Pregnancy Outcomes in Women with Sickle Cell Disease in Ireland: A Retrospective Review

Background: Sickle cell disease (SCD) is one of the most common single gene disorders worldwide and is characterised by significant morbidity and early mortality.[1] Pregnancy in SCD is associated with an increased risk of maternal and foetal complications.[2,3] The 2011 RCOG and the 2021 BSH guidelines[5,6] on the management of pregnancy in SCD have provided the basis for best practice care in the UK over the past decade and is the guidance which we follow in Ireland. To date, there is no published data on outcomes for pregnant women with SCD in Ireland. The number of Irish patients with SCD has risen over the past 20 years. Without a national database, the exact prevalence is not known but currently there are at least 600 adults and children with SCD in Ireland, whose population is just over 5 million.[4] Aims: Our study assesses outcomes of pregnant patients with SCD from 2015 to 2022. Our aims were to: * Assess adherence to current guidelines * Assess pregnancy outcomes and maternal complications * Assess transfusion rates amongst our patient cohort. Method(s): This is a retrospective cohort study. We do not have a directly matched cohort, but have compared our findings to published data on Irish pregnancy outcomes from the Irish Maternity Indicator System National Report and have correlated our findings with studies of women with SCD who were managed in UK centres.[8,9,10] Results: We reviewed outcomes of 29 pregnancies in 19 women over a 7-year period. The median age was 29 (range 20-41) and the predominant maternal sickle genotype was HbSS (65.5%). Before conception, 55.2% of cases had pre-existing complications of SCD, including acute chest syndrome (ACS), pulmonary hypertension (PHTN) and prior stroke. In accordance with current guidelines, 100% of women (n=29) were prescribed folic acid, penicillin, and aspirin prophylaxis. 51.7% (n=15) of women had documented maternal complications during pregnancy, including ACS (34%), vaso-occlusive crisis (34%), gestational diabetes (10%), VTE (3%) and UTI (3%). Two women (7%) developed Covid-19 pneumonitis despite vaccination. There was one case of maternal bacteraemia (3%). 65.5% of cases (n=19) required blood transfusion during pregnancy. One woman was already on a blood transfusion programme for disease modification prior to pregnancy. In 6 cases (20.6%), a transfusion programme was commenced during pregnancy due to prior pregnancy complications or intrauterine growth restriction. During pregnancy, 27.6% (n=8) of women required emergency red cell exchange for ACS. Prior studies have suggested that between 30% and 70% of pregnant women with SCD require at least one blood transfusion during pregnancy.[8,9,10] By comparison, only 2.6% of the Irish general obstetric population required transfusion during pregnancy.[7] 20.6% (n=6) of births were preterm at <37 weeks' gestation. There was one live preterm birth (3%) at <34 weeks and one intrauterine death (3%) at 23 weeks' gestation. Similar to UK data[9], 31% of women required critical care stay (n=9) during pregnancy, in comparison with 1.44% nationwide in 2020.[7] Conclusion(s): It is well established that pregnancy in SCD is high risk, and despite adherence to current guidelines, we have shown very high rates of critical care admission, significant transfusion requirement and hospital admissions. Our findings are comparable to published UK outcomes and they further support the need for a comprehensive specialist care setting for this patient cohort.

Vaccination status of the adult sickle cell anaemia population: The South Wales experience

The Sickle Cell Society have issued standards for additional immunisations that adults with sickle cell disease (SCD) require. These include annual influenza, 5-yearly pneumococcal conjugate vaccine (PPV23) and Hepatitis B vaccination. Patients who have not received their primary vaccination as part of the national schedule in the UK should also receive further additional vaccines. We reviewed whether adults with SCD in South Wales currently receive these. 49 adult patients were identified as having SCD under the care of the Hereditary Anaemia Service based in the University Hospital of Wales, Cardiff. GP records were not available for 5 patients leaving a final cohort of 44 patients to analyse. Average age was 33 years (range 17-67). Median age was 27 with the cohort predominantly lying in the 17-29 year category (52%). Results showed good compliance with the annual influenza vaccine in those over 40 (>80%). However, compliance for the 17-29 category and 30-39 categories were 37.5% and 42.8%, respectively. The improved compliance in those >40 was not seen with the 5-yearly pneumococcal vaccine. Compliance was worse in all age groups compared to the annual flu vaccine with only 23% compliance overall. However, when looking at those who had received a single dose of PPV23, the numbers improved to nearly 60%. Compliance with the SARS-CoV2 vaccination was highest at 61.3%. However, rates were lower in the 17-29 and 30-39 age groups in keeping with previous trends. Only 34.1% of patients had full hepatitis B cover. Again, trends in compliance mirrored previous with poorer rates in those under 40. Assessing compliance for the remainder of the standards was more challenging given that we could not confirm retrospectively how many of our cohort had received their primary vaccinations in other parts of the UK, thought to be around half. However, most of the cohort had not received any additional vaccines suggesting high non-compliance regardless. This review looked at data from 2020 and likely reflects the impact of the SARS-CoV2, whether positive or negative. The reduced compliance in 5-yearly pneumococcal compared to flu suggest better health-professional education is needed;if patients are attending for their annual flu vaccine, there is ample opportunity to administer other vaccines. The vaccination rate for our patient group is comparable to national rates by ethnicity although lower than the national average for age. Vaccination rates for the SCD population of South Wales are not adequate. Better education and engagement is needed.

