Validating evidence for the knowledge, management and involvement of dentists in a dental approach to sickle-cell disease.

This study validated the content of an instrument designed to assess the knowledge, involvement (attitudes) and management (practice) of dentists relative to sickle-cell disease (KAPD-SCD). The instrument consisted of five domains composed of a total of thirteen items: I. Dentist's self-assessment relative to sickle-cell disease; II. Dentist's knowledge of the repercussions of sickle-cell disease on the stomatognathic system; III. Dentist's knowledge of the complications of sickle-cell disease in the stomatognathic system; IV. Dentist's knowledge concerning the dental management of sickle-cell disease patients; and V. Dentist's involvement in an approach to sickle-cell disease. Twelve experts assigned scores to each item of the instrument. The criteria were clarity, understanding and appropriateness, leaving open fields for comments. Descriptive and content analyses of the data were made. Each expert analyzed 39 assessment units. The percentages considered for agreement were high (>80%), medium (70%-80%), or low (<70%), and each item was maintained or revised according to the percentage observed. There was high consensus in 74% of the assessment units (the corresponding items were maintained), medium consensus in 24% of them (the corresponding items were revised), and disagreement in 2% of them, namely as regards the "appropriateness" of item 5 ("Are there oral complications in sickle-cell disease?"), which was revised. The final version of the instrument had 16 items for different applications such as in the clinical care program, teaching program, or research program, with different cut-off scores for each application. In conclusion, the level of agreement among experts showed evidence of the content validity of the instrument.

Acute care utilization among individuals with sickle cell disease and related cardiopulmonary and renal complications.

Cardiopulmonary and renal end organ (CPR) complications are associated with early mortality among individuals with sickle cell disease (SCD). However, there is limited knowledge regarding acute care utilization for individuals with SCD and CPR complications. Our objective was to determine the prevalence of CPR complications in a state specific SCD population and compare acute care utilization among individuals with and without CPR complications. We leveraged 2017-2020 data for individuals with SCD identified by the Sickle Cell Data Collection program in Wisconsin. The prevalence of CPR complications is determined for distinct age groups. Generalized linear models adjusted for age compared the rate of acute care visits/person/year among individuals who had cardiopulmonary only, renal only, both cardiopulmonary and renal, or no CPR complications. There were 1378 individuals with SCD, 52% females, mean (SD) age 28.3 (18.5) years; 48% had at least one CPR complication during the study period. The prevalence of CPR complications was higher in adults (69%) compared to pediatric (15%) and transition (51%) groups. Individuals with SCD and cardiopulmonary complications had higher acute visit rates than those without CPR complications (5.4 (IQR 5.0-5.8) vs 2.4 (IQR 2.1-2.5), p <0.001)). Acute care visit rates were similar between individuals with SCD who had renal only complications and no CPR complications (2.7 (IQR 2.5-3.0) vs 2.4 (2.1-2.5), p = 0.24). The high acute care visit rates, especially for those with cardiopulmonary complications, warrant further investigation to understand risk factors for CPR complications, the underlying reasons and identify effective disease management strategies.

Translational Research and Health Equity: Gene Therapies for Sickle Cell Disease as a Case Study.

In August of 2023, the National Academies of Science, Engineering, and Medicine published a timely report titled "Toward Equitable Innovation in Health and Medicine: A Framework." Here, we review some of the key contributions of the report, focusing on two dimensions of equity: input equity and deployment equity. We then use the example of new gene therapies to treat sickle cell disease (SCD) as a case study of input and deployment equity in translational research. The SCD case study illustrates the need for a kind of translational bioethics with deep understanding of lived experiences and clinical realities as well as a high degree of economic and policy sophistication.

[Transition in sickle cell disease - recommendations of the transition initiative sickle cell disease]. / Transition bei der Sichelzellkrankheit ­ Empfehlungen der Transitionsinitiative Sichelzellkrankheit.

