Instructor, Psychiatry and Behavioral Sciences
B.A., Columbia University (2004)
A.M., Harvard University, Statistics (2005)
Ph.D., Columbia University, Statistics (2009)
I am interested in the application of statistical methods to advance the understanding of mental illnesses. I have a background in statistics with specific training in survival analysis. My areas of expertise are the robustness of regression-based inference in randomized or non-randomized studies, methods for analyzing survival data subject to non-standard sampling schemes, and spatial statistics.
Empirical ethics inquiry works from the notion that stakeholder perspectives are necessary for gauging the ethical acceptability of human studies and assuring that research aligns with societal expectations. Although common, studies involving different populations often entail comparisons of trends that problematize the interpretation of results. Using graphical model selection - a technique aimed at transcending limitations of conventional methods - this report presents data on the ethics of clinical research with two objectives: (1) to display the patterns of views held by ill and healthy individuals in clinical research as a test of the study's original hypothesis and (2) to introduce graphical model selection as a key analytic tool for ethics research.In this IRB-approved, NIH-funded project, data were collected from 60 mentally ill and 43 physically ill clinical research protocol volunteers, 47 healthy protocol-consented participants, and 29 healthy individuals without research protocol experience. Respondents were queried on the ethical acceptability of research involving people with mental and physical illness (i.e., cancer, HIV, depression, schizophrenia, and post-traumatic stress disorder) and non-illness related sources of vulnerability (e.g., age, class, gender, ethnicity). Using a statistical algorithm, we selected graphical models to display interrelationships among responses to questions.Both mentally and physically ill protocol volunteers revealed a high degree of connectivity among ethically-salient perspectives. Healthy participants, irrespective of research protocol experience, revealed patterns of views that were not highly connected.Between ill and healthy protocol participants, the pattern of views is vastly different. Experience with illness was tied to dense connectivity, whereas healthy individuals expressed views with sparse connections. In offering a nuanced perspective on the interrelation of ethically relevant responses, graphical model selection has the potential to bring new insights to the field of ethics.
View details for DOI 10.1080/23294515.2014.995836
View details for PubMedID 25961066
The authors explore the experiences of residents with respect to informal care related to personal health, including "curbside consultation," self-diagnosis, and self-prescription-self-care practices that run counter to ethical guidelines in medicine.Residents at one medical school completed a written survey regarding their personal health care practices, including their experiences in seeking or providing informal consultation, self-diagnosis, and self-prescribing. The authors obtained frequency data and analyzed responses via cross-tabulation. They used logistic regression models to assess the association of reported informal care practices and potential confounders, such as age, gender, and training program.One hundred and fifty-five residents volunteered (71 % response rate). Most respondents had sought health care formally (70 %), and more had sought informal care in the previous 12 months (80 %). Of those who had pursued informal care, 90 % endorsed having requested a physical exam, a laboratory test, or a medication prescription from an attending, resident, or medical student. Respondents (28 %) commonly endorsed prescribing medication for themselves. Most respondents (90 %) reported being approached for informal care at least once in the previous year, including 84 % who were approached for prescriptions and 22 % who were approached by attending physicians. Main reasons endorsed for informal care seeking related to busy schedules and to cost and confidentiality advantages. Psychiatry residents reported using both formal and informal channels for personal health care, and 31 % acknowledged prescribing medications for themselves.Informal care was a common practice among the residents in this study. Residents reported time constraints as the greatest influence on informal care seeking, rather than reasons found in previous studies related to cost and quality of care, protection of confidentiality, or prevention of embarrassment. The effects of informal care practices involving resident physicians warrant additional study.