Age, race/Hispanic origin, and COVID-19 mortality among sickle cell disease patients in the United States

The COVID-19 pandemic remains a global health challenge, with 6.7 million deaths worldwide as of January 2023. It has illuminated the health iniquities in underserved communities and populations like those with sickle cell disease (SCD). Researchers have associated the COVID-19 outcome among SCD patients in other regions of the globe. The purpose of this retrospective cross-sectional observational study was to investigate the relationship between age, race/Hispanic origin, and COVID-19 mortality among persons with SCD in the United States from January 2020 to March 2021. The Krieger ecosocial theory of disease distribution framed the study. Data were drawn from an existing Centers for Disease Control and Prevention provisional SCD death data set (N = 140). The binary logistic regression analysis result showed a statistically significant relationship between age and race/Hispanic origin and COVID-19 mortality. The variability between ages was 42.9%;race/Hispanic origin was 29.9%;and age and race/Hispanic origin were the highest, with 62.4% dying from COVID-19. Non-Hispanic Black patients were 9.6 times more likely to die overall but those aged 60+ were 17.5 times more likely to die from COVID-19 than the reference groups (0-19-year-old and other race). This study can benefit the research community, public health workers, medical professionals, and policymakers to understand better and influence policy on developing and prioritizing age- and race-tailored preventive protocols and medical care. They may minimize pain and suffering while mitigating mortality from COVID-19 and other unforeseen future pandemics within the SCD community at home and abroad and positively effect social change. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

The Evolution of the Covid-19 Pandemic in Pediatric Patients with Sickle Cell Disease: From Alpha to Omicron

Background: Approximately two years ago, COVID-19 was declared a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and through genomic surveillance, we have seen the emergence of variants of SARS-CoV-2. In the United States, over 78 million cases and >900,000 deaths attributable to COVID-19 have been reported. SCD was identified as a risk factor for severe COVID-19 disease in adults and pediatric patients. The emergence of novel SARs- CoV-2 variants has led to challenges in diagnosis, treatment, and prediction of long-term sequelae in individuals with SCD and COVID-19. Aim(s): We compare the overall seasonal variation of COVID-19 variants and patterns of healthcare utilization and clinical presentation over time in pediatric patients with SCD and COVID-19 at Children's National Hospital (CNH). Method(s): Our single-center, observational cohort study included 193 pediatric patients with SCD (0-21 years) with PCR-confirmed SARSCoV- 2 infection between March 31, 2020, and January 31, 2022. Per the SECURE SCD Registry definitions, clinical severity was classified as asymptomatic, mild, moderate, and severe. Result(s): A total of 193 unique patients with SCD and positive SARS-CoV-2 PCRs between March 2020-January 2022 were included in our registry. Most patients were female (51.8%), and the mean age was 11.2 years (SD 6.5 years). Most of the cohort resides in Maryland (N=135), and HbSS was the dominant genotype (69.4%). During the alpha dominant variant of the COVID-19 pandemic (March 2020- June 2021) there were 70 cases, followed by 40 cases during the Delta variant (July 2021- December 19, 2021), and 83 cases during the Omicron variant dominance (from December 20, 2021-January 31,2022). There were 149 patients (77%) that presented to the emergency department (ED) or were hospitalized. There were a total of 80 hospitalizations (41.5%), and a relative comparison showed that the percentage of hospitalizations was highest during the delta wave (47.5%) and lowest during the omicron wave (36.1%) (p= 0.407). ED-only utilization was highest in the era of omicron (43.4%, N=36), followed by delta (32.5%, N=13), and then alpha (30%, N=21)(p=0.197). The most common SCD-related complication was vaso-occlusive (VOC) pain (33%, N=64) which accounted for half of all hospital admissions (51%, N=41 of 80). Acute chest syndrome (ACS) was reported in 40% (N=32) of admitted patients and was highest in the alpha era (54.8%, N=17). The use of blood transfusion therapy was highest in the alpha (N=17) and delta (N=14) variants, while Remdesivir use was highest in omicron (N=15). A total of 6 patients received monoclonal antibodies (Delta, N=4;omicron, N=2). Throughout all the variants, there was a significant difference in COVID-19 clinical severity (p>0.005). Of the patients classified as asymptomatic (13%, N=25), seventy-two percent (n=18) were diagnosed during the alpha variant. Mild severity was the most prevalent (69%, N=134), with the omicron variant having the highest cases (51.5%, N=69). Severe cases were observed in all variants (6.7%, N=13) but were most prevalent during the alpha variant (46.2%, N=6). Summary - Conclusion(s): Interestingly, while the relative percentage of hospitalizations was lowest during the omicron wave, it saw the highest percentages of ER utilization. Overall, COVID-19 remains mild in pediatric patients with SCD, and notably, there was higher health care utilization in the omicron era.

