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Full-Text Articles in Statistics and Probability

Mental Health Services Provision In Primary Care And Emergency Department Settings: Analysis Of Blended Fee-For-Service And Blended Capitation Models In Ontario, Canada., Thyna Vu, Kelly K Anderson, Nibene H Somé, Amardeep Thind, Sisira Sarma Jul 2021

Mental Health Services Provision In Primary Care And Emergency Department Settings: Analysis Of Blended Fee-For-Service And Blended Capitation Models In Ontario, Canada., Thyna Vu, Kelly K Anderson, Nibene H Somé, Amardeep Thind, Sisira Sarma

Epidemiology and Biostatistics Publications

Treating mental illnesses in primary care is increasingly emphasized to improve access to mental health services. Although family physicians (FPs) or general practitioners are in an ideal position to provide the bulk of mental health care, it is unclear how best to remunerate FPs for the adequate provision of mental health services. We examined the quantity of mental health services provided in Ontario's blended fee-for-service and blended capitation models. We evaluated the impact of FPs switching from blended fee-for-service to blended capitation on the provision of mental health services in primary care and emergency department using longitudinal health administrative data …


Quality Of Diabetes Care In Blended Fee-For-Service And Blended Capitation Payment Systems., Mary Aderayo Bamimore, Rose Anne Devlin, Gregory S Zaric, Amit X Garg, Sisira Sarma Apr 2021

Quality Of Diabetes Care In Blended Fee-For-Service And Blended Capitation Payment Systems., Mary Aderayo Bamimore, Rose Anne Devlin, Gregory S Zaric, Amit X Garg, Sisira Sarma

Epidemiology and Biostatistics Publications

OBJECTIVES: In the middle to late 2000s, many family physicians switched from a Family Health Group (FHG; a blended fee-for-service model) to a Family Health Organization (FHO; a blended capitation model) in Ontario, Canada. The evidence on the link between physician remuneration schemes and quality of diabetes care is mixed in the literature. We examined whether physicians who switched from the FHG to FHO model provided better care for individuals living with diabetes relative to those who remained in the FHG model.

METHODS: Using longitudinal health administrative data from 2006 to 2016, we investigated the impact of physicians switching from …


Emergency Department Use Following Incentives To Provide After-Hours Primary Care: A Retrospective Cohort Study., Michael Hong, Amardeep Thind, Gregory S Zaric, Sisira Sarma Jan 2021

Emergency Department Use Following Incentives To Provide After-Hours Primary Care: A Retrospective Cohort Study., Michael Hong, Amardeep Thind, Gregory S Zaric, Sisira Sarma

Epidemiology and Biostatistics Publications

BACKGROUND: Access to primary care outside of regular working hours is limited in many countries. This study investigates the relation between the after-hours premium, an incentive for primary care physicians to provide services after hours, and less-urgent visits to the emergency department in Ontario, Canada.

METHODS: We analyzed a retrospective cohort of a random sample of Ontario residents from April 2002 to March 2006, and a subcohort of patients followed from April 2005 to March 2016. We linked patient and primary care physician data with emergency department visit data. We used fixed-effects regression models to analyze the association between the …


Physician Remuneration Schemes, Psychiatric Hospitalizations And Follow-Up Care: Evidence From Blended Fee-For-Service And Capitation Models., Thyna Vu, Kelly K Anderson, Rose Anne Devlin, Nibene H Somé, Sisira Sarma Jan 2021

Physician Remuneration Schemes, Psychiatric Hospitalizations And Follow-Up Care: Evidence From Blended Fee-For-Service And Capitation Models., Thyna Vu, Kelly K Anderson, Rose Anne Devlin, Nibene H Somé, Sisira Sarma

Epidemiology and Biostatistics Publications

Psychiatric hospitalizations could be reduced if mental illnesses were detected and treated earlier in the primary care setting, leading to the World Health Organization recommendation that mental health services be integrated into primary care. The mental health services provided in primary care settings may vary based on how physicians are incentivized. Little is known about the link between physician remuneration and psychiatric hospitalizations. We contribute to this literature by studying the relationship between physician remuneration and psychiatric hospitalizations in Canada's most populous province, Ontario. Specifically, we study family physicians (FPs) who switched from blended fee-for-service (FFS) to blended capitation remuneration …


