Acute Pain Episodes Research Articles

Acute abdomen as a clinical presentation of lymphoma: A case report

Rationale: Acute abdomen is a medical emergency that requires prompt diagnosis and management. Lymphoma is a rare cause of acute abdomen. Patient concerns: A 54 year old patient complained of repeated episodes of acute abdominal pain over the past 3 months. Diagnosis: Mantle cell lymphoma. Interventions: Chemotherapy and stem cell transplantation. Outcomes: Abdomen pain disappeared and the patient was discharged uneventfully. Lessons: Although it is a rare cause of acute abdomen, lymphoma should be included in the differential diagnosis workup of patients with unexplained and unusual acute abdomen.

Association of fetal hemoglobin level with frequency of acute pain episodes in sickle cell disease (HbS-only phenotype) patients

BackgroundSickle cell disease (SCD) is a Mendelian single gene disorder with highly variable phenotypic expression. In the present study, we analyzed the influence of HbF, alpha thalassemia and other hematological indices to determine their association with acute pain episodes. MethodThis case control study consisted of SCD subjects with HbS phenotype experiencing three or more acute pain episodes in last twelve months (cases) and without any episode of acute pain during last twelve months (controls). Hematological parameters, HbF, and presence of alpha thalassemia were assessed in all subjects. ResultsA statistically significant difference between HbF levels (P < 0.025, χ2 test) and alpha thalassemia (P < 0.008, χ2 test) was observed between controls and cases group. Univariate analysis indicated that increased HbF levels > 25% (OR: 0.37, 95% CI: 0.18‐0.77, P < 0.008) and presence of alpha thalassemia (OR: 0.53, 95% CI: 0.33–0.85, P < 0.009) provided protection, while multivariate analysis revealed significant protection was attributable only by higher HbF levels (OR: 0.39, 95% CI: 0.17–0.88, P < 0.025). Significantly higher HbF levels were observed only in the 11–20 age group of cases in comparison to controls (Student's t-test, P < 0.001). ConclusionHigher concentrations of HbF are associated with protection against frequent episodes of acute pain crisis in SCD patients.

AAAPT Diagnostic Criteria for Acute Sickle Cell Disease Pain

Acute pain episodes are the most common complication in patients with sickle cell disease (SCD). Classically attributed to vaso-occlusion, recent insights suggest that chronic pain may also contribute to the pathogenesis of acute pain episodes, which adds complexity to their diagnosis and management. A taxonomy, or classification system, for acute pain in patients with SCD would aid research efforts and enhance clinical care. To meet this need, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public–private partnership with the U.S. Food and Drug Administration, the American Pain Society, and the American Academy of Pain Medicine formed the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks–American Pain Society–American Academy of Pain Medicine Pain Taxonomy initiative. One of the goals of this initiative was to develop taxonomies for acute pain disorders, including SCD. To accomplish this, a working group of experts in SCD and pain was convened. Based on available literature and expert opinion, the working group used a 5-dimenional structure (diagnostic criteria, common features, modulating factors, impact/functional consequences, and putative mechanisms) to develop an acute pain taxonomy that is specific to SCD. As part of this, a set of 4 diagnostic criteria, with 2 modifiers to account for the influence of chronic pain, are proposed to define the types of acute pain observed in patients with SCD. PerspectiveThis article presents a taxonomy for acute pain in patients with SCD. This taxonomy could help to standardize definitions of acute pain in clinical studies of patients with SCD.

I. ALTERNATIVE METHODS OF ANALGESIA Preoperative Cesarean Delivery Intravenous Acetaminophen Treatment for Postoperative Pain Control: A Randomized Double-blinded Placebo Control Trial

(Am J Obstet Gynecol. 2018;218:353.e1–353.e4) Most patients first encounter opioid medications after surgery or during an acute pain episode. The ongoing opioid use disorder epidemic in the United States has prompted research to minimize opioid treatment in the postsurgical setting. Nonobstetrical studies have reported improved pain scores and decreased opioid use after surgery with the preoperative administration of intravenous (IV) acetaminophen. The primary outcome in the current study was to examine if maternal opioid use was significantly less in the postoperative period when preoperative IV acetaminophen was given. Secondary outcomes included hospital length of stay, pain scores, and cord blood acetaminophen levels.

Defining Sickle Cell Disease Acute Painful Episodes: The Pisces Project

Background: For research purposes, painful crises in sickle cell disease (SCD) have either been self-defined by patients, or adjudicated by research experts, most often based on whether urgent care or hospital care was sought for pain related to SCD. The Pain in Sickle Cell Epidemiology Study (PiSCES) determined that three-fourths of self-defined crises days were not managed in urgent or hospital care. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (AAPT) published a taxonomy of chronic SCD pain, defined as pain on most days of 6 months duration, along with at least one clinical sign, and no better explanation for the pain. We served on a similar SCD consensus panel to propose a more expansive taxonomy of acute sickle cell pain or painful episodes, informed by the PiSCES dataset (manuscript under review). Here we present three PiSCES-derived definitions of acute painful episodes, and we analyze the impact of various definitions on pain outcome results potentially useful for research.Methods: PiSCES Patients (N=81) who completed at least 5 out of the expected 6 months of daily diaries and did not have gaps in their daily diary of 4 days or more were included. Patients self-reported their worst sickle cell pain intensity on a scale from 0 (none) to 9 (unbearable), and independently self-reported whether they were having a crisis that day, whether they went for an unscheduled physician visit, an Emergency Department visit, or whether they were hospitalized for sickle cell pain. Definitions of acute pain episodes compared here include self-reported crisis days, days with pain ≥ 5, and days with utilization of the ED or overnight hospitalization (other potential definitions not shown). To meet any definition, a crisis day (pain≥ 5, utilization) had to be reported for 2 or more consecutive days. Non-crisis intervals were 2 or more consecutive days without a self-reported crisis (pain ≥ 5, utilization). The average length of non-crisis intervals was considered to represent the time between crisis episodes. For <4 consecutive missing days, imputations were performed using non-missing data to calculate the probability that missing days were crisis days. We used PiSCES data to compare various pain outcomes (see Table) for patients with and without AAAPT-defined chronic pain, for the three definitions of an acute painful episode. We note that episode length, intensity, time between episodes and intensity of non-episodes were all estimated using only patients who had an acute painful episode.Results: (Table)For each definition of an acute painful episode, a larger percentage of patients with chronic pain had acute episodes than patients without chronic pain. Similarly, chronic pain patients had statistically significantly more episodes and higher mean pain intensity on non-episode days. For 2 of 3 definitions (but not ED or hospitalization use), chronic pain patients had longer episodes and shorter time between episodes. Only for the self-reported crisis definition, patients had higher mean pain intensity during episodes. Raising the pain intensity threshold from 5 to 6 to define an acute episode slightly decreased the absolute percentage with acute episodes, the number of episodes, and the length of episodes, but did not affect the relationships between outcomes for patients with and without chronic pain (results not shown in table).Conclusions: A comparison of various definitions of acute painful episodes using the PiSCES dataset yields slightly different pain outcome results. However, these differences are intuitive. For example, chronic pain patients still have more intense and more frequent acute painful episodes regardless of the definition used. The finding of more frequent acute pain in SCD adults with chronic pain has important implications for treatment and the design of SCD clinical trials. [Display omitted] DisclosuresField:Ironwood: Consultancy, Research Funding; Prolong: Research Funding; Incyte: Research Funding. Dampier:Pfizer: Research Funding.

