Publications by authors named "David Ahern"

62 Publications

Behavior-based diabetes management: impact on care, hospitalizations, and costs.

Am J Manag Care 2021 03;27(3):96-102

Abacus Health Solutions, 1210 Pontiac Ave, Cranston, RI 02920. Email:

Objectives: To (1) examine the impact of the Diabetes Care Rewards (DCR) program on adherence to care standards and (2) evaluate the economic impact of adherence to care standards.

Study Design: A retrospective observational cohort study design with propensity matching. Additional covariates adjustment was used to minimize residual imbalance.

Methods: Utilization and cost data were compared between individuals enrolled vs individuals eligible for but not enrolled in the DCR program using a standard mean difference. Individuals were employees or their dependents from self-insured companies throughout the United States. Outcomes included adherence to the care standards, service utilization, and costs.

Results: A total of 3318 propensity-matched participants were included. Primary analysis revealed that enrolled members increased adherence to semiannual glycated hemoglobin, annual lipid, and annual urine albumin-creatinine ratio testing. Additionally, enrolled members experienced less utilization of high-acuity services and increased rates of physician visits. In a secondary analysis, the enrolled group was associated with greater pharmaceutical costs but lower medical costs.

Conclusions: A behavioral science- and incentive-based diabetes management program was associated with greater rates of adherence to recommended diabetes monitoring care standards, increased routine clinic visits, decreased hospital admissions, and decreased inpatient days. Anticipated increases in pharmaceutical expenditures were offset by overall lower medical expenditures. Results indicate the economic benefits of adherence to evidence-based standards for diabetes care.
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http://dx.doi.org/10.37765/ajmc.2021.88597DOI Listing
March 2021

Hepcidin-Mediated Hypoferremia Disrupts Immune Responses to Vaccination and Infection.

Med (N Y) 2021 Feb;2(2):164-179.e12

MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.

Background: How specific nutrients influence adaptive immunity is of broad interest. Iron deficiency is the most common micronutrient deficiency worldwide and imparts a significant burden of global disease; however, its effects on immunity remain unclear.

Methods: We used a hepcidin mimetic and several genetic models to examine the effect of low iron availability on T cells and on immune responses to vaccines and viral infection in mice. We examined humoral immunity in human patients with raised hepcidin and low serum iron caused by mutant . We tested the effect of iron supplementation on vaccination-induced humoral immunity in piglets, a natural model of iron deficiency.

Findings: We show that low serum iron (hypoferremia), caused by increased hepcidin, severely impairs effector and memory responses to immunizations. The intensified metabolism of activated lymphocytes requires the support of enhanced iron acquisition, which is facilitated by IRP1/2 and TFRC. Accordingly, providing extra iron improved the response to vaccination in hypoferremic mice and piglets, while conversely, hypoferremic humans with chronically increased hepcidin have reduced concentrations of antibodies specific for certain pathogens. Imposing hypoferremia blunted the T cell, B cell, and neutralizing antibody responses to influenza virus infection in mice, allowing the virus to persist and exacerbating lung inflammation and morbidity.

Conclusions: Hypoferremia, a well-conserved physiological innate response to infection, can counteract the development of adaptive immunity. This nutrient trade-off is relevant for understanding and improving immune responses to infections and vaccines in the globally common contexts of iron deficiency and inflammatory disorders.

Funding: Medical Research Council, UK.
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http://dx.doi.org/10.1016/j.medj.2020.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895906PMC
February 2021

Digital Phenotyping to Enhance Substance Use Treatment During the COVID-19 Pandemic.

JMIR Ment Health 2020 Oct 26;7(10):e21814. Epub 2020 Oct 26.

Division of Addiction Psychiatry, Brigham and Women's Hospital, Boston, MA, United States.

Due to the COVID-19 pandemic, many clinical addiction treatment programs have been required to transition to telephonic or virtual visits. Novel solutions are needed to enhance substance use treatment during a time when many patients are disconnected from clinical care and social support. Digital phenotyping, which leverages the unique functionality of smartphone sensors (GPS, social behavior, and typing patterns), can buttress clinical treatment in a remote, scalable fashion. Specifically, digital phenotyping has the potential to improve relapse prediction and intervention, relapse detection, and overdose intervention. Digital phenotyping may enhance relapse prediction through coupling machine learning algorithms with the enormous amount of collected behavioral data. Activity-based analysis in real time can potentially be used to prevent relapse by warning substance users when they approach locational triggers such as bars or liquor stores. Wearable devices detect when a person has relapsed to substances through measuring physiological changes such as electrodermal activity and locomotion. Despite the initial promise of this approach, privacy, security, and barriers to access are important issues to address.
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http://dx.doi.org/10.2196/21814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592462PMC
October 2020

ROS-producing immature neutrophils in giant cell arteritis are linked to vascular pathologies.

JCI Insight 2020 10 15;5(20). Epub 2020 Oct 15.

Kennedy Institute of Rheumatology and.

Giant cell arteritis (GCA) is a common form of primary systemic vasculitis in adults, with no reliable indicators of prognosis or treatment responses. We used single cell technologies to comprehensively map immune cell populations in the blood of patients with GCA and identified the CD66b+CD15+CD10lo/-CD64- band neutrophils and CD66bhiCD15+CD10lo/-CD64+/bright myelocytes/metamyelocytes to be unequivocally associated with both the clinical phenotype and response to treatment. Immature neutrophils were resistant to apoptosis, remained in the vasculature for a prolonged period of time, interacted with platelets, and extravasated into the tissue surrounding the temporal arteries of patients with GCA. We discovered that immature neutrophils generated high levels of extracellular reactive oxygen species, leading to enhanced protein oxidation and permeability of endothelial barrier in an in vitro coculture system. The same populations were also detected in other systemic vasculitides. These findings link functions of immature neutrophils to disease pathogenesis, establishing a clinical cellular signature of GCA and suggesting different therapeutic approaches in systemic vascular inflammation.
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http://dx.doi.org/10.1172/jci.insight.139163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605529PMC
October 2020

Mending Disconnects in Cancer Care: Setting an Agenda for Research, Practice, and Policy.

