Manisha Desai (She/Her/Hers)

All Publications

• Asthma phenotypes, associated comorbidities, and long-term symptoms in COVID-19 European Journal of Allergy and Clinical Immunology Eggert, L. E., He, Z., Collins, W., Lee, A. S., Nadeau, K., Chinthrajah, R. 2021

  View details for DOI 10.1111/all.14972

• The authors reply. Critical care medicine Rogers, A. J., Desai, M., Matthay, M. A., Choi, A. M., Baron, R. M. 2020; 48 (1): e78

  View details for DOI 10.1097/CCM.0000000000004081

  View details for PubMedID 31833991

• Clinical and Economic Impact of Tailoring Screening to Predicted Colorectal Cancer Risk: A Decision Analytic Modeling Study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Ladabaum, U. n., Mannalithara, A. n., Mitani, A. n., Desai, M. n. 2019

  Abstract

  Global increases in colorectal cancer (CRC) risk have spurred debate about optimal use of screening resources. We explored the potential clinical and economic impact of CRC screening tailored to predicted CRC risk.We compared screening tailored to predicted risk vs. uniform screening in a validated decision analytic model, considering the average risk population's actual CRC risk distribution, and a risk-prediction tool's discriminatory ability and cost. Low, moderate, and high risk tiers were identified as CRC risk after age 50 of <=3%, >3 to <12%, and >=12%, respectively, based on threshold analyses with willingness-to-pay <$50,000/quality-adjusted life-year (QALY) gained. Tailored colonoscopy (once at 60 for low risk, every 10 years for moderate risk, every 5 years for high risk) was compared to colonoscopy every 10 years for all. Tailored fecal immunochemical testing [FIT]/colonoscopy (annual FIT for low and moderate risk, colonoscopy every 5 years for high risk) was compared to annual FIT for all.Assuming no CRC risk misclassification or risk-prediction tool costs, tailored screening was preferred over uniform screening. Tailored colonoscopy was minimally less effective than uniform colonoscopy, but saved $90,200-$889,000/QALY; tailored FIT/colonoscopy yielded more QALYs/person than annual FIT at $10,600-$60,000/QALY gained. Relatively modest CRC risk misclassification rates or risk-prediction tool costs resulted in uniform screening as the preferred approach.Current risk-prediction tools may not yet be accurate enough to optimize CRC screening.Uniform screening is likely to be preferred over tailored screening if a risk-prediction tool is associated with even modest misclassification rates or costs.

  View details for DOI 10.1158/1055-9965.EPI-19-0949

  View details for PubMedID 31796524

• A Predictive Model for Postembolization Syndrome after Transarterial Hepatic Chemoembolization of Hepatocellular Carcinoma. Radiology Khalaf, M. H., Sundaram, V., AbdelRazek Mohammed, M. A., Shah, R., Khosla, A., Jackson, K., Desai, M., Kothary, N. 2018: 180257

  Abstract

  Purpose To develop and validate a predictive model for postembolization syndrome (PES) following transarterial hepatic chemoembolization (TACE) for hepatocellular carcinoma. Materials and Methods In this single-center, retrospective study, 370 patients underwent 513 TACE procedures between October 2014 and September 2016. Seventy percent of the patients were randomly assigned to a training data set and the remaining 30% were assigned to a testing data set. Variables included demographic, laboratory, clinical, and procedural details. PES was defined as pain and/or nausea beyond 6 hours after TACE that required intravenous medication for symptom control. The predictive model was developed by using conditional inference trees and Lasso regression. Results Demographics, laboratory data, performance, tumor characteristics, and procedural details were statistically similar for the training and testing data sets. Overall, 83 of 370 patients (22.4%) after 107 of 513 TACE procedures (20.8%) met the predefined criteria. Factors identified at univariable analysis included large tumor burden (P = .004), drug-eluting embolic TACE (P = .03), doxorubicin dose (P = .003), history of PES (P < .001) and chronic pain (P < .001), of which history of PES, tumor burden, and drug-eluting embolic TACE were identified as the strongest predictors by the multivariable analysis and were used to develop the predictive model. When applied to the testing data set, the model demonstrated an area under the curve of 0.62, sensitivity of 79% (22 of 28), specificity of 44.2% (53 of 120), and a negative predictive value of 90% (53 of 59). Conclusion The model identified history of postembolization syndrome, tumor burden, and drug-eluting embolic chemoembolization as predictors of protracted recovery because of postembolization syndrome. © RSNA, 2018.

  View details for PubMedID 30299233

• Healthcare Service Utilization under a New Virtual Primary Care Delivery Model. Telemedicine journal and e-health : the official journal of the American Telemedicine Association Cheung, L., Leung, T. I., Ding, V. Y., Wang, J. X., Norden, J., Desai, M., Harrington, R. A., Desai, S. 2018

  Abstract

  BACKGROUND: Telemedicine holds great promise for changing healthcare delivery. While telemedicine has been used significantly in the direct-to-consumer setting, the use of telemedicine in a preventive primary care setting is not well studied.INTRODUCTION: ClickWell Care (CWC) is the first known implementation of a technology-enabled primary care model. We wanted to quantify healthcare utilization of primary care by patient characteristics and modality of care delivery.MATERIALS AND METHODS: Our study population included those who completed a visit to a CWC clinic between January 1, 2015 and September 30, 2015. We compared patients based on utilization of CWCs in-person and virtual visits across the following domains: patient demographics, distance from clinic, responses to a Health Risk Assessment, and top 10 conditions treated.RESULTS: Thousand two hundred seven patients completed a visit with a CWC physician in 2015. Nearly three-quarters of our patients were ≤40 years and sex was significantly different (p=0.015) between visit cohorts. The greatest representation of men (47%) was seen in the virtual-only cohort. Patients' proximity to the clinic was also significantly different across visit cohorts (p=0.018) with 44% of in-person-only and 34% of virtual-only patients living within 5 miles of Stanford Hospital.DISCUSSION: We found men were more likely to engage in virtual-only care. Young patients are willing to accept virtual care although many prefer to complete an in-person visit first.CONCLUSIONS: Our findings suggest that a "bricks-and-clicks" care model where telemedicine is supported by a brick-and-mortar location may be an effective way to leverage telemedicine to deliver primary care.

  View details for PubMedID 30192211

• Effect of a Lay Health Worker Intervention on Goals-of-Care Documentation and on Health Care Use, Costs, and Satisfaction Among Patients With Cancer: A Randomized Clinical Trial. JAMA oncology Patel, M. I., Sundaram, V., Desai, M., Periyakoil, V. S., Kahn, J. S., Bhattacharya, J., Asch, S. M., Milstein, A., Bundorf, M. K. 2018

  Abstract

  Importance: Although lay health workers (LHWs) improve cancer screening and treatment adherence, evidence on whether they can enhance other aspects of care is limited.Objective: To determine whether an LHW program can increase documentation of patients' care preferences after cancer diagnosis.Design, Setting, and Participants: Randomized clinical trial conducted from August 13, 2013, through February 2, 2015, among 213 patients with stage 3 or 4 or recurrent cancer at the Veterans Affairs Palo Alto Health Care System. Data analysis was by intention to treat and performed from January 15 to August 18, 2017.Interventions: Six-month program with an LHW trained to assist patients with establishing end-of-life care preferences vs usual care.Main Outcomes and Measures: The primary outcome was documentation of goals of care. Secondary outcomes were patient satisfaction on the Consumer Assessment of Health Care Providers and Systems "satisfaction with provider" item (on a scale of 0 [worst] to 10 [best possible]), health care use, and costs.Results: Among the 213 participants randomized and included in the intention-to-treat analysis, the mean (SD) age was 69.3 (9.1) years, 211 (99.1%) were male, and 165 (77.5%) were of non-Hispanic white race/ethnicity. Within 6 months of enrollment, patients randomized to the intervention had greater documentation of goals of care than the control group (97 [92.4%] vs 19 [17.5%.]; P<.001) and larger increases in satisfaction with care on the Consumer Assessment of Health Care Providers and Systems "satisfaction with provider" item (difference-in-difference, 1.53; 95% CI, 0.67-2.41; P<.001). The number of patients who died within 15 months of enrollment did not differ between groups (intervention, 60 of 105 [57.1%] vs control, 60 of 108 [55.6%]; P=.68). In the 30 days before death, patients in the intervention group had greater hospice use (46 [76.7%] vs 29 [48.3%]; P=.002), fewer emergency department visits (mean [SD], 0.05 [0.22] vs 0.60 [0.76]; P<.001), fewer hospitalizations (mean [SD], 0.05 [0.22] vs 0.50 [0.62]; P<.001), and lower costs (median [interquartile range], $1048 [$331-$8522] vs $23 482 [$9708-$55 648]; P<.001) than patients in the control group.Conclusions and Relevance: Incorporating an LHW into cancer care increases goals-of-care documentation and patient satisfaction and reduces health care use and costs at the end of life.Trial Registration: ClinicalTrials.gov Identifier: NCT02966509.

  View details for PubMedID 30054634

• Association between physical health and cardiovascular diseases: Effect modification by chronic conditions SAGE OPEN MEDICINE Saquib, N., Brunner, R., Desai, M., Allison, M., Garcia, L., Stefanick, M. L. 2018; 6: 2050312118785335

  Abstract

  This study assessed whether the physical component summary score of the RAND-36 health-related quality-of-life survey was associated with incidence of coronary heart disease, stroke, congestive heart failure, angina, or peripheral arterial disease, and whether baseline chronic conditions modified these associations.Analysis was limited to 69,155 postmenopausal women (50-79 years) in the Women's Health Initiative Study who had complete data on the RAND-36, the outcomes, and covariates. Chronic conditions were defined as blood pressure ⩾140/90 mm or self-reported heart disease, diabetes, hypertension, arthritis, asthma, emphysema, cancer, and/or cholesterol-reducing medication use. Outcomes data were ascertained during follow-up (1993-2005) with medical records.There were 2451 coronary heart disease, 1896 stroke, 1533 congestive heart failure, 1957 angina, and 502 peripheral arterial disease events during follow-up (median 8.2 years). Participants in the lowest physical component summary quintile, compared to the highest, had a significantly higher risk of developing coronary heart disease (hazard ratio (95% confidence interval) 2.0 (1.7, 2.3)), stroke (1.8 (1.5, 2.2)), angina (2.4(2.0, 2.9)), and peripheral arterial disease (3.0 (2.0, 4.4)), irrespective of chronic conditions. Interactions between physical component summary and existing chronic conditions were not significant for any outcome except congestive heart failure (p = 0.005); after adjustment, participants in the lowest physical component summary quintile and with any chronic condition had nearly a twofold higher risk of congestive heart failure (Yes = 4.4 (3.3, 5.8) vs No = 2.4 (1.2, 4.3)).We found a low physical component summary score was a significant risk factor for individual cardiovascular disease incidence in postmenopausal women.

