Browsing by Author "Licciardone, John C."
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Item A Case Study of Osteopathic Medicine's "Catch-22"(2010-02-26) Licciardone, John C.John Licciardone, D.O., M.S., M.B.A., describes why and how he decided to become an Open Access journal founder of the Osteopathic Medicine and Primary Care Journal.Item A Study of Pharmacologic Therapy in Patients with Chronic Low Back Pain(2021) Powell, Jake; Licciardone, John C.Purpose: This study aimed to examine the effects of different pharmacologic therapies on patients with chronic low back pain, including nonsteroidal anti-inflammatory drugs(NSAIDs), opioids, antidepressants, muscle relaxants, antipsychotics, and anticonvulsants. Outcomes included low back pain intensity, back-related functioning, and quality of life. Methods: This was a cross-sectional study of patients within the PRECISION Pain Research Registry who met criteria for chronic low back pain established by the National Institutes of Health. Pharmacologic therapy was self-reported by patients. Back pain intensity was measured with an 11-point numerical rating scale (NRS). Back-related functioning was measured using the Roland-Morris Disability Questionnaire (RMDQ). Quality of life was measured using the SPADE cluster (sleep disturbance, pain interference with activities, anxiety, depression and low energy/fatigue) derived from the Patient-Reported Outcomes Measurement Information System (PROMIS-29). Higher scores represent worse health on all outcome measures. Results: Of 977 eligible patients, 323(33.1%) used opioids, 593(60.7%) used NSAIDs, 222(22.7%) used antidepressants, 160(16.4%) used muscle relaxants, 44(4.5%) used atypical antipsychotics, and 153(15.7%) used anticonvulsants. Mean NRS score for patients using opioids was 6.5 vs. 5.9 for non-users (p=0.13,95%CI(-0.925 - -0.390)). Mean RMDQ score for opioid users was 16.7 vs. 13.2 for non-users (p< 0.001,95%CI(-4.287 - -2.720)). Mean SPADE score for opioid users was 59.4 vs. 56.4 for non-users (p=0.15,95%CI(-3.910 - -1.9798)). Conclusion: Patients used a variety of pharmacologic therapies for chronic low back pain. Opioid users reported worse outcomes than non-users, including significant deficits in back-related functioning.Item Analysis of the Patient-Physician Relationship, Race, and Pain Control and Physical Function Among Adults With Chronic Low Back Pain(American Medical Association, 2022-06-01) Licciardone, John C.; Ganta, Sweta; Goehring, Leah; Wallace, Kendall; Pu, RyanImportance: Racial and ethnic disparities in pain outcomes are widely reported in the United States. However, the impact of the patient-physician relationship on such outcomes remains unclear. Objective: To determine whether the patient-physician relationship mediates the association of race with pain outcomes. Design, Setting, and Participants: This cross-sectional study uses data from the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation, collected from April 2016 to December 2021. All registry enrollees who identified as Black or White with chronic low back pain who had a regular physician who provided pain care were included. Data were analyzed during December 2021. Exposures: Participant-reported aspects of their patient-physician relationship, including physician communication, physician empathy, and satisfaction with physician encounters. Main Outcomes and Measures: The primary outcomes included low back pain intensity, measured with a numerical rating scale and physical function, measured with the Roland-Morris Disability Questionnaire. Mediator variables were derived from the Communication Behavior Questionnaire, Consultation and Relational Empathy measure, and Patient Satisfaction Questionnaire. Results: Among 1177 participants, the mean (SD) age was 53.5 (13.1) years, and there were 876 (74.4%) women. A total of 217 participants (18.4%) were Black, and 960 participants (81.6%) were White. The only difference between Black and White participants in the patient-physician relationship involved effective and open physician communication, which favored Black participants (mean communication score, 72.1 [95% CI, 68.8-75.4] vs 67.9 [95% CI, 66.2-69.6]; P = .03). Black participants, compared with White participants reported worse outcomes for pain intensity (mean pain score, 7.1 [95% CI, 6.8-7.3] vs 5.8 [95% CI, 5.7-6.0]; P < .001) and back-related disability (mean disability score, 15.8 [95% CI, 15.1-16.6] vs 14.1 [95% CI, 13.8-14.5]; P < .001). In mediation analyses that controlled for potential confounders using disease risk scores, virtually none of the associations of race with each outcome was mediated by the individual or combined factors of physician communication, physician empathy, and patient satisfaction. Similarly, no mediation was observed in sensitivity analyses that included only participants with both chronic low back pain and the same treating physician for more than 5 years. Conclusions and Relevance: These findings suggest that factors other than the patient-physician relationship were important to pain disparities experienced by Black participants. Additional research on systemic factors, such as access to high-quality medical care, may be helpful in identifying more promising approaches to mitigating racial pain disparities.Item Association between GDF5 single nucleotide polymorphism rs143383 and chronic lower back pain(2019-03-05) Phillips, Nicole R.; Aryal, Subhash; Licciardone, John C.; Tran, ApolloIntroduction. Low back pain presents a unique and ongoing challenge for patients and physicians. Of those who experience an episode of low back pain, 10% go on to develop persistent chronic low back pain (CLBP). However, the cause of this progression is not understood and it is unclear why the clinical manifestation of CLBP differs across individuals. There is a large body of evidence demonstrating the role of genetics as a risk factor CLBP. Growth