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Bio

Bio

During the COVID pandemic, Dr. Kao is available to see patients via video visits. Dr. Kao is also providing pain relief procedures, with strict observation of Stanford Health Care infection control policies.

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Dr. Kao is the Clinic Chief at Stanford Pain Management. A Taiwanese American, Dr. Kao studied molecular biology and psychology at UC Berkeley. At Harvard University, he earned a PhD in biostatistics after developing statistical methods in genomics and computational biology. He then pursued medical training at the University of Michigan, Yale, and Stanford.

He is the author of more than 30 scientific journal articles, ranging from genetics, genomics, proteomics, combinatorial chemistry, artificial intelligence, oncology, epidemiology, rehabilitation, and pain, . His mission is to offer all of his patients comprehensive interdisciplinary pain care, leveraging the full extent of what is known in state-of-the-art Pain Medicine.

In addition to providing clinical care, Dr. Kao teaches physicians and trainees on diagnostic work-up of complex pain, techniques of interventional procedures, and scientific methods of pain studies.

Dr. Kao is a Certified Interventional Pain Sonographer (CIPS) as well as a Fellow in Interventional Pain Practice (FIPP).

Clinical Focus

  • Pain Medicine
  • Musculoskeletal pain
  • Ultrasound procedures
  • Nerve entrapment
  • Abdominal pain
  • Opioid alternatives
  • Non-drug treatments
  • Dietary Supplements
  • CRPS
  • Complex Regional Pain Syndromes
  • Peripheral nerve stimulation

Academic Appointments

  • Clinical Assistant Professor, Orthopaedic Surgery
  • Clinical Assistant Professor, Anesthesiology, Perioperative and Pain Medicine

Administrative Appointments

  • Clinic Chief, Stanford Pain (2017 - Present)
  • Associate Division Chief of Operations, Stanford Pain (2015 - 2017)
  • Chief Fellow, Stanford Pain (2013 - 2014)
  • Chief Resident, Stanford Physical Medicine and Rehabilitation (2012 - 2013)

Honors & Awards

  • Concurrent Poster Research Highlights, American Academy of Pain Medicine (Mar 2016)
  • Concurrent Poster Research Highlight, American Academic of Pain Medicine 2015 (Mar 2015)
  • Best Original Research, PM&R Journal (Oct 2015)
  • Best Spine and Pain Research Presentation, American Association of Physical Medicine & Rehabilitation (Nov 2014)
  • Concurrent Poster Research Highlights, American Academy of Pain Medicine (Mar 2014)
  • Best Poster Finalist, Center for Disease Control, Center for Health Statistics (Aug 2012)
  • Best Poster Award, SpineWeek, International Society for Study of the Lumbar Spine (ISSLS) (Jun 2012)
  • Peter Singleton Award, Stanford PM&R (Jun 2012)
  • Best Musculoskeletal Research Presentation, American Association of Physical Medicine & Rehabilitation (Nov 2011)
  • 2013 Outstanding Paper Award for Medical/Interventional Science, Spine Journal & North American Spine Society (NASS) (Oct 2013)
  • First Place, Health 2.0 Developer Challenge Code-a-thon (Oct 2010)
  • NIH Training Grant, National Institute of Mental Health (1999)
  • Howard Hughes Pre-Doctoral Fellowship, Howard Hughes Medical Institute (2000)

Boards, Advisory Committees, Professional Organizations

  • Member, American Association of Pain Medicine (2013 - Present)

Professional Education

  • FIPS, World Institute of Pain, Fellow of Interventional Pain Practice (2018)
  • CIPS, World Institute of Pain, Certified Interventional Pain Sonologist (2018)
  • Board Certification: American Board of Physical Medicine and Rehab, Pain Medicine (2014)
  • Board Certification: American Board of Physical Medicine and Rehab, Physical Medicine and Rehab (2013)
  • Fellowship: Stanford University Pain Management Fellowship (2013) CA
  • Residency: Stanford University Physical Medicine and Rehabiliation (2012) CA
  • Internship: Yale University Internal Medicine Residency (2008) CT
  • Medical Education: University of Michigan School of Medicine (2007) MI
  • PhD, Harvard University, Biostatistics & Computational Biology (2005)
  • BA, UC Berkeley (1999)

Contact

  • Wendy Schadle Administrative Assistant
  • Stanford Pain Management Center 450 Broadway St Redwood City, CA 94063
    • Tel: (650) 723-6238
    Fax: (650) 721-3414

Links

Research & Scholarship

Current Research and Scholarly Interests

1. Patient-reported outcomes. Efficient, multi-feature item-response theory (IRT) based computerized adaptive testing (CAT) algorithm using item banks from PROMIS and NIH Toolbox

2. Activity monitoring. Novel analytic framework for physical activity monitoring in the context of pain.

3. Operations research. Multi-variable discrete and continuous optimization for Lean Hospital Management

4. National trends in pain medication prescription

Publications

All Publications

  • Self-reported traumatic etiology of pain and psychological function in tertiary care pain clinic patients: a collaborative health outcomes information registry (CHOIR) study. Scandinavian journal of pain Taub, C. J., Sturgeon, J. A., Chahal, M. K., Kao, M. C., Mackey, S. C., Darnall, B. D. 2020

    Abstract

    Background and aims A sizable body of research has elucidated the significant role of psychological reactions to trauma on pain coping and outcomes. In order to best inform intervention development and clinical care for patients with both trauma and pain at the tertiary care level, greater clarity is needed regarding the magnitude of these effects and the specific pathways through which they may or may not function at the time of first presentation to such a treatment setting. To achieve this, the current study examined the cross-sectional relationships between traumatic etiology of pain, psychological distress (anger, depressive symptoms, and PTSD symptoms), and pain outcomes (pain catastrophizing, physical function, disability status). Methods Using a structural path modeling approach, analyses were conducted using a large sample of individuals with chronic pain (n?=?637) seeking new medical evaluation at a tertiary pain management center, using the Collaborative Health Outcomes Information Registry (CHOIR). We hypothesized that the relationships between traumatic etiology of pain and poorer pain outcomes would be mediated by higher levels of psychological distress. Results Our analyses revealed modest relationships between self-reported traumatic etiology of pain and pain catastrophizing, physical function, and disability status. In comparison, there were stronger relationships between indices of psychological distress and pain catastrophizing, but a weaker pattern of associations between psychological distress and physical function and disability measures. Conclusions To the relatively small extent that self-reported traumatic etiology of pain correlates with pain-related outcomes, these relationships appear to be due primarily to the presence of psychiatric symptoms and manifest most notably in the context of psychological responses to pain (i.e. catastrophizing about pain). Implications Findings from this study highlight the need for early intervention for patients with traumatic onset of pain and for clinicians at tertiary pain centers to include more detailed assessments of psychological distress and trauma as a component of comprehensive chronic pain treatment.

    View details for DOI 10.1515/sjpain-2019-0154

    View details for PubMedID 32191626

  • Smoking Is Associated with Pain in All Body Regions, with Greatest Influence on Spinal Pain. Pain medicine (Malden, Mass.) Smuck, M., Schneider, B. J., Ehsanian, R., Martin, E., Kao, M. J. 2019

    Abstract

    OBJECTIVE: Examine the interrelationship between smoking and pain in the US population.DESIGN: A cross-sectional population-based study.SETTING: Nationwide survey.METHODS: Comprehensive pain reports categorically defined as head, spine, trunk, and limb pain; smoking history; demographics; medical history from a total of 2,307 subjects from the 2003-2004 National Health and Nutrition Examination Survey obtained from the Centers for Disease Control were analyzed. Unpaired t tests were used to analyze independent continuous variables, and chi-square tests were used to analyze categorical variables between smoker and nonsmoker groups. Weighted multivariate logistic regression analyses determined the association of current smoking with the presence of pain in various body regions.RESULTS: Smoking is most strongly associated with spine pain (odds ratio [OR] = 2.89, 95% confidence interval [CI] = 2.21-3.77), followed by headache (OR = 2.47, 95% CI = 1.73-3.53), trunk pain (OR = 2.17, 95% CI = 1.45-2.74), and limb pain (OR = 1.99, 95% CI = 1.45-2.73).CONCLUSIONS: Current smoking is associated with pain in every region of the body. This association is strongest for spine and head pain. Given that pain is a strong motivator and that current smoking was associated with pain in all body regions, we recommend that these results be used to further raise public awareness about the potential harms of smoking.