  View details for PubMedID 30013784

• SAME HOSPITALIZATION CHOLECYSTECTOMY FOR ACUTE GALLSTONE PANCREATITIS: A NATIONWIDE ANALYSIS ACROSS A DECADE Bilal, M., Kline, K., Saraireh, H., Desai, M., Parupudi, S., Abougergi, M. S. MOSBY-ELSEVIER. 2018: AB589–AB590

  View details for Web of Science ID 000435509900523

• Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKD. Journal of the American Society of Nephrology : JASN Kurella Tamura, M., Desai, M., Kapphahn, K. I., Thomas, I., Asch, S. M., Chertow, G. M. 2018

  Abstract

  Background Appropriate patient selection and optimal timing of dialysis initiation among older adults with advanced CKD are uncertain. We determined the association between dialysis versus medical management and survival at different ages and levels of kidney function.Methods We assembled a nationally representative 20% sample of United States veterans with eGFR<30 ml/min per 1.73 m2 between 2005 and 2010 (n=73,349), with follow-up through 2012. We used an extended Cox model to determine associations among the time-varying exposures, age (<65, 65-74, 75-84, and ≥85 years), eGFR (<6, 6-<9, 9-<12, 12-<15, and 15-<29 ml/min per 1.73 m2), and provision of dialysis, and survival.Result Over the mean±SEM follow-up of 3.4±2.2 years, 15% of patients started dialysis and 52% died. The eGFR at which dialysis, compared with medical management, associated with lower mortality varied by age (P<0.001). For patients aged <65, 65-74, 75-84, and ≥85 years, dialysis associated with lower mortality for those with eGFR not exceeding 6-<9, <6, 9-<12, and 9-<12 ml/min per 1.73 m2, respectively. Dialysis initiation at eGFR<6 ml/min per 1.73 m2 associated with a higher median life expectancy of 26, 25, and 19 months for patients aged 65, 75, and 85 years, respectively. When dialysis was initiated at eGFR 9-<12 ml/min per 1.73 m2, the estimated difference in median life expectancy was <1 year for these patients.Conclusions Provision of dialysis at higher levels of kidney function may extend survival for some older patients.

  View details for PubMedID 29789430

• Dialysis Initiation and Mortality Among Older Veterans With Kidney Failure Treated in Medicare vs the Department of Veterans Affairs JAMA INTERNAL MEDICINE Tamura, M., Thomas, I., Montez-Rath, M. E., Kapphahn, K., Desai, M., Gale, R. C., Asch, S. M. 2018; 178 (5): 657–64

  Abstract

  The benefits of maintenance dialysis for older adults with end-stage renal disease (ESRD) are uncertain. Whether the setting of pre-ESRD nephrology care influences initiation of dialysis and mortality is not known.To compare initiation of dialysis and mortality among older veterans with incident kidney failure who received pre-ESRD nephrology care in fee-for-service Medicare vs the Department of Veterans Affairs (VA).Retrospective cohort study of patients from the US Medicare and VA health care systems evaluated 11 215 veterans aged 67 years or older with incident kidney failure between January 1, 2008, and December 31, 2011. Data analysis was performed March 15, 2016, through September 20, 2017.Pre-ESRD nephrology care in Medicare vs VA health care systems.Dialysis treatment and death within 2 years.Of the 11 215 patients included in the study, 11 085 (98.8%) were men; mean (SD) age was 79.1 (6.9) years. Within 2 years of incident kidney failure, 7071 (63.0%) of the patients started dialysis and 5280 (47.1%) died. Patients who received pre-ESRD nephrology care in Medicare were more likely to undergo dialysis compared with patients who received pre-ESRD nephrology care in VA (82% vs 53%; adjusted risk difference, 28 percentage points; 95% CI, 26-30 percentage points). Differences in dialysis initiation between Medicare and VA were more pronounced among patients aged 80 years or older and patients with dementia or metastatic cancer, and less pronounced among patients with paralysis (P < .05 for interaction). Two-year mortality was higher for patients who received pre-ESRD care in Medicare compared with VA (53% vs 44%; adjusted risk difference, 5 percentage points; 95% CI, 3-7 percentage points). The findings were similar in a propensity-matched analysis.Veterans who receive pre-ESRD nephrology care in Medicare receive dialysis more often yet are also more likely to die within 2 years compared with those in VA. The VA's integrated health care system and financing appear to favor lower-intensity treatment for kidney failure in older patients without a concomitant increase in mortality.

  View details for PubMedID 29630695

• Development of a tool predicting severity of allergic reaction during peanut challenge. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology Chinthrajah, R. S., Purington, N., Andorf, S., Rosa, J. S., Mukai, K., Hamilton, R., Smith, B. M., Gupta, R., Galli, S. J., Desai, M., Nadeau, K. C. 2018

  Abstract

  BACKGROUND: Reliable prognostic markers for predicting severity of allergic reactions during oral food challenges (OFC) have not been established.OBJECTIVE: We sought to develop a predictive algorithm of a food challenge severity score (CSS) to identify those at higher risk for severe reactions to a standardized peanut OFC.METHODS: Medical history and allergy tests were obtained for 120 peanut-allergic participants who underwent double-blind, placebo-controlled food challenges (DBPCFCs). Reactions were assigned a CSS between 1 to 6 based on cumulative tolerated dose and a "severity clinical indicator." Demographic characteristics, clinical features, peanut component IgE values, and a basophil activation marker were considered in a multi-step analysis to derive a flexible decision rule to understand risk during peanut of OFC.RESULTS: 18.3% participants had a severe reaction (CSS >4). The decision rule identified the following three variables (in order of importance) as predictors of reaction severity: ratio of %CD63hi stimulation with peanut to %CD63hi anti-IgE (CD63 ratio), history of exercise-induced asthma, and forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC) ratio. The CD63 ratio alone was a strong predictor of CSS (p<0.001).CONCLUSION: The CSS is a novel tool that combines dose thresholds and allergic reactions to understand risks associated with peanut OFCs. Lab-values (CD63 ratio), along with clinical variables (exercise-induced asthma and FEV1/FVC ratio) contribute to the predictive ability of the severity of reaction to peanut OFC. Further testing of this decision rule is needed in a larger external data source before it can be considered outside of research settings.

  View details for PubMedID 29709643

• Uninstrumented Posterior Lumbar Interbody Fusion: Have Technological Advances in Stabilizing the Lumbar Spine Truly Improved Outcomes? World neurosurgery Prolo, L. M., Oklund, S. A., Zawadzki, N., Desai, M., Prolo, D. J. 2018

  Abstract

  BACKGROUND: Since the 1980s, numerous operations have replaced posterior lumbar interbody fusion (PLIF) with human bone. These operations often involve expensive implants and complex procedures. Escalating expenditures in lumbar fusion surgery warrant re-evaluation of classical PLIF with allogeneic ilium and without instrumentation. The purpose of this study was to determine the long-term fusion rate and clinical outcomes of PLIF with allogeneic bone (allo-PLIF).METHODS: Between 1981 and 2006, 321 patients aged 12-80 years underwent 339 1-level or 2-level allo-PLIFs for degenerative instability and were followed for 1-28 years. Fusion status was determined by radiographs and as available, by computed tomography scans. Clinical outcome was assessed by the Economic/Functional Outcome Scale.RESULTS: Of the 321 patients, 308 were followed postoperatively (average 6.7 years) and 297 (96%) fused. Fusion rates were lower for patients with substance abuse (89%, P= 0.007). Clinical outcomes in 87% of patients were excellent (52%) or good (35%). Economic/Functional Outcome Scale scores after initial allo-PLIF on average increased 5.2 points. Successful fusion correlated with nearly a 2-point gain in outcome score (P= 0.001). A positive association between a patient characteristic and outcome was observed only with age 65 years and greater, whereas negative associations in clinical outcomes were observed with mental illness, substance abuse, heavy stress to the low back, or industrial injuries. The total complication rate was7%.CONCLUSIONS: With 3 decades of follow-up, we found that successful clinical outcomes are highly correlated with solid fusion using only allogeneic iliac bone.

  View details for PubMedID 29631080

• CANAGLIFLOZIN AND RENAL OUTCOMES IN PATIENTS WITH CHRONIC KIDNEY DISEASE Perkovic, V., Neuen, B. L., Ohkuma, T., Neal, B., Matthews, D. R., de Zeeuw, D., Mahaffey, K. W., Fulcher, G., Desai, M., Li, Q., Deng, H., Rosenthal, N., Bakris, G. W B SAUNDERS CO-ELSEVIER INC. 2018: 574

  View details for Web of Science ID 000428167100243

• Osteoarthritis and Reproductive History in the Women's Health Initiative. Wang, A., Zawadzki, N., Hedlin, H., Desai, M., Westphal, L., Stefanick, M. L. SAGE PUBLICATIONS INC. 2018: 87A

  View details for Web of Science ID 000429928200092

• Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion The DIETFITS Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Gardner, C. D., Trepanowski, J. F., Del Gobbo, L. C., Hauser, M. E., Rigdon, J., Ioannidis, J. A., Desai, M., King, A. C. 2018; 319 (7): 667–79

  Abstract

  Dietary modification remains key to successful weight loss. Yet, no one dietary strategy is consistently superior to others for the general population. Previous research suggests genotype or insulin-glucose dynamics may modify the effects of diets.To determine the effect of a healthy low-fat (HLF) diet vs a healthy low-carbohydrate (HLC) diet on weight change and if genotype pattern or insulin secretion are related to the dietary effects on weight loss.The Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) randomized clinical trial included 609 adults aged 18 to 50 years without diabetes with a body mass index between 28 and 40. The trial enrollment was from January 29, 2013, through April 14, 2015; the date of final follow-up was May 16, 2016. Participants were randomized to the 12-month HLF or HLC diet. The study also tested whether 3 single-nucleotide polymorphism multilocus genotype responsiveness patterns or insulin secretion (INS-30; blood concentration of insulin 30 minutes after a glucose challenge) were associated with weight loss.Health educators delivered the behavior modification intervention to HLF (n = 305) and HLC (n = 304) participants via 22 diet-specific small group sessions administered over 12 months. The sessions focused on ways to achieve the lowest fat or carbohydrate intake that could be maintained long-term and emphasized diet quality.Primary outcome was 12-month weight change and determination of whether there were significant interactions among diet type and genotype pattern, diet and insulin secretion, and diet and weight loss.Among 609 participants randomized (mean age, 40 [SD, 7] years; 57% women; mean body mass index, 33 [SD, 3]; 244 [40%] had a low-fat genotype; 180 [30%] had a low-carbohydrate genotype; mean baseline INS-30, 93 μIU/mL), 481 (79%) completed the trial. In the HLF vs HLC diets, respectively, the mean 12-month macronutrient distributions were 48% vs 30% for carbohydrates, 29% vs 45% for fat, and 21% vs 23% for protein. Weight change at 12 months was -5.3 kg for the HLF diet vs -6.0 kg for the HLC diet (mean between-group difference, 0.7 kg [95% CI, -0.2 to 1.6 kg]). There was no significant diet-genotype pattern interaction (P = .20) or diet-insulin secretion (INS-30) interaction (P = .47) with 12-month weight loss. There were 18 adverse events or serious adverse events that were evenly distributed across the 2 diet groups.In this 12-month weight loss diet study, there was no significant difference in weight change between a healthy low-fat diet vs a healthy low-carbohydrate diet, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss. In the context of these 2 common weight loss diet approaches, neither of the 2 hypothesized predisposing factors was helpful in identifying which diet was better for whom.clinicaltrials.gov Identifier: NCT01826591.