Systemic Vascular Basement Membrane Markers Linked to Synovial Vascular Remodeling Are Bio-Markers of Hemarthrosis in Patients with Hemophilia

Introduction: Acute painful joint episodes in hemophilia are not always associated with hemarthrosis. Point-of-Care Musculoskeletal Ultrasound with Power Doppler (POC MSKUS/PD) is a fast and sensitive imaging modality to determine the presence of hemarthrosis and direct management. Systemic collagen cleavage products reflecting extracellular matrix, bone and soft tissue turnover may serve as an alternative tool for the detection of hemarthrosis. Based on previous observations of pronounced vascular remodeling within the synovial tissue during hemarthrosis in patients and hemophilic mouse models, we hypothesized that cleavage products of collagen IV, found in the basement membrane of blood vessels may differentiate between bleeding and non-bleeding states.Methods: Joint bleeding was induced in FVIII-/- mice (+/- FVIII-treatment before and shortly after injury). Synovial vascular remodeling was assessed 14 days later by MSKUS/PD and histology including αSmooth Muscle Actin (αSMA)-staining. Murine plasma samples were analyzed for C4M2 and P4NP-7S, which are type IV collagen turnover products. To determine human relevance, 31 adult patients with hemophilia (PWH), ≥ age 21, were studied prospectively for 3 years with MSKUS/PD during pain-free intervals and painful events for bleed status, vascular flow and 11 plasma markers of collagen turnover(C2M, ARGS, C3M, Pro-C3, C5M, Pro C5, C4M2, P4NP-7S, Col18N, DCN- CS, ColNeo10, NIC).Results: Type IV collagen turn-over markers were significantly elevated in plasma of FVIII-/- deficient mice 14 days after joint bleeding when compared to baseline (C4M2: 2.575 ng/mL vs. 1.94 ng/mL, p=0.029 and P4NP-7S: 80.3 ng/mL vs. 67.81 ng/mL, p= 0.0152 respectively ). This increase coincided with a significant increase in vessel number (2.3 fold, p=0.0008), vascular flow by PD (2.3 fold, p= 0.014) and αSMA staining (5.1 fold, p= 0.0007). C4M2 and P4NP7S plasma levels correlated negatively with αSMA staining, suggesting a role for αSMA in vessel stabilization (C4M2 p=0.02, Pearson r= -0.5707; P4NP-7S p= 0.0130, Pearson r= -0.6238). FVIII-treatment reduced plasma C4M2 and P4NP-7S levels to baseline (C4M2 1.98 ng/mL vs. 1.94 ng/mL, P4NP-7S 59.98 ng/mL vs. 67.81 ng/mL), but had no effect on the other vascular parameters. In patients, results from 91 visits were compiled. Twenty five were due to acute painful episodes with 16 confirmed hemarthroses. Of the 11 biomarkers evaluated, only C4M2 and P4NP-7S were transiently but significantly elevated in plasma during joint bleeding compared to pain free intervals or to non-bleeding painful episodes. Plasma C4M2 levels during acute painful bleeding episodes when compared to non-bleeding states were 41.65 vs. 29.69 ng/mL (p=0.0003), and P4NP-7S levels were 418.9 vs 278.1 ng/mL (p=0.0007), respectively. Baseline levels of C4M2 and P4NP-7S in PWH were above the lab reported normal range, indicating ongoing high vascular basement membrane turnover. Additionally, PWH who developed joint bleeding episodes had a higher level of collagen IV biomarkers at baseline when compared to PWH who did not experience joint bleeding (C4M2 33.91 vs 29.07 ng/mL, P4NP7s 320.6 vs 292.8 ng/mL), although this was not statistically significant. Hemarthrosis was accompanied by pronounced abnormal synovial microvascular flow evidenced by PD, while plasma levels of both biomarkers correlated positively with joint PD signal (C4M2, p= 0.0400, Pearson r=0.4409; P4NP7S-p=0.0141, Pearson r=0.5154).Conclusions: Our findings suggest that systemic vascular collagen turn-over products may be novel biomarker candidates to identify patients at high risk for joint bleeding and to diagnose acute hemarthrosis. Hemarthrosis in hemophilia is associated with pronounced synovial vascular remodeling. Cleavage products of type IV collagen, but not of any other collagen, were systemically elevated in PWH and distinguished bleeding from non-bleeding painful episodes. Type IV collagen is found exclusively in basement membranes and in the case of joint bleeding, the presumed source of these turnover markers is newly formed synovial blood vessels. Therefore, our findings support the concept that vascular instability during neovascularization is involved in the dynamics of hemophilic joint bleeding. These findings broaden the scope of potential diagnostic tools substantially, opening new avenues for personalized treatment of PWH. Disclosuresvon Drygalski:Bioverativ/Sanofi: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novo Nordisk: Consultancy, Honoraria; HemaBiologics: Consultancy; Genentech: Consultancy; Biomarin: Consultancy, Honoraria; Uniqure: Consultancy, Honoraria; Shire: Consultancy, Honoraria; Hematherix: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.