factor differentiation factor 5 (GDF5) is a protein involved in the growth and development of bone and cartilage. A variant of GDF5, single-nucleotide polymorphism (SNP) rs143383 has been implicated with increased susceptibility and severity of musculoskeletal disorders such as osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. Considering that the cause of low back pain often involves musculoskeletal pathology, rs143383 may be implicated with symptomatology and the progression to persistent CLBP. Objective. This study seeks to determine whether the rs143383 SNP is associated with pain severity in CLBP. We hypothesize that subjects with the CC genotype experience higher levels of pain compared to the TT and CT genotypes. Methods. This project is an observational cohort study based on data retrieved from The Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION). Subjects were divided into three groups, TT, CT, and CC. Average pain levels based on the Numerical Rating Scale (NRS) for low back pain were compared among the groups. Results. Using a general linear model, we found that the rs143383 SNP was significantly associated with NRS scores (P = 0.001). We also found that the CC genotype had a statistical higher mean NRS score than the CT (P = 0.0370) and TT (P = 0.0004) genotypes. However, when the data was adjusted for race, ethnicity, gender and age, no significance was found between rs143383 and NRS scores. Conclusion. Our findings indicate that there is no association between the GDF5 rs143383 polymorphism after adjusting for race and ethnicity. We were unable to complete a stratified analysis due to the distribution of participants in each strata. Larger studies should consider a stratified analysis to determine whether there is an association between rs143383 and CLBP within different ethnicities and racial groups.Item Association of ABCB1 (rs1045642) single nucleotide polymorphism and drug metabolism reserve index (DMRI) with pain intensity among adults with chronic low back pain(2019-03-05) Licciardone, John C.; Phillips, Nicole R.; Salman, JustinPurpose Low back pain is the leading cause of disability in the United States. It is often associated with long term opioid use, which may lead to opioid misuse and serious adverse events. Current clinical guidelines caution that opioids may provide only a small to moderate therapeutic effect, despite these potential risks. This study explores the use of pharmacogenetics in patients with chronic low back pain who are managed with opioids by investigating nucleotide variants in ABCB1,a gene implicated in drug bioavailability. Additionally, a three gene model using CYP2D6, CYP2C9, and CYP2C19, will be used to determine opioid drug metabolism on a quantitative scale. We aim to identify pharmacogenetics variants that may lead to safer and more effective treatment of chronic low back pain in patients being managed with opioids. Methods This study included 102 patients with low back pain within the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION). All patients in the study reported using opioids for their low back pain. DNA genotyping of biological samples from all patients was conducted on Illumnina iScan Global Screening Array. A common SNP locus (C3435T, rs1045642) in ABCB1was genotyped. Additionally, SNPs for CYP2D6, CYP2C9, and CYP2C19 were used to construct the drug metabolism reserve index (DMRI) for each patient, which was then stratified as Sub-functional (DMRI 6). Outcome measures included a numerical rating scale for low back pain intensity, the Roland-Morris Disability Questionnaire, and the PROMIS-SPADE cluster for quality of life. The Mann-Whitney test was used for statistical analysis in SPSS. Results Patients with the T allele at rs1045642, which inhibits ABCB1 protein function and increases drug bioavailability, reported significantly lower pain intensity within the functional DMRI group (p = 0.01). However, there was no significant difference in pain intensity with the sub-functional DMRI group (p = 0.186). Conclusion The results suggest that gene variants in ABCB1 may potentially affect pain relief in opioid users, and may be useful in guiding opioid prescribing for pain management. Longitudinal pharmacogenetic studies in larger cohorts are necessary to establish the utility of such gene variants in ABCB1 in guiding safer and more effective pain management in patients with low back pain.Item Association of Pain Catastrophizing with Clinical Outcomes for Chronic Widespread Pain: A Retrospective Cohort Study(2022) Vu, Stephanie; Thornton, Tyler; Baker, Joshua; Licciardone, John C.Purpose: Chronic widespread pain (CWP) is diffuse musculoskeletal pain lasting for 3 months or longer and is associated with numerous psychological symptoms, including fatigue, distress, difficulty concentrating, and depression. It affects over 20% of the population and may contribute to adverse health effects. Pain catastrophizing is defined an exaggerated negative mental set brought to bear during actual or anticipated painful experience. This study aimed to measure the association between pain catastrophizing and CWP, focusing on such clinically relevant outcomes as pain intensity, disability, and health-related quality-of-life (HRQOL) deficits. Methods: Study participants were selected from the PRECISION Pain Research Registry during the period from April 2016-December 2021. Eligible participants had chronic low back pain according to the National Institutes of Health case definition at registry enrollment and ranged from 21 to 79 years of age. Participants were classified as having CWP if they reported being "bothered a lot" by widespread pain or pain in most of their body in the 4 weeks prior to enrollment. Pain catastrophizing was measured at enrollment with the Pain Catastrophizing Scale and participants were classified as low, intermediate, or high pain catastrophizers based on tercile cutpoints. Multiple