Physical Sciences and Mathematics Commons^™

Effects Of Cost Sharing On Seeking Care For Serious And Minor Symptoms. Results Of A Randomized Controlled Trial, Martin Shapiro, John Ware, Cathy Sherbourne

Martin Shapiro

To estimate the effect of cost sharing on seeking care for serious and minor symptoms, we analyzed data for 3539 persons aged 17 to 61 from the Rand Health Insurance Experiment. Participants were randomly assigned to a free-care group or to insurance plans requiring them to pay part of the costs (cost-sharing group). Annual surveys were administered to determine if participants had serious and minor symptoms during the preceding month and whether they saw a physician. Serious symptoms were judged by a panel of physicians to warrant care in most instances; minor symptoms were judged neither to be severe nor …

An Omnibus Nonparametric Test Of Equality In Distribution For Unknown Functions, Alexander Luedtke, Marco Carone, Mark Van Der Laan

Alex Luedtke

We present a novel family of nonparametric omnibus tests of the hypothesis that two unknown but estimable functions are equal in distribution when applied to the observed data structure. We developed these tests, which represent a generalization of the maximum mean discrepancy tests described in Gretton et al. [2006], using recent developments from the higher-order pathwise differentiability literature. Despite their complex derivation, the associated test statistics can be expressed rather simply as U-statistics. We study the asymptotic behavior of the proposed tests under the null hypothesis and under both fixed and local alternatives. We provide examples to which our tests …

Neoadjuvant Or Adjuvant Therapy For Resectable Esophageal Cancer: A Systematic Review And Meta-Analysis, Richard Malthaner, Rebecca Wong, R. Rumble, Lisa Zuraw

Richard A. Malthaner

Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis.

Methods: A systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced.MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the …

Neoadjuvant Or Adjuvant Therapy For Resectable Esophageal Cancer: A Clinical Practice Guideline, Richard Malthaner, Rebecca Wong, R. Rumble, Lisa Zuraw

Richard A. Malthaner

Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. A clinical practice guideline was developed based on a systematic review investigating neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer. Methods: A systematic review with meta-analysis was developed and clinical recommendations were drafted. External review of the practice guideline report by practitioners in Ontario, Canada was obtained through a mailed survey, and incorporated. Final approval of the practice guideline was obtained from the Practice Guidelines Coordinating Committee. Results: The systematic review …

Neoadjuvant Or Adjuvant Therapy For Resectable Esophageal Cancer: A Systematic Review And Meta-Analysis, Richard Malthaner, Rebecca Wong, R. Rumble, Lisa Zuraw

Richard A. Malthaner

Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis.

Methods: A systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced.MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the …

Neoadjuvant Or Adjuvant Therapy For Resectable Esophageal Cancer: A Clinical Practice Guideline, Richard Malthaner, Rebecca Wong, R. Rumble, Lisa Zuraw

Richard A. Malthaner

Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. A clinical practice guideline was developed based on a systematic review investigating neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer.

Methods: A systematic review with meta-analysis was developed and clinical recommendations were drafted. External review of the practice guideline report by practitioners in Ontario, Canada was obtained through a mailed survey, and incorporated. Final approval of the practice guideline was obtained from the Practice Guidelines Coordinating Committee.

Results: The systematic review …

Nonparametric Methods For Doubly Robust Estimation Of Continuous Treatment Effects, Edward Kennedy, Zongming Ma, Matthew Mchugh, Dylan Small

Edward H. Kennedy

Continuous treatments (e.g., doses) arise often in practice, but available causal effect estimators require either parametric models for the effect curve or else consistent estimation of a single nuisance function. We propose a novel doubly robust kernel smoothing approach, which requires only mild smoothness assumptions on the effect curve and allows for misspecification of either the treatment density or outcome regression. We derive asymptotic properties and also discuss an approach for data-driven bandwidth selection. The methods are illustrated via simulation and in a study of the effect of nurse staffing on hospital readmissions penalties.