Neutrophil Extracellular Traps Are an Intrinsic Feature in Sickle Cell Disease

Polymerisation of deoxygenated-HbS in sickle cell disease (SCD) leads to alteration of the shape and function of the red blood cells (RBC), resulting in hemolytic anemia and recurrent episodes of micro-vascular occlusion, triggering a cascade of downstream events and inflammation that underlies the progressive multi-systemic organ damage. Neutrophils have a critical role in promoting sickle pathophysiology; patients with higher leukocyte count, particularly neutrophils, tend to have a higher risk for more severe manifestations as well as earlier mortality. SCD neutrophils display a specific overreactive phenotype, including increased adhesive properties and production of reactive oxygen species. Activated neutrophils can also produce extracellular traps (NETs) in response to pathogens or other inflammatory stimuli. Studies have shown that prolonged exposure of healthy neutrophils to SCD plasma leads to formation of mature string-like NETs. These strings of decondensed chromatin covered with elastase (NE) or myeloperoxidase (MPO) might contribute to SCD pathophysiology. Here, we investigated if SCD neutrophils had enhanced intrinsic potential for NETs formation (i.e. could form NETs in the absence of a stimulus).We evaluated NETosis both indirectly, in which neutrophils isolated from healthy subjects were incubated with plasma from HbSS patients and directly, in which neutrophils isolated from HbSS patients were compared with those isolated from healthy donors. 17 HbSS patients in steady-state (all on hydroxyurea) and 11 race and sex matched healthy donors were included in the direct assays; the NETosis-related events were observed over a period of 7 minutes to 4 hours. For the indirect assay, we used plasma from 19 HbSS patients (14 on hydroxyurea, 5 off hydroxyurea and/or transfused), all of whom provided samples in steady-state and acute pain crisis (paired samples); the healthy neutrophils were treated with SCD plasma for up to 7 hours. A pain crisis was defined as an episode of acute pain that has no evident cause other than SCD, resulting in hospitalization and treatment with parenteral opioids. Steady state was defined as the period from at any time 8 weeks prior to or after a crisis. Patients were excluded when they were <18 or >80 years of age, pregnant or had a history of blood transfusion in the previous 8 weeks. The IRB approved the studies under NIH protocol numbers NCT00081523 (SCD subjects) and 03-H-0015 (healthy controls and SCD subjects). The NETosis features (histone citrullination H4cit3, nuclear decondensation, DNA-NE-MPO strings) were assessed by imaging flow cytometry and fluorescence microscopy.In the indirect assays, healthy neutrophils made more string NETs when treated with the SCD plasma (from both steady state and crisis) compared to plasma from healthy donors (Figure 1A), and NETs response was further increased with plasma from acute compared to their paired steady state sample (N=19, p=0.0114) (Figure 1B). Plasma from patients on or off hydroxyurea induced comparable NETosis responses. This confirmed a higher ability for the crisis milieu to modulate NETosis.Directly, neutrophils isolated from SCD patients as compared to those from healthy controls, showed increased number of decondensed H4cit3 positive nuclei, after only 7 min of incubation in RPMI (N=7, p=0.0688). By comparison the response to high concentration (20 uM) of Hemin - a regular product of hemolysis, was similar in the SCD and the healthy neutrophils (p=0.6871) (Figure 1C). This data suggested that the SCD environment might activate neutrophils to produce NETs in the absence of a specific stimulus. Fluorescence microscopy confirmed that neutrophils isolated from the patients did produce significantly more DNA-NE strings without any stimulation compared to healthy neutrophils (N=9, p=0.0079). After Hemin treatment, NETs response in SCD neutrophils was also higher than that of the healthy controls, but not statistically significant (Figure 1D).Our data provide the first direct in vitro evidence that neutrophils in SCD are innately prone to NETosis but whether and how these might contribute to the initiation or progress of SCD vaso-occlusive crises is yet to be determined. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Five Fold Decrease in Admissions for Uncomplicated Vaso-Occlusive Crisis and Other Benefits from Care in Infusion Clinics: Results from the Escaped Trial

Background: Patients with sickle cell disease (SCD) suffer from frequent vaso-occlusive crises (VOC), the leading cause of hospitalization and ED visits for these patients. Infusion centers (IC) are alternatives to ED care and may provide patients with a better care experience. We previously demonstrated in a single center that the use of such centers provides more rapid pain control and can decrease the risk of a hospital admission. For the management of VOC the NHLBI's guidelines recommend that patients receive analgesic therapy within 60 minutes of registration and that pain be reassessed every 15-30 minutes until it is controlled. In the ESCAPED study, we aimed to learn whether the ED or IC more rapidly provides analgesia to patients who present with an uncomplicated VOC.Methods: The ESCAPED study is a prospective cohort study that recruited subjects at four sites (Baltimore, Cleveland, Milwaukee and Baton Rouge). The Baltimore and Milwaukee sites have dedicated ICs that treat only adults with SCD; the Cleveland and Baton Rouge sites have ICs that treat a diverse group of patients requiring infusion services. Patients were enrolled during regular outpatient visits between 4/2015 and 12/2016. Uncomplicated crisis was defined as an acute episode of pain with no known other cause and required treatment with parenteral pain medications. Upon study entry, participants completed surveys to collect demographic data; chart abstraction was done for information on comorbidities. Data was extracted after the acute visits for the primary endpoint: time to first dose of pain medication. We also extracted data on reassessment of pain after the first dose of parenteral pain medication and admission or discharge status. Patients' comorbidities were updated through chart abstraction after each visit. Each participant was followed for 18 months and data from visits for acute, uncomplicated VOC were collected. All acute visits were recorded and complete data was collected for each patient from the first visit each month to each site of care for uncomplicated crisis. Time-varying propensity scores estimated by a random effects model was used to balance covariates in the two arms. The treatment effects were estimated using a sub-classification approach and standard errors were computed by nonparametric bootstrapping at the individual level.Results: 483 subjects were enrolled and 444 completed 18 months of follow up (29 withdrew, 10 died). The median follow-up was 8.2 months (IQR, 5.7-12.0) for the 39 subjects who did not complete the study. There were 4851 acute visits for uncomplicated VOC of which 2910 had the complete data collected. 1445 visits to an ED and 1465 visits to an IC. The mean number of visits per patient was 10.0 (SD, 15.5) and median number was 4 (IQR, 1-12.5). 115 subjects had no acute visits during the study period. In the adjusted analyses, the mean time to first dose of parenteral pain medications was 125 minutes in an ED setting and 63 minutes in an IC setting (95% CI, 54-69). Patients seen in an IC were significantly more likely to have their pain reassessed 30 minutes after their first dose of pain medication than patients treated in an ED (OR, 2.5; 95% CI, 2.1-3.0) and visits to the ED were significantly more likely to end in the patient being admitted than visits to the IC (OR, 5.9; 95% CI, 4.7-7.3).Conclusions: With adjustment for differences between patients treated in the ED and IC, we demonstrated that those treated in an IC have significantly better treatment experiences than subjects treated in an ED: a 50% reduction in time to first dose of pain medication and an almost 6-fold decrease in hospital admission. Increasing access to infusion clinics is essential to improving the quality of care of uncomplicated VOC in adults with SCD. DisclosuresLanzkron:GBT: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Prolong: Research Funding; NHLBI: Research Funding; PCORI: Research Funding; Selexys: Research Funding; Ironwood: Research Funding. Little:Doris Duke Charitable Foundations: Research Funding; PCORI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; NHLBI: Research Funding. Field:Incyte: Research Funding; Ironwood: Consultancy, Research Funding; Prolong: Research Funding. Haywood:PCORI: Research Funding. Varadhan:PCORI: Research Funding. Saheed:PCORI: Research Funding. Proudford:PCORI: Research Funding. Robertson:PCORI: Research Funding. Kincaid:PCORI: Research Funding. Burgess:PCORI: Research Funding. Green:PCORI: Research Funding. Wang:PCORI: Research Funding. Seufert:PCORI: Research Funding. Brooks:PCORI: Research Funding. Piehet:PCORI: Research Funding. Griffin:PCORI: Research Funding. Arnold:PCORI: Research Funding. Frymark:PCORI: Research Funding. Huang:PCORI: Research Funding. Wallace:PCORI: Research Funding. Segal:PCORI: Research Funding.

