Comparison of in-hospital mortality in children and adolescents with sickle cell disease in a resource-limited setting before and during the COVID-19 pandemic.

BACKGROUND: COVID-19 in children and adolescents with sickle cell disease (SCD) has variable presentations (from mild to severe disease), and the main symptoms are vaso-occlusive crises (VOC) and acute chest syndrome (ACS). We hypothesized that the desertion of hospitals due to the pandemic would lead to late arrival at the emergency room and an increased mortality. In this study, we sought to measure and compare the mortality of children with sickle cell disease before and during the COVID-19 pandemic. MATERIAL AND METHODS: We conducted a retrospective cohort study at the sickle cell disease management center of Laquintinie Hospital in Douala (Cameroon). The study period was divided into two, i.e., from March 2019 to February 2020 (Pre-COVID-19) and from March 2020 to February 2021 (COVID-19). All administrative and ethical considerations were fully respected. Data were analyzed using SPSS 20.0. RESULTS: Overall, 823 patients were admitted during the study period. Males represented 52.4% of the overall population, giving a sex ratio of 1.1:1. We admitted 479 patients during the pre-COVID-19 period versus 344 patients during the COVID-19 period, which is a 28.2% drop in admissions during the COVID-19 period. The mortality rate was 3.5% during the pre-COVID-19 period and 3.2% during the COVID-19 period (p>0.05). The most common causes of death were ACS (39.3%, n = 11), severe anemia (25.0%, n = 7), and VOC (17.9%, n = 5). ACS (adjusted odds ratio [aOR]=3.628, 95% confidence interval [CI], [1.645-7.005], p<0.001) was significantly associated with mortality. CONCLUSION: During the COVID-19 pandemic, although the consultation frequency decreased, the mortality rate of sickle cell disease patients remained unchanged.

Acute pain episodes, acute chest syndrome, and pulmonary thromboembolism in pregnancy.

Pregnancy in women with sickle cell disease (SCD) is a life-threatening condition. In both high- and low-income countries, there is an 11-fold increased risk of maternal death and a 4-fold increased risk of perinatal death. We highlight the epidemiology of SCD-specific and obstetric complications commonly seen during pregnancy in SCD and propose definitions for acute pain and acute chest syndrome (ACS) episodes during pregnancy. We conducted a systematic review of the recent obstetric and hematology literature using full research articles published within the last 5 years that reported outcomes in pregnant women with SCD. The prevalence of acute pain episodes during pregnancy ranged between 4% and 75%. The prevalence of ACS episodes during pregnancy ranged between 4% and 13%. The estimated prevalence of pulmonary thromboembolism in women with SCD during pregnancy is approximately 0.5 to 1%. ACS is the most common cause of death and is often preceded by acute pain episodes. The most crucial time to develop these complications in pregnancy is during the third trimester and postpartum period. In a pooled analysis from studies in low- and middle-income settings, maternal death in women with SCD is approximately 2393 and 4300 deaths per 100 000 live births with and without multidisciplinary care, respectively. In comparison, in the US and northern Europe, the general maternal mortality rate is approximately 23.8 and 8 deaths per 100 000 live births, respectively. A multidisciplinary SCD obstetrics care approach reduces maternal and perinatal morbidity and mortality in low- and middle-income countries.

Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Following Implementation of the 13-Valent Pneumococcal Conjugate Vaccine in France.