Semiparametric Causal Inference In Matched Cohort Studies, Edward Kennedy, Arvid Sjolander, Dylan Small

Edward H. Kennedy

Odds ratios can be estimated in case-control studies using standard logistic regression, ignoring the outcome-dependent sampling. In this paper we discuss an analogous result for treatment effects on the treated in matched cohort studies. Specifically, in studies where a sample of treated subjects is observed along with a separate sample of possibly matched controls, we show that efficient and doubly robust estimators of effects on the treated are computationally equivalent to standard estimators, which ignore the matching and exposure-based sampling. This is not the case for general average effects. We also show that matched cohort studies are often more efficient …

Leukoaraiosis Predicts Poor 90-Day Outcome After Acute Large Cerebral Artery Occlusion, Nils Henninger, Eugene Lin, Stephen Baker, Ajay Wakhloo, Deepak Takhtani, Majaz Moonis

Nils Henninger

BACKGROUND: To date limited information regarding outcome-modifying factors in patients with acute intracranial large artery occlusion (ILAO) in the anterior circulation is available. Leukoaraiosis (LA) is a common finding among patients with ischemic stroke and has been associated with poor post-stroke outcomes but its association with ILAO remains poorly characterized. This study sought to clarify the contribution of baseline LA and other common risk factors to 90-day outcome (modified Rankin Scale, mRS) after stroke due to acute anterior circulation ILAO. METHODS: We retrospectively analyzed 1,153 consecutive patients with imaging-confirmed ischemic stroke during a 4-year period (2007-2010) at a single academic …

Surrogate Markers For Time-Varying Treatments And Outcomes, Jesse Hsu, Edward Kennedy, Jason Roy, Alisa Stephens-Shields, Dylan Small, Marshall Joffe

Edward H. Kennedy

A surrogate marker is a variable commonly used in clinical trials to guide treatment decisions when the outcome of ultimate interest is not available. A good surrogate marker is one where the treatment effect on the surrogate is a strong predictor of the effect of treatment on the outcome. We review the situation when there is one treatment delivered at baseline, one surrogate measured at one later time point, and one ultimate outcome of interest and discuss new issues arising when variables are time-varying. Most of the literature on surrogate markers has only considered simple settings with one treatment, one …

Optimal Restricted Estimation For More Efficient Longitudinal Causal Inference, Edward Kennedy, Marshall Joffe, Dylan Small

Edward H. Kennedy

Efficient semiparametric estimation of longitudinal causal effects is often analytically or computationally intractable. We propose a novel restricted estimation approach for increasing efficiency, which can be used with other techniques, is straightforward to implement, and requires no additional modeling assumptions.

Trends In The Prevalence And Mortality Of Cognitive Impairment In The United States: Is There Evidence Of A Compression Of Cognitive Morbidity, Kenneth Langa, Eric Larson, Jason Karlawish, David Cutler, Mohammed Kabeto, Scott Kim, Allison Rosen

Jason Karlawish

BACKGROUND: Recent medical, demographic, and social trends might have had an important impact on the cognitive health of older adults. To assess the impact of these multiple trends, we compared the prevalence and 2-year mortality of cognitive impairment (CI) consistent with dementia in the United States in 1993 to 1995 and 2002 to 2004. METHODS: We used data from the Health and Retirement Study (HRS), a nationally representative population-based longitudinal survey of U.S. adults. Individuals aged 70 years or older from the 1993 (N = 7,406) and 2002 (N = 7,104) waves of the HRS were included. CI was determined …

Pubertal And Adult Leydig Cell Function In Mullerian Inhibiting Substance-Deficient Mice, Xiufeng Wu, Ramamani Arumugam, Stephen Baker, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) causes Mullerian duct regression during sexual differentiation and regulates postnatal Leydig cell development. MIS knockout (MIS-KO) mice with targeted deletions of MIS develop Leydig cell hyperplasia, but their circulating androgen concentrations are reportedly unaltered. We compared reproductive hormone profiles, androgen biosynthesis, and the expression of key steroidogenic and metabolic enzymes in MIS-KO and wild-type (WT) mice at puberty (36 d) and sexual maturity (60 d). In pubertal animals, basal testosterone and LH concentrations in plasma were lower in MIS-KO than WT mice, whereas human chorionic gonadotropin-stimulated testosterone concentrations were similar. In adults, basal LH, and both …

Targeted Maximum Likelihood Estimation Of Natural Direct Effect, Wenjing Zheng, Mark Van Der Laan