A Novel Filtering Tool for Detecting Sickle Cell Disease in the Pediatric Population

Human migration has reached an unprecedented level. Progressive globalization has integrated people and facilitated the introduction of deleterious genes into populations in which they were originally absent, thus impacting negatively on public health. A great challenge encountered by clinicians in the era of “migration hematology” lies in the hemoglobinopathies, a group of conditions representing the commonest, life-threatening, monogenic disorders globally. Of the ±400 000 newborn children affected annually, ~65% have sickle cell disease (SCD), a disorder that has spread far beyond its origins because of slave trade and contemporary population movements. More than 70% of all global SCD cases are due to autosomal recessive homozygous inheritance of a βS-mutation (missense Glu6Val) in the HBB gene, creating sickle hemoglobin (HbS), a structural variant of adult hemoglobin (HbA) and causing the most severe form of SCD, sickle cell anemia (SCA). Other forms result from inheritance of HbS in combination with different mutations, most commonly a second structural β-globin variant, βC (S/C) or one of many that lead to decreased β-globin synthesis (S/β-thalassemia). Clinical consequences are due to polymerization of deoxygenated HbS and its deleterious effects on erythrocytes. It is a debilitating syndrome characterized by chronic hemolysis and vaso-occlusive crises, manifesting as acute painful episodes, organ infarction and eventual multi-organ damage.Early diagnosis of SCD is vital so that appropriate management can be initiated timeously. Current diagnostic tests include hemoglobin electrophoresis (HE), high performance liquid chromatography (HPLC), isoelectric focusing (IEF) and DNA analysis. These specialized expensive modalities have been successfully incorporated into antenatal/neonatal screening programmes of some high-income countries such as in the UK. However, implementation of similar initiatives in various other regions has been difficult due to practical, political and economic challenges.The present study outlines a simple algorithm for use in the pediatric population to identify children at risk for SCD. Residual EDTA-anticoagulated capillary blood samples were analyzed in a tertiary hospital laboratory using an automated benchtop hematology instrument (Sysmex XN-450) that provides a CBC, differential white cell count and reticulocyte percentage (RET%). Patients with known SCD (85% SCA), confirmed by HE and HPLC, presenting for routine out-patient clinic review, were included (n=107; 1 month to 18 years old; 54% male). Samples were processed within 12 hours of collection and those who had received blood transfusions in the preceding 12 weeks were excluded.The mean ± SD was determined for each CBC parameter and RET%. Of these, 5 parameters were used to establish an algorithm with reference limits specific for each age category of patients with SCD (Table 1). When compared to the population-based normal reference ranges, these limits were statistically significantly different (p<0.05). The algorithm was validated against 107 random blood results previously obtained on routine follow up of pediatric patients with SCD. If a single outlying parameter was allowed, the algorithm demonstrated a sensitivity of 95.3% for SCD. The 4.7% of outlying cases (n=5) exhibited severe microcytosis and had a coexisting thalassemia component. The sensitivity with a complete match, i.e. 5/5 parameters, was 86.9%. Other CBC parameters were not informative.To combat the burden of SCD early and accurate diagnosis is critical. The algorithm described here is a cost-effective and sensitive filtering tool that can quickly be used to identify children at risk for SCD at any age and exclude those who do not require definitive testing, thereby limiting unnecessary expenditure. It will be beneficial in resource-constrained low-income countries; regions where SCD is not historically present and clinical suspicion is low; or in scenarios where it is difficult to obtain a medical history due to a language barrier and/or health-related stigma. Since using the algorithm only requires a CBC and RET%, it is suitable for application at any healthcare level. Assessment may be conveniently conducted in line with a child's immunization schedule prior to symptomatic presentation, and if combined with the Mentzer index and a family origin questionnaire, the sensitivity can be enhanced. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Examining the Role of Sickle Cell Disease Patients As Teachers in the Emergency Department: Patient Directed Physician Education