Social Determinants of Health and Their Impact on Families of Children with Sickle Cell Disease during Covid-19 Pandemic

Background: According to national prevalence data, SCD has an estimated economic burden of $2.98 billion per year in the United States and caring for a child with sickle cell disease (SCD) carries its own financial burden, resulting in higher healthcare costs and unintended days lost from employment. Social experiences are known to impact health outcomes in the general pediatric population. These experiences can be examined through the construct of social determinants of health (SDOH), the "condition in which people are born, grow, work, live and age" that impact their health. Since the WHO has designated COVID-19 a pandemic in January 2020, many families in the US have suffered financially, and during the shutdowns, there was a record number of jobs lost. The objective of this study was to determine the impact of the COVID-19 pandemic on financial and employment status of SCD Families Methods: This study was part of the larger CNH Sickle Cell Disease Social Determinants of Health study that was IRB approved. Caregivers of children with SCD completed a 30-question survey reporting their experiences with SDOH that included Demographics, USDA Food Security Scale, the We Care housing screening tool, and the validated COVID-19 Employment Status/COVID-19 related household finances survey in RedCap during clinic visits and hospitalizations Results: 99 caregivers of SCD patients responded to our survey (82.5% Female, 17.5% Male) (N=97). 93.9% identified as African-American, 3% identified as Hispanic or Latinx, 1% identified as "other". Of respondents, 66% were insured through on Medicaid and 33% had private insurance. Twenty-six percent endorsed food insecurity and 2724% relied on low-cost food. Thirty-one percent lived in an apartment, 67.768% lived in a home, 1% lived in shelter or transitional housing. Sixteen percent lived in subsidized or public housing. Thirty-seven (36.8%) percent reported at least once they were being unable to pay the mortgage or rent on time at least once, 9% (8.5%) reported living with other people because of financial difficulties, 55.2% reported their home not being heated, 7.2% reported being evicted from their home and 3.1% lived in an emergency shelter or transitional housing. 6.1% had an educational level of high school graduation or less, 42.2% were college graduates or completed additional post-graduate education (N=98). Two weeks prior to the pandemic, 61.5% worked full time, 13.5% worked part time, 6.3% were unemployed with only 2.1% working from home of the 96 caregivers who responded to this question. 15.5% (N=12 of 77) reported losing their job or were furloughed during the pandemic;34.4% (N=33 of 96) reporting at least one household member losing a job or a significant amount of income. Twenty-five percent (N=21 of 83) reported it was difficult to get work/school done because of the home environment. 36.4 % (N=35 of 96) reported household income was significantly less since February 2020. 53% (N=52 of 97) worried their household income has been or will be negatively impacted by the COVID-19 pandemic. Additionally, 48.9% (N=47 of 96) worried the value of their assets (housing, savings, other financial assets) has been or will be negatively impacted by COVID-19 and its effects. Since February 2020, 9.8% (N= 9 of 97) received unemployment insurance, 30.9% (N=29 of 94) received SNAP or food stamps, 16.5% (N= 15 of 91) received from the food pantry, 6.6% (N=6 of 90) applied for temp ass.