View details for DOI 10.1007/s40596-014-0170-3
View details for Web of Science ID 000349304800005
View details for PubMedID 24923781
Ethical controversy surrounds clinical research involving seriously ill participants. While many stakeholders have opinions, the extent to which protocol volunteers themselves see human research as ethically acceptable has not been documented. To address this gap of knowledge, authors sought to assess views of healthy and ill clinical research volunteers regarding the ethical acceptability of human studies involving individuals who are ill or are potentially vulnerable.Surveys and semi-structured interviews were used to query clinical research protocol participants and a comparison group of healthy individuals. A total of 179 respondents participated in this study: 150 in protocols (60 mentally ill, 43 physically ill, and 47 healthy clinical research protocol participants) and 29 healthy individuals not enrolled in protocols. Main outcome measures included responses regarding ethical acceptability of clinical research when it presents significant burdens and risks, involves people with serious mental and physical illness, or enrolls people with other potential vulnerabilities in the research situation.Respondents expressed decreasing levels of acceptance of participation in research that posed burdens of increasing severity. Participation in protocols with possibly life-threatening consequences was perceived as least acceptable (mean = 1.82, sd = 1.29). Research on serious illnesses, including HIV, cancer, schizophrenia, depression, and post-traumatic stress disorder, was seen as ethically acceptable across respondent groups (range of means = [4.0, 4.7]). Mentally ill volunteers expressed levels of ethical acceptability for physical illness research and mental illness research as acceptable and similar, while physically ill volunteers expressed greater ethical acceptability for physical illness research than for mental illness research. Mentally ill, physically ill, and healthy participants expressed neutral to favorable perspectives regarding the ethical acceptability of clinical research participation by potentially vulnerable subpopulations (difference in acceptability perceived by mentally ill - healthy = -0.04, CI [-0.46, 0.39]; physically ill - healthy = -0.13, CI [-0.62, -.36]).Clinical research volunteers and healthy clinical research-"naïve" individuals view studies involving ill people as ethically acceptable, and their responses reflect concern regarding research that poses considerable burdens and risks and research involving vulnerable subpopulations. Physically ill research volunteers may be more willing to see burdensome and risky research as acceptable. Mentally ill research volunteers and healthy individuals expressed similar perspectives in this study, helping to dispel a misconception that those with mental illness should be presumed to hold disparate views.
View details for DOI 10.1016/j.jpsychires.2014.05.007
View details for Web of Science ID 000340318600012
View details for PubMedID 24931849
The authors sought to compare investigators' predictions of clinical research participants' attitudes regarding ethically-important considerations in serious illness research with attitudes expressed by participants ("attunement"), to compare the personal attitudes of investigators and clinical research participants ("alignment"), and to explore the association between views expressed and covariates.The authors queried clinical research participants with either physical or mental illness (n=100) and faculty investigators conducting the clinical research protocols in which these participants were enrolled (n=77). Outcomes included attitudes regarding importance of medical research, attributes of seriously ill people in the research situation, and influences on enrollment decisions by seriously ill people. Generalized estimating equations and linear regression models were used.Investigators underestimated the importance of research about physical illness, mental illness, and healthy people to participants (βPI=0.59, 95% CI [0.36, 0.83]; βMI=0.60, 95% CI [0.27, 0.92]; βH=0.93, 95% CI [0.57, 1.29]). Investigators incorrectly predicted that participants would assess seriously ill people as more vulnerable in the research situation than participants did (β=-0.68, 95% CI [-1.11, -0.25]). Investigators and participants were aligned on the importance of illness research. Participants expressed greater agreement than investigators regarding the influences of ill individuals indicative of will and cognition in their enrollment decisions (β=0.69, 95% CI [0.25, 1.13]).Investigators are attuned to and aligned with research participants in many, but not all, respects. Investigators may bring a protective bias in their predictions of the vulnerabilities of ill volunteers.
