Frequency Of Painful Crises Research Articles

Prescribing Hydroxyurea in Sickle Cell Disease Patients: The Pattern and Association with Co-Prescribed Medications Used to Manage the Disease Complications.

Background and Objectives: Hydroxyurea (HU) is an effective medication used to reduce the frequency of painful crises associated with sickle cell disease (SCD). However, data describing its prevalence among SCD patients in the Eastern Region of Saudi Arabia are scarce. This is a multi-center, retrospective, cross-sectional study that aims to investigate the pattern of prescribing HU in SCD patients and to determine the association between prescribing HU and other co-prescribed medications used to manage SCD complications. Methods: Data were collected from patients who visited the hematology clinics of Al-Qatif Central Hospital (QCH) and King Fahad Hospital in Hofuf (KFHH) between June 2021 to May 2023. The data included demographics, prescribed medications, and recent laboratory test results, all of which were collected from patients' medical records. Descriptive statistics were utilized to assess the difference between HU users vs. non-users. A binary logistic regression model was used to determine the association between prescribing HU and co-prescribed medications used to manage SCD complications. The results are presented as the odds ratio (OR) and 95% confidence interval (95% CI). Results: This study included 2816 SCD patients with a 56% prevalence of HU prescription. HU was prescribed for young age groups more often compared to old age group patients. Young males were more likely to be prescribed with HU compared to females, and it becomes dominant in females after the age of 36. HU users were more likely to have paracetamol (69% vs. 53%, OR = 1.9, 95% CI 1.6-2.2), NSAIDs (50% vs. 35%, OR = 1.7, 95% CI 1.5-2), and opioids (41% vs. 37%, OR = 1.3, 95% CI 1.1-1.6) co-prescribed, and less often to have laxatives (8% vs. 5%, OR = 0.66, 95% CI 0.48-0.9) and anticoagulants (22% vs. 15%, OR = 0.56, 95% CI 0.46-0.68) co-prescribed compared to non-users. Conclusions: The pattern of prescribing HU, supported by the association findings, raises concerns about patients' compliance and adherence to HU therapy. Early health education, specifically to young female SCD patients, is warranted to increase the success rate of HU therapy.

Impact of Etonogestrel-releasing contraceptive implant use in cisgender women with Sickle cell disease

BackgroundSickle cell disease is a hereditary hemolytic anemia that exposes women to increased health risks especially in pregnancy, with serious implications for the woman and fetus. Acute pain episodes can occur multiple times per month and result in reduction of quality of life and disruption of her life. ObjectiveTo assess the clinical, including pain and metabolic parameters of women with sickle cell disease using etonogestrel-releasing contraceptive implants. MethodsWomen with sickle cell disease, aged 18–40 years, with reports of pain crises in the preceding 3 months were included and followed up for 12 months. Blood samples were collected to evaluate the blood count, reticulocytes, liver profile (alkaline phosphatase, gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, and total bilirubin and its fractions), lipid profile, and lactate dehydrogenase levels before and 6 and 12 months after implant insertion. The following clinical variables were analyzed every 3 months: bleeding pattern, blood pressure, weight, body mass index, pain intensity (assessed using a visual analogic scale (VAS) from 0 to 10), and frequency of pain crises. ResultsTwenty-three women completed the study. There were no differences in laboratory variables between baseline and 6 and 12 months after implant insertion. Similarly, clinical variables did not differ, except for pain intensity (VAS pre-insertion = 8 vs. VAS 12 months post insertion = 4; p = 0.005) and frequency of pain crises (pre-insertion = 6 vs. 12 days/month post insertion = 0; p = 0.000). ConclusionsEtonogestrel-releasing contraceptive implants were associated with a reduction in the intensity and frequency of pain crises in women with sickle cell disease. Moreover, it was safety among these population due to no changes in laboratory parameters during the first 12 months of use.

Maximizing longevity: erythropoietin's impact on sickle cell anaemia survival rates.

Sickle cell anaemia (SCA) stands as a hereditary blood disorder characterized by mutated haemoglobin, causing red blood cells to adopt a sickle shape, leading to complications like vaso-occlusive crises, anaemia, and organ damage. Despite advancements in treatment, managing SCA remains challenging, with limited options to increase life expectancy and improve quality of life for affected individuals. This paper reviews the potential impact of erythropoietin (EPO) therapy in enhancing life expectancy and ameliorating complications in individuals with SCA. EPO, primarily recognized for its role in stimulating red blood cell production, holds promise in mitigating anaemia, reducing transfusion dependence, and possibly diminishing the frequency and severity of vaso-occlusive crises in SCA patients. Moreover, by stimulating red blood cell production, EPO therapy might alleviate the vaso-occlusive process, thus reducing the frequency of painful crises and associated complications. Additionally, considering the potential side effects and the need for continuous monitoring, the use of EPO in SCA treatment requires cautious consideration. The potential of EPO therapy in SCA offers a glimpse into novel strategies aimed at improving the quality of life and extending the life expectancy of affected individuals. In conclusion, while the application of EPO in SCA treatment holds promise, additional research is indispensable to comprehend its precise role, optimize dosing strategies, and ensure safety, thereby paving the way for enhanced life expectancy and improved outcomes for individuals living with SCA.

