levels of physical activity. Women aged 70-79 lost fat mass at all PA levels. In contrast, change in lean mass from baseline and time-varying PA did not differ by age group (p=0.1935). CONCLUSIONS: The association between PA and change in fat mass varies by age group, with younger, but not older, women benefitting from higher levels of aerobic PA. Higher levels of aerobic activity are not associated with changes in lean mass, which tends to decrease in older women regardless of activity level. Greater attention to resistance training exercises may be needed to prevent lean mass loss as women age.

    View details for DOI 10.1249/MSS.0b013e31828af8bd

    View details for PubMedID 23439422

  • Piecewise exponential models to assess the influence of job-specific experience on the hazard of acute injury for hourly factory workers BMC MEDICAL RESEARCH METHODOLOGY Kubo, J., Cullen, M. R., Cantley, L., Slade, M., Tessier-Sherman, B., Taiwo, O., Desai, M. 2013; 13

    Abstract

    An inverse relationship between experience and risk of injury has been observed in many occupations. Due to statistical challenges, however, it has been difficult to characterize the role of experience on the hazard of injury. In particular, because the time observed up to injury is equivalent to the amount of experience accumulated, the baseline hazard of injury becomes the main parameter of interest, excluding Cox proportional hazards models as applicable methods for consideration.Using a data set of 81,301 hourly production workers of a global aluminum company at 207 US facilities, we compared competing parametric models for the baseline hazard to assess whether experience affected the hazard of injury at hire and after later job changes. Specific models considered included the exponential, Weibull, and two (a hypothesis-driven and a data-driven) two-piece exponential models to formally test the null hypothesis that experience does not impact the hazard of injury.We highlighted the advantages of our comparative approach and the interpretability of our selected model: a two-piece exponential model that allowed the baseline hazard of injury to change with experience. Our findings suggested a 30% increase in the hazard in the first year after job initiation and/or change.Piecewise exponential models may be particularly useful in modeling risk of injury as a function of experience and have the additional benefit of interpretability over other similarly flexible models.

    View details for DOI 10.1186/1471-2288-13-89

    View details for Web of Science ID 000322382600001

    View details for PubMedID 23841648

  • Self-perceived physical health predicts cardiovascular disease incidence and death among postmenopausal women BMC PUBLIC HEALTH Saquib, N., Brunner, R., Kubo, J., Tindle, H., Kroenke, C., Desai, M., Daviglus, M. L., Allen, N., Martin, L. W., Robinson, J., Stefanick, M. L. 2013; 13
  • Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women The Women's Health Initiative CANCER Gamba, C. A., Swetter, S. M., Stefanick, M. L., Kubo, J., Desai, M., Spaunhurst, K. M., Sinha, A. A., Asgari, M. M., Sturgeon, S., Tang, J. Y. 2013; 119 (8): 1562-1569

    Abstract

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with decreased risk of gastric, colorectal, and breast cancer. However, the impact of NSAIDs on the risk of melanoma has been inconsistent. The authors evaluated the association between NSAID use and cutaneous melanoma risk in the Women's Health Initiative (WHI) Observational Study (OS).At study entry, use of aspirin (acetylsalicylic acid [ASA]) and nonaspirin NSAIDs was assessed among 59,806 postmenopausal Caucasian women ages 50 to 79 years. Cox proportional hazards models were constructed after adjusting for participant skin type, sun exposure history, and medical indications for NSAID use among other confounders.During a median follow-up of 12 years, 548 incident melanomas were confirmed by medical review. Women who used ASA had a 21% lower risk of melanoma (hazard ratio, 0.79; 95% confidence interval, 0.63-0.98) relative to nonusers. Increased duration of ASA use (<1 year, 1-4 years, and ? 5 years) was associated with an 11% lower risk of melanoma for each categorical increase (Ptrend = .01), and women with ? 5 years of use had a 30% lower melanoma risk (hazard ratio, 0.70; 95% confidence interval, 0.55-0.94). In contrast, use of non-ASA NSAIDs and acetaminophen were not associated with melanoma risk.Postmenopausal women who used ASA had a significantly lower risk of melanoma, and longer duration of ASA use was associated with greater protection. Although this study was limited by the observational design and self-report of NSAID use, the findings suggest that ASA may have a chemopreventive effect against the development of melanoma and warrant further clinical investigation.

    View details for DOI 10.1002/cncr.27817

    View details for Web of Science ID 000317618700016

    View details for PubMedID 23483536

  • Risk of Cardiovascular Disease from Antiretroviral Therapy for HIV: A Systematic Review PLOS ONE Bavinger, C., Bendavid, E., Niehaus, K., Olshen, R. A., Olkin, I., Sundaram, V., Wein, N., Holodniy, M., Hou, N., Owens, D. K., Desai, M. 2013; 8 (3)

    Abstract

    Recent studies suggest certain antiretroviral therapy (ART) drugs are associated with increases in cardiovascular disease.We performed a systematic review and meta-analysis to summarize the available evidence, with the goal of elucidating whether specific ART drugs are associated with an increased risk of myocardial infarction (MI).We searched Medline, Web of Science, the Cochrane Library, and abstract archives from the Conference on Retroviruses and Opportunistic Infections and International AIDS Society up to June 2011 to identify published articles and abstracts.Eligible studies were comparative and included MI, strokes, or other cardiovascular events as outcomes.Eligibility screening, data extraction, and quality assessment were performed independently by two investigators.Random effects methods and Fisher's combined probability test were used to summarize evidence.Twenty-seven studies met inclusion criteria, with 8 contributing to a formal meta-analysis. Findings based on two observational studies indicated an increase in risk of MI for patients recently exposed (usually defined as within last 6 months) to abacavir (RR 1.92, 95% CI 1.51-2.42) and protease inhibitors (PI) (RR 2.13, 95% CI 1.06-4.28). Our analysis also suggested an increased risk associated with each additional year of exposure to indinavir (RR 1.11, 95% CI 1.05-1.17) and lopinavir (RR 1.22, 95% CI 1.01-1.47). Our findings of increased cardiovascular risk from abacavir and PIs were in contrast to four published meta-analyses based on secondary analyses of randomized controlled trials, which found no increased risk from cardiovascular disease.Although observational studies implicated specific drugs, the evidence is mixed. Further, meta-analyses of randomized trials did not find increased risk from abacavir and PIs. Our findings that implicate specific ARTs in the observational setting provide sufficient evidence to warrant further investigation of this relationship in studies designed for that purpose.

    View details for DOI 10.1371/journal.pone.0059551

    View details for Web of Science ID 000317418500051

    View details for PubMedID 23555704

  • Trends in the incidence of intestinal perforation in US dialysis patients (1992-2005). Journal of nephrology Yang, J., Lee, T., Montez-Rath, M. E., Desai, M., Winkelmayer, W. C. 2013; 26 (2): 281-288

    Abstract

    Little is known about the incidence of intestinal perforation in patients undergoing dialysis. Concerns exist that sevelamer hydrochloride may increase the risk of intestinal perforation. We examined long-term trends for the incidence of intestinal perforation among US dialysis patients.We studied all dialysis patients (1992-2005) who had Medicare as primary payer. We used ICD-9 diagnosis code 569.83 to ascertain events of intestinal perforation. We studied (a) all perforations and (b) perforations that did not appear to be associated with specific causative conditions (specific diseases or iatrogenic procedures within 7 days of perforation). We used Poisson regression to model the annual number of intestinal perforations and tested for any changes in levels and temporal trends of incidence rates before versus after January 1, 1999.Overall, 1,060,132 patients contributed 2.7 million patient-years. We observed 12,355 events of intestinal perforation and 7,814 spontaneous perforations. The corresponding incidence rates were 4.6 (total) and 2.9 (spontaneous perforation) episodes per 1,000 person-years, respectively. For both outcome definitions, 30-day mortality was 42%. Unadjusted and adjusted incidence rates were not materially different over time. Formal tests for any changes in the level or slope of incidence comparing time periods before and after January 1, 1999, indicated no evidence for any changes in the incidence of intestinal perforation over time.In US dialysis patients, incidence of intestinal perforation was low, but associated with high short-term mortality. We did not detect any significant changes in the incidence of intestinal perforation before versus after approval of sevelamer hydrochloride in late 1998.

    View details for DOI 10.5301/jn.5000104

    View details for PubMedID 22419235

  • On the use of robust estimators for standard errors in the presence of clustering when clustering membership is misspecified CONTEMPORARY CLINICAL TRIALS Desai, M., Bryson, S. W., Robinson, T. 2013; 34 (2): 248-256

    Abstract

    This paper examines the implications of using robust estimators (REs) of standard errors in the presence of clustering when cluster membership is unclear as may commonly occur in clustered randomized trials. For example, in such trials, cluster membership may not be recorded for one or more treatment arms and/or cluster membership may be dynamic. When clusters are well defined, REs have properties that are robust to misspecification of the correlation structure. To examine whether results were sensitive to assumptions about the clustering membership, we conducted simulation studies for a two-arm clinical trial, where the number of clusters, the intracluster correlation (ICC), and the sample size varied. REs of standard errors that incorrectly assumed clustering of data that were truly independent yielded type I error rates of up to 40%. Partial and complete misspecifications of membership (where some and no knowledge of true membership were incorporated into assumptions) for data generated from a large number of clusters (50) with a moderate ICC (0.20) yielded type I error rates that ranged from 7.2% to 9.1% and 10.5% to 45.6%, respectively; incorrectly assuming independence gave a type I error rate of 10.5%. REs of standard errors can be useful when the ICC and knowledge of cluster membership are high. When the ICC is weak, a number of factors must be considered. Our findings suggest guidelines for making sensible analytic choices in the presence of clustering.

    View details for DOI 10.1016/j.cct.2012.11.006

    View details for Web of Science ID 000317169100009

    View details for PubMedID 23220255

  • Real-Time Optical Biopsy of Colon Polyps With Narrow Band Imaging in Community Practice Does Not Yet Meet Key Thresholds for Clinical Decisions GASTROENTEROLOGY Ladabaum, U., Fioritto, A., Mitani, A., Desai, M., Kim, J. P., Rex, D. K., Imperiale, T., Gunaratnam, N. 2013; 144 (1): 81-91

    Abstract

    Accurate optical analysis of colorectal polyps (optical biopsy) could prevent unnecessary polypectomies or allow a "resect and discard" strategy with surveillance intervals determined based on the results of the optical biopsy; this could be less expensive than histopathologic analysis of polyps. We prospectively evaluated real-time optical biopsy analysis of polyps with narrow band imaging (NBI) by community-based gastroenterologists.We first analyzed a computerized module to train gastroenterologists (N = 13) in optical biopsy skills using photographs of polyps. Then we evaluated a practice-based learning program for these gastroenterologists (n = 12) that included real-time optical analysis of polyps in vivo, comparison of optical biopsy predictions to histopathologic analysis, and ongoing feedback on performance.Twelve of 13 subjects identified adenomas with >90% accuracy at the end of the computer study, and 3 of 12 subjects did so with accuracy ?90% in the in vivo study. Learning curves showed considerable variation among batches of polyps. For diminutive rectosigmoid polyps assessed with high confidence at the end of the study, adenomas were identified with mean (95% confidence interval [CI]) accuracy, sensitivity, specificity, and negative predictive values of 81% (73%-89%), 85% (74%-96%), 78% (66%-92%), and 91% (86%-97%), respectively. The adjusted odds ratio for high confidence as a predictor of accuracy was 1.8 (95% CI, 1.3-2.5). The agreement between surveillance recommendations informed by high-confidence NBI analysis of diminutive polyps and results from histopathologic analysis of all polyps was 80% (95% CI, 77%-82%).In an evaluation of real-time optical biopsy analysis of polyps with NBI, only 25% of gastroenterologists assessed polyps with ?90% accuracy. The negative predictive value for identification of adenomas, but not the surveillance interval agreement, met the American Society for Gastrointestinal Endoscopy-recommended thresholds for optical biopsy. Better results in community practice must be achieved before NBI-based optical biopsy methods can be used routinely to evaluate polyps; ClinicalTrials.gov number, NCT01638091.

    View details for DOI 10.1053/j.gastro.2012.09.054

    View details for Web of Science ID 000312965100029

    View details for PubMedID 23041328

  • Donor Recipient Sex Mismatch in Kidney Transplantation GENDER MEDICINE Tan, J. C., Kim, J. P., Chertow, G. M., Grumet, F. C., Desai, M. 2012; 9 (5): 335-347

    Abstract

    The lack of reliable human proxies for minor (ie, non-HLA) histocompatibility loci hampers the ability to leverage these factors toward improving transplant outcomes. Despite conflicting reports of the effect of donor-recipient sex mismatch on renal allografts, the association between acute rejection of renal allografts and the development of human alloantibodies to the male H-Y antigen suggested to us that donor-recipient sex mismatch deserved re-evaluation.To evaluate whether the relationships between donor sex and allograft failure differed by recipient sex.We studied recipients of deceased-donor (n = 125,369) and living-donor (n = 63,139) transplants in the United States Renal Data System. Using Cox proportional hazards models stratified by donor type, we estimated the association between donor-recipient sex mismatch and death-censored allograft failure with adjustment for known risk factors, with and without the use of multiple imputation methods to account for potential bias and/or loss of efficiency due to missing data.The advantage afforded by male donor kidneys was more pronounced among male than among female recipients (8% vs 2% relative risk reduction; interaction P < 0.01). This difference is of the order of magnitude of several other risk factors affecting donor selection decisions.Donor-recipient sex mismatch affects renal allograft survival in a direction consistent with immune responses to sexually determined minor histocompatibility antigens. Our study provides a paradigm for clinical detection of markers for minor histocompatibility loci.

