Sickle cell disease (SCD) is a group of inherited disorders of the blood that causes a chronic multisystem disease, leading to organ damage and premature death. Key learning points: Sickle cell ...disease is the most common clinically significant genetic disorder affecting newborn children in England. It is characterised by painful crises and increased risk of infection, chronic organ damage and early death. Patients with sickle cell disease require multidisciplinary approach to their management and primary care is pivotal in overseeing delivery of care 20 references
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Background
Children with sickle cell disease (SCD), particularly those with the homozygous form designated HbSS, have frequently been reported to suffer from impaired growth, delayed onset of ...puberty and poor nutritional status (1). However, improvement in healthcare of children with SCD in more economically developed countries, along with increased use of SCD-directed therapies such as hydroxyurea and chronic transfusions along with the recent rise in childhood obesity rates may have influenced growth of children with SCD. Two recent reports in the US found that 19-22% of children with SCD were overweight or obese (2, 3) . It is not known whether high body mass index (BMI) in children with SCD results in a worse clinical phenotype. Known association of childhood obesity with obstructive sleep apnoea (OSA) raises the potential of worsening clinical phenotype of SCD by increasing the incidence of nocturnal hypoxaemia which in turn may give rise to increased vaso-occlusive episodes (4). This study aimed to determine the prevalence of high body mass index (BMI) in an urban population of children in the UK with SCD and assess if there is correlation between BMI and disease severity.
Methods
A retrospective chart review was performed on all patients aged 2-18 years with SCD who attended an outpatient clinic at Kings College Hospital, London between April 2015 and April 2017. Acute sickle cell-related emergency department (ED) attendances and hospital admissions in this period were recorded. BMI percentile, demographic information and laboratory markers of disease were recorded from the most recent clinic visit. Age and gender specific definitions of BMI percentiles were used, based on the British 1990 growth reference charts. Patients were assigned to 1 of 3 groups based on their BMI percentile: low, normal and high BMI. A high BMI was defined as >85th percentile for age and gender, whilst underweight was defined as <5th percentile.
Results
Data was collected on 385 children with SCD in a single tertiary Paediatric Haemoglobinopathy centre in London. 16.6% children with SCD were overweight or obese and 5.2% were underweight. In contrast, government figures indicate that in the South London Borough of Southwark, up to 28% children aged 10-11 years were overweight or obese and 0.9% children were underweight in 2016-2017 (data.london.gov.uk). A high BMI among our SCD patients was associated with HbSC genotype (P= 0.006) and females (P=< 0.001). HbSS patients taking hydroxycarbamide had a significantly higher mean BMI compared to those not taking it (P=0.006). No association was found between BMI group and the number of acute sickle cell-related A&E attendances or hospital admissions for HbSS patients (P=0.450 and 0.780 respectively) or HbSC patients (P=0.838 and P=0.750 respectively). Patients with HbSS SCD in the high BMI group had a significantly higher haemoglobin (Hb) and fetal Hb (HbF) than those in the normal BMI group (P=<0.001 and P=0.010 respectively). HbSS patients in the high BMI group had a significantly lower absolute reticulocyte count (ARC) than those in the normal BMI group (P=0.022), see Table 1. These results suggest that HbSS patients with a high BMI may have a less severe disease than those with a normal BMI. These associations were not demonstrated in patients with HbSC disease.
Conclusions
Nearly one-sixth of children and adolescents with SCD in this urban population were overweight or obese. The association of hydroxycarbamide therapy and higher BMI in children with HbSS has been demonstrated in this study for the first time. There was no association between BMI group and the number of acute sickle cell-related A&E attendances or hospital admissions. In patients with HbSS disease, laboratory markers of disease severity, including Hb, HbF and ARC, suggest than patients with a high BMI may have a less severe disease than those with a normal BMI. Longitudinal studies monitoring BMI of children over time and markers of severity in SCD would produce greater evidence of the impact of a high BMI on disease severity.
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No relevant conflicts of interest to declare.
Sickle cell disease (SCD) is a hereditary red cell disorder with clinical manifestations secondary to sickling or crescent-shaped distortion of the red blood cells. Musculoskeletal complications of ...SCD are often the main causes for acute and chronic morbidities in children with manifestations including osteomyelitis, osteoporosis and osteonecrosis. This article aims to familiarise the paediatric radiologist with appendicular skeletal complications of SCD in the paediatric population and their imaging appearance.