    View details for DOI 10.1093/pm/pnz224

    View details for PubMedID 31578562

  • Managing twin crises in chronic pain and prescription opioids. BMJ (Clinical research ed.) Mackey, S., Kao, M. 2019; 364: l917

    View details for PubMedID 30842099

  • International Stakeholder Community of Pain Experts and Leaders Call for an Urgent Action on Forced Opioid Tapering PAIN MEDICINE Darnall, B. D., Juurlink, D., Kerns, R. D., Mackey, S., Van Dorsten, B., Humphreys, K., Gonzalez-Sotomayor, J. A., Furlan, A., Gordon, A. J., Gordon, D. B., Hoffman, D. E., Katz, J., Kertesz, S. G., Satel, S., Lawhern, R. A., Nicholson, K. M., Polomano, R. C., Williamson, O. D., McAnally, H., Kao, M., Schug, S., Twillman, R., Lewis, T. A., Stieg, R. L., Lorig, K., Mallick-Searle, T., West, R. W., Gray, S., Ariens, S. R., Potter, J., Cowan, P., Kollas, C. D., Laird, D., Ingle, B., Grove, J., Wilson, M., Lockman, K., Hodson, F., Palackdharry, C. S., Fillingim, R. B., Fudin, J., Barnhouse, J., Manhapra, A., Henson, S. R., Singer, B., Ljosenvoor, M., Griffith, M., Doctor, J. N., Hardin, K., London, C., Mankowski, J., Anderson, A., Ellsworth, L., Budzinski, L., Brandt, B., Hartley, G., Heck, D., Zobrosky, M. J., Cheek, C., Wilson, M., Laux, C. E., Datz, G., Dunaway, J., Schonfeld, E., Cady, M., LeDantec-Boswell, T., Craigie, M., Sturgeon, J., Flood, P., Giummarra, M., Whelan, J., Thorn, B. E., Martin, R. L., Schatman, M. E., Gregory, M. D., Kirz, J., Robinson, P., Marx, J. G., Stewart, J. R., Keck, P. S., Hadland, S. E., Murphy, J. L., Lumley, M. A., Brown, K. S., Leong, M. S., Fillman, M., Broatch, J. W., Perez, A., Watford, K., Kruska, K., You, D., Ogbeide, S., Kukucka, A., Lawson, S., Ray, J. B., Martin, T., Lakehomer, J. B., Burke, A., Cohen, R. I., Grinspoon, P., Rubenstein, M. S., Sutherland, S., Walters, K., Lovejoy, T. 2019; 20 (3): 429?33

    View details for DOI 10.1093/pm/pny228

    View details for Web of Science ID 000467966600003

  • Comparative Effectiveness of Cognitive Behavioral Therapy for Chronic Pain and Chronic Pain Self-Management within the Context of Voluntary Patient-Centered Prescription Opioid Tapering: The EMPOWER Study Protocol. Pain medicine (Malden, Mass.) Darnall, B. D., Mackey, S. C., Lorig, K., Kao, M. C., Mardian, A., Stieg, R., Porter, J., DeBruyne, K., Murphy, J., Perez, L., Okvat, H., Tian, L., Flood, P., McGovern, M., Colloca, L., King, H., Van Dorsten, B., Pun, T., Cheung, M. 2019

    Abstract

    Evidence to date, while sparse, suggests that patients taking long-term opioids require special considerations and protections to prevent potential iatrogenic harms from opioid de-prescribing, such as increased pain or suffering. Following this study protocol, the EMPOWER study seeks to address multiple unmet needs of patients with chronic pain who desire to reduce long-term opioid therapy, and provide the clinical evidence on effective methodology.EMPOWER applies patient-centered methods for voluntary prescription opioid reduction conducted within a comprehensive, multi-state, 3-arm randomized controlled comparative effectiveness study of three study arms (1) group cognitive behavioral therapy for chronic pain; (2) group chronic pain self-management; and (3) usual care (taper only). Specialized electronic data capture systems collect patient reported symptoms and satisfaction data weekly and monthly during the taper, with real-time clinical alerts and electronic feedback loops informing, documenting, and steering needed care actions.The EMPOWER study seeks to provide granular evidence on patient response to voluntary opioid tapering, and will provide evidence to inform clinical systems changes, clinical care, patient satisfaction, and patient outcomes for opioid reduction.

    View details for DOI 10.1093/pm/pnz285

    View details for PubMedID 31876947

  • Central mechanisms of real and sham electroacupuncture in the treatment of chronic low back pain: study protocol for a randomized, placebo-controlled clinical trial. Trials Kong, J., MacIsaac, B., Cogan, R., Ng, A., Law, C. S., Helms, J., Schnyer, R., Karayannis, N. V., Kao, M., Tian, L., Darnall, B. D., Gross, J. J., Mackey, S., Manber, R. 2018; 19 (1): 685

    Abstract

    BACKGROUND: Chronic low back pain (CLBP) is the most common chronic pain condition and is often resistant to conventional treatments. Acupuncture is a popular alternative for treating CLBP but its mechanisms of action remain poorly understood. Evidence suggests that pain regulatory mechanisms (particularly the ascending and secondarily the descending pain modulatory pathways) and psychological mechanisms (e.g., expectations, pain catastrophizing and self-efficacy) may be involved in the pathogenesis of CLBP and its response to treatments. We will examine these mechanisms in the treatment of CLBP by electroacupuncture (EA).METHODS: We present the aims and methods of a placebo-controlled, participant-blinded and assessor-blinded mechanistic study. Adult patients with CLBP will be randomized to receiving 16 sessions of real (active) or sham (placebo) EA over the course of 8weeks. The primary pain regulatory measure for which the study was powered is temporal summation (TS), which approximates ascending pain facilitation. Conditioned pain modulation (CPM), representing a descending pain modulatory pathway, will be our secondary pain regulatory measure. The primary psychological measure is expectations of benefit, and the secondary psychological measures are pain catastrophizing and self-efficacy in managing pain. Main clinical outcomes are back pain bothersomeness on a 0-100 visual analog scale (primary), Roland Morris Disability Questionnaire (secondary), and relevant items from the National Institutes of Health (NIH) Patient-Reported Outcome Measures Information System (secondary). We hypothesize that compared to sham, real EA will lead to greater reduction in TS after 8 treatment sessions (4weeks); and that reduction in TS (and secondarily, increase in CPM) after 8 treatment sessions will mediate reduction in back pain bothersomeness from baseline to week 10 (clinical response) to EA. We also hypothesize that the three psychological factors are moderators of clinical response. With 100 treatment completers, the study is designed to have 80% power to detect a medium-sized between-group effect (d=0.5) on temporal summation.DISCUSSION: To the best of our knowledge, this is the first appropriately powered, placebo-controlled clinical trial evaluating mechanisms of EA in the treatment of CLBP.TRIAL REGISTRATION: ClinicalTrials.gov, NCT02503475 . Registered on 15 July 15 2015. Retrospectively registered.

    View details for PubMedID 30541586

  • International Stakeholder Community of Pain Experts and Leaders Call for an Urgent Action on Forced Opioid Tapering. Pain medicine (Malden, Mass.) Darnall, B. D., Juurlink, D., Kerns, R. D., Mackey, S., Van Dorsten, B., Humphreys, K., Gonzalez-Sotomayor, J. A., Furlan, A., Gordon, A. J., Gordon, D. B., Hoffman, D. E., Katz, J., Kertesz, S. G., Satel, S., Lawhern, R. A., Nicholson, K. M., Polomano, R. C., Williamson, O. D., McAnally, H., Kao, M., Schug, S., Twillman, R., Lewis, T. A., Stieg, R. L., Lorig, K., Mallick-Searle, T., West, R. W., Gray, S., Ariens, S. R., Sharpe Potter, J., Cowan, P., Kollas, C. D., Laird, D., Ingle, B., Julian Grove, J., Wilson, M., Lockman, K., Hodson, F., Palackdharry, C. S., Fillingim, R. B., Fudin, J., Barnhouse, J., Manhapra, A., Henson, S. R., Singer, B., Ljosenvoor, M., Griffith, M., Doctor, J. N., Hardin, K., London, C., Mankowski, J., Anderson, A., Ellsworth, L., Davis Budzinski, L., Brandt, B., Harkootley, G., Nickels Heck, D., Zobrosky, M. J., Cheek, C., Wilson, M., Laux, C. E., Datz, G., Dunaway, J., Schonfeld, E., Cady, M., LeDantec-Boswell, T., Craigie, M., Sturgeon, J., Flood, P., Giummarra, M., Whelan, J., Thorn, B. E., Martin, R. L., Schatman, M. E., Gregory, M. D., Kirz, J., Robinson, P., Marx, J. G., Stewart, J. R., Keck, P. S., Hadland, S. E., Murphy, J. L., Lumley, M. A., Brown, K. S., Leong, M. S., Fillman, M., Broatch, J. W., Perez, A., Watford, K., Kruska, K., Sophia You, D., Ogbeide, S., Kukucka, A., Lawson, S., Ray, J. B., Wade Martin, T., Lakehomer, J. B., Burke, A., Cohen, R. I., Grinspoon, P., Rubenstein, M. S., Sutherland, S., Walters, K. R., Lovejoy, T. 2018

    View details for PubMedID 30496540

  • Guidelines for Composing and Assessing a Paper on the Treatment of Pain: A Practical Application of Evidence-Based Medicine Principles to the Mint Randomized Clinical Trials PAIN MEDICINE McCormick, Z. L., Vorobeychik, Y., Gill, J. S., Kao, M. J., Duszynski, B., Smuck, M., Stojanovic, M. P. 2018; 19 (11): 2127?37

    Abstract

    To perform a thorough assessment of the recently published Mint Trials in order to illustrate how to read and analyze a study critically, according to principles of evidence-based medicine.Narrative review.We have applied the recently published guidelines for composing and assessing studies on the treatment of pain to a recently published article describing a large study that claimed its "findings do not support the use of radiofrequency denervation to treat chronic low back pain." These guidelines describe the critical components of a high-quality manuscript that allows communication of all relevant information from authors to readers.Application of evidence-based medicine principles to the publication describing the Mint Trials reveals significant issues with the methodology and conclusions drawn by the authors. A thorough assessment demonstrates issues with inclusion/exclusion criteria, diagnostic block protocols, radiofrequency neurotomy technique, co-interventions, outcome measurement, power analysis, study sample characteristics, data analysis, and loss to follow-up. A failure to definitively establish a diagnosis, combined with use of an inadequate technique for radiofrequency neurotomy and numerous other methodological flaws, leaves the reader unable to draw meaningful conclusions from the study data.Critical analysis, rooted in principles of evidence-based medicine, must be employed by writers and readers alike in order to encourage transparency and ensure that appropriate conclusions are drawn from study data.

