Browsing by Subject "Chronic pain"
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Item Open Access Association of chronic non-cancer pain status and buprenorphine treatment retention among individuals with opioid use disorder: Results from electronic health record data.(Drug and alcohol dependence reports, 2022-06) John, William S; Mannelli, Paolo; Hoyle, Rick H; Greenblatt, Lawrence; Wu, Li-TzyBackground
Although chronic non-cancer pain (CNCP) is common among individuals with opioid use disorder (OUD), its impact on buprenorphine treatment retention is unclear. The goal of this study was to use electronic health record (EHR) data to examine the association of CNCP status and 6-month buprenorphine retention among patients with OUD.Methods
We analyzed EHR data of patients with OUD who received buprenorphine treatment in an academic healthcare system between 2010 and 2020 (N = 676). We used Kaplan-Meier curves and Cox proportional hazards regression to estimate risk of buprenorphine treatment discontinuation (≥90 days between subsequent prescriptions). We used Poisson regression to estimate the association of CNCP and the number of buprenorphine prescriptions over 6 months.Results
Compared to those without CNCP, a higher proportion of patients with CNCP were of older age and had comorbid diagnoses for psychiatric and substance use disorders. There were no differences in the probability of buprenorphine treatment continuation over 6 months by CNCP status (p = 0.15). In the adjusted cox regression model, the presence of CNCP was not associated with time to buprenorphine treatment discontinuation (HR = 0.90, p = 0.28). CNCP status was associated with a higher number of prescriptions over 6 months (IRR = 1.20, p < 0.01).Conclusions
These findings suggest that the presence of CNCP alone cannot be reliably associated with buprenorphine retention in patients with OUD. Nonetheless, providers should be aware of the association between CNCP and greater psychiatric comorbidity among patients with OUD when developing treatment plans. Research on the influence of additional characteristics of CNCP on treatment retention is needed.Item Open Access Chronic Lyme disease.(Infect Dis Clin North Am, 2015-06) Lantos, Paul MChronic Lyme disease is a poorly defined diagnosis that is usually given to patients with prolonged, unexplained symptoms or with alternative medical diagnoses. Data do not support the proposition that chronic, treatment-refractory infection with Borrelia burgdorferi is responsible for the many conditions that get labeled as chronic Lyme disease. Prolonged symptoms after successful treatment of Lyme disease are uncommon, but in rare cases may be severe. Prolonged courses of antibiotics neither prevent nor ameliorate these symptoms and are associated with considerable harm.Item Open Access Chronic non-cancer pain among adults with substance use disorders: Prevalence, characteristics, and association with opioid overdose and healthcare utilization.(Drug and alcohol dependence, 2020-02-11) John, William S; Wu, Li-TzyBACKGROUND:Chronic non-cancer pain (CNCP) among patients with substance use disorder (SUD) poses a risk for worse treatment outcomes. Understanding the association of CNCP with SUD is important for informing the need and potential benefits of pain assessment/management among those with SUDs. METHODS:We analyzed electronic health record data from 2013 to 2018 among adults aged ≥18 years (N = 951,533; mean age: 48.4 years; 57.4 % female) in a large academic healthcare system. Adjusted logistic regression models were conducted to estimate the association of CNCP conditions with opioid overdose, emergency department utilization, and inpatient hospitalization stratified by different SUD diagnoses and by gender. RESULTS:Among the total sample, the prevalence of CNCP was 46.6 % and any SUD was 11.2 %. The majority of patients with a SUD had CNCP (opioid: 74.7 %; sedative: 72.3 %; cannabis: 64.3 %; alcohol: 58.7 %; tobacco: 59.5 %). The prevalence of CNCP was greater in females vs. males for most SUD diagnoses. The presence of CNCP was associated with more mental health disorders and chronic medical conditions among each SUD group. CNCP was associated with significantly decreased odds of overdose among those with opioid use disorder but increased odds of overdose and healthcare utilization among other SUDs. CNCP was positively associated with overdose in females, but not males, with alcohol or non-opioid drug use disorders. CONCLUSIONS:The direction and magnitude of the association between CNCP and negative health indicators differed as a function of SUD type and gender, respectively. Greater awareness of potential unmet pain treatment need may have implications for improving SUD outcomes.Item Open Access Framework for improving outcome prediction for acute to chronic low back pain transitions.