Pain Management In Sickle Cell Disease Research Articles

Sickle Cell Disease Associated Changes in the Gut Microbiome Contribute to Persistent Pain

Many patients with sickle cell disease (SCD) suffer from chronic pain, the underlying causes of which are unclear. Recent 16s ribosomal RNA sequencing studies revealed differences in the number and types of bacteria in the gastrointestinal tract of patients and mouse models of SCD relative to controls, but it is unclear if or how these changes contribute to symptomology. In these experiments, we used transgenic SCD mice to determine the extent to which disease related gut dysbiosis contributes to persistent pain. Reflexive pain behaviors were first measured in SCD mice following longitudinal probiotic or antibiotic treatment. Vehicle-treated SCD mice displayed significant mechanical allodynia relative to vehicle-treated wildtype mice, and antibiotic treatment further exacerbated mechanical allodynia in both genotypes. In contrast, probiotic treatment completely reversed persistent touch hypersensitivity in SCD mice. Persistent touch pain was also transiently reversed in SCD mice following fecal material transplant from healthy mice. In complementary experiments, wildtype recipient mice developed cold and touch hypersensitivity that persisted for several weeks after fecal material transplant from SCD donors. Using whole-cell patch clamp recordings, we further determined that these behavioral observations were accompanied by altered intrinsic plasticity in a select class of nodose ganglia sensory neurons, the peripheral terminals of which are well positioned to detect sensory information in the gut. Nodose ganglia neurons isolated from animals that received sickle cell fecal material transplants were hyperexcitable relative to those isolated from animals that received control fecal material transplants. These data are the first to suggest that disease-related gut dysbiosis induces pain through changes in vagal nerve activity. Ongoing studies are examining specific bacterial populations and/or metabolites responsible for these functional changes in order to develop novel therapeutics for chronic SCD pain management. Grant support from National Institutes of Health grants K99HL155791 and R01NS070711.

Moving Toward a Multimodal Analgesic Regimen for Acute Sickle Cell Pain with Non-Opioid Analgesic Adjuncts: A Narrative Review.

Purpose of ReviewSickle cell disease (SCD) is an inherited hemoglobinopathy with potential life-threatening complications that affect millions of people worldwide. Severe and disabling acute pain, referred to as a vaso-occlusive crisis (VOC), is a fundamental symptom of the disease and the primary driver for acute care visits and hospitalizations. Despite the publication of guidelines for VOC management over the past decade, management of VOCs remains unsatisfactory for patients and providers.Recent FindingsAcute SCD pain includes pain secondary to VOCs and other forms of acute pain. Distinguishing VOC from non-VOC pain may be challenging for both patients and clinicians. Further, although opioids have been the gold-standard for VOC pain management for decades, the current highest standard of care for all acute pain is a multimodal approach that is less dependent on opioids, and, instead incorporates analgesics and adjuvants from different mechanistic pathways. In this narrative review, we focus on a multimodal pharmacologic approach for acute SCD pain management and explore the evidence for existing non-opioid pharmacological adjuncts. Moreover, we present an explanatory model of pain, which is not only novel in its application to SCD pain but also captures the multidimensional nature of the SCD pain experience and supports the need for such a multimodal approach. This model also highlights opportunities for new investigative and therapeutic targets – both pharmacological and non-pharmacological.SummaryMultimodal pain regimens that are less dependent on opioids are urgently needed to improve acute pain outcomes for individuals with SCD. The proposed explanatory model for SCD pain offers novel opportunities to improve acute pain management for SCD patients.

Impact of a Standardized Emergency Department Pain Protocol for Children with Sickle Cell Disease

Background/Objective: Sickle cell disease (SCD) is a common heritable red blood cell disorder that transcends the lifespan. Abnormal sickle-shaped erythrocytes interfere with blood flow in small vessels resulting in vaso-occlusion. This vaso-occlusion leads to tissue ischemia and inflammation which causes severe pain and is commonly referred to as a vaso-occlusive crisis (VOC). VOC is the most common complication seen in SCD and accounts for the majority of Emergency Department (ED) visits and hospitalizations. The primary objective of this study was to evaluate if pain management of SCD in pediatric patients at our institution was in accordance with national and institutional pain management guidelines before and after implementation of a standardized pain management algorithm.
 Methods: We retrospectively analyzed electronic medical record (EMR) data at Riley Hospital for Children between June 2015-May 2018, as well as from January 2019-December 2019 from for all pediatric patients (0-21 years old) who presented to the Riley ED with a confirmed diagnosis of SCD and uncomplicated VOC. These timeframes represented pre and post implementation of a standardized pain management algorithm, which has been described separately. The data collected included time to first dose of analgesia, type and dose of analgesia, change in pain score, length of stay in the ED, and disposition (discharge or admission). Univariate analyses were used to compare data between encounters.
 Results: Prior to implementation, 186 patients were seen for a total of 504 encounters, the majority of whom were male (59%, p<0.001) and had Hb SS disease (67%, p<0.001). The mean length of an ER visit was approximately 5 hours (+/-113 minutes). The median pain score at presentation was 9 (0-10 scale), with an average of 23 minutes from check in to first documented pain score. However, 19% of patients had no initial pain score documented, which occurred more often if the patient’s initial analgesic was given orally (p<0.001). The mean time from ED check in to first dose of analgesia (PO, IV, IN) was 76 minutes. The mean time between pain scores and medication administration increased between subsequent doses. 70% of these encounters resulted in hospitalization, with an average LOS of 4.1 days. Analysis of data following implementation of a standardized pain management algorithm is ongoing.
 Conclusion: Acute pain episodes are the leading cause of ED visits and hospitalizations for those with SCD. Thus, to properly meet the needs of patients with SCD and improve their outcomes, there needs to be collaborative, standardized and SCD- specific clinical guidelines for ED providers to utilize. Pre-implementation of a standardized acute pain management algorithm, our institution was not meeting national guidelines for administration of analgesia and assessment of pain. Post-implementation results are currently under analysis.
 Impact and Implications: Patients with SCD experience longer wait times in the ED and significant bias and mistrust regarding pain concerns. Standardized clinical guidelines have the potential to improve care and decrease variation in care delivery. The results from our study can inform institutional and national policy makers on gaps that exist in pediatric SCD, so that research funding can be appropriately allocated.