The National Health Service (NHS) in England and Wales provides care for approximately 15000 children and adults with HbO. A national peer review of paediatric and adult HbO services against a set of ...quality standards was commenced in 2010 aiming to obtain a clear picture of service provision. These initial visits confirmed a lack of investment and marked inequalities of care highlighting the need for improved facilities, staffing and the establishment of networks of care. The results of the second national peer review programme (2015/6) are reported here with comparative analysis of performance against quality standards allowing an opportunity to establish whether the programme has led to improvements in the quality of, and access to, care.
Methods
Services were reviewed against a set of 51 quality standards established by a steering group of experienced UK clinicians from the UK Forum for Haemoglobin Disorders. They examined support for patients, staffing, training, facilities/equipment, service organisation, guidelines, governance/audit, clinical networks and commissioning. 32 centres were visited including all major city hospitals in England and smaller hospitals with significant HbO patient populations. Review visits were conducted by a team of doctors, nurses, patient representatives, psychologists and NHS managers and the process was overseen and supported by the West Midlands Quality Review Service. Following each review the centre received a standardised report of compliance highlighting areas of good practice and concerns.
Results
Overall the visits provide evidence of a progressive increase in compliance with the quality standard, more marked in paediatric services (fig 1 and 2). 14/16 (82%) of paediatric and 21/31 (68%) of adult centres showed an improvement in compliance. The percentage of change in compliance ranged from -12 to +39% in paediatric and -22 to +59% in adult centres.
Other findings from the peer review visits showed:•Themes from patient feedback were difficulties accessing adequate emergency care and support for Day Care units providing open access pain control.•Out of hours transfusion was only available in 50% services, throughout the review process.•Inequity of access to automated apheresis with several large centres not being able to provide this service.•Inadequate dedicated medical and nursing time with a decrease in number of adult services with named lead nurse from 68% to 58% in successive reviews. A lack of specialist psychological support was almost universal and unchanged throughout the review period.•In the 2015/16 review only 25% of services had completed audits specified in the standards, but increased numbers of services were developing a rolling programme of audit and participating in research.•Assessment of pain control according to NICE Guidelines had been performed in most centres, however very few services were able to meet the 30 minute arrival to analgesia target.•Transcranial Doppler services were of an inconsistent standard and no national quality assurance tool existed for this investigation.•Increasing numbers of services (67% paediatrics, 75% adults) were participating in multidisciplinary meetings and this had improved from 47% in the previous review.
Conclusion
Peer review of NHS quality of care in England is mostly voluntary but generally valued. This is the first ever report of a nationwide iterative, quality standards-based HbO peer review programme. It was conducted with almost universal participation from individual services, highlighting the willingness of service providers to engage with this voluntary process. Thearguments to sustain such programmes include evidence of cost effectiveness but impact on outcomes is more difficult to demonstrate. This report demonstrates that higher rates of compliance with quality standards were observed following implementation of the peer review programme. In part this is likely to be driven by the peer review process and shows that this process can promote excellence in patient care.
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Howard:Bluebird Bio: Consultancy, Honoraria; Novartis: Honoraria, Speakers Bureau.
Summary
With the developing COVID‐19 pandemic, patients with inherited anaemias require specific advice regarding isolation and changes to usual treatment schedules. The National Haemoglobinopathy ...Panel (NHP) has issued guidance on the care of patients with sickle cell disease, thalassaemia, Diamond Blackfan anaemia (DBA), congenital dyserythropoietic anaemia (CDA), sideroblastic anaemia, pyruvate kinase deficiency and other red cell enzyme and membrane disorders. Cascading of accurate information for clinicians and patients is paramount to preventing adverse outcomes, such as patients who are at increased risk of fulminant bacterial infection due to their condition or its treatment erroneously self‐isolating if their fever is mistakenly attributed to a viral cause, delaying potentially life‐saving antibiotic therapy. Outpatient visits should be minimised for most patients, however some, such as first transcranial dopplers for children with sickle cell anaemia should not be delayed as known risk of stroke will outweigh the unknown risk from COVID‐19 infection. Blood transfusion programmes should be continued, but specific changes to usual clinical pathways can be instituted to reduce risk of patient exposure to COVID‐19, as well as contingency planning for possible reductions in blood available for transfusions. Bone marrow transplants for these disorders should be postponed until further notice. With the current lack of evidence on the risk and complications of COVID‐19 infection in these patients, national data collection is ongoing to record outcomes and eventually to identify predictors of disease severity, particularly important if further waves of infection travel through the population.