(Pain reports, 2020-03-04) George, Steven Z; Lentz, Trevor A; Beneciuk, Jason M; Bhavsar, Nrupen A; Mundt, Jennifer M; Boissoneault, JeffClinical practice guidelines and the Federal Pain Research Strategy (United States) have recently highlighted research priorities to lessen the public health impact of low back pain (LBP). It may be necessary to improve existing predictive approaches to meet these research priorities for the transition from acute to chronic LBP. In this article, we first present a mapping review of previous studies investigating this transition and, from the characterization of the mapping review, present a predictive framework that accounts for limitations in the identified studies. Potential advantages of implementing this predictive framework are further considered. These advantages include (1) leveraging routinely collected health care data to improve prediction of the development of chronic LBP and (2) facilitating use of advanced analytical approaches that may improve prediction accuracy. Furthermore, successful implementation of this predictive framework in the electronic health record would allow for widespread testing of accuracy resulting in validated clinical decision aids for predicting chronic LBP development.Item Open Access Model Based Optimization of Spinal Cord Stimulation(2015) Zhang, TianheChronic pain is a distressing, prevalent, and expensive condition that is not well understood and difficult to treat. Spinal cord stimulation (SCS) has emerged as a viable means of managing chronic pain when conventional therapies are ineffective, but the efficacy of SCS has improved little since its inception. The mechanisms underlying SCS, in particular the neuronal responses to SCS, are not well understood, and prior efforts to optimize SCS have focused on electrode design and spatial selectivity without considering how the temporal aspects of SCS (stimulation frequency, pattern) may affect neuronal responses to stimulation. The lack of a biophysical basis in prior attempts to optimize therapy may have contributed to the plateau in the clinical efficacy of SCS over time. This dissertation combines computational modeling and in vivo electrophysiological approaches to investigate the effects of SCS on sensory neuron activity in the dorsal horn and uses the insights gained from these experiments to design novel temporal patterns for SCS that may be more effective than conventional therapy.
To study the mechanisms underlying SCS, we constructed a biophysically-based network model of the dorsal horn circuit consisting of interconnected dorsal horn interneurons and a wide dynamic range (WDR) projection neuron and representations of both local and surround receptive field inhibition. We validated the network model by reproducing cellular and network responses relevant to pain processing including wind-up, A-fiber mediated inhibition, and surround receptive field inhibition. To quantify experimentally the responses of spinal sensory projection neurons to SCS, we recorded the responses of antidromically identified sensory neurons in the lumbar spinal cord during 1-150 Hz SCS in both healthy rats and neuropathic rats following chronic constriction injury (CCI). In a subset of rats, we additionally assessed the impact of GABAergic inhibition on spinal neuron responses to SCS by conducting SCS experiments following the intrathecal administration of bicuculline, a GABAA receptor antagonist, and CGP 35348, a GABAB receptor antagonist. Finally, we used the computational model to design non-regular temporal patterns capable of inhibiting sensory neuron activity more effectively than conventional SCS and at lower equivalent stimulation frequencies than clinical standard 50 Hz SCS, and we experimentally validated model predictions of the improved efficacy of select patterns against conventional SCS.
Computational modeling revealed that the response of spinal sensory neurons to SCS depends on the SCS frequency; SCS frequencies of 30-100 Hz maximally inhibited the model WDR neuron consistent with clinical reports, while frequencies under 30 Hz and over 100 Hz excited the model WDR neuron. SCS-mediated inhibition was also dependent on GABAergic inhibition in the spinal cord: reducing the influence GABAergic interneurons by weakening their inputs or their connections to the model WDR neuron reduced the range of optimal SCS frequencies and changed the frequency at which SCS had a maximal effect. Experimentally, we observed that the relationship between SCS frequency and projection neuron activity predicted by the Gate Control circuit described a subset of observed SCS-frequency dependent responses but was insufficient to account for the heterogeneous responses measured experimentally. In addition, intrathecal administration of bicuculline, a GABAA receptor antagonist, increased spontaneous and evoked activity in projection neurons, enhanced excitatory responses to SCS, and reduced inhibitory responses to SCS, consistent with model predictions. Finally, computational modeling of dual frequency SCS, implemented by delivering two distinct frequencies simultaneously to distinct fiber populations, revealed frequency pairs that were more effective at inhibiting sensory neuron activity than equivalent conventional SCS and at lower average frequencies than clinically employed 50 Hz SCS. Experimental assessments of the effect of dual frequency SCS on spinal sensory neurons confirmed model predictions of greater efficacy at lower equivalent stimulation frequencies and suggest the use of non-regular temporal patterns as a novel approach to optimizing SCS. The outcomes of this dissertation are an improved understanding of the mechanisms underlying SCS, computational and experimental tools with which to continue the development and improvement of SCS. The insights and knowledge gained from the work described in this dissertation may result in translational applications that significantly improve the therapeutic outcomes of SCS and the quality of life of individuals affected by chronic pain.