The comfort ability program for adolescents with sickle cell pain: Evaluating feasibility and acceptability of an inpatient group-based clinical implementation.

Integration of nonpharmacological therapies, such as cognitive and behavioral pain management strategies, is recommended to support comprehensive disease and pain management among children and adolescents with sickle cell disease (SCD). The Comfort Ability Program for Sickle Cell Pain (CAP for SCP) introduces psychological and biobehavioral pain management strategies to children and adolescents with SCD. This study aimed to pilot the implementation of the CAP for SCP in a group setting to children and adolescents hospitalized for SCD pain examining feasibility, acceptability, and preliminary effectiveness on improving pain knowledge and coping efficacy. Adaptation of CAP for SCP into a three-session group format was guided by four phases of the Dynamic Adaptation Process model: Exploration, Preparation, Implementation, and Sustainment. Youth with SCD (n=57) hospitalized for pain participated in at least one session and completed self-report of knowledge of pain management skills, pain coping efficacy, and treatment acceptance. Completion rates of sessions and qualitative feedback were gathered to evaluate feasibility and acceptability. Feasibility of conducting inpatient group sessions was suboptimal; however, patients and medical providers reported moderate to high levels of treatment acceptance. Patients also reported significant improvements in knowledge of pain management skills following session 1. CAP for SCP is a patient-centered first-line psychoeducational intervention that can be integrated into clinical practice settings to introduce youth to cognitive and behavioral pain management strategies to support SCD pain management.

Parental Psychosocial Distress in Pediatric Sickle Cell Disease and Chronic Pain.

Pediatric sickle cell disease (SCD) management can result in considerable caregiver distress. Parents of youth with chronic SCD pain may face the additional challenge of managing children's chronic pain and chronic illness. This study examined associations between parent psychological distress and child functioning and the moderating role of chronic pain among youth with SCD. Youth presenting to pediatric outpatient comprehensive SCD clinics and their primary caregivers completed a battery of questionnaires. Parents reported on parenting stress, parent mental and physical health, and family functioning. Children completed measures of pain characteristics, depressive symptoms, catastrophic thinking, functional disability, and quality of life. Patients (N = 73, Mage = 14.2 years, 57% female) and their caregivers (Mage = 41.1 years, 88% mothers, 88% Black) participated. Worse parent functioning was associated with worse child pain, functioning, quality of life, and depressive symptoms. Beyond the effects of SCD, chronic SCD pain magnified the negative associations between parenting stress frequency and child quality of life, parent physical health and child quality of life, and parent depressive symptoms and child depressive symptoms. Chronic pain may exacerbate the relations between parent and child functioning beyond the effects of SCD alone. The management of both SCD and chronic pain may present additional challenges for parents that limit their psychosocial functioning. Family-focused interventions to support parents and youth with chronic SCD pain are warranted to optimize health outcomes.

Considerations for Cannabis Use to Treat Pain in Sickle Cell Disease.

Pain in Sickle Cell Disease (SCD) is a major comorbidity and unique with acute pain due to recurrent and episodic vaso-occlusive crises as well as chronic pain, which can span an individual’s entire life. Opioids are the mainstay treatment for pain in SCD. Due to recent health crises raised by adverse effects including deaths from opioid use, pain management in SCD is adversely affected. Cannabis and its products are most widely used for pain in multiple conditions and also by patients with SCD on their own. With the availability of “Medical Cannabis” and approval to use cannabis as medicine across majority of States in the United States as well as over-the-counter preparations, cannabis products are being used increasingly for SCD. The reliability of many of these products remains questionable, which poses a major health risk to the vulnerable individuals seeking pain relief. Therefore, this review provides up to date insights into available categories of cannabis-based treatment strategies, their mechanism of action and pre-clinical and clinical outcomes in SCD. It provides evidence for the benefits and risks of cannabis use in SCD and cautions about the unreliable and unvalidated products that may be adulterated with life-threatening non-cannabis compounds.

Barriers and Resident Attitudes Surrounding Care of Patients with Sickle Cell Disease