Importance: Acute chest syndrome (ACS) is one of the leading acute severe complications of sickle-cell disease (SCD). Although Streptococcus pneumoniae (S pneumoniae) is highly prevalent in children with SCD, its precise role in ACS is unclear. The efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) implementation on ACS is still unknown. Objective: To assess the association of PCV13 implementation in the general pediatric population with the incidence of ACS in children with SCD. Design, Setting, and Participants: This cohort study used an interrupted time-series analysis of patient records from a national hospital-based French surveillance system. All children younger than 18 years with SCD (based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision definition) hospitalized in France between January 2007 and December 2019 were included. Exposures: PCV13 implementation. Main Outcomes and Measures: Monthly incidence of ACS per 1000 children with SCD over time as analyzed by segmented linear regression with autoregressive error; monthly incidence of hospitalization for vaso-occlusive crisis, asthma crisis, and acute pyelonephritis per 1000 children with SCD over the same period as the control outcomes. Results: Among the 107 694 hospitalizations of children with SCD, 4007 episodes of ACS were included (median [IQR] age, 8 [4-12] years; 2228 [55.6%] boys). PCV13 implementation in 2010 was followed by a significant decrease in the incidence of ACS (-0.9% per month; 95% CI, -1.4% to -0.4%; P < .001), with an estimated cumulative change of -41.8% (95% CI, -70.8% to -12.7%) by 2019. Sensitivity analyses yielded the same results, including the incidence of ACS adjusted for that of vaso-occlusive crisis over time. The results were similar among different age groups. By contrast, no change was found for the 3 control outcomes over the study period. Conclusions and Relevance: PCV13 implementation was associated with an important reduction in the incidence of ACS in children with SCD. This vaccine benefit provides new evidence of the key role of S pneumoniae in ACS and should be considered when estimating outcomes associated with current PCVs and the potential benefit of next-generation PCVs in children.

[Acute chest syndrome in adult sickle cell patients]. / Syndrome thoracique aigu chez les patients drépanocytaires adultes.

Sickle cell disease is a frequent genetic condition, due to a mutation of the ß-globin gene, leading to the production of an abnormal S hemoglobin and characterized by multiple vaso-occlusive events. The acute chest syndrome is a severe complication associated with a significant disability and mortality. It is defined by the association of one or more clinical respiratory manifestations and a new infiltrate on lung imaging. Its pathophysiology is complex and implies vaso-occlusive phenomena (pulmonary vascular thrombosis, fat embolism), infection, and alveolar hypoventilation. S/S or S/ß0-thalassemia genotype, a history of vaso-occlusive crisis or acute chest syndrome, a low F hemoglobin level (<5%), a high steady-state hemoglobin level (> 10 g/dL), or a high steady-state leukocytosis (>10 G/L) are the main risk factors. Febrile chest pain, dyspnea, sometimes cough with expectorations are its main clinical manifestations, and bi-basal crackles are found at auscultation. Inferior alveolar opacities with or without pleural effusions are identified on chest X-ray or CT-scan. Management of the acute chest syndrome should be prompt and implies, besides the recognition of severity signs, a multimodal analgesia, oxygen supplementation, sometimes a parenteral antibiotic treatment and the frequent use of blood transfusions especially in the most severe cases. Prevention is important and includes a regular monitoring of hospitalized patients and the use of incentive spirometry.

Clinical management of the acute complications of sickle cell anemia: 11 years of experience in a tertiary hospital.

INTRODUCTION: Sickle cell disease is an emerging anemia in Europe leading to high morbidity with severe acute complications requiring hospital admission and chronic consequences. The management of these patients is complex and needs interdisciplinary care. The objective is to analyze clinical characteristics and management of patients with sickle cell disease admitted for acute complications. METHODS: Retrospective descriptive study of admissions for acute complications of patients with sickle cell disease under 16 years of age in a tertiary hospital between 2010 and 2020. Clinical, laboratory and radiological data were reviewed. RESULTS: We included 71 admissions corresponding to 25 patients, 40% diagnosed by neonatal screening. Admissions increased during this period. The most frequent diagnoses were vaso-occlusive crisis (35.2%), febrile syndrome (33.8%) and acute chest syndrome (32.3%). Nine patients required critical care at PICU. Positive microbiological results were confirmed in 20 cases, bacterial in 60%. Antibiotic therapy was administered in 86% of cases and the vaccination schedule of asplenia was adequately fulfilled by 89%. Opioid analgesia was required in 28%. Chronic therapy with hydroxyurea prior to admission was used in 41%. CONCLUSIONS: Acute complications requiring hospital admission are frequent in patients with sickle cell disease, being vaso-occlusive crisis and febrile syndrome the most common. These patients need a high use of antibiotics and opioid analgesia. Prior diagnosis facilitates the recognition of life-threatening complications such as acute chest syndrome and splenic sequestration. Despite the prophylactic and therapeutic measures currently provided to these patients, many patients suffer acute complications that require hospital management.