Celebrating the Sickle Cell Disease World Day on June 19th after Two Years of Pandemic: My Life with Scd, Patients' Perspective

Background: After two years of COVID in which activities were reduced due to the pandemic and each one's life was affected by restrictions and limitations, the Sickle Cell Disease (SCD) Association in Padova teamed up with the Sickle Cell Group at the Pediatric Hematology Oncology and Bone Marrow Transplant Unit to celebrate the Sickle Cell Disease world day by organizing an online meeting with children/youths and their families. Theme of the meeting was: "My Life with SCD: poems, pictures and writings express our view on disease and care". Aim(s): One of the goals of this meeting was to create an opportunity for individuals with SCD to meet and have a constructive discussion with each other about the disease and express their feelings after two years of pandemic. Method(s): One month before the meeting children, teenager and parents were asked to sharer with the organizing team any drawing, painting, poem, writing, that they felt could express their feelings or experience of the disease itself or how it affected their life, or their experience in the hospital. The materials received were organized in a power point presentation and At the meeting, families were able to see a PowerPoint presentation with the poems, drawings, writings. Each author had the choice to personally share their production or have it read out loud by a member of the team. Free time to comment or share experiences was given. Result(s): 20 children, teenagers and parents participated. Countries of origin (Nigeria, Ghana, Congo, Albania, Italy), religious background (catholic, muslim, no religion, other) were different as well as disease genotype (HbSS, HbSC, HbSBdegree), severity or treatment received (Hydroxyurea, transfusion, Hematopoietic stem cell transplantation -HSCT, none). Drawings and writings regarded experience with the disease (mechanism of action, admissions), feelings experienced (fear, hope, light at the end of the tunnel), aspirations (sports) and gratitude (to the social and medical team, to parents) (Figure 1). Surprisingly, families who had a child having undergone HSCT, reported on the need and importance to talk about this experience for years after the event and made a request of a support goup. Finally, all families underlined the need to meet again soon to discuss together issues related to personal experience with SCD, even via web. of discussion with each other and with the drepanocytosis group;and that throug the online telematics platform it is still possible to involve all families, listening and trying to comfort them on doubts and perplexities about the disease, In conclusion, it can be said that after two years of pandemic, in our setting, online meeting can help patients and families reconnect with each other and activities can be planned to aid experiences and feelings. Patients' associations and Health Care Teams can collaborate in this area.

Real-World effectiveness of voxelotor for the treatment of sickle cell disease

Introduction: Voxelotor is a first-in- class sickle haemoglobin polymerisation inhibitor that targets the pathophysiology of sickle cell disease (SCD). Studies have shown that voxelotor increases haemoglobin and reduces markers of haemolysis. Emerging evidence suggests that voxelotor may improve the clinical symptoms of SCD, lower vaso-occlusive crisis (VOC) rates, and reduce transfusion needs. Objective(s): To examine the real-world impact of voxelotor on transfusion, VOC, and hospitalisation rates among patients with SCD. Method(s): Medical and pharmacy claims data for patients >=4 years with SCD who started voxelotor between November 2019 and March 2022 were obtained from the Symphony Health database. Patients with >=1 year of data before the index date (date of first voxelotor claim) were included. Annualised study outcomes were calculated for patients with >=1 occurrence of the corresponding event in the 3-month preindex period. Outcomes from a 90-day lookback were reported for the total and paediatric (aged 4 to <18 years) populations. Result(s): Of 4023 eligible patients from the Symphony Health database included in the analysis, 596 were <18 years. Compared with the 3-month preindex period, significantly lower annualised rates of transfusions, VOCs, and hospitalizations, and lower annualised mean number of inpatient days, were observed in the total population and paediatric subgroup over the 3-month postindex period. For the total population, the annualised event rates declined by 50.6% for transfusions (n = 248), 23.1% for VOCs (n = 1368), 35.5% for VOC-related hospitalizations (n = 757), and 39.4% for all-cause hospitalizations (n = 928). The annualised mean number of inpatient days declined by 29.6% for VOC-related hospitalizations (n = 757) and by 22.9% for all-cause hospitalizations (n = 928). For paediatric patients, the annualised event rates declined by 79.6% for transfusions (n = 18), 42.4% for VOCs (n = 157), 56.8% for VOC-related hospitalizations (n = 81), and 51.5% for all-cause hospitalizations (n = 106). The annualised mean number of inpatient days declined by 54.1% for VOC-related hospitalizations (n = 81) and by 45.8% for all-cause hospitalizations (n = 106). Conclusion(s): Treatment with voxelotor may provide a clinical benefit to patients with SCD by reducing the frequencies of transfusions, VOCs, and hospitalizations and decreasing inpatient days. Greater reductions were observed in the paediatric subgroup, potentially due to the smaller sample size, historically greater treatment compliance in paediatric patients, or younger patients having accumulated fewer SCD-related complications, enabling a greater clinical response. Limitations include the study's non-randomized design, reliance on claims data, and changes in healthcare use during the COVID-19 pandemic confounding the data.