ObjectivesTo develop patient-reported experience measure surveys for patients with sickle cell disease (SCD) to understand their healthcare and lived experience in the UK and for their use in future ...to inform healthcare service development.DesignPicker methodology was used as follows: (1) qualitative scoping by focus group discussions; (2) questionnaire development through stakeholder consultations; (3) construct validation of questionnaires through cognitive testing; and (4) further assessment of construct validity by a nationwide pilot survey.SettingPatients with SCD and their carers were eligible. Focus group discussions took place in non-hospital settings, arranged out of hours. Cognitive testing took place in specialist sickle cell clinics. The pilot survey was available to UK participants only and was administered through web-based questionnaires, face-to face completion and in sickle cell community events.ParticipantsThirty-three patients and carers took part in the focus groups, 21 participants undertook cognitive testing and 722 respondents completed the pilot survey.ResultsFindings highlighted a widespread prevalence of poor knowledge about SCD among healthcare providers and the public. Poorer experience of care was present in the emergency setting compared with planned care, of which lack of timely provision of pain relief was of concern. Adolescents and young people reported significantly poorer experience of care in several domains compared with children or adults.ConclusionsThe new surveys functioned well, with good evidence of validity, and were accessible to the SCD patient population, supporting their future use in assessing patient experience to inform service delivery and improvements in care quality.
Introduction
17% of children with sickle cell disease (SCD) between the ages of 6 and 16 could have silent infarcts1. Depending on the area of the brain affected silent infarcts can cause problems ...with attention, coordination, visual-motor speed and executive function. Children with SCD in the UK do not receive routine MRI scans. Subtle defects in cognition can be assessed with neuropsychometric testing which involves multiple tests assessing many areas of cognition. However, testing is limited to those with known neurological deficits due to lack of funding and shortage of specialist staff. There is a need for a robust screening tool for assessment of cognition, which could identify children for further specialist testing.
The Cogstate battery is computer-based program that assesses cognition and has been used in several clinical settings, both adult and paediatric2-3. The Cogstate battery is reported to be culturally neutral and is available in several languages. Additionally the Cogstate battery is free from practice effects and so could be used as an annual assessment tool in order to identify any declines as early as possible. The Cogstate battery has not yet been used to assess cognition in children with SCD.
Research Objectives
The aim of this study was to assess the feasibility of using the Cogstate Battery as a tool for the assessment of cognition in children with SCD. It was hypothesised that the Cogstate battery would be easy to use within this setting and would be acceptable to patients, parents and assessors.
Methods
Eight clinically well children, aged 10-17 with SCD were recruited through St Mary's Hospital paediatric haematology outpatient clinics. The Cogstate software was downloaded onto a Windows laptop computer and an anonymous profile was created for each child before testing. A battery of 6 tests (Table 1) was created aiming to assess a range of cognitive domains within a reasonable amount of time. Every child completed the battery of tests once, which included a short practice before each test. After testing each patient was asked to give an opinion of how they found the tests. Upon completion of the test the patients' results were uploaded to the Cogstate website which generated a test report and a case report form. A mark was given for each test and a score of over 90 represents normal cognition in the area tested, 81-90 represents mild impairment and below 81 represents impairment. Table 1Tests used in the Cogstate battery and corresponding cognitive domains assessedTest NameCognitive Domain TestedContinuous paired associate learning (CPAL)Paired associate learningDetection (DET)Psychomotor functionGroton maze learning test (ME)Executive functionGroton maze learning test-delayed recall (ME)Delayed recallIdentification (IDN)AttentionOne card learning (OCL)LearningOne-back memory (ONBA)Working memory
Results
8 patients completed the battery, taking on average 29 minutes (Table 2). The battery was easy to carry out and although some children reported it as boring, they all finished the tests without distress. The test report generated by the Cogstate website allowed results to be analysed quickly and with ease. An overall score from each test is clearly indicated. The Continuous Paired Associate Learning test was not displayed as part of the test report as there was insufficient normal data to draw conclusions from the results within the age group tested.