    View details for PubMedID 29579232

  • Patient-Centered Prescription Opioid Tapering in Community Outpatients with Chronic Pain JAMA Internal Medicine Darnall, B., Ziadni, M., Stieg, R., Mackey, I., Kao, M., Flood, P. 2018; Feb 19

    View details for DOI 10.1001/jamainternmed.2017.8709

  • The Impact of Perceived Injustice on Pain-related Outcomes: A Combined Model Examining the Mediating Roles of Pain Acceptance and Anger in a Chronic Pain Sample. The Clinical journal of pain Carriere, J. S., Sturgeon, J. A., Yakobov, E., Kao, M. C., Mackey, S. C., Darnall, B. D. 2018; 34 (8): 739?47

    Abstract

    Perceived injustice (PI) has been identified as an important risk factor for pain-related outcomes. To date, research has shown that pain acceptance and anger are mediators of the association between PI and pain-related outcomes. However, a combined conceptual model that addresses the interrelationships between these variables is currently lacking. Therefore, the current study aimed to examine the potential mediating roles of pain acceptance and anger on the association between PI and adverse pain-related outcomes (physical function, pain intensity, opioid use status).This cross-sectional study used a sample of 354 patients with chronic pain being treated at a tertiary pain treatment center. Participants completed measures of PI, pain acceptance, anger, physical function, pain intensity, and opioid use status. Mediation analyses were used to examine the impact of pain acceptance and anger on the association between PI and pain-related outcomes.Examination of the specific indirect effects revealed that pain acceptance fully mediated the relationship between PI and physical function, as well as the relationship between PI and opioid use status. Pain acceptance emerged as a partial mediator of the relationship between PI and pain intensity.This is the first study to provide a combined conceptual model investigating the mediating roles of pain acceptance and anger on the relationship between PI and pain outcomes. On the basis of our findings, low levels of pain acceptance associated with PI may help explain the association between PI and adverse pain outcomes. Clinical and theoretical implications are discussed.

    View details for PubMedID 29485535

  • Patient-Centered Prescription Opioid Tapering in Community Outpatients With Chronic Pain. JAMA internal medicine Darnall, B. D., Ziadni, M. S., Stieg, R. L., Mackey, I. G., Kao, M. C., Flood, P. 2018; 178 (5): 707?8

    View details for PubMedID 29459978

  • Comparative Efficacy and Mechanisms of a Single-Session Pain Psychology Class in Chronic Low Back Pain: Study Protocol for a Randomized Controlled Trial. Trials Darnall, B. D., Ziadni, M. S., Roy, A., Kao, M. C., Sturgeon, J. A., Cook, K. F., Lorig, K., Burns, J. W., Mackey, S. C. 2018; 19 (1): 165

    Abstract

    The Institute of Medicine (IOM) reported that chronic pain affects about 100 million U.S. adults, with chronic low back pain (CLBP) cited as the most prevalent type. Pain catastrophizing is a psychological construct shown to predict the development and trajectory of chronic pain and patient response to pain treatments. While effective treatment for pain catastrophizing typically includes eight-session groups of cognitive behavioral therapy (CBT), a single-session targeted treatment class yielded promising results which, if replicated and extended, could prove to efficiently and cost-effectively reduce pain catastrophizing. In this trial, we seek to determine the comparative efficacy of this novel single-session pain catastrophizing class to an eight-session course of pain CBT and a single-session back pain health education class. We will also explore the psychosocial mechanisms and outcomes of pain catastrophizing treatment.In this trial we will randomize 231 individuals with CLBP to one of three treatment arms: (1) pain-CBT (eight weekly 2-h group sessions with home exercises and readings); (2) a single 2-h pain catastrophizing class; or (3) a single 2-h back pain health education class (active control). For the primary outcome of pain catastrophizing, the trial is designed as a non-inferiority test between pain-CBT and the single-session pain catastrophizing class, and as a superiority test between the single-session pain catastrophizing class and the health education class. Team researchers masked to treatment assignment will assess outcomes up to six months post treatment.If the single-session targeted pain catastrophizing class is found to be an effective treatment for patients with CLBP, this low cost and low burden treatment could dismantle many of the current barriers and burdens of effective pain care. Further, elucidation of the mechanisms of pain catastrophizing treatments will facilitate future research on the topic as well as further development and refinement of treatments.ClinicalTrials.gov, NCT03167086 . Registered on 22 May 2017.

    View details for PubMedID 29510735

  • The impact of perceived injustice on pain-related outcomes: A combined model examining the mediating roles of pain acceptance and anger in a chronic pain sample Clin J Pain Carrier, J., Sturgeon, J., Yakabov, E., Kao, M., Mackey, S., Darnall, B. 2018: 739?47

    Abstract

    Perceived injustice (PI) has been identified as an important risk factor for pain-related outcomes. To date, research has shown that pain acceptance and anger are mediators of the association between PI and pain-related outcomes. However, a combined conceptual model that addresses the interrelationships between these variables is currently lacking. Therefore, the current study aimed to examine the potential mediating roles of pain acceptance and anger on the association between PI and adverse pain-related outcomes (physical function, pain intensity, opioid use status).This cross-sectional study used a sample of 354 patients with chronic pain being treated at a tertiary pain treatment center. Participants completed measures of PI, pain acceptance, anger, physical function, pain intensity, and opioid use status. Mediation analyses were used to examine the impact of pain acceptance and anger on the association between PI and pain-related outcomes.Examination of the specific indirect effects revealed that pain acceptance fully mediated the relationship between PI and physical function, as well as the relationship between PI and opioid use status. Pain acceptance emerged as a partial mediator of the relationship between PI and pain intensity.This is the first study to provide a combined conceptual model investigating the mediating roles of pain acceptance and anger on the relationship between PI and pain outcomes. On the basis of our findings, low levels of pain acceptance associated with PI may help explain the association between PI and adverse pain outcomes. Clinical and theoretical implications are discussed.

    View details for DOI 10.1097/AJP.0000000000000602

  • Comparative Efficacy and Mechanisms of a Single-Session Pain Psychology Class in Chronic Low Back Pain: Study Protocol for a Randomized Controlled Trial Trials Darnall, B., Siadni, M., Roy, A., Kao, M., Sturgeon, J., Cook, K., Lorig, K., Burns, J., Mackey, S. 2018: 165

    Abstract

    The Institute of Medicine (IOM) reported that chronic pain affects about 100 million U.S. adults, with chronic low back pain (CLBP) cited as the most prevalent type. Pain catastrophizing is a psychological construct shown to predict the development and trajectory of chronic pain and patient response to pain treatments. While effective treatment for pain catastrophizing typically includes eight-session groups of cognitive behavioral therapy (CBT), a single-session targeted treatment class yielded promising results which, if replicated and extended, could prove to efficiently and cost-effectively reduce pain catastrophizing. In this trial, we seek to determine the comparative efficacy of this novel single-session pain catastrophizing class to an eight-session course of pain CBT and a single-session back pain health education class. We will also explore the psychosocial mechanisms and outcomes of pain catastrophizing treatment.In this trial we will randomize 231 individuals with CLBP to one of three treatment arms: (1) pain-CBT (eight weekly 2-h group sessions with home exercises and readings); (2) a single 2-h pain catastrophizing class; or (3) a single 2-h back pain health education class (active control). For the primary outcome of pain catastrophizing, the trial is designed as a non-inferiority test between pain-CBT and the single-session pain catastrophizing class, and as a superiority test between the single-session pain catastrophizing class and the health education class. Team researchers masked to treatment assignment will assess outcomes up to six months post treatment.If the single-session targeted pain catastrophizing class is found to be an effective treatment for patients with CLBP, this low cost and low burden treatment could dismantle many of the current barriers and burdens of effective pain care. Further, elucidation of the mechanisms of pain catastrophizing treatments will facilitate future research on the topic as well as further development and refinement of treatments.ClinicalTrials.gov, NCT03167086 . Registered on 22 May 2017.

    View details for DOI 10.1186/s13063-018-2537-3

    View details for PubMedCentralID PMC5838852

  • Radiofrequency Denervation for Chronic Low Back Pain JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Kao, M., Leong, M. S., Mackey, S. 2017; 318 (22): 2256

    View details for DOI 10.1001/jama.2017.16382

    View details for Web of Science ID 000417822700026

  • Stagnant Physical Therapy Referral Rates Alongside Rising Opioid Prescription Rates in Patients With Low Back Pain in the United States 1997-2010 SPINE Zheng, P., Kao, M., Karayannis, N. V., Smuck, M. 2017; 42 (9): 670-674

    Abstract

    A cross-sectional observational study utilizing the National Ambulatory and National Hospital Ambulatory Medical Care Surveys between 1997 and 2010.The aim of this study was to characterize national physical therapy (PT) referral trends during primary care provider (PCP) visits in the United States.Despite guidelines recommending PT for the initial management of low back pain (LBP), national PT referral rates remain low.Race, ethnicity, age, payer type, and PT referral rates were collected for patients aged 16 to 90 years who were visiting their PCPs. Associations among demographic variables and PT referral were determined using logistic regression.Between 1997 and 2010, we estimated 170 million visits for LBP leading to 17.1 million PT referrals. Average proportion of PCP visits associated with PT referrals remained stable at about 10.1% [odds ratio (OR) 1.00, 95% confidence interval (95% CI) 0.96-1.04)], despite our prior finding of increasing number of visits associated with opioid prescriptions in the same timeframe.Lower PT referral rates were observed among visits by patients who were insured by Medicaid (OR 0.48, 95% CI 0.33-0.69) and Medicare (OR 0.50, 95% CI 0.35-0.72). Furthermore, visits not associated with PT referrals were more likely to be associated with opioid prescriptions (OR 1.69, 95% CI 1.22-2.35).Although therapies delivered by PTs are promoted as a first-line treatment for LBP, PT referral rates remain low. There also exist disparately lower referral rates in populations with more restrictive health plans and simultaneous opioid prescription. Our findings provide a broad overview to PT prescription trend and isolate concerning associations requiring further explorations.3.