    View details for DOI 10.1016/j.genm.2012.07.004

    View details for Web of Science ID 000310170000005

    View details for PubMedID 22906727

  • Validation of Reported Predialysis Nephrology Care of Older Patients Initiating Dialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kim, J. P., Desai, M., Chertow, G. M., Winkelmayer, W. C. 2012; 23 (6): 1078-1085

    Abstract

    The Centers for Medicare and Medicaid Services (CMS) Medical Evidence Report (form CMS-2728) queries providers about the timing of the patient's first nephrologist consultation before initiation of dialysis. The monitoring of disease-specific goals in the Healthy People 2020 initiative will use information from this question, but the accuracy of the reported information is unknown. We defined a cohort of 80,509 patients aged ?67 years who initiated dialysis between July 2005 and December 2008 with ?2 years of uninterrupted Medicare coverage as their primary payer. The primary referent, determined from claims data, was the first observed outpatient nephrologist consultation; secondary analyses used the earliest nephrology consultation, whether inpatient or outpatient. We used linear regression models to assess the associations among the magnitude of discrepant reporting and patient characteristics and we tested for any temporal trends. When using the earliest recorded outpatient nephrology encounter, agreement between the two sources of ascertainment was 48.2%, and the ? statistic was 0.29 when we categorized the timing of the visit into four periods (never, <6, 6-12, and >12 months). When we dichotomized the timing of first predialysis nephrology care at >12 or ?12 months, accuracy was 70% (?=0.36), but it differed by patient characteristics and declined over time. In conclusion, we found substantial disagreement between information from the CMS Medical Evidence Report and Medicare physician claims on the timing of first predialysis nephrologist care. More-specific instructions may improve reporting and increase the utility of form CMS-2728 for research and public health surveillance.

    View details for DOI 10.1681/ASN.2011080871

    View details for Web of Science ID 000310256300017

    View details for PubMedID 22518002

  • Influence of donor and recipient sex mismatch on heart transplant outcomes: Analysis of the International Society for Heart and Lung Transplantation Registry JOURNAL OF HEART AND LUNG TRANSPLANTATION Khush, K. K., Kubo, J. T., Desai, M. 2012; 31 (5): 459-466

    Abstract

    Prior studies have presented contradictory results after analyzing associations between donor and recipient sex on survival after heart transplantation and causes of death such as acute rejection (AR) and cardiac allograft vasculopathy (CAV). We used the International Society for Heart and Lung Transplantation (ISHLT) Registry, the largest repository of heart transplant outcomes worldwide, to comprehensively address these questions.We studied 60,584 adult recipients of heart transplants performed between 1990 and 2008. Outcomes of interest were overall survival, death-censored allograft survival, AR, and CAV, which were studied using regression models. To assess whether donor/recipient sex mismatch affected outcomes, the experience of male recipients with female vs male donors was compared with that of female recipients with female vs male donors through inclusion of an interaction term between donor and recipient sex.Significant differences were observed between male and female recipients in overall survival and death-censored allograft survival for female vs male donors. Male recipients of female allografts had a 10% increase in adjusted mortality relative to male recipients of male allografts, whereas female recipients of female allografts had a 10% decrease in adjusted mortality relative to female recipients of male allografts (p < 0.0001). Findings were similar for death-censored allograft survival. Differences in the effect of donor sex on AR or CAV between male and female recipients were not significant.Analysis of the ISHLT data set has demonstrated a strong association between donor/recipient sex mismatch and reduced survival after heart transplantation.

    View details for DOI 10.1016/j.healun.2012.02.005

    View details for Web of Science ID 000302756700005

    View details for PubMedID 22418079

  • Trends in Acute Nonvariceal Upper Gastrointestinal Bleeding in Dialysis Patients JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Yang, J., Lee, T., Montez-Rath, M. E., Paik, J., Chertow, G. M., Desai, M., Winkelmayer, W. C. 2012; 23 (3): 495-506

    Abstract

    Impaired kidney function is a risk factor for upper gastrointestinal (GI) bleeding, an event associated with poor outcomes. The burden of upper GI bleeding and its effect on patients with ESRD are not well described. Using data from the US Renal Data System, we quantified the rates of occurrence of and associated 30-day mortality from acute, nonvariceal upper GI bleeding in patients undergoing dialysis; we used medical claims and previously validated algorithms where available. Overall, 948,345 patients contributed 2,296,323 patient-years for study. The occurrence rates for upper GI bleeding were 57 and 328 episodes per 1000 person-years according to stringent and lenient definitions of acute, nonvariceal upper GI bleeding, respectively. Unadjusted occurrence rates remained flat (stringent) or increased (lenient) from 1997 to 2008; after adjustment for sociodemographic characteristics and comorbid conditions, however, we found a significant decline for both definitions (linear approximation, 2.7% and 1.5% per year, respectively; P<0.001). In more recent years, patients had higher hematocrit levels before upper GI bleeding episodes and were more likely to receive blood transfusions during an episode. Overall 30-day mortality was 11.8%, which declined significantly over time (relative declines of 2.3% or 2.8% per year for the stringent and lenient definitions, respectively). In summary, despite declining trends worldwide, crude rates of acute, nonvariceal upper GI bleeding among patients undergoing dialysis have not decreased in the past 10 years. Although 30-day mortality related to upper GI bleeding declined, perhaps reflecting improvements in medical care, the burden on the ESRD population remains substantial.

    View details for DOI 10.1681/ASN.2011070658

    View details for Web of Science ID 000301206900017

    View details for PubMedID 22266666

  • Validity of Surrogate Measures for Functional Nephron Mass TRANSPLANTATION Tan, J. C., Paik, J., Chertow, G. M., Grumet, F. C., Busque, S., Lapasia, J., Desai, M. 2011; 92 (12): 1335-1341

    Abstract

    Transplanted nephron mass is an important determinant of long-term allograft survival, but accurate assessment before organ retrieval is challenging. Newer radiologic imaging techniques allow for better determination of total kidney and cortical volumes.Using volume measurements reconstructed from magnetic resonance or computed tomography imaging from living donor candidates, we characterized total kidney (n=312) and cortical volumes (n=236) according to sex, age, weight, height, body mass index (BMI), and body surface area (BSA).The mean cortical volume was 204 mL (range 105-355 mL) with no significant differences between left and right cortical volumes. The degree to which existing anthropomorphic surrogates predict nephron mass was quantified, and a diligent attempt was made to derive a better surrogate model for nephron mass. Cortical volumes were strongly associated with sex and BSA, but not with weight, height, or BMI. Four prediction models for cortical volume constructed using combinations of age, sex, race, weight, and height were compared with models including either BSA or BMI.Among existing surrogate measures, BSA was superior to BMI in predicting renal cortical volume. We were able to construct a statistically superior proxy for cortical volume, but whether relevant improvements in predictive accuracy could be gained needs further evaluation in a larger population.

    View details for DOI 10.1097/TP.0b013e31823705ef

    View details for Web of Science ID 000298149200012

    View details for PubMedID 22011765

  • The Balance Between Mutators and Nonmutators in Asexual Populations GENETICS Desai, M. M., Fisher, D. S. 2011; 188 (4): 997-1014

    Abstract

    Mutator alleles, which elevate an individual's mutation rate from 10 to 10,000-fold, have been found at high frequencies in many natural and experimental populations. Mutators are continually produced from nonmutators, often due to mutations in mismatch-repair genes. These mutators gradually accumulate deleterious mutations, limiting their spread. However, they can occasionally hitchhike to high frequencies with beneficial mutations. We study the interplay between these effects. We first analyze the dynamics of the balance between the production of mutator alleles and their elimination due to deleterious mutations. We find that when deleterious mutation rates are high in mutators, there will often be many "young," recently produced mutators in the population, and the fact that deleterious mutations only gradually eliminate individuals from a population is important. We then consider how this mutator-nonmutator balance can be disrupted by beneficial mutations and analyze the circumstances in which fixation of mutator alleles is likely. We find that dynamics is crucial: even in situations where selection on average acts against mutators, so they cannot stably invade, the mutators can still occasionally generate beneficial mutations and hence be important to the evolution of the population.

    View details for DOI 10.1534/genetics.111.128116

    View details for Web of Science ID 000293700000020

    View details for PubMedID 21652523

  • The Handling of Missing Data in Molecular Epidemiology Studies CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Desai, M., Kubo, J., Esserman, D., Terry, M. B. 2011; 20 (8): 1571-1579

    Abstract

    Molecular epidemiology studies face a missing data problem, as biospecimen or imaging data are often collected on only a proportion of subjects eligible for study. We investigated all molecular epidemiology studies published as Research Articles, Short Communications, or Null Results in Brief in Cancer Epidemiology, Biomarkers & Prevention from January 1, 2009, to March 31, 2010, to characterize the extent that missing data were present and to elucidate how the issue was addressed. Of 278 molecular epidemiology studies assessed, most (95%) had missing data on a key variable (66%) and/or used availability of data (often, but not always the biomarker data) as inclusion criterion for study entry (45%). Despite this, only 10% compared subjects included in the analysis with those excluded from the analysis and 88% with missing data conducted a complete-case analysis, a method known to yield biased and inefficient estimates when the data are not missing completely at random. Our findings provide evidence that missing data methods are underutilized in molecular epidemiology studies, which may deleteriously affect the interpretation of results. We provide practical guidelines for the analysis and interpretation of molecular epidemiology studies with missing data.

    View details for DOI 10.1158/1055-9965.EPI-10-1311

    View details for Web of Science ID 000293625600002

    View details for PubMedID 21750174

  • Intradialytic Hypotension and Vascular Access Thrombosis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chang, T. I., Paik, J., Greene, T., Desai, M., Bech, F., Cheung, A. K., Chertow, G. M. 2011; 22 (8): 1526-1533

    Abstract

    Identifying potential modifiable risk factors to reduce the incidence of vascular access thrombosis in hemodialysis could reduce considerable morbidity and health care costs. We analyzed data from a subset of 1426 HEMO study subjects to determine whether more frequent intradialytic hypotension and/or lower predialysis systolic BP were associated with higher rates of vascular access thrombosis. Our primary outcome measure was episodes of vascular access thrombosis occurring within a given 6-month period during HEMO study follow-up. There were 2005 total episodes of vascular access thrombosis during a median 3.1 years of follow-up. The relative rate of thrombosis of native arteriovenous fistulas for the highest quartile of intradialytic hypotension was approximately twice that of the lowest quartile, independent of predialysis systolic BP and other covariates. There was no significant association of intradialytic hypotension with prosthetic arteriovenous graft thrombosis after multivariable adjustment. Higher predialysis systolic BP was associated with a lower rate of fistula and graft thrombosis, independent of intradialytic hypotension and other covariates. In conclusion, more frequent episodes of intradialytic hypotension and lower predialysis systolic BP associate with increased rates of vascular access thrombosis. These results underscore the importance of including vascular access patency in future studies of BP management in hemodialysis.

    View details for DOI 10.1681/ASN.2010101119

    View details for Web of Science ID 000294083300019

    View details for PubMedID 21803971

  • Accuracy of the Kattan nomogram across prostate cancer risk-groups BJU INTERNATIONAL Korets, R., Motamedinia, P., Yeshchina, O., Desai, M., McKiernan, J. M. 2011; 108 (1): 56-60

    Abstract

    • To investigate the predictive ability of nomograms at the extremes of preoperative clinical parameters by examining the predictive ability across all prostate cancer risk groups.• The Columbia University Urologic Oncology Database was reviewed: 3663 patients underwent radical prostatectomy from 1988 to 2008. Patients who had received neoadjuvant or adjuvant therapy, or had insufficient clinical parameters for estimation of 5-year progression-free probability using the preoperative Kattan nomogram were excluded. • A total of 1877 patients were included and stratified by D'Amico risk criteria. Mean estimated nomogram progression rates were compared with actuarial Kaplan-Meier survival statistics. • A regression model to predict progression-free survival was fitted with estimated nomogram score and concordance indices were calculated for the entire model and subsequently for each risk group.• Of 1877 patients, 857 (45.6%) were low risk, 704 (37.5%) were intermediate risk, and 316 (16.8%) were high risk by D'Amico criteria. • Mean estimated nomogram survival and actuarial Kaplan-Meier survival at 5 years were 90.5% and 92.2% (95% CI 89.2-94.3) for low-risk, 76.7% and 77.8% (73.3-81.7) for intermediate-risk, and 65.8% and 60.4% (52.0-67.7) for high-risk groups, respectively. Using nomogram score in the regression model, the c-index for the full model was 0.61. • For low-, intermediate- and high-risk patients independently the c-index was 0.60, 0.59 and 0.57, respectively. When low-, intermediate- and high-risk patients were independently removed from the model the c-index was 0.64, 0.65 and 0.55, respectively. • The c-index for the full model using the categorical nomogram risk scores was 0.67. Similar to the D'Amico model, the c-index improved to 0.69 when intermediate-risk patients were removed from the model.• The study confirms the ability of preoperative nomograms to accurately predict actuarial survival across all risk groups. • The predictive ability of the nomogram varies by risk group, yet even at the extremes of high-risk and low-risk prostate cancer the nomogram accurately predicts outcome.

