In a trial evaluating two daily-dose levels of voxelotor, which binds to sickle hemoglobin and prevents polymerization under hypoxic conditions, hemoglobin levels increased by more than 1 g per ...deciliter in approximately half the patients who received the drug, and markers of hemolysis decreased. Toxic effects were mainly low grade and not different from those with placebo.
Initiation of regular transfusion in transfusion-dependent thalassemia (TDT) is based on the assessment of clinical phenotype. Pathogenic HBB variants causing β-thalassemia are important determinants ...of phenotype and could be used to aid decision making. We investigated the association of HBB genotype with survival in a cohort study in the four thalassemia centres in Cyprus. HBB genotype was classified as severe (β0/β0 or β+/β0), moderate (β+/β+), or mild (β0/β++ or β+/β++). Risk factors for mortality were evaluated using multivariate Cox proportional-hazards regression. 537 subjects were followed for a total of 20,963 person years. 80.4% (95% CI 76.4-84.7) of individuals survived to 50 years of age with increasing rates of liver, infection and malignancy-related deaths observed during recent follow-up. We evaluated non-modifiable risk factors and found worse outcomes associated with male sex (Hazard ratio 1.9, 95% CI 1.1-3.0, p=0.01) and milder genotype (Hazard ratio 1.6, 95% CI 1.1-2.3, p=0.02). The effect of genotype was confirmed in a second model, which included treatment effects. Patients with a milder genotype initiated transfusion significantly later and had reduced blood requirements compared to those with moderate or severe genotypes, although pre-transfusion hemoglobin levels did not differ between genotypes. Our results suggest that early treatment decisions to delay transfusion and different long-term treatment strategies in milder genotypes have led to adverse long-term effects of under-treated thalassemia and worse survival. We propose that HBB genotype determination and use of this information to aid in decision making can improve long-term outcomes of thalassaemia patients.
Children with sickle cell anemia (SCA) are commonly reported to experience executive dysfunction. However, the development of executive function (EF) in preschool-age children without stroke in this ...patient population has not been investigated so it is unclear when and how these deficits emerge.
This case-control study examines the feasibility of assessing the early development of executive functioning in 22 preschool children years with SCA in the domains of processing speed, working memory, attention, inhibitory control, and cognitive flexibility, as well as everyday function, in comparison to matched control children.
A pattern of potential deficits in early emerging executive skills was observed in the domains of inhibitory control and cognitive flexibility. Parents reported no differences for everyday EF and no significant differences were observed for working memory and processing speed.
Results suggest that deficits in everyday executive difficulties, working memory, and processing speed, as commonly reported for older children with SCA, may not yet have emerged at this early developmental stage, despite specific deficits in cognitive flexibility and inhibitory control on behavioral measures. The feasibility of using available executive measures with preschool age children to characterize the development of early EF skills is discussed. (JINS, 2018, 24, 949-954).
Young people's experiences of healthcare as they move into adult services can have a major impact on their health, and the transition period for young people with sickle cell disease (SCD) needs ...improvement. In this study, we explore how young people with SCD experience healthcare during this period of transition.
We conducted a co-produced longitudinal qualitative study, including 80 interviews in 2016-2017 with young people with SCD aged 13-21 (mean age 16.6) across two cities in England. We recruited 48 participants (30 female, 18 male): 27 interviews were one-off, and 53 were repeated 2-3 times over approximately 18 months. We used an inductive analytical approach, combining elements of Grounded Theory and thematic analysis.
Participants reported significant problems with the care they received in A&E during painful episodes, and in hospital wards as inpatients during unplanned healthcare. They experienced delays in being given pain relief and their basic care needs were not always met. Participants said that non-specialist healthcare staff did not seem to know enough about SCD and when they tried to work with staff to improve care, staff often seemed not prepared to listen to them or act on what they said. Participants said they felt out of place in adult wards and uncomfortable with the differences in adult compared with paediatric wards. Because of their experiences, they tried to avoid being admitted to hospital, attempting to manage their painful episodes at home and accessing unplanned hospital care only as a last resort. By contrast, they did not report having problems within SCD specialist services during planned, routine care.
Our study underscores the need for improvements to make services youth-friendly and youth-responsive, including training staff in SCD-specific care, compassionate care and communication skills that will help them elicit and act on young people's voices to ensure they are involved in shaping their own healthcare. If young people are prevented from using transition skills (self-management, self-advocacy), or treated by staff who they worry do not have enough medical competency in their condition, they may well lose their trust in services, potentially compromising their own health.
Full text
Available for:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sickle cell disease (SCD) is a genetic red blood cell disorder that often leads to stroke and executive dysfunction in school-age children and adults. This study aimed to characterize the development ...of the neural correlates of selective attention, an early component of executive function, in preschool children with SCD.
Auditory event-related potentials (ERPs) were recorded while children attended to a story stream in one ear and ignored a second story in the other ear interchangeably. In total, 12 patients (mean age = 5.5, 7 males) and 22 typically developing children (mean age = 4.4, 10 males) were included in the final analyses.
