OBJECTIVEThe purpose of this retrospective cross-sectional study was to investigate whether changes in white matter integrity are related to slower processing speed in sickle cell anemia.
...METHODSThirty-seven patients with silent cerebral infarction, 46 patients with normal MRI, and 32 sibling controls (age range 8–37 years) underwent cognitive assessment using the Wechsler scales and 3-tesla MRI. Tract-based spatial statistics analyses of diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) parameters were performed.
RESULTSProcessing speed index (PSI) was lower in patients than controls by 9.34 points (95% confidence interval4.635–14.855, p = 0.0003). Full Scale IQ was lower by 4.14 scaled points (95% confidence interval−1.066 to 9.551, p = 0.1), but this difference was abolished when PSI was included as a covariate (p = 0.18). There were no differences in cognition between patients with and without silent cerebral infarction, and both groups had lower PSI than controls (both p < 0.001). In patients, arterial oxygen content, socioeconomic status, age, and male sex were identified as predictors of PSI, and correlations were found between PSI and DTI scalars (fractional anisotropy r = 0.614, p < 0.00001; r = −0.457, p < 0.00001; mean diffusivity r = −0.341, p = 0.0016; radial diffusivity r = −0.457, p < 0.00001) and NODDI parameters (intracellular volume fraction r = 0.364, p = 0.0007) in widespread regions.
CONCLUSIONOur results extend previous reports of impairment that is independent of presence of infarction and may worsen with age. We identify processing speed as a vulnerable domain, with deficits potentially mediating difficulties across other domains, and provide evidence that reduced processing speed is related to the integrity of normal-appearing white matter using microstructure parameters from DTI and NODDI.
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.
Previous studies have pointed to a role for regional cerebral hemodynamic stress in neurological complications in patients with sickle cell anemia (SCA), with watershed regions identified as ...particularly at risk of ischemic tissue injury. Using single- and multi-inflow time (TI) arterial spin labeling sequences (ASL) in 94 patients with SCA and 42 controls, the present study sought to investigate cerebral blood flow (CBF) and bolus arrival times (BAT) across gray matter, white matter with early arrival times, and in individual watershed areas (iWSAs). In iWSAs, associations between hemodynamic parameters, lesion burden, white matter integrity, and general cognitive performance were also explored. In patients, increases in CBF and reductions in BAT were observed in association with reduced arterial oxygen content across gray matter and white matter with early arrival times using both sequences (all
< 0.001, d = -1.55--2.21). Across iWSAs, there was a discrepancy between sequences, with estimates based on the single-TI sequence indicating higher CBF in association with reduced arterial oxygen content in SCA patients, and estimates based on the multi-TI sequence indicating no significant between-group differences or associations with arterial oxygen content. Lesion burden was similar between white matter with early arrival times and iWSAs in both patients and controls, and using both sequences, only trend-level associations between iWSA CBF and iWSA lesion burden were observed in patients. Further, using the multi-TI sequence in patients, increased iWSA CBF was associated with reduced iWSA microstructural tissue integrity and slower processing speed. Taken together, the results highlight the need for researchers to consider BAT when estimating CBF using single-TI sequences. Moreover, the findings demonstrate the feasibility of multi-TI ASL for objective delineation of iWSAs and for detection of regional hemodynamic stress that is associated with reduced microstructural tissue integrity and slower processing speed. This technique may hold promise for future studies and treatment trials.