Background: Sickle Cell Disease (SCD) patients are amongst the most frequent utilizers of the emergency department (ED) for acute vaso-occlusive pain episodes (“crisis”). Unfortunately, ED SCD care often fails to meet guideline recommendations. This results in preventable morbidity and mortality as well as substantial resource utilization. Current care interventions across multiple domains have not led to sustained improvements, likely due in part to negative attitudes and beliefs among health care providers (HCP). Novel mechanisms of physician education are required to improve outcomes. An emerging method of education in SCD is the use of patients as “just in time” teachers. We refer to this as Patient Directed Physician Education (PDPE) and define it as a broad range of activities in which patients relay actionable information to HCPs in the clinical setting. While there is a growing body of research supporting patients as teachers, no group has specifically examined point of care PDPE in a SCD population.Objective: This study seeks to understand the current use and feasibility of SCD PDPE in the ED.Methods: This is a multi-centered, prospective descriptive qualitative design with semi-structured, audio taped individual interviews. SCD patients and ED physicians across Ontario, Canada were recruited to participate in the study through purposeful sampling. Qualitative analysis was performed using phenomenological inquiry, which encompasses qualitative approaches to inductively and holistically understand a human phenomenon (i.e. teaching and learning in sickle cell disease) in a context specific setting.Results: In total, 11 patients and 8 physicians participated in the study. Patient ages ranged from 21-67 and physician years in practice ranged from 3-21. The patient group predominately consisted of female Black Canadians (81%) while the physician group was mainly Caucasian males (63%) but did include representation from other ethnicities. There was significant variability in both self-described disease severity (patients) and frequency of SCD exposure (physicians). Both groups assessed themselves as having good to excellent SCD general knowledge or clinical acumen respectively.Within the qualitative analysis both groups responded favourably to PDPE and expressed confidence in its feasibility and ability to improve ED care. Barriers to the implementation of PDPE were expressed across three major domains; 1) patient factors, 2) health care worker factors, and 3) health care system factors. The ability of patients to present reliable health information was highlighted as a key factor in the success of PDPE by both groups. However, physicians and patients had strikingly different perspectives towards the inherent challenges. Patients identified triage delays and difficulty speaking due to intractable pain as the major barriers to shared decision making. Conversely, physicians largely did not appreciate these elements of the vaso-occlusive pain episode experience and instead expressed concerns regarding patient credibility, particularly in the context of high dose opiates. Overt racism or the perception of patient as “drug seeker” were not identified as major themes from either group.There was consensus towards written patient care plans, corroborating electronic health records, and collaboration from SCD experts as mechanisms to bridge the SCD patient/ED physician divide and facilitate PDPE. In addition, despite not being directly involved in PDPE, nurses experienced in SCD management were consistently noted to be instrumental in supporting the patient-physician interaction.Conclusions: Patient directed physician education is a feasible and novel SCD care innovation with support from both patients and ED physicians. Successful implementation will require credible educational adjuncts (e.g. patient pocket cards, care plans) and support from ED nurses and SCD experts. Our findings will serve as part of a continuum of research to engage patients as partners in improving SCD knowledge and care outcomes. DisclosuresNo relevant conflicts of interest to declare.

Allergic Sensitization Is Associated with Decreased Risk of ED Visits and Hospitalizations for Pain in Sickle Cell Disease

Rationale: Lower airway disease is common in pediatric sickle cell disease (SCD) and is often diagnosed as asthma. This condition may be a risk factor for acute chest syndrome (ACS) and pain episodes. There are conflicting data about whether SCD-associated lower airway disease is due to allergic inflammation, as is typical in non-SCD childhood asthma. However, transgenic SCD mouse models have suggested a propensity toward allergic inflammation, and a recent study in children with SCD suggested allergic sensitization was associated with increased risk of acute chest syndrome (ACS). Allergic sensitization may be a risk factor for pulmonary inflammation and may trigger pain episodes. We hypothesized that allergic sensitization to a panel of indoor allergens would be associated with more frequent ED visits and hospitalizations for pain, ACS, and asthma symptoms in children and adolescents with SCD.Methods: Patients were recruited from two large academic children's hospitals. Ninety-nine participants with SCD ages 5-21 who were not receiving chronic exchange transfusions completed pre- and post-bronchodilator spirometry and allergy testing at a baseline visit. Allergen-specific IgE in blood was measured to Alternaria, Aspergillus, cat, cockroach, dog, dust mite (D. farinae), and mouse urine protein; we examined baseline characteristics by stratified groups (not sensitized vs. sensitized to one or more allergens) via t-tests, chi square, and Mann-Whitney U tests; we created a count variable with number of sensitizations. ED visits and hospitalizations were reviewed retrospectively two years prior to study entry. Asthma was defined as physician diagnosis in medical records plus at least one home asthma medication (albuterol or controller/preventative medication). We used negative binomial models to examine relationships between atopy [number of positive specific IgE (³0.35kU/L)] and the number of ED visits and hospitalizations, adjusting for age, sex, hydroxyurea use, and head of household (HOH) education level. FEV1 and positive bronchodilator response (³10%) were compared via multiple linear regression and multiple logistic regression.Results: Participants were 41% male, 66% HbSS or HbSb0 genotype, 52% on hydroxyurea, and 32% had a HOH with a high school education or less [Table]. Twenty-eight percent had a physician diagnosis of asthma, and 57% (N=56) were sensitized to at least one allergen. Allergic sensitization was associated with decreased risk of total ED visits1 (IRR 0.80[0.66-0.97] p=0.022), ED visits for pain (IRR 0.80[0.67-0.97] p=0.019), and fever (IRR 0.63[0.45-0.88] p=0.007), but not associated with a significant difference in ED visits for asthma or ACS. Allergic sensitization was neither associated with differences in rates of hospitalization (total, or for pain, fever, ACS, or asthma) nor with differences in FEV1 percent predicted, FEV1/FVC ratio, or positive bronchodilator response.Conclusions: In a population of children with SCD, allergic sensitization was associated with decreased risk of ED visits (total, for pain, and for fever). The mechanism for an association between atopy and a less severe phenotype of SCD is unclear. These findings point to potential differences in immunologic endotype/phenotype and add support to the hypothesis that lower airway disease in children with SCD has a different mechanism than typical childhood atopic asthma. Further investigation into the immunologic phenotypes and mechanisms of lower airway disease in children with SCD is warranted.1All IRR presented are per allergen, adjusted for age, sex, hydroxyurea use, and HOH education level; 95% confidence interval. [Display omitted] DisclosuresStrouse:Global Blood Therapeutics: Consultancy.