JCO Clin Cancer Inform 2020 06;4:539-546

American Cancer Society, Washington, DC.

Cancer in the United States accounts for $600 billion in health care costs, lost work time and productivity, reduced quality of life, and premature mortality. The future of oncology delivery must mend disconnects to equitably improve patient outcomes while constraining costs and burden on patients, caregivers, and care teams. Embedding learning health systems into oncology can connect care, engaging patients and providers in fully interoperable data systems that remotely monitor patients; generate predictive and prescriptive analytics to facilitate appropriate, timely referrals; and extend the reach of clinicians beyond clinic walls. Incorporating functional learning systems into the future of oncology and follow-up care requires coordinated national attention to 4 synergistic strategies: (1) galvanize and shape public discourse to develop and adopt these systems, (2) demonstrate their value, (3) test and evaluate their use, and (4) reform policy to incentivize and regulate their use.
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http://dx.doi.org/10.1200/CCI.20.00046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328120PMC
June 2020

Histone H3K27me3 demethylases regulate human Th17 cell development and effector functions by impacting on metabolism.

Proc Natl Acad Sci U S A 2020 03 2;117(11):6056-6066. Epub 2020 Mar 2.

Botnar Research Center, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, National Institute for Health Research Oxford Biomedical Research Unit, University of Oxford, OX3 7LD Oxford, United Kingdom;

T helper (Th) cells are CD4 effector T cells that play a critical role in immunity by shaping the inflammatory cytokine environment in a variety of physiological and pathological situations. Using a combined chemico-genetic approach, we identify histone H3K27 demethylases KDM6A and KDM6B as central regulators of human Th subsets. The prototypic KDM6 inhibitor GSK-J4 increases genome-wide levels of the repressive H3K27me3 chromatin mark and leads to suppression of the key transcription factor RORγt during Th17 differentiation. In mature Th17 cells, GSK-J4 induces an altered transcriptional program with a profound metabolic reprogramming and concomitant suppression of IL-17 cytokine levels and reduced proliferation. Single-cell analysis reveals a specific shift from highly inflammatory cell subsets toward a resting state upon demethylase inhibition. The root cause of the observed antiinflammatory phenotype in stimulated Th17 cells is reduced expression of key metabolic transcription factors, such as PPRC1. Overall, this leads to reduced mitochondrial biogenesis, resulting in a metabolic switch with concomitant antiinflammatory effects. These data are consistent with an effect of GSK-J4 on Th17 T cell differentiation pathways directly related to proliferation and include regulation of effector cytokine profiles. This suggests that inhibiting KDM6 demethylases may be an effective, even in the short term, therapeutic target for autoimmune diseases, including ankylosing spondylitis.
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http://dx.doi.org/10.1073/pnas.1919893117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084125PMC
March 2020

Olfactory and Neuropsychological Functioning in Olfactory Reference Syndrome.

Psychosomatics 2020 May - Jun;61(3):261-267. Epub 2020 Jan 2.

Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, RI; Department of Psychiatry, Rhode Island Hospital, Providence, RI; Department of Psychiatry, Weill Cornell Medical College, New York, NY; Department of Psychiatry, New York-Presbyterian Hospital, New York, NY.

Background: Olfactory reference syndrome (ORS) is an underrecognized, understudied, and often severe psychiatric disorder characterized by a prominent and distressing or impairing preoccupation with a false belief of emitting an offensive body odor. As this condition has only recently been recognized in the International Classification of Diseases (the 11th Edition), no empirical evidence exists about the underlying features and etiology of the disorder.

Objective: To examine the neuropsychological and olfactory functioning of individuals with ORS and address whether there is central nervous system or sensory dysfunction associated with the condition.

Methods: In this preliminary investigation, 9 consecutive participants with ORS completed a structured clinical interview and neuropsychological and olfaction evaluations.

Results: A proportion of individuals with ORS displayed deficits in aspects of cognitive functioning (i.e., processing speed, executive functioning, recognition memory bias for ORS-related words), olfaction functioning (i.e., odor detection and discrimination), and emotional processing.

Conclusions: Based on these preliminary findings of cognitive, olfaction, and emotional processing deficits in individuals with ORS, further neuropsychological and olfaction studies are needed that better characterize this understudied patient group and address this study's limitations.
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http://dx.doi.org/10.1016/j.psym.2019.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211111PMC
January 2020

Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease.

Cell 2018 10 27;175(2):372-386.e17. Epub 2018 Sep 27.

MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK; Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK. Electronic address:

Intestinal mesenchymal cells play essential roles in epithelial homeostasis, matrix remodeling, immunity, and inflammation. But the extent of heterogeneity within the colonic mesenchyme in these processes remains unknown. Using unbiased single-cell profiling of over 16,500 colonic mesenchymal cells, we reveal four subsets of fibroblasts expressing divergent transcriptional regulators and functional pathways, in addition to pericytes and myofibroblasts. We identified a niche population located in proximity to epithelial crypts expressing SOX6, F3 (CD142), and WNT genes essential for colonic epithelial stem cell function. In colitis, we observed dysregulation of this niche and emergence of an activated mesenchymal population. This subset expressed TNF superfamily member 14 (TNFSF14), fibroblastic reticular cell-associated genes, IL-33, and Lysyl oxidases. Further, it induced factors that impaired epithelial proliferation and maturation and contributed to oxidative stress and disease severity in vivo. Our work defines how the colonic mesenchyme remodels to fuel inflammation and barrier dysfunction in IBD.
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http://dx.doi.org/10.1016/j.cell.2018.08.067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176871PMC
October 2018

Immune cell census in murine atherosclerosis: cytometry by time of flight illuminates vascular myeloid cell diversity.

