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Previous research has identified vaso-occlusive pain crisis as the most common reason for hospitalization among pediatric patients with sickle cell disease. We sought to identify contributors to hospitalization and length of stay (LOS) for this patient population. A descriptive design was used to determine factors associated with hospitalization and LOS for patients with sickle cell disease at an urban tertiary care pediatric hospital in the Midwest. Sickle cell disease as a principal or secondary diagnosis during calendar year 2003 was used to identify patients for study inclusion. Data were collected from subjects' medical records and the hospital accounting system. 72 African American subjects, ranging in age from infant to 24 years (mean = 10.3) met study inclusion criteria, and accounted for 186 hospitalizations. Sickle cell pain crisis was the most common diagnosis associated with hospitalization (n = 122). Adolescent age was significantly associated with longer LOS (r = .451; p

A 33-year-old female with a history of sickle cell disease is admitted with pain crisis (pain in extremities and back). The patient, who has no history of antibodies, has had several admissions to the hospital for pain crisis over the past 3 years and was transfused one unit of red blood cells (RBCs) 2 years ago; the RBCs were matched by extended phenotype (negative for C, E, and K antigens) as per your blood bank’s policy for sickle cell patients. The patient denies receiving any RBC transfusions since the one unit given 2 years ago at the hospital.

A 27-year-old female with a history of sickle cell disease is admitted with pain crisis (pain in extremities and back) and possible sepsis. The patient, who has a history of anti-Fya and anti-S alloantibodies, has had several admissions to the hospital for pain crisis over the past 5 years. She was transfused two units of red blood cells (RBCs) 1 year ago and received RBC exchange transfusion (six units) for acute chest syndrome 2 years ago; all RBCs were matched by extended phenotype (C, E, K negative) as per the blood bank’s policy for sickle cell patients.

Objectives: To determine the effect of intravenous (IV) magnesium sulfate on the length of stay (LOS) for children admitted with sickle cell pain crisis. Methods: This was a single arm study, with historical controls. Hemoglobin SS or Hemoglobin Sb8 children admitted for pain crisis were eligible. Two sequential treatment protocols of IV magnesium sulfate were added to standard inpatient therapy of IV fluids, opioids, and nonsteroidal anti-inflammatory drugs. The initial 12 children received 40 mg/kg (maximum of 1.5 g) of IV magnesium in the emergency department (ED), and eight and 16 hours later. Seven subsequent children received 40 mg/kg (maximum of 2.5 g) of IV magnesium in the ED, and every eight hours for up to four inpatient days. The main outcome measure was LOS, measured in days. Differences in LOS were analyzed between the admission with magnesium, and the two previous admissions meeting the same criteria, using a Wilcoxon signed-rank test for nonparametric paired data. Results: Nineteen children were enrolled. The results of the two protocols were combined for the analysis. A shorter LOS was found on study admissions (median LOS, 3.0 days compared with 5.0 and 4.0 days for the previous two admissions; p = 0.006). Conclusions: IV magnesium appears to decrease the LOS for children with sickle cell pain crisis. Key words: sickle cell anemia; magnesium; length of stay. ACADEMIC EMERGENCY MEDICINE 2004; 11:968‐972.

210 Background: The U.S. is in the throes of two concurrent epidemics: too many people die from opioid-related fatalities, but too many people continue to suffer in pain. In certain regions this dilemma is particularly pronounced. For example, Southwest (SW) Virginia is a rural area with disproportionately high cancer mortality rates and high rates of opioid fatalities. Little is known about how to most effectively and safely manage pain in a region where there exists both a high cancer burden and significant opioid misuse. Purpose: Describe prescription opioid medication (POM) use for patients with cancer in SW Virginia and potential harms. Methods: This is a longitudinal, exploratory, secondary data analysis using the Virginia All Payers Claims Database (APCD), which includes paid medical and pharmacy claims data on 4 million individuals in the Commonwealth of Virginia. Patients with a diagnosis of cancer who lived in far, rural SW Virginia between 2011–2015 were included. Outpatient prescription data were linked to hospitalization admission claims data to explore potential opioid-related harms. Analysis was conducted at the patient, prescription and prescriber level (SAS 9.4, STATA 13.1) to identify predictors of POM use and opioid-related substance use admissions. Results: Within the APCD, POMs represent 7.23% of all medications prescribed for patients with cancer, with hydrocodone- and oxycodone-combinations, oxycodone, fentanyl transdermal patch and morphine sulfate being the most common. Over 50% of patients were prescribed a POM at least once during the study period. Multi-level logistic regressions suggest age, payer source, cancer type, gender, prescriber type and specialty were all significant (p < .001) predictors of being prescribed POMs. Preliminary analyses of hospitalized cancer patients found no association between POM use and opioid-related substance use hospitalization. Conclusions: A clearer view of geographic patterns and predictors of both POM use and potential harms can inform targeted clinical interventions and policy initiatives that achieve a balanced approach to POMs – ensuring access for patients in need, while reducing risk.