  View details for PubMedID 29466592

• Anti-IgE treatment with oral immunotherapy in multifood allergic participants: a double-blind, randomised, controlled trial LANCET GASTROENTEROLOGY & HEPATOLOGY Andorf, S., Purington, N., Block, W. M., Long, A. J., Tupa, D., Brittain, E., Spergel, A., Desai, M., Galli, S. J., Nadeau, K. C., Chinthrajah, R. 2018; 3 (2): 85–94

  Abstract

  Despite progress in single food oral immunotherapy, there is little evidence concerning the safety and efficacy of treating individuals with multiple food (multifood) allergies. We did a pilot study testing whether anti-IgE (omalizumab) combined with multifood oral immunotherapy benefited multifood allergic patients.We did a blinded, phase 2 clinical trial at Stanford University. We enrolled participants, aged 4-15 years, with multifood allergies validated by double-blind, placebo-controlled food challenges to their offending foods. Inclusion criteria included a positive skin prick test of 6 mm or more (wheal diameter, above the negative control), a food-specific serum IgE concentration of more than 4 kU/L for each food, or both, and a positive double-blind, placebo-controlled food challenge at 500 mg or less of food protein. Exclusion criteria included eosinophilic oesophagitis and severe asthma. Participants were randomised (3:1) with a block size of four, to receive multifood oral immunotherapy to two to five foods, together with omalizumab (n=36) or placebo (n=12). 12 individuals who fulfilled the same inclusion and exclusion criteria were included as controls. These individuals were not randomised and received neither omalizumab nor oral immunotherapy. Omalizumab or placebo was administered subcutaneously for 16 weeks, with oral immunotherapy starting at week 8, and was stopped 20 weeks before the exit double-blind, placebo-controlled food challenge at week 36. The primary endpoint was the proportion of participants who passed double-blind, placebo-controlled food challenges to at least two of their offending foods. This completed trial is registered with ClinicalTrials.gov, number NCT02643862.Between March 25, 2015, and Aug 18, 2016, 165 participants were assessed for eligibility, of whom 84 did not meet the inclusion criteria and 21 declined to participate. We enrolled and randomised 48 eligible participants and the remaining 12 patients were included as nonrandomised, untreated controls. At week 36, a significantly greater proportion of the omalizumab-treated (30 [83%] of 36) versus placebo (four [33%] of 12) participants passed double-blind, placebo-controlled food challenges to 2 g protein for two or more of their offending foods (odds ratio 10·0, 95% CI 1·8-58·3, p=0·0044). All participants completed the study. There were no serious or severe (grade 3 or worse) adverse events. Participants in the omalizumab group had a significantly lower median per-participant percentage of oral immunotherapy doses associated with any adverse events (27% vs 68%; p=0·0082). The most common adverse events in both groups were gastrointestinal events.In multifood allergic patients, omalizumab improves the efficacy of multifood oral immunotherapy and enables safe and rapid desensitisation.US National Institutes of Health (NIH).

  View details for PubMedID 29242014

• Patterns of Disrespectful Physician Behavior at an Academic Medical Center: Implications for Training, Prevention, and Remediation. Academic medicine : journal of the Association of American Medical Colleges Hopkins, J., Hedlin, H., Weinacker, A., Desai, M. 2018

  Abstract

  PURPOSE: Physician disrespectful behavior affects quality of care, patient safety, and collaborative clinical team function. Evidence defining the demographics, ethnography, and epidemiology of disrespectful behavior is lacking.METHOD: The authors conducted a retrospective analysis of reports of disrespectful physician behavior at Stanford Hospital and Clinics from March 2011 through February 2015. Events were stratified by role, gender, specialty, and location in the hospital or clinics where the event occurred. Event rate ratios were estimated using a multivariable negative binomial regression model. Correlation of rates of faculty and trainees in the same specialty were assessed.RESULTS: One-hundred-ninety-nine events concerned faculty; 160 concerned trainees. Events were concentrated among a small number of physicians in both groups. The rates of faculty and trainee events within the same specialty were highly correlated (Spearman's rho: 0.90; P < .001). Male physicians had an adjusted event rate 1.86 (95% CI = 1.33 - 2.60; P < .001) times that of females. Procedural physicians were 3.67 times (95% CI = 2.63 - 5.13; P < .001) more likely to have a disrespectful behavior event than non-procedural physicians when adjusting for other covariates. Most common location for faculty was the operating rooms (69 events, 34%); for trainees, the medical/surgical units (43 events, 27%).CONCLUSIONS: Patterns of physician disrespectful behavior differed by role, gender, specialty, and location. Rates among faculty and trainees of the same specialty were highly correlated. These patterns can be used to create more focused education and training for specific physician groups and individualized remediation interventions.

  View details for DOI 10.1097/ACM.0000000000002126

  View details for PubMedID 29319539

• Higher Absolute Lymphocyte Counts Predict Lower Mortality from Early-Stage Triple-Negative Breast Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research Afghahi, A. n., Purington, N. n., Han, S. S., Desai, M. n., Pierson, E. n., Mathur, M. B., Seto, T. n., Thompson, C. A., Rigdon, J. n., Telli, M. L., Badve, S. S., Curtis, C. n., West, R. B., Horst, K. n., Gomez, S. L., Ford, J. M., Sledge, G. W., Kurian, A. W. 2018

  Abstract

  Tumor-infiltrating lymphocytes (TILs) in pre-treatment biopsies are associated with improved survival in triple-negative breast cancer (TNBC). We investigated whether higher peripheral lymphocyte counts are associated with lower breast cancer-specific mortality (BCM) and overall mortality (OM) in TNBC.Data on treatments and diagnostic tests from electronic medical records of two healthcare systems were linked with demographic, clinical, pathologic, and mortality data from the California Cancer Registry. Multivariable regression models adjusted for age, race/ethnicity, socioeconomic status, cancer stage, grade, neoadjuvant/adjuvant chemotherapy use, radiotherapy use, and germline BRCA1/2 mutations were used to evaluate associations between absolute lymphocyte count (ALC), BCM and OM. For a subgroup with TILs data available, we explored the relationship between TILs and peripheral lymphocyte counts.1,463 Stage I-III TNBC patients were diagnosed from 2000-2014; 1113 (76%) received neoadjuvant/adjuvant chemotherapy within one year of diagnosis. Of 759 patients with available ALC data, 481 (63.4%) were ever lymphopenic (minimum ALC <1.0 K/μL). On multivariable analysis, higher minimum ALC, but not absolute neutrophil count, predicted lower OM (hazard ratio [HR]: 0.23, 95% confidence interval [CI]: 0.16-0.35) and BCM (HR: 0.19, CI: 0.11-0.34). Five-year probability of BCM was 15% for patients who were ever lymphopenic versus 4% for those who were not. An exploratory analysis (N=70) showed a significant association between TILs and higher peripheral lymphocyte counts during neoadjuvant chemotherapy.Higher peripheral lymphocyte counts predicted lower mortality from early-stage, potentially curable TNBC, suggesting that immune function may enhance the effectiveness of early TNBC treatment.

  View details for PubMedID 29581131

• Initial Provider Specialty is Associated with Long-term Opiate Use in Patients with Newly Diagnosed Low Back and Lower Extremity Pain. Spine Azad, T. n., Vail, D. n., Bentley, J. n., Han, S. n., Suarez, P. n., Varshneya, K. n., Mittal, V. n., Veeravagu, A. n., Desai, M. n., Bhattacharya, J. n., Ratliff, J. n. 2018

  Abstract

  Retrospective longitudinal cohort analysis of patients diagnosed in 2010, with continuous enrollment six months prior to and 12 months following the initial visit.To determine whether provider specialty influences patterns of opiate utilization long after initial diagnosis.Patients with low back pain present to a variety of providers and receive a spectrum of treatments, including opiate medications. The impact of initial provider type on opiate use in this population is uncertain.We performed a retrospective analysis of opiate-naïve adult patients in the United States with newly diagnosed low back or lower extremity pain. We estimated the risk of early opiate prescription (≤ 14 days from diagnosis) and long-term opiate use (≥ six prescriptions in 12 months) based on the provider type at initial diagnosis using multivariable logistic regression, adjusting for patient demographics and comorbidities.We identified 478,981 newly diagnosed opiate-naïve patients. Of these, 40.4% received an opiate prescription within one year and 4.0% met criteria for long-term use. The most common initial provider type was family practice, associated with a 24.4% risk of early opiate prescription (95% CI, 24.1-24.6) and a 2.0% risk of long-term opiate use (95% CI, 2.0-2.1). Risk of receiving an early opiate prescription was higher among patients initially diagnosed by emergency medicine (43.1%; 95% CI, 41.6-44.5) or at an urgent care facility (40.8%; 95% CI, 39.4-42.3). Risk of long-term opiate use was highest for patients initially diagnosed by pain management/anesthesia (6.7%; 95% CI, 6.0-7.3) or physical medicine and rehabilitation (3.4%; 95% CI, 3.1-3.8) providers.Initial provider type influences early opiate prescription and long-term opiate use among opiate-naïve patients with newly diagnosed low back and lower extremity pain.3.