Mind It: Increasing Rate of Mental Health Disorders in Hospitalized Sickle Cell Patients

Abstract Introduction: The number of patients with sickle cell disease (SCD) approaches 100,000 in US after adjusting for early mortality (Hassell Am J Prev Med 2010). Management of SCD and its complications require frequent access to healthcare system lifelong, thus impacting patients' quality of life and cost of healthcare. Chronic pain inducing illnesses are known to increase susceptibility to mental health disorders (Rayner Pain 2016). Psychosocial disorders are common in this population and impact the course of hospitalization, however we have limited published data in this area. Hence, we performed a large retrospective study utilizing the National Inpatient Sample (NIS) data to evaluate the prevalence of mental health disorders in hospitalized sickle cell patients, and their influence on length of hospitalization. Methods: We identified hospitalized sickle cell patients using ICD 9 codes (282.5,282.6X -282.6X ) in the National Inpatient Sample (NIS) database. Similarly, ICD-9 codes were used to identify patients with mental health disorders of interest. The demographics and length of hospital stay of patients with and without mental health disorders were then compared. Surveyfreq was used to calculate proportions and surveymeans was used to calculate median length of stay and hospital charges. Cochran-Armitage test was used for analyzing trends. We used chi-square for categorical data frequency, P value of &lt; 0.05 was considered statistically significant. All analysis was performed using SAS 9.4. Results: We identified a total of 1,349,701 hospitalizations for sickle cell patients between 2003-2014, of which 221,279 (16%) had associated mental health disorders. Mood disorders were most common (40%), followed by substance abuse (28%) and anxiety disorder (16%) (Table 1). Over the timeline of our study, we found a longitudinal trend towards higher prevalence of mental health disorders in hospitalized sickle cell patients (Figure 1). There was higher prevalence of mental health disorders among patients aged between 21-40 years (24%). No difference in the rate of mental health disorders was noted in patients admitted with or without acute sickle cell pain episode. Median length of hospital stay (LOS) was 4 days in patients with mental health disorders (95% CI 4.04-4.12) compared to 3 days in those without (95% CI 3.17-3.20). Conclusion: The prevalence of mental health disorders in hospitalized sickle cell patients has been gradually increasing from 2003 to 2014 and approaches 16% overall. The length of hospital stay is longer for the individuals with these disorders than those without hence, increasing the cost of health care and reducing patient satisfaction. Therefore, early recognition and intervention for mental health disorders is paramount to promote quality of life and reduce health care costs. This demands for a multidisciplinary approach to provide better access to mental health resources to this population in the outpatient setting. Disclosures No relevant conflicts of interest to declare.

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.

Opioid Prescribing Habits in Sickle Cell Disease: An International Survey of Providers

Introduction: Vaso-occlusive pain crisis (VOC) are the hallmark of sickle cell disease (SCD) and the primary reason for which affected individuals seek acute care (Boussard et al JAMA, 2010). Both national and international guidelines recommend aggressive IV opioids, intravenous fluids and anti-inflammatory therapy as the mainstay of treatment for acute SCD pain. In an effort to avoid acute care for VOC, many pain crises are managed at home with oral agents, including anti-inflammatory and opioid medications. However, there are no current guidelines on the use and type of medications for home pain management, likely due to lack of clinical trials comparing the efficacy and safety of oral agents for use at home. Previous studies suggest geographic differences in the use of opioids for home pain management (Kanter et al, Br J Haem, 2018). Amplifying these issues is the growing concern for opioid abuse and misuse both in the US and internationally (WHO, 2013). This study aimed to describe the opioid prescribing habits among international providers treating individuals with SCD, to better assess the different medications used for outpatient management of SCD-related pain both in the United States (US) and internationally.Methods: A thirty-question REDcap survey was disseminated electronically. Participants were recruited using a combination purposive and snowball sampling strategy. Providers were initially identified by email using databases from SCD conferences. After the initial responses were received, responding participants were asked to refer other providers who treat SCD.Results: There were 17 countries represented. Over half of the respondents were from the US (59%,75/127). Most of the respondents were Hematologist/Oncologists both pediatric-focused (43%, 54/127) and adult-focused (34%,44/127). Providers from the US were more likely to prescribe opioids than non-US physicians (95% vs 73%, p<.001) and were more likely to be “very comfortable” prescribing opioids than non-US physicians (73% vs 37%, p<.001). In exploring the rationale of physicians that do not prescribe opioids for outpatient management of pain, non-US physicians were more likely to site “outpatient opioids not being allowed” (50%) vs 25%), although this was not significant. Of those physicians who prescribe opioids, most (70%) prescribed 30 doses or less at a time. However, non-US physicians were more likely to prescribe less than 10 doses at a time (64%vs 17%, p <.001). Overall, the top 5 most commonly prescribed medications for home pain management were; acetaminophen/paracetamol (98%), ibuprofen (88%), short acting morphine (55%), tramadol (52%) and oxycodone (48%). Non US physicians were more likely to prescribe acetaminophen/paracetamol (90%vs 68%, p<.05) and tramadol (69% vs 30%, p <.05), while US providers more likely to prescribe short acting morphine (64% vs 42%, p<.05), long acting morphine (60% vs 25%, p<.001), oxycodone (70% vs 15%, p<.001), oxycontin (44% vs 10%, p<.001) and dilaudid (64% vs 6%, p<.001). The most commonly ordered acute care parenteral medications were morphine (84%), dilaudid (55%) and Toradol (54%). Parenteral dilaudid was used almost entirely in the US alone (88% vs 8%, p<.001). US physicians were more likely to be concerned that patients were abusing opioids than non-US physicians (32% vs 27%, p<.05).Discussion: Acute vaso-occlusive pain episodes are the most common reason for healthcare utilization in SCD. Although many countries use oral opioids for outpatient pain management, the majority of non-US prescribers are more likely to prescribe less potent opioids in lower quantities. Non-US physicians are more likely to use Tylenol and NSAIDS before opioids, with Tramadol being prescribed most often. As concerns have increased for opioid-induced hyerpalgesia and other complications of long term opioid use, alternative disease-modifying agents for the prevention of SCD related pain remain a huge unmet need. However, identifying optimal home pain management strategies is also necessary to improve care in SCD. Finally, as more multinational studies of novel therapeutics are undertaken in SCD, it is important to note the significant geographic differences in medication prescribing both at home and in the hospital and to work to create multinational guidelines on outpatient management of VOC's. [Display omitted] DisclosuresKanter:bluebird bio: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; ASH: Membership on an entity's Board of Directors or advisory committees; Apopharma: Research Funding; Pfizer: Research Funding; NHLBI: Membership on an entity's Board of Directors or advisory committees, Research Funding; Global Blood Therapeutics: Research Funding; Sancilio: Research Funding.

