Scott Zeger

• Johns Hopkins Bloomberg School of Public Health

Estimating a patient’s disease trajectory as defined by clinical measures is an essential task in medicine. Given multiple biomarkers, there is a practical choice of whether to estimate the joint distribution of all biomarkers in a single model or to model the univariate marginal distribution of each marker separately ignoring the covariance struct...

Background Pneumococcal conjugate vaccines (PCVs) introduced in childhood national immunization programs lowered vaccine-type invasive pneumococcal disease (IPD), but replacement with non-vaccine-types persisted throughout the PCV10/13 follow-up period. We assessed PCV10/13 impact on pneumococcal meningitis incidence globally. Methods The number o...

Objectives CD209L and its homologous protein CD209 act as alternative entry receptors for the SARS‐CoV‐2 virus and are highly expressed in the virally targeted tissues. We tested for the presence and clinical features of autoantibodies targeting these receptors and compared these with autoantibodies known to be associated with COVID‐19. Methods Us...

Background Critically ill hospitalized patients with COVID-19 have greater antibody titers than those with mild to moderate illness, but their association with recovery or death from COVID-19 has not been characterized. Methods In a cohort study of 178 COVID-19 patients, 73 non-hospitalized and 105 hospitalized patients, mucosal swabs and plasma s...

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. Persistence of mutated NPM1 or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoietic cell transplant (a...

Routine genetic profiling of acute myeloid leukemia (AML) at initial diagnosis has allowed subgroup specific prognostication, drug development, and clinical management strategies. The optimal approach for treatment response assessment for AML subgroups has not yet however been determined. A nationwide cohort of 257 adult patients in first remission...

This cohort study examines racial and ethnic differences in varieties of advanced retinal imaging received among patients with diabetes at a single tertiary care institution.

Objectives Systemic sclerosis (SSc) is heterogeneous in its clinical presentation. Common manifestations cluster together, defining unique subgroups. This investigation aims to characterize gastrointestinal (GI) phenotypes and determine whether they can be distinguished by temporal progression. Methods We examined a well-established SSc patient co...

Objective To understand if autoantibodies account for racial variation in disease severity, we compared autoantibody distribution and associated phenotype between self-identified black and white systemic sclerosis (SSc) patients. Methods 803 black and 2178 white SSc patients had systematic testing for autoantibodies using Euroimmun (centromere (AC...

Dynamic prediction of causal effects under different treatment regimens is an essential problem in precision medicine. It is challenging because the actual mechanisms of treatment assignment and effects are unknown in observational studies. We propose a multivariate generalized linear mixed-effects model and a Bayesian g-computation algorithm to ca...

Background Systemic sclerosis (SSc) is very heterogenous in its clinical presentation. Common manifestations cluster together defining subgroups of disease. Objectives The goal of this investigation is to characterize and define gastrointestinal (GI) phenotypes. Methods We examine a well-established SSc patient cohort, with a modified Medsger GI...

The preclinical stage of many neurodegenerative diseases can span decades before symptoms become apparent. Understanding the sequence of preclinical biomarker changes provides a critical opportunity for early diagnosis and effective intervention prior to significant loss of patients' brain functions. The main challenge to early detection lies in th...

Background: A significant number of women die from pregnancy and childbirth complications globally, particularly in low- and middle-income countries (LMICs). Receiving at least four antenatal care (ANC) visits may be important in reducing maternal and perinatal deaths. This study investigates factors associated with attending ≥ 4 ANC visits in Sarl...

This cohort study investigates the association of neighborhood-level social determinants of health with lapses in diabetic retinopathy care by race and ethnicity.

Background Standard continuous glucose monitoring (CGM) metrics: mean glucose, standard deviation, coefficient of variation, and time in range, fail to capture the shape of variability in the CGM time series. This information could facilitate improved diabetes management. Methods We analyzed CGM data from 141 adults with type 2 diabetes in the Hyp...