Introduction Patients with sickle cell disease (SCD) commonly experience negative attitudes from health care providers, leading to significant barriers to care and management of pain (Haywood 2009). Incidence of SCD is high on the South Side of Chicago and the University of Chicago Medical Center (UCMC) is among the primary systems in the area caring for these patients. Based on the results of a small pilot study conducted at UCMC in 2019, providers can hold biased beliefs that lead to inadequate delivery of analgesia (Nelson 2019). Because internal medicine (IM) and emergency medicine (EM) residents are often at the frontline of caring for patients with SCD, we sought to explore attitudes and beliefs amongst IM and EM residents at our institution in order to address biases with future interventions. Methods We conducted anonymous surveys using validated questions (Haywood 2011) for UCMC IM and EM residents. The surveys were administered in paper form during conferences in July 2019 to IM and EM residents and January 2020 to IM residents. The surveys, which included questions that assess barriers to care of patients with SCD and attitudes amongst providers, utilize the 4-point Likert scale in which higher scores correspond to stronger agreement with the statement. Participants were asked to provide non-identifiable demographic information including sex, ethnicity, age range, training year (PGY-1- PGY-3), and residency program. Responses were pooled and analyzed to assess for differences in attitudes by residency program (EM vs. IM), sex, age, year of training, and ethnicity. Statistical analysis was performed using the student's t-tests to identify differences in average responses and ANOVA to examine for confounding variables. Results Sixty-six residents were included in this study: 44 IM and 22 EM. Residents were 41% female and 58% male, ranging in age from 20-39 (median 25-29 yrs). Forty-eight percent of residents were White, 20% Asian/Asian American, 11% Black/African American, 9% Latinx, and 12% unidentified/other. Resident training level included 20% PGY-1 (13), 53% PGY-2 (35), and 29% PGY-3 (19). In terms of attitudes, 38% of IM and EM residents overall believed that patients with SCD over-report pain and are "drug-seeking" (N=66). IM residents (84% N=44) were more likely to consider patients to be frustrating to work with compared to EM residents (23% N=22, p<0.0001). While 83% of residents overall said patients with SCD are easy to empathize with, only 50% of IM residents (N= 44) believed they could be friends with SCD patients compared to 82% amongst EM residents (N=22, p=0.001) (Figure 1). When comparing these responses by year of training, attitudes generally became more negative with increased training, with advanced residents more likely to believe that SCD patients over-report pain (p=0.011), feel more frustrated caring for patients (p<0.001), consider themselves less likely to be friends with the patients (p=0.004), and feel less satisfied about going into medicine in general (p=0.012). No significant differences were observed when comparing resident ethnicity or age group. Considering barriers to SCD pain management, 100% of IM residents (N=23) believed opioid tolerance was a significant barrier, followed by 92% reporting opioid dependence, 83% side effects, 79% addiction, and 67% regulatory oversight. Conclusion This study highlights gaps in resident understanding of SCD and reveals biases held amongst IM and EM residents. Biases are augmented amongst IM residents and tend to become more exaggerated with increased level of training. The latter result may be confounded by burnout, which was not directly assessed in this study. The differences observed between IM and EM residents may be due to variation in education, workflow, or program diversity (although effect of ethnicity was not statistically significant). Resident-perceived barriers also seem to be focused on negative patient-centered factors (dependence, addiction, tolerance) rather than systemic limitations (availability, training, efficacy), likely reflecting negative resident attitudes as seen in previous studies (Haywood 2009). These data demonstrate an unmet need, underlining the importance of developing education, training, and potentially wellness programs to confront biases, build positive attitudes toward patients with SCD and ultimately remove barriers to care of patients with SCD. Disclosures No relevant conflicts of interest to declare.

Marijuana use and health behaviors in a US clinic sample of patients with sickle cell disease.

IntroductionAs marijuana use becomes more common, it is essential clinicians understand the relationship between marijuana use and health behaviors.MethodsUsing a retrospective cohort of adolescents and adults with sickle cell disease (SCD) stratified into a young (<25 years) and older cohort (> = 25 years), we conducted multiple linear regression examining relationship of marijuana use (independent variable) on each dependent variable (SCD self-management score and pain management).ResultsAmong young cohort, 16.9% used marijuana compared to 21.8% of older cohort. The younger cohort reporting marijuana use had lower mean self-care scores (β = -2.74;p = 0.009) and were more likely to have admissions to the hospital for pain (β = 0.87;p = 0.047) compared to non-users. In contrast, the older cohort reporting marijuana use had more days treating pain at home (β = 0.44;p = 0.035).ConclusionsOnly a minority of patients with SCD reported lifetime marijuana use. Among those reporting marijuana use, there were different associations with self-care and health-related behaviors by age. The older cohort who endorsed marijuana use reported more days of treating pain at home, although this did not translate into increased acute care visits for pain crisis. Among youth, endorsing marijuana use was associated with worse SCD self-care.

A Pilot Study of a Functional Pain Assessment for Adult Patients Admitted with Sickle Cell Pain Crisis

Introduction Acute vaso-occlusive pain crises are the most common complications of sickle cell disease (SCD). Pain is a subjective sensation and is often difficult to describe and for practitioners to understand. The complexity and multidimensional nature of pain requires additional evaluation beyond pain intensity. Pain assessment is also influenced by implicit and explicit biases related to race and ethnicity which can negatively influence treatment (Wandner et al J Pain 2012). In this pilot quality improvement study, we studied resident perceptions to a functional assessment tool in adult patients hospitalized with sickle cell vaso-occlusive crises. We used the Youth Acute Pain Functional Ability Questionnaire (YAPFAQ), a validated questionnaire of physical function in youth experiencing acute pain (Zempsky et al J Pain 2014) (Figure 1). Resident responses to using the YAPFAQ were measured as an initial step to implementation of functional pain assessment in hospitalized adults with SCD pain crises. Methods We piloted this study on internal medicine residents. First, residents completed the Resident Acute SCD Pain Assessment Survey regarding their current management of acute pain in SCD (Figure 2). This was done to determine their baseline demographic information, methods of pain assessment, satisfaction with the numerical pain score system, and to understand barriers in assessing acute pain. This survey included a combination of multiple choice, free response, and binary response options. The residents then trialed the YAPFAQ with a patient admitted with vaso-occlusive pain crisis then the residents completed The Post YAPFAQ Evaluation Survey in response to this assessment tool (Figure 3). This survey included a combination of multiple choice, free response, and binary response options. The goal of this survey was to assess resident satisfaction with YAPFAQ, perceived patient receptiveness to YAPFAQ, and feasibility of using this tool during daily assessments. Patients were not surveyed during this pilot study. We performed descriptive statistics to describe the survey results. Results Sixteen residents completed the Acute SCD Pain Management survey prior to using the YAPFAQ. Sixty-nine percent of residents reported dissatisfaction with using numerical pain scores. Reported barriers to assessing pain included: subjectivity of pain scores, concern for malingering, and the ceiling effect of the numeric scale. Seven residents completed the post YAPFAQ evaluation survey. A majority of residents (86%) were extremely satisfied or satisfied with using the YAPFAQ. Fifty seven percent of residents felt that patients were extremely receptive or receptive to using this tool. The majority of residents (85%) felt that the YAPFAQ improved their understanding of patients' pain. All YAPFAQs were completed with patients in 10 minutes or less. Most residents (57%) reported that the tool would be feasible for implementation on rounds. Conclusions Similar to previous studies, our residents felt that numerical pain score systems inadequately describe pain. Residents had generally positive responses to the YAPFAQ. One resident stated that the questionnaire was "structured and easy to compare day to day." Functional pain assessment allows providers to better understand how pain limits daily activities and can provide useful functional targets for safe hospital discharge. Future directions of this project include performing a larger study of patients hospitalized with vaso-occlusive pain crises to validate the YAPFAQ in adult patients, survey patients regarding experiences with the YAPFAQ, and to create tailored pain management plans based on functional pain assessments. Disclosures No relevant conflicts of interest to declare.

