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Objectives: To evaluate how payers utilize Institute for Clinical and Economic Review (ICER) assessments to inform coverage or formulary decisions. Method(s): Double-blinded, web-based survey was fielded through Xcenda's research panel, the Managed Care Network, from June to July 2022. Result(s): A total of 51 payers from health plans (n=27), integrated delivery networks (n=12), and pharmacy benefit managers (n=12) participated in the survey. When assessing the usefulness of ICER's value assessment framework (VAF) to inform formulary decisions within their organizations, 57% of payers indicated it was extremely/very useful, 33% indicated somewhat useful, and 10% indicated not at all/not very useful. Most respondents (73%) agreed that ICER assessments are aligned with their organization's internal assessment. Utilization of ICER's VAF was most prevalent in high-cost drug or disease states (78%), rare/orphan disease states (71%), and oncology/hematology disease states (67%). Payers reported less use in primary care disease states (29%), COVID-19 (8%), and digital therapeutics (4%). In the last 24 months, 20% of payers reported ICER's recommendations often influenced coverage decisions, 59% indicated occasional influence, and 22% indicated no influence. In the last 24 months, payers indicated the top 5 ICER assessments that influenced their coverage decisions included high cholesterol (38%), Alzheimer's disease (36%), atopic dermatitis (33%), multiple myeloma (31%), and chemotherapy-induced neutropenia (28%). ICER assessments that were less impactful included beta thalassemia (3%), digital health technologies (3%), and supervised injection facilities (3%). Payers reported using ICER assessments to inform both expanded and restricted coverage decisions. Conclusion(s): Payers find ICER's VAF useful to inform their organization's formulary decisions. ICER's assessments often align with payers' internal assessments and are most frequently utilized for high-cost drugs or disease states. Payers indicate ICER assessments have affected both expansion and restriction in their coverage policies.Copyright © 2023
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HbA1c measurement is widely used for diagnosis/ management/remission of diabetes with international schemes certifying comparability. A) 75 year-old Chinese female with type 2 diabetes was admitted in April 2020 with Covid-19 and diabetic ketoacidosis. Glucose was 35mmol/l and HbA1c 150mmol/mol with previous HbA1c of 45mmol/mol on metformin and alogliptin. She was treated for ketoacidosis and once-daily Lantus introduced along with supportive management of viral illness. B) 68 year-old Afro-Caribbean with type 2 diabetes on metformin before admission, presented with new onset, jerky ballistic movements of high amplitude in right arm, 10-15 movements every 5 min. Admission glucose was >33mmol/l, ketones 1.8mmol/l and HbA1c >217mmol/ mol. Hemichorea-hemiballism, a hyperglycaemia related movement was diagnosed and insulin commenced. Glucose decreased to 8-20mmol/ l, reaching 5-15mmol/ l by time of discharge. Ballistic movements resolved when glycaemic control improved with HbA1c 169mmol/mol, 25 days after discharge. C) Several days before admission, a female with diabetes over 20 years required attention from paramedics on four occasions for hypoglycaemia. Months beforehand metformin was replaced by gliclazide due to chronic kidney disease with HbA1c 50mmol/mol, and she was transfused six weeks before admission for microcytic anaemia. Gliclazide was discontinued and her diet modified which prevented further hypoglycaemic episodes. Variant haemoglobin, beta-thalassaemia which can overestimate glycaemia;undetected by HbA1c HPLC method, invalidated HbA1c as did the blood transfusion. These cases highlight that inadequate understanding of HbA1c can lead to acute presentations of dysglycaemia. As HbA1c accuracy can be affected by multiple factors, clinical assessment and triangulation are key to the management of such patients.
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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.
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Background: Parvovirus B19 is an icosahedral, single-strand DNA, non-enveloped virus. Its DNA genome has 5596 bases and is from the Parvoviridae family. Beta thalassemia, a hereditary illness, causes ruptured red blood cells and acute anemia due to aberrant haemoglobin synthesis. Aim(s): Detect parvovirus (B19) in beta-thalassemia major and study its association with demographic factors like sex, age, place of residence, etc. in specific patient groups. Method(s): From August 2022 to the end of February 2023. This study included the collection of serum samples for the detection of human parvovirus antigen in 60 patients with beta-thalassemia major. The control group consisted of 30 individuals of different ages who did not have beta-thalassemia. All these serum samples are detected for parvovirus antigen by the ELISA method. Result(s): The results of this study showed that the rate of detection of the presence of human parvovirus B19 in the group of patients with beta-thalassemia major was not affected by most of the demographic factors. As there were no statistically significant differences between the study groups in terms of gender, age, in addition to COVID-19 infection, and vaccination against COVID-19. However, the rate of beta-thalassemia major was significantly higher in rural areas than in urban areas (p = 0.040).Copyright © 2021 Muslim OT et al.