  View details for PubMedID 30095796

• Triclosan and triclocarban exposure, infectious disease symptoms and antibiotic prescription in infants-A community-based randomized intervention. PloS one Ley, C., Sundaram, V., Sanchez, M. d., Desai, M., Parsonnet, J. 2018; 13 (6): e0199298

  Abstract

  BACKGROUND: Triclosan and triclocarban (TCs) are broad-spectrum antimicrobials that, until recently, were found in a wide variety of household and personal wash products. Popular with consumers, TCs have not been shown to protect against infectious diseases.OBJECTIVES: To determine whether use of TC-containing wash products reduces incidence of infection in children less than one year of age.METHODS: Starting in 2011, we nested a randomized intervention of wash products with and without TCs within a multiethnic birth cohort. Maternal reports of infectious disease symptoms and antibiotic use were collected weekly by automated survey; household visits occurred every four months. Antibiotic prescriptions were identified by medical chart review. Urinary triclosan levels were measured in a participant subset. Differences by intervention group in reported infectious disease (primary outcome) and antibiotic use (secondary outcome) were assessed using mixed effects logistic regression and Fisher's Exact tests, respectively.RESULTS: Infectious illness occurred in 6% of weeks, with upper respiratory illness the predominant syndrome. Among 60 (45%) TC-exposed and 73 (55%) non-TC-exposed babies, infectious disease reports did not differ in frequency between groups (likelihood ratio test: p = 0.88). Medical visits with antibiotic prescriptions were less common in the TC group than in the non-TC group (7.8% vs. 16.6%, respectively; p = 0.02).CONCLUSIONS: Although randomization to TC-containing wash products was not associated with decreased infectious disease reports by mothers, TCs were associated with decreased antibiotic prescriptions, suggesting a benefit against bacterial infection. The recent removal of TCs from consumer wash products makes further elucidation of benefits and risks impracticable.

  View details for DOI 10.1371/journal.pone.0199298

  View details for PubMedID 29953463

• Assessing the Relationship between Atherosclerotic Cardiovascular Disease Risk Score and Carotid Artery Imaging Findings. Journal of neuroimaging : official journal of the American Society of Neuroimaging Li, Y. n., Zhu, G. n., Ding, V. n., Huang, Y. n., Jiang, B. n., Ball, R. L., Rodriguez, F. n., Fleischmann, D. n., Desai, M. n., Saloner, D. n., Saba, L. n., Hom, J. n., Wintermark, M. n. 2018

  Abstract

  To characterize the relationship between computed tomography angiography (CTA) imaging characteristics of carotid artery and the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) score.We retrospectively identified all patients who underwent a cervical CTA at our institution from January 2013 to July 2016, extracted clinical information, and calculated the 10-year ASCVD score using the Pooled Cohort Equations from the 2013 ACC/AHA guidelines. We compared the imaging features of artery atherosclerosis derived from the CTAs between low and high risk.One hundred forty-six patients met our inclusion criteria. Patients with an ASCVD score ≥7.5% (64.4%) had significantly more arterial stenosis than patients with an ASCVD score <7.5% (35.6%, P < .001). Maximal plaque thickness was significantly higher (mean 2.33 vs. .42 mm, P < .001) and soft plaques (55.3% vs. 13.5%, P < .001) were significantly more frequent in patients with an ASCVD score ≥7.5%. However, among patients with a 10-year ASCVD score ≥7.5%, 33 (35.1%) had no arterial stenosis, 35 (37.2%) had a maximal plaque thickness less than. 9 mm, and 42 (44.7%) had no soft plaque. Furthermore, among the patients with a 10-year ASCVD score <7.5%, 8 (15.4%) had some arterial stenosis, 8 (15.4%) had a maximal plaque thickness more than. 9 mm, and 7 (13.5%) had soft plaque.There is some concordance but not a perfect overlap between the 10-year ASCVD risk scores calculated from clinical and blood assessment and carotid artery imaging findings.

  View details for PubMedID 30357980

• Effect of Interferon-Free Regimens on Disparities in Hepatitis C Treatment of US Veterans. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research Barnett, P. G., Joyce, V. R., Lo, J. n., Gidwani-Marszowski, R. n., Goldhaber-Fiebert, J. D., Desai, M. n., Asch, S. M., Holodniy, M. n., Owens, D. K. 2018; 21 (8): 921–30

  Abstract

  To determine whether implementation of interferon-free treatment for hepatitis C virus (HCV) reached groups less likely to benefit from earlier therapies, including patients with genotype 1 virus or contraindications to interferon treatment, and groups that faced treatment disparities: African Americans, patients with HIV co-infection, and those with drug use disorder.Electronic medical records of the US Veterans Health Administration (VHA) were used to characterize patients with chronic HCV infection and the treatments they received. Initiation of treatment in 206,544 patients with chronic HCV characterized by viral genotype, demographic characteristics, and comorbid medical and mental illness was studied using a competing events Cox regression over 6 years.With the advent of interferon-free regimens, the proportion treated increased from 2.4% in 2010 to 18.1% in 2015, an absolute increase of 15.7%. Patients with genotype 1 virus, poor response to previous treatment, and liver disease had the greatest increase. Large absolute increases in the proportion treated were observed in patients with HIV co-infection (18.6%), alcohol use disorder (11.9%), and drug use disorder (12.6%) and in African American (13.7%) and Hispanic (13.5%) patients, groups that were less likely to receive interferon-containing treatment. The VHA spent $962 million on interferon-free treatments in 2015, 1.5% of its operating budget.The proportion of patients with HCV treated in VHA increased sevenfold. The VHA was successful in implementing interferon treatment in previously undertreated populations, and this may become the community standard of care.

  View details for PubMedID 30098669

• ACIST-FFR Study (Assessment of Catheter-Based Interrogation and Standard Techniques for Fractional Flow Reserve Measurement). Circulation. Cardiovascular interventions Fearon, W. F., Chambers, J. W., Seto, A. H., Sarembock, I. J., Raveendran, G., Sakarovitch, C., Yang, L., Desai, M., Jeremias, A., Price, M. J., ACIST-FFR Study Investigators 2017; 10 (12)

  Abstract

  BACKGROUND: Measurement of fractional flow reserve (FFR) to guide coronary revascularization lags despite robust supportive data, partly because of the handling characteristics of traditional coronary pressure wires. An optical pressure-monitoring microcatheter, which can be advanced over a traditional coronary guidewire, facilitates FFR assessment but may underestimate pressure wire-derived FFR.METHODS AND RESULTS: In this prospective, multicenter trial, 169 patients underwent FFR assessment with a pressure wire alone and with a pressure microcatheter over the pressure wire. An independent core laboratory performed quantitative coronary angiography and evaluated all pressure tracings. The primary end point was the bias or difference between the microcatheter FFR and the pressure wire FFR, as assessed by Bland-Altman analysis. The mean difference between the microcatheter and the pressure wire-derived FFR values was -0.022 (95% confidence interval, -0.029 to -0.015). On multivariable analysis, reference vessel diameter (P=0.027) and lesion length (P=0.044) were independent predictors of bias between the 2 FFR measurements. When the microcatheter FFR was added to this model, it was the only independent predictor of bias (P<0.001). The mean FFR value from the microcatheter was significantly lower than from the pressure wire (0.81 versus 0.83; P<0.001). In 3% of cases (95% confidence interval, 1.3%-6.7%), there was clinically meaningful diagnostic discordance, with the FFR from the pressure wire >0.80 and that from the microcatheter <0.75. These findings were similar when including all 210 patients with site-reported paired FFR data.CONCLUSIONS: An optical, pressure-monitoring microcatheter measures lower FFR compared with a pressure wire, but the diagnostic impact appears to be minimal in most cases.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02577484.

  View details for PubMedID 29246917

• Cangrelor reduces the risk of ischemic complications in patients with single-vessel and multi-vessel disease undergoing percutaneous coronary intervention: Insights from the CHAMPION PHOENIX trial. American heart journal Abnousi, F., Sundaram, V., Yong, C. M., Prats, J., Deliargyris, E. N., Stone, G. W., Hamm, C. W., Steg, P. G., Gibson, C. M., White, H. D., Price, M. J., Généreux, P., Desai, M., Yang, L., Ding, V. Y., Harrington, R. A., Bhatt, D. L., Mahaffey, K. W. 2017; 188: 147-155

  Abstract

  To examine the safety and efficacy of cangrelor in patients with single-vessel disease (SVD) and multi-vessel disease (MVD).Cangrelor, an intravenous, rapidly acting P2Y12 inhibitor, is superior to clopidogrel in reducing ischemic events among patients receiving percutaneous coronary intervention (PCI).We studied a modified intention to treat population of patients with SVD and MVD from the CHAMPION PHOENIX trial. The primary efficacy outcome was the composite of death, myocardial infarction (MI), ischemia-driven revascularization (IDR), and stent thrombosis (ST) at 48hours. The key safety outcome was non-coronary artery bypass grafting GUSTO severe bleeding at 48hours.Among 10,921 patients, 5,220 (48%) had SVD and 5,701 (52%) had MVD. MVD patients were older and more often had diabetes, hyperlipidemia, hypertension, prior stroke, and prior MI. After adjustment, MVD patients had similar rates of 48-hour death/MI/IDR/ST (6.3% vs 4.2%, adjusted odds ratio [OR] 1.6 [95% CI 0.42-6.06]) and GUSTO severe bleeding (0.1% vs 0.2%, P=.67) compared with SVD patients. Consistent with overall trial findings, cangrelor use reduced ischemic complications in patients with both SVD (3.9% vs 4.5%; OR 0.86, 95% CI 0.65-1.12) and MVD (5.5% vs 7.2%; OR 0.74, 95% CI 0.6-0.92, P-interaction=.43). GUSTO severe bleeding outcomes were not significantly increased with cangrelor or clopidogrel in either SVD or MVD patients.In the CHAMPION PHOENIX trial, MVD and SVD patients had similar ischemic outcomes at 48hours and 30days. Cangrelor consistently reduced ischemic complications in both SVD and MVD patients without a significant increase in GUSTO severe bleeding. CLINICAL PERSPECTIVES.