Item Open Access Non-Pharmacological Approaches for Pain Management in Sickle Cell Disease: Development of a Mindfulness-Based Intervention(2016) Williams, HantsBackground: Sickle Cell Disease (SCD) is a genetic hematological disorder that affects more than 7 million people globally (NHLBI, 2009). It is estimated that 50% of adults with SCD experience pain on most days, with 1/3 experiencing chronic pain daily (Smith et al., 2008). Persons with SCD also experience higher levels of pain catastrophizing (feelings of helplessness, pain rumination and magnification) than other chronic pain conditions, which is associated with increases in pain intensity, pain behavior, analgesic consumption, frequency and duration of hospital visits, and with reduced daily activities (Sullivan, Bishop, & Pivik, 1995; Keefe et al., 2000; Gil et al., 1992 & 1993). Therefore effective interventions are needed that can successfully be used manage pain and pain-related outcomes (e.g., pain catastrophizing) in persons with SCD. A review of the literature demonstrated limited information regarding the feasibility and efficacy of non-pharmacological approaches for pain in persons with SCD, finding an average effect size of .33 on pain reduction across measurable non-pharmacological studies. Second, a prospective study on persons with SCD that received care for a vaso-occlusive crisis (VOC; N = 95) found: (1) high levels of patient reported depression (29%) and anxiety (34%), and (2) that unemployment was significantly associated with increased frequency of acute care encounters and hospital admissions per person. Research suggests that one promising category of non-pharmacological interventions for managing both physical and affective components of pain are Mindfulness-based Interventions (MBIs; Thompson et al., 2010; Cox et al., 2013). The primary goal of this dissertation was thus to develop and test the feasibility, acceptability, and efficacy of a telephonic MBI for pain catastrophizing in persons with SCD and chronic pain.
Methods: First, a telephonic MBI was developed through an informal process that involved iterative feedback from patients, clinical experts in SCD and pain management, social workers, psychologists, and mindfulness clinicians. Through this process, relevant topics and skills were selected to adapt in each MBI session. Second, a pilot randomized controlled trial was conducted to test the feasibility, acceptability, and efficacy of the telephonic MBI for pain catastrophizing in persons with SCD and chronic pain. Acceptability and feasibility were determined by assessment of recruitment, attrition, dropout, and refusal rates (including refusal reasons), along with semi-structured interviews with nine randomly selected patients at the end of study. Participants completed assessments at baseline, Week 1, 3, and 6 to assess efficacy of the intervention on decreasing pain catastrophizing and other pain-related outcomes.
Results: A telephonic MBI is feasible and acceptable for persons with SCD and chronic pain. Seventy-eight patients with SCD and chronic pain were approached, and 76% (N = 60) were enrolled and randomized. The MBI attendance rate, approximately 57% of participants completing at least four mindfulness sessions, was deemed acceptable, and participants that received the telephonic MBI described it as acceptable, easy to access, and consume in post-intervention interviews. The amount of missing data was undesirable (MBI condition, 40%; control condition, 25%), but fell within the range of expected missing outcome data for a RCT with multiple follow-up assessments. Efficacy of the MBI on pain catastrophizing could not be determined due to small sample size and degree of missing data, but trajectory analyses conducted for the MBI condition only trended in the right direction and pain catastrophizing approached statistically significance.
Conclusion: Overall results showed that at telephonic group-based MBI is acceptable and feasible for persons with SCD and chronic pain. Though the study was not able to determine treatment efficacy nor powered to detect a statistically significant difference between conditions, participants (1) described the intervention as acceptable, and (2) the observed effect sizes for the MBI condition demonstrated large effects of the MBI on pain catastrophizing, mental health, and physical health. Replication of this MBI study with a larger sample size, active control group, and additional assessments at the end of each week (e.g., Week 1 through Week 6) is needed to determine treatment efficacy. Many lessons were learned that will guide the development of future studies including which MBI strategies were most helpful, methods to encourage continued participation, and how to improve data capture.