The Impact Of The Diabetes Management Incentive On Diabetes-Related Services: Evidence From Ontario, Canada., Thaksha Thavam, Rose Anne Devlin, Amardeep Thind, Gregory S Zaric, Sisira Sarma Dec 2020

The Impact Of The Diabetes Management Incentive On Diabetes-Related Services: Evidence From Ontario, Canada., Thaksha Thavam, Rose Anne Devlin, Amardeep Thind, Gregory S Zaric, Sisira Sarma

Epidemiology and Biostatistics Publications

Financial incentives have been introduced in several countries to improve diabetes management. In Ontario, the most populous province in Canada, a Diabetes Management Incentive (DMI) was introduced to family physicians practicing in patient enrollment models in 2006. This paper examines the impact of the DMI on diabetes-related services provided to individuals with diabetes in Ontario. Longitudinal health administrative data were obtained for adults diagnosed with diabetes and their family physicians. The study population consisted of two groups: DMI group (patients enrolled with a family physician exposed to DMI for 3 years), and comparison group (patients affiliated with a family physician …


Participatory Video As A Novel Recovery-Oriented Intervention In Early Psychosis: A Pilot Study., Arlene G Macdougall, Sahana Kukan, Elizabeth Price, Sarah Glen, Richelle Bird, Laura Powe, Joshua C. Wiener, Paul H Lysaker, Kelly K Anderson, Ross Mg Norman Dec 2020

Participatory Video As A Novel Recovery-Oriented Intervention In Early Psychosis: A Pilot Study., Arlene G Macdougall, Sahana Kukan, Elizabeth Price, Sarah Glen, Richelle Bird, Laura Powe, Joshua C. Wiener, Paul H Lysaker, Kelly K Anderson, Ross Mg Norman

Epidemiology and Biostatistics Publications

BACKGROUND: Personal narrative plays an important role in the process of recovery from psychotic illnesses. Participatory video is a novel, active intervention that can be used as a tool for fostering narrative development among people with psychosis.

AIM: To assess the feasibility, acceptability and potential clinical utility of participatory video as an innovative tool for promoting recovery in early psychosis.

METHODS: Ten outpatients of an early psychosis intervention programme were recruited to participate in 13 biweekly workshops to plan, film and produce documentary-style videos of their experiences. Feasibility was measured through recruitment and retention. Acceptability was measured through workshop attendance …


Stirring The Pot: Switching From Blended Fee-For-Service To Blended Capitation Models Of Physician Remuneration., Nibene H Somé, Rose Anne Devlin, Nirav Mehta, Gregory S Zaric, Sisira Sarma Nov 2020

Stirring The Pot: Switching From Blended Fee-For-Service To Blended Capitation Models Of Physician Remuneration., Nibene H Somé, Rose Anne Devlin, Nirav Mehta, Gregory S Zaric, Sisira Sarma

Epidemiology and Biostatistics Publications

In Canada's most populous province, Ontario, family physicians may choose between the blended fee-for-service (Family Health Group [FHG]) and blended capitation (Family Health Organization [FHO] payment models). Both models incentivize physicians to provide after-hours (AH) and comprehensive care, but FHO physicians receive a capitation payment per enrolled patient adjusted for age and sex, plus a reduced fee-for-service while FHG physicians are paid by fee-for-service. We develop a theoretical model of physician labor supply with multitasking to predict their behavior under FHG and FHO, and estimable equations are derived to test the predictions empirically. Using health administrative data from 2006 to …


Risk Of New Bloodstream Infections And Mortality Among People Who Inject Drugs With Infective Endocarditis., Charlie Tan, Esfandiar Shojaei, Joshua C. Wiener, Meera Shah, Sharon Koivu, Michael Silverman Aug 2020

Risk Of New Bloodstream Infections And Mortality Among People Who Inject Drugs With Infective Endocarditis., Charlie Tan, Esfandiar Shojaei, Joshua C. Wiener, Meera Shah, Sharon Koivu, Michael Silverman

Epidemiology and Biostatistics Publications

IMPORTANCE: People who inject drugs (PWID) who are being treated for infective endocarditis remain at risk of new bloodstream infections (BSIs) due to ongoing intravenous drug use (IVDU).