    View details for DOI 10.1097/BRS.0000000000001875

    View details for Web of Science ID 000401015100015

    View details for PubMedID 28441685

  • Pain behavior mediates the relationship between perceived injustice and opioid prescription for chronic pain: A Collaborative Health Outcomes Information Registry (CHOIR) study Carriere, J., Martel, M., Kao, M., Sullivan, M., Darnall, B. CHURCHILL LIVINGSTONE. 2017: S33

    View details for DOI 10.1016/j.jpain.2017.02.123

    View details for Web of Science ID 000398755400136

  • PREEMPT: Prospective from complex patients in practice Flood, P., Barad, M., Sturgeon, J., Kao, M., Fish, S., Mackey, S. CHURCHILL LIVINGSTONE. 2017: S67

    View details for DOI 10.1016/j.jpain.2017.02.345

    View details for Web of Science ID 000398755400276

  • Physical performance analysis: A new approach to assessing free-living physical activity in musculoskeletal pain and mobility-limited populations. PloS one Smuck, M., Tomkins-Lane, C., Ith, M. A., Jarosz, R., Kao, M. J. 2017; 12 (2)

    Abstract

    Accurate measurement of physical performance in individuals with musculoskeletal pain is essential. Accelerometry is a powerful tool for this purpose, yet the current methods designed to evaluate energy expenditure are not optimized for this population. The goal of this study is to empirically derive a method of accelerometry analysis specifically for musculoskeletal pain populations.We extracted data from 6,796 participants in the 2003-4 National Health and Nutrition Examination Survey (NHANES) including: 7-day accelerometry, health and pain questionnaires, and anthropomorphics. Custom macros were used for data processing, complex survey regression analyses, model selection, and statistical adjustment. After controlling for a multitude of variables that influence physical activity, we investigated whether distinct accelerometry profiles accompany pain in different locations of the body; and we identified the intensity intervals that best characterized these profiles.Unique accelerometry profiles were observed for pain in different body regions, logically clustering together based on proximity. Based on this, the following novel intervals (counts/minute) were identified and defined: Performance Sedentary (PSE) = 1-100, Performance Light 1 (PL1) = 101-350, Performance Light 2 (PL2) = 351-800, Performance Light 3 (PL3) = 801-2500, and Performance Moderate/Vigorous (PMV) = 2501-30000. The refinement of accelerometry signals into these new intervals, including 3 distinct ranges that fit inside the established light activity range, best captures alterations in real-life physical performance as a result of regional pain.These new accelerometry intervals provide a model for objective measurement of real-life physical performance in people with pain and musculoskeletal disorders, with many potential uses. They may be used to better evaluate the relationship between pain and daily physical function, monitor musculoskeletal disease progression, gauge disease severity, inform exercise prescription, and quantify the functional impact of treatments. Based on these findings, we recommend that future studies of pain and musculoskeletal disorders analyze accelerometry output based on these new "physical performance" intervals.

    View details for DOI 10.1371/journal.pone.0172804

    View details for PubMedID 28235039

    View details for PubMedCentralID PMC5325560

  • Radiofrequency Denervation for Chronic Low Back Pain. JAMA Kao, M. C., Leong, M. S., Mackey, S. 2017; 318 (22): 2256

    View details for PubMedID 29234799

  • Pain Catastrophizing Moderates Relationships between Pain Intensity and Opioid Prescription: Nonlinear Sex Differences Revealed Using a Learning Health System. Anesthesiology Sharifzadeh, Y., Kao, M. C., Sturgeon, J. A., Rico, T. J., Mackey, S., Darnall, B. D. 2017; 127 (1): 136?46

    Abstract

    Pain catastrophizing is a maladaptive response to pain that amplifies chronic pain intensity and distress. Few studies have examined how pain catastrophizing relates to opioid prescription in outpatients with chronic pain.The authors conducted a retrospective observational study of the relationships between opioid prescription, pain intensity, and pain catastrophizing in 1,794 adults (1,129 women; 63%) presenting for new evaluation at a large tertiary care pain treatment center. Data were sourced primarily from an open-source, learning health system and pain registry and secondarily from manual review of electronic medical records. A binary opioid prescription variable (yes/no) constituted the dependent variable; independent variables were age, sex, pain intensity, pain catastrophizing, depression, and anxiety.Most patients were prescribed at least one opioid medication (57%; n = 1,020). A significant interaction and main effects of pain intensity and pain catastrophizing on opioid prescription were noted (P < 0.04). Additive modeling revealed sex differences in the relationship between pain catastrophizing, pain intensity, and opioid prescription, such that opioid prescription became more common at lower levels of pain catastrophizing for women than for men.Results supported the conclusion that pain catastrophizing and sex moderate the relationship between pain intensity and opioid prescription. Although men and women patients had similar Pain Catastrophizing Scale scores, historically "subthreshold" levels of pain catastrophizing were significantly associated with opioid prescription only for women patients. These findings suggest that pain intensity and catastrophizing contribute to different patterns of opioid prescription for men and women patients, highlighting a potential need for examination and intervention in future studies.

    View details for PubMedID 28614083

  • Pain catastrophizing moderates the relationship between pain intensity and opioid prescription: Non-linear gender differences revealed using a learning health system Anesthesiology Sharifzadeh, Y., Kao, M., Sturgeon, J., Mackey, S., Darnall, B. 2017: 136?46

    Abstract

    Pain catastrophizing is a maladaptive response to pain that amplifies chronic pain intensity and distress. Few studies have examined how pain catastrophizing relates to opioid prescription in outpatients with chronic pain.The authors conducted a retrospective observational study of the relationships between opioid prescription, pain intensity, and pain catastrophizing in 1,794 adults (1,129 women; 63%) presenting for new evaluation at a large tertiary care pain treatment center. Data were sourced primarily from an open-source, learning health system and pain registry and secondarily from manual review of electronic medical records. A binary opioid prescription variable (yes/no) constituted the dependent variable; independent variables were age, sex, pain intensity, pain catastrophizing, depression, and anxiety.Most patients were prescribed at least one opioid medication (57%; n = 1,020). A significant interaction and main effects of pain intensity and pain catastrophizing on opioid prescription were noted (P < 0.04). Additive modeling revealed sex differences in the relationship between pain catastrophizing, pain intensity, and opioid prescription, such that opioid prescription became more common at lower levels of pain catastrophizing for women than for men.Results supported the conclusion that pain catastrophizing and sex moderate the relationship between pain intensity and opioid prescription. Although men and women patients had similar Pain Catastrophizing Scale scores, historically "subthreshold" levels of pain catastrophizing were significantly associated with opioid prescription only for women patients. These findings suggest that pain intensity and catastrophizing contribute to different patterns of opioid prescription for men and women patients, highlighting a potential need for examination and intervention in future studies.

    View details for DOI 10.1097/ALN.0000000000001656

    View details for PubMedCentralID PMC5478434

  • Tensile-strained Ge/SiGe multiple quantum well microdisks Photonics Research Chen, X., Fenrich, C. S., Xue, M., Kao, M., Zang, K., Lu, C., Fei, E. T., Chen, Y., Huo, Y., Kamins, T. I., Harris, J. S. 2017; 5 (6): B7-B14

    View details for DOI 10.1364/PRJ.5.0000B7

  • Pain behavior mediates the relationship between perceived injustice and opioid prescription for chronic pain: a Collaborative Health Outcomes Information Registry study JOURNAL OF PAIN RESEARCH Carriere, J. S., Martel, M., Kao, M., Sullivan, M. J., Darnall, B. D. 2017; 10

    Abstract

    Perceived injustice has been defined as an appraisal regarding the severity and irreparability of loss associated with pain, blame and a sense of unfairness. Recent findings have identified perceived injustice as an important risk factor for pain-related outcomes. Studies suggest that perceived injustice is associated with opioid prescription in patients with pain conditions. However, the mechanisms by which perceived injustice is linked to opioid prescription are not well understood. The primary objective of this study was to examine the potential mediating roles of pain intensity, depressive symptoms and pain behavior in the association between perceived injustice and opioid prescription among patients with chronic pain.This cross-sectional study used a sample of 344 patients with chronic pain being treated at a tertiary pain treatment center. Participants completed measures of perceived injustice, pain intensity, depressive symptoms, pain behavior and opioid prescription. Bootstrapped multiple mediation analyses were used to examine the mediating role of patients' pain intensity, depressive symptoms and pain behavior in the association between perceived injustice and opioid prescription.Consistent with previous research, we found a significant association between perceived injustice and opioid prescription. Interestingly, results revealed that pain behavior was the only variable that mediated the association between perceived injustice and opioid prescription.This study was the first to examine the mechanisms by which perceived injustice is associated with opioid prescription in patients with chronic pain. We found that pain behavior, rather than pain intensity and depressive symptoms, mediated the association between perceived injustice and opioid prescription. Future research in this area should employ a longitudinal research design in order to arrive at clearer causal conclusions about the relationships between pain behavior, perceived injustice and opioid prescription.

    View details for DOI 10.2147/JPR.S128184

    View details for Web of Science ID 000396321100001

    View details for PubMedID 28331358

  • Social Disruption Mediates the Relationship Between Perceived Injustice and Anger in Chronic Pain: a Collaborative Health Outcomes Information Registry Study. Annals of behavioral medicine Sturgeon, J. A., Carriere, J. S., Kao, M. J., Rico, T., Darnall, B. D., Mackey, S. C. 2016: -?