    View details for DOI 10.1111/j.1464-410X.2010.09838.x

    View details for Web of Science ID 000291928500014

    View details for PubMedID 21062396

  • The interaction of body mass index and race in predicting biochemical failure after radical prostatectomy BJU INTERNATIONAL Lee, D. J., Ritch, C., Desai, M., Benson, M. C., McKiernan, J. M. 2011; 107 (11): 1741-1747

    Abstract

    Therapy (case series).4To examine the interaction of body mass index (BMI) and race in predicting biochemical failure (BCF) after radical prostatectomy (RP). The relative contribution of BMI and race to BCF after RP has not been well characterized.From 1988 to 2008, 969 white and black men underwent RP and BMI data were available. In all, 168 (17.3%) were black and 801 (82.7%) were white men. BCF was defined as a post-surgery PSA level?0.2 ng/mL on ?2 measurements. Cox regression methods were used to model the relationship between race, BMI and BCF.The 969 men had a mean age of 59.8±7.2 years. There was no significant difference in BMI between black and white men (P=0.32). The 5-year disease-free survival for black obese men was the lowest at 48%, compared with non-obese black (73%), obese white (82%) and non-obese white men (83%, P<0.001). BMI did not have a significant impact on BCF. In a multivariate analysis, black race remained an independent predictor of BCF [hazard ratio (HR)=1.76, P=0.01]. BMI does not affect the risk of BCF in black men differently than white men (P value for interaction 0.93).Black race is an independent predictor of biochemical failure after adjusting for pathological factors. The impact of BMI on BCF did not vary among different races. These findings suggest that elevated BMI does not affect the BCF rates of black men more than in other races, and that other factors may influence the racial variability in disease-free survival and BCF risk.

    View details for DOI 10.1111/j.1464-410X.2010.09768.x

    View details for Web of Science ID 000290770000006

    View details for PubMedID 20942835

  • Kidney Function and Long-Term Medication Adherence after Myocardial Infarction in the Elderly CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chang, T. I., Desai, M., Solomon, D. H., Winkelmayer, W. C. 2011; 6 (4): 864-869

    Abstract

    The association of kidney function with long-term outpatient medication adherence in the elderly remains understudied.A cohort of 2103 patients over the age of 65 years enrolled in a pharmacy benefits program after hospital discharge for myocardial infarction was studied. Using linear mixed effects models, the association of baseline kidney function with long-term adherence to recommended medications after myocardial infarction was examined, including angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), ?-blockers, and statins. The primary outcome measure was the percentage of days covered as calculated by pharmacy refill data for 12 serial 3-month intervals (totaling 36 months of follow-up).Overall long-term adherence to ACEIs/ARBs, ?-blockers, and statins was poor. The mean percentage of days covered by 36 months was only 50% to 60% for all three medication classes. Patients with baseline kidney dysfunction had significantly lower long-term ACEI/ARB and ?-blocker adherence compared with patients with higher baseline kidney function. Long-term statin adherence did not vary by baseline level of kidney function.Long-term medication adherence after myocardial infarction in the elderly is low, especially in patients with kidney dysfunction. Future strategies to improve medication adherence should pay special attention to the elderly with kidney dysfunction because they may be especially vulnerable to its adverse clinical consequences.

    View details for DOI 10.2215/CJN.07290810

    View details for Web of Science ID 000289223600025

    View details for PubMedID 21233459

  • Systolic blood pressure and mortality in prevalent haemodialysis patients in the HEMO study JOURNAL OF HUMAN HYPERTENSION Chang, T. I., Friedman, G. D., Cheung, A. K., Greene, T., Desai, M., Chertow, G. M. 2011; 25 (2): 98-105

    Abstract

    Previous studies of blood pressure and mortality in haemodialysis have yielded mixed results, perhaps due to confounding by comorbid conditions. We hypothesized that after improved accounting for confounding factors, higher systolic blood pressure (SBP) would be associated with higher all-cause mortality. We conducted a secondary analysis of data from the haemodialysis study, a randomized trial in prevalent haemodialysis patients. We used three proportional hazard models to determine the relative hazard at different levels of SBP: (1) Model-BL used baseline SBP; (2) Model-TV used SBP as a time-varying variable; and (3) Model-TV-Lag added a 3-month lag to Model-TV to de-emphasize changes in SBP associated with acute illness. In all the models, pre-dialysis SBP <120?mm?Hg was associated with a higher risk of mortality compared with the referent group (140-159?mm?Hg); higher pre-dialysis SBP was not associated with higher risk of mortality. In conclusion, we observed a robust association between lower pre-dialysis SBP and higher risk for all-cause and cardiovascular mortality in a well-characterized cohort of prevalent haemodialysis patients. Randomized clinical trials are needed to define optimal blood pressure targets in the haemodialysis population.

    View details for DOI 10.1038/jhh.2010.42

    View details for Web of Science ID 000286179500005

    View details for PubMedID 20410919

  • Blocking the NOTCH Pathway Inhibits Vascular Inflammation in Large-Vessel Vasculitis CIRCULATION Piggott, K., Deng, J., Warrington, K., Younge, B., Kubo, J. T., Desai, M., Goronzy, J. J., Weyand, C. M. 2011; 123 (3): 309-U180

    Abstract

    Giant cell arteritis is a granulomatous vasculitis of the aorta and its branches that causes blindness, stroke, and aortic aneurysm. CD4 T cells are key pathogenic regulators, instructed by vessel wall dendritic cells to differentiate into vasculitic T cells. The unique pathways driving this dendritic cell-T-cell interaction are incompletely understood, but may provide novel therapeutic targets for a disease in which the only established therapy is long-term treatment with high doses of corticosteroids.Immunohistochemical and gene expression analyses of giant cell arteritis-affected temporal arteries revealed abundant expression of the NOTCH receptor and its ligands, Jagged1 and Delta1. Cleavage of the NOTCH intracellular domain in wall-infiltrating T cells indicated ongoing NOTCH pathway activation in large-vessel vasculitis. NOTCH activation did not occur in small-vessel vasculitis affecting branches of the vasa vasorum tree. We devised 2 strategies to block NOTCH pathway activation: ?-secretase inhibitor treatment, preventing nuclear translocation of the NOTCH intracellular domain, and competing for receptor-ligand interactions through excess soluble ligand, Jagged1-Fc. In a humanized mouse model, NOTCH pathway disruption had strong immunosuppressive effects, inhibiting T-cell activation in the early and established phases of vascular inflammation. NOTCH inhibition was particularly effective in downregulating Th17 responses, but also markedly suppressed Th1 responses.Blocking NOTCH signaling depleted T cells from the vascular infiltrates, implicating NOTCH- NOTCH ligand interactions in regulating T-cell retention and survival in vessel wall inflammation. Modulating the NOTCH signaling cascade emerges as a promising new strategy for immunosuppressive therapy of large-vessel vasculitis.

    View details for DOI 10.1161/CIRCULATIONAHA.110.936203

    View details for Web of Science ID 000286507800018

    View details for PubMedID 21220737

  • The use of complete-case and multiple imputation-based analyses in molecular epidemiology studies that assess interaction effects. Epidemiologic perspectives & innovations : EP+I Desai, M., Esserman, D. A., Gammon, M. D., Terry, M. B. 2011; 8 (1): 5-?

    Abstract

    In molecular epidemiology studies biospecimen data are collected, often with the purpose of evaluating the synergistic role between a biomarker and another feature on an outcome. Typically, biomarker data are collected on only a proportion of subjects eligible for study, leading to a missing data problem. Missing data methods, however, are not customarily incorporated into analyses. Instead, complete-case (CC) analyses are performed, which can result in biased and inefficient estimates.Through simulations, we characterized the performance of CC methods when interaction effects are estimated. We also investigated whether standard multiple imputation (MI) could improve estimation over CC methods when the data are not missing at random (NMAR) and auxiliary information may or may not exist.CC analyses were shown to result in considerable bias and efficiency loss. While MI reduced bias and increased efficiency over CC methods under specific conditions, it too resulted in biased estimates depending on the strength of the auxiliary data available and the nature of the missingness. In particular, CC performed better than MI when extreme values of the covariate were more likely to be missing, while MI outperformed CC when missingness of the covariate related to both the covariate and outcome. MI always improved performance when strong auxiliary data were available. In a real study, MI estimates of interaction effects were attenuated relative to those from a CC approach.Our findings suggest the importance of incorporating missing data methods into the analysis. If the data are MAR, standard MI is a reasonable method. Auxiliary variables may make this assumption more reasonable even if the data are NMAR. Under NMAR we emphasize caution when using standard MI and recommend it over CC only when strong auxiliary data are available. MI, with the missing data mechanism specified, is an alternative when the data are NMAR. In all cases, it is recommended to take advantage of MI's ability to account for the uncertainty of these assumptions.

    View details for DOI 10.1186/1742-5573-8-5

    View details for PubMedID 21978450

  • Is Pregnancy After Breast Cancer Safe? BREAST JOURNAL Kranick, J. A., Schaefer, C., Rowell, S., Desai, M., Petrek, J. A., Hiatt, R. A., Senie, R. T. 2010; 16 (4): 404-411

    Abstract

    The impact of treatment on subsequent fertility and the safety of childbearing are major complicating factors for young women diagnosed with breast cancer. As national data indicate women are postponing first pregnancy to older ages; therefore, many young patients are seeking clinical guidance regarding the safety of conception and treatment options that may not prevent subsequent pregnancy. Newly developed chemotherapy protocols of brief duration have improved life expectancy enabling some women to consider childbearing. This study was conducted to compare prognosis among breast cancer patients with and without a subsequent pregnancy. Medical record review of female members of a Northern California prepaid health care plan enabled the identification of 107 women with one or more subsequent pregnancies and 344 cases without a pregnancy, who were diagnosed between 1968 and 1995. Sets were matched on age, year and stage at diagnosis, months of survival and recurrence status at conception. Among the matched sets, neither risk of recurrence nor death differed significantly by subsequent pregnancy history during an average 12 years of follow-up (adjusted hazard ratio [HR] recurrence: 1.2 [0.8, 2.0]; adjusted HR death: 1.0 [0.6, 1.9]). Women interested in preserving their fertility and considering pregnancy are a self-selected population; therefore, to reduce potential bias, cases were matched on recurrence status at time of conception. Although the number of cases was limited, subgroup analyzes indicated a small, nonsignificant adverse effect among women who conceived within 12 months of diagnosis. This analysis of carefully matched cases provides reassurance that long-term prognosis was not adversely affected by subsequent pregnancy.

    View details for DOI 10.1111/j.1524-4741.2010.00939.x

    View details for Web of Science ID 000279539900011

    View details for PubMedID 20522097

  • The role of vitamin D and SLCO1B1*5 gene polymorphism in statin-associated myalgias. Dermato-endocrinology Linde, R., Peng, L., Desai, M., Feldman, D. 2010; 2 (2): 77-84

    Abstract

    Myalgias are the most common side effect of statin use and the commonest cause for discontinuing therapy. Vitamin D has known physiologic functions in muscle and vitamin D deficiency is known to cause myalgias, with its correction leading to disappearance of muscle symptoms. The 521T>C SLCO1B1*5 gene polymorphism decreasing function in the gene coding for a liver anion transporter that is responsible for statin uptake has been found to explain the majority of statin-associated muscle symptoms. Patients with statin-associated myalgias have been reported to improve with vitamin D supplementation. We therefore investigated (i) whether repletion of vitamin D in deficient patients with myalgias could lead to tolerance for subsequent statin therapy and (ii) whether vitamin D status modifies the effect of the SLCO1B1*5 genotype on myalgia risk. Using a retrospective cohort of 64 patients in whom 25-hydroxyvitamin D [25(OH)D] had been measured for any reason while on statin therapy, including 46 patients who consented to be genotyped, we found strong evidence showing that repletion of vitamin D in vitamin D deficient patients improved myalgias. Of 21 vitamin D deficient patients with intolerable statin-associated myalgias, 14 of 15 rechallenged with statins were subsequently symptomfree, with one patient experiencing mild and tolerable symptoms, far exceeding expected rates of acquired tolerability with no therapy (p = 0.01). In addition, while the SLCO1B1*5 genotype was associated with a three-fold increased risk of myalgias (p = 0.07), this risk was not found to differ by vitamin D status (p = 0.60).

    View details for DOI 10.4161/derm.2.2.13509

    View details for PubMedID 21547103

  • The number of negative pelvic lymph nodes removed does not affect the risk of biochemical failure after radical prostatectomy BJU INTERNATIONAL Murphy, A. M., Berkman, D. S., Desai, M., Benson, M. C., McKiernan, J. M., Badani, K. K. 2010; 105 (2): 176-179

    Abstract

    To assess patients who had radical prostatectomy (RP) and pelvic lymph node dissection (PLND) for pT2-4 N0M0 prostate cancer, to determine if LN yield affects the risk of biochemical failure (BCF), as the extent of PLND at the time of RP has become increasingly uncertain with the decreasing trend in tumour stage.We reviewed the Columbia University Urologic Oncology Database for patients with pT2-4 N0M0 prostate cancer treated with RP from 1990 to 2005. Exclusion criteria included <12 months of follow-up, incomplete clinical and pathological data, and neoadjuvant androgen-deprivation therapy (ADT) or immediate adjuvant ADT or external beam radiotherapy. Unadjusted and adjusted models were used to determine the ability of clinical and pathological variables to predict BCF.The final dataset included 964 patients, with a mean age of 60.5 years and median preoperative prostate-specific antigen (PSA) level of 6.2 ng/mL. The median (range) LN yield was 7 (1-42) and the median follow-up 59 (12-190) months. In the unadjusted and adjusted models, preoperative PSA, pathological Gleason score, pathological stage, surgical margin status and year of surgery were significant predictors of BCF. The LN group was not a significant predictor of BCF in both the unadjusted and adjusted model (P = 0.759 and 0.408, respectively). When patients were stratified into high- and low-risk groups, LN yield remained an insignificant predictor of BCF.A higher LN yield at the time of RP does not increase the chance of cure for patients with pT2-4N0M0 prostate cancer. This lack of a survival advantage holds true for patients with high-risk disease.