This qualitative research aimed to describe the clinical, social and demographic profile of patients with sickle cell anemia attended in a specialist outpatient center for Pediatric Hematology in Curitiba, Parana. Between the 1st and 19th of October 2012, all the medical records of persons with hemoglobinopathies in the outpatient center were sought; 58 persons were identified who met the inclusion criteria. Data from case histories and clinical tests, from the first attendance up to the date of collection, were organized in categories. There was a predominance (76%) of children (1 to 12 years old), originating from 14 health regions in the state (70.5%), diagnosed in the first year of life (80%), monitored for three years or more (86.2%), with clinical signs of skin paleness (94.8%) and fever (93.1%), with pain crisis as the main complication (70.7%). The results may support planning and operations in the care of the patient with sickle cell anemia and her family members in this outpatient service and also in other similar services.

La fibrodisplasia osificante progresiva es una enfermedad de escasa prevalencia, 1 caso cada 2 millones de habitantes, hereditaria, severamente incapacitante, caracterizada por un proceso de osificación en músculos esqueléticos, fascias, tendones y ligamentos, sin tratamiento eficaz y que evoluciona por empujes, que se acompañan de dolor intenso, dando lugar a posteriori, después de varios empujes, a la instalación de dolor basal permanente. Analizamos las características más salientes de la enfermedad, su historia habitual, su forma de presentación, su evolución, el dolor acompañante y su tratamiento. Este se realiza para combatir el dolor, ya que no existe tratamiento en el momento actual, para la enfermedad de fondo, y será variable de acuerdo al momento evolutivo de la misma, comenzándose con paracetamol y AINE en etapas iniciales, para dar lugar luego al uso de opioides. En lo que se refiere a las crisis de dolor, secundarias a brotes de osificación heterotópicos, existe consenso actualmente en cuanto a la utilización de corticoides de alta potencia antiinflamatoria. Siendo el dolor un hecho relevante en esta patología, no hemos encontrado ninguna publicación que lo aborde específicamente, por lo cual entendemos oportuna esta comunicación. Presentamos el caso de persona de 27 años, sexo femenino, portadora de fibrodisplasia osificante progresiva, controlada desde hace años en nuestra Unidad por sus crisis dolorosas severas, así como también por dolor basal instalado en los últimos años. Se relata la presentación de la enfermedad, su evolución, su estado actual, los tratamientos que se han realizado, así como el manejo de su última, reciente y más severa crisis de dolor, en base a dexametasona en altas dosis, y al uso de pregabalina como coadyuvante. Se concluye con recomendaciones para tratar los empujes dolorosos, basadas en el uso de corticoides, así como el manejo del dolor basal siempre presente en estos pacientes, fundamentado en el uso de opioides. The fibrodysplasia ossificans progressiva is a disease of low prevalence, 1 case per 2 million inhabitants, hereditary, severely disabling, characterized by a process of ossification in skeletal muscles, fascia, tendons and ligaments, without effective treatment, evolving by thrusts which are accompanied by severe pain, resulting in a posteriori, after several thrusts, to installing permanent baseline pain. We analyze the most salient features of the disease, common history, its presentation, its evolution, the accompanying pain and its treatment. This is done to combat the pain, since there is no treatment at present, for the underlying disease, and will vary according to the time course of the same, beginning itself with paracetamol and NSAIDs in early stages, giving rise then to the use of opioids. In regard to pain crises, buds secondary heterotopic ossification, currently there is consensus regarding the use of high potency anti-inflammatory corticosteroids. With pain as a relevant in this disease, we found no publication that specifically addresses; therefore we consider this presentation timely. We report the case of a person of 27 years, female gender, fibrodysplasia ossificans progressiva carrier controlled for years in our unit, for its severe painful crises and baseline pain also installed in recent years. We report the presentation of the disease, its evolution, its current status, as well as treatments that have been made, well as the handling of her latest, recent and more severe pain thrust, based on high-dose dexamethasone, and the use of pregabalin as an adjuvant. It concludes with recommendations for treating painful crises, based on the use of corticosteroids, and baseline pain management always present in these patients, based on the use of opioids.

