Sickle Cell Disease In England Research Articles

Co-morbidities and mortality in patients with sickle cell disease in England: A 10-year cohort analysis using hospital episodes statistics (HES) data

Patients with a primary diagnosis of sickle cell disease (SCD) with or without crisis during the 10-year period January 2009 to December 2018 were identified in the HES Admitted Patient Care (APC) dataset and matched with the Office for National Statistics (ONS) mortality dataset. Three sub-cohorts were defined: ‘crises’, ‘transfusions’ and ‘other SCD’. APC records were examined for co-morbidities commonly associated with SCD and 10-year mortality rates compared with the general population.After data cleaning and exclusions, 9503 patients remained (entire cohort), with 1171, 201, and 8131 in crises, transfusions, and other SCD sub-cohorts, respectively. Median numbers of co-morbidities per patient were 2 (Interquartile range (IQR): 1–4), 2 (IQR: 1–3), and 1 (IQR: 0–2) in the crises, transfusions, and other SCD sub-cohorts, respectively. The majority of patients in the crises (63.2%) and transfusions (56.3%) cohorts had ≥2 co-morbidities, compared with 25.3% in the other SCD sub-cohort. Crude 10-year mortality rate was 5.3% (entire cohort), compared with 8.0% (crises) and 11.4% (transfusions) sub-cohorts; all rates were substantially higher than in age-sex matched general population.Our study adds further evidence that morbidity and mortality associated with SCD in England is high.

No Demonstrable Benefit of Penicillin in a Vaccinated Population of Children with Sickle Cell Disorder

UK and many National guidelines advise on the use of prophylactic antibiotics, immunisation and patient education to minimise the risk of severe infections by encapsulated organisms in patients with Sickle Cell Disorder. The UK vaccination schedule for sickle cell anaemia patients includes Pneumococcal, Meningococcal and Haemophilus influenzae type B (Hib) immunisation. Prophylactic Penicillin V is recommended as additional protection against Streptococcus pneumoniae (S.pneumoniae).In light of the findings in the papers by Oligbu et al, 2017, and Martin et al 2018, we aimed to retrospectively compare compliance with prophylactic Penicillin V against infection rates by S.pneumoniae,Neisseria meningitidis (N.meningitidis) and Hib . We hypothesised that the incidence of infections with IPD and other encapsulated organisms would be greater in patients who were not adherent with Penicillin V. Patients were considered compliant with prophylactic Penicillin V if 75% or more of their urine samples gave positive results.The study population consisted of 52 Sickle Cell patients, ranging from age 3 to 20years.Three patients were excluded as no urine samples had been collected from them in the 5 year period. Of the remaining 49 patients only 9 patients (18%) were had good adherence with Penicillin V over a 5 year period.100% of patients received prevenar vaccination (PCV-7 or PCV 13).73% received additional pneumovax.We retrospectively reviewed microbiology culture reports over a five year period. All microbiology reports were reviewed from the period, with the virulent encapsulated organisms of S.pneumoniae,N.meningitidis and Hib recorded, alongside any other bacterial infections.No patients had microbiological evidence of infection by virulent encapsulated bacteria. Six patients had cultures positive for other organisms: two Staphylococcus aureus positive sputum cultures, one Salmonella positive stool culture, two urine cultures positive for Escherichia coli, and one skin wound swab positive for Streptococcus pyogenes.Of the 6 organisms identified, 3 occurred in patients compliant with Penicillin V, and 3 occurred in patients who were non-compliant. Patients compliant with Penicillin V formed a small cohort (n=9), resulting in an apparently high incidence of infection (33%). In the non-compliant cohort (n=40), 8% had shown infection. Analysis by Fisher's Exact Test confirmed no significant difference in the incidence of infection between the two groups (p= 0.06).In a sickle cell disorder population where 82% of the patients were not 100% compliant with prophylactic Penicillin V, no significant encapsulated bacteria (S.pneumoniae,N.meningitidis or Hib) were cultured in a 5 year period in our cohort. Non-compliance with prophylactic Penicillin V was not associated with an increased incidence of infections by encapsulated organisms.The UK study (Oligbu et al) on IPD was performed in the PCV13 era and states a 49x increased risk of developing IPD and a 5x increase in mortality in children with sickle cell compared to their peers. However, most IPD cases were due to non-vaccine serotypes. A similar study from the US (Martin et al) found deaths only in the PCV7 cohort, it does not state if the patients were vaccinated with pneumovax 23.In conclusion 82% of children did not adhere to penicillin. We have not demonstrated any benefit in adhering to prophylactic penicillin. Adherence is poor and alternative approaches of standby antibiotics should be considered. We suggest focusing on vaccination as a preventative strategy is of more benefit. Martin OO, Moquist KL, Hennessy,JM, Nelson SC. Invasive pneumococcal disease in children with sickle cell disease in the pneumococcal conjugate vaccine era. Pediatr Blood Cancer. 2018;65:e26713. https://doi.org/10.1002/pbc.26713Oligbu G, Collins S , Streetly A, Dick, M, Ladhany, S. Risk of invasive pneumococcal disease in children with sickle cell disease in England: National observational cohort study, 2010 - 2015. Arch Dis Child 2017;102(Suppl1):A4-A4 DisclosuresNo relevant conflicts of interest to declare.