17th Annual Sickle Cell and Thalassaemia Conference

The proceedings contain 115 papers. The topics discussed include: clinical and genetic predictors of sickle cell nephropathy in Malawi;clinicohematological characteristics of iron deficiency anemia and hemoglobinopathies in Pakistan;an experience of non-hospital based laboratory;assessment of hematological parameters of petrol filling workers at petrol stations in Ethiopia: a comparative cross-sectional study;burden and risk factor to acute myocardial ischemia in children with sickle cell anemia;dyslipidemia in transfusion-dependent-thalassemia patients and its correlation with serum vitamin D level;impact of COVID-19 pandemic to pre-transfusion hemoglobin level and frequency of transfusion in transfusion-dependent thalassemia patients in Indonesia;retinopathy in Egyptian patients with sickle cell disease;and dietary pattern, socio-demographic characteristics and nutritional status of pregnant women attending Barau Dikko teaching hospital and the need to develop recommended dietary allowance and dietary reference intakes for sickle cell disease patients.

The Impact of Sickle Cell Disease on Academic Performance among Affected Students.

BACKGROUND: Sickle cell disease (SCD) is a genetic disease that is highly prevalent in Jazan Province, Saudi Arabia, and is mostly characterized by many complications such as vaso-occlusive crises (VOC), acute chest syndrome (ACS) and well-documented neurological complications. These complications may affect patients' academic performance. METHODS: An observational, cross-sectional, retrospective study was conducted in Jazan Province. General and demographic data were collected and questions about academic performance of students with SCD were answered. Both t-tests and chi-square tests, along with multiple logistic regression, were used for analysis. RESULTS: 982 participants were selected for this study with a mean age of 23 years (SD: 7). Most of the participants were female (64%). The number of participants with SCD was 339 (36%), of whom 42% were male. Students with SCD recorded lower grade point averages (GPA) and more absences compared to healthy participants. Further, about 60% of students with SCD thought they performed better than 40% of the participants without SCD during the COVID-19 pandemic when most of the educational activities were online. CONCLUSION: As has been previously reported, this study suggested that the academic performance of students with SCD is negatively affected compared to healthy individuals, and this is mostly due to complications associated with the disease. Further, students with SCD acknowledged better performance with online education, an option that should be considered to improve their academic performance. National studies on a larger population are required by health and education officials, and supportive online educational programs are warranted to enhance the academic performance of this population.

Enhanced IgG immune response to COVID-19 vaccination in patients with sickle cell disease.

Patients with sickle cell disease (SCD) are considered to be immunocompromised, yet data on the antibody response to SARS-CoV-2 vaccination in SCD is limited. We investigated anti-SARS-CoV-2 IgG titres and overall neutralizing activity in 201 adults with SCD and demographically matched non-SCD controls. Unexpectedly, patients with SCD generate a more robust and durable COVID-19 vaccine IgG response compared to matched controls, though the neutralizing activity remained similar across both cohorts. These findings suggest that patients with SCD achieve a similar antibody response following COVID-19 vaccination compared to the general population, with implications for optimal vaccination strategies for patients with SCD.

Outcomes of COVID-19 hospitalizations in patients with sickle cell disease: A nationwide analysis.