Introduction: Understanding the association between low glucose readings (hypoglycemia) detected by CGM and hypoglycemic symptoms experienced by people with diabetes is critically important for diabetes management. However, tools that capture hypoglycemic symptoms in real-time are lacking. Objective: Implement a real-time hypoglycemia symptom repor...

Introduction: Understanding factors that influence glycemic response to meals can inform strategies for diabetes management. Continuous glucose monitoring (CGM) facilitates analyzing glycemic regulation, but concurrent meal timing, required to study meal-induced excursions, is rarely collected. Objective: We develop a framework for extracting meal-...

INTRODUCTION In addition to the accumulation of amyloid plaques and neurofibrillary tangles, the presence of excess neural activity is a pathological hallmark of Alzheimer's disease (AD) and a prognostic indicator for progression of AD pathology and clinical/cognitive worsening in mild cognitive impairment due to Alzheimer's disease (MCI due to AD)...

Introduction: Detection of measurable residual disease (MRD) in AML patients during remission is associated with adverse clinical outcomes after allogeneic hematopoietic cell transplant (alloHCT), including recent strong evidence from our group regarding residual NPM1 and/or FLT3-ITD variants (PMID: 36881031). Large studies examining the significan...

Introduction: Detection of measurable residual disease (MRD) prior to allogeneic hematopoietic cell transplant (alloHCT) in patients with acute myeloid leukemia (AML) in remission is associated with increased relapse and inferior survival after transplant. We recently reported that next-generation sequencing (NGS) detection of mutated NPM1 or FLT3-...

Introduction: Next-generation sequencing (NGS) represents a promising modality for measurable residual disease (MRD) testing in patients with acute myeloid leukemia (AML), but systematic efforts are required to define the appropriate targets, test characteristics, and clinical implications. We recently reported that detection of persistent NPM1 or...

Objectives We examined whether an array of scleroderma autoantibodies associates with risk of cancer and could be useful tools for risk stratification. Methods Scleroderma cancer cases and scleroderma controls without cancer from the Johns Hopkins Scleroderma Center and the University of Pittsburgh Scleroderma Center were studied. Sera were assaye...

The first edition of Analysis for Longitudinal Data has become a classic. Describing the statistical models and methods for the analysis of longitudinal data, it covers both the underlying statistical theory of each method, and its application to a range of examples from the agricultural and biomedical sciences. The main topics discussed are design...

Critically ill people with COVID-19 have greater antibody titers than those with mild to moderate illness, but their association with recovery or death from COVID-19 has not been characterized. In 178 COVID-19 patients, 73 non-hospitalized and 105 hospitalized patients, mucosal swabs and plasma samples were collected at hospital enrollment and up t...

Background Despite growing interest in monitoring improvements in quality of care, data on service quality in low-income and middle-income countries (LMICs) is limited. While health systems researchers have hypothesized the relationship between facility readiness and provision of care, there have been few attempts to quantify this relationship in L...

Objectives To assess the association between maternal characteristics, adverse birth outcomes (small-for-gestational-age (SGA) and/or preterm) and neonatal mortality in rural Nepal. Design This is a secondary observational analysis to identify risk factors for neonatal mortality, using data from a randomised trial to assess the impact of newborn m...

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. The persistence of mutated NPM1 or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoetic cell transplant...

Introduction: Risk factors for hypoglycemia in very old adults with type 2 diabetes are uncharacterized. CGM identifies biochemical hypoglycemia but is not widely used in type 2 diabetes. Methods: We conducted a cross-sectional analysis of 282 adults with type 2 diabetes (mean age 84 years; 32% using insulin or sulfonylureas [SUs]) in the Atheroscl...

Purpose Few have studied the relationship between employment and health in the Medicaid population. The purpose of this study is to estimate the impact of job loss on the mental health of working Medicaid beneficiaries. Design/methodology/approach This study conducted a post hoc analysis of 1,538 adult Medicaid beneficiaries enrolled in a prospect...