    View details for DOI 10.1111/j.1464-410X.2009.08707.x

    View details for Web of Science ID 000273300900007

    View details for PubMedID 19549117

  • The Role of vitamin D and the SLC01B1 gene polymorphism in statin-associated myalgias Dermato-Endocrinology Linde R, Pen L, Desai M, Feldman D 2010; 2 (2): 77-84
  • Long-term Clinical Outcomes of a Phase I Trial of Intravesical Docetaxel in the Management of Non-muscle-invasive Bladder Cancer Refractory to Standard Intravesical Therapy UROLOGY Laudano, M. A., Barlow, L. J., Murphy, A. M., Petrylak, D. P., Desai, M., Benson, M. C., McKiernan, J. M. 2010; 75 (1): 134-137

    Abstract

    To report the long-term clinical outcomes and durability of response after treatment with induction intravesical docetaxel. Most novel agents used to treat bacillus Calmette-Guerin refractory high-grade non-muscle-invasive (NMI) bladder cancer are evaluated only after short follow-up periods. Our previously published phase I trial demonstrated that docetaxel is a safe agent for intravesical therapy with minimal toxicity and no detectable systemic absorption. We sought to determine long-term clinical outcomes after treatment with intravesical docetaxel.Eighteen patients with recurrent Ta (n = 7), T1 (n = 5), and Tis (n = 6) transitional cell carcinoma who experienced treatment failure with at least 1 prior intravesical therapy completed the phase I trial. Docetaxel was administered as 6 weekly intravesical instillations using a dose-escalation model terminated at 0.75 mg/mL. Efficacy was evaluated by interval cystoscopy with biopsies when indicated, cytology, and computed tomography imaging. Follow-up consisted of quarterly cystoscopy, cytology, computed tomography, and biopsy when indicated.With a median follow-up of 48.3 months, 4 patients (22%) have demonstrated a complete durable response and currently remain disease-free without further treatment. Three patients (17%) had a partial response, defined as a single NMI recurrence with no further therapy for bladder cancer. Eleven patients (61%) failed treatment, and required another intervention. One patient developed stage progression. No delayed toxicities were noted. The median disease-free survival time was 13.3 months.After 4 years of follow-up without maintenance therapy, intravesical docetaxel has demonstrated the ability to prevent recurrence in a select number of patients with refractory NMI bladder cancer and warrants further investigation.

    View details for DOI 10.1016/j.urology.2009.06.112

    View details for Web of Science ID 000274393200040

    View details for PubMedID 19913890

  • Medical Advances and Racial/Ethnic Disparities in Cancer Survival CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Tehranifar, P., Neugut, A. I., Phelan, J. C., Link, B. G., Liao, Y., Desai, M., Terry, M. B. 2009; 18 (10): 2701-2708

    Abstract

    Although advances in early detection and treatment of cancer improve overall population survival, these advances may not benefit all population groups equally and may heighten racial/ethnic differences in survival.We identified cancer cases in the Surveillance, Epidemiology and End Results program, who were ages > or = 20 years and diagnosed with one invasive cancer in 1995 to 1999 (n = 580,225). We used 5-year relative survival rates to measure the degree to which mortality from each cancer is amenable to medical interventions (amenability index). We used Kaplan-Meier methods and Cox proportional hazards regression to estimate survival differences between each racial/ethnic minority group relative to Whites, by the overall amenability index, and three levels of amenability (nonamenable, partly amenable, and mostly amenable cancers, corresponding to cancers with 5-year relative survival rate < 40%, 40-69%, and > or = 70%, respectively), adjusting for gender, age, disease stage, and county-level poverty concentration.As amenability increased, racial/ethnic differences in cancer survival increased for African Americans, American Indians/Native Alaskans, and Hispanics relative to Whites. For example, the hazard ratios (95% confidence intervals) for African Americans versus Whites from nonamenable, partly amenable, and mostly amenable cancers were 1.05 (1.03-1.07), 1.38 (1.34-1.41), and 1.41 (1.37-1.46), respectively. Asians/Pacific Islanders had similar or longer survival relative to Whites across amenability levels; however, several subgroups experienced increasingly poorer survival with increasing amenability.Cancer survival disparities for most racial/ethnic minority populations widen as cancers become more amenable to medical interventions. Efforts in developing cancer control measures must be coupled with specific strategies for reducing the expected disparities.

    View details for DOI 10.1158/1055-9965.EPI-09-0305

    View details for Web of Science ID 000270702100018

    View details for PubMedID 19789367

  • Significant Change in Predicted Risk of Biochemical Recurrence After Radical Prostatectomy More Common in Black Than in White Men UROLOGY Laudano, M. A., Badani, K. K., McCann, T. R., Mann, M. J., Ritch, C., Desai, M., Benson, M. C., McKiernan, J. M. 2009; 74 (3): 660-664

    Abstract

    To examine by race how frequently the data after radical prostatectomy translates into a substantial change in prognosis. Many nomograms exist to predict the survival outcomes using the pretreatment clinical parameters and post-treatment pathologic parameters. Race might be an important factor affecting their predictive ability.Kattan nomograms were used to calculate the pretreatment and post-radical prostatectomy 5-year progression-free probability for each patient. The difference between the nomogram scores was used to divide the patients into 3 groups. A decrease in probability of >or=15 percentage points was classified as a significant increase in the probability of recurrence, an increase of >or=15 points was classified as a significant decrease in the probability of recurrence, and an absolute change of <15 points was considered no significant change.The data from 1709 (132 black and 1577 white) men were analyzed. Among the black men, 26.5% had an increase in the probability of recurrence, 57.6% had no change, and 15.9% had a decrease in the probability of recurrence. Among the white men, 13.8% had an increase in the probability of recurrence, 64.5% had no change, and 21.7% had a decrease in the probability of recurrence. Black men were twice as likely to have a significant increase in the probability of recurrence postoperatively compared with white men after adjusting for preoperative prostate-specific antigen level, clinical stage, and biopsy Gleason sum (odds ratio 2.0, 95% confidence interval 1.3-3.1, P = .002).These data could assist clinicians when counseling black men regarding their treatment options according to their preoperative risk profile.

    View details for DOI 10.1016/j.urology.2008.10.075

    View details for Web of Science ID 000270207100065

    View details for PubMedID 19589568

  • Prevalence and Predictors of Antioxidant Supplement Use During Breast Cancer Treatment The Long Island Breast Cancer Study Project CANCER Greenlee, H., Gammon, M. D., Abrahamson, P. E., Gaudet, M. M., Terry, M. B., Hershman, D. L., Desai, M., Teitelbaum, S. L., Neugut, A. I., Jacobson, J. S. 2009; 115 (14): 3271-3282

    Abstract

    Although many patients take antioxidant dietary supplements during breast cancer treatment, the benefits of such supplementation are unproven. The authors of this report analyzed the prevalence of and factors associated with antioxidant supplement use during breast cancer (BC) treatment among women who participated in the Long Island Breast Cancer Study Project.From 2002 through 2004, women with BC who had participated a case-control study from 1996 to 1997 were invited to participate in a follow-up interview. Antioxidant supplement use was defined as any self-reported intake of supplemental vitamin C, vitamin E, beta-carotene, or selenium in individual supplements or multivitamins.Follow-up interview participants were younger, more predominantly white, and of higher socioeconomic status than women who did not respond. Among 764 participants who completed the follow-up interview, 663 (86.8%) reported receiving adjuvant treatment for their BC. Of those 663 women, 401 (60.5%) reported using antioxidants during adjuvant treatment: One hundred twenty of 310 women (38.7%) used antioxidants during chemotherapy, 196 of 464 women (42.2%) used them during radiation, and 286 of 462 women (61.9%) used them during tamoxifen therapy. Of 401 antioxidant users, 278 women (69.3%) used high doses (doses higher than those contained in a Centrum multivitamin). The factors that were associated with high antioxidant supplement use during treatment were higher fruit and vegetable intake at diagnosis (relative risk [RR], 1.71; 95% confidence interval [CI], 1.13-2.59), tamoxifen use (RR, 3.66; 95% CI, 2.32-5.78), ever using herbal products (RR, 3.49; 95% CI, 2.26-5.38), and ever engaging in mind-body practices (RR, 1.72; 95% CI, 1.13-2.64).Given the common use of antioxidant supplements during BC treatment, often at high doses and in conjunction with other complementary therapies, future research should address the effects of antioxidant supplementation on BC outcomes.

    View details for DOI 10.1002/cncr.24378

    View details for Web of Science ID 000267813700015

    View details for PubMedID 19507173

  • USING AUXILIARY DATA IN MOLECULAR EPIDEMIOLOGIC STUDIES AMERICAN JOURNAL OF EPIDEMIOLOGY Desai, M., Terry, M. B. 2009; 169: S85-S85
  • Association between Plasma 25-Hydroxyvitamin D and Breast Cancer Risk CANCER PREVENTION RESEARCH Crew, K. D., Gammon, M. D., Steck, S. E., Hershman, D. L., Cremers, S., Dworakowski, E., Shane, E., Terry, M. B., Desai, M., Teitelbaum, S. L., Neugut, A. I., Santella, R. M. 2009; 2 (6): 598-604

    Abstract

    Vitamin D has been associated with decreased risk of several cancers. In experimental studies, vitamin D has been shown to inhibit cell proliferation and induce differentiation and apoptosis in normal and malignant breast cells. Using a population-based case-control study on Long Island, New York, we examined the association of breast cancer with plasma 25-hydroxyvitamin D (25-OHD) levels, a measure of vitamin D body stores. In-person interviews and blood specimens were obtained from 1,026 incident breast cancer cases diagnosed in 1996 to 1997 and 1,075 population-based controls. Plasma 25-OHD was measured in batched, archived specimens by Diasorin RIA. The mean (SD) plasma 25-OHD concentration was 27.1 (13.0) and 29.7 (15.1) ng/mL in the cases and controls, respectively (P < 0.0001). Plasma 25-OHD was inversely associated with breast cancer risk in a concentration-dependent fashion (P(trend) = 0.002). Compared with women with vitamin D deficiency (25-OHD, <20 ng/mL), levels above 40 ng/mL were associated with decreased breast cancer risk (odds ratio, 0.56; 95% confidence interval, 0.41-0.78). The reduction in risk was greater among postmenopausal women (odds ratio, 0.46; 95% confidence interval, 0.09-0.83), and the effect did not vary according to tumor hormone receptor status. In summary, these results add to a growing body of evidence that adequate vitamin D stores may prevent breast cancer development. Whereas circulating 25-OHD levels of >32 ng/mL are associated with normal bone mineral metabolism, our data suggest that the optimal level for breast cancer prevention is >or=40 ng/mL. Well-designed clinical trials are urgently needed to determine whether vitamin D supplementation is effective for breast cancer chemoprevention.

    View details for DOI 10.1158/1940-6207.CAPR-08-0138

    View details for Web of Science ID 000266629700013

    View details for PubMedID 19470790

  • Interaction of obesity and race in predicting recurrence rates after radical prostatectomy JOURNAL OF CLINICAL ONCOLOGY Lee, D. J., Ritch, C., Desai, M., McKiernan, J. M. 2009; 27 (15)
  • Association of estimated glomerular filtration rate (eGFR) with odds of a renal lesion JOURNAL OF CLINICAL ONCOLOGY Hruby, G., Van Batavia, J., Wosnitzer, M., Benson, M., Desai, M., McKiernan, J., Newhouse, J. 2009; 27 (15)
  • A combined phase I/II trial of intravesical nanoparticle albumin-bound paclitaxel in the treatment of refractory non-muscle- invasive transitional cell bladder cancer JOURNAL OF CLINICAL ONCOLOGY Barlow, L., Laudano, M., Mann, M., Desai, M., Petrylak, D., Benson, M., McKiernan, J. 2009; 27 (15)
  • Role of obesity and race in predicting recurrence rates and survival in renal cell carcinoma JOURNAL OF CLINICAL ONCOLOGY Ritch, C., Lee, D. J., Desai, M., McKiernan, J. M. 2009; 27 (15)
  • beta-carboline alkaloid-enriched extract from the amazonian rain forest tree pao pereira suppresses prostate cancer cells. Journal of the Society for Integrative Oncology Bemis, D. L., Capodice, J. L., Desai, M., Katz, A. E., Buttyan, R. 2009; 7 (2): 59-65

    Abstract

    Bark extracts from the Amazonian rain forest tree Geissospermum vellosii (pao pereira), enriched in alpha-carboline alkaloids have significant anticancer activities in certain preclinical models. Because of the predominance of prostate cancer as a cause of cancer-related morbidity and mortality for men of Western countries, we preclinically tested the in vitro and in vivo effects of a pao pereira extract against a prototypical human prostate cancer cell line, LNCaP. When added to cultured LNCaP cells, pao pereira extract significantly suppressed cell growth in a dose-dependent fashion and induced apoptosis. Immunodeficient mice heterotopically xenografted with LNCaP cells were gavaged daily with pao pereira extract or vehicle control over 6 weeks. Tumor growth was suppressed by up to 80% in some groups compared with tumors in vehicle-treated mice. However, we observed a striking U-shaped dose-response curve in which the highest dose tested (50 mg/kg/d) was much less effective in inducing tumor cell apoptosis and in reducing tumor cell proliferation and xenograft growth compared with lower doses (10 or 20 mg/kg/d). Although this study supports the idea that a pao pereira bark extract has activity against human prostate cancer, our in vivo results suggest that its potential effectiveness in prostate cancer treatment may be limited to a narrow dose range.