OBJECTIVES: To characterize new BSIs in PWID receiving treatment for infective endocarditis, to determine the clinical factors associated with their development, and to determine whether new BSIs and treatment setting are associated with mortality.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was performed at 3 tertiary care hospitals in London, Ontario, Canada, from April 1, 2007, to March 31, 2018. Participants included a consecutive sample of all PWID 18 years or …


The Impact Of Improved Access To After-Hours Primary Care On Emergency Department And Primary Care Utilization: A Systematic Review., Michael Hong, Amardeep Thind, Gregory S Zaric, Sisira Sarma Aug 2020

The Impact Of Improved Access To After-Hours Primary Care On Emergency Department And Primary Care Utilization: A Systematic Review., Michael Hong, Amardeep Thind, Gregory S Zaric, Sisira Sarma

Epidemiology and Biostatistics Publications

Access to after-hours primary care is problematic in many developed countries, leading patients to instead visit the emergency department for non-urgent conditions. However, emergency department utilization for conditions treatable in primary care settings may contribute to emergency department overcrowding and increased health system costs. This systematic review examines the impact of various initiatives by developed countries to improve access to after-hours primary care on emergency department and primary care utilization. We performed a systematic review on the impact of improved access to after-hours primary and searched CINAHL, EMBASE, MEDLINE, and Scopus. We identified 20 studies that examined the impact of …


Age At Migration And The Risk Of Psychotic Disorders: A Systematic Review And Meta-Analysis., Kelly K. Anderson, Jordan Edwards May 2020

Age At Migration And The Risk Of Psychotic Disorders: A Systematic Review And Meta-Analysis., Kelly K. Anderson, Jordan Edwards

Epidemiology and Biostatistics Publications

OBJECTIVE: To conduct a systematic review and meta-analysis of the existing evidence on the association between age at migration and the risk of psychotic disorders.

METHODS: Observational studies were eligible for inclusion if they presented data on the association between age at migration and the risk of psychotic disorders among first-generation migrant groups. We used two random effects meta-analyses to pool effect estimates for each stratum of age at migration relative to (i) a native-born reference category and (ii) the youngest age stratum (0 to 2 years).

RESULTS: Ten studies met inclusion criteria, and five were included in the meta-analysis. …


Evaluating The Effectiveness Of Aquatic Therapy On Mobility, Balance, And Level Of Functional Independence In Stroke Rehabilitation: A Systematic Review And Meta-Analysis., Alice Mary Iliescu, Amanda Mcintyre, Joshua C. Wiener, Jerome Iruthayarajah, Andrea Lee, Sarah Caughlin, Robert Teasell Jan 2020

Evaluating The Effectiveness Of Aquatic Therapy On Mobility, Balance, And Level Of Functional Independence In Stroke Rehabilitation: A Systematic Review And Meta-Analysis., Alice Mary Iliescu, Amanda Mcintyre, Joshua C. Wiener, Jerome Iruthayarajah, Andrea Lee, Sarah Caughlin, Robert Teasell

Epidemiology and Biostatistics Publications

OBJECTIVE: To meta-analyze and systematically review the effectiveness of aquatic therapy in improving mobility, balance, and functional independence after stroke.

DATA SOURCES: Articles published in Medline, Embase, CINAHL, PsycINFO, and Scopus up to 20 August 2019.

STUDY SELECTION: Studies met the following inclusion criteria: (1) English, (2) adult stroke population, (3) randomized or non-randomized prospectively controlled trial (RCT or PCT, respectively) study design, (4) the experimental group received >1 session of aquatic therapy, and (5) included a clinical outcome measure of mobility, balance, or functional independence.