logistic regression was used to identify predictors of CWP at enrollment, and clinical outcomes were measured at quarterly encounters over 12 months. The primary outcomes included low back pain intensity measured with a numerical rating scale, back-related disability measured with the Roland-Morris Disability Questionnaire (RMDQ), and HRQOL measured with the SPADE cluster (sleep disturbance, pain interference with activities, anxiety, depression, and low energy/fatigue). Repeated measures analysis of variance was used to compare outcomes over 12 months according to pain catastrophizing level, including adjustment for potential confounders using propensity scores. Results: A total of 1,260 participants were studied. There were 337 (26.7%) participants with CWP, of whom 212 (62.9%) had complete follow-up data. Pain catastrophizing was the strongest predictor of CWP (OR, 1.93, 95% CI, 1.39-2.68; P< 0.001 and OR, 3.22, 95% CI, 2.10-4.94; P< 0.001 for intermediate and high pain catastrophizers vs. low pain catastrophizers, respectively). A strong association was initially observed between pain catastrophizing and all longitudinal outcomes (P=0.004 for low back pain intensity, and P< 0.001 for back-related disability and HRQOL). However, only the findings for back-related disability and HRQOL remained significant following adjustment for confounders. The overall mean RMDQ scores were 16.0 (95% CI, 14.7-17.3), 16.6 (95% CI, 15.7-17.5), and 18.4 (95% CI, 17.7-19.1) (P< 0.001) for low, intermediate, and high pain catastrophizers, respectively. Similarly, the overall mean SPADE scores were 57.9 (95% CI, 56.3-59.6), 60.5 (95% CI, 59.4-61.6), and 63.2 (95% CI, 62.3-64.1) (P< 0.001) for low, intermediate, and high pain catastrophizers, respectively. Conclusions: This study demonstrates that pain catastrophizing strongly predicts long-term disability and HRQOL deficits in patients with CWP. There is a need for further investigation into psychological treatments aimed at reducing pain catastrophizing to mitigate its impact in this population.Item Association of Pain Sensitivity with Outcome Measures for Quality of Life, Functional Ability and Current Pain Intensity in Chronic Low Back Pain(2021-05) Doud, Ronnie L.; Sumien, Nathalie; Licciardone, John C.; Kearns, Cathleen; Phillips, Nicole R.Pain sensitivity, as measured by the self-reported Pain Sensitivity Questionnaire (PSQ), was investigated using data from the PRECISION Pain Research Registry. Outcome measures for quality of life, functional ability, and current pain intensity were found to be significantly associated with PSQ Total in participants reporting chronic low back pain, even when controlling for age, sex, race, ethnicity, smoking status, and body mass index. Higher reported pain sensitivity correlated with reported higher pain intensity, lower quality of life, and increased physical disability.Item Association of the Patient-Physician Relationship with Racial Disparities in Chronic Pain Outcomes(2023) Pu, Ryan; Licciardone, John C.; Ganta, Sweta; Goehring, Leah; Wallace, KendallAbstract Summary : Purpose: Racial disparities involving health outcomes in the United States have been widely investigated. However, the role of the patient-physician relationship in these disparities remains unclear. Of interest, Black patients may experience different treatment and outcomes relating to pain management. This research aims to determine if the patient-physician relationship mediates the association between race and pain outcomes among patients with chronic low back pain. Methods: Participants in this study were selected from the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION Pain Research Registry) from April 2016 through December 2021. All participants were 21 to 79 years of age, had chronic low back pain according to criteria established by the National Institutes of Health, and had a physician who regularly treated their low back pain. Primary outcomes included low back pain intensity measured with a numerical rating scale and physical function measured with the Roland-Morris Disability Questionnaire. The patient-physician relationship variables were derived from the Communication Behavior Questionnaire, Consultation and Relational Empathy Measure, and Patient Satisfaction Questionnaire. Mediation analyses were performed with the PROCESS v4 software, using multiple mediation models and 95% bootstrap confidence intervals. Results: A total of 1177 participants were studied, including 217 and 960 Black and White participants, respectively. Black participants reported worse outcomes for pain intensity (mean, 7.1; 95% CI, 6.8-7.3 vs. mean, 5.8 95% CI, 5.7-6.0; P< 0.001) and back-related disability (mean, 15.8; 95% CI, 15.1-16.6 vs. mean, 14.1; 95% CI, 13.8-14.5; P< 0.001). The differences in the patient-physician relationship between Black and White participants were not significant, with the exception that Black participants experienced more open and effective communication with their physicians than White participants (mean, 72.1; 95% CI, 68.8-75.4 vs. mean, 67.9; 95% CI, 66.2-69.6; P=0.03). In the mediation analyses, virtually none of the association between race and each outcome was mediated by the individual or combined effects of physician communication, physician empathy, and patient satisfaction. Conclusions: These findings suggest that factors other than the patient-physician relationship are important drivers of pain disparities experienced by Black patients in the United States. Additional research on system factors, such as access to high-quality medical care, may be helpful in identifying more promising approaches to mitigating racial pain disparities.Item Candidate gene analysis of 535 "pain genes" and associations with reported intensity of chronic low back pain(2022) Hurd, Christine A.; Phillips, Nicole R.; Lin, Emily; Broadbent, Dallen; Doederlein, Alexander R.; Dubakula, Vishnu; Licciardone, John