    View details for PubMedID 19476740

  • How often do available preoperative risk factors accurately predict the risk assessed after surgery for localized prostate cancer? BJU INTERNATIONAL Laudano, M. A., Lambert, S. M., Masson, P., McCann, T. R., Desai, M., Benson, M. C., McKiernan, J. M. 2009; 103 (3): 317-320

    Abstract

    To describe how frequently new information obtained at surgery translates into a substantial change in the risk of recurrence for patients with localized prostate cancer, and to determine what factors contribute to this increase in risk, as the preferred therapy for prostate cancer is often chosen based on available preoperative variables and therefore appropriate decision-making requires an accurate preoperative assessment.Using the Columbia Comprehensive Clinical Database of Urologic Oncology, we retrospectively analysed 3460 men who had radical prostatectomy (RP) for prostate cancer from 1988 to 2006. Kattan nomograms were used to calculate the 5-year progression-free probabilities before and after RP. The difference between these nomogram scores was used to divide patients into three groups, those with a decrease in the probability of disease-free survival (DFS) of > or =15%, those with an increase in the probability of DFS of > or =15%, and those with an absolute change of <15%.In all, 1804 men with complete data before and after RP were analysed; 1220 (68.4%) had no significant change in nomogram score, 238 (13.3%) had a significant increase and 327 (18.3%) had a significant decrease in the probability of recurrence. Those patients with an increased probability of recurrence had a greater proportion of patients with pathological Gleason sum of > or =8, higher rates of extraprostatic capsular invasion, positive margins, seminal vesical invasion and lymph node involvement (all P < 0.001).Accurate risk predictions both before and after RP are central to effective patient counselling and optimal management. Notably, 13.3% of the present patients were faced with a substantial increase of > or =15% in their risk of biochemical failure after pathological variables became available.

    View details for DOI 10.1111/j.1464-410X.2008.08031.x

    View details for Web of Science ID 000262509200009

    View details for PubMedID 18778341

  • The relationship between preoperative prostate-specific antigen and biopsy Gleason sum in men undergoing radical retropubic prostatectomy: a novel assessment of traditional predictors of outcome BJU INTERNATIONAL Pierorazio, P., Desai, M., McCann, T., Benson, M., McKiernan, J. 2009; 103 (1): 38-42

    Abstract

    To investigate the relationship between prostate-specific antigen (PSA) level and Gleason sum, and its impact on biochemical failure (persistent PSA level of >0.2 ng/mL) after radical prostatectomy (RP), as the PSA, Gleason sum and clinical stage are commonly used preoperative predictors of outcome in men with localized prostate cancer.The Columbia Urologic Oncology Database was reviewed (1988-2006); 3460 had undergone RP. Patients who received neoadjuvant/adjuvant therapy or had incomplete data were excluded, yielding 1932 in the analysed sample. Analysis of variance (ANOVA) methods were used to assess differences in PSA level (on a log scale) among three different groups of patients, categorized by their Gleason sum scores, as <7, 7 and >7. To account for full penetrance of PSA screening, surgery before 1998 was considered as a potential confounder. ANOVA was used to determine whether the association of Gleason score and PSA levels differed before and after 1998. The effect of PSA level on biochemical failure was examined for variance among the three Gleason score groups using a Cox proportional hazards model with time to biochemical failure as the outcome, logPSA, Gleason sum (<7, 7 and >7), their interaction, and clinical stage as the predictors. Concordance indices (c-index) were calculated for the model with and without the interaction term between PSA and Gleason sum to determine its significance.Of 1932 patients, 1190 (61.6%) had a Gleason sum of <7, 595 (30.8%) of 7 and 146 (7.6%) of >7. The median PSA level was 5.9, 6.1 and 7.8 ng/mL, respectively (P < 0.001). After adjusting for clinical stage, there was no significant interaction effect (P = 0.34) between Gleason sum and time of surgery on PSA level, implying that the relationship between Gleason sum and PSA levels has not changed over these two periods, despite changes in PSA screening. Results from the Cox model showed that PSA level, Gleason sum, their interaction term and clinical stage were significant predictors of biochemical failure. The c-index for the model without the interaction term was 0.70 and increased to 0.72 when including it, indicating an increase in the predictive ability of the model when including the interaction term.PSA level and Gleason sum are highly interrelated variables, although they each carry additional information that significantly contributes to the prediction of biochemical failure. This study shows that, for an individual patient, the higher the initial PSA level the higher the risk of having poorly differentiated prostate cancer. Also, predictive models of biochemical failure can be improved by considering the interaction between PSA and Gleason sum.

    View details for DOI 10.1111/j.1464-410X.2008.07952.x

    View details for Web of Science ID 000261683700009

    View details for PubMedID 18778352

  • Inhibition of BCL2 expression and activity increases H460 sensitivity to the growth inhibitory effects of polyphenon E. Journal of experimental therapeutics & oncology Borgovan, T., Bellistri, J. S., Slack, K. N., Kopelovich, L., Desai, M., Joe, A. K. 2009; 8 (2): 129-144

    Abstract

    The anti-cancer properties of the green tea-derived mixture Polyphenon E (Poly E) have been demonstrated in a variety of cell culture and animal models. We recently discovered that the H460 lung cancer cell line is markedly resistant to the growth inhibitory effects of Poly E compared with SW480 colon and Flo-1 esophageal cancer cells. We investigated the mechanism of H460 resistance by comparing gene expression profiles of Poly E-sensitive and -resistant cells. Unsupervised hierarchical clustering revealed that Poly E-sensitive cells clustered separately from Poly E-resistant cells, and 6,242 genes were differentially expressed between the two groups at the 0.01 level of significance. We discovered that BCL2 gene and protein expression were significantly higher in H460 cells compared with SW480 and Flo-1 cells (10.60-fold higher gene expression; P < 0.0001). Inhibition of BCL2 expression and activity, using siRNA and the small molecule inhibitor HA14-1 respectively, restored sensitivity to Poly E and induced BCL2-related apoptosis by decreasing mitochondrial membrane potential and inducing PARP cleavage. Our results suggest that increased BCL2 expression may contribute to H460 resistance to the growth inhibitory effects of Poly E. If validated in additional laboratory and clinical models, BCL2 could ultimately be used as a marker of Poly E resistance.

    View details for PubMedID 20192119

  • Predictive Significance of Surgical Margin Status After Prostatectomy for Prostate Cancer During PSA Era UROLOGY Mann, M. J., DeCastro, G. J., Desai, M., Benson, M. C., McKiernan, J. M. 2008; 72 (6): 1203-1207

    Abstract

    The presence of positive surgical margins (PSMs) after prostatectomy for prostate cancer has long been an indicator of poor survival outcomes. However, with the downstaging of cancer occurring in the prostate-specific antigen testing era, we sought to determine whether the risk associated with PSMs retains the same effect on prognosis as before the prostate-specific antigen testing era.Of the 3460 patients in the Columbia University Urologic Oncology database, 2215 (64%) were identified who had undergone radical prostatectomy from 1991 to 2005 and had sufficient pathologic data to be analyzed and >or=1 year of follow-up. Three epochs were chosen: 1991-1995, 1996-2000, and 2001-2005.The median age, preoperative prostate-specific antigen, and Gleason score was 61.6 years, 6 ng/mL, and 7, respectively, and >50% of patients had pathologic Stage T2 disease. On multivariate analysis, PSMs were a risk factor for biochemical failure for each epoch (P < .01). The Wald's test indicated that the significance of PSMs had not changed over time (P = .8). The contribution of PSMs to the accuracy of predicting biochemical failure in a multivariate model was found only for the earliest epoch, because it improved the model by 0.15 (95% confidence interval 0.03-0.27). In the second epoch, it was 0.13 (95% confidence interval -0.01 to 0.27), and it was 0.13 for the third (95% confidence interval -0.06 to 0.32).The results of this study suggest that the predictive contribution of PSMs to the accuracy of a multivariate model or nomogram used to predict the outcomes after prostatectomy has decreased during the past 15 years.

    View details for DOI 10.1016/j.urology.2008.04.068

    View details for Web of Science ID 000262121500005

    View details for PubMedID 18674807

  • Genomic Profiling of Left and Right Ventricular Hypertrophy in Congenital Heart Disease JOURNAL OF CARDIAC FAILURE Kaufman, B. D., Desai, M., Reddy, S., Osorio, J. C., Chen, J. M., Mosca, R. S., Ferrante, A. W., Mital, S. 2008; 14 (9): 760-767

    Abstract

    The right ventricle (RV) has a lower ability than the left ventricle (LV) to adapt to systemic load. The molecular basis of these differences is not known. We compared hypertrophy-signaling pathways between the RV and the LV in patients with congenital heart disease (CHD).Gene expression was measured using DNA microarrays in myocardium from children with CHD with LV or RV obstructive lesions undergoing surgery. The expression of 175 hypertrophy-signaling genes was compared between the LV (n=7) and the RV (n=11). Hierarchic clustering was performed.Seventeen genes (10%) were differentially expressed between the LV and the RV. Expression of genes for angiotensin, adrenergic, G-proteins, cytoskeletal, and contractile components was lower (P < .05) and expression of maladaptive factors (fibroblast growth factors, transforming growth factor-beta, caspases, ubiquitin) was higher in the RV compared with the LV (P < .05). Five of 7 LV samples clustered together. Only 4 of 11 RV samples clustered with the LV. Genes critical to adaptive remodeling correlated with the degree of LV hypertrophy but not RV hypertrophy.The transcription of pathways of adaptive remodeling was lower in the RV compared with the LV. This may explain the lower ability of the RV to adapt to hemodynamic load in CHD.

    View details for DOI 10.1016/j.cardfail.2008.06.002

    View details for Web of Science ID 000261269800008

    View details for PubMedID 18995181

  • Pathological tumour diameter predicts risk of conventional subtype in small renal cortical tumours BJU INTERNATIONAL Laudano, M. A., Klafter, F. E., Katz, M., McCann, T. R., Desai, M., Benson, M. C., McKiernan, J. M. 2008; 102 (10): 1385-1388

    Abstract

    To examine whether pathological tumour diameter assists in predicting conventional vs other histological subtypes in renal cortical tumours (RCTs) of

    View details for DOI 10.1111/j.1464-410X.2008.07876.x

    View details for Web of Science ID 000260333300007

    View details for PubMedID 18710458

  • Barriers to adherence to cystic fibrosis infection control guidelines PEDIATRIC PULMONOLOGY Garber, E., Desai, M., Zhou, J., Alba, L., Angst, D., Cabana, M., Saiman, L. 2008; 43 (9): 900-907

    Abstract

    In 2003, the American Cystic Fibrosis (CF) Foundation published revised, evidence-based guidelines for infection control. We sought to assess potential barriers to adherence to these guidelines experienced by health care professionals (HCPs) caring for CF patients.From April 2004 to December 2005, a knowledge, attitude, and practice survey was administered to HCPs at randomly selected CF centers in the United States to explore potential barriers to adherence to selected guidelines: (1) obtaining quarterly cultures from CF patients, (2) discouraging socialization among CF patients during hospitalization, (3) educating patients and families about hand hygiene, (4) educating patients and families to clean and disinfect home nebulizers, and (5) cleaning the clinic exam rooms between CF patients.The survey was completed by 528 HCPs from 25 sites (5-50 respondents per site). Only 60% of respondents were aware of the guidelines, but despite awareness, 31-47% were unfamiliar with the specific guidelines. Self-reported adherence was low; only 23-63% of respondents reported practicing the selected guidelines >75% of the time/opportunities. Lack of self-efficacy, that is, confidence in adequately performing the guidelines, was commonly experienced by respondents. Access to a copy of the guidelines was associated with increased agreement with the recommendations and increased self-efficacy.Strategies to reduce barriers to adherence to CF infection control guidelines are needed. Strategies could include quality improvement initiatives with enhanced education and skills workshops, sharing successful interventions among CF centers, and linking adherence to improved patient outcomes.

    View details for DOI 10.1002/ppul.20876

    View details for Web of Science ID 000259114300009

    View details for PubMedID 18671274

  • A comparison of regression approaches for analyzing clustered data AMERICAN JOURNAL OF PUBLIC HEALTH Desai, M., Begg, M. D. 2008; 98 (8): 1425-1429

    Abstract

    We used 3 approaches to analyzing clustered data to assess the impact of model choice on interpretation.Approaches 1 and 2 specified random intercept models but differed in standard versus novel specification of covariates, which impacts ability to separate within- and between-cluster effects. Approach 3 was based on standard analysis of paired differences. We applied these methods to data from the National Collaborative Perinatal Project to examine the association between head circumference at birth and intelligence (IQ) at age 7 years.Approach 1, which ignored within- and between-family effects, yielded an overall IQ effect of 1.1 points (95% confidence interval [CI]=0.9, 1.3) for every 1-cm increase in head circumference. Approaches 2 and 3 found comparable within-family effects of 0.6 points (95% CI = 0.4, 0.9) and 0.69 points (95% CI = 0.4, 1.0), respectively.Our findings confirm the importance of applying appropriate analytic methods to clustered data, as well as the need for careful covariate specification in regression modeling. Method choice should be informed by the level of interest in cluster-level effects and item-level effects.