Cardiovasc Res 2018 08;114(10):1360-1371

Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7FY, UK.

Aims: Atherosclerosis is characterized by the abundant infiltration of myeloid cells starting at early stages of disease. Myeloid cells are key players in vascular immunity during atherogenesis. However, the subsets of vascular myeloid cells have eluded resolution due to shared marker expression and atypical heterogeneity in vascular tissues. We applied the high-dimensionality of mass cytometry to the study of myeloid cell subsets in atherosclerosis.

Methods And Results: Apolipoprotein E-deficient (ApoE-/-) mice were fed a chow or a high fat (western) diet for 12 weeks. Single-cell aortic preparations were probed with a panel of 35 metal-conjugated antibodies using cytometry by time of flight (CyTOF). Clustering of marker expression on live CD45+ cells from the aortas of ApoE-/- mice identified 13 broad populations of leucocytes. Monocyte, macrophage, type 1 and type 2 conventional dendritic cell (cDC1 and cDC2), plasmacytoid dendritic cell (pDC), neutrophil, eosinophil, B cell, CD4+ and CD8+ T cell, γδ T cell, natural killer (NK) cell, and innate lymphoid cell (ILC) populations accounted for approximately 95% of the live CD45+ aortic cells. Automated clustering algorithms applied to the Lin-CD11blo-hi cells revealed 20 clusters of myeloid cells. Comparison between chow and high fat fed animals revealed increases in monocytes (both Ly6C+ and Ly6C-), pDC, and a CD11c+ macrophage subset with high fat feeding. Concomitantly, the proportions of CD206+ CD169+ subsets of macrophages were significantly reduced as were cDC2.

Conclusions: A CyTOF-based comprehensive mapping of the immune cell subsets within atherosclerotic aortas from ApoE-/- mice offers tools for myeloid cell discrimination within the vascular compartment and it reveals that high fat feeding skews the myeloid cell repertoire toward inflammatory monocyte-macrophage populations rather than resident macrophage phenotypes and cDC2 during atherogenesis.
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http://dx.doi.org/10.1093/cvr/cvy109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054192PMC
August 2018

Trail-Making Test Part B: Evaluation of the Efficiency Score for Assessing Floor-Level Change in Veterans.

Arch Clin Neuropsychol 2019 Mar;34(2):243-253

Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.

Objective: The Trail Making Test - Part B (TMT-B) is a commonly used executive control measure with a known floor effect, limiting the ability to distinguish impairment among individuals unable to complete this task in the standard time limit. Our group previously proposed the TMT-B Efficiency Score (TMT-Be), which captures performance variability among examinees who fail to complete the task. The present study assesses the TMT-Be in a longitudinal clinical sample.

Method: Data were collected via record review of veterans who underwent two clinical neuropsychological evaluations. We identified 30 veterans (mean age Visit 1:69 ± 8.7 years) who were unable to complete TMT-B during at least one evaluation (mean days between visits = 615). Two scoring systems were utilized to examine performance variability: TMT-Be and TMT-B Prorated Score (TMT-Bpr).

Results: TMT-Be distribution was less skewed, but more platykuric, compared to TMT-Bpr. TMT-Be and TMT-Bpr were highly correlated. Both metrics correlated with psychomotor speed and another executive task, but not confrontation naming, providing both convergent and discriminant evidence of validity. TMT-Be, but not TMT-Bpr, detected significant decline in performance longitudinally. Age and education were significant predictors of the TMT-Be, but not TMT-Bpr, difference scores.

Conclusions: Both metrics captured performance variability in a clinical sample and provided sufficient variance for examining floor-level performance on the TMT-B. TMT-Be appeared to be less prone to creating outliers and more likely to detect change. The results support the utility of the TMT-Be metric in research and clinical settings.
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http://dx.doi.org/10.1093/arclin/acy025DOI Listing
March 2019

Cognitive Impairment in Men with Prostate Cancer Treated with Androgen Deprivation Therapy: A Systematic Review and Meta-Analysis.

J Urol 2018 06 2;199(6):1417-1425. Epub 2018 Feb 2.

Division of Urological Surgery, Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address:

Purpose: Use of androgen deprivation therapy may increase the risk of cognitive impairment in men with prostate cancer. We performed a systematic review of the risk of overall cognitive impairment as an outcome in men receiving androgen deprivation therapy for prostate cancer.

Materials And Methods: Studies were identified through PubMed®, MEDLINE®, PsycINFO®, Cochrane Library and Web of Knowledge/Science™. Articles were included if they 1) were published in English, 2) had subjects treated for prostate cancer with androgen deprivation therapy, 3) incorporated longitudinal comparisons and 4) used control groups. In addition, prospective studies were required to assess an established cognitive related end point using International Cognition and Cancer Task Force criteria defining impaired cognitive performance as scoring 1.5 or more standard deviations below published norms on 2 or more tests, or scoring 2.0 or more standard deviations below published norms on at least 1 test. The effect of androgen deprivation therapy on cognitive impairment was pooled using a random effects model.

Results: Of 221 abstracts 26 were selected for full text review, and 2 prospective and 4 retrospective studies were analyzed. Androgen deprivation therapy was not associated with overall cognitive impairment when the prospective cohort studies were pooled (OR 1.57, 95% CI 0.50 to 4.92, p = 0.44) with significant heterogeneity between estimates (I = 83%). In retrospective data the relative risk of any cognitive impairment, including senile dementia and Alzheimer disease, was increased in men receiving androgen deprivation therapy, although the difference was not statistically significant (HR 1.28, 95% CI 0.93 to 1.76, p = 0.13) with moderate heterogeneity between estimates (I = 67%).