INTRODUCTION: There is a paucity of data on the outcomes of coronavirus disease 2019 (COVID-19) in patients with sickle cell disease (SCD) in the United States. We examined the outcomes of patients with COVID-19 and SCD. METHODS: We utilized the National Inpatient Sample (NIS) to identify the data of patients diagnosed with COVID-19 and SCD in 2020 using the International Classification of Disease, Tenth Revision codes. In-hospital outcomes (invasive mechanical ventilation and mortality) were compared between SCD and non-SCD groups. RESULTS: Of the 1 057 550 COVID-19 hospitalizations, 2870 (0.3%) had SCD. The median age of the SCD group was 42 (IQR: 31) vs. 66 (IQR: 23) in the non-SCD group (p < .0001). Patients with SCD were likely to be females (62.02% vs. 37.98%, p < .0001), Blacks (87.81% vs. 12.19%, p < .0001), and in the lowest income quartile (50.62% vs. 11.15%, p < .0001). There was no difference in the outcomes between the two groups. There were increased odds of invasive mechanical ventilation and in-hospital mortality in COVID-19 in Asians, Hispanics, Native Americans, and Blacks (except for in-hospital mortality) compared to Whites. CONCLUSION: In-hospital mortality and invasive mechanical ventilation outcomes in SCD are comparable to that in non-SCD patients hospitalized with COVID-19.

Side effects following COVID-19 vaccination in pediatric patients with sickle cell disease.

Vulnerable patient populations have seen decreased rates of vaccination against SARS-CoV2-19 (COVID-19) due to hesitancies and distrust, magnified by a paucity of data for certain populations. The rate of COVID-19 vaccination in children with sickle cell disease (SCD) remains low despite the risk for severe complications, resulting in continued infections and hospitalizations from COVID-19. We sought to describe vaccine reactions, including vaso-occlusive crises, emergency department visits, and hospitalizations, in children with SCD. Our findings will start to provide the necessary vaccine side effect data to inform patients, caregivers, and clinicians considering the COVID-19 primary vaccination series.

Explainable artificial intelligence (XAI) in medical decision systems (MDSSs): healthcare systems perspective

The healthcare sector is very interested in machine learning (ML) and artificial intelligence (AI). Nevertheless, applying AI applications in scientific contexts is difficult due to explainability issues. Explainable AI (XAI) has been studied as a potential remedy for the problems with current AI methods. The usage of ML with XAI may be capable of both explaining models and making judgments, in contrast to AI techniques like deep learning. Computer applications called medical decision support systems (MDSS) affect the decisions doctors make regarding certain patients at a specific moment. MDSS has played a crucial role in systems' attempts to improve patient safety and the standard of care, particularly for non-communicable illnesses. They have moreover been a crucial prerequisite for effectively utilizing electronic healthcare (EHRs) data. This chapter offers a broad overview of the application of XAI in MDSS toward various infectious diseases, summarizes recent research on the use and effects of MDSS in healthcare with regard to non-communicable diseases, and offers suggestions for users to keep in mind as these systems are incorporated into healthcare systems and utilized outside of contexts for research and development.

An Evaluation of the Causes and Outcomes of Haemophagocytic Lymphohistiocytosis in Sheffield Teaching Hospitals: 2016 to 2021

Background/Aims Haemophagocytic lymphiohistiocytosis (HLH) is a rare, underrecognised hyperinflammatory syndrome, characterised by immune dysregulation. Without treatment, the ensuing cytokine storm leads to high mortality. Secondary HLH (sHLH) is triggered by malignancy, infection, autoimmunity and medicines;treatment with immunosuppression is consensus- rather than evidence-based and extrapolated from primary HLH. Sheffield hosts a mature HLH multidisciplinary advisory group (MDAG). Here we evaluate the cause, treatment, requirement for critical care and mortality of people with HLH managed through the MDAG in a period including the coronavirus pandemic but prior to NHS England approval of anakinra (IL-1 antagonist) for HLH. Methods This retrospective evaluation (approved locally STH 10850) identified patients from MDAG records 1st October 2016 to 30th September 2021. Data from electronic/paper records was analysed using Microsoft Excel. Results HLH triggers were infection (viral 34%, bacterial 10%), haematological (35%), rheumatological (13%) and other (8%). Rheumatological causes were Still's disease (n=5);antiphospholipid syndrome (n=2);JO1 dermatomyositis (n=1);SLE (n=1);and rheumatoid arthritis (n=1). Other causes included unknown (n=3);combined systemic JIA and sickle cell crisis (n=1);medication (alemtuzumab) (n=1);and primary HLH (n=1). Overall mortality was 53% and highest in HLH with a haematological malignancy trigger (82%) Prior to the COVID19 pandemic (pre-March 2020), the commonest trigger of HLH was haematological malignancy (47%);after March 2020, the commonest trigger was infection (64%);COVID-19 explained 42% of cases. Mortality fell from 72% to 31%. Conclusion In this real-world series of people with HLH, mortality and critical care requirement was high. HLH triggers reflect published evidence as does poor prognosis in haematological malignancy-associated HLH. No-HLH associated with non-haematological malignancy was identified;we may need to improve MDAG reach into oncology. Seeming reduction in mortality following the COVID-19 pandemic may reflect increased recognition of COVID-19 induced hyperinflammation along with locallyagreed access to anakinra for COVID-19-induced HLH. The increase in infection related HLH cases since March 2020 is explained largely by COVID-19 cases. This has led to a relative reduction in cases related to haematological malignancy. HLH requires multidisciplinary management and better research to improve treatment. (Table Presented).