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Background: Haemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening systemic hyperinflammatory disease, which can have several aetiologies. Clinical case: a 48-year-old woman affected by a transfusion-dependent β-thalassemia was hospitalized in our haematology unit presenting with intermittent fever, haepatosplenomegaly and pancytopenia, which developed a few days after the booster dose of anti-SARS-CoV-2 mRNA vaccine. The investigations performed during hospitalization led to a diagnosis of HLH and steroid therapy where IV dexam-ethasone was initiated and provided benefits. Conclusions: the severity of HLH mandates early treatment, but the management of patients with post-vaccine HLH is still challenging and requires further study. No cases of HLH in patients with thalassemia were previously described.
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The proceedings contain 278 papers. The topics discussed include: genotoxic preventive potential of ethanol leaves extract of Annona muricata on N-Nitroso-N-Ethylurea pro-leukemia carcinogenin mice by bone marrow micronucleus assay;performance evaluation of TOSOH G11 high performance liquid chromatography analyzer (beta thalassemia analysis mode);the accuracy of manual platelet counting;new insights in the biochemical analysis of stored irradiated blood;can somatic mutations be used in the diagnosis of myelodysplastic syndrome?;assessment of reference intervals for platelet aggregation tests on samples with low platelet counts;hematological profile of patients with COVID-19 at Oran University hospital in Algeria by hematology analyzer BC-6800;prevalence of myeloproliferative neoplasm mutations among Pakistani population;utility of reticulated platelets (RETPLTS) and their qualitative parameters on ADVIA 2120I siemens in the differential diagnosis of thrombocytopenia;evaluation of reticulated platelets (RETPLTS) and their qualitative parameters on ADVIA 2120I siemens: a new diagnostics tool;and evaluation of the ability of the differential count on two hematology analyzers to detect leukemias, verified by bone marrow and peripheral blood smear evaluation of the ability of the differential count on two hematology analyzers to detect leukemias, verified by bone marrow and peripheral blood smears.
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Patients with chronic diseases are severely affected by acute coronavirus syndrome. In this regard, patients with beta thalassemia intermedia and diabetes mellitus (DM) are also at high risk for coronavirus-induced respiratory failure. The present study aimed to report a case with COVID-19 with a history of chronic diseases, beta thalassemia intermedia, and DM. A 25-year-old man visited with complaints of severe shortness of breath, fever, cough without sputum, and tachypnea and admitted to the Intensive Care Unit. The patient had a history of DM, beta thalassemia intermedia, and pervious history of the splenectomy. In peripheral complete blood count (CBC diff), the number of white blood cell count was 41,100 of which 38.6% were lymphocytes. We measured the normal platelet count, hemoglobin level (9.4), and red blood cell count (3.56). ESR was 97, CRP = pos+++ and PCR was positive. The high-resolution lung CT indicated ground glass opacities in peripheral areas. The patient underwent 13 days of oxygen therapy with reservoir bag-mask, non-invasive ventilation, nasal oxygen, and pharmacological treatment with IFN-ß1a and meropenem, and finally discharged with an improvement of the clinical condition. Timely initiation of treatment is very important and significant for patients with beta thalassemia intermedia with COVID-19, especially despite the underlying disease of DM. According to the present report, the use of IFN-ß1a was effective as a treatment option for COVID-19.
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Background: beta thalassemia is one of the most common hereditary hemoglobinopathy requiring regular blood transfusion to help reduce the complications of anemia and allow normal growth in children. Materials and Methods: It was a cross-sectional study done on 50 numbers of transfusion dependent beta thalassemia patients between 18 months and 18 years of age in North east India. Growth parameters like weight, height, BMI were recorded. Results: Overall prevalence of stunting was 68%, a significant association was found between stunting and religious connotation.