C.Purpose: Numerous genome-wide association studies have been able to elucidate potential underlying genetic associations with clinical diagnoses. Chronic low back pain (CLBP) is a clinical presentation that has not yet been strongly associated with specific genetic markers. Several studies however have found genetic associations with other various pain disorders, such as the 535 genes identified by Ultsch et al. as "pain genes." Our group aims to find associations between previously identified pain-related genes and clinical reports of the intensity of low back pain using genetic and clinical data collected by the PRECISION Pain Research Registry. Methods: The PRECISION Pain Research Registry is a national registry that has collected demographic, clinical, and genetic information of patients with CLBP. Our analysis is querying associations between these identified "pain genes" and the intensity of low back pain reported by registry participants using a numerical rating scale (NRS). Methods: Participants in the PRECISION Pain Research Registry were genotyped via an Illumina iScan Array Scanner and Global Screening Array. The phenotype of CLBP will be measured by the NRS, which is an 11-point quantifier of pain intensity. The collected genotypes and phenotypic expression of pain will be compared via the Multi-marker Analysis of GenoMic Annotation (MAGMA), which enables candidate gene analysis of the 535 "pain genes" via congregation of single nucleotide polymorphisms (SNPs) and subsequent projection onto principal components in a matrix. Pain intensity will be evaluated as a function of genetic effects accounting for selected covariates-comorbid conditions with a documented relationship to CLBP, smoking status, and genetic ancestry plus residuals, with F-tests to determine the p-values of associations. Results: FN1 and STARD13 were found to be significantly associated with pain intensity in AA registry participants and VEGF-A was found to be significantly associated with widespread pain in NHW registry participants Conclusion: For treatment that is refractory to other strategies, targeted drugs for these protein products can be explored as treatments. These mentioned genes also have significant epigenetic regulation that could be explored in further studies.Item Candidate Gene Association Study of Low Back Pain Using SNP Derived Gene Expression Profiling: A PRECISION PAIN Research Registry Study(2019-03-05) Pathak, Gita; Aryal, Subhash; Phillips, Nicole R.; Licciardone, John C.; Bhatnagar, ShwetaCandidate Gene Association Study of Low Back Pain Using SNP Derived Gene Expression Profiling: A PRECISION PAIN Research Registry Study Shweta Bhatnagar, Gita Pathak, Subhash Aryal, Nicole Phillips, John Licciardone Abstract Objective: The Global Burden of Disease Study estimated that 632 million persons worldwide are affected by low back pain (LBP), making it the leading cause of disability worldwide. Furthering our understanding of genetic-based risk for LBP may allow for development of targeted gene therapy for pain which may help mitigate the healthcare and financial burden. Inflammatory genes have been implicated in pain disorders. Variability in how these genes are expressed may determine their association in low back pain. This study aims to predict the expression of candidate genes and their association with pain in participants of the PRECISION Pain Research Registry. Hypothesis: Elevated self-reported pain intensity and disability from LBP is associated with the higher expression of inflammatory genes. Methods: The DNA was collected, extracted, and genotyped using the Infinium® Global Screening Array (Illumina). Data were filtered based on standard quality control protocols (Anderson et al., 2010). Gene expression data of monocytes from the Multi-Ethnic Study for Atherosclerosis (MESA) was used for gene expression imputation using PrediXcan. Twenty-six candidate genes involved with inflammation and immune response processes (based on Gene Ontology Analysis) were analyzed. The imputed gene expression levels were transformed to dichotomized gene expression levels, over-expressed and under-expressed. The highly expressed gene levels were then tested for association with PRECISION participant outcomes data, including Roland-Morris Disability Score and a pain intensity score using SPSS. Results: Seven genes showed positive correlation between their predicted expression levels and scores on the Roland-Morris Questionnaire and the pain intensity scale for LBP: STAT-1, STAT-2, HLA-A, CD48, CD209, CLEC4G and SLAMF8. Also, as expected, many of these genes demonstrated co-expression patterns due to their common role in immune mediation. Conclusions: The results demonstrate a positive correlation between the increased expression of inflammatory genes and how the subjects perceived and reported LBP. Understanding the relationship between pain and variability in inflammatory genes could play a role in future precision medicine and pain management.Item DETERMINATION OF GENETIC FACTORS ASSOCIATED WITH RESPONSE TO OSTEOPATHIC MANIPULATIVE TREATMENT IN INDIVIDUALS WITH CHRONIC LOWER BACK PAIN(2014-03) Richardson, Kayla; Cross, Deanna; Kearns, Cathy; Planz, John; Licciardone, John C.OMT (Osteopathic Manipulative Treatment) is an often overlooked, low risk treatment option for management of (Chronic Lower Back Pain) CLBP. My overarching hypothesis is that genetics contributes to OMT response. The study used 216 samples consisting of 111 individuals who received OMT, and a placebo group of 105 individuals who received a sham treatment. Genetic differences between subjects who benefited from OMT (responders) and those who did not benefit from OMT (non-responders) were compared. We found an association between 3 genes (IL-8, GCH1, and LARGE) and response to OMT in individuals who suffer from CLBP. Purpose (a): OMT (Osteopathic Manipulative Treatment) is an often overlooked, low