Risk of Invasive Pneumococcal Disease in Children with Sickle Cell Disease in England: A National Observational Cohort Study, 2010–2015

ObjectiveTo describe the clinical presentation, risk factors, serotype distribution and outcomes of invasive pneumococcal disease (IPD) in children with sickle cell disease (SCD) following the introduction of the 13-valent pneumococcal...

Socio-economic deprivation and risk of emergency readmission and inpatient mortality in people with sickle cell disease in England: observational study

Sickle cell disease (SCD) is a cause of frequent emergency readmissions. We examined trends in SCD emergency readmissions and inpatient mortality in England in relation to socio-economic status. Data from Hospital Episode Statistics were extracted for all SCD patients admitted in 2005/06. The financial year 2005/06 was taken as the index year for analysis. We calculated readmission rates and inpatient mortality for patients admitted with a primary or secondary diagnosis of sickle cell anaemia with crisis and without crisis in the index year during the subsequent 5 years (2006/07-2010/11). Charlson Score was used to measure comorbidity. Using Cox proportional hazards models, we also examined the relationship between patient characteristics and both emergency readmissions and inpatient mortality. In 2005/06, there were 7679 SCD index admissions. Over the subsequent 5-year period, patients living in the most socio-economically deprived areas were at highest risk of readmission (54.2% readmitted over the study period compared with 28% of the least deprived group). Inpatient mortality amongst readmissions was highest in patients living in the most deprived areas [hazard ratio (HR) 2.34, 95% CI 1.41-3.90]. SCD patients from the most socio-economically deprived areas and with comorbidities are at highest risk of both SCD readmissions and in-hospital mortality, suggesting that there are inequalities in healthcare access and health outcomes amongst people with SCD.