Objectives Pain is the hallmark symptom of sickle cell disease (SCD), yet the types of pain that these patients experience, and the underlying mechanisms, have not been well characterized. The study purpose was to determine the safety and utility of a mechanical and thermal quantitative sensory testing (QST) protocol and the feasibility of utilizing neuropathic pain questionnaires among adults with SCD. Methods A convenience sample (N = 25, 18 women, mean age 38.5 ± 12.5 [20–58 years]) completed self-report pain and quality-of-life tools. Subjects also underwent testing with the TSA-II NeuroSensory Analyzer and calibrated von Frey microfilaments. Results We found that the QST protocol was safe and did not stimulate a SCD pain crisis. There was evidence of central sensitization (n = 15), peripheral sensitization (n = 1), a mix of central and peripheral sensitization (n = 8), or no sensitization (n = 1). The neuropathic pain self-report tools were feasible with evidence of construct validity; 40% of the subjects reported S-LANSS scores that were indicative of neuropathic pain and had evidence of central, peripheral or mixed sensitization. Discussion The QST protocol can be safely conducted in adults with SCD and provides evidence of central or peripheral sensitization, which is consistent with a neuropathic component to SCD pain. These findings are novel, warrant a larger confirmatory study, and indicate the need for normative QST data from African American adults and older adults.

To the editor: We are honored that our work merits the attention of Dr Bunn and colleagues[1][1] but disagree with some of their conclusions. Traditional risk factors for vaso-occlusive pain crisis, such as leukocytosis and high hemoglobin levels, incompletely predict vasculopathic events and

The purpose of this study is to determine the frequency and variety of strategies being used in the Emergency Department (ED) management of sickle cell pain crisis (SCPC). One thousand randomly selected academic emergency physicians received a multiple-choice survey; 549 (55%) completed the survey. Forty-five percent of respondents treat patients with SCPC every week or almost every shift. Twenty percent use protocols for management of SCPC. Respondents consider pain refractory to outpatient treatment if it is persistent after two (23%) or three (53%) doses of parenteral analgesic. Meperidine or morphine is the most common initial analgesic. In the routine management of uncomplicated SCPC, i.v. analgesics, i.v. hydration, oxygen therapy, and complete blood counts are often or always used by 67, 71, 66, and 82% of respondents, respectively. Some patterns in the diagnostic and therapeutic management of patients with SCPC in the ED are identified, but overall practice is highly variable. Some popular elements of care are divergent from those suggested by the scientific literature.

Sickle cell/β+thalassemia (Hb S/β+thal) is considered as a variant form of sickle cell disease. Acute episodes of vasoocclusive pain crisis are characteristic for sickle cell disorders and may be complicated by an acute or chronic life-threatening organ dysfunction. Chronic intrahepatic cholestasis is a rare and severe complication in sickle cell disease, characterized by marked hyperbilirubinemia and acute hepatic failure with an often fatal course. Despite the fact that patients with Hb S/β+thal usually have a mild type of disease, herein we describe an interesting case of chronic intrahepatic cholestasis with successful outcome in an adult patient with Hb S/β+thal.

A matched case-control study was performed in order to identify some associated factors for ACS or to confirm the published data. Controls were children hospitalized during the same period for pain crisis who did not develop an ACS during hospitalization. Between January 2006 and October 2010, there were 24 episodes of ACS distributed among 19 patients (8 girls and 11 boys). The median age was 7.5 years (range: 3 to 17 years) for the cases and 7 years (range: 3–18 years) for the controls. Four cases and 11 controls were treated with hydroxyurea (HU). In 75% of the cases, the ACS had arisen 24–72 hours following admission. The independent factors associated with ACS were average Hb rate P=0.04), annual number of hospitalizations >3 (OR = 5.44, 95% CI = 3.59–8.21, andP=0.003), average length of hospitalization >7 days (OR = 3.69, 95% CI = 3.59–8.21, andP=0.003), and a pathological transthoracic echocardiography (TTE) (OR = 13.77, 95% CI = 2.07–91.46, andP=0.003). Although the retrospective design and small sample size are weaknesses of the present study, these results are consistent with those of previous studies and allowed identifying associated factors such as a pathological TTE.