Depressive Symptoms among Children with Sickle Cell Anemia in a Tertiary Health Facility in North-western Nigeria

Abstract Context: Sickle cell anemia (SCA) being a chronic debilitating condition places affected children at risk of depression. Aims: The aim of this study is to determine the prevalence of depressive symptoms in children with SCA, the perceived causes, intervention sought, and associated factors. Settings and Design: This was a cross-sectional survey involving children with SCA aged 7–15 years attending pediatric hematology clinic of Usmanu Danfodiyo University Teaching Hospital, Sokoto. Materials and Methods: Information on depressive symptoms was obtained using the short mood and feelings questionnaire for children and adolescents. Statistical Analysis Used: Data were analyzed using IBM-SPSS version 25.0. Results: Respondents consisted of 291 child–caregiver pair with M:F of the children 1.6:1 and mean age of 11.0 ± 2.7 years. Majority [239 (82.1%)] of the caregivers were females with mean age 38.4 ± 7.4 years. Most [217 (74.6%)] of the caregivers were Hausa by tribe, married (269, 92.5%), in a monogamous setting, 159 (58.5%) with 129 (44.3%) of them having low socioeconomic status. One hundred and forty-nine (51.2%) children had depressive symptoms. Requirement for daily drug intake (125, 83.9%), missed school days (119, 79.9%), recurrent illness (115, 77.2%), and stress (114, 76.5%) were the commonest perceived causes. Prayers (138, 94.5%) and use of distraction (100, 68.5%) were the commonest interventions adopted. Child age category (P = 0.002), caregiver’s gender (P < 0.001), family setting (P < 0.001), socioeconomic status (P = 0.008), comorbidity (P = 0.021), frequent painful crises (P = 0.001), and frequent hospital admission (P = 0.024) were associated with depressive symptoms and remained independent predictors of depressive symptoms on logistic regression. Conclusions: Depressive symptoms were common among the subjects and associated with some sociodemographic and medical factors.

Brain morphofunctional changes associated with pain in children, adolescents and young adults with sickle cell disease

INTRODUCTION: Neuroimaging has been widely used to investigate the brain signature in patients with pain, but the results are heterogeneous, especially when the brain is under development, and in specific health conditions. Sickle cell disease (SCD) is often associated with chronic pain that starts in infancy, and there is a need to understand the brain of such children. OBJECTIVES: This systematic review aims to summarize the findings in the literature on brain morphofunctional changes in children, adolescents, young adults, and young adults with SCD. METHODS: Data search was performed in PubMed, LILACS, and SciELO, and results were organized to identify brain regions that showed significant structural and functional changes assessed through structural or functional MRI, or electroencephalography. RESULTS: The synthesis of five studies showed that children with SCD present decreased cerebral cortex thickness, and increased functional connectivity, mainly concentrated in the precuneus and anterior cingulate cortex, regions that make up the default mode network (DMN), and/or the pro-nociceptive network. DISCUSSION: These alterations were related to the frequency of pain and hospitalizations, and the increased connectivity in structures of the antinociceptive network is associated with a decrease in the frequency of pain crises and their consequences. CONCLUSION: Children, adolescents and young adults with SCD have decreased thickness and connectivity in the anterior cingulate cortex and precuneus.

Establishing Mental Wellness Screening As Standard of Care in Pediatric Sickle Cell Patients

Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized with multi-organ involvement and frequent pain crises. Somatic complaints can give rise to neuropsychiatric disorders, among which anxiety and depression are the most common. Although mental health plays an important role in health outcomes, there is not a standardized approach to screen sickle cell patients for depression at most sickle cell centers across the country and at Texas Children's Hospital (TCH). The long-term goal of this project is to screen sickle cell patients over the age of 12 for depression across TCH hospitals: TCH-West Campus (TCH-WC), TCH-Woodlands (TCH-WL) and TCH-Medical Center (TCH-MC). Over the past two years, we successfully implemented depression screening at TCH-WC as standard of care through a series of PDSA cycles. The focus of this quality improvement project is to implement depression screening at TCH-WL. At TCH-WC, all sickle cell patients aged 12 years of greater are screened for depression using the Patient Health Questionnaire-9 modified for Adolescents (PHQ-A) . From October 2022 to July 2023, 71% of the patients that qualified for screening identified low risk, 16% identified mild risk and 12% identified moderate to severe risk of depression. Eleven percent endorsed suicidality. Psychology/Social Work (SW) saw 77.4% of patients with moderate to severe depression and 100% who screened positive for suicidality on the same day as screening. Now that our depression screening protocol is standard of care at TCH-WC, we extended this screening to TCH-WL in February 2023. Our goal is to increase the annual depression screening rate from 0 to 50% in English/Spanish speaking patients aged 12 years and older with sickle cell disease who present for follow-up care to the TCH-WL. During our first PDSA cycle at TCH-WL, one hematologist administered the PHQ-A to sickle cell patients > 12 years. No intervention was needed if patient scored 0-6 on the PHQ-A. Psychological resources were provided via handout if patient scored 7-9. SW referral was placed and patient was preferably seen same day if patient scored > 10 on the PHQ-A. If unable to be seen same day, SW followed-up via phone call. If patient screened positive for suicidality, an urgent SW referral was made and patient was seen in clinic the same day. Three sickle cell patients >12 years presented for follow up with the assigned provider. Two-thirds (67%) of patients were given the PHQ-A; half (50%) screened positive. During the second PDSA cycle at TCH-WL, all patients with SCD over the age of 12 who presented to TCH-WL Hematology Clinic were screened. The patients were given the PHQ-A by the Medical Assistant/nurse prior to the start of the appointment and then they followed the outlined and detailed algorithm listed above based on score.Forty-five patients were eligible for screening. Forty-two percent (19/45) were given the PHQ-A; 73% endorsed mild risk of depression; 26% endorsed moderate to severe risk; 22% endorsed suicidal ideation. 80% of patients with moderate to severe risk received same day SW assessment; 100% of patients with suicidal ideation received same day SW assessment. Over the course of our project, we have been able to maintain our goals at TCH-WC and came close to achieving our goal of screening 50% of eligible patients for depression at TCH-WL. We are working with staff and providers at TCH-WL to determine barriers and optimize clinic flow in order to achieve >50% screening. In the future, we plan to expand our project to our largest sickle cell clinic, TCH-Medical Center, and for depression screening to become standard of care for all sickle cell patients at Texas Children's Hospital.

Catechol-O-methyltransferase gene (COMT) is associated with neurocognitive functioning in patients with sickle cell disease

PurposeNeurocognitive impairment is a common and debilitating complication of sickle cell disease (SCD) resulting from a combination of biological and environmental factors. The catechol-O-methyltransferase (COMT) gene modulates levels of dopamine availability in the prefrontal cortex. COMT has repeatedly been implicated in the perception of pain stimuli and frequency of pain crises in patients with SCD and is known to be associated with neurocognitive functioning in the general population. The current study aimed to examine the associations of genetic variants in COMT and neurocognitive functioning in patients with SCD. Patients and MethodsThe Sickle Cell Clinical Research and Intervention Program (SCCRIP) longitudinal cohort was used as a discovery cohort (n = 166). The genotypes for 5 SNPs (rs6269, rs4633, rs4818, rs4680, and rs165599) in COMT were extracted from whole genome sequencing data and analyzed using a dominant model. A polygenic score for COMT (PGSCOMT) integrating these 5 SNPs was analyzed as a continuous variable. The Cooperative Study of Sickle Cell Disease (CSSCD, n = 156) and the Silent Cerebral Infarction Transfusion (SIT, n = 114) Trial were used as 2 independent replication cohorts. Due to previously reported sex differences, all analyses were conducted separately in males and females. The Benjamini and Hochberg approach was used to calculate false discovery rate adjusted p-value (q-value). ResultsIn SCCRIP, 1 out of 5 SNPs (rs165599) was associated with IQ at q<0.05 in males but not females, and 2 other SNPs (rs4633 and rs4680) were marginally associated with sustained attention at p<0.05 in males only but did not maintain at q<0.05. PGSCOMT was negatively associated with IQ and sustained attention at p<0.05 in males only. Using 3 cohorts’ data, 4 out of 5 SNPs (rs6269, rs4633, rs4680, rs165599) were associated with IQ (minimum q-value = 0.0036) at q<0.05 among male participants but not female participants. The PGSCOMT was negatively associated with IQ performance among males but not females across all cohorts. ConclusionSelect COMT SNPs are associated with neurocognitive abilities in males with SCD. By identifying genetic predictors of neurocognitive performance in SCD, it may be possible to risk-stratify patients from a young age to guide implementation of early interventions.