Wenjing Zheng

In many causal inference problems, one is interested in the direct causal effect of an exposure on an outcome of interest that is not mediated by certain intermediate variables. Robins and Greenland (1992) and Pearl (2000) formalized the definition of two types of direct effects (natural and controlled) under the counterfactual framework. Since then, identifiability conditions for these effects have been studied extensively. By contrast, considerably fewer efforts have been invested in the estimation problem of the natural direct effect. In this article, we propose a semiparametric efficient, multiply robust estimator for the natural direct effect of a binary treatment …

Managed Care, Hospice Use, Site Of Death, And Medical Expenditures In The Last Year Of Life, Ezekiel Emanuel, Arlene Ash, Wei Yu, Gail Gazelle, Norman Levinsky, Olga Saynina, Mark Mcclellan, Mark Moskowitz

wei yu

BACKGROUND: We examined deaths of Medicare beneficiaries in Massachusetts and California to evaluate the effect of managed care on the use of hospice and site of death and to determine how hospice affects the expenditures for the last year of life.

METHODS: Medicare data for beneficiaries in Massachusetts (n = 37 933) and California (n = 27 685) who died in 1996 were merged with each state's death certificate files to determine site and cause of death. Expenditure data were Health Care Financing Administration payments and were divided into 30-day periods from the date of death back 12 months.

RESULTS: …

Estimating The Effect Of A Community-Based Intervention With Two Communities, Mark Van Der Laan, Maya Petersen, Wenjing Zheng

Wenjing Zheng

Due to the need to evaluate the effectiveness of community-based programs in practice, there is substantial interest in methods to estimate the causal effects of community-level treatments or exposures on individual level outcomes. The challenge one is confronted with is that different communities have different environmental factors affecting the individual outcomes, and all individuals in a community share the same environment and intervention. In practice, data are often available from only a small number of communities, making it difficult if not impossible to adjust for these environmental confounders. In this paper we consider an extreme version of this dilemma, in …

Evaluation Of Student Outcomes In Online Vs. Campus Biostatistics Education In A Graduate School Of Public Health, John Mcgready, Ron Brookmeyer

Ron Brookmeyer

Objective: To compare student outcomes between concurrent online and on-campus sections of an introductory biostatistics course offered at a U.S. school of public health in 2005. Methods: Enrolled students (95 online, 92 on-campus) were invited to participate in a confidential online survey. The course outcomes were compared between the two sections adjusting for differences in student characteristics. Results: Seventy-two online (76%) and 66 (72%) on-campus enrollees participated. Unadjusted final exam scores for the online and on-campus sections were respectively 85.1 and 86.3 (p = 0.50) in term 1, and 87.7 and 86.9 (p=0.58) in term 2. After adjustment for student …

Estimation Of Hiv Incidence Using Multiple Biomakers, Ron Brookmeyer, Jacob Konikoff, Oliver Laeyendecker, Susan Eshleman

Ron Brookmeyer

The incidence of human immunodeficiency virus (HIV) is the rate at which new HIV infections occur in populations. The development of accurate, practical, and cost-effective approaches to estimation of HIV incidence is a priority among researchers in HIV surveillance because of limitations with existing methods. In this paper, we develop methods for estimating HIV incidence rates using multiple biomarkers in biological samples collected from a cross-sectional survey. An advantage of the method is that it does not require longitudinal follow-up of individuals. We use assays for BED, avidity, viral load, and CD4 cell count data from clade B samples collected …

Instrumental Variable Analyses: Exploiting Natural Randomness To Understand Causal Mechanisms, Theodore Iwashyna, Edward Kennedy

Edward H. Kennedy

Instrumental variable analysis is a technique commonly used in the social sciences to provide evidence that a treatment causes an outcome, as contrasted with evidence that a treatment is merely associated with differences in an outcome. To extract such strong evidence from observational data, instrumental variable analysis exploits situations where some degree of randomness affects how patients are selected for a treatment. An instrumental variable is a characteristic of the world that leads some people to be more likely to get the specific treatment we want to study but does not otherwise change thosepatients’ outcomes. This seminar explains, in nonmathematical …

Prediction Of Radiation Pneumonitis By Dose-Volume Histogram Parameters In Lung Cancer--A Systematic Review, George Rodrigues, Michael Lock, David D'Souza, Edward Yu, Jake Van Dyk

Michael Lock

BACKGROUND AND PURPOSE: To perform a systematic review of the predictive ability of various dose-volume histogram (DVH) parameters (V(dose), mean lung dose (MLD), and normal tissue complication probability (NTCP)) in the incidence of radiation pneumonitis (RP) caused by external-beam radiation therapy.