risk treatment option for management of (Chronic Lower Back Pain) CLBP. Underutilization of OMT is partially due to an undefined mechanism of action for the therapy. Our overarching hypothesis is through analysis of genotypic attributes; it is possible to determine which individuals are more likely to respond to OMT leading to insights into mechanisms of action. The current study investigated potential polymorphisms associated with OMT and pain reduction using data previously collected from a CLBP clinical study, which was part of The OSTEOPATHIC Trials. Methods (b): We performed a candidate gene study using single nucleotide polymorphisms (SNPs) within genes previously associated with pain: Catechol-o-methyltransferase (COMT), beta 2 adrenergic receptor (ADRB2), GTP cyclohydrolase GCH1, Interleukin 1 alpha (IL1A), interleukin 1 beta (IL1B), interleukin 1 receptor antagonist (IL1RN), Interleukin 8 (IL8), and like- glycosyltransferase (LARGE). Genotypes from subjects who benefited from OMT (responders) were compared to subjects who did not benefit from OMT (non-responders) using a chi-square analysis to test for associations. For SNPs that showed significance (α=0.05) an odds ratio (O.R.) was calculated. The study utilized 216 samples consisting of 111 individuals who received OMT, and a placebo group of 105 individuals who received a sham treatment. Results (c): SNPs in IL-8, GCH1, and LARGE showed significance (α=0.05) in the OMT group only: IL-8 SNP rs2227543 (O.R. 2.2824 CT, confidence interval (C.I.) 1.0053-5.1818), LARGE SNP rs240070 (O.R. 2.8546 TA, 1.0508-7.7548), and GCH1 SNP rs998259 (O.R. 0.4016 GA, C.I. 0.1600-1.0080). A SNP by SNP interaction was detected within GCH1 between rs998259 and rs3783641. When the rs998259 genotype is GG, rs3783641 is associated with response to OMT (α=0.05, O.R. 2.9630 TA, C.I. 1.1269-7.7907). Conclusions (d): There is an association between genetics and response to OMT in individuals who suffer from CLBP. Individuals with genotype CT in rs2227543 or TA in rs240070 are more likely to respond to OMT whereas individuals with genotype GA in rs998259 are less likely to respond to OMT. Furthermore, if an individual has genotype GG in rs998259 and TA in rs3783641 they are more likely to respond to OMT. Genes in neuronal, immunological, and muscular pathways affect OMT response.Item Differences in race-specific outcome measures for chronic low back pain patients with relation to HTR2A variations(2021) Holden, Jeremy; Phillips, Nicole R.; Licciardone, John C.Purpose: The effects of many genes involved in the pathogenesis of chronic low back pain (CLBP) are not fully understood, especially concerning racial variation. This study aims to determine if variations of the serotonin receptor gene HTR2A, which has been implicated in psychological and pain disorders, correlate to differences in clinical outcome measures of patients with CLBP in the PRECISION Pain Research Registry. Methods: The base population includes 283 (68.4%) Caucasians and 131 (31.6%) African Americans who were genotyped for their haplotype in 2 haploblocks: A (rs6313;A/G, rs6311;T/C, rs1928040;A/G, rs9567746;A/G) and B (rs7997012;A/G, rs7330636;T/C). Race-specific Kruskal-Wallis analyses were used to determine differences in outcome measures when comparing haplotypes within haploblocks. Separate regression analyses looked at whether haplotypes that are overrepresented in one racial group versus the other had effects on the same outcomes. Results: There were differences in scores for the Roland-Morris Disability Questionnaire (RMDQ) (p=0.04), pain catastrophizing (PCS) (p=0.04), and pain self-efficacy (PSEQ) (p< 0.01) within haploblock A for African Americans. There were also differences in the RMDQ (p=0.02) and PSEQ (p< 0.01) scores within haploblock B for Caucasians. Regressions showed having at least one allele with the haplotype GC in haploblock B is associated with a lower numerical rating scale value for pain intensity after adjusting for additional variables (beta=-0.59; p=0.02). Conclusions: Haplotypes of HTR2A may have a relationship with the pain intensity, disability, and pain response of CLBP patients. Further studies would look at additional race-specific factors and their interplay with HTR2A.Item Disability and quality of life following long-term opioid therapy in patients with chronic low back pain(2020) Licciardone, John C.; Schultz, MatthewPurpose: To compare the effects of long-term opioid therapy versus no opioid therapy on self-reported disability and quality of life (QOL) in patients with chronic low back pain (CLBP). Methods: Patients with CLBP enrolled in the PRECISION Pain Research Registry were grouped according to opioid use. Patients reporting opioid use for 12 consecutive months were classified as opioid users; patients reporting no opioid use for 12 consecutive months were classified as opioid non-users. Disability (Roland Morris Disability Questionnaire) and QOL (29-item Patient-Reported Outcomes Measurement Information System) were compared using multiple linear regression. Results: There were 78 opioid users and 134 non-users. Opioid users were significantly older and reported significantly higher measures of depression and pain intensity. Opioid users reported greater disability (17.1 vs 10.84, p< 0.001), sleep disturbance (57.9 vs 54.7, p< 0.001), pain interference with activities (66.1 vs 57.9, P< 0.001), anxiety (54.1 vs 51.0, p=0.04), and fatigue (61.3 vs 55.0, p< 0.001); less participation in social roles (40.9 vs 48.5, p< 0.001); and lower physical function (34.3 vs 40.6, p< 0.001). With the exception of anxiety, these findings did not change after controlling for age, body mass index (BMI), depression, and pain intensity. Conclusions: After controlling for age, BMI, depression, and pain intensity, patients with CLBP receiving long-term opioid therapy reported significantly greater disability and poorer QOL compared to those receiving no opioid therapy. The findings of this study draw into question the utility of long-term opioid therapy for CLBP.Item Does Osteopathic Manipulative Treatment Improve Dyspnea and Exercise Tolerance Subjects with Stable Chronic Obstructive Pulmonary Disease?