    Abstract

    Perceptions of pain as unfair are a significant risk factor for poorer physical and psychological outcomes in acute injury and chronic pain. Chief among the negative emotions associated with perceived injustice is anger, arising through frustration of personal goals and unmet expectations regarding others' behavior. However, despite a theoretical connection with anger, the social mediators of perceived injustice have not been demonstrated in chronic pain.The current study examined two socially based variables and a broader measure of pain interference as mediators of the relationships between perceived injustice and both anger and pain intensity in a sample of 302 patients in a tertiary care pain clinic setting.Data from the Collaborative Health Outcomes Information Registry (CHOIR) were analyzed using cross-sectional path modeling analyses to examine social isolation, satisfaction with social roles and activities, and pain-related interference as potential mediators of the relationships between perceived injustice and both anger and pain intensity.When modeled simultaneously, ratings of social isolation mediated the relationship between perceived injustice and anger, while pain-related interference and social satisfaction did not. Neither social variable was found to mediate the relationship between perceived injustice and pain intensity, however.The current findings highlight the strongly interpersonal nature of perceived injustice and anger in chronic pain, though these effects do not appear to extend to the intensity of pain itself. Nevertheless, the results highlight the need for interventions that ameliorate both maladaptive cognitive appraisal of pain and pain-related disruptions in social relationships.

    View details for PubMedID 27325314

  • Seated Tai Chi to alleviate pain and improve quality of life in individuals with spinal cord disorder. journal of spinal cord medicine Shem, K., Karasik, D., Carufel, P., Kao, M., Zheng, P. 2016; 39 (3): 353-358

    Abstract

    Previous research studies have confirmed therapeutic physical and psychological benefits of Tai Chi for both the able-bodied and disabled populations. However, given the limited availability of seated Tai Chi, there have not been any studies to date that have examined the effectiveness of seated Tai Chi in individuals with spinal cord disorder (SCD). We designed a customized seated Tai Chi program to meet the need for improved exercise options for individuals with SCD.Twenty-six participants were enrolled in a 12-week seated Tai Chi course consisting of weekly sessions. After each Tai Chi session, patients reported improved visual analog scale (VAS) monitoring pain (P) (3.18 v 2.93; P 1.63E-03), emotional sense of well-being (EWB) (2.61 vs 2.04; P 2.86E-07), mental distraction (MD) (3.13 v 2.29; P 9.36E-08), physical sense of well-being (PWB) (2.84 v 2.25; p 7.38E-08), and sense of spiritual connection (SC) (3.28 v 2.50; P 6.46E-08). In our limited follow-up of 9 participants who completed half of the sessions and the long term surveys after the 12-week course, there were no detectable differences in weekly P, EWB, MD, PWB, and SC before each session.Individuals with SCD demonstrated benefits in pain, emotional sense of well-being, mental distraction, physical sense of well-being, and sense of spiritual connection immediately after seated Tai Chi exercise sessions in our pilot study. More research in a larger population would be needed to study the long-term impact of seated Tai Chi.

    View details for DOI 10.1080/10790268.2016.1148895

    View details for PubMedID 26914968

  • COLLABORATIVE HEALTH OUTCOMES INFORMATION REGISTRY (CHOIR): OPEN SOURCE PLATFORM FOR LEARNING HEALTH SYSTEMS Kao, M., Cook, K., Olson, G., Darnall, B. D., Weber, S., Mackey, S., Flood, P. LIPPINCOTT WILLIAMS & WILKINS. 2016

    View details for Web of Science ID 000403582200185

  • (180) Development and validation of a Daily Pain Catastrophizing Scale (Daily PCS) measure. journal of pain Darnall, B., Sturgeon, J., Cook, K., Taub, C., Kao, M., RICO, T., Mackey, S. 2016; 17 (4S): S20-S21

    View details for DOI 10.1016/j.jpain.2016.01.083

    View details for PubMedID 28162404

  • (448) Perceived injustice, pain behavior and opioid prescriptions: a vicious circle? A Collaborative Health Outcomes Information Registry (CHOIR) Study. journal of pain Carriere, J., Darnall, B., Sullivan, M., Kao, M., Mackey, S. 2016; 17 (4S): S86-?

    View details for DOI 10.1016/j.jpain.2016.01.425

    View details for PubMedID 28162695

  • (489) An examination of the roles of perceived injustice and pain acceptance on pain interference and pain intensity in patients with chronic pain: A Collaborative Health Outcomes Information Registry (CHOIR) Study. journal of pain Carriere, J., Darnall, B., Kao, M., Mackey, S. 2016; 17 (4S): S97-?

    View details for DOI 10.1016/j.jpain.2016.01.296

    View details for PubMedID 28162741

  • (418) A novel glial cell inhibitor, low dose naltrexone, reduces pain and depression, and improves function in chronic pain: A CHOIR study. journal of pain Noon, K., Sturgeon, J., Kao, M., Darnall, B., Mackey, S. 2016; 17 (4S): S79-?

    View details for DOI 10.1016/j.jpain.2016.01.395

    View details for PubMedID 28162662

  • Social Disruption Mediates the Relationship Between Perceived Injustice and Anger in Chronic Pain: a Collaborative Health Outcomes Information Registry Study Annals of Behavioral Medicine Sturgeon, J. A., Carriere, J. S., Kao, M. J., Rico, T. J., Darnall, B. D., Mackey, S. C. 2016: 802?12

    Abstract

    Perceptions of pain as unfair are a significant risk factor for poorer physical and psychological outcomes in acute injury and chronic pain. Chief among the negative emotions associated with perceived injustice is anger, arising through frustration of personal goals and unmet expectations regarding others' behavior. However, despite a theoretical connection with anger, the social mediators of perceived injustice have not been demonstrated in chronic pain.The current study examined two socially based variables and a broader measure of pain interference as mediators of the relationships between perceived injustice and both anger and pain intensity in a sample of 302 patients in a tertiary care pain clinic setting.Data from the Collaborative Health Outcomes Information Registry (CHOIR) were analyzed using cross-sectional path modeling analyses to examine social isolation, satisfaction with social roles and activities, and pain-related interference as potential mediators of the relationships between perceived injustice and both anger and pain intensity.When modeled simultaneously, ratings of social isolation mediated the relationship between perceived injustice and anger, while pain-related interference and social satisfaction did not. Neither social variable was found to mediate the relationship between perceived injustice and pain intensity, however.The current findings highlight the strongly interpersonal nature of perceived injustice and anger in chronic pain, though these effects do not appear to extend to the intensity of pain itself. Nevertheless, the results highlight the need for interventions that ameliorate both maladaptive cognitive appraisal of pain and pain-related disruptions in social relationships.

    View details for DOI 10.1007/s12160-016-9808-6

    View details for PubMedCentralID PMC5127748

  • The State of Triptan Prescription for the Management of Migraine in the US Zheng, P., Kao, M., Barad, M., Mackey, S. WILEY-BLACKWELL. 2015: 151?52

    View details for Web of Science ID 000356430500062

  • Anger mediates the relationship between trauma and pain catastrophizing in chronic pain Taub, C., Chahal, M., Darnall, B., Kao, M., Mackey, S. CHURCHILL LIVINGSTONE. 2015: S99

    View details for DOI 10.1016/j.jpain.2015.01.412

    View details for Web of Science ID 000352748600393

  • Sub-clinical range of pain catastrophizing moderates the effect of pain intensity on opioid prescription Sharifzadeh, Y., Darnall, B., Kao, M., Mackey, S. CHURCHILL LIVINGSTONE. 2015: S16?S16

    View details for Web of Science ID 000352748600065

  • Physical and psychological correlates of fatigue and physical function: a Stanford-NIH CHOIR study Sturgeon, J., Darnall, B., Kao, M., Mackey, S. CHURCHILL LIVINGSTONE. 2015: S18

    View details for DOI 10.1016/j.jpain.2015.01.084

    View details for Web of Science ID 000352748600072

  • Implications of pain interference on restoration of physical function for people with chronic pain Karayannis, N., Kao, M., Prasad, R., Cooley, C., Mackey, S. CHURCHILL LIVINGSTONE. 2015: S109

    View details for DOI 10.1016/j.jpain.2015.01.452

    View details for Web of Science ID 000352748600433

  • Stanford Patient Experience Questionnaire (SPEQ): network of patient experience touch points revealed by Bayesian network reconstruction suggests targets for intervention Kao, M., Leong, M., Prasad, R., Cullen, A., Pacht, T., Wellisch, O., Olson, G., Darnall, B., Weber, S., Mackey, S. CHURCHILL LIVINGSTONE. 2015: S36

    View details for DOI 10.1016/j.jpain.2015.01.159

    View details for Web of Science ID 000352748600145

  • Stanford Patient Experience Questionnaire (SPEQ): Machine-mediated classification of patient experience feedback using natural language processing Kao, M., Leong, M., Prasad, R., Cullen, A., Pacht, T., Olson, G., Darnall, B., Weber, S., Mackey, S. CHURCHILL LIVINGSTONE. 2015: S37

    View details for DOI 10.1016/j.jpain.2015.01.160

    View details for Web of Science ID 000352748600146

  • Assessment of anxiety as mediator of the relationship between sleep disturbance and pain catastrophizing in chronic pain Chahal, M., Taub, C., Darnall, B., Kao, M., Mackey, S. CHURCHILL LIVINGSTONE. 2015: S5

    View details for DOI 10.1016/j.jpain.2015.01.030

    View details for Web of Science ID 000352748600018

  • Somatic distributions of pain characterized with a pain registry (CHOIR) Johnson, K., Foote, A., Kao, M., Mackey, S. CHURCHILL LIVINGSTONE. 2015: S8

    View details for DOI 10.1016/j.jpain.2015.01.042

    View details for Web of Science ID 000352748600030

  • Physical and Psychological Correlates of Fatigue and Physical Function: A Collaborative Health Outcomes Information Registry (CHOIR) Study. journal of pain Sturgeon, J. A., Darnall, B. D., Kao, M. J., Mackey, S. C. 2015; 16 (3): 291-298 e1

    Abstract

    Fatigue is a multidimensional construct that has significant implications for physical function in chronic non-cancer pain populations but remains relatively understudied. The current study characterized the independent contributions of self-reported ratings of pain intensity, sleep disturbance, depression, and fatigue to ratings of physical function and pain-related interference in a diverse sample of treatment-seeking individuals with chronic pain. Methods: These relationships were examined as a path modeling analysis of self-report scores obtained from 2,487 individuals with chronic pain from a tertiary care outpatient pain clinic.Our analyses revealed unique relationships of pain intensity, sleep disturbance, and depression with self-reported fatigue. Further, fatigue scores accounted for significant proportions of the relationships of both pain intensity and depression with physical function and pain-related interference, and accounted for the entirety of the unique statistical relationship between sleep disturbance and both physical function and pain-related interference.Fatigue is a complex construct with relationships to both physical and psychological factors that has significant implications for physical functioning in chronic non-cancer pain. The current results identify potential targets for future treatment of fatigue in chronic pain, and may provide directions for future clinical and theoretical research in the area of chronic non-cancer pain.Fatigue is an important physical and psychological variable that factors prominently in the deleterious consequences of pain intensity, sleep disturbance, and depression for physical function in chronic non-cancer pain.