Sickle cell disease (SCD) is an autosomal recessive genetic disorder caused by a point mutation in the human β-globin gene. Patients harboring this mutation can exhibit long-chain polymers of hemoglobin and sickle-shaped red blood cells, and suffer from severe medical manifestations including hemolysis and vaso-occlusive crises. Multiple preclinical, clinical and epidemiologic studies have shown that the levels of unmutated fetal hemoglobin (HbF encoded by the γ-globin gene) correlate with less severe disease, validating HbF induction as a therapeutic approach in SCD. Treatment with hydroxyurea (HU), the only approved therapy for SCD, results in a variable induction of HbF and significant improvement in the frequency of pain crises. However, a significant percentage of patients treated with HU fail to exhibit durable benefit, necessitating the need for alternative therapeutic agents. The human γ-globin gene is repressed in the post-natal period by epigenetic mechanisms, and therefore may lend itself to pharmacological intervention aimed at derepressing gene expression. One of the most important of these epigenetic mechanisms is catalyzed by lysine-specific demethylase 1 (LSD1), a histone demethylase that removes mono-/dimethyl marks from the lysine 4 and 9 residues of histone H3 through an FAD-directed redox process. Here, we report the characterization of selective, potent, and orally bioavailable LSD1 inhibitors from two classes - FAD-directed inhibitors that achieve inhibitory activity through formation of covalent FAD-adducts and non-FAD-directed, reversible inhibitors - and demonstrate their ability to induce γ-globin gene expression in murine and primate preclinical models. In the Towne's SCD mouse model, oral administration of LSD1 inhibitors significantly increased HbF+ cell (F cell) production. Concurrent with the increase in F cells, sickle cell numbers, reticulocyte counts, and bilirubin levels were all markedly reduced, indicating an amelioration of several pathophysiological features of SCD. FAD- and non-FAD-directed LSD1 inhibitors were more effective than HU in increasing F cells production, and the combination of HU and suboptimal doses of LSD1 inhibitors resulted in a greater induction of F cells and more pronounced reductions in reticulocyte counts and bilirubin levels. In addition to the humanized SCD model, HbF induction in response to LSD1 inhibitor treatment was evaluated in non-anemic cynomolgus monkeys. Oral administration of LSD1 inhibitors significantly induced F cells and HbF in a dose-dependent manner and over a sustained period (>50 days) following the discontinuation of treatment. The percentage of induced F cells in total RBCs was linearly correlated with the percentage of HbF protein induced by LSD1 inhibition. Taken together, these results support the potential utility of LSD1 inhibition as a novel therapeutic approach to increase HbF production. Disclosures Lee: Incyte Corporation: Employment, Other: Stock. Soloviev:Incyte Corporation: Employment, Other: Stock. Zhang:Incyte Corporation: Employment, Other: Stock. Roman:Incyte Corporation: Employment, Other: Stock. Yang:Incyte Corporation: Employment, Other: Stock. Bowman:Incyte Corporation: Employment, Other: Stock. Burke:Incyte Corporation: Employment, Other: Stock. Margulis:Incyte Corporation: Employment, Other: Stock. O'Connor:Incyte Corporation: Employment, Other: Stock. Yang:Incyte Corporation: Employment, Other: Stock. Wu:Incyte Corporation: Employment, Other: Stock. Wynn:Incyte Corporation: Employment, Other: Stock. Burn:Incyte Corporation: Employment, Other: Stock. Shuey:Incyte Corporation: Employment, Other: stock. Diamond:Incyte Corporation: Employment, Other: Stock. Yao:Incyte Corporation: Employment, Other: Stock. Hollis:Incyte Corporation: Employment, Other: Stock. Yeleswaram:Incyte Corporation: Employment, Other: Stocks. Roberts:Incyte Corporation: Employment, Other: Stock. Huber:Incyte Corporation: Employment, Other: Stock. Scherle:Incyte Corporation: Employment, Other: Stock. Ruggeri:Incyte Corporation: Employment, Other: Stock.

The treatment of pain can raise ethical dilemmas. This article presents a case of a young woman with a pain crisis from severe neuropathic pain that is complicated by comorbidities of depression and prior (but not active) heroin use. Medical and ethical justifications for either withholding or providing opioids for her pain are examined. State and federal laws governing opioid prescriptions by physicians for pain management are reviewed.

Chronic pain is present in epidemic proportions in most countries, is often unrelieved, and has a huge socioeconomic impact. It is not just a “medical” illness but indeed is a problem that faces all healthcare professional fields. Several steps are identified to address this crisis. These include approaches to enhance pain awareness and access to timely and effective care for pain, and educational and research approaches to improve the knowledge base of healthcare professionals and students and diagnostic and management procedures for pain. Several opportunities to enhance pain understanding, access, and management are also identified.

More than 50% of obstetric patients with sickle cell disease will have a pain crisis during pregnancy, and the management of these cases can be challenging.A 20-year-old African American with sickle cell disease presented at 29 4/7 weeks of gestation with severe, debilitating leg and back pain. Large doses of intravenous narcotics did not result in significant pain relief, so a lumbar epidural was placed. This resulted in complete pain relief within several minutes. The patient's symptoms resolved over several days and after a short course of narcotics she was discharged to home, and the remainder of her pregnancy was uncomplicated.Epidural anesthesia should be considered as a potentially effective treatment for a severe sickle cell crisis in obstetric patients.