View details for DOI 10.1016/j.jpsychires.2014.01.012
View details for PubMedID 24507883
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 Web of Science ID 000325153400007
View details for PubMedID 23959519
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
We propose a unified estimation method for semiparametric linear transformation models under general biased sampling schemes. The new estimator is obtained from a set of counting process-based unbiased estimating equations, developed through introducing a general weighting scheme that offsets the sampling bias. The usual asymptotic properties, including consistency and asymptotic normality, are established under suitable regularity conditions. A closed-form formula is derived for the limiting variance and the plug-in estimator is shown to be consistent. We demonstrate the unified approach through the special cases of left truncation, length-bias, the case-cohort design and variants thereof. Simulation studies and applications to real data sets are presented.
View details for PubMedID 23667280
The lack of reliable human proxies for minor (ie, non-HLA) histocompatibility loci hampers the ability to leverage these factors toward improving transplant outcomes. Despite conflicting reports of the effect of donor-recipient sex mismatch on renal allografts, the association between acute rejection of renal allografts and the development of human alloantibodies to the male H-Y antigen suggested to us that donor-recipient sex mismatch deserved re-evaluation.To evaluate whether the relationships between donor sex and allograft failure differed by recipient sex.We studied recipients of deceased-donor (n = 125,369) and living-donor (n = 63,139) transplants in the United States Renal Data System. Using Cox proportional hazards models stratified by donor type, we estimated the association between donor-recipient sex mismatch and death-censored allograft failure with adjustment for known risk factors, with and without the use of multiple imputation methods to account for potential bias and/or loss of efficiency due to missing data.The advantage afforded by male donor kidneys was more pronounced among male than among female recipients (8% vs 2% relative risk reduction; interaction P < 0.01). This difference is of the order of magnitude of several other risk factors affecting donor selection decisions.Donor-recipient sex mismatch affects renal allograft survival in a direction consistent with immune responses to sexually determined minor histocompatibility antigens. Our study provides a paradigm for clinical detection of markers for minor histocompatibility loci.
View details for DOI 10.1016/j.genm.2012.07.004
View details for Web of Science ID 000310170000005
View details for PubMedID 22906727
Despite the widespread use of computed tomography(CT)-guided percutaneous lung biopsy (PLB) in immunocompetent patients, the diagnostic yield and safety in solid organ transplant (SOT)recipients is unknown. The purpose of this investigation was to determine the test performance of CT-PLB in SOT recipients.We performed a 10-yr single-center, retrospective analysis among heart, lung, kidney, and liver transplant recipients. We included all adult patients who underwent a PLB of a parenchymal lung nodule following their transplantation.Within the study period, 1754 SOTs were performed, of which 45 biopsies met study criteria. Overall, the incidence of PLB in SOT was 3%.PLB established a diagnosis in 24 of 45 cases. The yield of PLB was better for combined biopsy technique (fine-needle aspiration biopsy [FNAB]) and core biopsy than for FNAB alone (odds ratio [OR]: 4.2, 95% confidence interval [CI]: 1.2, 15.6), and for lesions that were malignant (OR: 10.0, 95%CI: 1.8, 75.4) or caused by an invasive fungal infection (OR: 5.0, 95% CI:1.1, 27.9). Complications occurred in 13% (6/45) of patients.CT-guided PLB is a safe modality that provides a moderate yield for diagnosing pulmonary nodules of malignant or fungal etiology in SOT recipients.
View details for DOI 10.1111/j.1399-0012.2011.01582.x
View details for Web of Science ID 000307344400032
View details for PubMedID 23050274
The Centers for Medicare and Medicaid Services (CMS) Medical Evidence Report (form CMS-2728) queries providers about the timing of the patient's first nephrologist consultation before initiation of dialysis. The monitoring of disease-specific goals in the Healthy People 2020 initiative will use information from this question, but the accuracy of the reported information is unknown. We defined a cohort of 80,509 patients aged ?67 years who initiated dialysis between July 2005 and December 2008 with ?2 years of uninterrupted Medicare coverage as their primary payer. The primary referent, determined from claims data, was the first observed outpatient nephrologist consultation; secondary analyses used the earliest nephrology consultation, whether inpatient or outpatient. We used linear regression models to assess the associations among the magnitude of discrepant reporting and patient characteristics and we tested for any temporal trends. When using the earliest recorded outpatient nephrology encounter, agreement between the two sources of ascertainment was 48.2%, and the ? statistic was 0.29 when we categorized the timing of the visit into four periods (never, <6, 6-12, and >12 months). When we dichotomized the timing of first predialysis nephrology care at >12 or ?12 months, accuracy was 70% (?=0.36), but it differed by patient characteristics and declined over time. In conclusion, we found substantial disagreement between information from the CMS Medical Evidence Report and Medicare physician claims on the timing of first predialysis nephrologist care. More-specific instructions may improve reporting and increase the utility of form CMS-2728 for research and public health surveillance.