    View details for DOI 10.2105/AJPH.2006.108233

    View details for Web of Science ID 000257940800017

    View details for PubMedID 18556621

  • Prediction of long-term survival conditional on years survived following nephrectomy JOURNAL OF CLINICAL ONCOLOGY Laudano, M. A., Desai, M., Badani, K. K., Hirsh, A. L., Benson, M. C., McKiernan, J. M. 2008; 26 (15)
  • WHERE TO BIOPSY IN THE GASTROINTESTINAL (GI) TRACT TO DIAGNOSE ACUTE GRAFT VERSUS HOST DISEASE (AGVHD) IN PEDIATRIC ALLOGENEIC STEM CELL TRANSPLANT RECIPIENTS (AlloSCT) BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Martinez, M., Billore, G., Desai, M., Chu, K., Remotti, H., Satwani, P., Cairo, I. S., DeFelice, A. 2008; 14 (2): 132-132
  • Effect of breast cancer radiotherapy and cigarette smoking on risk of second primary lung cancer JOURNAL OF CLINICAL ONCOLOGY Kaufman, E. L., Jacobson, J. S., Hershman, D. L., Desai, M., Neugut, A. I. 2008; 26 (3): 392-398

    Abstract

    Prior studies have found that postmastectomy radiotherapy (PMRT) for breast cancer (BC) increases the risk of lung cancer (LC). We explored the joint effects of cigarette smoking and PMRT on LC risk.We conducted a population-based nested case-control study among women registered in the Connecticut Tumor Registry diagnosed with nonmetastatic BC between January 1, 1965 and December 31, 1989. Patient cases developed a LC >or= 10 years after BC diagnosis. Controls were matched to patient cases on age, year of BC diagnosis, and length of survival. Medical records were reviewed for pathology, BC therapy, and smoking history. We used conditional logistic regression to estimate odds ratios for the independent and joint effects of smoking and PMRT on risk of overall, ipsilateral, and contralateral LC.Among 113 second primary LC patient cases and 364 controls, compared with nonsmoking women who did not receive PMRT, nonsmoking women who received PMRT had no higher risk of LC; adjusted odds ratios were 5.9 (95% CI, 2.7 to 12.8) for ever-smokers who did not receive PMRT and 18.9 (95% CI, 7.9 to 45.4) for ever-smokers who received PMRT. Adjusted odds ratios for the joint effects of smoking and PMRT were 10.5 (95% CI, 2.9 to 37.8) for the contralateral lung and 37.6 (95% CI, 10.2 to 139.0) for the ipsilateral lung. Smoking and PMRT were associated with increased risk for all histologic types of LC.PMRT after a diagnosis of BC sharply increased the risk of second primary LC, especially in the ipsilateral lung, among ever-smokers. Clinicians should consider including smoking history in their discussions with patients about the risks and benefits of PMRT.

    View details for DOI 10.1200/JCO.2007.13.3033

    View details for Web of Science ID 000254177200012

    View details for PubMedID 18202415

  • The gemcitabine, docetaxel, and capecitabine (GTX) regimen for metastatic pancreatic cancer: a retrospective analysis CANCER CHEMOTHERAPY AND PHARMACOLOGY Fine, R. L., Fogelman, D. R., Schreibman, S. M., Desai, M., Sherman, W., Strauss, J., Guba, S., Andrade, R., Chabot, J. 2008; 61 (1): 167-175

    Abstract

    We developed a laboratory based regimen called GTX which induces synergistic apoptosis in human pancreatic cancer cells. This retrospective review summarizes our clinical experience with GTX in an initial group of 35 patients; 66% untreated and 34% failed prior therapies.All patients treated with GTX for metastatic pancreatic cancer, prior to initiation of a prospective phase II trial of GTX were assessed and followed until death. GTX consisted of capecitabine (X), 750 mg/m(2) p.o. BID on days 1-14, gemcitabine (G) (750 mg/m(2)) over 75 min and docetaxel (T) (30 mg/m(2)) on days 4 and 11. Thus one cycle of GTX was 14 days with 7 days off for a 21 day cycle. Tumor assessments were repeated every 3 cycles.All 35 patients had metastatic pancreatic cancer (94% liver, 6% lung sites). Grade 3-4 hematological toxicities were: leukopenia and thrombocytopenia-both 14%, and anemia 9%, respectively. The overall response rate of all 35 patients treated with GTX (from 0.5 cycles onward) was 29% (CR/PR) by WHO criteria, and 31% had a minor response or stable disease (MR, SD). At the metastatic sites for the 35 patients, there were 9% complete (CR) and 31% partial (PR) responses (total 40%). For the 31 patients who had their primary tumor (4 patients had a prior Whipple resection), there were 13% CR and 19% PR for a response rate of 32% at the primary tumor site. Overall median progression free survival of responders was 6.3 months (95% C.I. 4.4-10.4 months) and median survival was 11.2 months (95% C.I. 8.1-15.1 months). Survival after initiation of GTX at 12, 18, 24 and 30 months was 43, 29, 20, and 11%, respectively.Our retrospective review suggests that GTX has potential as a regimen for untreated and treated metastatic pancreatic cancer.

    View details for DOI 10.1007/s00280-007-0473-0

    View details for Web of Science ID 000249916800019

    View details for PubMedID 17440727

  • Global DNA hypomethylation in liver cancer cases and controls - A Phase I preclinical biomarker development study EPIGENETICS Guerrero-Preston, R., Santella, R. M., Blanco, A., Desai, M., Berdasco, M., Fraga, M. 2007; 2 (4): 223-226

    Abstract

    Global genomic DNA hypomethylation is a feature of genomic DNA derived from solid and hematologic tumors in animal models and human carcinogenesis. Global genomic DNA hypomethylation may be the earliest epigenetic change from a normal to a pre-malignant cell.To test if global hypomethylation is a good marker for early detection of cancer we used a novel quantification method of 2'-deoxynucleosides to evaluate DNA methylation in liver cancer cases and controls.Frozen tissue from liver cancer patients and controls were obtained from the Cooperative Human Tissue Network. DNA was extracted using standard methods. Genomic DNA samples were boiled and treated with nuclease P1 and alkaline phosphatase. Global genomic DNA methylation patterns were obtained using HPLC for fraction separation and mass spectrometry for quantification. A two-sample t-test was performed using Welch's approximation for samples with unequal variances. A Wilcoxon rank sum test was also performed.A global genomic DNA methylation index measuring methylated cytidine relative to global cytidine in the genome was significantly lower (p value = 0.001) for all cases, mean = 2.43 (95% CI, 2.08, 2.78), when compared to controls, mean = 3.55 (95% CI, 3.16, 3.93).A correlation between global genomic DNA methylation patterns and type of liver tissue was observed. These results add to the accumulating body of evidence suggesting that global DNA hypomethylation may be a useful biomarker to distinguish between liver cancer cases and controls.

    View details for Web of Science ID 000256339000004

    View details for PubMedID 18032927

  • Changes in prognostic significance and predictive accuracy of Gleason grading system throughout PSA era: Impact of grade migration in prostate cancer UROLOGY Mitchell, R. E., Shah, J. B., Desai, M., Mansukhani, M. M., Olsson, C. A., Benson, M. C., McKiernan, J. M. 2007; 70 (4): 706-710

    Abstract

    To describe the changes in the Gleason grading system over time and evaluate how a shift in Gleason grading has affected the overall predictive accuracy of the system in predicting biochemical disease-free survival after radical prostatectomy.The Columbia University Urologic Oncology Database was reviewed, and 1515 patients who met the inclusion criteria were identified who had undergone radical prostatectomy from 1988 to 2004. The patients were divided into two time cohorts (1988 to 1997 and 1998 to 2004). To determine whether a shift in the Gleason sum distribution has occurred, a chi-square test was performed. Survival curves and log-rank tests were used to compare the biochemical disease-free survival between cohorts stratified by the Gleason sum. To estimate the predictive ability of the Gleason system over time, concordance indexes were calculated.A shift toward greater Gleason sums over time was confirmed using the chi-square test (P <0.001). A significant difference was observed in biochemical disease-free survival between the two time cohorts for those with Gleason sum 6 cancer (P <0.01). The concordance indexes corresponding to Gleason sum alone for each time cohort were 0.71 and 0.87, demonstrating that the Gleason sum's predictive ability improved significantly over time. After adjusting for other variables, the Gleason sum continued to demonstrate a significantly improved predictive ability in the more recent time cohort.We found a trend toward the assignment of increasing Gleason sums over time in our data set. This shift in Gleason sum distribution between the two time cohorts has resulted in a significant improvement in the predictive ability of the Gleason system.

    View details for DOI 10.1016/j.urology.2007.06.1084

    View details for Web of Science ID 000251145400019

    View details for PubMedID 17707892

  • Implementing academic detailing for breast cancer screening in underserved communities IMPLEMENTATION SCIENCE Gorin, S. S., Ashford, A. R., Lantigua, R., Desai, M., Troxel, A., Gemson, D. 2007; 2

    Abstract

    African American and Hispanic women, such as those living in the northern Manhattan and the South Bronx neighborhoods of New York City, are generally underserved with regard to breast cancer prevention and screening practices, even though they are more likely to die of breast cancer than are other women. Primary care physicians (PCPs) are critical for the recommendation of breast cancer screening to their patients. Academic detailing is a promising strategy for improving PCP performance in recommending breast cancer screening, yet little is known about the effects of academic detailing on breast cancer screening among physicians who practice in medically underserved areas. We assessed the effectiveness of an enhanced, multi-component academic detailing intervention in increasing recommendations for breast cancer screening within a sample of community-based urban physicians.Two medically underserved communities were matched and randomized to intervention and control arms. Ninety-four primary care community (i.e., not hospital based) physicians in northern Manhattan were compared to 74 physicians in the South Bronx neighborhoods of the New York City metropolitan area. Intervention participants received enhanced physician-directed academic detailing, using the American Cancer Society guidelines for the early detection of breast cancer. Control group physicians received no intervention. We conducted interviews to measure primary care physicians' self-reported recommendation of mammography and Clinical Breast Examination (CBE), and whether PCPs taught women how to perform breast self examination (BSE).Using multivariate analyses, we found a statistically significant intervention effect on the recommendation of CBE to women patients age 40 and over; mammography and breast self examination reports increased across both arms from baseline to follow-up, according to physician self-report. At post-test, physician involvement in additional educational programs, enhanced self-efficacy in counseling for prevention, the routine use of chart reminders, computer- rather than paper-based prompting and tracking approaches, printed patient education materials, performance targets for mammography, and increased involvement of nursing and other office staff were associated with increased screening.We found some evidence of improvement in breast cancer screening practices due to enhanced academic detailing among primary care physicians practicing in urban underserved communities.

    View details for DOI 10.1186/1748-5908-2-43

    View details for Web of Science ID 000206783100043

    View details for PubMedID 18086311

  • Randomized study of paclitaxel and tamoxifen deposition into human brain tumors: Implications for the treatment of metastatic brain tumors CLINICAL CANCER RESEARCH Fine, R. L., Chen, J., Balmaceda, C., Bruce, J. N., Huang, M., Desai, M., Sisti, M. B., McKhann, G. M., Goodman, R. R., Bertino, J. S., Nafziger, A. N., Fetell, M. R. 2006; 12 (19): 5770-5776

    Abstract

    Drug resistance in brain tumors is partially mediated by the blood-brain barrier of which a key component is P-glycoprotein, which is highly expressed in cerebral capillaries. Tamoxifen is a nontoxic inhibitor of P-glycoprotein. This trial assessed, in primary and metastatic brain tumors, the differential deposition of paclitaxel and whether tamoxifen could increase paclitaxel deposition.Patients for surgical resection of their primary or metastatic brain tumors were prospectively randomized to prior paclitaxel alone (175 mg/m(2)/i.v.) or tamoxifen for 5 days followed by paclitaxel. Central and peripheral tumor, surrounding normal brain and plasma, were analyzed for paclitaxel and tamoxifen.Twenty-seven patients completed the study. Based on a multivariate linear regression model, no significant differences in paclitaxel concentrations between the two study arms were found after adjusting for treatment group (tamoxifen versus control). However, in analysis for tumor type, metastatic brain tumors had higher paclitaxel concentrations in the tumor center (1.93-fold, P = 0.10) and in the tumor periphery (2.46-fold, P = 0.039) compared with primary brain tumors. Pharmacokinetic analyses showed comparable paclitaxel areas under the serum concentration between treatment arms.Paclitaxel deposition was not increased with this tamoxifen schedule as the low plasma concentrations were likely secondary to concurrent use of P-450-inducing medications. However, the statistically higher paclitaxel deposition in the periphery of metastatic brain tumors provides functional evidence corroborating reports of decreased P-glycoprotein expression in metastatic versus primary brain tumors. This suggests that metastatic brain tumors may respond to paclitaxel if it has proven clinical efficacy for the primary tumor's histopathology.

    View details for DOI 10.1158/1078-0432.CCR-05-2356

    View details for Web of Science ID 000241098100025

    View details for PubMedID 17020983

  • Polymorphisms in nucleotide excision repair genes and DNA repair capacity phenotype in sisters discordant for breast cancer CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Shen, J., Desai, M., Agrawal, M., Kennedy, D. O., Senie, R. T., Santella, R. M., Terry, M. B. 2006; 15 (9): 1614-1619

    Abstract

    Interindividual differences in DNA repair capacity (DRC) may play a critical role in breast cancer risk. Previously, we determined that DRC measured via removal of in vitro-induced benzo[a]pyrene diolepoxide-DNA adducts in lymphoblastoid cell lines was lower in cases compared with controls among sisters discordant for breast cancer from the Metropolitan New York Registry of Breast Cancer Families. We have now determined genotypes for seven single nucleotide polymorphisms in five nucleotide excision repair genes, including Xeroderma pigmentosum complementation group A (XPA +62T>C), group C (XPC Lys939Gln and Ala499Val), group D (XPD Asp312Asn and Lys751Gln), and group G (XPG His1104Asp) and ERCC1 (8092 C>A) in a total of 160 sister pairs for whom DRC phenotype data were available. Overall, there were no statistically significant differences in average DRC for most of the genotypes. A final multivariate conditional logistic model, including three single nucleotide polymorphisms (XPA +62T>C, XPC Ala499Val, and XPG His1104Asp) and smoking status, only modestly predicted DRC after adjusting for case-control status and age of blood donation. The overall predictive accuracy was 61% in the model with a sensitivity of 78% and specificity of 39%. These findings suggest that those polymorphisms we have investigated to date in nucleotide excision repair pathway genes explain only a small amount of the variability in DRC.