    View details for DOI 10.1016/j.jpain.2014.12.004

    View details for PubMedID 25536536

  • Determinants of Physical Activity in America: A First Characterization of Physical Activity Profile Using the National Health and Nutrition Examination Survey (NHANES) PM&R Kao, M. J., Jarosz, R., Goldin, M., Patel, A., Smuck, M. 2014; 6 (10): 882-892

    Abstract

    To develop and implement methodologies for characterizing accelerometry-derived patterns of physical activity (PA) in the United States in relation to demographics, anthropometrics, behaviors, and comorbidities using the National Health and Nutrition Examination Survey (NHANES) dataset.Retrospective analysis of nationally representative database.Computer-generated modeling in silico.A total of 6329 adults in the United States from the NHANES 2003-2004 database.To discover subtle multivariate signal in the dynamic and noisy accelerometry data, we developed a novel approach, termed discretized multiple adaptive regression and implemented the algorithm in SAS 9.2 (SAS Institute, Cary, NC).Demographic, anthropometric, comorbidity, and behavioral variables.The intensity of PA decreased with both increased age and increased body mass index. Both greater education and greater income correlate with increased activity over short durations and reduced activity intensity over long durations. Numerous predictors demonstrated effects within activity ranges that may be masked by use of the standard activity intensity intervals. These include age, one of the most robust variables, where we discovered decreasing activities inside the moderate activity range. It also includes gender, where women compared with men have increased proportions of active times up to the center of light activity range, and income greater than $45,000, where a complex effect is seen with little correspondence to existing cut-points.The results presented in this study suggest that the method of multiple regression and heat map visualization can generate insights otherwise hidden in large datasets such as NHANES. A review of the provided heat maps reveals the trends discussed previously involving demographic, anthropometric, comorbidity, and behavioral variables. It also demonstrates the power of accelerometry to expose alterations in PA. Ultimately, this study provides a US population-based norm to use in future studies of PA.

    View details for DOI 10.1016/j.pmrj.2014.03.004

    View details for Web of Science ID 000344234600004

  • Determinants of physical activity in America: a first characterization of physical activity profile using the National Health and Nutrition Examination Survey (NHANES). PM & R : the journal of injury, function, and rehabilitation Kao, M. J., Jarosz, R., Goldin, M., Patel, A., Smuck, M. 2014; 6 (10): 882-892

    Abstract

    To develop and implement methodologies for characterizing accelerometry-derived patterns of physical activity (PA) in the United States in relation to demographics, anthropometrics, behaviors, and comorbidities using the National Health and Nutrition Examination Survey (NHANES) dataset.Retrospective analysis of nationally representative database.Computer-generated modeling in silico.A total of 6329 adults in the United States from the NHANES 2003-2004 database.To discover subtle multivariate signal in the dynamic and noisy accelerometry data, we developed a novel approach, termed discretized multiple adaptive regression and implemented the algorithm in SAS 9.2 (SAS Institute, Cary, NC).Demographic, anthropometric, comorbidity, and behavioral variables.The intensity of PA decreased with both increased age and increased body mass index. Both greater education and greater income correlate with increased activity over short durations and reduced activity intensity over long durations. Numerous predictors demonstrated effects within activity ranges that may be masked by use of the standard activity intensity intervals. These include age, one of the most robust variables, where we discovered decreasing activities inside the moderate activity range. It also includes gender, where women compared with men have increased proportions of active times up to the center of light activity range, and income greater than $45,000, where a complex effect is seen with little correspondence to existing cut-points.The results presented in this study suggest that the method of multiple regression and heat map visualization can generate insights otherwise hidden in large datasets such as NHANES. A review of the provided heat maps reveals the trends discussed previously involving demographic, anthropometric, comorbidity, and behavioral variables. It also demonstrates the power of accelerometry to expose alterations in PA. Ultimately, this study provides a US population-based norm to use in future studies of PA.

    View details for DOI 10.1016/j.pmrj.2014.03.004

    View details for PubMedID 24631950

  • Trends in ambulatory physician opioid prescription in the United States, 1997-2009. PM & R : the journal of injury, function, and rehabilitation Jeffrey Kao, M., Minh, L. C., Huang, G. Y., Mitra, R., Smuck, M. 2014; 6 (7): 575-582 e4

    Abstract

    To describe the changing practice pattern of opioid medication prescription by health care providers and its relationship to shifts in the incidence of back pain, demographics, and health care access.Retrospective analysis of nationally representative databases.In silico.Patients who presented at a set of randomly selected health care facilities on the days of data collection.Nationally representative surveys from the Centers for Disease Control and Prevention (National Hospital and Ambulatory Medical Center Survey and National Ambulatory Medical Center Survey) were investigated for 3 ambulatory settings-emergency department (ED), primary care physician (PCP), and specialist physician offices-between the years 1997 and 2009. Diagnoses, prescription medications, insurance source, and demographics were determined. Weighted logistic regression modeling with the SAS program (SAS Institute, Cary, NC) was used to estimate 5-year odds ratios (ORs) and covariate effects.Diagnoses, prescription medications, insurance source, and demographics were measured. The relationships between opioid medication prescription and (1) the chief complaint and (2) back pain diagnoses were studied. Domain analysis was used to properly account for the stochasticity introduced by subset analyses.From 1997 to 2009, increasing all-diagnosis opioid prescription was accompanied by significant shifts in patient demographics and insurance access. For all-diagnosis opioid prescription, after we adjusted for age, gender, race, and insurance source, the increase persisted at a 5-year OR of 1.33, 1.29, and 1.53 for ED, PCP clinics, and specialist clinics (95% confidence interval 1.26-1.41, 1.19-1.40, and 1.37-1.69), respectively. The increasing prevalence of back pain diagnosis was eclipsed by increasing opioid prescriptions, estimated at 5-year ORs of 1.35, 1.38, and 1.75 for ED, PCP clinics, and specialist clinics (95% confidence interval 1.22-1.48, 1.19-1.61, 1.40-2.19), respectively.In the United States, from 1997-2009, (1) variable increases in opioid prescription across ambulatory care settings were not accounted for by changing demographics and health care access; (2) significant disparities existed in opioid prescription as a function of age, gender, race/ethnicity, and payer source; and (3) for back pain, increasing opioid prescription was not accounted for by changing incidence.

    View details for DOI 10.1016/j.pmrj.2013.12.015

    View details for PubMedID 24412267

  • National Trends of Opioid Treatment for Adult and Pediatric Migraine Headache Patients in the Emergency Department Eaton, K., Kao, M., Barad, M. WILEY-BLACKWELL. 2014: 15

    View details for Web of Science ID 000337950600030

  • Novel characterization of between-individual variability in thermal temporal summation response Ojha, R., Kong, J., Kao, M., Bagarinao, E., Olshen, R., Mackey, S. CHURCHILL LIVINGSTONE. 2014: S65

    View details for DOI 10.1016/j.jpain.2014.01.269

    View details for Web of Science ID 000334648700259

  • Stanford-NIH Pain Registry: open source platform for large-scale longitudinal assessment and tracking of modern patient-reported outcomes Kao, M., Weber, S., Cook, K., Garrick, O., Pacht, T., Darnall, B., Mackey, S. CHURCHILL LIVINGSTONE. 2014: S40?S40

    View details for Web of Science ID 000334648700158

  • Stanford-NIH Pain Registry: catalyzing the rate limited step of psychometrics with modern patient-reported outcomes Kao, M., Cook, K., Olson, G., Pacht, T., Darnall, B., Weber, S., Mackey, S. CHURCHILL LIVINGSTONE. 2014: S3?S3

    View details for Web of Science ID 000334648700012

  • "Control over catastrophizing": development of a single-session psychobehavioral intervention to reduce pain catastrophizing Darnall, B., Sturgeon, J., Kao, M., Mackey, S. CHURCHILL LIVINGSTONE. 2014: S109

    View details for DOI 10.1016/j.jpain.2014.01.445

    View details for Web of Science ID 000334648700432

  • Trends in benzodiazepine prescription and co-prescription with opioids in primary care clinics in the United States, 2002 to 2009 Kao, M., Zheng, P., Hah, J., Mackey, S. CHURCHILL LIVINGSTONE. 2014: S41

    View details for DOI 10.1016/j.jpain.2014.01.168

    View details for Web of Science ID 000334648700160

  • Assessment and management of back pain. JAMA internal medicine Kao, M., Zheng, P., Smuck, M. 2014; 174 (3): 479-?