  View details for DOI 10.1016/j.ahj.2017.02.031

  View details for PubMedID 28577670

• ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2016 Appropriate Use Criteria for Coronary Revascularization in Patients With Acute Coronary Syndromes JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Patel, M. R., Calhoon, J. H., Dehmer, G. J., Grantham, J. A., Maddox, T. M., Maron, D. J., Smith, P. K., Wolk, M. J., Patel, M. R., Dehmer, G. J., Smith, P. K., Blankenship, J. C., Bove, A. A., Bradley, S. M., Dean, L. S., Duffy, P. L., Ferguson, T. B., Grover, F. L., Guyton, R. A., Hlatky, M. A., Lazar, H. L., Rigolin, V. H., Rose, G. A., Shemin, R. J., Tamis-Holland, J. E., Tommaso, C. L., Wann, L. S., Wong, J. B., Doherty, J. U., Dehmer, G. J., Bailey, S. R., Bhave, N. M., Brown, A. S., Daugherty, S. L., Desai, M. Y., Duvernoy, C. S., Gillam, L. D., Hendel, R. C., Kramer, C. M., Lindsay, B. D., Manning, W. J., Patel, M. R., Sachdeva, R., Wann, L. S., Winchester, D. E., Wolk, M. J., Allen, J. M. 2017; 69 (5): 570-591

  View details for DOI 10.1016/j.jacc.2016.10.034

  View details for Web of Science ID 000392994900013

• Characterizing CD137 upregulation on NK cells in patients receiving monoclonal antibody therapy ANNALS OF ONCOLOGY MAKKOUK, A., Sundaram, V., Chester, C., Chang, S., Colevas, A. D., Sunwoo, J. B., Maecker, H., Desai, M., Kohrt, H. E. 2017; 28 (2): 415-420

  Abstract

  In the era of personalized cancer medicine, identifying techniques for effectively matching patients to efficacious treatments is a critical step in the treatment process. The advent of anti-cancer immunotherapies necessitates novel approaches to biomarker identification beyond traditional genomic profiling. One promising approach is incorporation of nomograms into treatment decisions. Nomograms are prediction tools, based on statistical modeling, designed to predict treatment outcomes. As a first step toward developing a nomogram, we conducted analyses to predict CD137 expression of natural killer cells after monoclonal antibody (mAb) treatment.Patient, tumor and immune characteristics were collected from 199 patients with breast cancer (N = 62), head/neck cancers (N = 46) and non-Hodgkin's lymphoma (NHL) (N = 91), who were receiving mAb therapy as part of clinical trials. The difference in CD137 expression before and after mAb therapy was assessed by flow cytometry. To evaluate those who respond to mAb therapy via increased CD137 expression, we applied classification and regression trees (CART), multivariable lasso regression tools and Random Forest.The CD137 expression was significantly different for each cancer type [mean (SD): Breast: 6.6 (6.5); Head/Neck: 11.0 (7.0); NHL: 7.5 (7.1), P < 0.0001]. For breast cancer and NHL, FcR polymorphism and baseline CD137 expression were significant predictors of increased CD137 expression; for head/neck cancer, FcR polymorphism and age were significant predictors of increased expression.Our preliminary results suggest that FcR polymorphism, pre-treatment CD137 expression and age are significant predictors of CD137 upregulation in patients. This study demonstrates that the development of a nomogram for therapy response is feasible. Further work validating our models in an independent cohort will provide the next steps in developing a nomogram that may be used to individualize this therapeutic approach for patients (NCT01114256).

  View details for DOI 10.1093/annonc/mdw570

  View details for Web of Science ID 000397278300032

• Accuracy of Models to Identify Lung Nodule Cancer Risk in the National Lung Screening Trial. American journal of respiratory and critical care medicine Nair, V. S., Sundaram, V. n., Desai, M. n., Gould, M. K. 2017

  View details for PubMedID 29064264

• Risk of Cardiovascular Events Associated With Current Exposure to HIV Antiretroviral Therapies in a US Veteran Population. Clinical infectious diseases Desai, M., Joyce, V., Bendavid, E., Olshen, R. A., Hlatky, M., Chow, A., Holodniy, M., Barnett, P., Owens, D. K. 2015; 61 (3): 445-452

  Abstract

   To characterize the association of antiretroviral drug combinations on risk of cardiovascular events. Certain antiretroviral medications for human immunodeficiency virus (HIV) have been implicated in increasing risk of cardiovascular disease. However, antiretroviral drugs are typically prescribed in combination. We characterized the association of current exposure to antiretroviral drug combinations on risk of cardiovascular events including myocardial infarction, stroke, percutaneous coronary intervention, and coronary artery bypass surgery. We used the Veterans Health Administration Clinical Case Registry to analyze data from 24 510 patients infected with HIV from January 1996 through December 2009. We assessed the association of current exposure to 15 antiretroviral drugs and 23 prespecified combinations of agents on the risk of cardiovascular event by using marginal structural models and Cox models extended to accommodate time-dependent variables. Over 164 059 person-years of follow-up, 934 patients had a cardiovascular event. Current exposure to abacavir, efavirenz, lamivudine, and zidovudine was significantly associated with increased risk of cardiovascular event, with odds ratios ranging from 1.40 to 1.53. Five combinations were significantly associated with increased risk of cardiovascular event, all of which involved lamivudine. One of these-efavirenz, lamivudine, and zidovudine-was the second most commonly used combination and was associated with a risk of cardiovascular event that is 1.60 times that of patients not currently exposed to the combination (odds ratio = 1.60, 95% confidence interval, 1.25-2.04). In the VA cohort, exposure to both individual drugs and drug combinations was associated with modestly increased risk of a cardiovascular event.

  View details for DOI 10.1093/cid/civ316

  View details for PubMedID 25908684

• Calcium and vitamin D supplementation do not influence menopause-related symptoms: Results of the Women's Health Initiative Trial MATURITAS LeBlanc, E. S., Hedlin, H., Qin, F., Desai, M., Wactawski-Wende, J., Perrin, N., Manson, J. E., Johnson, K. C., Masaki, K., Tylavsky, F. A., Stefanick, M. L. 2015; 81 (3): 377-383

  Abstract

  It is unknown whether supplementation with calcium and vitamin D has an impact on menopause-related symptoms.As part of the Women's Health Initiative Calcium/Vitamin D Supplementation Trial (CaD), women were randomized at 40 clinical sites to elemental calcium carbonate 1000 mg with vitamin D 400 IU daily or placebo. At the CaD baseline visit (year 1 or year 2) and during a mean follow-up of 5.7 years, participants provided data on menopause-related symptoms via questionnaires. Generalized linear mixed effects techniques were used to address research questions.After excluding participants with missing data (N=2125), we compared menopause-related symptoms at follow-up visits of 17,101 women randomized to CaD with those of 17,056 women given the placebo. Women in the CaD arm did not have a different number of symptoms at follow-up compared to women taking the placebo (p=0.702). Similarly, there was no difference between sleep disturbance, emotional well-being, or energy/fatigue at follow-up in those who were randomized to CaD supplementation compared to those taking the placebo.Our data suggest that supplementation with 1000 mg of calcium plus 400 IU of vitamin D does not influence menopause-related symptoms over an average of 5.7 years of follow-up among postmenopausal women with an average age of 64 at the WHI baseline visit.

  View details for DOI 10.1016/j.maturitas.2015.04.007

  View details for Web of Science ID 000357229600009

  View details for PubMedID 26044075

  View details for PubMedCentralID PMC4469550

• Real world effectiveness of primary implantable cardioverter defibrillators implanted during hospital admissions for exacerbation of heart failure or other acute co-morbidities: cohort study of older patients with heart failure. BMJ (Clinical research ed.) Chen, C., Stevenson, L. W., Stewart, G. C., Bhatt, D. L., Desai, M., Seeger, J. D., Williams, L., Jalbert, J. J., Setoguchi, S. 2015; 351: h3529-?

  Abstract

  To examine the effectiveness of primary implantable cardioverter defibrillators (ICDs) in elderly patients receiving the device during a hospital admission for exacerbation of heart failure or other acute co-morbidities, with an emphasis on adjustment for early mortality and other factors reflecting healthy candidate bias rather than the effect of the ICD.Retrospective cohort study.Linked data from the Centers for Medicare and Medicaid Services and American College of Cardiology-National Cardiovascular Data Registry ICD registry, nationwide heart failure registry, and Medicare claims data 2004-09.23 111 patients aged ≥66 who were admitted to hospital for exacerbation of heart failure or other acute co-morbidities and eligible for primary ICDs.All cause mortality and sudden cardiac death. Latency analyses with Cox regression were used to derive crude hazard ratios and hazard ratios adjusted for high dimension propensity score for outcomes after 180 days from index implantation or discharge.Patients who received an ICD during a hospital admission had lower crude mortality risk than patients who did not receive an ICD (40% v 60% at three years); however, with conditioning on 180 day survival and with adjustment for high dimension propensity score, the apparent benefit with ICD was no longer evident for sudden cardiac death (adjusted hazard ratio 0.95, 95% confidence interval 0.78 to 1.17) and had a diminished impact on total mortality (0.91, 0.82 to 1.00). There were trends towards a benefit with ICD in reducing mortality or sudden cardiac death in patients who had had a myocardial infarction more than 40 days previously, left bundle branch block, or low serum B type natriuretic peptide; however, these trends did not reach significance.After adjustment for healthy candidate bias and confounding, the benefits of primary ICD therapy seen in pivotal trials were not apparent in patients aged 66 or over who received ICDs during a hospital admission for exacerbation of heart failure or other acute co-morbidities. Future research is warranted to further identify subgroups of elderly patients who are more likely to benefit from ICDs. Recognition of those patients whose dominant risk factors are from decompensated heart failure and non-cardiac co-morbidities will allow better focus on ICDs in those patients for whom the device offers the most benefit and provides meaningful prolonging of life.