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Background: An erythroid maturation agent, Luspatercept is approved to treat adults with β -thalassemia. Its availability in Greece coincided with severe blood shortages due to the COVID outbreak, making its administration even more necessary. Aims: Luspatarept's usage in patients with comorbidities. Methods: Between May and December 2021, luspatercept was administered for a period of 12 to 24 weeks to twelve individuals with confirmed β -thalassemia (β 0/β +: 4/12, β +/β +:3/12, β 0/β ++:1/12, β 0/β 0 :1/12,β +/β ++:1/12) and significant comorbidities such as chronic heart failure (3/12), osteoporosis (3/12), atrial fibrillation (2/12), extramedullary hematopoiesis (2/12) and cirrhosis (1/12). The average age was 48.3 years;7male /5 female. Prior to initiating luspatercept, the patient's medical history was reviewed for risk factors for thrombophilia (9/12 had low protein S and C and 2/12 had also low ATIII) as well as anticoagulant (4/12 on acenocoumarol) and antiplatelet (3/12 on aspirin ) medication related to splenectomy (10/12) or past thrombotic episodes (4/12).Transfusion requirements, transfusion intervals, mean hemoglobin and LDH values were documented for 12 weeks prior to and during luspatercept initiation. To maintain stable blood volumes in each transfusion, prestorage leukoreduced RBCs with an average volume per unit of 320 ml was used. Results: Table 1 summarizes the study's main results.Statistical significance is p <0.05. Throughout treatment, all but one patient (11/12) received a dose of 1 mg/kg. One patient did not respond to a dose increase of 1.25 g / kg and discontinued on week 12. Additionally, two other luspatercept responders discontinued treatment after the 12th and 24th week, respectively, due to significant fatigue. After 12 and 24 weeks, all patients who continued in luspatercept had a significant decrease in transfusion blood needs, approximately -29.4% and -36.1 % compared to baseline. They also showed significant increase in transfusion intervals for an average of 20.7 days. In addition, it became apparent that, although the volume of blood supplied was reduced and the interval between transfusions increased, the patients' hemoglobin levels remained adequately high in luspatercept treated patients. LDH as hemolysis biomarker, did not reveal any significant changes. During the follow-up period, no patient reported progression of existing comorbidities or the development of new ones. As far as their cardiovascular disease is concerned, the patients clinical status was stable NYHA II despite the reduction of transfusions. Six months after taking luspatercept, one patient showed an improvement in extramedullary hematopoiesis as evaluated by magnetic resonance imaging. Additionally, despite the presence of predisposing factors and the significant increase of platelets, no new thrombosis developed. Summary/Conclusion: In patients with significant comorbidities, luspatercept significantly decreased transfusion burden and prolonged transfusion intervals , without any observed worsening of their comorbidities or development of new ones. (Table Presented).
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CRISPR is a gene editing technique that has revolutionised research and has the potential to transform the treatment of many diseases. This article discusses the principles of the technique, its therapeutic applications and potential safety issues.
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People living with transfusion dependent thalassemia have a high risk of getting infected by COVID-19. This can be caused both by internal factors, namely the formation of alloantibodies and autoimmune disorders, and external factors such as routine visits for blood transfusions. Chronic complications of thalassemia also render the patients more vulnerable to infectious diseases, including COVID-19. However, anecdotal data shows that thalassemia patients have less incidence of COVID-19 if compared to the general population. This study aims to find the correlation between COVID-19 in thalassemia-dependent transfusion patients in Indonesia and South-East Asia. This research used a cross-sectional design. The study was conducted at the Division of Haematology and Medical Oncology of the Cipto Mangunkusumo Hospital in Jakarta, from May 2020 to August 2021. Total sampling method was used involving all thalassemia major patients who had been infected with COVID-19 obtained directly from medical records and through the thalassemia patients’ parents foundation. In 10,397 patients with thalassemia, 67 (0.64%) people were infected by COVID-19 and two (2.9%) died. Meanwhile, the incidence of COVID-19 in the general population of Indonesia was 0.87%, more than in the thalassemia population. This means that thalassemia might provide additional protection against COVID-19 due to several mechanisms. This phenomenon is also seen in other countries with a high prevalence of thalassemia, which show less COVID-19 cases despite the pandemic. On the contrary countries with low rates of thalassemia carriers had experienced deadly surges of the pandemic. Indonesia and other countries with a high prevalence of thalassemia have lower COVID-19 incidence than countries with a low prevalence of thalassemia. Thalassemia might provide additional protection against COVID-19. Well designed studies are needed to provide better evidence on the protective effect of thalassemia against COVID-19.