High risk and low prevalence diseases: Acute chest syndrome in sickle cell disease.

INTRODUCTION: Acute chest syndrome (ACS) in sickle cell disease (SCD) is a serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of ACS in SCD, including diagnosis and management in the emergency department (ED) based on current evidence. DISCUSSION: ACS is defined by respiratory symptoms and/or fever and a new radiodensity on chest imaging in a patient with SCD. There are a variety of inciting causes, including infectious and non-infectious etiologies. Although ACS is more common in those with homozygous SCD, clinicians should consider ACS in all SCD patients, as ACS is a leading cause of death in SCD. Patients typically present with or develop respiratory symptoms including fever, cough, chest pain, and shortness of breath, which can progress to respiratory failure requiring mechanical ventilation in 20% of adult patients. However, the initial presentation can vary. While the first line imaging modality is classically chest radiograph, lung ultrasound has demonstrated promise. Further imaging to include computed tomography may be necessary. Management focuses on analgesia, oxygen supplementation, incentive spirometry, bronchodilators, rehydration, antibiotics, consideration for transfusion, and specialist consultation. Empiric antibiotics that cover atypical pathogens are necessary along with measures to increase oxygen-carrying capacity in those with hypoxemia such as simple transfusion or exchange transfusion. CONCLUSIONS: An understanding of ACS can assist emergency clinicians in diagnosing and managing this potentially deadly disease.

Benefit of pulmonary subspecialty care for children with sickle cell disease and asthma.

OBJECTIVE: Asthma is a recognized comorbidity in children with sickle cell disease (SCD). It increases the risk of acute chest syndrome (ACS), vaso-occlusive episodes, and early mortality. We aim to determine whether evaluation and management of children with SCD and asthma by a pulmonologist reduce rate of asthma exacerbation and ACS. METHODS: The study included 192 patients with SCD (0-21 years) followed at Children's Hospital of Philadelphia Hematology between January 1, 2015, and December 31, 2018, with a diagnosis of asthma, wheeze, or cough. Patients were placed in two groups: those evaluated by a pulmonologist (SCD-A-P) and those not (SCD-A). Rates of emergency department (ED) visits and hospitalizations for asthma exacerbation and ACS were compared between groups and over time. RESULTS: SCD-A-P patients (n = 70) were predominantly SCD type SS with lower hemoglobin and hematocrit compared to SCD-A patients (n = 122). SCD-A-P started with a higher average rate of hospital visits for asthma exacerbation and ACS per year (2.69 [1.02-4.37]) compared to SCD-A (0.43 [0.24-0.63]), (p < 0.001). For SCD-A-P patients with at least one hospital visit (n = 48), the average rate decreased from 3.93 (1.57-6.29) to 0.85 (0.48-1.23) following pulmonary consultation (p = 0.014) and was comparable to the SCD-A rate by study end. CONCLUSION: SCD-A-P was mainly SCD type SS and had higher ED/hospitalization rates for asthma exacerbation and ACS compared to SCD-A, but the rates significantly decreased following pulmonology consultation. These findings support the pulmonologist's role in the multidisciplinary care of SCD patients and highlight the need for evidence-based asthma guidelines for children with SCD.

Adverse childhood experiences in children and adolescents with sickle cell disease: A retrospective cohort study.