DATA EXTRACTION: Participant characteristics, treatment protocols, between-group outcomes, point measures, and measures of variability …


Impact Of Motor Therapy With Dynamic Body-Weight Support On Functional Independence Measures In Traumatic Brain Injury: An Exploratory Study, Emily F. Anggelis, Elizabeth Salmon Powell, Philip M. Westgate, Amanda C. Glueck, Lumy Sawaki Dec 2019

Impact Of Motor Therapy With Dynamic Body-Weight Support On Functional Independence Measures In Traumatic Brain Injury: An Exploratory Study, Emily F. Anggelis, Elizabeth Salmon Powell, Philip M. Westgate, Amanda C. Glueck, Lumy Sawaki

Physical Medicine and Rehabilitation Faculty Publications

BACKGROUND: Contemporary goals of rehabilitation after traumatic brain injury (TBI) aim to improve cognitive and motor function by applying concepts of neuroplasticity. This can be challenging to carry out in TBI patients with motor, balance, and cognitive impairments.

OBJECTIVE: To determine whether use of dynamic body-weight support (DBWS) would allow safe administration of intensive motor therapy during inpatient rehabilitation and whether its use would yield greater improvement in functional recovery than standard-of-care (SOC) therapy in adults with TBI.

METHODS: Data in this retrospective cohort study was collected from patients with TBI who receive inpatient rehabilitation incorporating DBWS (n = …


Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito Dec 2019

Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito

Physiology Faculty Publications

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …


Production Of Physician Services Under Fee-For-Service And Blended Fee-For-Service: Evidence From Ontario, Canada., Nibene H Somé, Rose Anne Devlin, Nirav Mehta, Greg Zaric, Lihua Li, Salimah Shariff, Bachir Belhadji, Amardeep Thind, Amit Garg, Sisira Sarma Dec 2019

Production Of Physician Services Under Fee-For-Service And Blended Fee-For-Service: Evidence From Ontario, Canada., Nibene H Somé, Rose Anne Devlin, Nirav Mehta, Greg Zaric, Lihua Li, Salimah Shariff, Bachir Belhadji, Amardeep Thind, Amit Garg, Sisira Sarma

Epidemiology and Biostatistics Publications

We examine family physicians' responses to financial incentives for medical services in Ontario, Canada. We use administrative data covering 2003-2008, a period during which family physicians could choose between the traditional fee for service (FFS) and blended FFS known as the Family Health Group (FHG) model. Under FHG, FFS physicians are incentivized to provide comprehensive care and after-hours services. A two-stage estimation strategy teases out the impact of switching from FFS to FHG on service production. We account for the selection into FHG using a propensity score matching model, and then we use panel-data regression models to account for observed …


Healthcare Utilization Costs Of Emerging Adults With Mood And Anxiety Disorders In An Early Intervention Treatment Program Compared To A Matched Cohort, Ava A. John-Baptiste, Lihua Li, Wanrudee Isaranuwatchai, Elizabeth Osuch, Kelly K. Anderson Dec 2019

Healthcare Utilization Costs Of Emerging Adults With Mood And Anxiety Disorders In An Early Intervention Treatment Program Compared To A Matched Cohort, Ava A. John-Baptiste, Lihua Li, Wanrudee Isaranuwatchai, Elizabeth Osuch, Kelly K. Anderson

Epidemiology and Biostatistics Publications

AIM: The First Episode Mood and Anxiety Disorder Program (FEMAP) provides treatment to emerging adults with mood and anxiety disorders in an accessible, youth-friendly environment. We sought to investigate FEMAP's impact on the costs of care.

METHODS: We conducted a retrospective observational study of one-year health service costs using linked administrative datasets to compare emerging adults treated at FEMAP (FEMAP users) to propensity-score matched controls (non-users). Costs from the perspective of the Ontario Ministry of Health and Long-Term Care, included drug benefit claims, inpatient, physician and ambulatory care services. We used bootstrapping to perform unadjusted comparisons between FEMAP users and …


Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha Nov 2019

Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha

Neurology Faculty Publications

BACKGROUND: Disparate research sites using identical or near-identical magnetic resonance imaging (MRI) acquisition techniques often produce results that demonstrate significant variability regarding volumetric quantification of white matter hyperintensities (WMH) in the aging population. The sources of such variability have not previously been fully explored.

NEW METHOD: 3D FLAIR sequences from a group of randomly selected aged subjects were analyzed to identify sources-of-variability in post-acquisition processing that can be problematic when comparing WMH volumetric data across disparate sites. The methods developed focused on standardizing post-acquisition protocol processing methods to develop a protocol with less than 0.5% inter-rater variance.