Conclusions: Analyses between overall cognitive impairment and use of androgen deprivation therapy defined according to International Cognition and Cancer Task Force criteria in a pooled analysis were inconclusive. In retrospective cohort studies the risk of overall cognitive impairment after androgen deprivation therapy was not significant. Better prospective studies need to be designed for the assessment of this end point.
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http://dx.doi.org/10.1016/j.juro.2017.11.136DOI Listing
June 2018

Information technology-enabled team-based, patient-centered care: The example of depression screening and management in cancer care.

Health Policy Technol 2017 Mar 20;6(1):67-71. Epub 2016 Aug 20.

Health Communications and Informatics Research Branch, Behavioral Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, United States.

The existing healthcare delivery systems across the world need to be redesigned to ensure high-quality care is delivered to all patients. This redesign needs to ensure care is knowledge-based, patient-centered and systems-minded. The rapid advances in the capabilities of information and communication technology and its recent rapid adoption in healthcare delivery have ensured this technology will play a vital role in the redesign of the healthcare delivery system. This commentary highlights promising new developments in health information technology (IT) that can support patient engagement and self-management as well as team-based, patient-centered care. Collaborative care is an effective approach to screen and treat depression in cancer patients and it is a good example of the benefits of team-based and patient-centered care. However, this approach was developed prior to the widespread adoption and use of health IT. We provide examples to illustrate how health IT can improve prevention and treatment of depression in cancer patients. We found several knowledge gaps that limit our ability to realize the full potential of health IT in the context of cancer and comorbid depression care. These gaps need to be filled to improve patient engagement; enhance the reach and effectiveness of collaborative care and web-based programs to prevent and treat depression in cancer patients. We also identify knowledge gaps in health IT design and implementation. Filling these gaps will help shape policies that enable clinical teams to deliver high-quality cancer care globally.
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http://dx.doi.org/10.1016/j.hlpt.2016.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609681PMC
March 2017

A Randomized Controlled Trial of Medication and Cognitive-Behavioral Therapy for Hypochondriasis.

Am J Psychiatry 2017 08 29;174(8):756-764. Epub 2017 Jun 29.

From the New York State Psychiatric Institute, New York; and Brigham and Women's Hospital, Boston.

Objective: Prior studies of hypochondriasis demonstrated benefits for pharmacotherapy and for cognitive-behavioral therapy (CBT). This study examined whether joint treatment offers additional benefit.

Method: Patients with DSM-IV hypochondriasis (N=195) were randomly assigned to one of four treatments-placebo, CBT, fluoxetine, or joint treatment with both fluoxetine and CBT. Evaluations assessed hypochondriasis, other psychopathology, adverse events, functional status, and quality of life. The primary analysis assessed outcome at week 24 among the intent-to-treat sample, with responders defined as having a 25% or greater improvement over baseline on both the Whiteley Index and a modified version of the Yale-Brown Obsessive Compulsive Scale for hypochondriasis (H-YBOCS-M). The Cochran-Armitage trend test assessed the hypothesized pattern of response: joint treatment > CBT or fluoxetine treatment > placebo treatment.

Results: The predicted pattern of response was statistically significant, as shown by the following responder rates: joint treatment group, 47.2%; single active treatment group, 41.8%; and placebo group, 29.6%. Responder rates for each active treatment were not significantly different from the rate for placebo. Secondary analyses of the Whiteley Index as a continuous measure revealed that, compared with placebo, fluoxetine (but not CBT) was significantly more effective at week 24 in reducing hypochondriasis and had a significantly faster rate of improvement over 24 weeks. Fluoxetine also resulted in significantly less anxiety and better quality of life than placebo. Dropout rates did not differ between groups, and treatment-emergent adverse events were evenly distributed.

Conclusions: This study supports the safety, tolerance, and efficacy of fluoxetine for hypochondriasis. Joint treatment provided a small incremental benefit. Because approximately 50% of patients did not respond to the study treatments, new or more intensive approaches are needed.
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http://dx.doi.org/10.1176/appi.ajp.2017.16020189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5957509PMC
August 2017

Public use of electronic personal health information: Measuring progress of the Healthy People 2020 Objectives.

Health Policy Technol 2017 Mar 20;6(1):33-39. Epub 2016 Aug 20.

Department of Psychiatry, Brigham and Women's Hospital, Boston, MA.

Use of the internet for seeking and managing health information in the U.S., Europe, and emerging and developing nations is growing. Recent global trends indicate more interactive uses of the internet including online communication with providers. In the U.S., The Healthy People 2020 (HP2020) initiative was created by the Department of Health and Human Services to provide 10-year goals for improving the health of American citizens. Two goals of HP2020 were to increase the proportion of individuals who use the Internet to keep track of their personal health information (PHI) online and to increase the proportion of individuals who use the internet to communicate with their healthcare provider. In the present study, we use data from the seven administrations of the Health Information National Trends Survey (HINTS) to assess progress towards these goals. These data were analyzed using descriptive, bivariate, and logistic regression analytic techniques. Results of this study suggested that the HP2020 target of having 15.7% of individuals manage their PHI online by 2020 has already been exceeded (28.1%); similarly, the goal for proportion of individuals communicating with their provider using the internet (15.0%) was exceeded by 2014 (29.7%). While progress towards these goals was positive in all sociodemographic groups for both goals, differences in the rate of progress were seen by gender, race/ethnicity, income, and education, but not by age group. The rapidly increasing proportion of individuals globally who use the internet to manage their health information provides unique opportunities for patient-centered health information technology interventions.
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http://dx.doi.org/10.1016/j.hlpt.2016.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415302PMC
March 2017

Patient-facing Technology for Identification of COPD in Primary Care.

J Innov Health Inform 2016 07 15;23(2):824. Epub 2016 Jul 15.

Center for Primary Care and Prevention, Memorial Hospital of Rhode Island and Department of Family Medicine, Alpert Medical School of Brown University.