Verbal autopsies (VAs) are extensively used to determine cause of death (COD) in many low- and middle-income countries. However, COD determination from VA can be inaccurate. Computer coded verbal autopsy (CCVA) algorithms used for this task are imperfect and misclassify COD for a large proportion of deaths. If not accounted for, this misclassificat...

The Countrywide Mortality Surveillance for Action platform is collecting verbal autopsy (VA) records from a nationally representative sample in Mozambique. These records are used to estimate the national and subnational cause-specific mortality fractions (CSMFs) for children (1–59 months) and neonates (1–28 days). Cross-tabulation of VA-based cause...

Sub-Saharan Africa lacks timely, reliable, and accurate national data on mortality and causes of death (CODs). In 2018 Mozambique launched a sample registration system (Countrywide Mortality Surveillance for Action [COMSA]-Mozambique), which collects continuous birth, death, and COD data from 700 randomly selected clusters, a nationally representat...

Importance: Preventing relapse for adults with acute myeloid leukemia (AML) in first remission is the most common indication for allogeneic hematopoietic cell transplant. The presence of AML measurable residual disease (MRD) has been associated with higher relapse rates, but testing is not standardized. Objective: To determine whether DNA sequen...

Dynamic prediction of causal effects under different treatment regimes conditional on an individual's characteristics and longitudinal history is an essential problem in precision medicine. This is challenging in practice because outcomes and treatment assignment mechanisms are unknown in observational studies, an individual's treatment efficacy is...

Objective: To develop a novel methodology to identify lapses in diabetic retinopathy care in electronic health records (EHRs) and evaluate health disparities by race and ethnicity. Design: Retrospective cohort study. Subjects: Adult patients with diabetes mellitus who were evaluated at the Wilmer Eye Institute from January 1, 2013 to April 2,...

Introduction: Continuous glucose monitoring (CGM) devices record blood glucose every few minutes over a maximum 2-week wear period. Despite the richness of these data, existing first and second moment statistics (such as mean glucose) fail to capture the “shape” of variation in the CGM time-series. Objective: We developed novel, reproducible CGM sh...

As clinicians are faced with a deluge of clinical data, data science can play an important role in highlighting key features driving patient outcomes, aiding in the development of new clinical hypotheses. Insight derived from machine learning can serve as a clinical support tool by connecting care providers with reliable results from big data analy...

Background Despite growing interest in monitoring improvements in quality of care, data on service quality in low-income and middle-income countries (LMICs) is limited. While health systems researchers have hypothesized the relationship between facility readiness and provision of care, there have been few attempts to quantify this relationship in L...

Background: Prior observation has shown differences in COVID-19 hospitalization risk between SARS-CoV-2 variants, but limited information describes hospitalization outcomes. Methods: Inpatients with COVID-19 at five hospitals in the eastern United States were included if they had hypoxia, tachypnea, tachycardia, or fever, and SARS-CoV-2 variant...

Background The within-person and between-sensor variability of metrics from different interstitial continuous glucose monitoring (CGM) sensors in adults with type 2 diabetes not taking insulin is unclear. Methods Secondary analysis of data from 172 participants from the Hyperglycemic Profiles in Obstructive Sleep Apnea randomized clinical trial. P...

Objectives: Ectopic calcification (calcinosis) is a common complication of systemic sclerosis, but a subset of systemic sclerosis patients has a heavy burden of calcinosis. We examined whether there are unique risk factors for a heavy burden of calcinosis, as compared with a light burden or no calcinosis. Methods: We reviewed the medical records...

Objective Preterm birth can have short-term and long-term complications for a child. Socioeconomic factors and pregnancy-related morbidities may be important to predict and prevent preterm births in low-resource settings. The objective of our study was to find prevalence and predictors of spontaneous preterm birth in rural Nepal. Design This is a...

Severe COVID-19 is characterized by a prothrombotic state associated with thrombocytopenia, with microvascular thrombosis being almost invariably present in the lung and other organs at postmortem examination. We evaluated the presence of antibodies to platelet factor 4 (PF4)-polyanion complexes using a clinically validated immunoassay in 100 hospi...