RESULTS: A series …


Enhancing Timeliness Of Drug Overdose Mortality Surveillance: A Machine Learning Approach, Patrick J. Ward, Peter J. Rock, Svetla Slavova, April M. Young, Terry L. Bunn, Ramakanth Kavuluru Oct 2019

Enhancing Timeliness Of Drug Overdose Mortality Surveillance: A Machine Learning Approach, Patrick J. Ward, Peter J. Rock, Svetla Slavova, April M. Young, Terry L. Bunn, Ramakanth Kavuluru

Kentucky Injury Prevention and Research Center Faculty Publications

BACKGROUND: Timely data is key to effective public health responses to epidemics. Drug overdose deaths are identified in surveillance systems through ICD-10 codes present on death certificates. ICD-10 coding takes time, but free-text information is available on death certificates prior to ICD-10 coding. The objective of this study was to develop a machine learning method to classify free-text death certificates as drug overdoses to provide faster drug overdose mortality surveillance.

METHODS: Using 2017–2018 Kentucky death certificate data, free-text fields were tokenized and features were created from these tokens using natural language processing (NLP). Word, bigram, and trigram features were created …


Differences In Duration Of Untreated Psychosis For Racial And Ethnic Minority Groups With First-Episode Psychosis: An Updated Systematic Review And Meta-Analysis., Nicole Schoer, Chen Wei Huang, Kelly K. Anderson Oct 2019

Differences In Duration Of Untreated Psychosis For Racial And Ethnic Minority Groups With First-Episode Psychosis: An Updated Systematic Review And Meta-Analysis., Nicole Schoer, Chen Wei Huang, Kelly K. Anderson

Epidemiology and Biostatistics Publications

PURPOSE: Ethnic minority groups with early psychosis may have longer treatment delays, potentially leading to poorer outcomes. We updated a previous systematic review of the literature on racial and ethnic differences in duration of untreated psychosis (DUP) among people with first-episode psychosis.

RESULTS: Six of 17 studies described significant differences across aggregated racial groups; however, the pooled estimates did not show differences across groups. Additional data from this update allowed for disaggregated analyses, finding that Black-African groups have a shorter DUP, whereas Black-Caribbean groups have longer DUP, relative to White groups.

CONCLUSIONS: These findings highlight the importance of in-depth research …


Socioemotional Selectivity And Psychological Health In Amyotrophic Lateral Sclerosis Patients And Caregivers: A Longitudinal, Dyadic Analysis, Suzanne C. Segerstrom, Edward J. Kasarskis, David W. Fardo, Philip M. Westgate Oct 2019

Socioemotional Selectivity And Psychological Health In Amyotrophic Lateral Sclerosis Patients And Caregivers: A Longitudinal, Dyadic Analysis, Suzanne C. Segerstrom, Edward J. Kasarskis, David W. Fardo, Philip M. Westgate

Psychology Faculty Publications

Objective: Socioemotional selectivity theory predicts that as the end of life approaches, goals and resources that provide immediate, hedonic reward become more important than those that provide delayed rewards. This study tested whether these goal domains differentially affected psychological health in the context of marital dyads in which one partner had been diagnosed with amyotrophic lateral sclerosis (ALS), a life-limiting disease.

Design: ALS patients (N = 102) being treated in three multidisciplinary clinics and their spouses (N = 100) reported their loneliness, financial worry and psychological health every 3 months for up to 18 months.

Main …


Effectiveness Of High-Intensity Interval Training For Fitness And Mobility Post Stroke: A Systematic Review., Joshua C. Wiener, Amanda Mcintyre, Scott Janssen, Jeffrey Ty Chow, Cristina Batey, Robert Teasell Aug 2019

Effectiveness Of High-Intensity Interval Training For Fitness And Mobility Post Stroke: A Systematic Review., Joshua C. Wiener, Amanda Mcintyre, Scott Janssen, Jeffrey Ty Chow, Cristina Batey, Robert Teasell

Epidemiology and Biostatistics Publications

OBJECTIVE: To evaluate the evidence on the effectiveness of high-intensity interval training (HIIT) in improving fitness and mobility post stroke. TYPE: Systematic review.