(2006-05-01) Pickett, Carolyn M.; Stoll, Scott; Cruser, des Anges; Licciardone, John C.Pickett, Carolyn M., D.O., M.S. Does Osteopathic Manipulative Treatment Improve Dyspnea and Exercise Tolerance in Subjects with Stable Chronic Obstructive Pulmonary Disease? Master of Science (Clinical Research and Education – OMM), May 2006, 54 pages, 10 tables, 4 figures, references 48 titles. Chronic Obstructive Pulmonary Disease (COPD) is the fourth leading cause of death globally and is projected to increase. This highly prevalent and costly disease causes reduced physical and social functioning, and none of the existing medications for COPD seem to modify long-term decline in lung function. COPD patients with the severe dyspnea have more deficits in the health status and energy. Reduced functional status has been significantly correlated with health related quality of life. Osteopathic Manipulative Treatment (OMT) has been suggested for treatment of COPD as early as 1902, some research indicates that OMT may improve dyspnea and exercise tolerance, yet there are few published studies on OMT and COPD. Study goals were to increase scientific knowledge about how OMT may immediately improve dyspnea and exercise tolerance in stable COPD following exertion. This RCT was approved by the Institutional Review Board at the University of North Texas Health Science Center (UNTHSC) in Fort Worth and funded by the Osteopathic Research Center (ORC) at UNTHSC. –Hypothesis 1: A single intervention of OMT will improve dyspnea in a stable COPD subject, as measured by response to the Borg scale with exertion, when compared to no treatment. –Hypothesis: a single intervention of OMT will improve exercise tolerance in a stable COPD subject, as measured by distance walked during the six-minute walk test, when compared to no treatment. Twenty-one subjects completed the trial, 10 in the OMT group and 11 in the no-treatment group. No significant differences were found in the Borg scale or 6MWT following OMT. This study is limited by a small sample size and single OMT intervention design; however, it does demonstrate the feasibility of this research at this institution and may lead to a larger, more definitive and funded clinical trial.Item Epidemiology and Diagnostic Testing of Tuberculosis (Mycobacterium bovis) Infection in Ungulates in a Texas Zoo(1998-06-01) Hodges, Connie M.; Bidaut-Russell, Michelle; Licciardone, John C.; Murnane, ThomasTuberculosis infection among ungulates with Mycobacterium bovis (M. bovis) in a Texas zoo resulted in epidemiological assessment and testing of 161ungulates because of concerns about the validity of tuberculosis infection in the zoo. Three intradermal tests and one serological test were used to assess M.bovis infection : 1)the comparative cervical tuberculin test (CCT) consisting of biologically balanced bovine purified protein derivative (PPD) and avian PPD; 2) the single cervical bovine PPD tuberculin (BPDD); 3) the Tuberculin-Mammalian (MOT) intradermal tuberculin; and 4) the serological blood tuberculosis test (BTB). All four tests were evaluated. Validity (i.e. sensitivity and specificity), positive predictive value (PPV), and negative predictive value (NPV) were measured. The MOT followed by the BPPD were the most sensitive tests, correctly identifying 100% and 67%, respectively of tuberculosis infected/exposed ungulates. The BTB test was the third order of recommendation followed by the combined CCT and BTB (CCT+BTB) tests, where a positive result in either test denoted a positive response. The CCT test ranked last, as this test had the lowest sensitivity and would have allowed tuberculosis infection to remain in the zoo.Item Examining SLC6A4 Variations in the PRECISION Pain Research Registry(2019-03-05) Phillips, Nicole R.; Aryal, Subhash; Licciardone, John C.; Lopez, JonathanPurpose: Chronic low back pain is the leading cause of disability globally and has been linked to comorbidities such as depression. Common pathways involving serotonin and norepinephrine may play a role in both pain and mood disorders. The SLC6A4 gene, encoding a serotonin reuptake transporter, has been heavily studied with regard to depression. Polymorphisms within the gene are thought to influence the expression of the transporter, thereby modulating serotonin transmission. More recently, this gene has been studied in the context of chronic pain. This study seeks to further our understanding of chronic pain with respect to depression and other outcome measures in participants with chronic low back pain to aid in the development of better treatments. Methods: Participants with chronic low back pain in the PRECISION Pain Research Registry provided DNA samples that were genotyped on the Infinium Global Screening Array (Illumina). Long and short length polymorphisms of the SLC6A4 gene were predicted using an eight single nucleotide polymorphism (SNP) machine learning model. Of the eight, one SNP was collected from the array, and the other seven were imputed. Additionally, the rs25531A [greater than] G SNP was imputed. Using the length of the polymorphism and the rs25531 SNP, subjects were divided into high, intermediate and low expression groups. Participants also reported clinical status measures such as low back pain intensity, back-specific functioning, PROMIS quality of life, levels of pain self-efficacy, and pain catastrophizing. Results: There was no significant association between self-reported depression and expression levels (high, intermediate, low) of SLC6A4. No correlation was found between PROMIS depression scores and SLC6A4 expression. Analyses for depression values were conducted using logistic