View details for DOI 10.1681/ASN.2011080871
View details for Web of Science ID 000310256300017
View details for PubMedID 22518002
Impaired kidney function is a risk factor for upper gastrointestinal (GI) bleeding, an event associated with poor outcomes. The burden of upper GI bleeding and its effect on patients with ESRD are not well described. Using data from the US Renal Data System, we quantified the rates of occurrence of and associated 30-day mortality from acute, nonvariceal upper GI bleeding in patients undergoing dialysis; we used medical claims and previously validated algorithms where available. Overall, 948,345 patients contributed 2,296,323 patient-years for study. The occurrence rates for upper GI bleeding were 57 and 328 episodes per 1000 person-years according to stringent and lenient definitions of acute, nonvariceal upper GI bleeding, respectively. Unadjusted occurrence rates remained flat (stringent) or increased (lenient) from 1997 to 2008; after adjustment for sociodemographic characteristics and comorbid conditions, however, we found a significant decline for both definitions (linear approximation, 2.7% and 1.5% per year, respectively; P<0.001). In more recent years, patients had higher hematocrit levels before upper GI bleeding episodes and were more likely to receive blood transfusions during an episode. Overall 30-day mortality was 11.8%, which declined significantly over time (relative declines of 2.3% or 2.8% per year for the stringent and lenient definitions, respectively). In summary, despite declining trends worldwide, crude rates of acute, nonvariceal upper GI bleeding among patients undergoing dialysis have not decreased in the past 10 years. Although 30-day mortality related to upper GI bleeding declined, perhaps reflecting improvements in medical care, the burden on the ESRD population remains substantial.
View details for DOI 10.1681/ASN.2011070658
View details for Web of Science ID 000301206900017
View details for PubMedID 22266666
Transplanted nephron mass is an important determinant of long-term allograft survival, but accurate assessment before organ retrieval is challenging. Newer radiologic imaging techniques allow for better determination of total kidney and cortical volumes.Using volume measurements reconstructed from magnetic resonance or computed tomography imaging from living donor candidates, we characterized total kidney (n=312) and cortical volumes (n=236) according to sex, age, weight, height, body mass index (BMI), and body surface area (BSA).The mean cortical volume was 204 mL (range 105-355 mL) with no significant differences between left and right cortical volumes. The degree to which existing anthropomorphic surrogates predict nephron mass was quantified, and a diligent attempt was made to derive a better surrogate model for nephron mass. Cortical volumes were strongly associated with sex and BSA, but not with weight, height, or BMI. Four prediction models for cortical volume constructed using combinations of age, sex, race, weight, and height were compared with models including either BSA or BMI.Among existing surrogate measures, BSA was superior to BMI in predicting renal cortical volume. We were able to construct a statistically superior proxy for cortical volume, but whether relevant improvements in predictive accuracy could be gained needs further evaluation in a larger population.