Benefits of Aquatic Therapy in Pediatric Patients with Sickle Cell Disease

Introduction: Individuals with sickle cell disease (SCD) experience both acute vaso-occlusive pain (VOC) and chronic pain, both primarily treated with opioids. However, opioids only address the sensory dimension of pain and repeated use of opioids can cause short and long-term side effects such as respiratory system depression, increased risk of cardiovascular events, and hyperalgesia. Non-pharmacologic approaches to the management of acute and chronic SCD pain, such as cognitive behavioral therapy, biofeedback, acupuncture, hypnosis, and megavitamins, have shown positive effects for pain management and may reduce opioid use. Among non-pharmacologic pain management methods, aquatic therapy has been underutilized and understudied in patients with SCD, despite showing benefits for pain management and quality of life in adults with musculoskeletal conditions. At Vidant Medical Center, aquatic therapy has been introduced for patients with SCD in 2015 and has been increasingly used since then. To describe the use of aquatic therapy and outcomes in pediatric patients with SCD, we retrospectively evaluated the use of this therapy at Vidant Medical Center among children hospitalized for acute VOC pain. Methods: The study was approved by the Institutional Review Board at East Carolina University. Children with SCD between 7-18 years of age at the time of admission for acute VOC pain between the years 2015-2018 were included in the analysis. During the review period, orders for aquatic therapy were placed at the provider's discretion. Our primary outcome was utilization of aquatic therapy during a given hospitalization, determined by retrospective query of the electronic medical record (EMR). Secondary outcomes include length of stay and time to readmission for VOC. Covariates were assessed at the time of the index admission included age, sex, and insurance coverage. Mixed-effects logistic or Poisson regression models were fitted to account for multiple hospitalizations per patient. Results: The analysis included 316 hospitalizations of 87 patients (48% female; median age at the earliest hospitalization, 11 years). The median duration of hospital admissions was 4 days (interquartile range [IQR]: 3, 7). Aquatic therapy was used in 38% of admissions, with a trend of increasing use during the study period (Figure 1). On multivariable logistic regression analysis of aquatic use during a given admission, characteristics associated with greater likelihood of aquatic therapy use included older age and more recent year of admission. Aquatic therapy was associated with 69% longer hospital stays, although this may be related to availability of aquatic therapy services. Among 52 patients with multiple admissions, use of aquatic therapy during a given admission was associated with 26% more days between hospitalizations (incidence rate ratio = 1.26; 95% CI: 1.21, 1.31; p=&lt;0.001). Conclusion: Research into the use of non-pharmacologic pain management strategies for sickle cell disease has recently increased in order to better address the multidimensional aspects of pain. Of these management strategies, aquatic therapy has been very underutilized and under researched. Analysis of the utilization of aquatic therapy in our institution showed improved use over the last 3 years as well as increased duration between hospitalizations after the use of aquatic therapy. These positive results point towards the need for more research into other outcome measures derived from the use of aquatic therapy in pain management of pediatric SCD patients. Figure 1 Disclosures No relevant conflicts of interest to declare.

Continuous Pain Assessment Using Ensemble Feature Selection from Wearable Sensor Data.

Sickle cell disease (SCD) is a red blood cell disorder complicated by lifelong issues with pain. Management of SCD related pain is particularly challenging due to its subjective nature. Hence, the development of an objective automatic pain assessment method is critical to pain management in SCD. In this work, we developed a continuous pain assessment model using physiological and body movement sensor signals collected from a wearable wrist-worn device. Specifically, we implemented ensemble feature selection methods to select robust and stable features extracted from wearable data for better understanding of pain. Our experiments showed that the stability of feature selection methods could be substantially increased by using the ensemble approach. Since different ensemble feature selection methods prefer varying feature subsets for pain estimation, we further utilized stacked generalization to maximize the information usage contained in the selected features from different methods. Using this approach, our best performing model obtained the root-mean-square error of 1.526 and the Pearson correlation of 0.618 for continuous pain assessment. This indicates that subjective pain scores can be estimated using objective wearable sensor data with high precision.

Keys to Recruiting and Retaining Seriously Ill African Americans With Sickle Cell Disease in Longitudinal Studies: Respectful Engagement and Persistence.