  View details for DOI 10.1136/bmj.h3529

  View details for PubMedID 26174233

• Smoking behavior and association of melanoma and nonmelanoma skin cancer in the Women's Health Initiative JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Henderson, M. T., Kubo, J. T., Desai, M., David, S. P., Tindle, H., Sinha, A. A., Hou, L., Messina, C., Saquib, N., Stefanick, M. L., Tang, J. Y. 2015; 72 (1): 190-191

  View details for DOI 10.1016/j.jaad.2014.09.024

  View details for Web of Science ID 000346404500053

  View details for PubMedID 25497923

• Active and passive smoking in relation to lung cancer incidence in the Women's Health Initiative Observational Study prospective cohort†. Annals of oncology Wang, A., Kubo, J., Luo, J., Desai, M., Hedlin, H., Henderson, M., Chlebowski, R., Tindle, H., Chen, C., Gomez, S., Manson, J. E., Schwartz, A. G., Wactawski-Wende, J., Cote, M., Patel, M. I., Stefanick, M. L., Wakelee, H. A. 2015; 26 (1): 221-230

  Abstract

  Lung cancer is the leading cause of worldwide cancer deaths. While smoking is its leading risk factor, few prospective cohort studies have reported on the association of lung cancer with both active and passive smoking. This study aimed to determine the relationship between lung cancer incidence with both active and passive smoking (childhood, adult at home, and at work).The Women's Health Initiative Observational Study (WHI-OS) was a prospective cohort study conducted at 40 US centers that enrolled postmenopausal women from 1993 to 1999. Among 93 676 multiethnic participants aged 50-79, 76 304 women with complete smoking and covariate data comprised the analytic cohort. Lung cancer incidence was calculated by Cox proportional hazards models, stratified by smoking status.Over 10.5 mean follow-up years, 901 lung cancer cases were identified. Compared with never smokers (NS), lung cancer incidence was much higher in current [hazard ratio (HR) 13.44, 95% confidence interval (CI) 10.80-16.75] and former smokers (FS; HR 4.20, 95% CI 3.48-5.08) in a dose-dependent manner. Current and FS had significantly increased risk for all lung cancer subtypes, particularly small-cell and squamous cell carcinoma. Among NS, any passive smoking exposure did not significantly increase lung cancer risk (HR 0.88, 95% CI 0.52-1.49). However, risk tended to be increased in NS with adult home passive smoking exposure ≥30 years, compared with NS with no adult home exposure (HR 1.61, 95% CI 1.00-2.58).In this prospective cohort of postmenopausal women, active smoking significantly increased risk of all lung cancer subtypes; current smokers had significantly increased risk compared with FS. Among NS, prolonged passive adult home exposure tended to increase lung cancer risk. These data support continued need for smoking prevention and cessation interventions, passive smoking research, and further study of lung cancer risk factors in addition to smoking.NCT00000611.

  View details for DOI 10.1093/annonc/mdu470

  View details for PubMedID 25316260

• Non-melanoma skin cancer and NSAID use in women with a history of skin cancer in the Women's Health Initiative PREVENTIVE MEDICINE Wysong, A., Ally, M. S., Gamba, C. S., Desai, M., Swetter, S. M., Seiffert-Sinha, K., Sinha, A. A., Stefanick, M. L., Tang, J. Y. 2014; 69: 8-12

  Abstract

  Evidence for the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on non-melanoma skin cancer (NMSC) risk is inconsistent. We prospectively examined whether regular, inconsistent, or no/low-use of NSAIDs is associated with lower NMSC risk among 54,728 postmenopausal Caucasian women in the Women's Health Initiative Observational Study enrolled between 1993 and 1998.Logistic regression models were used to assess odds of NMSC after adjusting for skin type, sun exposure history and indication for NSAID use.There were 7652 incident cases of NMSC (median follow-up: 6.9years). There was no association between regular NSAID-use and NMSC risk relative to no/low-users. However, in a subgroup analysis of 5325 women with a history of skin cancer (incident NMSC: 1897), odds of NMSC were lower among regular NSAID users whether <5years (OR 0.82, 95% CI: 0.70-0.95) or ≥5years (OR 0.82, 95% CI: 0.69-0.98) of use compared to no/low-users. Inconsistent NSAID use and acetaminophen use were not associated with NMSC risk.Overall, NSAID use was not associated with NMSC risk. However, in women with a history of skin cancer, regular NSAID use was associated with 18% lower odds of NMSC. Future studies on potential chemopreventative effects of NSAIDs should focus on subjects with prior history of NMSC.

  View details for DOI 10.1016/j.ypmed.2014.08.024

  View details for Web of Science ID 000346221600003

• Vitamin D levels and menopause-related symptoms. Menopause (New York, N.Y.) LeBlanc, E. S., Desai, M., Perrin, N., Wactawski-Wende, J., Manson, J. E., Cauley, J. A., Michael, Y. L., Tang, J., Womack, C., Song, Y., Johnson, K. C., O'Sullivan, M. J., Woods, N., Stefanick, M. L. 2014; 21 (11): 1197-1203

  Abstract

  This study aims to determine whether vitamin D levels are associated with menopause-related symptoms in older women.A randomly selected subset of 1,407 women, among 26,104 potentially eligible participants of the Women's Health Initiative Calcium and Vitamin D trial of postmenopausal women aged 51 to 80 years, had 25-hydroxyvitamin D [25(OH)D] levels measured at the Women's Health Initiative Calcium and Vitamin D trial baseline visit. Information about menopause-related symptoms at baseline was obtained by questionnaire and included overall number of symptoms and composite measures of sleep disturbance, emotional well-being, and energy/fatigue, as well as individual symptoms. After exclusions for missing data, 530 women (mean [SD] age, 66.2 [6.8] y) were included in these analyses.Borderline significant associations between 25(OH)D levels and total number of menopausal symptoms were observed (with P values ranging from 0.05 to 0.06 for fully adjusted models); however, the effect was clinically insignificant and disappeared with correction for multiple testing. No associations between 25(OH)D levels and composite measures of sleep disturbance, emotional well-being, or energy/fatigue were observed (P's > 0.10 for fully adjusted models).There is no evidence for a clinically important association between serum 25(OH)D levels and menopause-related symptoms in postmenopausal women.

  View details for DOI 10.1097/GME.0000000000000238

  View details for PubMedID 24736200

• Energy behaviours of northern California Girl Scouts and their families ENERGY POLICY Boudet, H., Ardoin, N. M., Flora, J., Armel, K. C., Desai, M., Robinson, T. N. 2014; 73: 439-449

  View details for DOI 10.1016/j.enpol.2014.05.044

  View details for Web of Science ID 000341474100040

• Challenges and solutions to pre- and post-randomization subgroup analyses. Current cardiology reports Desai, M., Pieper, K. S., Mahaffey, K. 2014; 16 (10): 531-?

  Abstract

  Subgroup analyses are commonly performed in the clinical trial setting with the purpose of illustrating that the treatment effect was consistent across different patient characteristics or identifying characteristics that should be targeted for treatment. There are statistical issues involved in performing subgroup analyses, however. These have been given considerable attention in the literature for analyses where subgroups are defined by a pre-randomization feature. Although subgroup analyses are often performed with subgroups defined by a post-randomization feature--including analyses that estimate the treatment effect among compliers--discussion of these analyses has been neglected in the clinical literature. Such analyses pose a high risk of presenting biased descriptions of treatment effects. We summarize the challenges of doing all types of subgroup analyses described in the literature. In particular, we emphasize issues with post-randomization subgroup analyses. Finally, we provide guidelines on how to proceed across the spectrum of subgroup analyses.

  View details for DOI 10.1007/s11886-014-0531-2

  View details for PubMedID 25135344

• Association between Latent Proviral Characteristics and Immune Activation in Antiretrovirus-Treated Human Immunodeficiency Virus Type 1-Infected Adults. Journal of virology Liang, E. C., Sceats, L., Bayless, N. L., Strauss-Albee, D. M., Kubo, J., Grant, P. M., Furman, D., Desai, M., Katzenstein, D. A., Davis, M. M., Zolopa, A. R., Blish, C. A. 2014; 88 (15): 8629-8639

  Abstract

  Generalized immune activation during HIV infection is associated with an increased risk of cardiovascular disease, neurocognitive disease, osteoporosis, metabolic disorders, and physical frailty. The mechanisms driving this immune activation are poorly understood, particularly for individuals effectively treated with antiretroviral medications. We hypothesized that viral characteristics such as sequence diversity may play a role in driving HIV-associated immune activation. We therefore sequenced proviral DNA isolated from peripheral blood mononuclear cells from HIV-infected individuals on fully suppressive antiretroviral therapy. We performed phylogenetic analyses, calculated viral diversity and divergence in the env and pol genes, and determined coreceptor tropism and the frequency of drug resistance mutations. Comprehensive immune profiling included quantification of immune cell subsets, plasma cytokine levels, and intracellular signaling responses in T cells, B cells, and monocytes. These antiretroviral therapy-treated HIV-infected individuals exhibited a wide range of diversity and divergence in both env and pol genes. However, proviral diversity and divergence in env and pol, coreceptor tropism, and the level of drug resistance did not significantly correlate with markers of immune activation. A clinical history of virologic failure was also not significantly associated with levels of immune activation, indicating that a history of virologic failure does not inexorably lead to increased immune activation as long as suppressive antiretroviral medications are provided. Overall, this study demonstrates that latent viral diversity is unlikely to be a major driver of persistent HIV-associated immune activation.Chronic immune activation, which is associated with cardiovascular disease, neurologic disease, and early aging, is likely to be a major driver of morbidity and mortality in HIV-infected individuals. Although treatment of HIV with antiretroviral medications decreases the level of immune activation, levels do not return to normal. The factors driving this persistent immune activation, particularly during effective treatment, are poorly understood. In this study, we investigated whether characteristics of the latent, integrated HIV provirus that persists during treatment are associated with immune activation. We found no relationship between latent viral characteristics and immune activation in treated individuals, indicating that qualities of the provirus are unlikely to be a major driver of persistent inflammation. We also found that individuals who had previously failed treatment but were currently effectively treated did not have significantly increased levels of immune activation, providing hope that past treatment failures do not have a lifelong "legacy" impact.

  View details for DOI 10.1128/JVI.01257-14

  View details for PubMedID 24850730

  View details for PubMedCentralID PMC4135944

• Addressing Missing Data in Clinical Studies of Kidney Diseases CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Montez-Rath, M. E., Winkelmayer, W. C., Desai, M. 2014; 9 (7): 1328-1335

  Abstract

  Missing data constitute a problem present in all studies of medical research. The most common approach to handling missing data-complete case analysis-relies on assumptions about missing data that rarely hold in practice. The implications of this approach are biased and inefficient descriptions of relationships of interest. Here, various approaches for handling missing data in clinical studies are described. In particular, this work promotes the use of multiple imputation methods that rely on assumptions about missingness that are more flexible than those assumptions relied on by the most common method in use. Furthermore, multiple imputation methods are becoming increasingly more accessible in mainstream statistical software packages, making them both a sound and practical choice. The use of multiple imputation methods is illustrated with examples pertinent to kidney research, and concrete guidance on their use is provided.