Table 2Summary Report of 8 patients testedPatientIDDET(Psychomotor function)IDN(Attention)OCL(Learning)ONBS(Processing speed)ONBA(Working memory)ME(Executive function & delayed recall)00018775827883990002106105949011799000396101959511798000476769481949300058684988189890006981049797941110007949091831018600089188108909695
Conclusion
The Cogstate battery is a feasible tool for paediatric SCD patients and can be undertaken in a clinic setting. This feasibility study will help design a prospective, comparative study of cognition in children with SCD using the Cogstate battery and conventional neuropsychometric assessment and once validated, would be a useful tool to assess cognition and institute timely educational and medical intervention.
References:
1. Pegelow J Pediatr. 2002 Mar;140(3):348-54.
2. Hammers, Am J Alzheimers Dis. 2011 Jun;26(4):326-33
3. Harel PLoS One. 2014 Jul 11;9(7):e101750
No relevant conflicts of interest to declare.
Background: Sickle cell anemia (SCA) is associated with cognitive challenges that often worsen as children age. Previous work has established relationships between hematological markers of disease ...severity (i.e., hemoglobin concentration) and various neurological outcomes, including cognitive impairment. However, most studies have related static, often isolated hemoglobin concentration (Hb) values obtained from a single time-point closest to data collection. Studies of pediatric patients with phenylketonuria and Type I diabetes have demonstrated that longitudinal change and variability in phenylalanine and glucose, respectively, are better indicators of neurological and cognitive outcomes than a single value alone. Our study aimed to be the first study of pediatric patients with SCA to examine the extent to which indices of Hb control (e.g., lifetime average and variability), collected routinely in this patient group, may provide additional prognostic information.
Methods: Data were collected from pediatric patients (aged 4-18 years at enrolment) with and without SCA enrolled on the Sleep Asthma Cohort-III (SAC-III) follow-up study. SAC is a mixed retrospective-prospective study assessing the impact of nocturnal oxygen desaturation on SCA complications. The present investigation assessed participants (see Figure 1 for complete participant demographics) who underwent cognitive evaluation using Wechsler scales measuring domains of IQ, processing speed (i.e., processing speed index PSI and Cancellation subtest), and executive function (working memory index WMI). Participant demographics and appropriate medical data and history (i.e., hydroxyurea therapy, silent infarction) were obtained via questionnaires and analysis of medical records. Hb (d/L) measures assessed included average lifetime values (i.e., mean and median), variability over the lifetime (i.e., standard deviation), and the single value obtained closest to data collection.
Results: Correlation analyses indicated a strong positive relationship between the mean and median Hb values along with large positive associations between the average and contemporaneous values. Small non-significant correlations were demonstrated between variability and average Hb values (see Figure 1). Initial hierarchical linear regression analyses demonstrated that neither hydroxyurea use nor silent infarct (SCI) status were predictors of any cognitive outcomes or Hb values, so they were not included in any further analyses. Separate regression analyses for each cognitive outcome found that mean lifetime Hb values was the only significant predictor of IQ (p = .04, η 2 = .13) and the Cancellation subtest (p = .005, η 2 = .22). Mean lifetime Hb values approached significance for PSI (p = .09, η 2 = .08), but was not a predictor for WMI (p = .33, η 2 = .03).
Conclusion: Our study demonstrated that despite strong correlations between Hb obtained closest to testing and average lifetime values (i.e., rs = .64 and .69), only lifetime Hb predicted cognitive outcomes, particularly processing speed scores from the Cancellation subtest. Variability was not strongly related to other indices of Hb control and did not predict any cognitive outcomes. These results mirror those obtained from other pediatric populations indicating that static, one time values may not best represent clinical manifestations of chronic illness, and the choice of Hb value can differentially influence research study results and clinical prognosis. Future longitudinal work in larger samples is needed, but Hb obtained over the lifetime appears to provide a more precise picture of patients' cognitive developmental trajectory than a single contemporaneous Hb value alone.