Background: The proliferation of mobile devices and emergence of interoperable 'mHealth' apps is accelerating development and deployment of patient-facing risk assessments in primary care. The present study describes a user-centered design and an agile development approach to creation of an app for assessing lungfunction as part of a randomized controlled trial for the   dentification of chronic obstructive lung disease in primary care.

Method: Seventeen patients recruited from a hospital-based, ambulatory family medicine clinic agreed to be videotaped while using the app, Lung Age, on a first-generation iPad prior to their provideR encounter. Subsequently, participants were interviewed using a semi-structured interview guide upon exiting their medical visit.

Results: Observational data indicated that participants took advantage of the portability and flexibility of the tablet device in the exam room to engage with the Lung Age app with the optionto share and discuss their results with their providers. Results from the semistructured interviews indicated that participants perceived the Lung Age app as intuitive and easy to use.

Conclusions: These results demonstrate that tablet computers and mHealth apps can be used to deploy acceptable and useable electronic risk assessments in primary care settings. Future research focused on the impact and outcomes of patient-centered, mHealth apps for risk screening in primary care is warranted.
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http://dx.doi.org/10.14236/jhi.v23i2.824DOI Listing
July 2016

Neuropsychological assessment without upper limb involvement: a systematic review of oral versions of the Trail Making Test and Symbol-Digit Modalities Test.

Neuropsychol Rehabil 2018 Oct 18;28(7):1055-1077. Epub 2016 Oct 18.

a Center of Excellence for Neurorestoration and Neurotechnology , Providence VA Medical Center , Providence , RI , USA.

The Trail Making Test (TMT) and written version of the Symbol Digit Modalities Test (SDMT) assess attention, processing speed, and executive functions but their utility is limited in populations with upper limb dysfunction. Oral versions of the TMT and SDMT exist, but a systematic review of their psychometric properties and clinical utility has not been conducted, which was the goal of this study. Searches were conducted in PubMed and PsycINFO, test manuals, and the reference lists of included articles. Four measures were identified: the SDMT-oral, oral TMT-A, oral TMT-B, and the Mental Alternation Test (MAT). Two investigators independently reviewed abstracts to identify peer-reviewed articles that reported on these measures in adult populations. From each article, one investigator extracted information on reliability, validity, responsiveness, minimum detectable change, normative data, and demographic influences. A second investigator verified the accuracy of the data in a random selection of 10% of papers. The quality of the evidence for each psychometric property was rated on a 4-point scale (unknown, poor, adequate, excellent). Results showed excellent evidence for the SDMT-oral, adequate evidence for the oral TMT-B and MAT, and adequate to poor evidence for the oral TMT-A. These findings inform the clinical assessment of attention, processing speed, and executive functions in individuals with upper limb disability.
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http://dx.doi.org/10.1080/09602011.2016.1240699DOI Listing
October 2018

Behavior change interventions: the potential of ontologies for advancing science and practice.

J Behav Med 2017 Feb 1;40(1):6-22. Epub 2016 Aug 1.

Clinical Research Division, Fred Hutch, Seattle, WA, USA.

A central goal of behavioral medicine is the creation of evidence-based interventions for promoting behavior change. Scientific knowledge about behavior change could be more effectively accumulated using "ontologies." In information science, an ontology is a systematic method for articulating a "controlled vocabulary" of agreed-upon terms and their inter-relationships. It involves three core elements: (1) a controlled vocabulary specifying and defining existing classes; (2) specification of the inter-relationships between classes; and (3) codification in a computer-readable format to enable knowledge generation, organization, reuse, integration, and analysis. This paper introduces ontologies, provides a review of current efforts to create ontologies related to behavior change interventions and suggests future work. This paper was written by behavioral medicine and information science experts and was developed in partnership between the Society of Behavioral Medicine's Technology Special Interest Group (SIG) and the Theories and Techniques of Behavior Change Interventions SIG. In recent years significant progress has been made in the foundational work needed to develop ontologies of behavior change. Ontologies of behavior change could facilitate a transformation of behavioral science from a field in which data from different experiments are siloed into one in which data across experiments could be compared and/or integrated. This could facilitate new approaches to hypothesis generation and knowledge discovery in behavioral science.
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http://dx.doi.org/10.1007/s10865-016-9768-0DOI Listing
February 2017

Cognitive predictors of skilled performance with an advanced upper limb multifunction prosthesis: a preliminary analysis.

Disabil Rehabil Assist Technol 2017 07 6;12(5):504-511. Epub 2016 Apr 6.

g Research Career Scientist, Providence VA Medical Center , Providence , RI , USA.

Purpose The objectives were to 1) identify major cognitive domains involved in learning to use the DEKA Arm; 2) specify cognitive domain-specific skills associated with basic versus advanced users; and 3) examine whether baseline memory and executive function predicted learning. Method Sample included 35 persons with upper limb amputation. Subjects were administered a brief neuropsychological test battery prior to start of DEKA Arm training, as well as physical performance measures at the onset of, and following training. Multiple regression models controlling for age and including neuropsychological tests were developed to predict physical performance scores. Prosthetic performance scores were divided into quartiles and independent samples t-tests compared neuropsychological test scores of advanced scorers and basic scorers. Baseline neuropsychological test scores were used to predict change in scores on physical performance measures across time. Results Cognitive domains of attention and processing speed were statistically significantly related to proficiency of DEKA Arm use and predicted level of proficiency. Conclusions Results support use of neuropsychological tests to predict learning and use of a multifunctional prosthesis. Assessment of cognitive status at the outset of training may help set expectations for the duration and outcomes of treatment. Implications for Rehabilitation Cognitive domains of attention and processing speed were significantly related to level of proficiencyof an advanced multifunctional prosthesis (the DEKA Arm) after training. Results provide initial support for the use of neuropsychological tests to predict advanced learningand use of a multifunctional prosthesis in upper-limb amputees. Results suggest that assessment of patients' cognitive status at the outset of upper limb prosthetictraining may, in the future, help patients, their families and therapists set expectations for theduration and intensity of training and may help set reasonable proficiency goals.
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http://dx.doi.org/10.3109/17483107.2016.1158326DOI Listing
July 2017

The Relationship of Hypochondriasis to Anxiety, Depressive, and Somatoform Disorders.