  View details for DOI 10.2215/CJN.10141013

  View details for Web of Science ID 000338615300024

• Influence of healthy candidate bias in assessing clinical effectiveness for implantable cardioverter-defibrillators: cohort study of older patients with heart failure BMJ-BRITISH MEDICAL JOURNAL Setoguchi, S., Stevenson, L. W., Stewart, G. C., Bhatt, D. L., Epstein, A. E., Desai, M., Williams, L. A., Chen, C. 2014; 348

  Abstract

  To assess the potential contribution of unmeasured general health status to patient selection in assessments of the clinical effectiveness of implantable cardioverter-defibrillator (ICD) therapy.Retrospective cohort study.Linked data from an ICD registry, heart failure registry, and Medicare claims data for ICDs implanted in 2005 through 2009.29,426 patients admitted to hospital with heart failure aged 66 years or older and eligible for ICD therapy for primary prevention.Non-traumatic hip fracture, admission to a skilled nursing facility, and 30 day mortality-outcomes unlikely to be improved by ICD therapy.Compared with 17,853 patients without ICD therapy, 11,573 patients with ICD therapy were younger and had lower ejection fraction and more cardiac admissions to hospital but fewer non-cardiac admissions to hospital and comorbid conditions. Patients with ICD therapy had greater freedom from unrelated events after adjusting for age and sex: hip fracture (hazard ratio 0.77, 95% confidence interval 0.64 to 0.92), skilled nursing facility admission (0.53, 0.50 to 0.55), and 30 day mortality (0.12, 0.10 to 0.15).Lower risks of measured outcomes likely reflect unmeasured differences in comorbidity and frailty. The findings highlight potential pitfalls of observational comparative effectiveness research and support physician consideration of general health status in selecting patients for ICD therapy.

  View details for DOI 10.1136/bmj.g2866

  View details for Web of Science ID 000335819700002

  View details for PubMedCentralID PMC4014056

• Visual illusions and plate design: the effects of plate rim widths and rim coloring on perceived food portion size INTERNATIONAL JOURNAL OF OBESITY McClain, A. D., van den Bos, W., Matheson, D., Desai, M., McClure, S. M., Robinson, T. N. 2014; 38 (5): 657-662

  Abstract

  The Delboeuf Illusion affects perceptions of the relative sizes of concentric shapes. This study was designed to extend research on the application of the Delboeuf illusion to food on a plate by testing whether a plate's rim width and coloring influence perceptual bias to affect perceived food portion size.Within-subjects experimental design. Experiment 1 tested the effect of rim width on perceived food portion size. Experiment 2 tested the effect of rim coloring on perceived food portion size. In both experiments, participants observed a series of photographic images of paired, side-by-side plates varying in designs and amounts of food. From each pair, participants were asked to select the plate that contained more food. Multilevel logistic regression examined the effects of rim width and coloring on perceived food portion size.Experiment 1: participants overestimated the diameter of food portions by 5% and the visual area of food portions by 10% on plates with wider rims compared with plates with very thin rims (P<0.0001). The effect of rim width was greater with larger food portion sizes. Experiment 2: participants overestimated the diameter of food portions by 1.5% and the visual area of food portions by 3% on plates with rim coloring compared with plates with no coloring (P=0.01). The effect of rim coloring was greater with smaller food portion sizes.The Delboeuf illusion applies to food on a plate. Participants overestimated food portion size on plates with wider and colored rims. These findings may help design plates to influence perceptions of food portion sizes.

  View details for DOI 10.1038/ijo.2013.169

  View details for Web of Science ID 000335445300006

  View details for PubMedID 24005858

  View details for PubMedCentralID PMC3947396

• Increasing energy- and greenhouse gas-saving behaviors among adolescents: a school-based cluster-randomized controlled trial ENERGY EFFICIENCY Cornelius, M., Armel, K. C., Hoffman, K., Allen, L., Bryson, S. W., Desai, M., Robinson, T. N. 2014; 7 (2): 217-242

  View details for DOI 10.1007/s12053-013-9219-5

  View details for Web of Science ID 000332789200004

• 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

• Influence of healthy candidate bias in assessing clinical effectiveness for implantable cardioverter-defibrillators: cohort study of older patients with heart failure. BMJ (Clinical research ed.) Setoguchi, S., Warner Stevenson, L., Stewart, G. C., Bhatt, D. L., Epstein, A. E., Desai, M., Williams, L. A., Chen, C. 2014; 348: g2866-?

  Abstract

  To assess the potential contribution of unmeasured general health status to patient selection in assessments of the clinical effectiveness of implantable cardioverter-defibrillator (ICD) therapy.Retrospective cohort study.Linked data from an ICD registry, heart failure registry, and Medicare claims data for ICDs implanted in 2005 through 2009.29,426 patients admitted to hospital with heart failure aged 66 years or older and eligible for ICD therapy for primary prevention.Non-traumatic hip fracture, admission to a skilled nursing facility, and 30 day mortality-outcomes unlikely to be improved by ICD therapy.Compared with 17,853 patients without ICD therapy, 11,573 patients with ICD therapy were younger and had lower ejection fraction and more cardiac admissions to hospital but fewer non-cardiac admissions to hospital and comorbid conditions. Patients with ICD therapy had greater freedom from unrelated events after adjusting for age and sex: hip fracture (hazard ratio 0.77, 95% confidence interval 0.64 to 0.92), skilled nursing facility admission (0.53, 0.50 to 0.55), and 30 day mortality (0.12, 0.10 to 0.15).Lower risks of measured outcomes likely reflect unmeasured differences in comorbidity and frailty. The findings highlight potential pitfalls of observational comparative effectiveness research and support physician consideration of general health status in selecting patients for ICD therapy.

  View details for DOI 10.1136/bmj.g2866

  View details for PubMedID 24812112

• Breast Cancer Treatment Across Health Care Systems CANCER Kurian, A. W., Mitani, A., Desai, M., Yu, P. P., Seto, T., Weber, S. C., Olson, C., Kenkare, P., Gomez, S. L., de Bruin, M. A., Horst, K., Belkora, J., May, S. G., Frosch, D. L., Blayney, D. W., Luft, H. S., Das, A. K. 2014; 120 (1): 103-111

  Abstract

  Understanding of cancer outcomes is limited by data fragmentation. In the current study, the authors analyzed the information yielded by integrating breast cancer data from 3 sources: electronic medical records (EMRs) from 2 health care systems and the state registry.Diagnostic test and treatment data were extracted from the EMRs of all patients with breast cancer treated between 2000 and 2010 in 2 independent California institutions: a community-based practice (Palo Alto Medical Foundation; "Community") and an academic medical center (Stanford University; "University"). The authors incorporated records from the population-based California Cancer Registry and then linked EMR-California Cancer Registry data sets of Community and University patients.The authors initially identified 8210 University patients and 5770 Community patients; linked data sets revealed a 16% patient overlap, yielding 12,109 unique patients. The percentage of all Community patients, but not University patients, treated at both institutions increased with worsening cancer prognostic factors. Before linking the data sets, Community patients appeared to receive less intervention than University patients (mastectomy: 37.6% vs 43.2%; chemotherapy: 35% vs 41.7%; magnetic resonance imaging: 10% vs 29.3%; and genetic testing: 2.5% vs 9.2%). Linked Community and University data sets revealed that patients treated at both institutions received substantially more interventions (mastectomy: 55.8%; chemotherapy: 47.2%; magnetic resonance imaging: 38.9%; and genetic testing: 10.9% [P < .001 for each 3-way institutional comparison]).Data linkage identified 16% of patients who were treated in 2 health care systems and who, despite comparable prognostic factors, received far more intensive treatment than others. By integrating complementary data from EMRs and population-based registries, a more comprehensive understanding of breast cancer care and factors that drive treatment use was obtained.

  View details for DOI 10.1002/cncr.28395

  View details for Web of Science ID 000328443000017

  View details for PubMedCentralID PMC3867595

• Randomized Clinical Trial to Evaluate the Efficacy and Safety of Valganciclovir in a Subset of Patients With Chronic Fatigue Syndrome JOURNAL OF MEDICAL VIROLOGY Montoya, J. G., Kogelnik, A. M., Bhangoo, M., Lunn, M. R., Flamand, L., Merrihew, L. E., Watt, T., Kubo, J. T., Paik, J., Desai, M. 2013; 85 (12): 2101-2109

  Abstract

  There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have been proposed as infectious triggers. Thirty CFS patients with elevated IgG antibody titers against HHV-6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double-blind, placebo-controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI-20) and Fatigue Severity Scale (FSS) scores, self-reported cognitive function, and physician-determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels. VGCV patients experienced a greater improvement by MFI-20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI-20 mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive function (P = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders (P = 0.029). In the VGCV arm, monocyte counts decreased (P < 0.001), neutrophil counts increased (P = 0.037) and cytokines were more likely to evolve towards a Th1-profile (P < 0.001). Viral IgG antibody titers did not differ between arms. VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted.

  View details for DOI 10.1002/jmv.23713

  View details for PubMedID 23959519

• 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

• 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

• 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

  View details for PubMedCentralID PMC3924331

• Family, community and clinic collaboration to treat overweight and obese children: Stanford GOALS-A randomized controlled trial of a three-year, multi-component, multi-level, multi-setting intervention. Contemporary clinical trials Robinson, T. N., Matheson, D., Desai, M., Wilson, D. M., Weintraub, D. L., Haskell, W. L., McClain, A., McClure, S., A Banda, J., Sanders, L. M., Haydel, K. F., Killen, J. D. 2013; 36 (2): 421-435

  Abstract

  To test the effects of a three-year, community-based, multi-component, multi-level, multi-setting (MMM) approach for treating overweight and obese children.Two-arm, parallel group, randomized controlled trial with measures at baseline, 12, 24, and 36months after randomization.Seven through eleven year old, overweight and obese children (BMI≥85th percentile) and their parents/caregivers recruited from community locations in low-income, primarily Latino neighborhoods in Northern California.Families are randomized to the MMM intervention versus a community health education active-placebo comparison intervention. Interventions last for three years for each participant. The MMM intervention includes a community-based after school team sports program designed specifically for overweight and obese children, a home-based family intervention to reduce screen time, alter the home food/eating environment, and promote self-regulatory skills for eating and activity behavior change, and a primary care behavioral counseling intervention linked to the community and home interventions. The active-placebo comparison intervention includes semi-annual health education home visits, monthly health education newsletters for children and for parents/guardians, and a series of community-based health education events for families.Body mass index trajectory over the three-year study. Secondary outcome measures include waist circumference, triceps skinfold thickness, accelerometer-measured physical activity, 24-hour dietary recalls, screen time and other sedentary behaviors, blood pressure, fasting lipids, glucose, insulin, hemoglobin A1c, C-reactive protein, alanine aminotransferase, and psychosocial measures.The Stanford GOALS trial is testing the efficacy of a novel community-based multi-component, multi-level, multi-setting treatment for childhood overweight and obesity in low-income, Latino families.