AimsMoving from paediatric to adult services is a worrying and challenging time for young people with long-term conditions. Evidence suggests that effective transition between services can improve ...long-term outcomes,1 yet national data highlights that transition is often overlooked with little recognition as an area of importance within healthcare.2 However, there has recently been a drive to refine and improve the transition process through the NHS long term plan. This quality improvement project aimed to achieve the NICE Quality Standards for transition3 for 6 sub-sepcialties in one paediatric department, across a nine-month period.MethodsAn initial gap analysis was undertaken using 11 NICE quality transition-focused standards of care to demonstrate current performance of services for transition for 6 sub-sepcialties: allergy, asthma, diabetes, epilepsy, HIV, and sickle. Diagnostic tools including a process map, fishbone diagram, histogram and RAG rating were completed to help define the problem further. Following this, change ideas were generated and several PDSA cycles were conducted through transition workshops, regular progress meetings and implementation of individualised action points for each sub-specialty.ResultsBaseline measurement following the initial gap analysis showed that only 18% of standards were partially met and 45% of standards were met across the 6 sub-specialties. Diabetes, HIV and Sickle showed better performance, meeting at least 6 out of 11 standards of care for transition. Following the implementation of individualised action points and transition workshop meetings, the baseline measurement for partially meeting and meeting standards increased to 30%, and 58%, respectively. Standards 1 and 2 still require improvement across all specialties. Importantly, specialties such as asthma and epilepsy showed significant changes in partially meeting or meeting standards.ConclusionThis quality improvement project has enabled one paediatric department to better achieve the NICE standards of care for transition for young people with long-term conditions. Highlights during the process included: external talks from a transition improvement manager and a transition nurse consultant, regular transition workshop meetings and successfully obtaining funding for a new epilepsy transition specialist nurse through Roald Dahl’s children’s charity. In addition, there was implementation of the Ready, Steady, Go, paperwork, joint clinics between paediatric and adult services for asthma and epilepsy, along with asthma transition clinics within the local community.Measurable progress has been made in implementing transition-related standards of care, however; further work is needed to ensure young people and their families are actively involved in the design, delivery, and evaluation of transition services. Importantly, ongoing work is required to ensure that transition-related standards of care are met and provided for young people when moving from paediatric to adult healthcare services.(1) Implementing Transition: Ready Steady Go, Arvind Nagra(2) From the pond into the sea, children’s transition to adult health services, CQC(3) Transition from children’s to adults’ services, NICE Quality Standards
Research in sickle cell anemia (SCA) has used, with limited race-matched control data, binary categorization of patients according to the presence or absence of silent cerebral infarction (SCI). SCI ...have primarily been identified using low-resolution MRI, with radiological definitions varying in lesion length and the requirement for abnormality on both fluid attenuated inversion recovery (FLAIR) and T1-weighted images. We aimed to assess the effect of published SCI definitions on global, regional, and lobar lesion metrics and their value in predicting cognition. One hundred and six patients with SCA and 48 controls aged 8–30 years underwent 3T MRI with a high-resolution FLAIR sequence and Wechsler cognitive assessment. Prevalence, number, and volume of lesions were calculated using a semi-automated pipeline for SCI defined as: (1) Liberal: any length (L-SCI); (2) Traditional: >3 mm in greatest dimension (T-SCI); (3) Restrictive; >3 mm in greatest dimension with a corresponding T1-weighted hypo-intensity (R-SCI). Globally, as hypothesized, there were large effects of SCI definition on lesion metrics in patients and controls, with prevalence varying from 24–42% in patients, and 4–23% in controls. However, contrary to hypotheses, there was no effect of any global metric on cognition. Regionally, there was a consistent distribution of SCI in frontal and parietal deep and juxta-cortical regions across definitions and metrics in patients, but no consistent distribution in controls. Effects of regional SCI metrics on cognitive performance were of small magnitude; some were paradoxical. These findings expose the challenges associated with the widespread use of SCI presence as a biomarker of white-matter injury and cognitive dysfunction in cross-sectional high-resolution MRI studies in patients with SCA. The findings indicate that with high-resolution MRI: (1) radiological definitions have a large effect on resulting lesion groups, numbers, and volumes; (2) there is a non-negligible prevalence of lesions in young healthy controls; and (3) at the group-level, there is no cross-sectional association between global lesion metrics and general cognitive impairment irrespective of lesion definition and metric. With high-resolution multi-modal MRI, the dichotomy of presence or absence of SCI does not appear to be a sensitive biomarker for the detection of functionally significant pathology; the search for appropriate endpoints for clinical treatment trials should continue.
ObjectivesTransition to adult services is recognised as a challenging time for young people (YP) with chronic conditions, associated with loss to follow up and poor health outcomes. Although evidence ...suggests young people with sickle cell disease (YPSCD) feel unsupported during transition, many studies highlighted lack of engagement. We organised an engagement event for children, YPSCD and their families with these objectives:Educate YPSCD on their health in preparation towards adulthood.Equip YPSCD with self-efficacy and self-advocacy skills.Understand the challenges of living with sickle cell disease (SCD).MethodsA pilot regional engagement event was held for children, YPSCD and their families in a non-clinical setting, a premier league football club, fundraised by three NHS trusts.It was advertised as a fun, festival-like event with a range of activities including a DJ, celebrity appearance, street dance, rap performance, choir, and outdoor games.Social and health education was delivered by skilled professionals through workshops, stalls, and sessions on transition, breathwork, confidence building, career advice, citizen’s advice, treatment and research, dental health, complementary therapies, and inspirational stories from SC warriors.Attendees collected stamps in momento booklets on health education interactions.Thematic analysis was performed on qualitative data collected on event feedback, transition-related concerns, and experience of living with SCD.Results212 sickle cell warriors (59% 11–18 y/o) registered to attend with 800 of their friends and families. 123 adults and 153 CYP cared for by 11 NHS trusts attended.We collected 64 event feedback data. 9% of responders mentioned gaining knowledge about transition.Two transition workshops were attended by 60 people (23 carers, 26 YP and 11 health professionals). Primarily carers voiced concerns around transition which garnered discussions on themes below:Adult acute hospital careAccess and support from primary careYP’s efficacy in managing their healthYP’s ability to advocate for their healthData on experience of living with SCD was collected from 46 CYP 21 (11–15 y/o) and 8 (16 -18 y/o) and 47 carers 12 (carers of 12 -15 y/o) and 6 (carers of 16 -18 y/o).YP and carers across the age groups had similar worries:Missed educational opportunitiesDisease impact on future careerWell-being and social healthPainHelpful interventions suggestedImproved education and awarenessImproved hospital experienceAccess to a supportive communityAdvancement in researchConclusionsYPSCD are interested in educational health events in a non-clinical setting.Engagement events are a platform for equipping YPSCD with skills required to transition to adult care.YPSCD and their carers have similar worries about their chronic health condition.Transition-specific workshops provide an opportunity for discussing issues and strategies to overcome them.Workshops designed for YPSCD without their carers may be helpful to encourage participation and address their concerns.Generic, disease-specific transition workshops can complement individual transition work provided by local healthcare teams.