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Background: In context to CBME curriculum, the paradigm shift of encouraging students to become the active learners the didactic lectures were reduced to one-third of total teaching learning methods. Due to Covid-19 pandemic, the above context became a huge challenge wherein total education system was jeopardised. Students became passive listeners with no option for interaction with teachers or peers during the online didactic lecture class and with no scope for any interaction. Interactive small group teaching is one of the best ways to engage students in learning clinical applications during 1st MBBS year especially during the pandemic e-learning environment where there is no physical presence around of the peer and teacher interaction. Description: MBBS 1st phase students were the target population. This innovative method was initiated with a group of 20 members during March-June 2021 through FCC online platform. Students were taught about a particular unit (BLOOD) in Physiology, post which the clinical application related to the unit were taught using AID method. The total session is of two hours, Using SLIDO the online pre-test of 25 marks was conducted for the students. Post which the students were shown the pictures of signs and symptoms Students lab diagnosis, treatment related pictures will be displayed on the screen in haphazard way (Iron deficiency anaemia, Megaloblastic anaemia, Beta Thalassemia), (Prehepatic jaundice, Hepatic jaundice, Post hepatic jaundice). Then the students will be randomly will be divided into 3 groups. For a duration of 30 mins, in groups the students have to analyse, Integrate and display the interpretation of clinical diagnosis by connecting pictures followed by discussion for 15 minutes by each group. After the completion of all the three groups, post-test will be conducted again using SLIDO. Outcome: The post-test scores were significantly more than pre-test score. All the three groups interacted and presented the clinical case effectively. Conclusion: The students became the active learners, they interacted with their peers and could analyse, integrate the haphazard pictures of clinical cases and displayed their diagnosis with explanation even through the online mode. AID (analyse, integrate and display), an Interactive small group teaching is one of the best way to engage students in learning clinical applications during 1st MBBS year especially during the pandemic e-learning environment where there is no physical presence among of the peers and teachers.
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Cunninghamella spp. is a group of fungi belonging to the Mucorales order. Cases of fungal endocarditis are sporadic, but more frequent in immunocompromised patients. COVID-19 (SARS-CoV-2 Infection Disease 2019) infections, prematurity, deferoxamine treatment, iron overload, neutropenia, diabetes, and malignant hemopathies proved to be risk factors for mucormycosis. We present the case of a 7-year-old boy who was treated every three weeks with blood transfusion for major beta-thalassemia, receiving deferoxamine for secondary hemochromatosis. After two weeks with nonspecific respiratory and digestive symptoms, he was admitted for fever, followed by lower limb ischemia and neurological signs. Echocardiography revealed massive endocarditis affecting the mitral and tricuspid valves with embolization phenomena in the brain, lungs, kidney, spleen, and lower limbs. As a particular finding, IgG antibodies for COVID-19 were positive. Emergency cardiac surgery was performed. The mitral valve necessitated replacement with CarboMedics prosthesis. Unfortunately, the patient did not survive. Cunninghamella spp. was confirmed via the PCR analysis of vegetations. Cunninghamella endocarditis in the context of a systemic infection presented as an opportunistic infection affecting a child who had several risk factors. Mucormycosis is challenging to treat, with high mortality. Prophylactic treatment in beta-thalassemia patients with iron-chelator deprivation drugs, such as deferiprone, may help in preventing these particular fungal infections.
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BACKGROUND: People living with transfusion dependent thalassemia have a high risk of becoming infected with COVID-19. This can be caused by both internal factors, namely the formation of alloantibodies and autoimmune disorder, and external factors such as routine visits for blood transfusions. Chronic complications of thalassemia also render them more vulnerable to infectious diseases, including COVID-19. However, anecdotal data shows that thalassemia patients experience less incidence of COVID-19 compared to the general population. PURPOSE: This study aims to find the correlation between COVID-19 in thalassemia-dependent transfusion patients in Indonesia and Southeast Asia. PATIENTS AND METHODS: This study used a cross-sectional design. The study was conducted at the Division of Hematology and Medical Oncology of the Cipto Mangunkusumo Hospital in Jakarta from May 2020-August 2021. The total sampling method was used involving all thalassemia major patients who had been infected with COVID-19 (obtained directly from medical record and through the thalassemia patients-parents foundation). RESULTS: From 10,397 patients with thalassemia, 67 (0.64%) people were infected by COVID-19 and 2 (2.9%) were deceased. Meanwhile, the incidence of COVID-19 in the general population of Indonesia was 0.87% (more than in the thalassemia population). This means that thalassemia might provide additional protection against COVID-19 due to several mechanisms. This phenomenon has also been seen in other countries with a high prevalence of thalassemia, wherein there are less COVID-19 cases despite the pandemic. On the contrary, countries with low rates of thalassemia had experienced deadly surges of the pandemic. CONCLUSION: Indonesia and other countries with a high prevalence of thalassemia have lower COVID-19 incidence than countries with low prevalence of thalassemia. Thalassemia might provide additional protection against COVID-19. Well-designed studies are needed to provide better evidence on the protective effect of thalassemia on COVID-19.