Trends in hospital admissions for sickle cell disease in England

Sirs, The recent paper by AlJuburi et al.1 draws attention to the issue of hospital admissions for sickle cell disease. We would like to raise several points in response. AlJuburi et al. suggest that the increased prevalence of sickle cell disease (SCD) in England through domestic growth of the current at-risk population' is the most important factor contributing to the increase in SCD admissions. Data collected by the NHS Sickle Cell and Thalassaemia Screening Programme show that in England the birth prevalence of screen-positive babies for SCD (comprising FS, FSC, FS-other and FE screening positive results) has been stable between 2005 and 2011 (0.52–0.56/1000 babies screened), with about 360 screen-positive babies per year.2 This demonstrates that there has not been a dramatic increase in the prevalence of (SCD) in England through domestic growth of the current at-risk population, although migration in older children has been reported by some clinics. The authors' analysis gives an indication of the burden of hospital utilization from SCD in England. However, evidence on readmissions and multiple admissions in the same patient are better measures of quality of clinical and community care and are required to gain better understanding of the quality and efficiency of the SCD service rather than simply burden of disease. The NHS Atlas of Variation in Healthcare for Children and Young People reported (a nearly 2-fold) variation in emergency hospital admissions for SCD per individual patient aged 0–17 years by PCT in the 3 year period from 2007 to 2010.3 Highest readmission rates are seen in areas with less expertise in managing SCD, and in areas which have newly arrived populations, many areas in London with high rates of admission do not have high repeat admission rates. Data collected by the NHS Sickle Cell and Thalassaemia Programme shows that the highest birth prevalence is in London South East.2 However, analysis in AlJuburi's study show that five PCTs with highest admission rates are not in South East London. This could be explained with quality of care in above PCTs. We also think that it would be useful to compare the rise of SCD admissions to the overall rise of all hospital admissions. The National Haemoglobinopathy Project has reported a 70% increase in D57 code admissions in the period 1997–2007, while total admissions for all diagnoses rose by only 28% over a similar period.4 Finally, the authors might have considered a cohort effect in the high-risk population (Black African and Black Caribbean)5 and the impact of the changing age structure of those populations on the increase in SCD admissions in older age groups, with patient survival also increasing and thus larger cohorts moving up through the age groupings.

Trends in hospital admissions for sickle cell disease in England

Trends in hospital admissions for sickle cell disease in England

Trends in hospital admissions for sickle cell disease in England, 2001/02-2009/10

Sickle cell disease (SCD) is a rising cause of mortality and morbidity in England and consequently an important policy issue for the National Health Service. There has been no previous study that has examined SCD admission rates in England. Data from Hospital Episode Statistics were analysed for all hospital episodes (2001/10) in England with a primary diagnosis of sickle cell anaemia with crisis (D57.0) or without crisis (D57.1). Secondary and tertiary diagnoses were examined among those patients admitted with either of these codes as their primary diagnosis. The overall SCD admission rate per 100 000 has risen from 21.2 in 2001/02 to 33.5 in 2009/10, a rise of over 50%. London accounts for 74.9% of all SCD admissions in England. 57.9% of patients admitted are discharged within 24 h. The largest rise in admission rates was seen among males aged 40-49 years where admission rates per 100 000 increased from 7.6 to 26.8 over the study period. Our data show that SCD admissions are rising in England, particularly in London. Over half of patients admitted with SCD were discharged within 24 h, suggesting that some of these admissions could be prevented through better ambulatory care of patients.

UK national standards for sickle cell disease in childhood: using audit to improve clinical care

<h3>Background</h3> In the UK, Sickle cell disease (SCD) affects 1 in 2,400 live births and there is now a nationwide screening programme in place. There are currently estimated to be 12,500 individuals living with SCD in England where it is the most common and fastest growing genetic disorder. Treatment is aimed at reducing complications with preventative measures such as prophylactic antibiotics, immunisation, and cranial doppler ultrasound to assess stroke risk. <h3>Objectives</h3> This audit aims to compare local outcomes at the North Middlesex University Hospital with the recommended national standards for the management of sickle cell disease. This poster presents the results of 2 years of audit data (a full audit cycle) to assess whether recommendations made in 2009 have led to improvements in outcomes in 2010. <h3>Methods</h3> Information was retrieved via a retrospective database and notes audit of 249 patients on the haemoglobinopathy register at North Middlesex Hospital. Collated data was compared to national standards. <h3>Results</h3> The UK national standards for sickle cell disease, taken from 3 government documents (see references), were audited on 2 consecutive years. There are 13 national standards on the treatment and management of pediatric sickle cell disease covering recommendations for newborn screening, penicillin and pneumococcal prophylaxis, transcranial doppler ultrasound (TCD) scanning and annual review. Out of 13 national targets, 6 were met in 2009 and 9 were met in 2010. Patient non attendance appointments led to a number of standards not being met in both years. <h3>Conclusions</h3> Improvement in meeting national targets occurred between 2009 and 2010 as a result of the audit process and subsequent recommendations such as changes to note keeping, the introduction of patient held records, family clinics, and the introduction of after school appointments for adolescents. The audit process itself highlighted issues such as patient non attendance and its impact on meeting standards. Non attendance remains a costly and troubling problem to the NHS where there has been a great impetus to look at the cost analysis of providing services. Steps are now being taken to reduce non attendance including a research project examining the correlation between social factors and non attendance.