View details for DOI 10.1097/TP.0b013e31823705ef
View details for Web of Science ID 000298149200012
View details for PubMedID 22011765
Identifying potential modifiable risk factors to reduce the incidence of vascular access thrombosis in hemodialysis could reduce considerable morbidity and health care costs. We analyzed data from a subset of 1426 HEMO study subjects to determine whether more frequent intradialytic hypotension and/or lower predialysis systolic BP were associated with higher rates of vascular access thrombosis. Our primary outcome measure was episodes of vascular access thrombosis occurring within a given 6-month period during HEMO study follow-up. There were 2005 total episodes of vascular access thrombosis during a median 3.1 years of follow-up. The relative rate of thrombosis of native arteriovenous fistulas for the highest quartile of intradialytic hypotension was approximately twice that of the lowest quartile, independent of predialysis systolic BP and other covariates. There was no significant association of intradialytic hypotension with prosthetic arteriovenous graft thrombosis after multivariable adjustment. Higher predialysis systolic BP was associated with a lower rate of fistula and graft thrombosis, independent of intradialytic hypotension and other covariates. In conclusion, more frequent episodes of intradialytic hypotension and lower predialysis systolic BP associate with increased rates of vascular access thrombosis. These results underscore the importance of including vascular access patency in future studies of BP management in hemodialysis.
View details for DOI 10.1681/ASN.2010101119
View details for Web of Science ID 000294083300019
View details for PubMedID 21803971
Using statewide data, we evaluated whether the changing incidence of penile anomalies and hypospadias is reflected in the diverse California population of newborn males over the past 20 years.Discharge data from all California hospitals, prepared by the OSHPD (Sacramento, CA) was reviewed for the years 1985-2006 for male infant births with an ICD-9 code (752.6) for hypospadias, epispadias or other penile anomalies. Trends were examined by Generalized Estimation Equations for Poisson regression.From 1985 to 2006, the birth incidence of newborn penile anomalies increased in California from 47 to 57 cases per 10,000 newborn discharges, yet the trend for hypospadias alone appears stable from 1997. The rates for penile anomalies in newborns increased 1.4% annually (p < 0.001). All racial/ethnic groups analyzed showed this increase (p < 0.001 for each). During the study period there was a 2% increase per year in plural births (p < 0.001). Interestingly, the rate of change in penile anomaly incidence was greater in males of plural births compared to their singleton cohorts (2% vs 1% annually) (p < 0.001). The birth incidence of cleft palate, another congenital anomaly known to be stable over time, remained unchanged over this period.From 1985 to 2006 in California the incidence of penile anomalies increased in a statistically significant manner, but the incidence of hypospadias appears stable for the last decade. Our data support the notion that different racial/ethnic groups have distinct incidences of penile anomaly formation and that an association with plural births appears to be present.
View details for DOI 10.1016/j.jpurol.2011.03.006
View details for Web of Science ID 000292666200014
View details for PubMedID 21527236
When evaluating clinical characteristics and outcomes in patients on hemodialysis, the prevalence and severity of comorbidity may change over time. Knowing whether updated assessments of comorbidity enhance predictive power will assist the design of future studies. We conducted a secondary data analysis of 1846 prevalent hemodialysis patients from 15 US clinical centers enrolled in the HEMO study. Our primary explanatory variable was the Index of Coexistent Diseases score, which aggregates comorbidities, as a time-constant and time-varying covariate. Our outcomes of interest were all-cause mortality, time to first hospitalization, and total hospitalizations. We used Cox proportional hazards regression. Accounting for an updated comorbidity assessment over time yielded a more robust association with mortality than accounting for baseline comorbidity alone. The variation explained by time-varying comorbidity assessments on time to death was greater than age, baseline serum albumin, diabetes, or any other covariates. There was a less pronounced advantage of updated comorbidity assessments on determining time to hospitalization. Updated assessments of comorbidity significantly strengthen the ability to predict death in patients on hemodialysis. Future studies in dialysis should invest the necessary resources to include repeated assessments of comorbidity.
View details for DOI 10.1111/j.1542-4758.2010.00468.x
View details for Web of Science ID 000283174100021
View details for PubMedID 20955281