Abstract
Background
Young children with sickle cell anaemia (SCA) often have slowed processing speed associated with reduced brain white matter integrity, low oxygen saturation, and sleep-disordered ...breathing (SDB), related in part to enlarged adenoids and tonsils. Common treatments for SDB include adenotonsillectomy and nocturnal continuous positive airway pressure (CPAP), but adenotonsillectomy is an invasive surgical procedure, and CPAP is rarely well-tolerated. Further, there is no current consensus on the ability of these treatments to improve cognitive function. Several double-blind, randomised controlled trials (RCTs) have demonstrated the efficacy of montelukast, a safe, well-tolerated anti-inflammatory agent, as a treatment for airway obstruction and reducing adenoid size for children who do not have SCA. However, we do not yet know whether montelukast reduces adenoid size and improves cognition function in young children with SCA.
Methods
The Study of Montelukast In Children with Sickle Cell Disease (SMILES) is a 12-week multicentre, double-blind, RCT. SMILES aims to recruit 200 paediatric patients with SCA and SDB aged 3–7.99 years to assess the extent to which montelukast can improve cognitive function (i.e. processing speed) and sleep and reduce adenoidal size and white matter damage compared to placebo. Patients will be randomised to either montelukast or placebo for 12 weeks. The primary objective of the SMILES trial is to assess the effect of montelukast on processing speed in young children with SCA. At baseline and post-treatment, we will administer a cognitive evaluation; caregivers will complete questionnaires (e.g. sleep, pain) and measures of demographics. Laboratory values will be obtained from medical records collected as part of standard care. If a family agrees, patients will undergo brain MRIs for adenoid size and other structural and haemodynamic quantitative measures at baseline and post-treatment, and we will obtain overnight oximetry.
Discussion
Findings from this study will increase our understanding of whether montelukast is an effective treatment for young children with SCA. Using cognitive testing and MRI, the SMILES trial hopes to gain critical knowledge to help develop targeted interventions to improve the outcomes of young children with SCA.
Trial registration
ClinicalTrials.gov
NCT04351698. Registered on April 17, 2020. European Clinical Trials Database (EudraCT No. 2017-004539-36). Registered on May 19, 2020
ObjectivesTo evaluate trainee priorities and identify areas of improvement to achieve an excellent training programme. Report of trainee experiences and free text analysis from the London School of ...Paediatrics 2022 survey.Methods961 trainees were invited to complete a survey, of whom 759 were in programme (202 were out of programme or academic trainees).The survey comprised of two separate areas for analysis:Closed questions to allow for rating and comparison between trusts.Open comments -written responses by trainees on both positives and improvements/issues on their placements.Free text qualitative analysis was performed by DataSyrup and the Everyday Excellence subgroup of the London School of Paediatrics to code for and identify common themes.Results671 trainees responded to the survey – an 88% completion rate. This year 78% of trainees judged their placement to be ‘good’ or ‘excellent’ overall, which was similar to survey data from 2021. The most common themes identified for excellence and improvement are described below.What makes an excellent placement?The top three factors that create an excellence placement for a trainee are:A great variety in learning experiences, opportunities and exposureGood senior support, especially engaged and supportive consultantsA great wider team, supportive relationships and a friendly environment to work inA word cloud of common themes for excellence is represented in figure 1.What are the most pressing improvements?Rota issues and staffing levels continue to dominate concerns -they have increased and are now mentioned by over half of all trainees.The other most commonly identified areas of improvement are:Workload intensityPoor/lack of teachingA lack of learning opportunitiesTeam/relationship/morale issuesA word cloud of common themes for improvement is represented in Figure 2.Abstract 576 Figure 1ConclusionsTeamwork and clinical experience remain the cornerstones of an excellent trainee experience. However, the importance of consultant engagement and support is a new theme from this year’s survey. This, alongside the aforementioned areas for improvement, should be the focus for departments aiming to improve trainee experience in the future.