    View details for DOI 10.1001/jamainternmed.2013.13695

    View details for PubMedID 24590093

  • Does physical activity influence the relationship between low back pain and obesity? SPINE JOURNAL Smuck, M., Kao, M. J., Brar, N., Martinez-Ith, A., Choi, J., Tomkins-Lane, C. C. 2014; 14 (2): 209-216

    Abstract

    Evidence supporting an association between obesity and low back pain (LBP) continues to grow; yet little is known about the cause and effect of this relationship. Even less is known about the mechanisms linking the two. Physical activity is a logical suspect, but no study has demonstrated its role.This study was designed to examine the interrelationship between physical activity, obesity, and LBP. The specific aims were to determine if obesity is a risk factor for LBP in the U.S. population, measure the strength of any observed association, and evaluate the role of physical activity in modulating this association.A cross-sectional U.S. population-based study.A cohort of 6,796 adults from the 2003-2004 National Health and Nutrition Examination Survey.Demographic information, an in-depth health questionnaire, physical examination details, and 7-day free-living physical activity monitoring using accelerometry (ActiGraph AM-7164; ActiGraph, Pensacola, FL, USA).LBP status was determined by questionnaire response. Body mass index (BMI) was calculated during physical examination and divided here into four groups (normal weight <25, overweight 25-30, obese 31-35, and ultraobese 36+). Summary measures of physical activity were computed based on intensity cutoffs, percentile intensities, and bout. Demographics, social history, and comorbid health conditions were used to build adjusted weighted logistic regression models constructed using Akaike Information Criterion. All displayed estimates are significant at level <.05. No external funding was received to support this study. None of the authors report conflicts of interest directly related to the specific subject matter of this manuscript.In the U.S. population, the risk of low LBP increases in step with BMI from 2.9% for normal BMI (20-25) to 5.2% for overweight (26-30), 7.7% for obese (31-35), and 11.6% for ultraobese (36+). Smoking is consistently the strongest predictor of LBP across the BMI spectrum (odds ratio 1.6-2.9). Physical activity also modulates these risks. In the overall model, the best physical activity predictors of LBP are in the moderate and high intensity ranges with small effects (odds ratio 0.98 and 0.996 per standard deviation increase, respectively). When broken down by BMI, time spent in sedentary and moderate activity ranges demonstrate more robust influences on LBP status in the overweight, obese, and ultraobese groups.Increased BMI is a risk factor for back pain in Americans. More important, the role of physical activity in mitigating back pain risk is shown to be of greater consequence in the overweight and obese populations.

    View details for DOI 10.1016/j.spinee.2013.11.010

    View details for Web of Science ID 000329971900004

    View details for PubMedID 24239800

  • From Catastrophizing to Recovery: a pilot study of a single-session treatment for pain catastrophizing JOURNAL OF PAIN RESEARCH Darnall, B. D., Sturgeon, J. A., Kao, M., Hah, J. M., Mackey, S. C. 2014; 7: 219-226

    Abstract

    Pain catastrophizing (PC) - a pattern of negative cognitive-emotional responses to real or anticipated pain - maintains chronic pain and undermines medical treatments. Standard PC treatment involves multiple sessions of cognitive behavioral therapy. To provide efficient treatment, we developed a single-session, 2-hour class that solely treats PC entitled "From Catastrophizing to Recovery" [FCR].To determine 1) feasibility of FCR; 2) participant ratings for acceptability, understandability, satisfaction, and likelihood to use the information learned; and 3) preliminary efficacy of FCR for reducing PC.Uncontrolled prospective pilot trial with a retrospective chart and database review component. Seventy-six patients receiving care at an outpatient pain clinic (the Stanford Pain Management Center) attended the class as free treatment and 70 attendees completed and returned an anonymous survey immediately post-class. The Pain Catastrophizing Scale (PCS) was administered at class check-in (baseline) and at 2, and 4 weeks post-treatment. Within subjects repeated measures analysis of variance (ANOVA) with Student's t-test contrasts were used to compare scores across time points.All attendees who completed a baseline PCS were included as study participants (N=57; F=82%; mean age =50.2 years); PCS was completed by 46 participants at week 2 and 35 participants at week 4. Participants had significantly reduced PC at both time points (P<0001) and large effect sizes were found (Cohen's d=0.85 and d=1.15).Preliminary data suggest that FCR is an acceptable and effective treatment for PC. Larger, controlled studies of longer duration are needed to determine durability of response, factors contributing to response, and the impact on pain, function and quality of life.

    View details for DOI 10.2147/JPR.S62329

    View details for Web of Science ID 000364587600005

    View details for PubMedID 24851056

    View details for PubMedCentralID PMC4008292

  • Duration of fluoroscopic-guided spine interventions and radiation exposure is increased in overweight patients. PM & R : the journal of injury, function, and rehabilitation Smuck, M., Zheng, P., Chong, T., Kao, M., Geisser, M. E. 2013; 5 (4): 291-296

    Abstract

    The impact of patient body mass index (BMI) on image-guided spine interventions remains unknown. Higher BMI is known to complicate the acquisition of radiographic images. Therefore it can be hypothesized that the patient's body habitus can influence the delivery of a spinal injection.To quantify the impact of patient BMI on the length of fluoroscopy and procedure times during spine interventions.Secondary analysis of 2 prospective observational studies.All injections were performed in an outpatient university setting.A total of 209 patients in whom spine injections were performed (99 women), with a mean age of 54.6 years.The fluoroscopy times for 202 participants and total procedure times for 137 participants were recorded. Additional participant characteristics, including age, gender, BMI, and actual procedures performed, also were collected. Analysis of covariance and linear and nonlinear model analysis were performed to assess the effect of BMI on fluoroscopy and procedure times.Fluoroscopy time and procedure duration times.Participants had a mean age of 54.6 years, 51% were men, and 77% (n = 155) were overweight (BMI ?25). Participants received the following interventions: 40 zygapophyseal joint injections, 33 medial branch nerve blocks, 113 transforaminal epidural injections, and 16 combined zygapophyseal joint injections and epidural injections. Gender, procedure number, and procedure type did not differ between groups. The overweight group demonstrated a 30% increase in mean fluoroscopy time and a 35% increase in mean procedure time. Controlling for other variables, we found that differences in fluoroscopy time and procedure time were significant (P = .032 and P = .031, respectively) between the 2 groups.Significantly prolonged procedure time and fluoroscopy time in overweight patients increase the risks associated with spine interventions, not only to the patients but also to the operating room staff exposed to ionizing radiation.

    View details for DOI 10.1016/j.pmrj.2013.01.015

    View details for PubMedID 23435199

  • The value of physical examination in the diagnosis of hip osteoarthritis. Journal of back and musculoskeletal rehabilitation Chong, T., Don, D. W., Kao, M., Wong, D., Mitra, R. 2013; 26 (4): 397-400

    Abstract

    To compare the sensitivity of physical examination (internal rotation of the hip) with radiographs (using the Kellgren-Lawrence grading scale) in the diagnosis of clinically significant hip osteoarthritis.Case Series, Retrospective chart review of hip pain patients that underwent fluoroscopically guided hip steroid and anesthetic injections.10 patients with hip pain patients seen at an academic outpatient center over a 2 year period were analyzed.Fluoroscopically guided hip steroid and anesthetic injection.Pain relief and change in VAS pain score after intra-articular hip steroid and lidocaine injection was the main outcome measure.Based on Fisher's exact test, there was no association between severity of radiographic hip arthritis and pain relief with intra-articular anesthetic/steroid injection (p=0.45). Physical examination (provocative hip internal rotation) however was associated with a significant decrease in VAS pain score after intra-articular lidocaine and corticosteroid hip injection (p=0.022).Simple hip radiographs alone are not sufficient to diagnose clinically significant hip osteoarthritis. Physical examination (hip internal rotation) was found to be more accurate than simple radiographs in the diagnosis of clinically significant hip osteoarthritis. Radiographs seem to best utilized when they are an extension of the physical examination and patient history.

    View details for DOI 10.3233/BMR-130398

    View details for PubMedID 23948824

  • Diagnostic Accuracy of Bedside Swallow Evaluation Versus Videofluoroscopy to Assess Dysphagia in Individuals With Tetraplegia PM&R Shem, K. L., Castillo, K., Wong, S. L., Chang, J., Kao, M., Kolakowsky-Hayner, S. A. 2012; 4 (4): 283-289

    Abstract

    To assess the accuracy of bedside swallow evaluation (BSE) compared with videofluorosopic swallow study (VFSS) in diagnosing dysphagia in individuals with tetraplegia due to spinal cord injury (SCI).A prospective diagnostic accuracy study according to STAndards for the Reporting of Diagnostic accuracy studies (STARD) criteria.A county hospital with acute inpatient SCI unit.Thirty-nine subjects with SCI and tetraplegia were enrolled. All of the subjects underwent BSE, and 26 subjects completed the VFSS.Individuals with SCI underwent a BSE followed by a VFSS within 72 hours of the BSE. The subjects were diagnosed as having dysphagia if they had positive findings in either BSE or VFSS.Sensitivity, specificity, and positive and negative predictive values were calculated by using VFSS as the criterion standard.Fifteen subjects (38%) were diagnosed as having dysphagia based on the BSE results. Among the subjects who completed the VFSS, 11 were diagnosed with dysphagia (42%) and 4 were diagnosed with aspiration (10%). Of the 26 subjects who completed both BSE and VFSS, only 1 subject was diagnosed differently compared with BSE (3.8%). Different diet recommendations were made in 4 cases after VFSS versus BSE. Different liquid recommendations were made in 8 cases after VFSS versus BSE. Sensitivity of BSE was 100% (95% confidence interval [CI], 71.5%-100%), specificity was 93.3% (95% CI, 68.1%-99.8%). A positive predictive value of BSE was 91.7% (95% CI, 61.5%-100%), and the negative predictive value was 100% (95% CI, 76.8%-100%).Dysphagia is present in approximately 38% of individuals with acute tetraplegia. Because only one of the 21 subjects was diagnosed differently based on VFSS, we believe that BSE is an appropriate screening tool for dysphagia for individuals with cervical SCI. However, VFSS provided additional information on diet and liquid recommendations, so there appears to be an important clinical role for the VFSS.