LITERATURE SURVEY: Medline, Embase, CINAHL, PsycINFO, and Scopus were searched for articles published in English up to January 2018.

METHODOLOGY: Studies were included if the sample was adult human participants with stroke, the sample size was ≥3, and participants received >1 session of HIIT. Study and participant characteristics, treatment protocols, and results were extracted.

SYNTHESIS: Six studies with a total of 140 participants met inclusion criteria: three randomized controlled trials and three pre-post studies. HIIT protocols ranged …


Involuntary Hospitalization Among Young People With Early Psychosis: A Population-Based Study Using Health Administrative Data., Rebecca Rodrigues, Arlene G Macdougall, Guangyong Zou, Michael Lebenbaum, Paul Kurdyak, Lihua Li, Salimah Z Shariff, Kelly K Anderson Jun 2019

Involuntary Hospitalization Among Young People With Early Psychosis: A Population-Based Study Using Health Administrative Data., Rebecca Rodrigues, Arlene G Macdougall, Guangyong Zou, Michael Lebenbaum, Paul Kurdyak, Lihua Li, Salimah Z Shariff, Kelly K Anderson

Epidemiology and Biostatistics Publications

OBJECTIVE: Early psychosis is an important window for establishing long-term trajectories. Involuntary hospitalization during this period may impact subsequent service engagement in people with newly diagnosed psychotic disorder. However, population-based studies of involuntary hospitalization in early psychosis are lacking. We sought to estimate the proportion of people aged 16 to 35 years with early psychosis in Ontario who are hospitalized involuntarily at first admission, and to identify the associated risk factors and outcomes.

METHODS: Using linked population-based health administrative data, we identified incident cases of non-affective psychosis over a five-year period (2009-2013) and followed cases for two years to ascertain …


Tumor Heterogeneity As A Predictor Of Response To Neoadjuvant Chemotherapy In Locally Advanced Rectal Cancer, Alissa Greenbaum, David R. Martin, Therese J. Bocklage, Ji-Hyun Lee, Scott A. Ness, Ashwani Rajput Jun 2019

Tumor Heterogeneity As A Predictor Of Response To Neoadjuvant Chemotherapy In Locally Advanced Rectal Cancer, Alissa Greenbaum, David R. Martin, Therese J. Bocklage, Ji-Hyun Lee, Scott A. Ness, Ashwani Rajput

Pathology and Laboratory Medicine Faculty Publications

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays.

PATIENTS AND METHODS: DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral …


Tdp-43 Proteinopathy In Aging: Associations With Risk-Associated Gene Variants And With Brain Parenchymal Thyroid Hormone Levels, Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo May 2019

Tdp-43 Proteinopathy In Aging: Associations With Risk-Associated Gene Variants And With Brain Parenchymal Thyroid Hormone Levels, Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology …


Incorporating Pathway Information Into Feature Selection Towards Better Performed Gene Signatures, Suyan Tian, Chi Wang, Bing Wang Apr 2019

Incorporating Pathway Information Into Feature Selection Towards Better Performed Gene Signatures, Suyan Tian, Chi Wang, Bing Wang

Biostatistics Faculty Publications

To analyze gene expression data with sophisticated grouping structures and to extract hidden patterns from such data, feature selection is of critical importance. It is well known that genes do not function in isolation but rather work together within various metabolic, regulatory, and signaling pathways. If the biological knowledge contained within these pathways is taken into account, the resulting method is a pathway-based algorithm. Studies have demonstrated that a pathway-based method usually outperforms its gene-based counterpart in which no biological knowledge is considered. In this article, a pathway-based feature selection is firstly divided into three major categories, namely, pathway-level selection, …


A Parent-Led Intervention To Promote Recovery Following Pediatric Injury: Study Protocol For A Randomized Controlled Trial, Meghan L. Marsac, Ginny Sprang, Leila Guller, Kristen L. Kohser, John M. Draus Jr., Nancy Kassam-Adams Feb 2019