linear regression and non-parametric ANOVA respectively. There were no observed correlations between transporter expression level and the outcome variables of back-related disability, pain, pain catastrophizing, or pain self-efficacy. Disability was analyzed using ANOVA. Pain, pain catastrophizing, and pain self-efficacy were investigated using non-parametric ANOVA analyses. Conclusion: No correlations were found between serotonin transporter expression level and depression or other outcome variables. Similar previous studies investigating SLC6A4 used homogenous populations. We recommend conducting a larger study that takes into account race.Item Factors Associated with Pain Sensitivity and its Impact on Long-Term Outcomes in Patients with Chronic Pain: A Retrospective Cohort Study(2022) Beal, Jennifer; Fakes, Nicole; Herron, Breanna; Jacobs, Colleen; Vasudevan, Aditi; Licciardone, John C.Purpose Low back pain is estimated to affect 632 million people globally and treatment of back and neck pain in the United States costs upwards of $100 billion annually. Major clinical practice guidelines have been established for chronic pain in general, and for chronic low back pain (CLBP) in particular, with non-pharmacological and non-opioid therapies as first-line treatments. Nevertheless, these guidelines do not address how pain sensitivity may influence treatment. Pain sensitivity may be defined as the perception of pain in different situations, which varies from person to person. This study aims to determine if pain sensitivity is associated with long-term outcomes relating to low back pain intensity, back-related disability, and health-related quality of life in patients with CLBP. Methods Participants with CLBP were recruited from the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION Pain Research Registry) from April 2016 through December 2021. Pain sensitivity was measured for each participant using the Pain Sensitivity Questionnaire (PSQ), wherein scores range from 0 (least pain sensitivity) to 10 (greatest pain sensitivity). Participants were subsequently classified as having low (PSQ score ≤4) or high (PSQ score >4) pain sensitivity based on a median split. The primary outcomes were measured at quarterly encounters over 12 months, and included low back pain intensity measured with a numerical rating scale, back-related disability measured with the Roland-Morris Disability Questionnaire, and health-related quality of life measured with the SPADE cluster (sleep disturbance, pain interference, anxiety, depression, and low energy/fatigue) derived from the Patient-Reported Outcomes Measurement Information System. Multiple logistic regression was initially used to predict participant characteristics associated with high pain sensitivity. Longitudinal outcomes over 12 months were then compared according to pain sensitivity level using repeated measures analysis of variance, while simultaneously controlling for potential confounders using propensity scores. Results The strongest predictors of high pain sensitivity were being Black (OR, 6.43; 95% CI, 4.01-10.32; P< 0.001) and having high pain catastrophizing (OR, 3.11; 95% CI, 2.09-4.62; P< 0.001). High pain sensitivity was associated with greater overall levels of low back pain intensity (P< 0.001), back-related disability (P< 0.001), and health-related quality-of-life deficits (P< 0.001). However, after controlling for confounding variables, only the findings for pain intensity remained significant (P< 0.001). Conclusions High pain sensitivity is associated with greater low back pain intensity (but not with back-related disability or health-related quality of life) after controlling for confounding variables. Being Black and having high levels of pain catastrophizing were highly significant predictors of high pain sensitivity. The latter finding has important implications for rehabilitation of patients with chronic pain, as it highlights the importance of interventions that address patient pain catastrophizing, pain sensitivity, and ultimately adverse health outcomes. Physicians should be aware of how they can improve long-term chronic pain outcomes by addressing the patient's mental state relating to pain, as well as using other more conventional approaches to pain management.Item Feasibility Trial of an eHealth Intervention for Health-Related Quality of Life: Implications for Managing Patients with Chronic Pain during the COVID-19 Pandemic(MDPI, 2020-10-01) Licciardone, John C.; Pandya, VishrutiPURPOSE: This study was conducted to determine the feasibility of providing an eHealth intervention for health-related quality of life (HRQOL) to facilitate patient self-management. METHODS: A randomized controlled trial was conducted from 2019-2020 within the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation. Eligible patients included those with chronic low back pain and a SPADE (sleep disturbance, pain interference with activities, anxiety, depression, and low energy/fatigue) cluster score >/= 55 based on the relevant scales from the Patient-Reported Outcomes Measurement Information System instrument with 29 items (PROMIS-29). Patients were randomized to the eHealth treatment group, which received a tailored HRQOL report and interpretation guide, or to a wait-list control group. The primary outcome was change in the SPADE cluster score, including its five component scales, over 3 months. Secondary outcomes were changes in low back pain intensity and back-related disability. Treatment effects were measured using the standardized mean difference (SMD) in change scores between groups. The eHealth intervention was also assessed by a survey of the experimental treatment group 1 month following randomization. RESULTS: A total of 102 patients were randomized, including 52 in the eHealth treatment group and 50 in the wait-list control group, and 100 (98%) completed the trial. A majority of patients agreed that the