Improving Treatment Adherence in Patients with Sickle Cell Disease

BACKGROUND: Crizanlizumab is approved for treatment of sickle cell disease (SCD) patients with frequent pain crises and hospital admissions. Here, we address systemic factors that have led to sub-optimal adherence to monthly crizanlizumab infusions at our institution. Due to 340B status limitation, the drug was originally offered at a site affiliated to our hospital with little SCD team presence. In 2020, UW hospital (primary site of SCD care) acquired 340B status, but transferring crizanlizumab infusions to UW hospital was not prioritized. In 2022, our institution's crizanlizumab adherence was 22% 1. Patients receiving crizanlizumab were interviewed to identify adherence barriers. Top barriers included location (44%), scheduling (44%), and low knowledge about the medication (67%). A detailed analysis with SCD team input revealed barriers such as restriction on opioids for day treatment, scheduling delays after hospital admissions, onerous paper orders process, different EMRs, and poor communication/coordination between sites (Fig 1). METHODS: The hospital leadership was appraised of these barriers in a series of meetings by the SCD team and approval to administer crizanlizumab at UW hospital infusion center was granted. UW health pharmacy and infusion staff planned a transition phase with 5 patients transitioned each month between March-April 2023. Crizanlizumab orders were updated in the EMR, and infusion nursing staff received training about the drug. Smart phrases were created for patient education in after visit summaries (AVS). Day treatment with IV fluids and pain management was offered with infusions. SCD care coordinator and social worker helped with scheduling, transport, and childcare. Providers aimed to discuss treatment goals and pros/cons during visits. Goal was set to assess adherence at months 3 and 12 after implementation. Average rate of adherence was defined as percent of prescribed treatments taken by the patient over a specified time period. In case of hospitalization, adherence was defined as rescheduling and receiving the treatment. We aimed to improve adherence to 50% at 3 months and 75% at 12 months if crizanlizumab FDA approval is maintained. RESULTS: By mid-July 2023, 11 patients were transitioned to UW Hospital for crizanlizumab infusions. 10/11 patients received the drug during this period (1 patient taken off due to pregnancy). The average adherence rate increased from 22% to 71% at 3 months, exceeding the original goal. 5/10 patients had an adherence rate of 75% or more. Additionally, 70% received at least one visit from the SCD social worker (SW) during treatment and 70% saw their provider concurrently with at least one visit. All patients received day treatment with supportive IVFs and/or pain medications during the infusion visit (Fig. 2). Only 2/10 patients had 25% or less adherence which occurred due to scheduling errors that will be addressed moving forward. DISCUSSION: Our study aims to address both intentional and unintentional barriers to crizanlizumab adherence that included infusion location, scheduling, and patient education. Our team advocated for the transition of infusions to the main hospital where they receive all other SCD care. This provided patients with direct access to their SCD team during infusions. Care coordinator and social work involvement helped consolidate treatment-related orders to one EMR, standardize nursing and patient education, organize scheduling, and address social barriers. The adherence rate increased from 22% to 71% at 3 months after implementation. Although the current approval of crizanlizumab is under review, we believe the barriers addressed in this project can be extended to current SCD treatments and upcoming novel therapies. Splitting care sites due to insurance and logistical reasons can create barriers for this vulnerable population due to complex care coordination and psychosocial needs. The rapid improvement in crizanlizumab adherence displayed here is a testament to the impact of having a dedicated SCD team at one leading site to advocate for and address the unique barriers to healthcare experienced by people with SCD. Sources 1. Nixon G, Fallon M, Fulcer K, Curran W, Nazeef M, Pradhan R. How can infusion therapy adherence by improved in Sickle Cell Disease. American Society of Health-System Pharmacists; Dec. 2022. Las Vegas, NV.

Echocardiographic Evaluation in Paediatric Sickle Cell Disease Patients: A Pilot Study

Cardiovascular involvement has a great impact on morbidity and mortality in sickle cell disease (SCD). Currently, few studies are available regarding the paediatric setting and, moreover, current guidelines for the echocardiogram screening program in the asymptomatic paediatric population are controversial. We performed a retrospective observational monocentric study on 64 SCD patients (37 male and 27 female, median age 10) at the Bambino Gesù Childrens' Hospital, who had undergone a routine transthoracic echocardiogram. In total, 46 (72%) patients had at least one cardiac abnormality. Left atrial dilatation (LAD) was present in 41 (65%) patients and left ventricular hypertrophy (LVH) was found in 29 (45%) patients. Patients with LAD showed lower median haemoglobin levels (p = 0.009), and a higher absolute reticulocyte count (p = 0.04). LVH was negatively correlated with the median haemoglobin value (p = 0.006) and positively with the reticulocyte count (p = 0.03). Moreover, we found that patients with cardiac anomalies had higher transfusion needs and a lower frequency of pain crises. In our setting, cardiac involvement has a high prevalence in the paediatric cohort and seems to be associated with specific laboratory findings, and with a specific clinical phenotype characterized by complications related to high haemodynamic load.

Breaking Down Barriers and Addressing Mental Wellness in Pediatric Sickle Cell Patients