Purpose/Objective(s) Stereotactic body radiotherapy (SBRT) holds an expanding role in the treatment of bone metastases. As compared to conventional external beam radiation (cEBRT), SBRT may be best applied to specific subsets of patients with more favorable prognosis and may prolong survival time. This calls into question the generalizability of su...

Purpose/Objective(s) Up to half of patients with advanced cancer may meet diagnostic criteria for a psychiatric disorder. Yet, the impact of psychiatric diagnosis and/or medication prescription (psych Dx/Rx) on decision-making and outcomes for radiotherapy (RT) are not well-characterized. Statistical models and decision tools can be skewed when bui...

Background Prevention of relapse for adults with Acute Myeloid Leukemia (AML) in first remission (CR1) is the most common indication for allogeneic hematopoietic cell transplantation (alloHCT). Measurable residual disease (MRD) detection has been associated with higher relapse rates, but testing is not standardized. Establishment of validated AML M...

Purpose: The Bone Metastases Ensemble Trees for Survival Decision Support Platform (BMETS-DSP) provides patient-specific survival predictions and evidence-based recommendations to guide multidisciplinary management for symptomatic bone metastases. We assessed the clinical utility of the BMETS-DSP through a pilot prepost design in a simulated clini...

Background Estimates of SARS-CoV-2 seroprevalence in young children and risk factors for seropositivity are scarce. Using data from a prospective cohort study of households during the pre-COVID-19 vaccine period, we estimated SARS-CoV-2 seroprevalence by age and evaluated risk factors for SARS-CoV-2 seropositivity. Methods The SARS-CoV-2 Epidemiol...

(150 word limit) Background: Associations of mean glucose and time in range (70-180 mg/dL) from continuous glucose monitoring (CGM) with HbA1c in adults with type 2 diabetes are not well-characterized. Methods: We conducted a secondary analysis of 186 participants from the HYPNOS trial. Participants simultaneously wore Dexcom G4 and Abbott Libre...

Background Data that capture implementation strength can be combined in multiple ways across content and health system levels to create a summary measure that can help us to explore and compare program implementation across facility catchment areas. Summary indices can make it easier for national policymakers to understand and address variation in...

Policy Points Social determinants of health are an important predictor of future health care costs. Medicaid must partner with other sectors to address the underlying causes of its beneficiaries' poor health and high health care spending. Context: Social determinants of health are an important predictor of future health care costs but little is k...

Background In South Asia, a third of babies are born small-for-gestational age (SGA). The risk factors are well described in the literature, but many studies are in high-and-middle income countries or measure SGA on facility births only. There are fewer studies that describe the prevalence of risk factors for large-for-gestational age (LGA) in low-...

Objectives In low-income countries, birth weights for home deliveries are often measured at the nadir when babies may lose up of 10% of their birth weight, biasing estimates of small-for-gestational age (SGA) and low birth weight (LBW). We aimed to develop an imputation model that predicts the ‘true’ birth weight at time of delivery. Design We dev...

Age-related deficits in pattern separation have been postulated to bias the output of hippocampal memory processing toward pattern completion, which can cause deficits in accurate memory retrieval. Although the CA3 region of the hippocampus is often conceptualized as a homogeneous network involved in pattern completion, growing evidence demonstrate...

COVID-19 has challenged health systems to learn how to learn. This paper describes the context, methods and challenges for learning to improve COVID-19 care at one academic health center. Challenges to learning include: (1) choosing a right clinical target; (2) designing methods for accurate predictions by borrowing strength from prior patients' ex...

Background In South Asia, a third of babies are born small-for-gestational age (SGA) accounting for a quarter of all neonatal deaths. The risk factors are well described in the literature, but many studies are in high-and-middle income countries or measure SGA on facility births only. There are fewer studies that describe the prevalence of risk fac...