Johnny was a delightful little boy who was born with sickle-cell disease, an inherited genetic disorder that affects hemoglobin, a protein in the red blood cells responsible for transporting oxygen. Normal red blood cells are soft and round. In sickle-cell disease, the red blood cells are hard and sickle in shape. Consequently, they are likely to get stuck within blood vessels, causing severe pain and other medical complications. Specifically, sickle-cell disease is associated with increased incidence of vascular occlusions (pain crisis), cerebrovascular occlusions (stroke), infections, pulmonary difficulties, and organ damage. Some individuals with sickle-cell disease experience few complications, while others experience many.

Background: Emergency Department Observation Units (EDOUs) and Sickle Cell Pathways (SCPs) allow for protocol based rapid initiation of analgesic treatment for sickle cell disease (SCD) patients during a vaso-occlusive crisis (VOC). Initially, Emergency Department (ED) physicians managed patients on the SCP in the EDOU. After an administration change in September 2013, the Hospitalists service provided protocol based care in the EDOU for the SCP after the initial ED assessment. The Hospitalists service management model incorporates mid-level providers (Nurse Practitioners and Physicians Assistants) into the management of patients on the SCP. The SCP utilizes an individual dosage database using patient-controlled analgesia delivered narcotics. No other changes were made to the pathway during the study period other than the type of physician management. Objective: To compare admission rates between ED physicians and Hospitalists service management of patients on a SCP. Our secondary objective was to ascertain if there was a difference in the three and 30-day return rates of SCD patients managed by ED physicians as compared to hospitalists. Methods: This study was a retrospective database review using a database created from visits of patients with VOC to the EDOU. Data were analyzed for a 21-month period (December, 2011 - August, 2013) in which patient care was managed by ED physicians and the 21-month period (September, 2013 -May, 2015) in which it was managed by the Hospitalists service. 773 patient encounters were included from the ED physicians management period and 727 from the Hospitalists management period. The database was reviewed for information on length of stay (LOS), disposition, three and 30-day return, and readmission rates. Only uncomplicated pain crisis visits due to SCD presenting to the ED were included in this study. Results: The average EDOU length of stay (LOS) for a SCD patient during the ED management period was 17 hours and 54 minutes; during the Hospitalists management period, the average LOS was 18 hours and 23 minutes. The data were analyzed by patient disposition, three and 30-day return rate as shown in Figure 1 and Figure 2 below. Figures 1 and 2 show that the admittance rate for SCP patients during the ED management period was 16% while during the Hospitalist management period the admission rate was 24.8%. Statistical analysis shows that this difference is significant (p Discussion: Analysis of the data shows that the EDOU LOS was not statistically different between groups (p=.1853), suggesting that the disposition decision time and treatment time was similar for both types of physician management. Patients were admitted at a statistically significant higher rate under Hospitalist management than ED management. However, there is no statistically significant difference in the three day return rates between the two groups, indicating that this increased admittance did not lead to a decrease in return rates. The three-day return rate is a marker of the efficacy and appropriate disposition from the pathway. Similarly the 30-day return rates of the two groups were nearly identical (41.1% versus 39.8%). However, while the patients returned to the EDOU at the same rate, they were statistically more likely to be readmitted upon their return by hospitalists as compared to ED physicians (p This study demonstrates Hospitalists service management, staffed with midlevel providers, produces different outcomes than ED management. Although the study does not explain this difference it raises important questions for further study regarding adherence to treatment protocol, confidence in disposition decisions, and inter-professional communications. Despite the differences in the outcomes between the two management groups, the outcomes of the Hospitalists group are better than national averages. Thus, this is a viable model for the pathway management of patients with SC VOC. Figure 1. ED physician management of the EDOU (December, 2011 - August, 2013) Figure 1. ED physician management of the EDOU (December, 2011 - August, 2013) Figure 2. Hospitalist management of the EDOU (September, 2013 - May, 2015) Figure 2. Hospitalist management of the EDOU (September, 2013 - May, 2015) Disclosures No relevant conflicts of interest to declare.

Patient recruitment is a major challenge for randomised trials. Reviews of publicly funded UK trials have found that 45 to 69% fail to recruit to target. This increases costs, delays results, and adversely impacts on the feasibility of conducting trials for conditions where there is a limited patient pool. For some conditions a patient requires treatment on multiple occasions. For example, patients with sickle cell disease require pain relief for each pain crisis, or women having fertility treatment undergo multiple treatment cycles until becoming pregnant. The current norm is for patients to be included for only one treatment episode. We propose a re-randomisation design, allowing patients to be randomised on multiple occasions, which could substantially increase the recruitment rate. We describe some properties of the re-randomisation design, such as the conditions required to obtain unbiased estimates of the treatment effect and control type I error rates, and offer advice on practical design and analysis issues. We show that this design can reduce the required number of patients compared with a parallel group design. It can be used in a wider variety of settings than a crossover design and may be more patient-centred as the number of treatment periods is determined by participants rather than the trial design. We also highlight situations where this design would be inappropriate.