METHODS AND MATERIALS: Studies assessing the relationship between CT-based DVH reduction parameters and RP rate in radically treated lung cancer were eligible for the review. Synonyms for RP, lung cancer, DVH and its associated parameters (NTCP, V(20), V(30), MLD) were combined in a search strategy involving electronic databases, secondary reference searching, and consultation with experts. Individual or group data …

Technology Assessment Of Automated Atlas Based Segmentation In Prostate Bed Contouring, Jeremiah Hwee, Alexander Louie, Stewart Gaede, Glenn Bauman, David D'Souza, Tracy Sexton, Michael Lock, Belal Ahmad, George Rodrigues

Michael Lock

BACKGROUND: Prostate bed (PB) contouring is time consuming and associated with inter-observer variability. We evaluated an automated atlas-based segmentation (AABS) engine in its potential to reduce contouring time and inter-observer variability.

METHODS: An atlas builder (AB) manually contoured the prostate bed, rectum, left femoral head (LFH), right femoral head (RFH), bladder, and penile bulb of 75 post-prostatectomy cases to create an atlas according to the recent RTOG guidelines. 5 other Radiation Oncologists (RO) and the AABS contoured 5 new cases. A STAPLE contour for each of the 5 patients was generated. All contours were anonymized and sent back to the …

Racial And Ethnic Differences In Hospice Use Among Patients With Heart Failure, Jane Givens, Jennifer Tjia, Chao Zhou, Ezekiel Emanuel, Arlene Ash

Jennifer Tjia

BACKGROUND: Heart failure is the leading noncancer diagnosis for patients in hospice care and the leading cause of hospitalization among Medicare beneficiaries. Racial and ethnic differences in hospice patients are well documented for patients with cancer but poorly described for those with heart failure.

METHODS: On the basis of a national sample of 98 258 Medicare beneficiaries 66 years and older on January 1, 2001, with a diagnosis of heart failure who had at least 1 physician or hospital encounter and who were not enrolled in hospice care between January 1 and December 31, 2000, we determined the effect of …

Disparities In Combination Drug Therapy Use In Older Adults With Coronary Heart Disease: A Cross-Sectional Time-Series In A Nationally Representative Us Sample, Jennifer Tjia, Becky Briesacher, Dawei Xie, Jason Fu, Robert Goldberg

Jennifer Tjia

BACKGROUND: Despite evidence of effective combination drug therapy for secondary prevention of coronary heart disease (CHD), older adults with this condition remain undertreated.

OBJECTIVE: To describe time trends (1992-2003) in the adoption of combination cardiac drug therapies (beta-blockers [beta-adrenoceptor antagonists], ACE inhibitors or angiotensin II type 1 receptor antagonists [angiotensin receptor blockers; ARBs], and lipid-lowering agents) among older adults in the US with CHD and to identify factors associated with not using combination therapy.

METHODS: The study took the form of a cross-sectional time-series. The study population consisted of a nationally representative sample of adults aged >or=65 years with CHD …

Trends And Outcomes Associated With Angiotensin-Converting Enzyme Inhibitors, Chyke Doubeni, Carol Bigelow, Darleen Lessard, Frederick Spencer, Jorge Yarzebski, Joel Gore, Jerry Gurwitz, Robert Goldberg

Chyke A. Doubeni

BACKGROUND: Limited recent data are available describing the patterns of use of angiotensin converting enzyme inhibitor (ACEI) therapy in patients with acute myocardial infarction (AMI), particularly from the more generalizable population-based setting. The purpose of this study was to examine trends in the receipt of ACEIs and associated short-term outcomes in patients hospitalized with AMI in a large Northeastern community.

METHODS: We conducted a community-wide study of 7991 patients hospitalized with AMI in all metropolitan Worcester, Massachusetts, medical centers during 8 annual periods between 1990 and 2003.