Item Open Access Practice Patterns and Influential Factors of Nurse Practitioners Managing Chronic Pain(2021) Nikpour, JacquelineChronic pain impacts 100 million adult Americans in their lifetime, comprises the third-highest category of all health spending, and is responsible for up to 20% of primary care visits. Chronic pain treatment guidelines: recommend a biopsychosocial, multimodal management approach that addresses the physical and mental aspects of chronic pain. Nurse practitioners (NPs) have a unique role to play in chronic pain, due to their biopsychosocial training in chronic disease management in primary care that aligns well with this recommended approach. However, little is known about how NPs manage chronic pain or factors that influence those patterns. These gaps have implications on NP regulation and workforce development, as well as primary care transformation and clinical practice. Therefore, the purpose of this dissertation is to understand primary care NPs’ opioid and non-opioid prescribing patterns and the patient, provider, and system-level factors that influence those patterns.This dissertation includes a scoping review in Chapter 2 that demonstrates the negative impact of NP regulatory restrictions on patient access to chronic pain care, as well as treatment for OUD. Chapter 3 features a systematic review that examines primary care chronic pain prescribing patterns among physicians, NPs, and physician assistants (PA). This chapter highlights the lack of literature on NP and PA prescribing patterns specific to primary care, as well as the lack of prescribing pattern literature on non-opioid and non-pharmacologic modalities, despite the recommendations of these therapies in multiple national chronic pain guidelines. Chapter 4 presents the findings of a 31-item survey, developed by the authors, of 128 NPs from across the U.S. This survey examined the challenges and experiences of NPs who manage chronic pain and analyzed the impact of those experiences on the frequency with which NPs prescribe various pharmacologic and non-pharmacologic pain therapies. Findings indicate that NPs strongly identified with a variety of chronic pain management challenges, including patient access and insurance coverage of non-pharmacologic care, regulatory restrictions, and concerns of misuse. Additionally, NP-level factors such as setting of practice and education level significantly impacted NPs’ prescribing patterns and their perception of difficulty in managing chronic pain. Finally, Chapter 5 utilized a national VA dataset, including 39,936 12-month summary records between patients and their primary care providers, to compare opioid and non-opioid prescribing patterns of physicians, NPs, and PAs. After adjusting for patient factors, physicians had the highest odds of prescribing opioids and non-opioids compared to NPs and PAs. However, very small effect sizes may indicate that these differences do not hold significant clinical meaning. Patient factors, such as race/ethnicity, gender, age, level of education, number of comorbidities, number of chronic pain diagnoses, and self-reported health and mental health statuses, influenced prescription of opioid and non-opioid medications after adjusting for all other variables. Chronic pain is an exemplar of necessary primary care transformation priorities, including primary and behavioral health integration, value-based payment and delivery, team-based and well-coordinated care, and promotion accessible, equitable care. NPs are well-suited to address the complex needs of chronic pain patients. The findings of this dissertation indicate that NPs are slightly less likely than physicians to prescribe opioids and non-opioids; however, patient characteristics may increase the odds of a medication prescription more so than provider type. Furthermore, these findings identify patient, provider, and system-level challenges that NPs experience while managing chronic pain. The findings of this dissertation may contribute to important advancements in policy, practice, education, and research.
Item Open Access Spatiotemporal Approaches to Increase the Efficacy of Spinal Cord Stimulation(2022) Gilbert, JohnSpinal cord stimulation (SCS) is a surgically implanted therapy for chronic pain that delivers electrical stimulation to the spinal cord. Despite significant technological and clinical improvements, the therapeutic success of SCS has plateaued (North et al., 1993; Taylor et al., 2014), in part due to incomplete understanding of how changing stimulation parameters (i.e. amplitude, pulse duration, and timing) affect the neuronal circuitry that modulates pain perception. The work in this dissertation uses computational modeling and in vivo neural recordings to understand how dorsal horn circuitry changes in response to neuropathic pain and predict optimal stimulation parameters for SCS. Computational models are important tools for studying and predicting neural circuit responses and the first part of this dissertation concerns the development of novel computational models. The models are subsequently used to predict responses to neuropathic pain, and the models quantified distinct shifts in responses observed in experimental recordings, demonstrating their validity as a tool for understanding mechanisms of action of SCS. Multiple single unit recordings in the dorsal horn replicated the predictions made using the computational models and predicted that correlations between neurons could be used as a biomarker of neuropathic pain and stimulation efficacy. Model-based design uncovered multifrequency stimulation parameters and temporal patterns of stimulation that optimized neural responses and present promising avenues for improving clinical efficacy. We also used the computational model to predict the mechanism of action of a novel modality of SCS and validated our predicted mechanism of action through experimental recordings. Overall, this thesis work improved our understanding of dorsal horn circuits and the mechanisms of action underlying multiple modalities of SCS, developed new strategies for optimizing stimulation parameters, and demonstrated the effectiveness of optimized stimulation parameters in preclinical models.