23 Background: Survey studies have determined the prevalence of dissatisfaction among survivor caregivers related to end of life care. Toward improvement in care at EOL, we hypothesized that novel themes of distress would be identified in narratives of the “last day” from the recently bereaved. Methods: Extended narrative accounts of patients’ last day of life were collected from adult, English-speaking, caregivers (n=5) present at the death of a cancer patient. Interviews (45-120 minutes) featured open-ended questions prompting the subject to share an account of the last day, their care and coping experience. Interviews were conducted and transcribed by the author and analyzed thematically. Results: A theme of distressed communication with health care providers [HCP] could be identified in narrative segments in all 5 interviews, linked to transitions such as changes in treatment or clinical status. Narrative fragments exemplary of distress arising from communication are presented. I. A pain crisis so severe “she asked God to take her.” “I am ready to call the nurse practitioner…and she wouldn’t allow it... She doesn’t want to be a burden.” II. “I said, I don’t want you telling him directly anything. I want you to tell me first so we can go in together and tell him…the right way” including an option to “spend time together.” Soon after, the physician “came rushing into the room and as if we’d never had the conversation…, OK, we’re going to take you to the ICU.” III. “I had asked the nurse…to make sure that she had her clothes on when the funeral parlor came.” It was “important to me for her dignity.” The nurse responded: “they just cut the clothes off anyhow.” IV. “Now you’re going to pull chemo out of your hat? Look at him!...He doesn’t want to leave us but he’s ready to go.” “After we said no to chemo, [his doctor] never came near S again.” Conclusions: This pilot study of last day narratives obtained from surviving caregivers points toward a high prevalence of distress content relating to impaired communication with HCP with consequences including uncontrolled pain, conflict, perceived loss of dignity and abandonment. These data indicate the need for larger-scale studies focused on the content and style of bidirectional communication at the EOL.

Comment on Nolan et al, page [3264][1] Hemolytic anemia, while silent from a vaso-occlusive pain crisis standpoint, leads to sustained nitric oxide depletion, oxidant stress, vasoconstriction and proliferative vasculopathy in a number of organ systems, ultimately contributing to the development of

[Figure][1] A 44-year-old African American female presented with a pain crisis and a history of hemoglobinopathy, menometrorrhagia secondary to acquired von Willebrand factor (vWF) deficiency, and a history of multiple vaso-occlusive events necessitating lifelong warfarin therapy. Further

Aims Sickle cell disease (SCD) is a lifelong haematological disorder resulting in anaemia and pain crisis. Specialist centres use experienced staff and accredited protocols to manage pain crises in affected children. The main objective of this audit is to identify areas of management of crises which could be improved in line with recommendations set out locally, by the ‘Painful Sickle Cell Crisis Protocol’ and nationally, by the NHS Sickle Cell disease in Childhood Standards and Guidelines for Clinical Care. This may provide useful insight for service improvement and evidence for similar units throughout the UK and Europe. Of particular interest was timing and efficacy of administration of analgesia. Methods Baseline audit of management of patients presenting to Accident & Emergency (A&E) or the hospital’s haematology day unit (DU) due to acute pain crisis of SCD was conducted. The study cohort was all patients seen at the hospital with a diagnosis of SCD from 1st January 2010 to 31st December 2011. 43 patients met this criteria. Re-audit to be done January 2014. Results Of the 43 patients registered with the hospital haematology unit, 12 attended the hospital because of pain crises, whilst 31 had no pain crises within the allotted time frame. 5 patients experienced more than one acute pain crisis. Time to administer initial analgesia was 57 ± 37 minutes. Average length of stay in hospital was 4.5 ± 3 days. The most common initial analgesic administered was oral or IV morphine. 14 of the 25 children had tried medication at home prior to presenting. Conclusions Aspects of the service identified for improvement include: clear documentation of time patient presents, time they are seen by a doctor and time they are given their first analgesia; unequivocal inclusion of a drug kardex in patients notes and consistent use of a pain scoring system. Recommendations Implementation of a ‘Sickle Cell Pain Crisis Assessment and Management’ form. This would improve consistency of documentation of information relating to pain crises and therefore accuracy of future service monitoring.