    View details for DOI 10.1158/1055-9965.EPI-06-0218

    View details for Web of Science ID 000240587800011

    View details for PubMedID 16985021

  • Does unwantedness of pregnancy predict schizophrenia in the offspring? Findings from a prospective birth cohort study SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY Herman, D. B., Brown, A. S., Opler, M. G., Desai, M., Malaspina, D., Bresnahan, M., Schaefer, C. A., Susser, E. S. 2006; 41 (8): 605-610

    Abstract

    We sought to replicate (or refute) a previous report of an association between unwantedness of a pregnancy and the risk of schizophrenia in the offspring.The study was conducted using a large, prospectively collected birth cohort as part of the Prenatal Determinants of Schizophrenia study (PDS). Attitude toward the pregnancy was assessed at the time of the mother's first visit to the prenatal clinic. Cases of schizophrenia and other schizophrenia spectrum disorders in the offspring of these mothers were subsequently ascertained and diagnosed. In univariate and multivariate analyses, we examined the relationship between attitude toward the pregnancy and risk of adult schizophrenia and other schizophrenia spectrum disorders.The unadjusted hazard ratio for the association between ambivalent or negative maternal attitude toward the pregnancy and the risk of schizophrenia spectrum disorders was 1.75, (95% CI=0.97, 3.17, P=0.06). This result was unchanged after adjustment for social class, paternal age, race/ethnicity and other potential confounders. Similar results were observed when only cases with schizophrenia were included in the analysis.We did not find a statistically significant association in favor of the hypothesis that unwantedness of pregnancy is a risk factor for adult schizophrenia. On the other hand, the magnitude of the observed association was similar to the findings of the only previous study of this question and the confidence limits overlap those findings. Whether unwantedness of pregnancy is a risk factor for adult schizophrenia remains an open question that may be resolved by future research.

    View details for DOI 10.1007/s00127-006-0078-7

    View details for Web of Science ID 000239146200002

    View details for PubMedID 16732398

  • Phase I trial of intravesical docetaxel in the management of superficial bladder cancer refractory to standard intravesical therapy JOURNAL OF CLINICAL ONCOLOGY McKiernan, J. M., Masson, P., Murphy, A. M., Goetzl, M., Olsson, C. A., Petrylak, D. P., Desai, M., Benson, M. C. 2006; 24 (19): 3075-3080

    Abstract

    Up to 50% of patients treated with intravesical agents for superficial bladder cancer will experience recurrence. Response rates to second-line intravesical therapies range from 20% to 40%. For these high-risk patients, novel agents are necessary to prevent recurrence. Docetaxel is a microtubule depolymerization inhibitor with unique physiochemical properties, making it an excellent candidate for investigation as an intravesical agent.This phase I trial included patients with recurrent Ta, T1, and Tis transitional cell carcinoma who experienced treatment failure with at least one prior intravesical treatment. Docetaxel was administered as six weekly instillations at a starting dose of 5 mg, with a dose-escalation model used until a maximum tolerated dose (MTD) was achieved. Primary end points were dose-limiting toxicity (DLT) and MTD. Efficacy was evaluated by cystoscopy with biopsy, cytology, and computed tomography imaging.Eighteen patients (100%) completed the trial, and the distribution of stages included six patients with Tis, seven with Ta, and five with T1 disease. No grade 3 or 4 DLTs occurred in 108 infusions, and no patient had systemic absorption of docetaxel. Eight (44%) of 18 patients experienced grade 1 or 2 toxicities, with dysuria being the most common. Ten (56%) of 18 patients had no evidence of disease at their post-treatment cystoscopy and biopsy. None of the patients who experienced relapse had disease progression.Intravesical docetaxel exhibited minimal toxicity and no systemic absorption in the first human intravesical clinical trial. This suggests that docetaxel is a safe agent for further evaluation of efficacy in a phase II trial.

    View details for DOI 10.1200/JCO.2005.03.1161

    View details for Web of Science ID 000238987200018

    View details for PubMedID 16809732

  • Preoperative serum prostate specific antigen remains a significant prognostic variable in predicting biochemical failure after radical prostatectomy JOURNAL OF UROLOGY Mitchell, R. E., Desai, M., Shah, J. B., Olsson, C. A., Benson, M. C., McKiernan, J. M. 2006; 175 (5): 1663-1667

    Abstract

    Multiple investigators have argued that PSA may no longer be an accurate marker of prostate cancer biology. We determined whether the impact of PSA in predicting biochemical failure after radical prostatectomy has changed since the beginning of the PSA era.A total of 1,246 patients were identified from the Columbia University Comprehensive Urological Oncology Database who underwent radical prostatectomy by 1 of 3 surgeons between 1988 and 2003. Cox proportional hazards models were fit to the data to estimate the impact of PSA (logPSA) in predicting BCF (PSA 0.2 ng/ml or greater). To determine if the predictive impact of PSA changed over time, patients were classified based on year of surgery, and an interaction term between PSA and time was included. Finally concordance indexes were estimated to determine if the predictive ability of PSA has changed over time.In a Cox model including PSA, year of surgery and a year/PSA interaction term, the impact of PSA appears to change over time (p = 0.002). However, when correcting for the effects of stage and grade there was no significant change in the impact of PSA. In addition, concordance analysis indicated that the predictive ability of PSA has remained constant throughout the PSA era (0.65, 0.66 and 0.64 for each period, respectively).This study demonstrates that the predictive ability of PSA as a cancer outcomes biomarker has not changed significantly since the beginning of the PSA era. Despite suggestions to the contrary, PSA remains an important variable in predicting risk of BCF after RP.

    View details for DOI 10.1016/S0022-5347(05)01022-0

    View details for Web of Science ID 000236928400016

    View details for PubMedID 16600724

  • Compliance of clinical microbiology laboratories in the united states with current recommendations for processing respiratory tract specimens from patients with cystic fibrosis JOURNAL OF CLINICAL MICROBIOLOGY Zhou, J. Y., Garber, E., Desai, M., Saiman, L. 2006; 44 (4): 1547-1549

    Abstract

    Respiratory tract specimens from patients with cystic fibrosis (CF) require unique processing by clinical microbiology laboratories to ensure detection of all potential pathogens. The present study sought to determine the compliance of microbiology laboratories in the United States with recently published recommendations for CF respiratory specimens. Microbiology laboratory protocols from 150 of 190 (79%) CF care sites were reviewed. Most described the use of selective media for Burkholderia cepacia complex (99%), Staphylococcus aureus (82%), and Haemophilus influenzae (89%) and identified the species of all gram-negative bacilli (87%). Only 52% delineated the use of agar diffusion assays for susceptibility testing of Pseudomonas aeruginosa. Standardizing laboratory practices will improve treatment, infection control, and our understanding of the changing epidemiology of CF microbiology.

    View details for DOI 10.1128/JCM.44.4.1547-1549.2006

    View details for Web of Science ID 000236810500051

    View details for PubMedID 16597890

  • Effectiveness of academic detailing on breast cancer screening among primary care physicians in an underserved community JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE Sheinfeld Gorin, S., Ashford, A. R., Lantigua, R., Hossain, A., Desai, M., Troxel, A., Gemson, D. 2006; 19 (2): 110-121

    Abstract

    Urban minority groups, such as those living in northern Manhattan and the South Bronx, are generally underserved with regard to breast cancer prevention and screening practices. Primary care physicians are critical for the recommendation of mammography and clinical breast examinations to their patients.Two medically underserved communities were matched and block randomized. The aim of the study was to assess the efficacy of academic detailing in increasing recommendations for breast cancer screening in community-based primary care physicians.Ninety-four primary care community-based (ie, not hospital-based) physicians in northern Manhattan were compared with 74 physicians in the South Bronx who received no intervention. Intervention: Intervention participants received multicomponent physician-directed education, academic detailing, using the American Cancer Society guidelines for the early detection of breast cancer.We administered interviews to ask about primary care physicians' recommendation of mammography and clinical breast examination. They were also queried about their knowledge of major risk factors and perceived barriers to breast cancer screening. We conducted medical audits of 710 medical charts 2 years before and after the intervention.Using a mixed models linear analysis, we found a statistically significant intervention effect on the recommendation of mammography and clinical breast examination (according to medical audit) by female patients age 40 and over. Intervention group physicians correctly identified significantly more risk factors for breast cancer, and significantly fewer barriers to practice, than did comparison physicians.We found some evidence of improvement in breast cancer screening practices due to academic detailing among primary care physicians practicing in urban underserved communities.

    View details for Web of Science ID 000237804300002

    View details for PubMedID 16513899

  • A new mixture model approach to analyzing allelic-loss data using Bayes factors BMC BIOINFORMATICS Desai, M., Emond, M. J. 2004; 5

    Abstract

    Allelic-loss studies record data on the loss of genetic material in tumor tissue relative to normal tissue at various loci along the genome. As the deletion of a tumor suppressor gene can lead to tumor development, one objective of these studies is to determine which, if any, chromosome arms harbor tumor suppressor genes.We propose a large class of mixture models for describing the data, and we suggest using Bayes factors to select a reasonable model from the class in order to classify the chromosome arms. Bayes factors are especially useful in the case of testing that the number of components in a mixture model is n0 versus n1. In these cases, frequentist test statistics based on the likelihood ratio statistic have unknown distributions and are therefore not applicable. Our simulation study shows that Bayes factors favor the right model most of the time when tumor suppressor genes are present. When no tumor suppressor genes are present and background allelic-loss varies, the Bayes factors are often inconclusive, although this results in a markedly reduced false-positive rate compared to that of standard frequentist approaches. Application of our methods to three data sets of esophageal adenocarcinomas yields interesting differences from those results previously published.Our results indicate that Bayes factors are useful for analyzing allelic-loss data.

    View details for DOI 10.1186/1471-2105-5-182

    View details for Web of Science ID 000226618500001

    View details for PubMedID 15563371

  • Is Hispanic race an important predictor of treatment failure following radical prostatectomy for prostate cancer? JOURNAL OF UROLOGY Lam, J. S., Sclar, J. D., Desai, M., Mansukhani, M. M., Benson, M. C., Goluboff, E. T. 2004; 172 (5): 1856-1859

    Abstract

    Hispanic-Americans are the fastest growing minority group in the United States. Many studies have compared prostate cancer treatment outcomes between black and white men, but few such studies have been done with Hispanic men. We compared clinical and pathological features as well as the treatment failure rate of radical prostatectomy in contemporaneously treated groups of Hispanic and white men with prostate cancer.Between 1995 and 2002, 136 Hispanic men and 315 white men underwent radical prostatectomy. Treatment failure was defined as having a prostate specific antigen (PSA) of 0.2 or greater more than 8 weeks after surgery or receiving any adjuvant therapy. Known predictors of failure and race were evaluated for their ability to predict treatment failure.Median followup was 32 months for Hispanic and 36 months for white patients. Hispanic men were older, had a higher percentage of abnormal rectal examinations, Gleason 7 tumors and preoperative PSA levels greater than 10. Preoperative PSA, specimen Gleason score, pathological stage and surgical margin were all strongly associated with treatment failure (p<0.001). Despite differences in clinical characteristics, overall failure rates did not differ between Hispanic and white men (18.7% vs 17.8%). The odds ratio for treatment failure for Hispanic relative to white men after adjusting for the previously mentioned risk factors was 0.87 (95% CI [0.44, 1.68], p = 0.670).This study shows that Hispanic race does not influence the treatment failure rate of radical prostatectomy in contemporaneously treated patients with prostate cancer at 1 institution. To our knowledge this study represents the largest of its kind, but longer followup and other confirmatory studies are needed.

    View details for DOI 10.1097/01.ju.0000141783.67470.55

    View details for Web of Science ID 000224463600022

    View details for PubMedID 15540738

  • Prostate-specific antigen, sex steroid hormones, and the insulin-like growth factor axis in US-born, Jamaican, and Haitian black men: A pilot study UROLOGY Chen, A. C., Macchia, R. J., Conway, F., Magai, C., Desai, M., Neugut, A. I. 2004; 64 (3): 522-527

    Abstract

    African-Caribbean men have a risk of prostate cancer comparable to that of African-American men. To begin exploring potential risk factors for prostate cancer in these high-risk black subgroups, we conducted a pilot study in Brooklyn, New York, a community with large numbers of African-Americans and immigrants from Jamaica and Haiti.Black men, 35 to 65 years of age, who were born in the United States, Jamaica, or Haiti were recruited in Brooklyn. The subjects' serum samples were analyzed for prostate-specific antigen (PSA) and the following hormones, which may be related to prostate cancer: testosterone, sex hormone-binding globulin, 3alpha-androstanediol glucuronide, insulin-like growth factor-1 (IGF-1), and IGF-binding protein-3 (IGFBP-3). Subgroup differences in PSA and hormonal levels, adjusted for relevant covariates, were explored using analysis of variance techniques.For 3 months, we recruited 21 U.S.-born, 20 Jamaican-born, and 24 Haitian-born black men using various methods. The mean age-adjusted PSA level was 1.04 ng/mL in the U.S.-born men, 1.09 ng/mL in the Jamaican-born men, and 0.85 ng/mL in the Haitian-born men (P = 0.55). The mean age-adjusted hormone levels, as well as testosterone/sex hormone-binding globulin and IGF-1/IGFBP-3 ratios, also were not significantly different statistically across the subgroups.It is feasible to conduct epidemiologic studies of prostate cancer in these high-risk black subgroups in Brooklyn. Our preliminary data suggest that the serum levels of PSA and potential hormonal risk factors are similar among U.S.-born, Jamaican-born, and Haitian-born black men. Larger follow-up studies are being planned to confirm these findings.