Microglia-like Cells Derived from Hematopoietic Stem and Progenitor Cells Are a Model System to Investigate Chronic Pain in Sickle Cell Disease

Background: Patients with sickle cell disease (SCD) experience acute pain episodes in early childhood; over 50% of adult SCD patients go on to develop chronic pain. In animal models, microglia, derived from hematopoietic stem cells, play an important role in the transition from acute to chronic pain; in patients with chronic pain microglia are often activated with minimal stimuli, releasing TNF-alpha and stimulating neurons. Research involving microglia has been stymied by difficulty in obtaining and culturing microglia, particularly from humans. We therefore propose to culture microglia-like cells from peripheral blood mononuclear cells (PBMC) from pediatric patients with SCD with and without chronic pain (defined as pain for more than 50% of days for at least 3 months) and from normal blood donors.Objectives: Our goal was to determine if our cultured cells exhibited microglia morphology and surface markers, could be activated with inflammatory stimuli, and if donor characteristics were retained in the culture derived microglia-like cells.Methods: PBMC were obtained from peripheral blood by Ficoll separation from three unique patients with SCD and no history of chronic pain (SCD CP-), peripheral blood from three unique patients with SCD with history of chronic pain (SCD CP+), or buffy coat from three human blood donors. PBMC were cultured with recombinant human GM-CSF (10 ng/ml; R&D Systems, MN), recombinant human IL-34 (100 ng/ml; R&D Systems), as previously described (Ohgidani et al, 2014) to induce ramified microglia. On day 7 of culture, cells were collected and morphology analyzed by phase contrast microscopy, phenotyped by flow cytometry by staining with CD11b and CD45 antibodies, indirect immunofluorescence performed with anti-CX3CR1antibodies and imaging by confocal laser scanning microscope. Microglia-like cells from 3 normal blood donors, 3 SCD CP- and 3 SCD CP+, were stimulated by 100 ng/mL LPS for 24 hours, beginning on day 6 of culture. Deramification (activation) was assessed by immunofluorescence using anti-Iba1, and by flow using anti-CD68.Results: PBMCs from patients with SCD ± CP and normal blood donors developed microglial morphology, namely, soma bodies with branched collaterals, after incubation with GM-CSF and IL-34. When subjected to flow cytometry, treated cells were CD11bhigh and CD45low; fluorescence microscopy revealed CX3CR1 positivity in the cultured cells, all consistent with accepted microglia phenotype. PBMCs untreated with GM-CSF and IL-34 maintained their round morphology, and were CD11blow, CD45high by FACS.Microglia-like morphology differed significantly between PBMC sources. Microglia-like cells from SCD CP+ had shorter and fewer branches than normal individuals; branching of microglia-like cells from SCD CP- were intermediate in number and length, greater than to SCD CP+ but less than normal individuals.When treated with LPS, nearly 100% of microglia-like cells derived from patients with SCD CP+ became amoeboid in shape, indicating microglial deramification, or activation, compared to approximately 25% of microglial-like cells derived from normal human blood donors or SCD CP-.We also assessed deramification through flow measurement of CD68, a marker found on activated microglia and found that the microglia-like cells derived from HSPCs from SCD CP+ patients had significantly higher CD68 positivity compared to microglia-like cells derived from HSPCs from normal human blood donors or SCD CP-, and significantly higher Iba1 positivity as measured by immunofluorescence.Conclusions: We established the microglia-like nature of the cultured PBMCs derived from patients with SCD±CP and normal blood donors through morphologic examination and confirmation of characteristic surface markers via flow and fluorescence microscopy, and through demonstration of activation with LPS. Our microglial-like cells derived from patients with SCD CP+ were activated at higher percentages by LPs treatment than microglial-like cells derived from normal human blood donors and SCD CP-, suggesting that donor characteristics are retained by the microglial-like cells developed in culture. We propose to use this model system to derive mechanistic insights into the development of chronic pain in SCD, and to screen pharmacologic agents to treat and prevent chronic pain. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

NASAL POLYPS SAVE THE DAY

Introduction Idiopathic anaphylaxis is the most common diagnosis given to adults after their first anaphylaxis episode. Many diseases can mimic this diagnosis making follow up critical. Case Description A 35-year old male with newly diagnosed asthma and allergic rhinitis presented with a one-year history of intermittent acute onset episodes of red pruritic patches, abdominal pain, chest and throat tightness, and hypoxia that were preceded by rhinorrhea and nasal congestion. Many of these episodes would awaken him from sleep and were not temporally associated with food, non-steroidal ingestion, exercise, or insect stings. Epinephrine acutely resolved his symptoms. Initial physical examination was normal. Baseline tryptase and alpha-gal sp-IgE were normal. He was diagnosed with idiopathic anaphylaxis (IA) and treated with cetrizine, famotidine, and montelukast. At follow up, he reported a decrease in episode frequency and severity, although noted continued episodes with chest tightness, nasal congestion, coughing and wheezing that were only responsive to epinephrine. Examination was now remarkable for grade 1 nasal polyps. He had been ingesting ibuprofen for headaches, although denied symptom association. Because of worsening nasal polyp disease he underwent sinus surgery. Afterwards due to a high suspicion for AERD, he underwent aspirin desensitization with recurrence of his typical symptoms during desensitization. On aspirin therapy, his “anaphylactic episodes” resolved. Discussion ERD maypresent with multi-system symptoms mimicking anaphylaxis. This case highlights the importance of follow up for patients labeled with IA.