Sickle cell disease is a rare, but complex multi-systemic disorder with high need of interdisciplinary and specialized care and new structural requirements. Besides care of those chronically sick patients, transition process is a vulnerable phase which highly influences further treatment. To make matters worse, patients often have migration background with subsequent communication problems. A national guidance for a standardized transition process is lacking in Germany. In context of a structured consensus process, the "transition initiative sickle cell disease" developed specific recommendations for a structured transition of sickle cell patients on the basis of the S3 transition guideline of the DGfTM. These recommendations should improve this vulnerable process in this complex disease to ensure adequate further treatment and to avoid acute and chronic complications but also mental, social or job-related issues. Besides improvement of quality of life, medical treatment and survival, health economic aspects arise. Documents were developed to support and facilitate the transition process and are available under www.sichelzellkrankheit.info/transition/.

Effect of nutritional supplementation on bone mineral density in children with sickle cell disease: protocol for an open-label, randomised controlled clinical trial.

INTRODUCTION: Children with sickle cell disease show a significant decrease in bone mineral density, an increase in resting energy expenditure of more than 15%, a decrease in fat and lean mass as well as a significant increase in protein turnover, particularly in bone tissue. This study aims to evaluate the effectiveness of an increase in food intake on bone mineral density and the clinical and biological complications of paediatric sickle cell disease. METHODS AND ANALYSIS: The study is designed as an open-label randomised controlled clinical trial conducted in the Paediatrics Unit of the Orléans University Hospital Centre. Participants aged 3-16 years will be randomly divided into two groups: the intervention group will receive oral nutritional supplements (pharmacological nutritional hypercaloric products) while the control group will receive age-appropriate and gender-appropriate nutritional intake during 12 months. Total body less head bone mineral density will be measured at the beginning and the end of the trial. A rigorous nutritional follow-up by weekly 24 hours recall dietary assessment and planned contacts every 6 weeks will be carried out throughout the study. A school absenteeism questionnaire, intended to reflect the patient's school productivity, will be completed by participants and parents every 3 months. Blood samples of each patient of both groups will be stocked at the beginning and at the end of the trial, for future biological trial. Clinical and biological complications will be regularly monitored. ETHICS AND DISSEMINATION: The protocol has been approved by the French ethics committee (Comité de Protection des Personnes Sud-Ouest et Outre-Mer 2, Toulouse; approval no: 2-20-092 id9534). Children and their parents will give informed consent to participate in the study before taking part. Results will be disseminated through peer-reviewed journals or international academic conferences. TRIAL REGISTRATION NUMBER: NCT04754711.

[Population characterization of mutations for sickle cell anemia and its treatment: One step towards personalized medicine for the disease]. / Caracterización poblacional de mutaciones relevantes para la Anemia Falciforme y su tratamiento: Un paso hacia la personalización de la enfermedad.

Sickle cell anemia (SCA) is the most common genetic disease worldwide. There are countries with massive public health programs for early detection of this condition. In the literature, several specific haplotypes or single-base polymorphic variants (SNPs) have been associated with the SCA prognosis. OBJECTIVE: To demonstrate the significant correlation of SNPs relevant to the diagnosis and prognosis of SCA among different ethnic groups. METHODOLOGY: we analyzed population frequencies and correlations of several SNPs related to the prognosis of SCA (i.e., baseline fetal hemoglobin levels), response to hydroxyurea treatment, and response to other drugs used in the SCA treatment, collected from validated genomic databases among different ethnic groups. RESULTS: The calculation of the Hardy-Weinberg equilibrium and the logistic regression was successful in classifying the ethnic groups as African (0 = 0.78, 1 = 0.89), and with a lower efficiency as American (AMR) (0 = 0.88, 1 = 0.00), East Asian (EAS) (0 = 0.80, 1 = 0.00), European (EUR) (0 = 0.79, 1 = 0.00), and South Asian (SAS) (0 = 0.80, 1 = 0.00). CONCLUSIONS: The results extend those from previous reports and show that the profile of most of the SNPs studied presented statistically significant distributions among general ethnic groups, pointing to the need to carry out massive early screening of relevant SNPs for SCA in patients diagnosed with this disease. It is concluded that the application of a broad mutation detection program will lead to a more personalized and efficient response in the treatment of SCA.

Social determinants of health and treatment center affiliation: analysis from the sickle cell disease implementation consortium registry.