RESULTS: Among all patients, 44% received ACEI therapy during their acute hospitalization. There …

Treatment Practices And Outcomes Of Patients With Established Peripheral Arterial Disease Hospitalized With Acute Myocardial Infarction In A Community Setting, Frederick Spencer, Darleen Lessard, Chyke Doubeni, Jorge Yarzebski, Joel Gore, Robert Goldberg

Chyke A. Doubeni

BACKGROUND: There are little contemporary data available describing the hospital and long-term outcomes of patients with peripheral arterial disease (PAD) who are hospitalized with acute myocardial infarction (AMI). The objectives of our population-based study were to examine the hospital and long-term outcomes, as well as the use of different treatment practices, among patients with established PAD who were hospitalized with AMI. METHODS: The study sample consisted of 4480 patients hospitalized with AMI at all Worcester, Mass, medical centers in 4 alternate years between 1997 and 2003. RESULTS: Among the metropolitan Worcester residents hospitalized with AMI, 13.5% had a history of …

Targeted Maximum Likelihood Estimation Of Natural Direct Effects, Wenjing Zheng, Mark Van Der Laan

Wenjing Zheng

In many causal inference problems, one is interested in the direct causal effect of an exposure on an outcome of interest that is not mediated by certain intermediate variables. Robins and Greenland (1992) and Pearl (2001) formalized the definition of two types of direct effects (natural and controlled) under the counterfactual framework. The efficient scores (under a nonparametric model) for the various natural effect parameters and their general robustness conditions, as well as an estimating equation based estimator using the efficient score, are provided in Tchetgen Tchetgen and Shpitser (2011b). In this article, we apply the targeted maximum likelihood framework …

Adjusting Medicare Capitation Payments Using Prior Hospitalization Data, Arlene Ash, Frank Porell, Leonard Gruenberg, Eric Sawitz, Alexa Beiser

Frank Porell

The diagnostic cost group approach to a reimbursement model for health maintenance organizations is presented. Diagnostic information about previous hospitalizations is used to create empirically determined risk groups, using only diagnoses involving little or no discretion in the decision to hospitalize. Diagnostic cost group and other models (including Medicare's current formula and other prior-use models) are tested for their ability to predict future costs, using R2 values and new measures of predictive performance. The diagnostic cost group models perform relatively well with respect to a range of criteria, including administrative feasibility, resistance to provider manipulation, and statistical accuracy.

When Is Informed Consent Required In Cluster Randomized Trials In Health Research?, Andrew Mcrae, Charles Weijer, Ariella Binik, Jeremy Grimshaw, Robert Boruch, Jamie Brehaut, Allan Donner, Martin P Eccles, Raphael Saginur, Angela White, Monica Taljaard

Charles Weijer

This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, we set out six areas of inquiry that must be addressed if the cluster trial is to be set on a firm ethical foundation. This paper addresses the second of the questions posed, namely, from whom, when, and how must informed consent be obtained in CRTs in health research? The ethical principle of respect for persons implies that researchers are generally obligated to obtain the informed consent of research subjects. Aspects of CRT …

Who Is The Research Subject In Cluster Randomized Trials In Health Research?, Andrew Mcrae, Charles Weijer, Ariella Binik, Angela White, Jeremy Grimshaw, Robert Boruch, Jamie Brehaut, Allan Donner, Martin Eccles, Raphael Saginur, Merrick Zwarenstein, Monica Taljaard

Charles Weijer

This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, we set out six areas of inquiry that must be addressed if the CRT is to be set on a firm ethical foundation. This paper addresses the first of the questions posed, namely, who is the research subject in a CRT in health research? The identification of human research subjects is logically prior to the application of protections as set out in research ethics and regulation. Aspects of CRT design, including the fact …

30-Year Trends In Heart Failure In Patients Hospitalized With Acute Myocardial Infarction, David Mcmanus, Marcello Chinali, Jane Saczynski, Joel Gore, Jorge Yarzebski, Frederick Spencer, Darleen Lessard, Robert Goldberg

Jorge L. Yarzebski

Despite significant advances in its treatment, acute myocardial infarction (AMI) remains an important cause of heart failure (HF). Contemporary data remain lacking, however, describing long-term trends in incidence rates, demographic and clinical profiles, and outcomes of patients who develop HF as a complication of AMI. Our study sample consisted of 11,061 residents of the Worcester (Massachusetts) metropolitan area hospitalized with AMI at all greater Worcester hospitals in 15 annual study periods from 1975 to 2005. Overall, 32.4% of patients (n = 3,582) with AMI developed new-onset HF during their acute hospitalization. Patients who developed HF were generally older, more likely …