  View details for DOI 10.1016/j.cct.2013.09.001

  View details for PubMedID 24028942

• Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry. Science translational medicine Horowitz, A., Strauss-Albee, D. M., Leipold, M., Kubo, J., Nemat-Gorgani, N., Dogan, O. C., Dekker, C. L., Mackey, S., Maecker, H., Swan, G. E., Davis, M. M., Norman, P. J., Guethlein, L. A., Desai, M., Parham, P., Blish, C. A. 2013; 5 (208): 208ra145-?

  Abstract

  Natural killer (NK) cells play critical roles in immune defense and reproduction, yet remain the most poorly understood major lymphocyte population. Because their activation is controlled by a variety of combinatorially expressed activating and inhibitory receptors, NK cell diversity and function are closely linked. To provide an unprecedented understanding of NK cell repertoire diversity, we used mass cytometry to simultaneously analyze 37 parameters, including 28 NK cell receptors, on peripheral blood NK cells from 5 sets of monozygotic twins and 12 unrelated donors of defined human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) genotype. This analysis revealed a remarkable degree of NK cell diversity, with an estimated 6000 to 30,000 phenotypic populations within an individual and >100,000 phenotypes in the donor panel. Genetics largely determined inhibitory receptor expression, whereas activation receptor expression was heavily environmentally influenced. Therefore, NK cells may maintain self-tolerance through strictly regulated expression of inhibitory receptors while using adaptable expression patterns of activating and costimulatory receptors to respond to pathogens and tumors. These findings further suggest the possibility that discrete NK cell subpopulations could be harnessed for immunotherapeutic strategies in the settings of infection, reproduction, and transplantation.

  View details for DOI 10.1126/scitranslmed.3006702

  View details for PubMedID 24154599

• 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

  Abstract

  Past studies of relationships between alcohol and hip fracture have generally focused on total alcohol consumed and not type of alcohol. Different types of alcohol consist of varying components which may affect risk of hip fracture differentially. This study seeks to examine the relationship between alcohol consumption, with a focus on type of alcohol consumed (e.g. beer, wine, or hard liquor) and hip fracture risk in post-menopausal women.The longitudinal cohort consisted of U.S. post-menopausal women aged 50-79 years enrolled between 1993-1998 in the Women's Health Initiative Clinical Trials and Observational Study (N=115,655).Women were categorized as non-drinkers, past drinkers, infrequent drinkers and drinkers by preference of alcohol type (i.e. those who preferred wine, beer, hard liquor, or who had no strong preference). Mean alcohol consumption among current drinkers was 3.3 servings per week; this was similar among those who preferred wine, beer and liquor. After adjustment for potential confounders, alcohol preference was strongly correlated with hip fracture risk (p = 0.0167); in particular, women who preferred wine were at lower risk than non-drinkers (OR=0.78; 95% CI 0.64-0.95), past drinkers (OR=0.85; 95% CI 0.72-1.00), infrequent drinkers (OR=0.73; 95% CI 0.61-0.88), hard liquor drinkers (OR=0.87; 95% CI 0.71-1.06), beer drinkers (OR=0.72; 95% CI 0.55-0.95) and those with no strong preference (OR=0.89; 95% CI 0.89; 95% CI 0.73-1.10).Preference of alcohol type was associated with hip fracture; women who preferentially consumed wine had a lower risk of hip fracture compared to non-drinkers, past drinkers, and those with other alcohol preferences.

  View details for DOI 10.1186/1472-6874-13-36

  View details for Web of Science ID 000324754800001

  View details for PubMedCentralID PMC3848688

• 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

  View details for PubMedCentralID PMC3727940

• 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

  Abstract

  BACKGROUND: Physical and Mental Component Summary (PCS, MCS, respectively) scales of SF- 36 health-related-quality-of-life have been associated with all-cause and cardiovascular disease (CVD) mortality. Their relationships with CVD incidence are unclear. This study purpose was to test whether PCS and/or MCS were associated with CVD incidence and death. METHODS: Postmenopausal women (aged 50--79 years) in control groups of the Women's Health Initiative clinical trials (n = 20,308) completed the SF-36 and standardized questionnaires at trial entry. Health outcomes, assessed semi-annually, were verified with medical records. Cox regressions assessed time to selected outcomes during the trial phase (1993--2005). RESULTS: A total of 1075 incident CVD events, 204 CVD-specific deaths, and 1043 total deaths occurred during the trial phase. Women with low versus high baseline PCS scores had less favorable health profiles at baseline. In multivariable models adjusting for baseline confounders, participants in the lowest PCS quintile (reference = highest quintile) exhibited 1.8 (95%CI: 1.4, 2.3), 4.7 (95%CI: 2.3, 9.4), and 2.1 (95%CI: 1.7, 2.7) times greater risk of CVD incidence, CVD-specific death, and total mortality, respectively, by trial end; whereas, MCS was not significantly associated with CVD incidence or death. CONCLUSION: Physical health, assessed by self-report of physical functioning, is a strong predictor of CVD incidence and death in postmenopausal women; similar self-assessment of mental health is not. PCS should be evaluated as a screening tool to identify older women at high risk for CVD development and death.

  View details for DOI 10.1186/1471-2458-13-468

  View details for Web of Science ID 000321500700001

  View details for PubMedCentralID PMC3706392

• 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 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

  View details for PubMedCentralID PMC3608726

• 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

  View details for PubMedCentralID PMC3677755

• 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

• 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: 1053-?

  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 PubMedID 24207014

  View details for PubMedCentralID PMC3924331

• 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 PubMedID 23555704

  View details for PubMedCentralID PMC3608726

• 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 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 κ 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% (κ=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 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

  View details for PubMedCentralID PMC3322315

• A Standardized Learning Module Improves the Accuracy of Ex-Vivo Endoscopic Diagnosis of Polyp Histology With Narrow Band Imaging (NBI) by Community-Based Endoscopists 53rd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / Digestive Disease Week (DDW) / Meeting of the Pancreas-Club Ladabaum, U., Fioritto, A., Paik, J., Mitani, A., Desai, M., Rex, D. K., Imperiale, T. F., Gunaratnam, N. T. MOSBY-ELSEVIER. 2012: 152–52

  View details for Web of Science ID 000304328000149

• 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 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 PubMedID 22011765

• 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 PubMedID 21803971

• 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

• 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

  View details for PubMedCentralID PMC3176104

• 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), β-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, β-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 β-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

  View details for PubMedCentralID PMC3069380

• 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 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: γ-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

  View details for PubMedCentralID PMC3056570

• 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

  View details for PubMedCentralID PMC3217865

• 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

  View details for PubMedCentralID PMC3081682

• 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

  View details for PubMedCentralID PMC3665008

• 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

  View details for PubMedCentralID PMC2763503

• 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

  View details for PubMedCentralID PMC3077714

• Interaction of obesity and race in predicting recurrence rates after radical prostatectomy 45th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Lee, D. J., Ritch, C., Desai, M., McKiernan, J. M. AMER SOC CLINICAL ONCOLOGY. 2009

  View details for Web of Science ID 000276606603470

• Association of estimated glomerular filtration rate (eGFR) with odds of a renal lesion 45th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Hruby, G., Van Batavia, J., Wosnitzer, M., Benson, M., Desai, M., McKiernan, J., Newhouse, J. AMER SOC CLINICAL ONCOLOGY. 2009

  View details for Web of Science ID 000276606604066

• A combined phase I/II trial of intravesical nanoparticle albumin-bound paclitaxel in the treatment of refractory non-muscle- invasive transitional cell bladder cancer 45th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Barlow, L., Laudano, M., Mann, M., Desai, M., Petrylak, D., Benson, M., McKiernan, J. AMER SOC CLINICAL ONCOLOGY. 2009

  View details for Web of Science ID 000276606604088

• Role of obesity and race in predicting recurrence rates and survival in renal cell carcinoma 45th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Ritch, C., Lee, D. J., Desai, M., McKiernan, J. M. AMER SOC CLINICAL ONCOLOGY. 2009

  View details for Web of Science ID 000276606604093

• 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 53rd Annual Scientific Session of the American-College-of-Cardiology Kaufman, B. D., Desai, M., Reddy, S., Osorio, J. C., Chen, J. M., Mosca, R. S., Ferrante, A. W., Mital, S. CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. 2008: 760–67

  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

  View details for PubMedCentralID PMC2446458

• Prediction of long-term survival conditional on years survived following nephrectomy Laudano, M. A., Desai, M., Badani, K. K., Hirsh, A. L., Benson, M. C., McKiernan, J. M. AMER SOC CLINICAL ONCOLOGY. 2008

  View details for Web of Science ID 000208457401909

• WHERE TO BIOPSY IN THE GASTROINTESTINAL (GI) TRACT TO DIAGNOSE ACUTE GRAFT VERSUS HOST DISEASE (AGVHD) IN PEDIATRIC ALLOGENEIC STEM CELL TRANSPLANT RECIPIENTS (AlloSCT) Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation/Meeting on Center for International Blood and Marrow Transplant Research Tandem Martinez, M., Billore, G., Desai, M., Chu, K., Remotti, H., Satwani, P., Cairo, I. S., DeFelice, A. ELSEVIER SCIENCE INC. 2008: 132–32

  View details for Web of Science ID 000260330100361

• 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

  View details for PubMedCentralID PMC2266776

• 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 100th Annual Meeting of the American-Urological-Association McKiernan, J. M., Masson, P., Murphy, A. M., Goetzl, M., Olsson, C. A., Petrylak, D. P., Desai, M., Benson, M. C. AMER SOC CLINICAL ONCOLOGY. 2006: 3075–80

  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

  View details for PubMedCentralID PMC1448617

• Effectiveness of academic detailing on breast cancer screening among primary care physicians in an underserved community 26th Annual Meeting of the American-Society-of-Preventive-Oncology Sheinfeld Gorin, S., Ashford, A. R., Lantigua, R., Hossain, A., Desai, M., Troxel, A., Gemson, D. AMER BOARD FAMILY MEDICINE. 2006: 110–21

  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

  View details for PubMedCentralID PMC544187

• 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

  View details for PubMedCentralID PMC296995

• 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