BACKGROUND: Adults with sickle cell disease (SCD) suffer early mortality and high morbidity. Many are not affiliated with SCD centers, defined as no ambulatory visit with a SCD specialist in 2 years. Negative social determinants of health (SDOH) can impair access to care. HYPOTHESIS: Negative SDOH are more likely to be experienced by unaffiliated adults than adults who regularly receive expert SCD care. METHODS: Cross-sectional analysis of the SCD Implementation Consortium (SCDIC) Registry, a convenience sample at 8 academic SCD centers in 2017-2019. A Distressed Communities Index (DCI) score was assigned to each registry member's zip code. Insurance status and other barriers to care were self-reported. Most patients were enrolled in the clinic or hospital setting. RESULTS: The SCDIC Registry enrolled 288 Unaffiliated and 2110 Affiliated SCD patients, ages 15-45y. The highest DCI quintile accounted for 39% of both Unaffiliated and Affiliated patients. Lack of health insurance was reported by 19% of Unaffiliated versus 7% of Affiliated patients. The most frequently selected barriers to care for both groups were "previous bad experience with the healthcare system" (40%) and "Worry about Cost" (17%). SCD co-morbidities had no straightforward trend of association with Unaffiliated status. The 8 sites' results varied. CONCLUSION: The DCI economic measure of SDOH was not associated with Unaffiliated status of patients recruited in the health care delivery setting. SCDIC Registrants reside in more distressed communities than other Americans. Other SDOH themes of affordability and negative experiences might contribute to Unaffiliated status. Recruiting Unaffiliated SCD patients to care might benefit from systems adopting value-based patient-centered solutions.

Transfusing children with sickle cell disease using blood group genotyping when the pool of Black donors is limited.

BACKGROUND: Red blood cell transfusion is an effective treatment for patients with sickle cell disease (SCD). Alloimmunization can occur after a single transfusion, limiting further usage of blood transfusion. It is recommended to match for the ABO, D, C, E, and K antigens to reduce risks of alloimmunization. However, availability of compatible blood units can be challenging for blood providers with a limited number of Black donors. STUDY DESIGN AND METHODS: A prospective cohort of 205 pediatric patients with SCD was genotyped for the RH and FY genes. Transfusion and alloimmunization history were collected. Our capacity to find RhCE-matched donors was evaluated using a database of genotyped donors. RESULTS: Nearly 9.8% of patients carried a partial D variant and 5.9% were D-. Only 45.9% of RHCE alleles were normal, with the majority of variants affecting the RH5 (e) antigen. We found an alloimmunization prevalence of 20.7% and a Rh alloimmunization prevalence of 7.1%. Since Black donors represented only 1.40% of all blood donors in our province, D- Caucasian donors were mostly used to provide phenotype matched products. Compatible blood for patients with rare Rh variants was found only in Black donors. A donor with compatible RhCE could be identified for all patients. CONCLUSION: Although Rh-compatible donors were identified, blood units might not be available when needed and/or the extended phenotype or ABO group might not match the patient. A greater effort has to be made for the recruitment of Black donors to accommodate patients with SCD.

Using the daily rate of rise in hemoglobin S to manage RBC depletion/exchange treatment in sickle cell disease.

BACKGROUND: Red blood cell exchange is often used prophylactically in patients with sickle cell disease, with the goal to maintain hemoglobin S (HbS) below a target threshold level. We reviewed whether the daily "rate of rise" (RoR) in HbS that occurs between procedures can be used for patient management. For some patients not achieving their HbS goals despite efficient exchanges, the post-procedure hematocrit (Hct) target is increased to potentially suppress HbS production. This case series explores the utility of this approach, other clinical uses of the daily RoR in HbS, and the factors that influence it. STUDY DESIGN AND METHODS: A total of 660 procedures from 24 patients undergoing prophylactic RBC depletion/exchange procedures were included. Laboratory values and clinical parameters were collected and used to calculate the daily RoR in HbS. Factors such as Hct or medications that might influence the RoR in HbS were evaluated. RESULTS: The RoR in HbS varied widely between patients but remained relatively stable within individuals. Surprisingly, this value was not significantly influenced by changes in post-procedure Hct or concurrent hydroxyurea use. A patient's average RoR in HbS effectively predicted the pre-procedure HbS at the following visit (R2 = 0.65). DISCUSSION: The RoR in HbS is a relatively consistent parameter for individual patients that is unaffected by medication use or procedural Hct targets and may be useful in determining intervals between procedures.