Psychosomatics 2016 Mar-Apr;57(2):200-7. Epub 2015 Oct 23.

Department of Psychiatry, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA.

Background: Though the phenotype of anxiety about medical illness has long been recognized, there continues to be debate as to whether it is a distinct psychiatric disorder and, if so, to which diagnostic category it belongs.

Objective: Our objective was to investigate the pattern of psychiatric comorbidity in hypochondriasis (HC) and to assess the relationship of health anxiety to anxiety, depressive, and somatoform disorders.

Methods: Data were collected as part of a clinical trial on treatment methods for HC. In all, 194 participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) HC were assessed by sociodemographic variables, results of structured diagnostic interviews, and validated instruments for assessing various symptom dimensions of psychopathology.

Results: Most of the individuals with HC had comorbid psychiatric illness; the mean number of comorbid diagnoses was 1.4, and 35.1% had HC as their only diagnosis. Participants were more likely to have only comorbid anxiety disorders than only comorbid depressive or somatoform disorders. Multiple regression analysis of continuous measures of symptoms revealed the strongest correlation of health anxiety with anxiety symptoms, and a weaker correlation with somatoform symptoms; in multiple regression analysis, there was no correlation between health anxiety and depressive symptoms.

Conclusion: Our findings suggest that the entity of health anxiety (HC in DSM-IV and illness anxiety disorder in DSM-5) is a clinical syndrome distinct from other psychiatric disorders. Analysis of comorbidity patterns and continuous measures of symptoms suggest that its appropriate classification is with anxiety rather than somatoform or mood disorders.
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http://dx.doi.org/10.1016/j.psym.2015.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792743PMC
January 2017

Lowering the Floor on Trail Making Test Part B: Psychometric Evidence for a New Scoring Metric.

Arch Clin Neuropsychol 2015 Nov 11;30(7):643-56. Epub 2015 Jul 11.

School of Engineering, Brown University, Providence, RI 02903, USA Department of Radiology, School of Medicine, University of Colorado, Aurora, CO, 80045, USA.

The Trail Making Test Part B (TMT-B) is widely used in clinical and research settings as a measure of executive function. Standard administration allows a maximal time score (i.e., floor score) of 300 s. This practice potentially masks performance variability among cognitively impaired individuals who cannot complete the task. For example, performances that are nearly complete receive the same 300-s score as a performance of only a few moves. Such performance differences may have utility in research and clinical settings. To address this, we propose a new TMT-B efficiency metric designed to capture clinically relevant performance variability below the standard administration floor. Our metric takes into account time, correct moves, and errors of commission and omission. We demonstrate that the metric has concurrent validity, permits statistical analysis of performances that fall below the test floor, and captures clinically relevant performance variability missed by alternative methods.
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http://dx.doi.org/10.1093/arclin/acv040DOI Listing
November 2015

Executive Functioning in Alcohol Use Studies: A Brief Review of Findings and Challenges in Assessment.

Curr Drug Abuse Rev 2015 ;8(1):26-40

Center for Alcohol and Addiction Studies, Brown University, Box G-S121-4, Providence, RI 02912, USA.

There is a wealth of research about the links between executive functioning (EF) and alcohol use. However, difficulty may arise in interpreting findings because of the variability between studies regarding the specific components of EF measured, as well as the variability of tasks used to examine each EF construct. The current article considers each of these problems within the context of a literature review that focuses on two topics: (1) the efficacy of EF in predicting alcohol use and alcohol-related consequences, and (2) the effect of acute alcohol intoxication on EF task performance. An additional goal was to identify and describe commonly used EF measures with the intention of providing alcohol researchers information on the assessment of different EF domains. Our findings indicate that there is strong evidence supporting a relation between EF difficulties (particularly response inhibition and information updating) and alcohol use, with additional evidence of a significant interaction between EF and implicit associations on alcohol use. In contrast, research supporting a link between set shifting abilities and later alcohol use is scarce. Additionally, this review found evidence of alcohol acutely affecting many EF processes (particularly response inhibition). Overall, there is a need to replicate these findings with commonly used EF tasks (versus developing numerous tasks within individual laboratories) to better advance our understanding of the relation between EF and alcohol use.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638323PMC
http://dx.doi.org/10.2174/1874473708666150416110515DOI Listing
March 2016

Automated Internet-based pain coping skills training to manage osteoarthritis pain: a randomized controlled trial.

Pain 2015 May;156(5):837-848

Thurston Arthritis Research Center and Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA Duke University Medical Center, Durham, NC, USA Amgen, Inc, Thousand Oaks, CA, USA, Icahn School of Medicine at Mount Sinai, New York, NY, USA Harvard Medical School/Brigham and Women's Hospital, Boston, MA, USA Brown University, Pawtucket, RI, USA.