BACKGROUND: Adverse childhood experiences (ACEs) are linked to poor health outcomes; however, the relationship between ACEs and health outcomes among children and adolescents with sickle cell disease (SCD) has limited documentation in the published literature. PROCEDURE: This retrospective cohort study involved 45 children and 30 adolescents. Participants were screened using the Center for Youth Wellness ACE Questionnaire. Parents completed the questionnaire for children. Adolescents provided self-report. ACEs were treated as continuous and categorical scales: 0-1 verus ≥2 original ACEs (individual and/or familial level); 0-1 versus ≥2 additional ACEs (community level); and 0-3 versus ≥4 expanded ACEs (original + additional). Pain and acute chest syndrome events were compared using Wilcoxon rank-sum tests, and correlated with cumulative ACE scores using Spearman's correlation. Multivariable models were fitted to examine the association between ACEs and pain/acute chest syndrome. RESULTS: The cumulative number of original ACEs positively correlated with acute chest syndrome events (rho = .53, p = .003) and pain (rho = .40, p = .028) among adolescents. Adolescents with ≥2 versus 0-1 original ACEs had a higher number of acute chest syndrome events (4.9 ± 2.6 vs. 1.6 ± 2.2, p = .002); however, this association was confounded by asthma. Acute chest syndrome events and hospitalizations for pain did not differ among child ACE groups. Emergency department (ED) pain visits were higher among children with ≥4 versus 0-3 expanded ACEs (1.6 ± 2.8 vs. 3.3 ± 3.2, p = .042), even after controlling for SCD genotype, asthma, disease-modifying treatment, and follow-up years (p = .027). CONCLUSION: ACEs are linked to increased morbidity among children and adolescents with SCD. Prospective studies are needed to further understand this relationship and test ACE-protective remedies.

What is the role of chest X-ray imaging in the acute management of children with sickle cell disease?

Children with sickle cell disease (SCD) frequently present to hospital acutely unwell and are often exposed to diagnostic chest X-rays (CXRs). Little evidence exists to determine when CXRs are clinically useful. Using electronic hospital records, we audited CXR use in children aged 0-18 who presented to hospital over the past 10 years in both an inpatient and emergency department setting. From a total of 915 first CXRs, only 28·2% of CXRs (n = 258) had clinically significant findings that altered management or final diagnosis. Of these abnormalities, consolidation represented 52·3%, effusion 8·9%, cardiomegaly 8·4% and sickle cell-related bone changes 6·3%. Indications for CXR of respiratory distress (OR = 3·74, 95% CI 2·28-6·13), hypoxia (OR = 1·86, 95% CI 1·50-2·31) and cough (OR = 1·64, 95% CI 1·33-2·02), were more likely to have significant CXR findings. Patients who had higher peak fever (38·4°C vs. 37·4°C, P = 0·001), higher peak CRP (156·4 vs. 46·1, P < 0·001) and higher WCC (20·2 vs. 13·6, P < 0·001) were more likely to have clinically significant abnormalities on CXR. We found a decision tool using either hypoxia, cough, respiratory distress, T > 38°C, CRP > 50 or WCC > 15 × 109 /l as indications for CXR, to have a sensitivity of 88% (with 95% CI 0·78-0·95) and specificity of 46% (95% CI 0·43-0·50) for clinically significant findings.

Nationwide retrospective study of critically ill adults with sickle cell disease in France.

Little is known about patients with sickle cell disease (SCD) who require intensive care unit (ICU) admission. The goals of this study were to assess outcomes in patients admitted to the ICU for acute complications of SCD and to identify factors associated with adverse outcomes. This multicenter retrospective study included consecutive adults with SCD admitted to one of 17 participating ICUs. An adverse outcome was defined as death or a need for life-sustaining therapies (non-invasive or invasive ventilation, vasoactive drugs, renal replacement therapy, and/or extracorporeal membrane oxygenation). Factors associated with adverse outcomes were identified by mixed multivariable logistic regression. We included 488 patients admitted in 2015-2017. The main reasons for ICU admission were acute chest syndrome (47.5%) and severely painful vaso-occlusive event (21.3%). Sixteen (3.3%) patients died in the ICU, mainly of multi-organ failure following a painful vaso-occlusive event or sepsis. An adverse outcome occurred in 81 (16.6%; 95% confidence interval [95% CI], 13.3%-19.9%) patients. Independent factors associated with adverse outcomes were low mean arterial blood pressure (adjusted odds ratio [aOR], 0.98; 95% CI 0.95-0.99; p = 0.027), faster respiratory rate (aOR, 1.09; 95% CI 1.05-1.14; p < 0.0001), higher haemoglobin level (aOR, 1.22; 95% CI 1.01-1.48; p = 0.038), impaired creatinine clearance at ICU admission (aOR, 0.98; 95% CI 0.97-0.98; p < 0.0001), and red blood cell exchange before ICU admission (aOR, 5.16; 95% CI 1.16-22.94; p = 0.031). Patients with SCD have a substantial risk of adverse outcomes if they require ICU admission. Early ICU admission should be encouraged in patients who develop abnormal physiological parameters.