    View details for DOI 10.1016/j.pmrj.2012.01.002

    View details for Web of Science ID 000305438600006

    View details for PubMedID 22541374

  • An integrative approach to characterize disease-specific pathways and their coordination: a case study in cancer BMC GENOMICS Xu, M., Kao, M. J., Nunez-Iglesias, J., Nevins, J. R., West, M., Zhou, X. J. 2008; 9

    View details for DOI 10.1186/1471-2164-9-S1-S12

    View details for Web of Science ID 000206244100013

  • HumanUpstream and MouseUpstream: Databases of promoter sequences in the human and mouse genomes OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY Leykin, I., Kao, M. C., Wong, W. H. 2005; 9 (3): 220-224

    Abstract

    Large-scale genome annotations, based largely on gene prediction programs, may be inaccurate in their predictions of transcription start sites, so that the identification of promoter regions remains unreliable. Here we focus on the identification of reliable gene promoter regions, critical to the understanding of transcriptional regulation. We report the construction of databases of upstream sequences Human Upstream and Mouse Upstream based on information from both the human and mouse genomes and the database of expressed sequence tags (dbEST). Using the ENSEMBL generic genome annotation system, our approach allows more reliable identification of transcript start sites, and therefore extraction of more reliable promoters regions. The Human Upstream and Human Upstream databases are available free of charge.

    View details for Web of Science ID 000232649500002

    View details for PubMedID 16209636

  • Functional annotation and network reconstruction through cross-platform integration of microarray data NATURE BIOTECHNOLOGY Zhou, X. H., Kao, M. C., Huang, H. Y., Wong, A., Nunez-Iglesias, J., Primig, M., Aparicio, O. M., Finch, C. E., Morgan, T. E., Wong, W. H. 2005; 23 (2): 238-243

    Abstract

    The rapid accumulation of microarray data translates into a need for methods to effectively integrate data generated with different platforms. Here we introduce an approach, 2(nd)-order expression analysis, that addresses this challenge by first extracting expression patterns as meta-information from each data set (1(st)-order expression analysis) and then analyzing them across multiple data sets. Using yeast as a model system, we demonstrate two distinct advantages of our approach: we can identify genes of the same function yet without coexpression patterns and we can elucidate the cooperativities between transcription factors for regulatory network reconstruction by overcoming a key obstacle, namely the quantification of activities of transcription factors. Experiments reported in the literature and performed in our lab support a significant number of our predictions.

    View details for DOI 10.1038/nbt1058

    View details for Web of Science ID 000226797600032

    View details for PubMedID 15654329

  • GoSurfer: a graphical interactive tool for comparative analysis of large gene sets in Gene Ontology space. Applied bioinformatics Zhong, S., Storch, K., Lipan, O., Kao, M. J., Weitz, C. J., Wong, W. H. 2004; 3 (4): 261-264

    Abstract

    The analysis of complex patterns of gene regulation is central to understanding the biology of cells, tissues and organisms. Patterns of gene regulation pertaining to specific biological processes can be revealed by a variety of experimental strategies, particularly microarrays and other highly parallel methods, which generate large datasets linking many genes. Although methods for detecting gene expression have improved substantially in recent years, understanding the physiological implications of complex patterns in gene expression data is a major challenge. This article presents GoSurfer, an easy-to-use graphical exploration tool with built-in statistical features that allow a rapid assessment of the biological functions represented in large gene sets. GoSurfer takes one or two list(s) of gene identifiers (Affymetrix probe set ID) as input and retrieves all the Gene Ontology (GO) terms associated with the input genes. GoSurfer visualises these GO terms in a hierarchical tree format. With GoSurfer, users can perform statistical tests to search for the GO terms that are enriched in the annotations of the input genes. These GO terms can be highlighted on the GO tree. Users can manipulate the GO tree in various ways and interactively query the genes associated with any GO term. The user-generated graphics can be saved as graphics files, and all the GO information related to the input genes can be exported as text files.GoSurfer is a Windows-based program freely available for noncommercial use and can be downloaded at http://www.gosurfer.org. Datasets used to construct the trees shown in the figures in this article are available at http://www.gosurfer.org/download/GoSurfer.zip.

    View details for PubMedID 15702958

  • Determination of local statistical significance of patterns in Markov sequences with application to promoter element identification JOURNAL OF COMPUTATIONAL BIOLOGY Huang, H. Y., Kao, M. C., Zhou, X. H., Liu, J. S., Wong, W. H. 2004; 11 (1): 1-14

    Abstract

    High-level eukaryotic genomes present a particular challenge to the computational identification of transcription factor binding sites (TFBSs) because of their long noncoding regions and large numbers of repeat elements. This is evidenced by the noisy results generated by most current methods. In this paper, we present a p-value-based scoring scheme using probability generating functions to evaluate the statistical significance of potential TFBSs. Furthermore, we introduce the local genomic context into the model so that candidate sites are evaluated based both on their similarities to known binding sites and on their contrasts against their respective local genomic contexts. We demonstrate that our approach is advantageous in the prediction of myogenin and MEF2 binding sites in the human genome. We also apply LMM to large-scale human binding site sequences in situ and found that, compared to current popular methods, LMM analysis can reduce false positive errors by more than 50% without compromising sensitivity. This improvement will be of importance to any subsequent algorithm that aims to detect regulatory modules based on known PSSMs.

    View details for Web of Science ID 000220234300001

    View details for PubMedID 15072685

  • Chemical genetic modifier screens: Small molecule trichostatin suppressors as probes of intracellular histone and tubulin acetylation CHEMISTRY & BIOLOGY Koeller, K. M., Haggarty, S. J., Perkins, B. D., Leykin, I., Wong, J. C., Kao, M. C., Schreiber, S. L. 2003; 10 (5): 397-410

    Abstract

    Histone deacetylase (HDAC) inhibitors are being developed as new clinical agents in cancer therapy, in part because they interrupt cell cycle progression in transformed cell lines. To examine cell cycle arrest induced by HDAC inhibitor trichostatin A (TSA), a cytoblot cell-based screen was used to identify small molecule suppressors of this process. TSA suppressors (ITSAs) counteract TSA-induced cell cycle arrest, histone acetylation, and transcriptional activation. Hydroxamic acid-based HDAC inhibitors like TSA and suberoylanilide hydroxamic acid (SAHA) promote acetylation of cytoplasmic alpha-tubulin as well as histones, a modification also suppressed by ITSAs. Although tubulin acetylation appears irrelevant to cell cycle progression and transcription, it may play a role in other cellular processes. Small molecule suppressors such as the ITSAs, available from chemical genetic suppressor screens, may prove to be valuable probes of many biological processes.

    View details for DOI 10.1016/S1074-5521(03)00093-0

    View details for Web of Science ID 000183647400003

    View details for PubMedID 12770822

  • Novel mechanisms of T-cell and dendritic cell activation revealed by profiling of psoriasis on the 63,100-element oligonucleotide array PHYSIOLOGICAL GENOMICS Zhou, X. H., Krueger, J. G., Kao, M. C., Lee, E., Du, F. H., Menter, A., Wong, W. H., Bowcock, A. M. 2003; 13 (1): 69-78

    Abstract

    A global picture of gene expression in the common immune-mediated skin disease, psoriasis, was obtained by interrogating the full set of Affymetrix GeneChips with psoriatic and control skin samples. We identified 1,338 genes with potential roles in psoriasis pathogenesis/maintenance and revealed many perturbed biological processes. A novel method for identifying transcription factor binding sites was also developed and applied to this dataset. Many of the identified sites are known to be involved in immune response and proliferation. An in-depth study of immune system genes revealed the presence of many regulating cytokines and chemokines within involved skin, and markers of dendritic cell (DC) activation in uninvolved skin. The combination of many CCR7+ T cells, DCs, and regulating chemokines in psoriatic lesions, together with the detection of DC activation markers in nonlesional skin, strongly suggests that the spatial organization of T cells and DCs could sustain chronic T-cell activation and persistence within focal skin regions.

    View details for DOI 10.1152/physiolgenomics.00157.2002

    View details for Web of Science ID 000181684400009

    View details for PubMedID 12644634

  • Transitive functional annotation by shortest-path analysis of gene expression data PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Zhou, X. H., Kao, M. C., Wong, W. H. 2002; 99 (20): 12783-12788

    Abstract

    Current methods for the functional analysis of microarray gene expression data make the implicit assumption that genes with similar expression profiles have similar functions in cells. However, among genes involved in the same biological pathway, not all gene pairs show high expression similarity. Here, we propose that transitive expression similarity among genes can be used as an important attribute to link genes of the same biological pathway. Based on large-scale yeast microarray expression data, we use the shortest-path analysis to identify transitive genes between two given genes from the same biological process. We find that not only functionally related genes with correlated expression profiles are identified but also those without. In the latter case, we compare our method to hierarchical clustering, and show that our method can reveal functional relationships among genes in a more precise manner. Finally, we show that our method can be used to reliably predict the function of unknown genes from known genes lying on the same shortest path. We assigned functions for 146 yeast genes that are considered as unknown by the Saccharomyces Genome Database and by the Yeast Proteome Database. These genes constitute around 5% of the unknown yeast ORFome.

    View details for DOI 10.1073/pnas.192159399

    View details for Web of Science ID 000178391700053

    View details for PubMedID 12196633

    View details for PubMedCentralID PMC130537

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