Sickle cell disease is an inherited hemoglobinopathy that is characterized with multi-organ involvement and frequent pain crises. Over the last two decades, a growing body of clinical evidence has pointed out that these somatic complaints can give rise to neuropsychiatric disorders, among which anxiety and depression are the most common, that worsen the health-related quality of life of these patients. Mood disorders can in turn increase fatigue and pain through a psychosomatic component. Although mental health is deemed to play an important role in their health outcomes, at this time, we don't have standardized approach to screening sickle cell patients for depression at most sickle cell centers across the country and at Texas Children's Hospital(TCH). The objective of this Quality Improvement (QI) study is to increase the annual depression screening rate from 0 to 50% in English/Spanish speaking patients who are 12 years and older with an established diagnosis of Sickle Cell Disease (SCD) who present for follow-up care to the Texas Children's Hospital - West Campus (TCH-WC). Our QI project consisted of three distinct PDSA cycles. Prior to the start of the first PDSA cycle, we did not have a streamlined approach for depression screening. The physician team would verbally screen for depression and Social Work was consulted as needed. During our first PDSA cycle, a clinical psychologist was integrated into our monthly Hematology-Pulmonary Joint Clinic and all patients with SCD who presented to Joint Clinic were assessed for depression by the psychologist as part of the psychological evaluation. During the second PDSA cycle, all patients with SCD over the age of 12 who presented to Joint Clinic (with psychologist present) were given the Patient Health Questionnaire-9 modified for Adolescents (PHQ-A) by the Medical Assistant prior to the start of the medical appointment. After the physician team completed their visit, the psychologist addressed concerns raised on the PHQ-A, completed the psychological evaluation and provided appropriate intervention. During the third and final PDSA cycle, the PHQ-A was given to all patients with SCD above the age of 12 who presented to hematology clinic (including those outside of Joint Clinic during which the psychologist was not present). During this cycle, the MA gave the patient the PHQ-A at the start of the visit. The MA then followed an outlined and detailed algorithm. If patient scored 0-6 on the PHQ-A, no intervention was performed. If patient scored 7-9 on the PHQ-A, psychological resources were provided via handout. If patient scored > 10 on the PHQ-A, Social Work referral was placed and patient was preferably seen same day. If patient screened positive for suicide, an urgent Social Work referral was made and patient was seen same day prior to leaving clinic for further evaluation. During our first PDSA cycle, 19 patients above the age of 12 presented to Joint Clinic. Seventeen patients were seen by the psychologist. Twenty-four percent (4/17) of patients were given the PHQ-A; 50% of patients screened positive. Twenty-four percent (4/17) of patients were referred for outpatient follow-up with psychology. During our second PDSA cycle, 14 patients above the age of 12 presented to Joint Clinic. Ninety-three percent (13/14) of patients were given the PHQ-A; 7% (1/14) of patients screened positive for depression. Twenty-one percent (3/14) of patients were referred for outpatient follow-up with psychology. During our third PDSA cycle, 54 patients above the age of 12 presented to Hematology Clinic. Eighty percent (43/54) of eligible patients were given the PHQ-A. Fourteen percent of patients endorsed mild symptoms of depression; 23% of patients endorsed moderate to severe symptoms of depression; 23% of patients endorsed suicidal ideation. Eighty percent of patients with moderate to severe depression received same day Social Work Assessment. One hundred percent of patients with suicidal ideation received same day Social Work assessment. During the first three PDSA's cycle of our project, we achieved our goal of screening greater than 50% of eligible patients with SCD and providing same day intervention. In the future, we will need to examine if there are any downstream effects that negatively impact the clinic flow while administering the questionnaire. We also hope to expand screening for all patients with SCD over the age of 12 across Texas Children's Hospital campuses.

Red Blood Cell Utilization Among Patients with Sickle Cell Disease: A Single Center Experience

Introduction: Red blood cell (RBC) transfusion remains a mainstay of treatment for both acute and chronic complications of sickle cell disease (SCD). RBC transfusions improve oxygen-carrying capacity of blood, decrease hemoglobin S levels, and are indicated for the treatment of complications such as stroke, acute chest syndrome, sickle cell hepatopathy and multiorgan failure syndrome. RBC transfusions may also be considered to reduce the frequency of pain crises for those intolerant or non-responsive to hydroxyurea. Prior practice surveys havedemonstrated significant practice variation in the management of patients with SCD with respect to RBC transfusions. The utilization of both simple RBC transfusions and red cell exchange (RCE) is poorly described, and unknown in the Canadian context, including at our center. The objective of this study is to describe RBC utilization at our center in a cohort of patients with SCD. Methods: All adult patients with SCD who have received care [inpatient, outpatient, or emergency department (ED)] at the Ottawa Hospital, from January 2006 to May 2019 were identified for study inclusion. Transfusion and health care utilization data was obtained through to December 2021 from clinical, administrative and laboratory databases at the Ottawa Hospital. Results: A total of 273 patients with SCD were identified. The median age for the cohort was 25 years (IQR 19,33) at first visit, with females comprising 53.9% of the cohort. The median duration of follow-up was 8.1 years (IQR 5,12.4). O-positive was the most frequent blood type (41.8%), and 8 (2.9%) individuals were O-negative. The annual RBC and health care utilization for the study cohort is depicted in Figure 1. The total number of hospital visits during the study period was 23127, with a median of 45 visits (IQR 18,100) per patient. 165 patients (60.4%) received 22538 RBC units with a median of 2 units (IQR 1,19) per patient, per year. 86.5% of the RBC units were infused in the outpatient setting, 12.1% in the inpatient setting and 0.8% in the ED. 40.3% of inpatient hospital visits were associated with an RBC transfusion event, compared to 2.4% of ED encounters. The proportion of RBC units transfused that were O-negative was 29.1% (6557 units). 147 patients received 2205 (9.7%) as simple RBC transfusions. The median number of simple RBC units transfused per patient, per year was 1 unit (IQR 1,2). 88 patients received 20333 RBC units during 2702 RCE sessions (median of 14.5 RCE sessions per patient), with 91.5% occurring in the outpatient setting. Of the 88 patients who received RCE, 64 patients (72.7%) had more than one RCE session, 54 patients (61.4%) had more than 5 RCE sessions and 48 patients (54.5%) had more than 10 RCE sessions. The median number of RBC units transfused per RCE session was 7 (IQR 6,9), with a median duration of 30 days (IQR 28,40) between RCE sessions. Conclusions: RBC transfusion was common in our cohort, with the majority of patients having received at least one RBC transfusion. The largest proportion of transfused RBC units stem from RCE use, which represents a small proportion of on our SCD cohort. O-negative units represented a large proportion of units transfused, despite the predominance of non-group O patients, likely due to both differences in donor and patient blood group phenotypes, and recommendations for extended phenotype matching. With pressure on transfusion medicine to provide appropriately matched units and the scarcity of O-negative units, further data accrual on RBC utilization, particularly assessment of indications, requirements for matching, and review of RCE procedures will define further quality improvement interventions to ensure optimal utilization of RBCs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Self-Management in Children with Sickle Cell Anaemia in Enugu, Nigeria