Implementation of the newborn screening programme for sickle cell disease in England: results for 2003-2005

This paper reports early screening results from the newborn sickle cell disease screening programme recently implemented in England. England. Screening is offered at 5-8 days of age as part of the existing bloodspot test and offered to all babies irrespective of ethnicity. The laboratory methods recommended are high performance liquid chromatography (HPLC) and iso-electric focusing (IEF). Two methods of analysis must be applied to all screen positive results. The conditions screened for are:- Sickle cell anaemia (Hb SS), Hb SC disease, Hb S/beta-thalassaemia, Hb S/D(Punjab), Hb S/O(Arab), Hb S/HPFH. Carriers identified for the common haemoglobin variants are reported to parents and follow-up counselling is offered. A bespoke laboratory quality assurance programme has been established which has defined standards of satisfactory performance. Provisional figures from the first seven months of screening (up to March 2004) 108,255 infants were screened gave a screen positive rate of 1:900 for these high prevalence areas and a carrier rate of 2.7%. Figures for 2004-2005 show about 250 significant screen positive results for sickle cell disorders and about 6,500 carriers were identified. The birth prevalence for screen positive results from 2004-05 is 1:1500. We estimate that when there is countrywide data, the national birth prevalence will be about 1:2000-1:2,500. The results from the national newborn sickle cell screening programme in England-show that the sickle cell disorders are as common as cystic fibrosis (CF) in England, although the distribution of cases is concentrated in London and other urban areas. The findings and approach to implementation adopted in England may be of interest to other Western European countries with increasing rates of sickle cell disease who are considering such programmes and also to other developed countries.

Influence of in vivo prednisolone on increased in vitro O2-generation by neutrophils in emphysema

Evidence is accumulating that neutrophil-derived oxidants substantially contribute to the development of emphysema, especially in smoking individuals. It is not clear, however, why not all smokers develop emphysema. We tested the hypothesis that an abnormality in the oxidative metabolism of polymorphonuclear leucocytes (PMNs) might contribute to the development of emphysema. We investigated in vitro O2- production by peripheral PMNs in patients with stable emphysema and in healthy controls. In addition, we investigated whether in vivo prednisolone may modulate in vitro O2- production by PMNs in patients with emphysema during a stable phase of the disease. Spontaneous O2- production by PMNs was not significantly different in patients and controls. After stimulation with submaximal concentrations of calcium ionophore A23187 and phorbol myristate acetate, however, PMNs from patients with stable emphysema produced more O2- than those from healthy controls, especially in smoking subjects. Moreover, in vitro O2- generation by PMNs significantly decreased after in vivo prednisolone treatment in patients with emphysema. We suggest that our findings reflect an abnormality of PMNs, acting as one of the factors that contribute to the development of emphysema. This abnormality may, at least partially, be dampened by in vivo prednisolone treatment. These findings may provide new insights into the pathogenesis and treatment of pulmonary emphysema. Further studies on pulmonary PMNs are necessary to extend our findings.

Survey of sickle-cell disease in England and Wales

Survey of sickle-cell disease in England and Wales

Survey of sickle-cell disease in England and Wales.

The incidence and the clinical course of patients suffering from sickle-cell syndrome (Hb SS; Hb SC; Hb S thal) in England and Wales are not known. In 1979 an ad hoc committee was formed to investigate these problems. Initially, a questionnaire was sent to 227 haematologists in England and Wales to determine the number of cases in these countries. The replies have indicated that 1367 cases were seen in 1978 and 1979. Probably this may represent only half the total number of cases. From this survey it has been possible to draw up a composite map showing the location of patients, which has provided a basis to determine the clinical course of the disease, and for further studies into the complications and management of sickle-cell disease in England and Wales. From a second questionnaire preliminary data about the general management and mortality in England and Wales have been recorded.