Sickle cell disease (SCD) is a serious illness with disabling acute and chronic pain that needs better therapies, but insufficient patient participation in research is a major impediment to advancing SCD pain management. The purpose of this article is to discuss the challenges of conducting an SCD study and approaches to successfully overcoming those challenges. In a repeated-measures, longitudinal study designed to characterize SCD pain phenotypes, we recruited 311 adults of African ancestry. Adults with SCD completed 4 study visits 6 months apart, and age- and gender-matched healthy controls completed 1 visit. We recruited and completed measures on 186 patients with SCD and 125 healthy controls. We retained 151 patients with SCD with data at 4 time points over 18 months and 125 healthy controls (1 time point) but encountered many challenges in recruitment and study visit completion. Enrollment delays often arose from patients' difficulty in taking time from their complicated lives and frequent pain episodes. Once scheduled, participants with SCD cancelled 49% of visits often because of pain; controls canceled 30% of their scheduled visits. To facilitate recruitment and retention, we implemented a number of strategies that were invaluable in our success. Patients' struggles with illness, chronic pain, and their life situations resulted in many challenges to recruitment and completion of study visits. Important to overcoming challenges was gaining the trust of patients with SCD and a participant-centered approach. Early identification of potential problems allowed strategies to be instituted proactively, leading to success.

Management of Sickle Cell Disease Pain among Adolescent and Pediatric Patients

Management of sickle cell pain in adolescent and pediatric patients is inadequate, and the employment of proper management guidelines and practices are highly variable among different regions and populations. APPT, the multidimensional adolescent pediatric pain tool, promotes optimal pain management and introduces best practical guidelines for pain management. The goal of this study is to assess pain and pain management among young patients diagnosed with sickle cell disease (SCD) by introducing the APPT as a tool for pain management, and analyze factors contributing to pain management. Information relevant to demographic data, SCD characteristics, APPT assessment, and satisfaction of patients regarding pain management were collected using a structured questionnaire. Results showed that SCD is highly associated with gender (p = 0.022), consanguinity (p = 0.012), and number of surgeries (p = 0.013). Most patients (58.9%) indicated the involvement of more than six body areas affected during pain crisis. Severe pain was described by more than half the patients (55.6%), while moderate pain was reported by 31.1%. Most patients described their pain by sensory, affective, and temporal words. The number of painful areas, pain intensity, and use of descriptive pain words was correlated and interpreted by age, BMI, school absence, and number of surgeries. Results of this study could provide guidance to healthcare providers to improve current practices for SCD pain management in order to improve health outcomes and patients’ satisfaction.

The Role of Cognitive Behavioral Therapy in Opioid Use Reduction in Pediatric Sickle Cell Disease: Protocol for a Systematic Review.

BackgroundSickle cell disease (SCD) is a genetic disorder of red blood cells that results in acute and chronic health problems, including painful syndromes. Opioid analgesia is the mainstay of moderate to severe pain management in SCD, although adjunctive psychosocial approaches such as cognitive behavioral therapy (CBT) are increasingly incorporated. CBT has been used in populations of various ages to address a wide range of issues, such as mood disorders and chronic pain. It is unclear if effective CBT reduces the use of opioids to manage pain in pediatric SCD.ObjectiveThe aim of this study is to evaluate the association between CBT and decreased opioid use in children with SCD.MethodsIn this systematic review protocol, we describe our approach to applying predetermined eligibility criteria to searches of PubMed (including Medline), Embase, Cochrane, Web of Science, and PsycINFO databases, as well as Google Scholar and grey literature. In particular, we will use keywords to search for English-language studies of individuals with SCD aged 21 years old and younger published before November 2018. Keywords will allow us to assess for the primary outcome—total use of opioid medications—and the secondary outcomes—pain intensity and emotional functioning—during pain management using a combined opioid and CBT approach, opioids alone, or CBT alone. The review team will use standardized abstraction forms to review articles at the title, abstract, and full-text levels. Finally, reviewers will assess the risk for bias, quality of evidence, and adequacy of data for quantitative versus qualitative synthesis. If meta-analysis is deemed inappropriate, a narrative review will be conducted.ResultsWe will report a summary of findings across studies that meet eligibility criteria to compare the extent to which adjunctive CBT is associated with decreased opioid use among children with SCD.ConclusionsThis systematic review will present the current state of the evidence on CBT and opioid use in pediatric SCD, which may inform clinical practice and health policy to support optimized pain management.International Registered Report Identifier (IRRID)PRR1-10.2196/13211

Gabapentin alleviates chronic spontaneous pain and acute hypoxia-related pain in a mouse model of sickle cell disease.

Pain is the main complication of sickle cell disease (SCD). Individuals with SCD experience acute pain episodes and chronic daily pain, both of which are managed with opioids. Opioids have deleterious side effects and use-associated stigma that make them less than ideal for SCD pain management. After recognizing the neuropathic qualities of SCD pain, clinically-approved therapies for neuropathic pain, including gabapentin, now present unique non-opioid based therapies for SCD pain management. These experiments explored the efficacy of gabapentin in relieving evoked and spontaneous chronic pain, and hypoxia/reoxygenation (H/R)-induced acute pain in mouse models of SCD. When administered following H/R, a single dose of gabapentin alleviated mechanical hypersensitivity in SCD mice by decreasing peripheral fibre activity. Gabapentin treatment also alleviated spontaneous ongoing pain in SCD mice. Longitudinal daily administration of gabapentin failed to alleviate H/R-induced pain or chronic evoked mechanical, cold or deep tissue hypersensitivity in SCD mice. Consistent with this observation, voltage-gated calcium channel (VGCC) α2 δ1 subunit expression was similar in sciatic nerve, dorsal root ganglia and lumbar spinal cord tissue from SCD and control mice. Based on these data, gabapentin may be an effective opioid alternative for the treatment of chronic spontaneous and acute H/R pain in SCD.