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Ferritin overload is a frequent problem encountered in patients with beta thalassemia amounting to various complications. One of rare but important complication of ferritin overload is ferritin overload induced toxic encephalopathy. Serum ferritin has been recognised as a important marker of inflammation and cytokine storm in COVID19.We present a case of Long COVID syndrome presenting as toxic encephalopathy in a case of beta thalassemia in spite of the patient being compliant to desferroxamine therapy.This report highlights the synergistic effect of Severe Acute Respiratory Syndrome Coronavirus. 2(SARS CoV 2) mediated neuroinflammation through direct viral invasion and the release of inflammatory cytokines including ferritin resulting in toxic encephalopathy in a beta thalassemia major patient who was already prone to develop hyperferritenemia.Ferritin functions as a pro-inflammatory cytokine and it's level increases in both thalassemia and COVID-19 and the index case presented here had both the conditions predisoposing him to develop toxic encephalopathy even after being compliant to deferoxamine therapy. It is important to recognise and treat this condition in order to prevent mortality and morbidity in patients of beta thalassemia who contract COVID19.
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Background: β-thalassemia is an inherited hemoglobinopathy caused by mutations in the gene encoding the β-globin chain of hemoglobin (Hb), resulting in ineffective erythropoiesis, impaired red blood cell (RBC) maturation, and anemia. Patients (pts) with severe disease require regular, lifelong RBC transfusions and iron chelation therapy (ICT) shortly after diagnosis in early childhood. There is an unmet need for safe and effective treatments for pediatric pts to address the underlying pathophysiology of β-thalassemia and reduce the burden of chronic RBC transfusions early to prevent secondary iron overload and associated morbidity. Luspatercept is a first-in-class erythroid maturation agent approved in the USA and EU for the treatment of anemia in adult pts with β-thalassemia who require regular RBC transfusions. In previous studies, treatment with luspatercept resulted in clinically significant reductions in RBC transfusion burden in adults with TDT (phase 3 BELIEVE;Cappellini MD, et al. N Engl J Med 2020;382:1219-1231) and increased Hb levels in adults with non-TDT (phase 2 BEYOND study;Taher AT, et al. HemaSphere 2021;5[Suppl 2];S101). This phase 2a study (NCT04143724, EudraCT 2019-000208-13) will evaluate the safety and PK of luspatercept in pediatric pts with β-thalassemia who require regular RBC transfusions. The results will determine a recommended dose (RD) for each age group. Study Design and Methods: Eligible pts will be 6 to < 18 years of age;diagnosed with β-thalassemia, Hb E/β-thalassemia, or α-thalassemia/β-thalassemia;require ≥ 4 RBC units in the 24 weeks prior to enrollment (with no transfusion-free period ≥ 42 days and with a regular history of transfusions for ≥ 2 years);and have Karnofsky (≥ 16 years of age) or Lansky (< 16 years of age) performance status score ≥ 50 at baseline. Exclusion criteria include: a Hb S/β-thalassemia or α-thalassemia diagnosis, chronic anticoagulant therapy ≤ 28 days prior to enrollment, erythropoiesis-stimulating agent or hydroxyurea use ≤ 24 weeks prior to enrollment, ICT initiation ≤ 8 weeks prior to enrollment, use of any investigational drug ≤ 28 days prior to enrollment, or have undergone or are scheduled for transplant or gene therapy. A total of 54 pts will be enrolled in a staggered study design by age, beginning with a 12-week screening/run-in period. During Part A, pts 12 to < 18 years of age will receive luspatercept at 0.75 mg/kg (n = 6;Cohort 1) or 1.0 mg/kg (n = 6;Cohort 2) subcutaneously (s.c.) once every 21 days for ≤ 4 cycles (Figure A). The RD will be determined for each age group strata at the time of enrollment using descriptive statistics or frequency tabulations between and in aggregate across age-group arms. An expansion cohort (n = 30 pts 12 to < 18 years of age;Cohort 3) will then receive luspatercept for at least 1 year at the RD based on tolerability and safety data from Cohorts 1 and 2;if the RD is 1 mg/kg, titration up to 1.25 mg/kg is allowed in the expansion cohort based on erythroid response during the previous 2 dose cycles. Part B will be initiated following completion of Part A and review of overall safety data with the Data Monitoring Committee, Scientific Steering Committee, and health authorities. Pts 6 to < 12 years of age will be treated with luspatercept at 1.0 mg/kg (n = 6;Cohort 4) or 1.25 mg/kg (n = 6;Cohort 5) s.c. once every 21 days for ≤ 4 cycles (Figure B). Any pt who benefits from treatment can continue to receive luspatercept for ≤ 5 years from first dose and will be monitored for 5 years from first dose or 3 years from last dose, whichever occurs later. Pts may receive best supportive care, including RBC transfusions, ICT, antibiotics, antifungal