A Parent-Led Intervention To Promote Recovery Following Pediatric Injury: Study Protocol For A Randomized Controlled Trial, Meghan L. Marsac, Ginny Sprang, Leila Guller, Kristen L. Kohser, John M. Draus Jr., Nancy Kassam-Adams

Pediatrics Faculty Publications

Background: Injury is one of the most prevalent potentially emotionally traumatic events that children experience and can lead to persistent impaired physical and emotional health. There is a need for interventions that promote full physical and emotional recovery and that can be easily accessed by all injured children. Based on research evidence regarding post-injury recovery, we created the Cellie Coping Kit for Children with Injury intervention to target key mechanisms of action and refined the intervention based on feedback from children, families, and experts in the field. The Cellie Coping Kit intervention is parent-guided and includes a toy (for engagement), …


Saturated Fat Intake Is Associated With Lung Function In Individuals With Airflow Obstruction: Results From Nhanes 2007⁻2012, Kasey Cornell, Morshed Alam, Elizabeth Lyden, Lisa Wood, Tricia D. Levan, Tara M. Nordgren, Kristina L. Bailey, Corrine K. Hanson Jan 2019

Saturated Fat Intake Is Associated With Lung Function In Individuals With Airflow Obstruction: Results From Nhanes 2007⁻2012, Kasey Cornell, Morshed Alam, Elizabeth Lyden, Lisa Wood, Tricia D. Levan, Tara M. Nordgren, Kristina L. Bailey, Corrine K. Hanson

Journal Articles: Biostatistics

Nutritional status is a well-recognized prognostic indicator in chronic obstructive pulmonary disease (COPD); however, very little is known about the relationship between lung function and saturated fat intake. We used data from the cross-sectional National Health and Nutrition Examination Surveys (NHANES) to assess the relationship between saturated fatty acid (SFA) intake and lung function in the general US adult population. Adults in NHANES (2007⁻2012) with pre-bronchodilator spirometry measurements and dietary SFA intake were included. Primary outcomes were lung function including forced expiratory volume in one second (FEV₁)


Large-Scale Genome-Wide Meta-Analysis Of Polycystic Ovary Syndrome Suggests Shared Genetic Architecture For Different Diagnosis Criteria, Felix Day, Tugce Karaderi, Michelle R. Jones, Cindy Meun, Chunyan He, Alex Drong, Peter Kraft, Nan Lin, Hongyan Huang, Linda Broer, Reedik Magi, Richa Saxena, Triin Laisk, Margrit Urbanek, M. Geoffrey Hayes, Gudmar Thorleifsson, Juan Fernandez-Tajes, Anubha Mahajan, Benjamin H. Mullin, Bronwyn G. A. Stuckey, Timothy D. Spector, Scott G. Wilson, Mark O. Goodarzi, Lea Davis, Barbara Obermayer-Pietsch, André G. Uitterlinden, Verneri Anttila, Benjamin M. Neale, Marjo-Riitta Jarvelin, Bart Fauser Dec 2018

Large-Scale Genome-Wide Meta-Analysis Of Polycystic Ovary Syndrome Suggests Shared Genetic Architecture For Different Diagnosis Criteria, Felix Day, Tugce Karaderi, Michelle R. Jones, Cindy Meun, Chunyan He, Alex Drong, Peter Kraft, Nan Lin, Hongyan Huang, Linda Broer, Reedik Magi, Richa Saxena, Triin Laisk, Margrit Urbanek, M. Geoffrey Hayes, Gudmar Thorleifsson, Juan Fernandez-Tajes, Anubha Mahajan, Benjamin H. Mullin, Bronwyn G. A. Stuckey, Timothy D. Spector, Scott G. Wilson, Mark O. Goodarzi, Lea Davis, Barbara Obermayer-Pietsch, André G. Uitterlinden, Verneri Anttila, Benjamin M. Neale, Marjo-Riitta Jarvelin, Bart Fauser

Internal Medicine Faculty Publications

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related …


Serum Nutrient Levels And Aging Effects On Periodontitis, Jeffrey L Ebersole, Joshua Lambert, Heather Bush, Pinar Emecen Huja, Arpita Basu Dec 2018

Serum Nutrient Levels And Aging Effects On Periodontitis, Jeffrey L Ebersole, Joshua Lambert, Heather Bush, Pinar Emecen Huja, Arpita Basu