Assessment of Sickle Cell Disease Pain Management in the Whittington Hospital Emergency Department

Background and aimsSickle cell anaemia (SCA) is an autosomal recessive disorder caused by point mutation of the β-globin gene, resulting in abnormal forms of hemoglobin that cause increased red blood cell rigidity and hemolysis. It is one of the most common hereditary blood conditions, affecting over 14,000 adults in the UK (Dormandy el al, 2017).One of the manifestations of SCA is vaso-occlusive crises. These typically cause severe pain that may require emergency department (ED) attendance for pain management, typically with opioids. Pain relief should be given quickly and response to this assessed on a regular basis to ensure pain management is optimized. Those patients in whom pain relief is not well-controlled are at risk of further complications including acute chest syndrome.The UK National Institute of Clinical Excellence (NICE) published a quality standard in 2014 stating that patients presenting to hospital with an acute painful sickle cell episode should have a pain assessment, a clinical assessment and appropriate analgesia within 30 minutes of presentation (NICE, 2014).This study was performed to assess the Whittington Hospital's compliance to national recommendations and to establish which aspects of care in ED contributed to delays in management.MethodsIf a Whittington SCA patient attends ED, an automated email is generated that notifies the haematology team of the attendance. This system was used to identify acute sickle cell presentations to ED. Criteria for inclusion in the study was Whittington SCA patients that presented to ED with acute painful sickle cell crises between August 2017 to January 2018. Patients who received analgesia in the ambulance and patients with no documentation available were excluded. The time of presentation, analgesia prescription and administration for each attendance were noted from ED documentation.ResultsA total of 104 ED SCA attendances were included. 41% of patients presenting with an acute painful sickle cell crisis received analgesia during their first 30 minutes in ED. The average wait for analgesia was 47 minutes, with 75% of SCA patients receiving analgesia within 1 hour of arrival.The time taken to triage SCA patients was on average 8 minutes (range 0 to 29 minutes). Time from arrival to prescription of pain relief was much more variable with an average wait 40 minutes (range 10 minutes to 2 hours 22 minutes). Time from prescription to administration also varied, with 56% administered within 10 minutes of prescription and 87% within 30 minutesPatients who frequently attended Whittington ED (defined as 7 or more attendances within the 6 month period studied) had a shorter average wait for analgesia. Analgesia was given 36 minutes after arrival on average for frequent attenders, whereas patients presenting 6 or fewer times had an average wait of 53 minutes.ConclusionsWe are not currently meeting our audit standard for provision of analgesia in the emergency department, and performance appears to have worsened progressively since our earliest available date from 2012 (although methodological differences may have contributed to this). In 2015 49% of patients received analgesia within 30 minutes compared to 41% in 2017/18. Most of the delay appears to be due to the time taken for medication to be prescribed, although the time taken to triage the patient and administer the medication was also not insignificant and often amounted to greater than 30 minutes. It is unclear what is contributing to this delay, although it appears that performance is improved when the patient is a repeat attender and therefore known to the department. Educations sessions with the ED department and availability of a SCA specialist nurse may improve management of SCA painful crises in ED. DisclosuresShah:Novartis: Honoraria, Speakers Bureau; Sobi/Apotex: Honoraria; Celgene Corp: Other: Steering committee; Roche: Other: Advisory board meeting.

Painful Transitions—a Comparison of Acute Pain Management in Children, Adolescents and Young Adults with Sickle Cell Disease in Adjacent Pediatric and Adult Emergency Departments

Abstract Introduction: Qualitative research identifies delayed analgesia and under-dosing as common reasons for patient/caregiver dissatisfaction with the treatment of acute vaso-occlusive pain in sickle cell disease (SCD). Experts have identified quality measures for emergency department (ED) management of acute pain in SCD including early administration of IV analgesics (NHLBI 2014). Adolescent and young adult (AYA) patients are especially at risk for dissatisfaction, and qualitative studies identify the transition from pediatric (PED) to adult emergency department (AED) care as the most difficult site of transition. Information from empirical studies of SCD pain management in PEDs and AEDs is needed to facilitate overall improvements in care and facilitate transitions of care for AYA patients. The goal of this study was to examine differences in management of SCD pain between a PED and an AED. The primary outcome was time from triage to first opioid. Methods: We retrospectively reviewed patients with SCD and acute pain, age 3 - 27 years, seeking care from June 2015 to December 2016 in the AED and/or PED within our academic, tertiary care institution. Four visits per individual per ED were abstracted. Visits were excluded if no opioid was administered, for confounding sources of pain (e.g. post-operative), transfer from another ED or critical illness. Important encounter characteristics and outcomes were summarized by mean with standard deviation (SD) or median with interquartile range (IQR) for skewed data. We compared the difference between EDs for the primary outcome using a Cox proportional hazards model with a patient-level random effect. Results: Our initial electronic health record query yielded 353 visits by 66 patients to the PED and AED. Two patients accounted for 46% of visits (77 and 84 visits). After excluding visits by patients transferred from an outside facility (n=1), with confounding illness (n=6) or no opioid administered (n=3), we extracted data on up to 4 visits per ED per patient and analyzed 127 visits by 55 patients. Demographics, initial pain score, treatments and treatment timeline are summarized by ED (Table 1). The Kaplan-Meier plot (Figure 1) shows the proportion of patients receiving the first intravenous opioid dose, by ED, as a function of time from triage. At any given time, the probability of receiving the first opioid dose in the PED was approximately 3 times greater than in the AED (hazard ratio of 2.95 (95% CI 1.93, 4.50), p &lt; 0.001). Patients in the AED were more likely to receive hydromorphone than morphine and adjunctive NSAIDs were rarely given. More than an hour elapsed between the 1st and 2nd opioid doses in both EDs. Intravenous hydration with normal saline boluses was common in both EDs. An individualized prescribing and monitoring protocol, written by the patient's SCD provider (pain plan) was rarely available to ED providers. Conclusions: Optimal management of acute pain in patients with SCD is difficult, a challenge exacerbated by practice and cultural differences in pediatric versus adult settings. Considering the primary outcome, the PED administered IV analgesia more quickly than the AED, although neither site provided treatment consistently within 30 minutes from triage as per the NHLBI guidelines. Much of the delay in time to first opioid in the AED (Figure 1) is explained by longer rooming times. Our data are limited in that we cannot differentiate whether the delay is due to longer overall wait times or lower prioritization of patients. Nonetheless, this difference remains a known driver of patient dissatisfaction. Our results highlight multiple opportunities in both EDs to improve care including earlier administration and individualized dosing of opioids, reducing the time interval between subsequent doses, routine administration of NSAIDs, avoidance of fluid boluses in euvolemic patients and development of patient specific pain plans. Emergency providers could benefit from education and localized practice guidelines with written protocols and electronic alerts, targeted at quality improvement. The AED could also potentially benefit from focused effort to reduce time from triage to room. Subspecialty providers could assist the ED by routinely providing pain plans; this could help achieve more uniform care across individual encounters in both EDs, particularly in the few patients accounting for a large proportion of all encounters. Disclosures No relevant conflicts of interest to declare.