The acute pain crisis in sickle cell disease: What can be done to improve outcomes?

The acute pain crisis (APC) is the commonest complication of sickle cell disease (SCD). Severe episodes may require treatment in hospital with strong opioid analgesic drugs, combined with additional supportive care measures. Guidelines for APC management have been produced over the past two decades gathering evidence from published studies, expert opinion, and patient perspective. Unfortunately, reports from multiple sources indicate that guidelines are often not followed, and that acute care in emergency departments and on acute medical wards is suboptimal. It is important to understand what leads to this breakdown in health care, and to identify evidence-based interventions which could be implemented to improve care. This review focuses on recently published articles as well as information about on-going clinical trials. Aspects of care which could potentially make a difference to patient experience include availability and accessibility of individual care plans agreed between patient and treating specialist, innovative means of delivering initial opioids to reduce time to first analgesia, and availability of a specialist unit away from the ED, where expert care can be delivered in a more compassionate environment. The current evidence of improved outcomes and health economic advantage with these interventions is inadequate, and this is hampering their implementation into health care systems.

[The transition of adolescents with sickle cell disease: an interdisciplinary exchange]. / La transition des adolescents drépanocytaires, un échange interdisciplinaire.

With the rising incidence of sickle cell disease, this chronic pathology is becoming the most common genetic disease in France. Advances in care have led to a marked improvement in life expectancy. Caregivers in pediatric facilities are therefore increasingly confronted with the question of the transition to adulthood of the adolescents they have been following since birth. As nurses working in Robert-Debré's transfusion and curative medicine unit, in 2022, adolescents accounted for 57 % of sickle cell patients enrolled in our transfusion exchange program. Adolescence is a period of major change, and the repercussions of the disease are all the more pronounced. This raises the issue of transferring them to the adult sector.

Description of a national, multi-center registry of patients with sickle cell disease and SARS-CoV-2 infection: Data from the Pediatric COVID-19 United States Registry.

Children with sickle cell disease (SCD) are at risk of complications from viral infections, including SARS-CoV-2. We present the clinical characteristics and outcomes of pediatric patients with SCD from the Pediatric COVID-19 United States Registry who developed acute COVID-19 due to SARS-CoV-2 infection (n = 259) or multisystem inflammatory syndrome in children (MIS-C; n = 4). Nearly half of hospitalized children with SCD and SARS-CoV-2 infection required supplemental oxygen, though children with SCD had fewer intensive care (ICU) admissions compared to the general pediatric and immunocompromised populations. All registry patients with both SCD and MIS-C required ICU admission. Children with SCD are at risk of severe disease with SARS-CoV-2 infection, highlighting the importance of vaccination in this vulnerable population.

Self-management needs, strategies and support for sickle cell disease in developing countries: a scoping review protocol.

INTRODUCTION: Sickle cell disease (SCD) poses a significant global health burden, particularly affecting individuals in developing countries with constrained healthcare resources. While research on self-management in the context of SCD is emerging, it has predominantly focused on primary studies, and there is a notable dearth of evidence synthesis on SCD self-management in developing countries. This scoping review aims to identify and map self-management needs of individuals living with SCD, the strategies they employed to meet those needs, and the support systems available to them. METHODS AND ANALYSIS: The review will be conducted following the Arksey and O'Malley's (2005) 29 framework to comprehensively examine the landscape of SCD self-management research. Searches will be performed in PubMed, Scopus, Embase and Dimensions AI, with additional searches in other databases and grey literature. Indexed literature published in English from inception to January 2024 will be included. Reference list from included studies will also be searched manually. Two teams will be constituted to independently screen titles, abstracts and full text against the eligible criteria. Data will be extracted from included studies onto a customised data extraction form. ETHICS AND DISSEMINATION: Ethical approval is not required for this review due to the fact that it synthesises information from available publications. The findings will be disseminated through publication in a peer-reviewed journal. Also, the findings will possibly be presented at relevant international and national conferences. This protocol has already been registered with the Open Science Framework. The study characteristics such as design and setting will be descriptively analysed and presented as graphs, tables and figures. Thematic analysis will also be conducted based on the study objectives and presented as a narrative summary.