Background: COVID-19 is a global pandemic caused by the novel coronavirus SARS-CoV-2. Some clinical features of severe COVID-19 represent blood vessel damage induced by activation of host immune responses, initiated by the virus. We hypothesized that autoantibodies against angiotensin converting enzyme-2 (ACE2), the SARS-CoV-2 receptor expressed o...

Purpose: To assess factors associated with gender disparities in cataract surgery volume and evaluate how these differences have changed over time. Setting: Cataract surgeons in the 2012-2018 Medicare database. Design: Retrospective study. Methods: The association of provider gender with the number of cataract surgeries per office visit bill...

This paper describes and illustrates the functionality of the baker R package. The package estimates a suite of nested partially-latent class models (NPLCM) for multivariate binary responses that are observed under a case-control design. The baker package allows researchers to flexibly estimate population-level class prevalences and posterior proba...

Background: Knowing whether COVID-19 vaccine effectiveness wanes is crucial for informing vaccine policy, such as the need for and timing of booster doses. We aimed to systematically review the evidence for the duration of protection of COVID-19 vaccines against various clinical outcomes, and to assess changes in the rates of breakthrough infectio...

Background: Prior observation has shown differences in COVID-19 hospitalization rates between SARS-CoV-2 variants, but limited information describes differences in hospitalization outcomes. Methods: Patients admitted to 5 hospitals with COVID-19 were included if they had hypoxia, tachypnea, tachycardia, or fever, and data to describe SARS-CoV-2...

Background Little is known about the relationship between social determinants of health (SDH) and medication adherence among Medicaid beneficiaries with hypertension. Methods We conducted a posthoc subgroup analysis of 3044 adult Medicaid beneficiaries who enrolled in a parent prospective cohort study and had a diagnosis of hypertension based on t...

Rationale, aims and objectives: In the management of symptomatic bone metastases, current practice guidelines do not provide clear methodology for selecting palliative radiotherapy (RT) regimens based on specific patient and disease features. Decision support aids may offer an effective means for translating the complex data needed to render indiv...

Introduction Sudden cardiac death (SCD) is a devastating consequence often without antecedent expectation. Current risk stratification methods derived from baseline independently modeled risk factors are insufficient. Novel random forest machine learning (ML) approach incorporating time-dependent variables and complex interactions may improve SCD r...

Abstract Background As the global burden of malaria decreases, routine health information systems (RHIS) have become invaluable for monitoring progress towards elimination. The District Health Information System, version 2 (DHIS2) has been widely adopted across countries and is expected to increase the quality of reporting of RHIS. In this study, w...

As clinicians are faced with a deluge of new information, data science can play a key role in highlighting key features towards developing new clinical hypotheses. Indeed, insights derived from machine learning can serve as a clinical support tool by connecting care providers with results from big data analysis to identify latent patterns that may...

Older adults (≥65 years of age) bear a significant burden of severe disease and mortality associated with influenza, despite relatively high annual vaccination coverage and substantial pre-existing immunity to influenza. To test the hypothesis that host factors, including age and sex, play a role in determining the effect of repeated vaccination an...

Background Scleroderma is a serious chronic autoimmune disease in which a patient’s disease state manifests in several irregularly spaced longitudinal measures of lung, heart, skin, and other organ systems. Threshold crossings of pulmonary and cardiac measures indicate potentially life-threatening key clinical events including interstitial lung dis...

COVID-19 has challenged health systems to learn how to learn. This paper describes the context and methods for learning at one academic health center. Longitudinal regression models are used to represent the joint distribution of major clinical events including discharge, ventilation and death as well as multivariate biomarker processes that descri...

Background: Data that capture implementation strength can be combined in multiple ways across content and health system levels to create a summary measure that can help us to explore and compare program implementation across facility catchment areas. Summary indices can make it easier for national policymakers to understand and address variation in...

Age-related deficits in pattern separation have been postulated to bias the output of hippocampal memory processing toward pattern completion, which can cause deficits in accurate memory retrieval. While the CA3 region of the hippocampus is often conceptualized as a homogeneous network involved in pattern completion, growing evidence demonstrates a...