or antiviral therapy, and/or nutritional support, as needed. The primary objectives are to determine the RD of luspatercept that is safe and tolerable and the PK of luspatercept in pediatric pts with TDT. Key secondary objectives include evaluating mean change in RBC transfusion burden, change in Hb levels, mean change in daily dose of ICT, mean change in serum ferritin, and the immunogenicity and safety of luspatercept in pediatric pts. Safety endpoints include evaluating the type, frequency, seriousness, and severity of adverse events and their relationship to luspatercept treatment. Exploratory endpoints include evaluating exposure-response, health-related quality of life, biomarkers/markers of iron overload and ineffective erythropoiesis, and SARS-CoV-2 serology. [Formula presented] Disclosures: Viprakasit: Bristol Myers Squibb: Research Funding. Coates: Celgene: Consultancy, Honoraria, Research Funding;Forma Pharma: Consultancy;Sangamo: Consultancy;UpToDate: Patents & Royalties;Vifor Pharma: Consultancy;Apo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Bluebird Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees;Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Chiesi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Musallam: Celgene, Bristol Myers Squibb: Consultancy;Novartis: Consultancy;Agios Pharmaceuticals: Consultancy;CRISPR Therapeutics: Consultancy;Vifor Pharma: Consultancy. Vienne Buerki: Bristol Myers Squibb: Current Employment. Patturajan: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Holot: Bristol Myers Squibb: Current Employment. Aydinok: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Bristol Myers Squibb/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding;Resonance Health: Research Funding;CRISPR Therapeutics: Consultancy;SLN Therapeutics: Consultancy;Imara: Research Funding;Protagonist: Membership on an entity's Board of Directors or advisory committees, Research Funding;Ionis Pharmaceuticals: Research Funding;La Jolla: Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Introduction: The Grady Comprehensive Sickle Cell (SC) center is the largest adult sickle cell center in the United States (US) and has the first 24/7 acute care unit for management of sickle cell vaso-occlusive events (VOE). In 2019, the center provided 3077 sickle cell outpatient visits and 3695 acute care visits. When the COVID-19 pandemic reached the US, the center had a precipitous drop in the number of both outpatient clinic and acute care visits as state regulations for lockdown were passed. This report follows all the COVID-19 cases at a single adult center for sickle cell disease in one year. Methods: The clinical database has been tracking COVID-19 cases reported. Out of a total of 1343 patients, 55 patients contracted COVID-19 and were tracked in the clinical database with IRB approval. Results: Of the 55 patients with COVID-19, 28 were female and 27 were male. By genotype, 64% of patients were SS, 31% were SC and 5% were Sβ+ thalassemia. 35% of patient were on hydroxyurea for disease modification with the majority of them being of the SS genotype and 31% had elevated fetal hemoglobin determined by a percentage fetal hemoglobin above 5% by hemoglobin electrophoresis. Chronic pain (defined as patients experiencing daily pain episodes for more than 4 days a week for the last 3 months) and calculation of daily morphine equivalents were reported in clinic follow-up and the narcotic database utilization. 47% of the patients had chronic pain and the median morphine equivalents was 90 mg daily (45-225mg). The rate of emergency department (ED) visits or hospitalizations for the sickle cell patients with COVID-19 was 80%. 49% of the SC patients' visits were related to VOE and 27% related to COVID-19 primarily. 20% of SC patients with COVID-19 were not seen in any emergency setting or required any hospitalization. The COVID-19 signs and symptoms experienced by the patients were as follows: 58% had pain as the main presenting symptom, followed by cough and fever (40%), dyspnea (31%), and pneumonia with chest x-ray evidence (25%). 2 patients developed acute respiratory distress syndrome (ARDS) and were intubated, and 2 patients died. 29% of the patients had lung findings on imaging and 16 of 55 patients required treatment with the use of Remdesivir in 9, dexamethasone in 8 and red cell products in 7 of the 16 patients. The 2 patients who died had both presented with COVID-19 infection in June and July 2020 respectively. One patient had presented in June 2020 with VOE and was found to have bilateral lung opacities but was asymptomatic and was discharged home to return few days later with clinical picture of multi-organ failure for which a red cell erythrocytapheresis was attempted. The second patient had presented in July 2020 with COVID-19 pneumonia and was treated with Remdesivir and convalescent plasma with development of multi-organ failure and ARDS. Discussion: Several reports were published regarding the rate of COVID-19 related mortality and morbidity in sickle