Longitudinal analysis of inflammatory, psychological, and sleep-related factors following an acute low back pain episode: A potential factor in tissue effects in low back pain

Introduction: Systemic inflammation is observed in chronic low back pain (LBP) (Wang et al 2008) and may contribute to the transition from acute to persistent LBP (Klyne et al 2017). Lower back connective tissues are a possible source of this inflammation and can be modified by inflammation. Fibroblasts secrete inflammatory cytokines in response to stretch or injury of the connective tissues (Dodd et al 2006; Wilke et al 2017), which can “spill over” into the bloodstream, leading to widespread secondary tissue damage and activation of pain pathways in the central nervous system (Xin et al 2017). Whether an early increase in systemic cytokines is related to LBP outcome is unclear. This study aimed to determine whether systemic cytokines and C-reactive protein (CRP) during an acute episode of LBP differ between individuals who did and did not recover by 6 months and to identify subgroups based on patterns of inflammatory, psychological, and sleep features associated with recovery/non-recovery.

278 Opioid Pill Consumption After an Emergency Department Visit: How Many Pills Are People Using?

Recently published guidelines advise limiting opioids prescriptions for acute painful episodes to a 3-day supply; however, there is little literature available to quantify patterns of opioid use after an ED visit. Additionally, the number of pills included in a 3-day supply is not quantified in guidelines and may vary widely (eg, a 3-day supply of hydrocodone-acetaminophen using typical dosing intervals could be 12 tabs (1 PO Q6 hours) or 36 tabs (2 PO Q4 hours)). We sought to describe opioid consumption patterns after an ED visit for acute pain and quantify the proportion of patients who would exceed a 3-day supply at the commonly dispensed quantity of 12 tabs. As part of a larger interventional study promoting the safe use of opioids after an ED visit to an urban academic hospital (>88,000 visits), patients completed a 10-day medication diary documenting their medication consumption (including both analgesics and other home medications). Patients were enrolled if they were age >17 years, received a prescription for hydrocodone-acetaminophen and did not chronically use opioids. Patients were included in this analysis if they returned the completed medication diary and had a discharge diagnosis in 1 of 4 categories: back pain, kidney stone, fracture or musculoskeletal injury (non-fracture). Patient demographics and pain scores are reported. Opioid consumption is described using daily number of pills consumed and daily morphine milligram equivalents (MMEs) both for the sample overall and by diagnosis group. Additionally the proportion of patients continuing opioid use is reported by post-visit-day both overall and by diagnosis. 191 patients with the diagnoses listed above returned completed medication diaries [45 (24%) back pain, 52 kidney stone (27%), 54 fracture (28%), 40 (21%) musculoskeletal injury (non fracture)]. Mean Age a 6 years (sd 14), 57% female. Pain scores on ED presentation were high and remained high post discharge (eg, Day 1: 7 (N=161), Day 2: 7 (N=143), Day 3: 6 (N=122)). Mean quantity of opioid pills prescribed: 16 tabs. On the day of discharge (Day 1), 85% of patients consumed an opioid at home (87% back pain, 73% kidney stone, 93% fracture, 88% musculoskeletal injury) with a mean tabs consumed of 1.7 (sd 1), resulting in 11.2 (7.9) MME (13.9 (11.4) MME back pain, 9.5 (5.2) MME kidney stone, 10.7 (6.9) MME fracture, 11.1 (6.6) MME musculoskeletal injury). The proportion of patients consuming opioids on subsequent days decreased on the day after discharge for patients with kidney stones (42%) and fractures (81%), remained stable for those with musculoskeletal pain (90%) and increased for those with back pain (91%). Among those patients taking pills on the first 2 days after discharge (Day 2 and Day 3) the MME consumed increased (15 (10.2) and 15.6 (12.2) MME, respectively) before decreasing on subsequent days (Day 4: 13.5 (11.5) MME, Day 5 13.3 (9.2) MME). Only 7.7% of kidney stone patients consumed more than 12 pills; whereas 42.2% of back pain patients consumed more than 12 pills in the 10 days post-discharge. 81% of patients had leftover pills (66% back pain, 96% kidney stones, 74% fracture, 87% musculoskeletal injury). In this sample, pill consumption varied by illness category; however, overall patients were consuming low quantities of pills and the majority had unused pills 10-days after their ED visit. Further data could help support prescribing tailored by diagnosis and minimize unused pills.

Rate and Temporal Coding Mechanisms in the Anterior Cingulate Cortex for Pain Anticipation

Pain is a complex sensory and affective experience. Through its anticipation, animals can learn to avoid pain. Much is known about passive avoidance during a painful event; however, less is known about active pain avoidance. The anterior cingulate cortex (ACC) is a critical hub for affective pain processing. However, there is currently no mechanism that links ACC activities at the cellular level with behavioral anticipation or avoidance. Here we asked whether distinct populations of neurons in the ACC can encode information for pain anticipation. We used tetrodes to record from ACC neurons during a conditioning assay to train rats to avoid pain. We found that in rats that successfully avoid acute pain episodes, neurons that responded to pain shifted their firing rates to an earlier time, whereas neurons that responded to the anticipation of pain increased their firing rates prior to noxious stimulation. Furthermore, we found a selected group of neurons that shifted their firing from a pain-tuned response to an anticipatory response. Unsupervised learning analysis of ensemble spike activity indicates that temporal spiking patterns of ACC neurons can indeed predict the onset of pain avoidance. These results suggest rate and temporal coding schemes in the ACC for pain avoidance.

Effectiveness of intraarticular steroids in osteoarthritis of knee

Knee osteoarthritis is a degenerative disease characterized by cartilage destruction which manifests as pain, stiffness and loss of joint motion. With increasing longevity, aging of population and increased incidence of obesity, osteoarthritis remains a potentially major health problem as well as global economic burden. Intraarticular steroids are frequently & effectively used to treat acute and chronic inflammatory conditions of joints, especially during osteoarthritis flare with evidence of inflammation like increasing pain and joint effusion. This reduces acute episodes of pain and increases joint mobility and rehabilitation. This was a prospective hospital based study of 240 Patient with osteoarthritis knee. Average age was about 54±3 years, knee effusion detectable in 80% of patients and radiographic features of osteoarthritis in 91% cases at time of injection. Results showed significant improvement in pain and joint tenderness at 6 weeks after injection. There is consensus now that intraarticular steroids are extremely helpful in acute episodes of arthritic pain and efficacy is almost similar and equal to other modalities of intrarticular injection therapies. Intraarticular steroid injections are reasonably safe, reliable and time tested treatment of arthritic conditions and thus can be used as first line of treatment in flares of osteoarthritis with features of synovial inflammation to reduces crisis of pain and promote rehabilitaional activities and bring back smiles to patients.