Sex-based differences in the manifestations and complications of sickle cell disease: Report from the Sickle Cell Disease Implementation Consortium.

INTRODUCTION: Sex-based clinical outcome differences in sickle cell disease (SCD) remain largely unknown despite evidence that female sex is associated with an increased lifespan. To better characterize sex-based differences in SCD, we assessed pain, treatment characteristics, laboratory measures and complications among males and females currently enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. METHODS: The SCDIC consists of eight comprehensive SCD centers and one data coordinating center that received funding from the National Heart Lung and Blood Institute to improve outcomes for individuals with SCD. Eligibility criteria included: 15 to 45 years of age and a confirmed diagnosis of SCD. Self-report surveys were completed and data were also abstracted from the participants' medical records. RESULTS: A total of 2,124 participants were included (mean age: 27.8 years; 56% female). The majority had hemoglobin SS SCD genotype. Females had worse reports of pain severity (mean (SD) T-score 51.6 (9.6) vs 49.3 (10), p<0.001), more vaso-occlusive episodes (p = 0.01) and a higher occurrence of 3 or more hospital admissions in the past year (30.9% vs. 25.5, p = 0.03). On multivariable analysis, males had higher odds of acute chest syndrome (odds ratio (OR) 1.4, p = 0.002), cardiovascular (OR 1.70, p<0.001) and musculoskeletal (OR 1.33, p = 0.0034) complications and lower odds of depression (OR 0.77, p = 0.0381). Females had higher fetal hemoglobin levels with and without hydroxyurea use (9.6% vs 8.5%, p = 0.03 and 3% vs 2.2%, p = 0.0005, respectively). CONCLUSION: Our data suggests that sex differences in clinical outcomes do occur among individuals with SCD. Future research needs to explore the mechanisms underlying these differences.

Therapeutic approach to pediatric patients with acute chest syndrome: national multicenter survey of non invasive ventilation (NIV) and transfusion.

BACKGROUND: Intensive care units (ICUs) have seen a spike in the use of noninvasive ventilation (NIV) for many medical conditions. We sought to investigate the attitudes and clinical practice regarding the management of acute chest syndrome (ACS) with a focus on NIV in pediatric ICUs. METHOD: Members of the French Group for Pediatric Intensive Care Emergencies (GFRUP) were asked to complete an online survey on physicians' attitudes toward children with ACS admitted to the PICU during 2015. RESULTS: The survey was answered by teams from 17 PICUs (240 beds). In total, 15 centers (88%) had a local transfusion unit and 14 (82%) worked in connection with a sickle cell disease (SCD) reference center. During 2015, 360 patients with SCD were managed (median: 7 per center; 21) of whom 137 (38%) for an ACS (median: 4 ACS per center; 8). The median length of PICU stay for ACS was 5 days (3.1). Among the 137 patients who presented with ACS, 73 (53%) received simple blood transfusion and 16 (12%) received exchange transfusion. For patients who required noninvasive ventilatory support, NIV with bilevel pressure (BiPAP) was the most frequent method (n = 68, 50%), followed by continuous positive airway pressure (CPAP) (n = 23, 17%) and high-flow oxygen (n = 21, 15%). The proportion of patients on BiPAP was up to 71% in the centers most frequently managing ACS patients. CONCLUSION: BiPAP is commonly used in PICUs for SCD patients with ACS, especially in trained centers. Future physiological studies and randomized controlled trials might help to choose the best ventilatory support for ACS.

Impact of COVID-19 on vasooclusive crisis in patients with sickle cell anaemia.