Sickle cell anaemi (SCA) is a chronic, genetic disorder of haemoglobin structure resulting from inheritance of two abnormal ‘S’ globin genes. It is a disease characterized by episodic exacerbation (crises) of chronic low-grade haemolysis and vaso-occlusion and complicated by multiple infarcts of organ-systems which impair quality of life. Most crises occur and are managed at home. The frequency of pain crises and resulting hospitalizations may therefore increase without appropriate self-care at home. Self-care include therapeutic activities (self-action) that prevent complications, aid coping, improve psychosocial and health status as well as the individual’s perceived ability (self-ability) to perform these activities. An effective self-care plan requires an initial recommendation by a health care practitioner and is pivotal in the successful management of SCA in resource limited setting where secondary prevention strategies prevail. However, self‐care recommendations in SCA are limited, inconsistent and poorly complied to. The study aims to examine the self-care patterns and practices of Paediatric SCA patients in a tertiary hospital.

Clinical Evaluation of T-AYU-HM Premium in Sickle cell Anemia Patients: A Retrospective Study

Background: The orphan status of sickle cell invites many researchers toward drug development in the past decade. A substantial number of clinical trials either understudies or in the planning stage focused on sickle cell disease. Sickle cell traits are often considered asymptomatic and the silent condition is associated with diverse complications. &#x0D; Objective: To clinically evaluate the safety and effectiveness of T-AYU-HM Premium Tablets (300mg) in sickle cell anemia patients: an observational retrospective study&#x0D; Methodology: This is a single-arm case-control retrospective study of sickle cell trait patients admitted to Dhanvantari Clinic from 2018 to 2020. Patients' vital and clinical information based on inclusion and exclusion criteria were collected and analyzed using SPSS software.&#x0D; Result: A total of 100 patients with sickle cell traits were included in the study. The treatment exhibited significant improvement was seen in (P&lt;0.05) in hemoglobin and red blood corpuscles. There wasn’t any untoward response either from the patient or from laboratory parameters reported indicating no adverse effects were seen. There was an absolute improvement in overall health as a reduction of no of time hospitalization (0) and blood transfusion (0) in sickle cell trait patients. There was a significant improvement in minor and major clinical parameters of sickle cell trait patients.&#x0D; Conclusion: The effect of T-AYU-HM Premium treatment in sickle cell trait patients suggests it is safe and effective. There was no adverse effect observed in the observational study. During entire study period, no single blood transfusion or hospitalization required. The significant improvement in the rate and frequency of painful crises indicates an improvement in pain-related quality of life in patients. This treatment of T-AYU-HM Premium was safe, cost-effective, and exhibit therapeutic potential in the management of sickle cell trait patients

Inhaled nitric oxide for treating pain crises in people with sickle cell disease.

Inhaled nitric oxide for treating pain crises in people with sickle cell disease.