Clinical Characteristics and Health Care Utilization Patterns of Sickle Cell Disease Patients Using Marijuana

Background:Opioid analgesics have served as the cornerstone of acute and chronic pain management in patients with sickle cell disease (SCD) in the United States. Despite significant opioid use, hospitalization for painful crises comprises the majority of healthcare costs for patients with SCD. Moreover, greater use of opioids may correlate with poorer response to treatment of acute painful crises. Insufficient pain management, the rise of opioid use disorder and opioid-related fatal overdose have opened the door for new strategies of pain management for these patients. Medical cannabis represents a potential new strategy for the management of chronic SCD pain. There is a substantial body of literature describing the analgesic properties of cannabis, but little research has explored its role in the management of SCD-related pain. We sought to evaluate the prevalence of marijuana use in an urban SCD patient population and to identify demographic and clinical characteristics that may predict marijuana use in this cohort.Methods:Adult patients with SCD seen at an urban outpatient SCD center completed an intake form with questions regarding individual demographics, cumulative disease complications, current or prior marijuana use, ED utilization, frequency of pain, and opioid use. Data from 78 patients seen between October 2017 and June 2018 were available for analysis. Additional data including information regarding disease genotype and race were collected from the electronic medical record. Data were analyzed using Microsoft Excel and Chi-Square analysis.Results:Among the 78 patients, mean age of the population was 35.7 years (range 20-69), and 50% were male. Genotype was 69% HbSS/SB0 and 31% HbSC/SB+. Twenty-three patients (29%) reported ever using marijuana, and 15 (19%) endorsed current use; most patients (80%) reported smoking. Marijuana users were more likely than non-users to be male (67% v 46%), to have HbSS/SB0 (80% v 67%), to have avascular necrosis (AVN) (47% v 17%, p=.025), to report daily pain (40% v 13%, p=.013), and to be prescribed opioids (93% v 65%, p=.031). Frequent ED visits (at least monthly) were more common in marijuana users (33% v 6% p=.002) compared to non-users. Age, leg ulcers, priapism, and hydroxyurea use were not different in users versus non-users.Discussion:In this cohort of patients with SCD seeking outpatient care, 19% reported current marijuana use for the management of SCD-related symptoms. Most patients reported smoking marijuana, and only one patient reported ingestion of edible marijuana. These rates are similar to marijuana use in other populations with chronic pain. SCD marijuana users were similar in age but not in sex distribution, as men more commonly reported marijuana use than women in our population. Marijuana users were enriched for the HbSS genotype, reported more daily pain, had more frequent ED visits and were more likely to be diagnosed with AVN of bones. There was a strong association between marijuana use and self-reported opioid use for pain control. These preliminary data suggest that patients with more severe manifestations of SCD, namely daily pain, frequent ED visits, AVN of bones, and significant utilization of opioids, are more likely to be using marijuana as adjunctive therapy for their chronic pain.As of July 2018, 31 US states and the District of Columbia have legalized the use of medical cannabis, with chronic pain an indication in most states and opioid replacement an indication in some. The expansion of access to medical cannabis highlights the need for careful evaluation of the potential benefits and harms of medical cannabis in the SCD population. These benefits might include better control of daily pain, reduced visits to the ED, and possibly decreased utilization of opioids. As medical cannabis is becoming a more available therapy, carefully controlled prospective studies are needed to assess its efficacy in the management of debilitating symptoms of SCD. [Display omitted] DisclosuresStarrels:Opioid Post-Marketing Requirement Consortium: Other: Research and travel support from the Opioid Post-Marketing Requirement Consortium for a FDA-mandated observational study of the risks of opioid medications. Minniti:Novartis: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Other: Adjudicating Committee; Global Blood Therapeutics: Research Funding; Teutona: Membership on an entity's Board of Directors or advisory committees; Bayer: Research Funding.