Biostatistics Faculty Publications

Periodontal disease damages tissues as a result of dysregulated host responses against the chronic bacterial biofilm insult and approximately 50% of US adults > 30 years old exhibit periodontitis. The association of five blood nutrients and periodontitis were evaluated due to our previous findings regarding a potential protective effect for these nutrients in periodontal disease derived from the US population sampled as part of the National Health and Nutrition Examination Survey (1999–2004). Data from over 15,000 subjects was analyzed for blood levels of cis-β-carotene, β-cryptoxanthin, folate, vitamin D, and vitamin E, linked with analysis of the presence and severity of periodontitis. …


Subject Level Clustering Using A Negative Binomial Model For Small Transcriptomic Studies., Qian Li, Janelle R. Noel-Macdonnell, Devin C. Koestler, Ellen L. Goode, Brooke L. Fridley Dec 2018

Subject Level Clustering Using A Negative Binomial Model For Small Transcriptomic Studies., Qian Li, Janelle R. Noel-Macdonnell, Devin C. Koestler, Ellen L. Goode, Brooke L. Fridley

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Unsupervised clustering represents one of the most widely applied methods in analysis of high-throughput 'omics data. A variety of unsupervised model-based or parametric clustering methods and non-parametric clustering methods have been proposed for RNA-seq count data, most of which perform well for large samples, e.g. N ≥ 500. A common issue when analyzing limited samples of RNA-seq count data is that the data follows an over-dispersed distribution, and thus a Negative Binomial likelihood model is often used. Thus, we have developed a Negative Binomial model-based (NBMB) clustering approach for application to RNA-seq studies.

RESULTS: We have developed a Negative …


Safety, Tolerability, And Pharmacokinetics Of Long-Acting Injectable Cabotegravir In Low-Risk Hiv-Uninfected Individuals: Hptn 077, A Phase 2a Randomized Controlled Trial., Raphael J Landovitz, Sue Li, Beatriz Grinsztejn, Halima Dawood, Albert Y Liu, Manya Magnus, Mina C Hosseinipour, Ravindre Panchia, Leslie Cottle, Gordon Chau, Paul Richardson, Mark A Marzinke, Craig W Hendrix, Susan H Eshleman, Yinfeng Zhang, Elizabeth Tolley, Jeremy Sugarman, Ryan Kofron, Adeola Adeyeye, David Burns, Alex R Rinehart, David Margolis, William R Spreen, Myron S Cohen, Marybeth Mccauley, Joseph J Eron Nov 2018

Safety, Tolerability, And Pharmacokinetics Of Long-Acting Injectable Cabotegravir In Low-Risk Hiv-Uninfected Individuals: Hptn 077, A Phase 2a Randomized Controlled Trial., Raphael J Landovitz, Sue Li, Beatriz Grinsztejn, Halima Dawood, Albert Y Liu, Manya Magnus, Mina C Hosseinipour, Ravindre Panchia, Leslie Cottle, Gordon Chau, Paul Richardson, Mark A Marzinke, Craig W Hendrix, Susan H Eshleman, Yinfeng Zhang, Elizabeth Tolley, Jeremy Sugarman, Ryan Kofron, Adeola Adeyeye, David Burns, Alex R Rinehart, David Margolis, William R Spreen, Myron S Cohen, Marybeth Mccauley, Joseph J Eron

Epidemiology Faculty Publications

BACKGROUND: Cabotegravir (CAB) is a novel strand-transfer integrase inhibitor being developed for HIV treatment and prevention. CAB is formulated both as an immediate-release oral tablet for daily administration and as a long-acting injectable suspension (long-acting CAB [CAB LA]) for intramuscular (IM) administration, which delivers prolonged plasma exposure to the drug after IM injection. HIV Prevention Trials Network study 077 (HPTN 077) evaluated the safety, tolerability, and pharmacokinetics of CAB LA in HIV-uninfected males and females at 8 sites in Brazil, Malawi, South Africa, and the United States.

METHODS AND FINDINGS: HPTN 077 was a double-blind, placebo-controlled phase 2a trial. Healthy …