Impact of the SARS-CoV-2 infection in individuals with sickle cell disease: an integrative review.

Sickle cell disease is the most common hemoglobinopathy among humans. As the condition promotes susceptibility to infections, chronic inflammation, and hypercoagulability disorders, several international agencies have included individuals with this disease in the COVID-19 risk group for severe outcomes. However, available information about the subject is not properly systematized yet. This review aimed to understand and summarize the scientific knowledge about the impact of SARS-CoV-2 infection in patients with sickle cell disease. Searches were performed in the Medline, PubMed, and Virtual Health Library databases based on descriptors chosen according to the Medical Subject Headings. We analyzed studies published between 2020 and October 2022, developed with qualitative, quantitative, or mixed methodology, and written in English, Spanish, or Portuguese. The search resulted in 90 articles organized into six categories. There is disagreement in the literature about how different aspects related to sickle cell disease, such as chronic inflammation status, hypercoagulability, hemolytic anemia, use of hydroxyurea, and access to medical care interference with the clinical course of COVID-19. These topics deserve further investigation. It is evident, however, that the infection may manifest in an atypical way and act as a trigger for the development of sickle cell-specific complications, such as acute chest syndrome and vaso-occlusive crises, conditions that are associated with great morbidity and mortality. Therefore, healthcare professionals must be aware of the different forms of presentation of COVID-19 among these individuals. Specific guidelines and therapeutic protocols, as well as public policies for sickle cell individuals, must be considered. Systematic review registration: This review (https://doi.org/10.17605/OSF.IO/NH4AS) and the review protocol (https://osf.io/3y649/) are registered in the Open Science Framework platform.

The evolution of the COVID-19 pandemic in paediatric patients with sickle cell disease: From Alpha to Omicron.

We compare the impact of SARS-CoV-2 variants on healthcare utilization and clinical presentation in paediatric patients with sickle cell disease (SCD). One hundred and ninety-one unique patients with SCD and positive SARS-CoV-2 polymerase chain reactions were identified between March 2020 and January 2022. Hospitalizations, which accounted for 42% (N = 81) of cases, were highest during the Delta dominant era (48%) and lowest during Omicron (36%) (p = 0.285). The most common SCD-related complication was vaso-occlusive pain (37%, N = 71), which accounted for 51% of all hospital admissions (N = 41), and acute chest was highest in the Alpha variant era (N = 15). Overall, COVID-19 remained mild in clinical severity within most paediatric SCD patients.

Prevalence of SARS-CoV-2 in hemoglobinopathies is modified by age and race.

Prior literature has established a positive association between sickle cell disease and risk of contracting SARS-CoV-2. Data from a cross-sectional study evaluating COVID-19 testing devices (n = 10,567) was used to examine the association between underlying health conditions and SARS-CoV-2 infection in an urban metropolis in the southern United States. Firth's logistic regression was used to fit the model predicting SARS-CoV-2 positivity using vaccine status and different medical conditions commonly associated with COVID-19. Another model using the same method was built using SARS-CoV-2 positivity as the outcome and hemoglobinopathy presence, age (<16 Years vs. ≥16 Years), race/ethnicity and comorbidities, including hemoglobinopathy, as the factors. Our first model showed a significant association between hemoglobinopathy and SARS-CoV-2 infection (OR: 2.28, 95 % CI: (1.17,4.35), P = 0.016). However, in the second model, this association was not maintained (OR: 1.35, 95 % CI: (0.72,2.50), P = 0.344). We conclude that the association between SARS-CoV-2 positivity and presence of hemoglobinopathies like sickle cell disease is confounded by race, age, and comorbidity status. Our results illuminate previous findings by identifying underlying clinical/demographic factors that confound the reported association between hemoglobinopathies and SARS-CoV-2. These findings demonstrate how social determinants of health may influence disease manifestations more than genetics alone.