P1504: AN AUDIT OF PAIN EDUCATION IN PATIENTS WITH SICKLE CELL DISEASE

Background: Pain crises represent the primary reason for hospital care-seeking in individuals with sickle cell disease (SCD). The NICE guideline CG143 emphasises that patient should be treated as experts in the pain management of their sickle cell disease. Aims: To assess the performance of acute sickle cell pain crisis management at Cambridge University Hospital (CUH) and assess methods of secondary prevention of admission for pain crisis through patient pain education. Methods: Patient admission records during the year of 2021 were reviewed for a population of 85 SCD patients registered at Cambridge University Hospital (CUH). For these encounters, patient assessment at presentation, primary analgesia and ongoing management were audited against CG143 standards. All SCD patients registered with CUH were contacted for a telephone interview to discuss home pain management. Results: In a population of 85 patients living with SCD, there were 22 admissions in 17 patients during 2021, of which 5 patients had multiple admissions. Auditing CUH performance against the NICE CG143 guidelines, it was found that initial pain relief was provided within 30 minutes of presentation in 15 out of the 21 relevant admissions (71%). However, none of the patients had documented discussion of pain control education, any psychological support they may need nor were encouraged to use their own coping mechanisms for dealing with acute pain in their hospital notes. Following on from this, we conducted telephone interviews and received a total of 51 responses of which 13 patients were admitted to hospital with sickle cell pain in 2021. In the 46 patients who experience sickle cell pain crises, 20 had strong opiates, 27 had weak opiates, and all 46 had a supply of paracetamol/non-steroidal anti-inflammatory drugs (NSAIDs). 8/20 (40%) patients with a home supply of strong opiates were admitted to CUH with an acute sickle cell pain crisis in 2021 compared to 5/26(19.2%) in those who did not have strong opiates at home. Notably, only 6/46 patients were familiar with the World Health Organisation pain ladder. 2 of 6 patients who were aware of the WHO pain ladder had an admission to CUH in 2021, while 11 of 40 patients who were not aware had an admission to CUH in 2021. The findings are summarised in Table 1. Image:Summary/Conclusion: Our audit has demonstrated a significant gap in the management of acute sickle cell pain crises at CUH with the absence of patient pain education. This may have contributed to the number of admissions of SCD patients to CUH. The limited patient knowledge of optimal use of pain control in line with WHO pain ladder is significant, given that most episodes are managed at home. Frequent painful crises are associated with psychological issues and poor engagement in normal daily activities. Better home pain control should be a future priority for our service.

28-Year-Old Man With Joint Pain

28-Year-Old Man With Joint Pain

Pediatric Hydroxyurea Treatment Patterns, Sickle Cell Disease-Related Complication Rates, and Costs in a Large US Administrative Claims Database: A Retrospective Analysis

Introduction: Sickle cell disease (SCD) is an inherited blood disorder and hydroxyurea (HU) is the only pharmaceutical treatment approved for pediatric patients aged 9 months and older. In 2014, the National Heart, Lung, and Blood Institute (NHLBI) recommended that infants, children, and adolescents be offered treatment with HU regardless of disease severity to reduce SCD-related complications, such as pain and anemia. In 2017, the FDA approved HU in pediatric patients aged 2 and older to reduce the frequency of painful crises and the need for blood transfusions. This study aimed to describe SCD treatment patterns, SCD-related complications rates, and health care resource utilization and costs in pediatric patients with SCD using HU to identify gaps in care.Methods: This retrospective analysis of a large US commercial claims database included health plan enrollees aged 0-17 years old with 1+ SCD diagnosis code from July 1, 2013-March 31, 2020 (study period) and 1+ HU pharmacy claim from January 1, 2014-September 30, 2019 (identification period) in the Optum Research Database. Index date was defined as the first date with a HU claim. Patients were continuously enrolled for 6 months before (baseline period) and 6+ months after the index date (fixed 6-month and variable follow-up periods) and excluded if they had evidence of clinical trial participation or pregnancy amongst females. Demographics and the top five Agency for Healthcare Research and Quality (AHRQ) comorbidities were captured during baseline. Fixed 6-month follow-up treatment patterns included use of HU, short-acting opioids, and red blood cell transfusions. Follow-up rates of priapism among males, acute kidney injury (AKI), chronic kidney disease (CKD), stroke, and transient ischemic attack (TIA) per 1,000 person-years (PY), excluding those with baseline evidence, were calculated. Fixed 6-month follow-up all-cause health care resource utilization included ambulatory, emergency department (ED), and inpatient hospitalizations. Total all-cause health care costs included health plan- and patient-paid amounts and were calculated as per-patient-per-month (PPPM) to account for the variable follow-up period.Results: 160 pediatric patients met the selection criteria (mean [SD] age: 10 [4.5] years, 58.1% male, 53.13% HB-SS). Mean (SD) follow-up was 2.7 (1.7) years. Top five 6-month baseline AHRQ comorbidities were anemia: 154 (96.3%); respiratory infections: 65 (40.6%); asthma: 40 (25.0%); heart disease: 37 (23.1%), and other gastrointestinal disease 34 (21.3%). Nearly a third (32.5%) had baseline HU use and 74 (46.2%) continued HU use for 6+ months. Among 86 (53.8%) with < 6 months of HU use, 34 (39.5%) never restarted HU during the fixed 6-month follow-up period. Short-acting opioid use was observed in 65 (40.6%) of pediatric patients, with a median of 2 fills, and 25 (15.6%) had at least one red blood cell transfusion during the fixed 6-month follow-up period. SCD-complication rates per 1,000 PY for priapism among males, AKI, CKD, stroke and TIA were 16.4, 2.3, 11.9, 19.7, and 4.7, respectively. SCD-complication rates by age groups are shown in Table 1. In the first 6 months of HU treatment, 154 (96.3%), 59 (36.9%), and 37 (23.1%) had at least one ambulatory, ED, and inpatient hospitalization, respectively. Mean (SD) total all-cause health care costs in the first 6 months of HU treatment were $24,446 ($108,930), driven primarily by inpatient hospitalizations $17,467 ($103,639). Mean (SD) total PPPM costs in total follow-up were $2,703 ($5,028), attributed mostly to medical care $2,511 ($4,866).Conclusions: Despite a recommendation for HU use in pediatric patients with SCD, less than half of this large commercial claims study cohort had consistent HU use. Pediatric patients with recent or current HU use were noted to have SCD-related complications. Among patients with SCD less than 18 years old, health care costs were high. Notably, short acting opioid use and blood transfusions typically prescribed to alleviate pain and treat SCD-related complications were observed, demonstrating significant burden of disease. Alternative or concomitant SCD treatments for the pediatric population could potentially reduce SCD-related complications and associated health care costs when HU use alone may not be sufficient. [Display omitted] DisclosuresManwani: Novartis: Consultancy. Paulose: Novartis Pharmaceuticals Corporation: Current Employment. Yen: Novartis Pharmaceuticals: Current Employment; Merck & Co., Inc.: Current holder of stock options in a privately-held company, Ended employment in the past 24 months. Lee: Novartis Pharmaceuticals Corporation: Current Employment. Saraf: Pfizer: Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Genetic modifiers of fetal hemoglobin affect the course of sickle cell disease in patients treated with hydroxyurea.