    View details for DOI 10.1016/j.urology.2004.04.004

    View details for Web of Science ID 000224303900029

    View details for PubMedID 15351583

  • A concentrated aglycone isoflavone preparation (GCP) that demonstrates potent anti-prostate cancer activity in vitro and in vivo CLINICAL CANCER RESEARCH Bemis, D. L., Capodice, J. L., Desai, M., Buttyan, R., Katz, A. E. 2004; 10 (15): 5282-5292

    Abstract

    Isoflavones have anticancer activities, but naturally occurring isoflavones are predominantly glycosylated and poorly absorbed. Genistein combined polysaccharide (GCP; Amino Up Chemical Co., Sapporo, Japan), is a fermentation product of soy extract and basidiomycetes mycillae that is enriched in biologically active aglycone isoflavones. This study analyzes GCP in vitro and in vivo for potential utility as a prostate cancer chemopreventative agent.Androgen-sensitive LNCaP and androgen-independent PC-3 cells were grown with various concentrations of GCP. In vitro cell growth was analyzed by the WST-1 assay, and apoptosis was assessed by fluorescence-activated cell sorting and detection of poly(ADP-ribose) polymerase cleavage using Western blot techniques. Effects of GCP on expression of cell cycle-regulatory proteins p53 (LNCaP only), p21, and p27 and the protein kinase Akt were considered using Western blot techniques. An in vivo LNCaP xenograft model was used to study the effects of a 2% GCP-supplemented diet on tumor growth in comparison with a control diet.GCP significantly suppressed LNCaP and PC-3 cell growth over 72 h (89% and 78% in LNCaP and PC-3, respectively, at 10 microg/ml; P < 0.0001). This reduction was associated with apoptosis in LNCaP cells, but not in PC-3 cells. GCP induced p27 and p53 (LNCaP only) protein expression within 6 h and suppressed phosphorylated Akt in both cell lines. The 2% GCP-supplemented diet significantly slowed LNCaP tumor growth, increasing apoptosis (P < 0.001), and decreasing proliferation (P < 0.001) over 4 weeks.GCP has potent growth-inhibitory effects against prostate cancer cell lines in vitro and in vivo. These data suggest GCP has potential as an effective chemopreventive agent against prostate cancer cell growth.

    View details for Web of Science ID 000223257200044

    View details for PubMedID 15297432

  • Prenatal lead exposure, delta-aminolevulinic acid, and schizophrenia ENVIRONMENTAL HEALTH PERSPECTIVES Opler, M. G., Brown, A. S., Graziano, J., Desai, M., Zheng, W., Schaefer, C., Factor-Litvak, P., Susser, E. S. 2004; 112 (5): 548-552

    Abstract

    Schizophrenia is a severe mental disorder of unknown etiology. Recent reports suggest that a number of environmental factors during prenatal development may be associated with schizophrenia. We tested the hypothesis that environmental lead exposure may be associated with schizophrenia using archived serum samples from a cohort of live births enrolled between 1959 and 1966 in Oakland, California. Cases of schizophrenia spectrum disorder were identified and matched to controls. A biologic marker of lead exposure, delta-aminolevulinic acid (delta-ALA), was determined in second-trimester serum samples of 44 cases and 75 controls. delta-ALA was stratified into high and low categories, yielding 66 subjects in the high category, corresponding to a blood lead level (BPb) greater than or equal to 15 micro g/dL, and 53 in the low category, corresponding to BPb less than 15 micro g/dL. Using logistic regression, the odds ratio (OR) for schizophrenia associated with higher delta-ALA was 1.83 [95% confidence interval (CI), 0.87-3.87; p = 0.1]. Adjusting for covariates gave an OR of 2.43 (95% CI, 0.99-5.96; p = 0.051). This finding suggests that the effects of prenatal exposure to lead and/or elevated delta-ALA may extend into later life and must be further investigated as risk factors for adult psychiatric diseases.

    View details for Web of Science ID 000220770400040

    View details for PubMedID 15064159

  • Natural history and clinical outcome of sporadic renal cortical tumors diagnosed in the young adult UROLOGY Goetzl, M. A., Desai, M., Mansukhani, M., Goluboff, E. T., Katz, A. E., Sawczuk, I. S., Benson, M. C., Olsson, C. A., McKiernan, J. M. 2004; 63 (1): 41-45

    Abstract

    To determine the natural history of patients younger than 40 years (young patient [YP] group) who are diagnosed with a sporadic renal cortical tumor (RCT) and to compare the natural history of these patients with the more typical older patient (OP) with RCT.We reviewed our database and identified 34 patients (younger than 40 years old, median age 35) who underwent surgery for a sporadic RCT. The YP group outcomes were compared with 100 patients between 41 and 85 years (median 65). We fit a Cox proportional hazards model to examine the relationship between age at presentation and recurrence risk.The median tumor size in the YP group was 3.8 cm (range 0.6 to 19) and in the OP group was 5.0 cm (range 0.9 to 22; P = 0.225). Tumors were discovered incidentally in 51% and 56% of the YP and OP groups, respectively (P = 0.65). The frequency of partial nephrectomy did not differ between the two groups (35% YP and 30% OP, P = 0.55). The frequency of malignant histologic subtypes did not differ between the groups (P = 0.439). In the YP group, only larger tumor size (hazard ratio 1.23, 95% confidence interval 1.02 to 1.50, P = 0.034) was associated with a statistically significant increased risk of recurrence. Those in the YP group were not more or less likely to develop recurrence than those in the OP group (hazard ratio 0.79, 95% confidence interval 0.22 to 2.85, P = 0.72). The 5-year disease-free survival rate was 73% and 80% in the YP and OP groups, respectively (P = 0.23). The 5-year disease-specific survival rate was 85% and 84% in the YP and OP groups, respectively (P = 0.88).The findings of our study indicate that the natural history of RCTs is similar in both younger and older patients. Young patients were neither more nor less likely to develop recurrence compared with their older counterparts.

    View details for DOI 10.1016/j.urology.2003.08.020

    View details for Web of Science ID 000220538100012

    View details for PubMedID 14751345

  • Obesity is associated with macrophage accumulation in adipose tissue JOURNAL OF CLINICAL INVESTIGATION Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., Ferrante, A. W. 2003; 112 (12): 1796-1808

    Abstract

    Obesity alters adipose tissue metabolic and endocrine function and leads to an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. To further characterize the changes that occur in adipose tissue with increasing adiposity, we profiled transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob). We found that the expression of 1,304 transcripts correlated significantly with body mass. Of the 100 most significantly correlated genes, 30% encoded proteins that are characteristic of macrophages and are positively correlated with body mass. Immunohistochemical analysis of perigonadal, perirenal, mesenteric, and subcutaneous adipose tissue revealed that the percentage of cells expressing the macrophage marker F4/80 (F4/80+) was significantly and positively correlated with both adipocyte size and body mass. Similar relationships were found in human subcutaneous adipose tissue stained for the macrophage antigen CD68. Bone marrow transplant studies and quantitation of macrophage number in adipose tissue from macrophage-deficient (Csf1op/op) mice suggest that these F4/80+ cells are CSF-1 dependent, bone marrow-derived adipose tissue macrophages. Expression analysis of macrophage and nonmacrophage cell populations isolated from adipose tissue demonstrates that adipose tissue macrophages are responsible for almost all adipose tissue TNF-alpha expression and significant amounts of iNOS and IL-6 expression. Adipose tissue macrophage numbers increase in obesity and participate in inflammatory pathways that are activated in adipose tissues of obese individuals.

    View details for DOI 10.1172/JCI2000319246

    View details for Web of Science ID 000187348300007

    View details for PubMedID 14679176

  • Is Hispanic race an independent risk factor for pathological stage in patients undergoing radical prostatectomy? JOURNAL OF UROLOGY Lam, J. S., Desai, M., Mansukhani, M. M., Benson, M. C., Goluboff, E. T. 2003; 170 (6): 2288-2291

    Abstract

    Hispanic-Americans are the most rapidly growing population in the United States. Although many studies have assessed differences in pathological stage at radical prostatectomy between white and black American men, to our knowledge none has assessed it in Hispanic men. We compared pathological stage at radical prostatectomy in contemporaneous groups of Hispanic and white American men.A total of 141 consecutive Hispanic and 314 consecutive white American men underwent radical retropubic prostatectomy for clinically localized prostate cancer from 1995 to 2002 at a single institution, as performed by one of us (ETG or MCB). Preoperative prostate specific antigen (PSA), age at diagnosis, race, clinical stage, biopsy and specimen Gleason score, pathological stage, specimen volume and calculated specimen PSA density were collected for each patient. Data were compared using standard statistical methods.Biopsy Gleason score, biopsy Gleason score distribution, specimen Gleason score, specimen Gleason distribution, pathological stage, calculated specimen PSA density, Gleason score change from biopsy to specimen and specimen prostate volume did not differ statistically between Hispanic and white men. Mean age and median preoperative PSA were statistically significantly higher in Hispanic vs white men (62.1 vs 59.5 years and 6.6 vs 5.4 ng/ml, respectively). In addition, no differences in the incidence of positive surgical margins, nonorgan confined disease, seminal vesicle invasion or positive lymph nodes were found between Hispanic and white men undergoing radical prostatectomy.This study shows that in contemporaneously treated groups of Hispanic and white men at the same institution pathological stage was similar between the groups. To our knowledge this is the largest comparison of surgically treated prostate cancer between these 2 groups. Further followup in terms of PSA outcome in these groups is planned.

    View details for DOI 10.1097/01.ju.0000091101.31497.71

    View details for Web of Science ID 000186529000028

    View details for PubMedID 14634398

  • The relationship between hemodynamics and inflammatory activation in women at risk for preeclampsia OBSTETRICS AND GYNECOLOGY Carr, D. B., McDonald, G. B., Brateng, D., Desai, M., Thach, C. T., Easterling, T. R. 2001; 98 (6): 1109-1116

    Abstract

    This study evaluated: 1) whether women with risk factors for preeclampsia had a hyperdynamic circulation and increased markers of endothelial and inflammatory activation; and 2) whether hemodynamically directed therapy was associated with a change in markers.A controlled experimental study was performed for two groups: 1) women at risk for preeclampsia (high risk); and 2) women at low risk (controls). Tumor necrosis factor-alpha (TNF-alpha), TNF-alpha receptors 1 and 2, vascular cell adhesion molecule-1, cellular fibronectin, and cardiac output were measured at or before 24 weeks' gestation and at 6-8 week intervals. High-risk subjects with cardiac output greater than 7.4 L/minute were treated with atenolol. Atenolol therapy was not randomized. Therefore, the longitudinal data were descriptive. Data were analyzed by the t test, Wilcoxon rank sum test, chi(2) test, multivariable linear regression, and the standard two-stage test.There were 46 high-risk subjects and 25 controls. Maternal age, gestational age, and parity did not differ between the groups. Cardiac output (P <.001) and vascular cell adhesion molecule-1 (P =.02) at baseline were significantly increased in the high-risk group. A total of 42 women in the high-risk group received atenolol for high cardiac output. There was a slower rise in TNF-alpha receptor 1 in the treated group compared with the controls (P <.001).Women with risk factors for preeclampsia had a hyperdynamic circulation and endothelial activation. Hemodynamically directed therapy in women at risk was associated with a slower rise in TNF-alpha receptor 1 compared with low-risk women who were not treated, suggesting a relationship between hemodynamics and inflammatory activation.

    View details for Web of Science ID 000172474700021

    View details for PubMedID 11755562

  • False positive rates of randomized Phase II designs CONTROLLED CLINICAL TRIALS Liu, P. Y., LeBlanc, M., Desai, M. 1999; 20 (4): 343-352

    Abstract

    The randomized Phase II design for the purpose of selecting a treatment for eventual Phase III testing has recently gained popularity in cancer clinical research. Unfortunately, along with its wider use also come frequent misapplications. The major misuse of the design is the treatment of the Phase II results as ends in themselves without further, definitive evaluation. For binary and censored exponential survival data, we quantify the chance of observing "impressive" between-group differences when underlying distributions are exactly the same in 2-, 3-, and 4-arm selection designs. Depending on one's view of what is impressive, the "false-positive" rates range from 20% to over 40%. We stress that randomized Phase II results are pilots to Phase III evaluations. One should not regard them as conclusive. We caution especially against the inclusion of control arms in such designs because of the propensity for erroneous inferences. We also discuss the inappropriate practice of performing post-hoc hypothesis testing and presenting p-values that are less than 0.05.

    View details for Web of Science ID 000081555900004

    View details for PubMedID 10440561

Conference Proceedings


  • A Standardized Learning Module Improves the Accuracy of Ex-Vivo Endoscopic Diagnosis of Polyp Histology With Narrow Band Imaging (NBI) by Community-Based Endoscopists Ladabaum, U., Fioritto, A., Paik, J., Mitani, A., Desai, M., Rex, D. K., Imperiale, T. F., Gunaratnam, N. T. MOSBY-ELSEVIER. 2012: 152-152

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