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Kirkham: Bluebird Bio: Honoraria; Novartis: Honoraria; Global Blood Therapeutics: Consultancy. Howard: Imara: Consultancy, Honoraria; Global Blood Therapeutics: Consultancy; Novartis: Consultancy, Honoraria; Resonance Health: Honoraria; Novo Nordisk: Consultancy; Agios Pharmaceuticals: Consultancy; Forma Therapeutics: Consultancy; Bluebird Bio: Research Funding.
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Abstract
Background: In addition to pain, sickle cell anaemia (HbSS) complications include neurocognitive difficulties in attention and processing speed associated with low daytime and night-time ...oxygen saturation. These effects can be compounded by obstructive sleep apnoea (OSA). Continuous Positive Airways Pressure (CPAP) is an accepted treatment for OSA in the general population. However, supplementary oxygen therapy in SCA may lead to bone marrow suppression. The aim of this single-blind, randomised, controlled phase II trial is to compare Auto-adjusting CPAP (APAP) with standard care to standard care alone in subjects with HbSS to determine whether the intervention is safe and improves attention and processing speed and brain structure.
Methods: Eligibility criteria included ability to provide informed consent, age >8 and <16 years, diagnosis of HbSS and mean overnight saturation of <90% for <30% of the night. Key exclusion criteria were overnight respiratory support, respiratory or decompensated cardiac failure, chronic transfusion or contra-indications to APAP therapy or MRI.
Minimisation factors were age group (8-11, 12-15), silent infarction on MRI, minimum overnight oxygen saturation > or < 90%, and hydroxyurea (HU) use.
APAP adherence was defined as using APAP for an average of 4 hours a night for >50% of the time and was recorded using software documenting hours of use each night. Participant support in terms of appropriate facemask and facilitating adherence were provided by an unblinded sleep physiologist.
Full blood counts were obtained at baseline, 2 weeks, 3 months and 6 months.
Data were analysed by intention-to-treat. The primary outcome is change in the cancellation subtest from the Wechsler scales, and secondary outcomes include general cognitive functioning, assessed at baseline and after 6 months of treatment by assessors blind to treatment assignment. Analysis of Covariance (ANCOVA) models, adjusted for minimisation factors, were used to calculate least-square mean changes from baseline to 6 months.
Results: 30 children with HbSS were randomised to standard care + APAP (n=15) or standard care alone (n=15) for 6 months. One child in the standard care arm withdrew after 6 weeks, and 8 children in the APAP arm were not adherent to treatment. There was no difference in hemoglobin change between the arms, but hydroxyurea use was associated with an increase in haemoglobin (p=0.01). Increase in cancellation score was numerically greater in the APAP arm (mean 1.46, SE 0.59 vs 1.01, SE 0.61) but this was not significant (mean difference 0.44, 95% CI: -1.42; 2.31; p=0.626). Increase in cancellation score was greater (mean 2.63; 95%CI: 0.95, 4.30) in those whose adherence was in the highest quartile (> 2.4 hours/night) compared with the other 3 quartiles (mean 0.71, 95%CI: -0.32, 1.75; mean difference 1.91, 95%CI: -0.06, 3.88; p=0.057). In subjects assigned to APAP, cancellation scores were significantly higher with hydroxyurea use (p=0.01). There were 7 subjects with serious adverse events in the placebo group, compared to 3 in the APAP group, all related to SCD pain. There was no evidence of decline in haemoglobin in either group.
Discussion: APAP for 6 months is safe, and feasible in children with SCA but although >50% were not adherent by the pre-defined definition, those who were compliant appeared to have more benefit in terms of attention/processing speed. If delivery of the intervention can be improved, avoidance of oxygen desaturation with overnight respiratory support may play a role in improving cognition in SCD.
Trial registration: ISRCTN 46012373 10th July 2015
Protocol Version: 6.0 Date: 24th December 2015
Sponsor: University Hospital Southampton Sponsor's protocol code: RHMCHIOT53
Keywords Sickle Cell Anaemia; haemoglobin oxygen saturation; Auto-adjusting Continuous Positive Airways Pressure; Cancellation; Attention; Processing speed
No relevant conflicts of interest to declare.
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