OBJECTIVES: The study aimed to assess COVID-19 impact on the morbidity and mortality of vasooclusive crisis (VOC) in sickle cell anaemia (SCA) patients. METHODS: A prospective cohort study of 100 SCA patients; 50 with COVID-19 (COVID group) and 50 without (non-COVID group). All patients signed written informed consent. RESULTS: The COVID group had a significantly higher VOC episode median per year; 3 (IQR,1-6) vs 2 (IQR,2-12) (P < 0.05). The need for hospitalisation was similar in both groups. The non-COVID group had more history of culture-proven infection (P = 0.05). The COVID-group had more osteonecrosis (P < 0.05), splenic sequestration, splenomegaly and hepatic crisis (P = 0.05, 0.006, 0.02; respectively) and significantly higher (P < 0.05) symptoms of fever, cough, fatigue, abdominal pain and anosmia. Mean haemoglobin, lymphocyte subset, platelets, and reticulocytes were reduced in both groups, while lactate dehydrogenase and ferritin levels were significantly elevated. In the COVID group, the rise in white blood cell count, reticulocyte percentage, platelets and ferritin was subdued (P < 0.05). Two patients in the COVID group and 3 in the non-COVID group died; there was no statistically significant difference in mortality. CONCLUSIONS: Although COVID-19 may have triggered the onset of VOC, it did not significantly influence VOC-related morbidity or mortality in this SCA cohort.

Posterior Reversible Encephalopathy Syndrome.

PURPOSE OF REVIEW: This review provides an updated discussion on the clinical presentation, diagnosis and radiographic features, mechanisms, associations and epidemiology, treatment, and prognosis of posterior reversible encephalopathy syndrome (PRES). Headache is common in PRES, though headache associated with PRES was not identified as a separate entity in the 2018 International Classification of Headache Disorders. Here, we review the relevant literature and suggest criteria for consideration of its inclusion. RECENT FINDINGS: COVID-19 has been identified as a potential risk factor for PRES, with a prevalence of 1-4% in patients with SARS-CoV-2 infection undergoing neuroimaging, thus making a discussion of its identification and treatment particularly timely given the ongoing global pandemic at the time of this writing. PRES is a neuro-clinical syndrome with specific imaging findings. The clinical manifestations of PRES include headache, seizures, encephalopathy, visual disturbances, and focal neurologic deficits. Associations with PRES include renal failure, preeclampsia and eclampsia, autoimmune conditions, and immunosuppression. PRES is theorized to be a syndrome of disordered autoregulation and endothelial dysfunction resulting in preferential hyperperfusion of the posterior circulation. Treatment typically focuses on treating the underlying cause and removal of the offending agents.

Acute chest syndrome in pediatric sickle cell disease: Associations with racial composition and neighborhood deprivation.

BACKGROUND: Acute chest syndrome (ACS) is the leading cause of death for children with sickle cell disease (SCD). Recurrent ACS has detrimental effects on pulmonary health and health care costs. Neighborhood characteristics affect the outcomes of many pediatric chronic diseases, but their role in SCD is not well studied. In this study, we investigated the effects of area-level socioeconomic deprivation and racial composition on the recurrence of ACS. STUDY DESIGN: We performed a retrospective cross-sectional analysis of clinical data from a large pediatric SCD center. Patients' residential addresses were geocoded and linked to a composite area deprivation index (ADI) and percent African American population at the level of Census block groups. The association of recurrent ACS with neighborhood characteristics was evaluated using logistic regression analysis. RESULTS: The sample included 709 children with SCD. Residence in a socioeconomically deprived neighborhood was associated with 27% less risk of recurrent ACS, and residence in a predominantly African American neighborhood was associated with 41% less risk of ACS recurrence. The racial composition explained the protective effect of living in a high-deprivation area after adjusting for sociodemographic and clinical covariates. Demographic and clinical factors associated with recurrent ACS included older age, male gender, asthma, hydroxyurea use, and chronic transfusion therapy. CONCLUSIONS: This is the first study to report a protective effect of residing in a predominantly African American community for ACS recurrence. Further prospective studies are needed to confirm the association and to understand the mechanisms of such relationship.

The burden of respiratory syncytial virus infections among children with sickle cell disease.