Osteoarthritis (OA) places a significant burden on worldwide public health because of the large and growing number of people affected by OA and its associated pain and disability. Pain coping skills training (PCST) is an evidence-based intervention targeting OA pain and disability. To reduce barriers that currently limit access to PCST, we developed an 8-week, automated, Internet-based PCST program called PainCOACH and evaluated its potential efficacy and acceptability in a small-scale, 2-arm randomized controlled feasibility trial. Participants were 113 men and women with clinically confirmed hip or knee OA and associated pain. They were randomized to a group completing PainCOACH or an assessment-only control group. Osteoarthritis pain, pain-related interference with functioning, pain-related anxiety, self-efficacy for pain management, and positive and negative affect were measured before intervention, midway through the intervention, and after intervention. Findings indicated high acceptability and adherence: 91% of participants randomized to complete PainCOACH finished all 8 modules over 8 to 10 weeks. Linear mixed models showed that, after treatment, women who received the PainCOACH intervention reported significantly lower pain than that in women in the control group (Cohen d = 0.33). Intervention effects could not be tested in men because of their low pain and small sample size. Additionally, both men and women demonstrated increases in self-efficacy from baseline to after intervention compared with the control group (d = 0.43). Smaller effects were observed for pain-related anxiety (d = 0.20), pain-related interference with functioning (d = 0.13), negative affect (d = 0.10), and positive affect (d = 0.24). Findings underscore the value of continuing to develop an automated Internet-based approach to disseminate this empirically supported intervention.
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http://dx.doi.org/10.1097/j.pain.0000000000000121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402249PMC
May 2015

Enhancing patient engagement and blood pressure management for renal transplant recipients via home electronic monitoring and web-enabled collaborative care.

Telemed J E Health 2014 Sep 21;20(9):850-4. Epub 2014 Jul 21.

1 Abacus Health Solutions , Cranston, Rhode Island.

Background: Effective management of hypertension in chronic kidney disease and renal transplantation is a clinical priority and has societal implications in terms of preserving and optimizing the value of scarce organs. However, hypertension is optimally managed in only 37% of people with chronic kidney disease, and poor control can contribute to premature graft loss in renal transplant recipients. This article describes a telehealth system that incorporates home electronic blood pressure (BP) monitoring and uploading to a patient portal coupled with a Web-based dashboard that enables clinical pharmacist collaborative care in a renal transplant clinic.

Materials And Methods: The telehealth system was developed and implemented as a quality improvement initiative in a renal transplant clinic in a large, 700-bed, urban hospital with the aim of improving BP in posttransplant patients. A convenience sample of 66 posttransplant patients was recruited by the clinical pharmacist from consecutive referrals to the Transplant Clinic.

Results: Preliminary results show statistically significant reductions in average systolic and diastolic BP of 6.0 mm Hg and 3.0 mm Hg, respectively, at 30 days after enrollment. Two case reports describe the instrumental role of home BP monitoring in the context of medication therapy management.

Conclusions: Optimizing BP control for both pre- and post-renal transplant patients is likely to benefit society in terms of preserving scarce resources and reducing healthcare costs due to premature graft failure. Connected health systems hold great promise for supporting team-based care and improved health outcomes.
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http://dx.doi.org/10.1089/tmj.2013.0317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148065PMC
September 2014

Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts.

Immunology 2014 Aug;142(4):581-93

Department of Translational Immunology, Novo Nordisk A/S, Måløv, Denmark.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and synovial hyperplasia leading to progressive joint destruction. Fibroblast-like synoviocytes (FLS) are central components of the aggressive, tumour-like synovial structure termed pannus, which invades the joint space and cartilage. A distinct natural killer (NK) cell subset expressing the inhibitory CD94/NKG2A receptor is present in RA synovial fluid. Little is known about possible cellular interactions between RA-FLS and NK cells. We used cultured RA-FLS and the human NK cell line Nishi, of which the latter expresses an NK receptor repertoire similar to that of NK cells in RA synovial fluid, as an in vitro model system of RA-FLS/NK cell cross-talk. We show that RA-FLS express numerous ligands for both activating and inhibitory NK cell receptors, and stimulate degranulation of Nishi cells. We found that NKG2D, DNAM-1, NKp46 and NKp44 are the key activating receptors involved in Nishi cell degranulation towards RA-FLS. Moreover, blockade of the interaction between CD94/NKG2A and its ligand HLA-E expressed on RA-FLS further enhanced Nishi cell degranulation in co-culture with RA-FLS. Using cultured RA-FLS and the human NK cell line Nishi as an in vitro model system of RA-FLS/NK cell cross-talk, our results suggest that cell-mediated cytotoxicity of RA-FLS may be one mechanism by which NK cells influence local joint inflammation in RA.
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http://dx.doi.org/10.1111/imm.12271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107668PMC
August 2014

Dopamine: approaches to its side chain labeling with tritium.

Appl Radiat Isot 2014 Feb 22;84:19-21. Epub 2013 Oct 22.

PerkinElmer Life Sciences & Technology, Inc., 940 Winter Street, Waltham, MA 02451, USA. Electronic address:

Methods are presented to tritiate the side chain of dopamine.
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http://dx.doi.org/10.1016/j.apradiso.2013.10.006DOI Listing
February 2014

The study design and rationale of the randomized controlled trial: translating COPD guidelines into primary care practice.

BMC Fam Pract 2013 May 6;14:56. Epub 2013 May 6.

Family Medicine and Epidemiology, Alpert Medical School of Brown University, Providence, RI 02912, USA.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive, debilitating disease associated with significant clinical burden and is estimated to affect 15 million individuals in the US. Although a large number of individuals are diagnosed with COPD, many individuals still remain undiagnosed due to the slow progression of the disorder and lack of recognition of early symptoms. Not only is there under-diagnosis but there is also evidence of sub-optimal evidence-based treatment of those who have COPD. Despite the development of international COPD guidelines, many primary care physicians who care for the majority of patients with COPD are not translating this evidence into effective clinical practice.