Revolutionising healing: Gene Editing's breakthrough against sickle cell disease.

Recent advancements in gene editing illuminate new potential therapeutic approaches for Sickle Cell Disease (SCD), a debilitating monogenic disorder caused by a point mutation in the ß-globin gene. Despite the availability of several FDA-approved medications for symptomatic relief, allogeneic hematopoietic stem cell transplantation (HSCT) remains the sole curative option, underscoring a persistent need for novel treatments. This review delves into the growing field of gene editing, particularly the extensive research focused on curing haemoglobinopathies like SCD. We examine the use of techniques such as CRISPR-Cas9 and homology-directed repair, base editing, and prime editing to either correct the pathogenic variant into a non-pathogenic or wild-type one or augment fetal haemoglobin (HbF) production. The article elucidates ways to optimize these tools for efficacious gene editing with minimal off-target effects and offers insights into their effective delivery into cells. Furthermore, we explore clinical trials involving alternative SCD treatment strategies, such as LentiGlobin therapy and autologous HSCT, distilling the current findings. This review consolidates vital information for the clinical translation of gene editing for SCD, providing strategic insights for investigators eager to further the development of gene editing for SCD.

Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent ß-Thalassemia.

In 2020, Emmanuelle Charpentier and Jennifer Doudna were awarded the Nobel Prize in Chemistry for their research on the endonuclease, clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated protein 9 (CRISPR-Cas9) method for DNA editing. On 16 November 2023, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) was the first to approve the CRISPR-Cas9 gene editing therapy, Casgevy (exagamglogene autotemcel), for the treatment of patients with transfusion-dependent b-thalassemia and the treatment of sickle cell disease in patients aged ≥12 years with recurrent vaso-occlusive crises. On 8 December 2023, the US Food and Drug Administration (FDA) approved both Casgevy and Lyfgenia (lovotibeglogene autotemcel) for patients with sickle cell disease. On 15 December 2023, the European Medicines Agency (EMA) approved Casgevy for sickle cell disease and transfusion-dependent ß-thalassemia. This Editorial aims to present an update on the landmark first regulatory approvals of CRISPR-Cas9 for patients with sickle cell disease and transfusion-dependent b-thalassemia and the potential challenges for therapeutic gene (DNA) editing.

Knowledge and practices of sickle cell disease among healthcare providers in Kinshasa, Democratic Republic of the Congo.

BACKGROUND:  In Kinshasa, Democratic Republic of Congo, there is a low evocation of the diagnosis of sickle cell disease (SCD) by first-level healthcare providers (HCPs), most likely because of poor knowledge of the disease. AIM:  To assess the levels of knowledge and practices of SCD and to identify determinants of the practices among primary HCPs. SETTING:  Healthcare facilities in Selembao health zone in Kinshasa, Democratic Republic of the Congo. METHODS:  A cross-sectional study of HCPs randomly selected through a two-stage sampling design. Data were collected using a pre-tested interviewer-administered questionnaire. Univariate and bivariate analysis were done to describe the levels of knowledge and practices of SCD. Factors associated with better practices on SCD were determined using multiple linear regression. The threshold for statistical significance was p Ë‚ 0.05. RESULTS:  A total of 318 HCPs, which included 80 physicians and 238 nurses, participated in the study. The participants showed different scores on the components of the knowledge. All the participants showed poor practices on SCD. Multiple linear regression retained overall knowledge of SCD as a significant predictor of better practice for physicians. Knowledge of SCD and duration of work experience were significant predictors of better practices among nurses. CONCLUSION:  The practices of healthcare providers on SCD were far from optimal. These practices were significantly associated with knowledge and experience of healthcare providers.Contribution: This study highlighted the need for continuing professional education to enhance the management of SCD in the setting.