cell disease. The Grady comprehensive sickle cell center experience differs in the fact that 16 out of 55 patients who had contracted COVID-19 required treatment and 2 of those 16 had died. In fact, the deaths occurred early in the course of the pandemic in June and July 2020 when 20 total cases were diagnosed (from March to Septemeber 2020). The remaining 35 cases registered zero deaths (October 2020 to March 2021) with the rate of complicated COVID-19 hospitalizations decreasing with better treatment available. In addition, the timeline for the COVID-19 cases reported fits the population timeline of 2 peaks respectively happening in the summer of 2020 and the Winter of 2021. During the initial peak, we have noted a decrease in the number of clinic and acute care visits respectively. This was anticipated given the statewide lockdown that was implemented. To circumvent that, the center adopted virtual visits to deliver healthcare needs. This measure has aided in protecting patients against COVID-19. Additionally, it is interesting that despite the seco d peak in the winter of 2021, there were no reported deaths among the patients who developed COVID-19. This finding can suggest that despite the concern for morbidity and mortality of sickle cell patients, their diligence and awareness to stay home during the pandemic has proven crucial in reducing morbidity and mortality and the option of virtual visits for healthcare delivery was key and should be utilized further in sickle cell care. [Formula presented] Disclosures: No relevant conflicts of interest to declare.
ABSTRACT
A diagnosis of SCD is considered to be at risk for COVD19. To further define the association between SCD and infection with COVID-19, we estimated risk, by comparing presence or absence of COVID19 infections in individuals with and without SCD admitted concurrently to a large urban health care facility (Grady Memorial Hospital, Atlanta, GA;960 beds, 5th largest public hospital in the US). Primary outcome was a positive or negative COVID-19 diagnosis as defined bySARS-CoV-2 PCR testing. A patient was considered to be COVID-19 positive if tested positive withSARS-CoV-2 PCR for the first time, anytime during the study period, irrespective of number of tests. A patient was considered to be COVID-19 negative if patient had no positive tests during the study period, and had one or moreSARS-CoV-2 PCR negative tests. For COVID19 positive patients, the admission of theSARS-CoV-2 PCR positive test was included in the analysis. For COVID19 negative patients, the first admission with aSARS-CoV-2 PCR negative test was considered for analysis. For this interim analysis, SCD was defined by ICD10 and registry data. Clinical diagnosis such as obesity and respiratory failure were defined by ICD10 coding. Data was obtained from quarterly centralized Epic EMR data extractions. Analysis of outcome of COVID19 positive vs negatives was stratified in four separate analysis: all admissions, ICU admissions, those with respiratory failure and those who died. Multivariate dichotomous logistic regression analyses modeled binary outcome effect of SCD, adjusted for age (<40 vs. > 40 years), sex at birth (females vs. males) and obesity (SAS version 9.4 was used for statistical analyses and overall significance level was set at 0.05). To ensure population homogeneity analysis was conducted on patient ages 20 to 60 years that were Black/African American and admitted from the Emergency Department for a short stay and/or the medicine service (variable interactions at a p<0.01). The study was approved by the institutional review board and by the hospital research oversight committee. Overall, between 3/23/2020 and 6/30/2020, 23697 patients were admitted once or more to Grady Memorial Hospital with one or more PCR sars-cov-2 test, of these 405 were patients with SCD (1.7%). Of the total, 2566 patients (10.8%) tested positive for COVID-19, and 48 patients with SCD (11.8%) were positive. Of 7041 (29.7%) were part of the study population, 332 (4.7%) where patients with SCD (hemoglobin [hb] SS/Sbeta0 =252, hbSC n=55, hbS beta thalassemia+ or hbS beta thalassemia undetermined n=21). Among patients without SCD, 36.3% were female, (n=2557) and among patients with SCD, 53.6% (n=178). The mean age of patients without SCD was: 51.1 years (standard deviation [std]) +/- 19.5 years), and for those with SCD: 35.0 years (std +/- 12.0 years). Results of univariate and multivariate analysis are presented in the table. In conclusion, in a Black/African American patients admitted from the Emergency Room for observation and/or the internal medicine service, when adjusted for age, gender and obesity, with SCD are at a significant increased risk for admissions with COVID-19 infection in general as well as ICU admission or admission with respiratory failures. Further studies can help articulate the risk associated with SCD as well as its potential interaction with other factors, with attention to confounders. [Formula presented] Disclosures: No relevant conflicts of interest to declare.