The course of sickle cell disease (SCD) is modified by polymorphisms boosting fetal hemoglobin (HbF) synthesis. However, it has remained an open question how these polymorphisms affect patients who are treated with the HbF-inducing drug hydroxyurea/ hydroxycarbamide. The German SCD registry offers the opportunity to answer this question, because >90% of patients are treated according to national guidelines recommending the use of hydroxyurea in all patients above 2 years of age. We analyzed the modifying effect of HbF-related genetic polymorphisms in 417 patients with homozygous SCD >2 years old who received hydroxyurea. HbF levels were correlated with higher total hemoglobin levels, lower rates of hemolysis, a lower frequency of painful crises and of red blood cell transfusions. The minor alleles of the polymorphisms in the γ-globin promoter (rs7482144), BCL11A (rs1427407) and HMIP (rs66650371) were strongly associated with increased HbF levels. However, these associations did not translate into lower frequencies of vaso-occlusive events which did not differ between patients either carrying or not carrying the HMIP and BCL11A polymorphisms. Patients on hydroxyurea carrying the γ-globin promoter polymorphism demonstrated substantially higher hemoglobin levels (P<10-4) but also higher frequencies of painful crises and hospitalizations (P<0.01) when compared to patients without this polymorphism. Taken together, these data indicate that the γ-globin, HMIP and BCL11A polymorphisms correlate with increased HbF in SCD patients on hydroxyurea. While HbF is negatively correlated with the frequency of painful crises and hospitalizations, this was not observed for the presence of known HbF-boosting alleles.

Effectiveness of Hydroxyurea in the Management of the Painful Crisis in Sickle Cell Anemia

Background: Sickle cell syndromes are inbred disorders distinguished by the presence of blade (Sickle) hemoglobin in red blood corpuscles. The sickling of red cells in patients with SCA is caused by the polymerization of molecules of non-oxygenated hemoglobin S (α2ß2s) into rigid rod-like polymers. In the open-label study of hydroxyurea therapy, the synthesis of embryo hemoglobin increased in most patients with SCA resulting in a humane myelotoxicity and rise in painful crises. By suppressing the sickling process, increased levels of embryo hemoglobin sinew the less frequency of painful crises.

Alteration of grey matter volume is associated with pain and quality of life in children with sickle cell disease

Pain is the most common symptom experienced by patients with sickle cell disease (SCD) and is associated with poor quality of life. We investigated the association between grey matter volume (GMV) and the frequency of pain crises in the preceding 12 months and SCD-specific quality of life (QOL) assessed by the PedsQLTM SCD module in 38 pediatric patients with SCD. Using voxel-based morphometry methodology, high-resolution T1 structural scans were preprocessed using SPM and further analyzed in SPSS. The whole brain multiple regression analysis identified that perigenual anterior cingulate cortex (ACC) GMV was negatively associated with the frequency of pain crises (r=-0.656, P=0.003). A two-group t-test analysis showed that the subgroup having pain crisis/crises in the past year also showed significantly lower GMV at left supratemporal gyrus than the group without any pain crisis (p=0.024). The further 21 pain-related regions of interest (ROI) analyses identified a negative correlation between pregenual ACC (r=-0.551, P=0.001), subgenual ACC (r=-0.540, P=0.001) and the frequency of pain crises. Additionally, the subgroup with poorer QOL displayed significantly reduced GMV in the parahippocampus (left: P=0.047; right: P=0.024). The correlations between the cerebral structural alterations and the accentuated pain experience and QOL suggests a possible role of central mechanisms in SCD pain.