Development of a Questionnaire on Access to Sickle Cell Disease Care in the Indigenous Tharu Population of Nepal

Purpose of Study Sickle cell disease (SCD) disproportionately affects the Tharu population of Nepal, a marginalized indigenous group concentrated in the Dang district. SCD is a structural hemoglobinopathy resulting in abnormal red blood cells with a tendency to occlude microvasculature. Since 2015, University of British Columbia medical students and a local community partner, Creating Possibilities, have improved access to SCD screening and diagnosis for the Tharu population. However, interviews conducted in 2016- 2017 found that SCD-afflicted community members encounter a number of challenges to obtain treatment once diagnosed. The purpose of this study was to develop a questionnaire on barriers to accessing SCD care in this community. Methods Used The Barriers to Accessing SCD Care Questionnaire was developed from items in existing scales, deductive and inductive item generation, and feedback from expert local partners. Reviewing literature on barriers to accessing healthcare in the Western region of Nepal informed region-specific questionnaire items, while literature on accessing SCD treatment in resource-limited settings informed SCD-specific questionnaire items. We also reviewed the literature on barriers to treatment for various stigmatized chronic health conditions in low-resource settings. Summary of Results Qualitative interviews with SCD-afflicted Tharu individuals in 2016-2017 identified inadequate local medical resources, transportation, financial strain, and limited awareness as barriers to care. Based on the literature review, we organized all survey items under the themes transportation, medical infrastructure, finances, community attitudes, and personal attitudes. The questionnaire includes closed-ended questions using a Likert scale, as well as open-ended interview prompts. It was made in collaboration with local community members to ensure it is culturally appropriate, needs-specific, and easily understandable. The questionnaire received ethics board approval, and interviews will begin once local health authorities lift COVID-19 restrictions. Conclusions Results from the Barriers to Accessing SCD Care questionnaire will guide future community-based interventions.

Access to Sickle Cell Disease Treatment in the Indigenous Tharu Population of Nepal

Purpose of Study: Sickle cell disease (SCD) is a hemoglobinopathy that disproportionately affects the indigenous Tharu population of Nepal, a marginalized ethnic group concentrated in the Dang district. There are significant global disparities in the prognosis of SCD;in low-income countries, which lack screening and management infrastructure, up to 80% of those born with SCD are undiagnosed and less than half survive beyond 5 years of age. Since 2015, University of British Columbia medical student teams have collaborated with a local community partner, Creating Possibilities (CP), to improve SCD awareness, screening, diagnosis, and management for the Tharu population in and around Dang. Community members with SCD have previously expressed numerous challenges in obtaining treatment once diagnosed. This study aims to better understand difficulties in accessing SCD care for this community. Methods Used: The Access to SCD Care Questionnaire was developed from items in existing scales, deductive and inductive item generation, and feedback from expert local partners to ensure it is culturally appropriate, needs-specific, and easily understandable. The questionnaire includes closed-ended questions using a Likert scale and open-ended interview prompts. It centers around five core themes: personal beliefs, community attitudes, finances, transportation, and medical infrastructure. Interviews were conducted in Tharu (local dialect) by CP staff members in January to March 2022. Themes and sub-themes were qualitatively analyzed. Summary of Results: Participants aged from 14 to 42 with an equal sex ratio, a total of 12 interviews were conducted before study saturation was reached. All participants reported at least one minor or major problem with access to SCD care in each of the five core themes of the questionnaire. Inadequate healthcare infrastructure was the most frequently reported barrier, with participants reporting lack of local medication accessibility and low supplies at further district hospitals. Additionally, despite government funding for treatment coverage, participants reported difficulties obtaining the necessary legal documents to prove eligibility. The second largest perceived barrier to care was transportation, which was reported to be costly, time-consuming, and not readily available. Regardless of sub-theme, participants reported that system-wide effects from COVID-19 perpetuated these issues. Conclusion(s): Results from the Access to SCD Care Questionnaire demonstrate that availability and accessibility to medications and transportation services are the primary challenges to receiving SCD care in this indigenous community. Therefore, future interventions for this community should focus on these findings. In contrast with previous literature, community stigma and personal beliefs were not often reported as hindering SCD treatment. This may be attributed to successful education campaigns within this specific community or due to participation bias.