The gene for sickle cell disease is carried by 8% of the African-American population in the United States. The primary care physician is often called upon to recognize and treat one of the major sequelae of sickle cell disease--vaso-occlusive pain crisis. An injectable nonsteroidal anti-inflammatory drug has recently become available and may offer some improvement in outcome of vaso-occlusive pain crises. We present five case reports reviewing various current therapeutic options, including newer pharmacologic agents, and comment on alternatives to impatient management of pain crises. The use of the emergency department short-term observation unit as an alternative to hospitalization is discussed.

A anemia falciforme é uma hemoglobinopatia genética, caracterizada por uma alteração na estrutura da molécula de hemoglobina (HbA1), denominada hemoglobina S (HbS), que provoca uma distorção da estrutura dos eritrócitos, passando de forma esférica para forma de "foice" (sicke-cell). Este fenômeno é conhecido como falcização e é responsável por um quadro de anemia grave em indivíduos homozigotos e por quadros esporádicos de dor em indivíduos heterozigotos (portadores de traço falciforme), de acordo com a patofisiologia, em situações de baixa concentração de oxigênio. O teste mais específico e mais sensível usado para diagnosticar anemia é o teste eletroforese de hemoglobina, que é, contudo, difícil de ser incorporado em laboratórios de rotina, devido ao seu alto custo. O objetivo deste trabalho foi estimar a prevalência do traço falciforme na população da cidade de Araraquara-São Paulo. A prevalência de indivíduos assintomáticos com hemoglobina S (traço falciforme) na região de Araraquara-SP foi de 1,5%. Separandose o estudo de prevalência por raça, observamos 0,6 % de traço falciforme em indivíduos da raça branca e 15,4 % em indivíduos da raça negra.

The role of weather as a possible trigger of sickle cell acute painful episodes has been debated for over 30 years. Early studies based on anecdotal evidence, such as patients reporting pain during the colder parts of the day or when swimming in the cold ocean on a particularly hot day, argued for an association between weather and the occurrence of pain. Recently published studies have shown an association with cold and rainy seasons and with windy weather and low humidity. Other studies however, have found no associations. A limitation of these studies is that they are based on seasonal trend data, mean monthly temperatures, hospital-wide visit rates, but not data at the individual level. To more accurately describe the role of weather as a trigger of painful events, we conducted a case-crossover study of the association of local weather conditions with the occurrence of individual pain crises. From the Cooperative Study of Sickle Cell Disease, 813 patients with 3,580 acute painful episodes were identified. For each pain episode, the hazard period was defined as the 48 hours preceding the onset of pain, and control periods were two periods of 48 hours, two weeks before, and two weeks after the pain crisis. Local weather data including temperature, wind speed and relative humidity, were downloaded from weather-source.com for each of the 23 participating centers for the years 1979 through 1982. Weather data were merged with clinical data and the association between the occurrence of pain crises and local weather conditions were studied using conditional logistic regression. We found an association between wind speed and the onset of pain, specifically wind speed during the 24 hour period preceding the onset of pain. Continuous measures of wind speed, mean and median wind speed during the 24 first hours of the hazard/control windows, showed significant associations with the occurrence of pain (p = 0.03 and p = 0.009, respectively). Analyzing wind speed as a categorical trait, dichotomized at the median (10 mph) for the same 24 hour period, showed a 14% increase (95% CI: 4% – 12%) in odds of pain, when comparing the high wind speed to lower wind speed (p = 0.005). To determine the most likely induction time, average wind speeds were determined for 4 hour intervals and their association with the onset of pain analyzed. Assuming a non-specific induction time will bias the measure of association toward the null, the interval with the highest OR should contain the most relevant induction time. We found that the interval from 13 hours to 16 hours prior to onset of pain has the largest measure of association [OR =1.01 (1.00 – 1.02), p = 0.026]. These results are in agreement with another study that found an association between wind speed and hospital visits for pain in the United Kingdom (Jones et. al, BJH 2005). These findings lend support to recent physiological and clinical studies that have suggested that skin cooling is associated with sickle vasoocclusion (Mohan et al. Clin Sci, 1998), and perhaps pain (Resar et al., J Pediatr 1991). Though pain is a common complication, and likely to have many potential triggers, physicians may wish to advise patients to take precautions on windy days by limiting skin exposure.