ABSTRACT
Introduction Sickle cell disease is a genetic disease with acute and chronic complications. Pediatric mortality has decreased in recent decades with the introduction of systematic antibiotic therapy, preventive management of cerebral vasculopathy and therapeutic education of families. However, in the absence of cohort follow-up at birth, life expectancy, which is a different concept from age at death, cannot be assessed. In this retrospective, monocentric study, we describe causes and circumstances of death, acute chronic complications, long-term treatments and baseline biology of these patients. It seems important to analyze the risks of morbidity and mortality in order to decide on the necessary preventive measures. Material and method: Records of patients deceased between 2000 and 2020, from the national referral center (Henri Mondor Hospital), were retrospectively reviewed. The referral center follows 3500 patients. All deaths reported to the hospital, by families, other hospitals and health professionals were retrieved from computerized records. Deaths published by the INSEE (National Institute of Statistical and Economical study) from 2000 to December 2020 were accessible and compared with our databases to identify all our deceased patients. All patients with a medical record in our center were included for the study. Patients who had never visited our center were excluded. Results: During this period 226 patients including 128 women and 138 men are recorded. Genotypes for these patients were 204(76%) SS, 41 (15%) SC, 14(5%) Sβ°thalassemia and 7 (2%) Sβ+thalassemia. The median age at death was 41 years with an IQR [32-51]. 186 (70%) patients were hospitalized, 129 (70%) of whom were admitted to intensive care. 36 (13%) patients died at home, including 15 with opioid addiction and 5 patients with psychiatric pathology, and 4 patients on dialysis. This information was not available for 44 (16%) patients. The causes of death were vaso-occlusive complications with multivisceral failure in 44 cases, 42 sepsis, among which there were 11 renal failures, 9 of which were dialyzed. 5 patients died of COVID 19. Cerebral hemorrhage and neurological accident occurred in 22 cases, 4 of which were known to have macrovasculopathy. 25 patients died of a direct complication of renal failure, of which 17 were dialysed, 8 pre-dialysed and 3 transplanted. Acute liver failure in 16 cases, 10 precapillary pulmonary hypertension, 14 DHTR, 10 end-stage heart failure were noted. Two road accidents, 2 suicides, 1 dementia are repoted. For 51 cases, there was no information on the cause or circumstance of death. The causes of death according to genotype is on Table 1. Concerning the chronic complications, 94/266 (35%) patients had significant chronic organ damage. Sixteen patients had required renal or liver transplantation in their history. End-stage organ damage was frequent, 42 had end-stage renal failure, 21 had major liver failure, of which five were transplanted and 16 were awaiting transplantation. Twenty-one patients had known heart failure, 10 of which were associated with end-stage renal disease. Ten patients were followed for significant precapillary pulmonary hypertension. Transfusion difficulties due to a history of DHTR were found for 33 patients. Fourteen patients had an opioid addiction. Nine patients were pregnant and nine had received corticosteroids. Discussion: Causes of death have changed and chronic organ failure is the leading cause of death, especially in patients with kidney, liver and heart disease. This study does not calculate life expectancy, but there was an increase in age at death of about 1/4 of the patients who were between 51 and 81 years old.The management of sickle cell disease has progressed in recent years and new therapies are being proposed. Prevention of the development of these complications is one of the new challenges, especially for renal disease, which is associated with premature mortality. DHTR and cerebral hemorrhage, Covid-19 are new entities and DHTR was probably underdiagnosed in p evious publications. Pregnancy remains a period at risk, for which surveillance should be reinforced. The analysis is ongoing and correlations are currently being investigated between different parameters to find risk factors for mortality. [Formula presented] Disclosures: Habibi: Novartis: Consultancy, Honoraria;bluebird bio: Consultancy, Honoraria, Research Funding. Audard: Addmedica: Consultancy. Michel: Novartis: Consultancy;Amgen: Consultancy;Rigel: Honoraria;Alexion: Honoraria;UCB: Honoraria;Argenx: Honoraria. Galactéros: Addmedica: Membership on an entity's Board of Directors or advisory committees. Bartolucci: INNOVHEM: Other: Co-founder;Bluebird: Consultancy, Research Funding;F. Hoffmann-La Roche Ltd: Consultancy;GBT: Consultancy;Jazz Pharma: Other: Lecture fees;AGIOS: Consultancy;Hemanext: Consultancy;Emmaus: Consultancy;Fabre Foundation: Research Funding;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding;Addmedica: Consultancy, Other: Lecture fees, Research Funding.