HRQOL report was easy to understand (86%), provided new information (79%), and took actions to read or learn more about self-management approaches to improve their HRQOL (77%). Although the eHealth intervention met the criteria for a small treatment effect in improving the overall SPADE cluster score (SMD = 0.24; p= 0.23) and anxiety (SMD = 0.24; p = 0.23), and for a small-to-medium treatment effect in improving depression (SMD = 0.37; p = 0.06) and back-related disability (SMD = 0.36; p = 0.07), none of these results achieved statistical significance because of limited sample size. CONCLUSION: Given the feasibility of rapid online deployment, low cost, and low risk of adverse events, this eHealth intervention for HRQOL may be useful for patients with chronic pain during the COVID-19 pandemic.Item Gender Differences in Chronic Low Back Pain Perception and Chosen Treatment Modalities(2019-03-05) Licciardone, John C.; Hammack, LillyBackground: Differences in perceptions and reported levels of pain intensity between men and women are poorly understood. Current evidence indicates an increased prevalence of chronic pain syndromes in women. However, relationships among gender, reported pain and related clinical outcomes, and pain treatment modalities have not been adequately studied. Purpose: The purpose of this research was to examine differences between men and women in pain intensity and its clinical impact, including differences in pain treatment modalities according to gender. Hypotheses: Women are more likely to report higher levels of pain intensity than men, and thereby also experience greater back-related disability and poorer quality of life. Women are more likely to use non-pharmacological approaches to manage pain in addition to, or in place of, opioids and nonsteroidal anti-inflammatory agents (NSAIDs). Methods: 452 patients aged 21 to 79 years with chronic low back pain were selected from the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION Pain Research Registry). Patient data at registry enrollment included sociodemographic and clinical characteristics, including pharmacological and non-pharmacological treatments used. Clinical status measures included a numerical rating scale for pain intensity (NRS), the Roland-Morris Disability Questionnaire (RMDQ), and quality of life deficits on the SPADE cluster (sleep disturbance, pain interference with activities, anxiety, depression, and low energy/fatigue). Contingency table methods and t-tests were used for analysis. Results: No statistically significant differences between genders with respect to NRS, RMDQ, and SPADE scores (p= 0.75, 0.27, and 0.23, respectively). A statistically significant relationship was observed between females and NSAID usage (p=0.03). However, no significant relationships were observed between gender and use of opioids or other non-pharmacological pain treatment modalities. Conclusions: Women were not more likely to report higher levels of pain, nor to report higher levels of pain-related disability or quality of life deficits. Women were more likely than men to use NSAIDs for their low back pain, but were not more likely to use opioid therapy or other non-pharmacological pain treatment modalities. Further research is needed to determine what other factors might play into women using NSAIDs more frequently.Item Genetic Influences on Opioid Use in Low Back Pain: OPRM1 rs1799971(2019-03-05) Phillips, Nicole R.; Licciardone, John C.; Romanowski, BenjaminPurpose: The OPRM1 rs1799971 single nucleotide polymorphism (SNP) has been studied for its influence on drug abuse and opioid use. Opioids have a questionable long-term risk-benefit profile in chronic low back pain, and a genetic predisposition to taking higher doses could place a patient at higher risk of complications related to opioid use. Studies have demonstrated higher dosages of self-administered opioids in an acute post-surgical setting in subjects with the rs1799971 AG polymorphism. We hypothesize that subjects with the rs1799971 AG polymorphism will use higher doses of opioids than subjects with other rs1799971 polymorphisms in the setting of chronic low back pain. Methods: This study was conducted using data from the PRECISION Pain Research Registry at UNTHSC. A saliva sample from each subject was obtained to determine genotypes, including the OPRM1 rs1799971 SNP. Additionally, numerical ratings of low back pain intensity and opioid use in morphine milligram equivalents (MMEs) were measured. The MMEs were computed in accord with CDC guidelines, which further indicate that opioid doses greater than 50 MMEs per day double the risk of opioid complications as compared with doses under 20 MMEs per day. We analyzed pain intensity, daily MMEs, and the proportion of subjects taking doses in excess of 50 MMEs per day based on allele status at SNP rs1799971. Results: Of 351 subjects with subacute or chronic low back pain, 279 were AA and 72 were AG. There was no significant difference in MMEs between rs1799971 AA subjects (x̅=5.90, SD=17.03) and AG subjects (x̅=9.53, SD=22.85). AG subjects had statistically significant lower pain intensity (x̅=5.2777 SD=1.74) compared to AA subjects (x̅=5.985, SD=1.9489 Mann-Whitney U=7897.5 p=0.005). rs1799971 AG subjects were more likely to be taking opioid doses greater than 50 MMEs per day than AA subjects (OR=3.40 95% CI:1.01-11.46 p=0.04). Five and 6 subjects with AG and AA, respectively, were taking doses greater than 50 MMEs per day (OR, 3.40; 95% CI, 1.01-11.46; Fishers exact p=0.11) Conclusion: There was no significant difference in mean MMEs among rs1799971 AG and AA subjects. However, AG subjects were marginally more likely than AA subjects to be taking doses greater than 50 MMEs per day. This SNP could potentially place rs1799971 AG patients at higher risk of complications relating to higher opioid doses, indicating a less favorable risk-benefit profile for long-term opioid therapy.