There is conflicting evidence for a causal relationship between infection and haematological crisis of sickle cell disease. To find out whether changes in leucotaxis occur during pain crisis, in-vitro neutrophil migration was determined in 38 children with Hb SS during steady state and during pain crisis. Migrations of neutrophils of sickle cell patients was 29 +/ 12 microns in steady state and 27.5 +/- 10.5 microns during pain crisis. These rates were comparable to migration of neutrophils of control children with normal haemoglobin of 34 +/- 9.6 microns. However, with addition of autologous serum to the cell suspension, neutrophil migration of patients in pain crisis was significantly retarded (16 +/- 13 microns) as compared to those in steady state (26 +/- 10.2 microns) and control children (28.7 +/- 10 microns). Sera of children in pain crisis also inhibited migration of neutrophils of healthy adults with normal Hb. Pooled normal plasma reversed inhibitory action of pain crisis serum on autologous and homologous neutrophil migration; but pain crisis plasma did not. Chemotactic effect of sera of Hb SS children in steady state or pain crisis and control children on neutrophils of eight adults with normal Hb were similar and comparable to that of pooled normal serum. Thus, children with sickle cell disease develop chemotactic inhibitor(s) in their circulation during pain crisis. They may lead to defective leucotaxis and enhanced susceptibility to infection.

An increase in the number of irreversibly sickled cells (ISCs) in pain crisis has been found by some investigators but not others. We have used the technique of discontinuous arabinogalactan density-gradient ultracentrifugation of whole blood to study ISCs from patients with sickle cell anemia (SCA) during pain crisis and again when pain free (5- 331 days after crisis). Nine patients have been studied through ten episodes of pain crisis. Five layers with densities from 1.128 g/mL to 1.158 g/mL have been used. Careful classification of the cells using Nomarsky optics demonstrated highly significant changes occurring in the layers of the gradient. The changes involve the appearance of an increased percentage of echinocytic ISCs and echinocytic cells that were not ISCs, especially in the denser gradient layers, during crisis, and their replacement by normal-appearing discocytes in the pain-free state. There was no change in ISCs that were not echinocytic. Data collected previously demonstrated that reduced glutathione activity correlated with increased echinocytosis in our gradient layers. This indicates that the echinocytic change may occur as a result of oxidant stress. Hemoglobin F levels and the percentage of hemoglobin F from reticulocytes showed no consistent change to coincide with the rise in normal-appearing discocytes in the lightest layers after crisis. Our data indicate that pain crisis occurs in association with an echinocytic change, which may be induced by oxidant injury. The rise in normal-appearing cells after crisis may reflect increased hemoglobin F production in some patients but mainly relates to the disappearance of these echinocytic erythrocytes.

A study was conducted in a sample of 140 children with sickle cell anemia to evaluate the relationship between hematological variables (%HbF, %HbA2, %Hb, and mean cell volume) and disease severity. A patient’s severity status was determined by whether hetshe was hospitalized, had a transfusion, andlor had a pain crisis at 2 evaluation periods; the first was based on a patient’s history taken at the initial assessment visit to the Wayne State Comprehensive Sickle Cell Center, and the second was based on a 1-3 year follow-up at the center. Fetal hemoglobin was a strong predictor of a patient’s hospitalization and transfusion status. A decrease in %HbF of 4.76% (one SD of %HbF) was associated with a 3.58 fold (95% confidence interval, 1.18-7.28) greater odds of being hospiialized both prior to initial assessment and on foilow-up, compared to not being hospitalized at either evaluation. Similarly, a decrease in %HbF of 4.76% was associated with a 5.56 fold (95% confidence interval, 1.67-18.96) greater odds of having a transfusion both prior to initial assessment and on follow-up compared to not having a transfusion at either evaluation. Patients who were both hospitalized and transfused at initial assessment and on follow-up (n = 12) had a mean %HbF of 7.59%, while patients who were not hospitalized or transfused at either evaluation (n = 19) had a mean %HbF of 13.61%. Fetal hemoglobin was not a significant predictor of pain cris,es in this sample of patients. None of the other hematological variables were significant predictors of disease severity in this study. The strong relationship between %HbF and disease severity identified in this study suggests that a single %HbF measurernent may be useful in predicting important aspects of the clinical course of children with sickle cell anemia.

Transcutaneous electrical nerve stimulation (TENS) has been used in a variety of acute and chronic painful conditions, but has not been studied in sickle cell pain crises. We compared TENS versus placebo in a randomized, double-blind, cross-over study involving 60 trials in 4 crisis severity categories. TENS electrodes were applied to the area of severest pain and patients' pain ratings and medication usage were evaluated over a 4-hour period. Pain ratings and analgesic requirements at 1 and 4 h from onset of study were similar in the TENS and placebo groups. Patients assessments of overall treatment efficacy indicated that TENS was more frequently helpful, but there was a substantial placebo effect. Although the value of TENS in this condition was not established in this study, further trials, using varied stimulation parameters, are warranted.

Fulminant pneumococcal infections are rare in teen-agers with sickle cell anemia. A 16-year-old black male with sickle cell anemia was treated as an outpatient for cryptogenic pain crisis, which delayed antibiotic therapy for primary pneumococcal septicemia for seven hours. This patient did not appear ill upon initial presentation but rapidly developed disseminated intravascular coagulation and died.