By 100 ms, more positive ERP amplitudes were observed for attended relative to unattended stimuli in typically developing children but not those with SCD, suggesting deficits in the ability to focus attention. Reduced attention effects were associated with lower performance intellectual quotient.
There are deficits in early attention modulation in young children with SCD.
Few studies have investigated the potential impact of sickle cell anaemia (SCA) on temperament. The aim of the current study was to investigate temperament in preschool children with SCA and to ...establish the reliability of the Children's Behaviour Questionnaire (CBQ) in this population.
The CBQ, a parent-report measure of temperament, was completed by parents of 21 preschool children with SCA and a control group of parents of typically developing children, matched for age, ethnicity and socioeconomic status.
A significant difference between groups was identified for the dimension of negative affectivity only, with specific differences observed in the discomfort subdomain. Patients with a greater number of hospital admissions in the previous year were reported to have higher levels of discomfort.
Preschool children with SCA are reported to have higher rates of negative affectivity, particularly discomfort. Future research is required to investigate the potential influence of dysregulated negative emotions and discomfort on disease management and quality of life throughout childhood.
The Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) has been shown to be a reliable and valid questionnaire measuring health-related quality of life (HRQoL) in the US ...sickle cell disease (SCD) population. The study objective was to test the validity and reliability of the ASCQ-Me for use in the UK.
The US ASCQ-Me, Hospital Anxiety and Depression Scale (HADS), self-reported symptoms, and Medical Outcome Survey Short Form 36 (SF-36) were administered to 173 patients with SCD. Clinical severity was assessed by the number of painful episodes indicated by hospital admissions.
The results showed that the item banks of the UK ASCQ-Me had good internal consistency. Anxiety and depression were strongly correlated with the emotional, and social item banks of the UK ASCQ-Me, with moderate correlations between the UK ASCQ-Me item banks and SF-36 components suggesting convergent validity. A confirmatory factor analysis confirmed the conceptual framework of the scale as being the same as the US ASCQ-Me, indicating construct validity. Known groups validity was found, with the ASCQ-Me being able to differentiate by SCD severity groups.
The analysis of the sample shows evidence of both validity and reliability of the ASCQ-Me for use in the UK SCD population.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
From the Department of Paediatric Haematology and Oncology, Royal London Hospital, London (PT, JE, DR, SC, OW); Infection Control Office, The Windeyer Institute of Medical Science, University ...College, University of London (PC); Sickle and Thalassaemia Centre, London (BS); Department of Haematology, Homerton Hospital, Homerton Row, London (RA, AS); Neurosciences Unit, Wolfson Centre, London, UK (FK)
Correspondence: Paul Telfer, Department of Haematology Royal London Hospital, Whitechapel Road, London E1 1BB, UK. E-mail paul.telfer{at}bartsandthelondon.nhs.uk
Background and Objectives: We investigated outcomes in a UK neonatal cohort as a benchmark for care of children with sickle cell disease (SCD).
Design and Methods: Two-hundred and fifty-two children (180 with hemoglobin Hb SS, 64 with HbSC, and 8 with HbS/ß thalassemia), identified during 1983–2005 by universal birth screening in East London, were followed in a hospital and community-based program which included penicillin V prophylaxis from 3 months of age, 23-valent pneumococcal polysaccharide vaccine from 1993, conjugate pneumococcal vaccine from 2002 and transcranial Doppler screening from 1991.
Results: At the end of 2005, there were 2158 patient years of observation. The median age of the patients was 7.8 (interquartile range 3.3–13.0) years, and 2.8% of those enrolled had been lost to follow-up. The estimated survival of children with HbSS at 16 years was 99.0% (95% confidence interval, CI, 93.2 to 99.9%) and pneumococcal sepsis rate was 0.3 (95% CI 0.1–0.8) episodes per 100 patient-years. The risk of overt stroke was 4.3% (95%CI 1.5 to 11.4%) and could be further reduced by transcranial Doppler screening from infancy and transfusing all children with high-risk scans. No deaths, strokes or episodes of pneumococcal sepsis were observed in children with HbSC or HbS/ß thalassemia. The mortality rates from HbSS were significantly lower than those in other reported cohorts.
Interpretation and Conclusions: Mortality in childhood SCD can virtually be eliminated in a well-resourced health service setting linking community-based care with a specialized, hospital-based center. SCD continues to cause substantial morbidity from acute complications and chronic organ damage. We recommend setting up of clinical networks to optimize the management of SCD.
Key words: neonatal screening, sickle cell, mortality, infection, cerebrovascular disorders.
Executive functions are compromised in children with sickle cell anemia. There is limited research on the development of executive functions in preschool children with sickle cell anemia and the ...factors that contribute to executive dysfunction. We looked at the relation between biomedical and environmental factors, including family functioning and socioeconomic status, and executive functions in 22 preschool children with sickle cell anemia. We found that family functioning was the strongest predictor of executive outcomes in young children with sickle cell anemia with no evidence for an influence of disease severity at this early stage.
Full text
Available for:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
PDF