Method/design: This paper describes the design and rationale for a randomized, cluster design trial (RCT) aimed at translating the COPD evidence-based guidelines into clinical care in primary care practices. During Phase 1, a needs assessment evaluated barriers and facilitators to implementation of COPD guidelines into clinical practice through focus groups of primary care patients and providers. Using formative evaluation and feedback from focus groups, three tools were developed. These include a computerized patient activation tool (an interactive iPad with wireless data transfer to the spirometer); a web-based COPD guideline tool to be used by primary care providers as a decision support tool; and a COPD patient education toolkit to be used by the practice team. During phase II, an RCT will be performed with one year of intervention within 30 primary care practices. The effectiveness of the materials developed in Phase I are being tested in Phase II regarding physician performance of COPD guideline implementation and the improvement in the clinically relevant outcomes (appropriate diagnosis and management of COPD) compared to usual care. We will also examine the use of a patient activation tool - 'MyLungAge' - to prompt patients at risk for or who have COPD to request spirometry confirmation and to request support for smoking cessation if a smoker.

Discussion: Using a multi-modal intervention of patient activation and a technology-supported health care provider team, we are testing the effectiveness of this intervention in activating patients and improving physician performance around COPD guideline implementation.

Trial Registration: ClinicalTrials.gov, NCT01237561.
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http://dx.doi.org/10.1186/1471-2296-14-56DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651367PMC
May 2013

A randomized trial of treatments for high-utilizing somatizing patients.

J Gen Intern Med 2013 Nov 14;28(11):1396-404. Epub 2013 Mar 14.

Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA,

Background: Somatization and hypochondriacal health anxiety are common sources of distress, impairment, and costly medical utilization in primary care practice. A range of interventions is needed to improve the care of these patients.

Objective: To determine the effectiveness of two cognitive behavioral interventions for high-utilizing, somatizing patients, using the resources found in a routine care setting.

Design: Patients were randomly assigned to a two-step cognitive behavioral treatment program accompanied by a training seminar for their primary care physicians, or to relaxation training. Providers routinely working in these patients' primary care practices delivered the cognitive behavior therapy and relaxation training. A follow-up assessment was completed immediately prior to treatment and 6 and 12 months later.

Subjects: Eighty-nine medical outpatients with elevated levels of somatization, hypochondriacal health anxiety, and medical care utilization.

Measurements: Somatization and hypochondriasis, overall psychiatric distress, and role impairment were assessed with well-validated, self-report questionnaires. Outpatient visits and medical care costs before and after the intervention were obtained from the encounter claims database.

Results: At 6 month and 12 month follow-up, both intervention groups showed significant improvements in somatization (p < 0.01), hypochondriacal symptoms (p < 0.01), overall psychiatric distress (p < 0.01), and role impairment (p < 0.01). Outcomes did not differ significantly between the two groups. When both groups were combined, ambulatory visits declined from 10.3 to 8.8 (p = 0.036), and mean ambulatory costs decreased from $3,574 to $2,991 (pp = 0.028) in the year preceding versus the year following the interventions. Psychiatric visits and costs were unchanged.

Conclusions: Two similar cognitive behavioral interventions, delivered with the resources available in routine primary care, improved somatization, hypochondriacal symptoms, overall psychiatric distress, and role function. They also reduced the ambulatory visits and costs of these high utilizing outpatients.
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http://dx.doi.org/10.1007/s11606-013-2392-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797340PMC
November 2013

E-health blood pressure control program.

J Med Pract Manage 2012 Sep-Oct;28(2):91-100

Abacus Health Solutions, 1210 Pontiac Avenue, Cranston, RI 02920, USA.

Both technological and human factors design requirements for integration of home blood pressure monitoring (HBPM) into a patient centered medical home (PCMH) model primary care practice are described. Patients with uncontrolled hypertension were given home blood pressure (BP) monitors, and after a three-month run-in period introduced to either a high-tech only (HBPM connectivity to personal health record and tailored Web portal access) or a high-tech/"high-touch" (high-tech solution plus patient navigator [PN]) solution. Features of the Web portal included: BP graphing function, traffic-light feedback system of BP goal attainment, economic incentives for self-monitoring, and dual patient-facing and care-team-facing dashboard functions. The e-health BP control system with PN support was well received by patients, providers, and the healthcare team. Current e-health technology and limited technological literacy of many patients suggest that a PN or some other personnel resource may be required for the adoption of patient-facing technology in primary care.
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January 2013

Responsiveness of hypochondriacal patients with chronic low-back pain to cognitive-behavioral therapy.

Psychosomatics 2012 Mar-Apr;53(2):139-47

Division of Psychosomatic Medicine, Teikyo University Hospital, Tokyo, Japan.

Background: Evidence has suggested that cognitive-behavioral therapy (CBT) is effective in reducing hypochondriacal symptoms, and another line of evidence has suggested that CBT is also effective in reducing pain and the psychological conditions associated with chronic low-back pain (CLBP). The purpose of this study was to examine the effectiveness of CBT among hypochondriacal patients with and without CLBP.

Methods: A total of 182 hypochondriacal patients were randomly assigned to a CBT or control group. The Somatic Symptom Inventory was used to define CLBP, and the Symptom Checklist 90R (SCL90R) was used to assess psychological symptoms. The outcome measures for hypochondriasis, the Whiteley Index (WI) and the Health Anxiety Inventory (HAI) were administered before the intervention and at 6 and 12 months after completion of the intervention.

Results: In the total sample, both WI and HAI scores were significantly decreased after treatment in the CBT group compared with the control group. Ninety-three (51%) patients had CLBP; the SCL90R scores for somatization, depression, phobic anxiety, paranoid ideation, and general severity were significantly higher in CLBP(+) group than in the CLBP(-) group at baseline. Although the WI and HAI scores were significantly decreased after treatment in the CLBP(-) group, such significant pre- to post-changes were not found in the CLBP(+) group.

Conclusions: CBT was certainly effective among hypochondriacal patients without CLBP, but it appeared to be insufficient for hypochondriacal patients with CLBP. The core psychopathology of hypochondriacal CLBP should be clarified to contribute to the adequate management of hypochondriacal symptoms in CLBP patients.
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http://dx.doi.org/10.1016/j.psym.2011.09.006DOI Listing
July 2012