BACKGROUND: Although respiratory syncytial virus (RSV) is the leading cause of pediatric lower respiratory tract infections, the burden of RSV in children with sickle cell disease (SCD) is unknown. METHODS: We conducted a retrospective, nested, case-control study of children with SCD <18 years who had respiratory viral panels (RVPs) performed at Children's Healthcare of Atlanta from 2012 to 2019. We abstracted the medical records to describe the demographics, clinical features, and outcomes of children who tested positive for RSV (cases) versus children who tested negative (controls). We calculated the annual incidence of RSV and related hospitalization rates with 95% confidence intervals (CIs) and used multivariate logistic regression to evaluate associations. RESULTS: We identified 3676 RVP tests performed on 2636 patients over seven respiratory seasons resulting in 219/3676 (6.0%) RSV-positive tests among 160/2636 (6.1%) patients. The average annual incidence of laboratory-confirmed RSV infection among children with SCD was 34.3 (95% CI 18.7-49.8) and 3.8 (95% CI 0.5-7.0) cases per 1000 person-years for those <5 years and 5-18 years, respectively. The RSV-related hospitalization rate for children <5 years was 20.7 (95% CI 8.5-32.8) per 1000 person-years. RSV-positive cases were significantly younger than RSV-negative patients (3.8 years vs 7.6 years, P < .001). Of RSV-positive cases, 22 (13.8%) developed acute chest syndrome and nine (5.6%) required intensive care, which was not significantly different from RSV-negative children with SCD. CONCLUSION: RSV infections are common in children with SCD with higher burden in younger patients. RSV is associated with considerable morbidity, including higher rates of hospitalization compared to the general population.

Effect of hydroxyurea exposure before puberty on sperm parameters in males with sickle cell disease.

Sperm parameters are known to be impaired in men with sickle cell disease (SCD). Although treatment with hydroxyurea (HU) has an impact on sperm quality, sperm preservation is impossible before puberty. This study's primary objective was to analyze and compare sperm parameters in male patients with SCD exposed (or not) to HU before puberty. Twenty-six sperm samples from 15 patients (median age, 17 years; range, 16-23) treated with HU during childhood were compared with 46 samples from 23 HU-naïve patients (20 years; 16-24). The median age at HU initiation was 6 years (1-14 years), the median duration of HU treatment was 4 years (0.5-10), and the mean dose of HU was 22.4 ± 3.7 mg/kg per day. Although we observed substantial quantitative and qualitative semen abnormalities in all patients, there were no significant differences in semen volume, sperm concentration, total sperm count, or spermatozoa motility, morphology, and vitality between the HU-exposed and HU-naïve groups. At the time of the semen analysis, 100% of the patients in the HU-exposed group and 52% of the patients in the HU-naïve group received transfusion therapy. The specific effect of HU on spermatogenesis in very young infants and the putative value of transfusion for reversing the toxicity of HU warrant further investigation.

Clinical outcomes following bone marrow transplantation in patients with sickle cell disease: A cohort study of US Medicaid enrollees.

OBJECTIVES: Bone marrow transplantation (BMT) is currently the only curative therapy available for patients with sickle cell disease (SCD), but clinical outcomes in routine care are not well understood. We describe the rates of vaso-occlusive crises (VOCs), transplant complications, and mortality in SCD patients after BMT. METHODS: A cohort study of SCD patients who underwent BMT was designed using US Medicaid claims data (2000-2013). RESULTS: A total of 204 SCD patients undergoing BMT were identified with a mean (SD) age of 10.6 (7.3) years, with 52.9% male and 67.6% African American. The overall VOC rate was 0.99 per person-year (95% CI: 0.91-1.07) over a median follow-up time of 2.1 years (IQR: 0.8-4.3 years). A total of 138 (67.6%) remained free of VOCs. The mortality rate was 1.7 (95% CI: 0.9-3.1) per 100 person-years, transplant-related complications occurred among 113 (55.4%) patients with an incidence rate of 38.2 (95% CI: 31.7-45.9) per 100 person-years, while 47 (23%) patients had GvHD with an incidence rate of 8.0 (95% CI: 6.0-10.7) per 100 person-years. CONCLUSION: Two thirds of the BMT recipients remained VOC-free over 2 years of follow-up, but transplant-related complications, including GvHD occurred with high frequency. This highlights a continuing unmet need for alternative curative interventions in SCD.