AimTo evaluate incidences and management of acute paediatric sickle cell pain, and outcomes of safety and efficacy of codeine in patients at North Middlesex University Hospital (NMUH).MethodA ...retrospective audit was performed on all admissions with diagnosis of sickle cell pain from January to December 2013. Case notes of 54 patients were reviewed using pre-specified audit criteria in a data collection tool. Types of analgesics administered at home and in the accident and emergency (A&E) department and pain scores were recorded where available from the case notes. Particular attention was paid to the use of codeine and outcomes of efficacy and safety.ResultsOver the one-year period, 91 admissions were recorded. The average age of the population was 6.6 years ( plus or minus 4.1), with the majority (45%) of the population aged between 1 and 5 years. The most prevalent haemoglobinopathy was HbSS (82%), followed by HbSC (13%) and beta -thalassemia (4%). The majority of patients (61%) had a single painful crisis admission, 33% had 2-3 admissions, and the remainder presented with four or more admissions in the year.The audit revealed that most patients (93%) received one or more analgesics prior to admission, although the drug of choice varied, with paracetamol and ibuprofen been the most frequently utilised combination (43%) and 22% received opioids (20% had codeine). Similar to the pre-admission trends, a wide range of analgesics were utilized at the Trust, with the majority of patients receiving paracetamol and ibuprofen combination. However, the doses utilized at home were significantly less than those given on admission, suggesting inadequate pain management at home. Codeine was given in 37% of the cases after admission and it was observed that patients who received codeine had significantly higher initial pain scores on admission compared with those who did not receive codeine. There were also greater reductions in pain scores recorded post analgesia although accurate inferential statistics could not be carried out due to incomplete documentation of pre and post medication pain scores.In addition, the audit revealed compliance with guidelines was poor, particularly as documentations were mostly incomplete/not done. Although up to 82% documented fluid balance, only 7.7% recorded pain scores appropriately on the assessment scale, while 36.3% and 28.6% utilised the first hour sheet and fast track forms respectively (local assessment documentation sheets). Similarly, the time of assessment, analgesia and reassessment were recorded in 29%, 36% and 5.5% of cases respectively.ConclusionThe current audit revealed that only 2% of the admissions for sickle cell pain crisis at the Trust in 2013 met all criteria specified in the local and national guidelines for management of the condition. This was mostly attributed to poor documentation of assessments. In addition, clear analgesic benefits could not be demonstrated for codeine use with regards to the outcome of efficacy.According to the main outcome of the audit, efforts need to focus on increasing awareness of the objectives of utilisation of Trust documentation sheets to facilitate prompt and appropriate management.
To ascertain the prevalence of and risk factors for obstructive sleep apnea syndrome (OSAS) in children with sickle cell anemia (SCA).
Cross-sectional baseline data were analyzed from the Sleep and ...Asthma Cohort Study, a multicenter prospective study designed to evaluate the contribution of sleep and breathing abnormalities to SCA-related morbidity in children ages 4 to 18 years, unselected for OSAS symptoms or asthma. Multivariable logistic regression assessed the relationships between OSAS status on the basis of overnight in-laboratory polysomnography and putative risk factors obtained from questionnaires and direct measurements.
Participants included 243 children with a median age of 10 years; 50% were boys, 99% were of African heritage, and 95% were homozygous for β(S) hemoglobin. OSAS, defined by obstructive apnea hypopnea indices, was present in 100 (41%) or 25 (10%) children at cutpoints of ≥1 or ≥5, respectively. In univariate analyses, OSAS was associated with higher levels of habitual snoring, lower waking pulse oxygen saturation (Spo2), reduced lung function, less caretaker education, and non-preterm birth. Lower sleep-related Spo2 metrics were also associated with higher obstructive apnea hypopnea indices. In multivariable analyses, habitual snoring and lower waking Spo2 remained risk factors for OSAS in children with SCA.
The prevalence of OSAS in children with SCA is higher than in the general pediatric population. Habitual snoring and lower waking Spo2 values, data easily obtained in routine care, were the strongest OSAS risk factors. Because OSAS is a treatable condition with adverse health outcomes, greater efforts are needed to screen, diagnose, and treat OSAS in this high-risk, vulnerable population.
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