Patient Satisfaction of Care in the Treatment of Vaso-Occlusive Crises: A Comparison of Emergency Department and Infusion Centers in the Escaped Study

IntroductionPatients with sickle cell disease (SCD) suffer from frequent vaso-occlusive crises (VOC), the leading cause of hospitalization and emergency department (ED) visits for these patients. Patients and healthcare providers often report dissatisfaction with the quality of SCD pain management in the ED. Satisfaction has been defined as whether a patient's expectations about a health encounter were met. Infusion centers (IC) are alternatives to ED care for patients with VOC. The aim of this study is to describe adult patients' satisfaction with care for the treatment of uncomplicated VOC in EDs and ICs.MethodsAs part of a prospective cohort study (the ESCAPED study) comparing outcomes between ED and IC care for uncomplicated VOC, we conducted a descriptive analysis of patient satisfaction from the first acute visit of adult patients (>18 years) who were recruited from 4 sites (Baltimore, Baton Rouge, Cleveland, Milwaukee) from April 2015 to December 2016. Demographic and clinical variables were collected via medical record review. Participants were provided with a survey about their satisfaction of care within 72 hours after their acute visit to the ED or IC. The survey tool included questions about overall satisfaction with quality of care and with pain treatment received, satisfaction with pain management, communication with clinicians including physicians and nurses, interpersonal aspects of care, clinician competence, involvement of family and friends, and access to care. Responses were scored on a 7-point Likert scale from very strongly agree to very strongly disagree, except for “access to care” items, which were binary and categorical. We dichotomized Likert scale responses by grouping positive responses (very strongly agree, strongly agree, and agree) as being satisfied, and negative responses (very strongly disagree, strongly disagree, disagree, and uncertain) as being dissatisfied. Descriptive statistics were computed using Mann-Whitney U test for continuous variables and chi-squared test for categorical variables. All hypothesis testings were 2-sided and p values were not adjusted for multiple comparisons.ResultsWe enrolled 483 patients in ESCAPED and followed them for 18 months. We excluded 115 patients who did not have VOC visits during their observation period. Of the 368 patients with visits, 212 patients (58%) responded to the survey after their first acute visit: 89 (42%) had received care at an ED and 123 (58%) received care at an IC. Patients who received care at an IC were older, more likely to be married or with a significant other, and less likely to live alone. More patients who had a history of kidney disease received care at an IC than in an ED. Patients with higher numbers of ED visits in the previous year were more likely to seek care in an ED and those with higher numbers of IC visits in the previous year were more likely to seek care at an IC.The majority of patients (55%) in the ED responded to the survey by phone whereas the majority of patients (54%) in the IC responded to the survey in-person. Overall, patients who received care in an IC were more satisfied with the quality of care (95% vs. 73%, p< 0.001) and with their pain treatment (93% vs. 66%, p< 0.001) than patients who received care in an ED. (Table) Adults who received care at an IC were more satisfied with the pain management, communication with clinicians, interpersonal aspects of care, and clinician competence than adults who received care at an ED. The majority of patients in both groups (59%) came for care unaccompanied; ED-treated patients were more likely than IC-treated patients to agree that a companion helped improve the quality of care they received.ConclusionsPatients who received care in an IC were more satisfied with their care and with the quality of their pain management than patients who received care from an ED. Increasing access to IC models of care can improve delivery of patient-centered care for VOC. [Display omitted] DisclosuresBrooks:PCORI: Research Funding. Wang:PCORI: Research Funding. Seufert:PCORI: Research Funding. Haywood:PCORI: Research Funding. Varadhan:PCORI: Research Funding. Saheed:PCORI: Research Funding. Segal:PCORI: Research Funding. Field:Incyte: Research Funding; Ironwood: Consultancy, Research Funding; Prolong: Research Funding. Frymark:PCORI: Research Funding. Little:Doris Duke Charitable Foundations: Research Funding; NHLBI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; PCORI: Research Funding. Griffin:PCORI: Research Funding. Arnold:PCORI: Research Funding. Shows:PCORI: Research Funding. Piehet:PCORI: Research Funding. Proudford:PCORI: Research Funding. Robertson:PCORI: Research Funding. Wallace:PCORI: Research Funding. Kincaid:PCORI: Research Funding. Green:PCORI: Research Funding. Burgess:PCORI: Research Funding. Lanzkron:Selexys: Research Funding; Pfizer: Consultancy, Research Funding; GBT: Consultancy, Research Funding; Prolong: Research Funding; NHLBI: Research Funding; PCORI: Research Funding; Ironwood: Research Funding.

Pediatric residents’ perceived barriers to opioid use in sickle cell disease pain management

Current guidelines recommend high-priority treatment of severe sickle cell disease (SCD) pain with opioids; however, patients with SCD have historically been undertreated. We used mixed methods to assess pediatric residents' perceptions toward opioid use in SCD pain management. We distributed a survey to 88 residents at an urban pediatric medical center in a cross-sectional study. Participants responded to questions about perceived barriers to acute SCD pain management and attitudes toward patients with SCD. Responses were examined using bivariate analyses. Five pediatric residents were interviewed, to provide more in-depth understanding of barriers to SCD pain management. Fifty-three residents (60%) completed the survey. Participants were divided into "more experienced" (had seen ≥ 21 patients with SCD; 45.3%) or "less experienced." Both groups reported potential for tolerance and dependence as major barriers to opioid use in SCD. Less experienced residents reported a greater need for additional training in SCD pain management (P<0.05), more concern about addiction, and greater empathy for patients with SCD (P<0.05). Both groups agreed that patients with SCD were "frustrating to care for." Thematic analysis revealed that increased patient and provider barriers led to distrust, ultimately leading to undertreatment of pain and inadequate care. Although more experienced residents reported feeling more comfortable treating acute SCD pain and were less concerned with addiction compared with less experienced residents, certain negative views of patients with SCD were prevalent among all residents. Findings suggest that residency training must address provider attitudes as well as knowledge about SCD.