Introduction This study evaluates the association of multidimensional social determinants of health (SDoH) with non-adherence to diabetic retinopathy examinations. Research design and methods This was a post-hoc subgroup analysis of adults with diabetes in a prospective cohort study of enrollees in the Washington, DC Medicaid program. At study enr...

Background Males experience increased severity of illness and mortality from SARS-CoV-2 compared to females but the mechanisms of male susceptibility are unclear. Methods We performed a retrospective cohort analysis of SARS-CoV-2 testing and admission data at 5 hospitals in the Maryland/Washington DC area. Using age-stratified logistic regression...

Older adults (≥65 years of age) bear a significant burden of severe disease and mortality associated with influenza, despite relatively high annual vaccination coverage and substantial pre-existing immunity to influenza. To test the hypothesis that host factors, including age and sex, play a role in determining the effect of repeat vaccination and...

Background Topical treatment with sunflower seed oil (SSO) or Aquaphor® reduced sepsis and neonatal mortality in hospitalized preterm infants <33 weeks’ gestational age in Bangladesh. We sought to determine whether the emollient treatments improved neurodevelopmental outcomes during early childhood. Methods 497 infants were randomized to receive S...

Introduction: Sudden cardiac death (SCD) is the leading cause of death in the US and has significant public health impact. However, effective risk stratification for SCD remains lacking as current prediction models do not address the dynamic impact of time-varying risk factors including interim clinical events on SCD risk. Hypothesis: A recently de...

The plasma proteomic changes that precede the onset of dementia could yield insights into disease biology and highlight new biomarkers and avenues for intervention. We quantified 4,877 plasma proteins in nondemented older adults in the Atherosclerosis Risk in Communities cohort and performed a proteome-wide association study of dementia risk over f...

Longitudinal trajectories of vital signs and biomarkers during admission remain poorly characterized for COVID-19 patients despite their potential to provide critical insights about disease progression. We studied 1884 patients with SARS-CoV2 infection from 3/4/2020-6/25/2020 within one Maryland hospital system and used a retrospective longitudinal...

Background. Rates of severe illness and mortality from SARS-CoV-2 are greater for males, but the mechanisms for this difference are unclear. Understanding the differences in outcomes between males and females across the age spectrum will guide both public health and biomedical interventions. Methods. Retrospective cohort analysis of SARS-CoV-2 test...

Quantification learning is the task of prevalence estimation for a test population using predictions from a classifier trained on a different population. Quantification methods assume that the sensitivities and specificities of the classifier are either perfect or transportable from the training to the test population. These assumptions are inappro...

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5–7 years with primary series uptake above 70%. The dist...

Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococcal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) containing ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project gathered ST1 IPD surveillance data from sites globally and ai...

Importance Clinical effectiveness data on remdesivir are urgently needed, especially among diverse populations and in combination with other therapies. Objective To examine whether remdesivir administered with or without corticosteroids for treatment of coronavirus disease 2019 (COVID-19) is associated with more rapid clinical improvement in a rac...

Background: Predicting the clinical trajectory of individual patients hospitalized with coronavirus disease 2019 (COVID-19) is challenging but necessary to inform clinical care. The majority of COVID-19 prognostic tools use only data present upon admission and do not incorporate changes occurring after admission. Objective: To develop the Severe...

Study objective We evaluate the relationship between social determinants of health and emergency department (ED) visits in the Medicaid Cohort of the District of Columbia. Methods We conducted a retrospective cohort analysis of 8,943 adult Medicaid beneficiaries who completed a social determinants of health survey at study enrollment. We merged th...

PURPOSE The Bone Metastases Ensemble Trees for Survival (BMETS) model uses a machine learning algorithm to estimate survival time following consultation for palliative radiation therapy for symptomatic bone metastases (SBM). BMETS was developed at a tertiary-care, academic medical center, but its validity and stability when applied to external data...