Sickle Cell Disease Newborn Screening-An Audit of a Twin Island State Pilot Program.

The prevalence of Sickle Cell Disease (SCD) within the Caribbean region remains second only to that of West Africa. The Newborn Screening (NBS) Program in Antigua and Barbuda remains heavily dependent on grants, therefore ultimately facing sustainability challenges. Early intervention and implementation of preventative measures post-NBS result in significant improvements in morbidity, quality of life, and survival. This audit reviewed the pilot SCD NBS Program in Antigua and Barbuda from September 2020 to December 2021. A conclusive result was received by 99% of babies eligible for screening, 84.3% of which were HbFA, whilst 9.6% and 4.6% were HbFAS and HbFAC, respectively. This was comparable to other Caribbean countries. Sickle Cell Disease was noted in 0.5% of babies screened, which translates to 1 in 222 live births. Eighty-two percent of mothers were aware of their sickle cell status, compared to 3% of fathers. The importance of instituting a quality improvement team post the initiation of a screening program and the need for a robust public education program have been demonstrated by this audit.

Inhaled bronchodilators for acute chest syndrome in people with sickle cell disease.

BACKGROUND: Bronchodilators are used to treat bronchial hyper-responsiveness in asthma. Bronchial hyper-responsiveness may be a component of acute chest syndrome in people with sickle cell disease. Therefore, bronchodilators may be useful in the treatment of acute chest syndrome. This is an update of a previously published Cochrane Review. OBJECTIVES: The aim of the review is to determine whether the use of inhaled, short-acting bronchodilators for acute chest syndrome reduces morbidity and mortality in people with sickle cell disease and to assess whether this treatment causes adverse effects. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Additional searches were carried out on MEDLINE (1966 to 2004) and Embase (1981 to 2004) and ongoing trial registries (28 September 2022). Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 25 July 2022. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials. Trials using quasi-randomisation methods will be included in future updates of this review if there is sufficient evidence that the treatment and control groups are similar at baseline. DATA COLLECTION AND ANALYSIS: We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease. MAIN RESULTS: We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS: If bronchial hyper-responsiveness is an important component of some episodes of acute chest syndrome in people with sickle cell disease, the use of inhaled bronchodilators may be indicated. There is need for a well-designed, adequately-powered randomised controlled trial to assess the benefits and risks of the addition of inhaled bronchodilators to established therapies for acute chest syndrome in people with sickle cell disease.

Interventions for treating leg ulcers in people with sickle cell disease.

BACKGROUND: The frequency of skin ulceration makes an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease. This is an update of a previously published Cochrane Review. OBJECTIVES: To assess the clinical effectiveness and harms of interventions for treating leg ulcers in people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. We searched LILACS (1982 to January 2020), ISI Web of Knowledge (1985 to January 2020), and the Clinical Trials Search Portal of the World Health Organization (January 2020). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area. Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 13 January 2020; date of the last search of the Cochrane Wounds Group Trials Register: 17 February 2017. SELECTION CRITERIA: Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data. We used GRADE to assess the quality of the evidence. MAIN RESULTS: Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl® cream, arginine-glycine-aspartic acid (RGD) peptide dressing and topical antibiotics). No trials on non-pharmaceutical interventions were included in the review. All trials had an overall unclear or high risk of bias, and drug companies sponsored four of them. We were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the units of randomisation and analysis. Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, only arginine butyrate showed a reduction of ulcer size compared with a control group, mean reduction -5.10 cm² (95% CI -9.65 to -0.55), but we are uncertain whether this reduces ulcer size compared to standard care alone as the certainty of the evidence has been assessed as very low. Three trials reported on complete leg ulcer closure (isoxsuprine, arginine butyrate, RGD peptide matrix; very low quality of evidence). None reported a clinical benefit. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; incidence of amputation or harms. AUTHORS' CONCLUSIONS: Given the very low quality of the evidence identified in this updated Cochrane Review we are uncertain whether any of the assessed pharmaceutical interventions reduce ulcer size or result in leg ulcer closure in treated participants compared to controls. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having an unclear or high risk of bias. The harm profile of the all interventions remains inconclusive.

How Free Is Free Health Care? An Assessment of Universal Health Coverage Among Jamaicans with Sickle Cell Disease.

Purpose: In an effort to transition toward universal health coverage (UHC), Jamaica abolished user fees at all public health facilities in 2008. We aimed to determine the extent of out-of-pocket payments (OPPs) and the other cost barriers to UHC among patients with sickle cell disease (SCD). Methods: Patients presenting to the Sickle Cell Unit in Kingston, Jamaica, for routine care between October 2019 and August 2020 were consecutively recruited and interviewed about their latest hospitalization within the previous 4 weeks. Parents or guardians completed the questionnaire on behalf of pediatric patients. The questionnaire included the Patient Satisfaction Questionnaire Short Form (PSQ)-18 and the health module of the Jamaica Survey of Living Conditions. Results: There were 103 patients with ages ranging from 7 months to 56 years (51.5% female, 60.2% public hospitalizations, and 54.4% pediatric). The modal income (J$6200-$11,999 per week) was similar to the minimum wage and 48.5% lived in overcrowded households. Government drug-subsidy cards were owned by 39.8%. OPPs were made by 19.4% of persons for items and tests that were unavailable at public facilities. There were no costs reported by 69.6%, who visited public pharmacies. Similarly, the cost of admission to public hospitals was free for 95.4% of subjects. Using public transportation, private hospitalization, and having more disease complications were predictive of a perception that health care is unaffordable. Conclusion: Most SCD subjects reported no expense with public hospitalizations; however, approximately one in five reported OPPs. Efforts are needed to increase the availability of subsidized items, and the use of drug-subsidy cards, to improve UHC.

Antibiotics for treating acute chest syndrome in people with sickle cell disease.

BACKGROUND: The clinical presentation of acute chest syndrome is similar whether due to infectious or non-infectious causes, thus antibiotics are usually prescribed to treat all episodes. Many different pathogens, including bacteria, have been implicated as causative agents of acute chest syndrome. There is no standardized approach to antibiotic therapy and treatment is likely to vary from country to country. Thus, there is a need to identify the efficacy and safety of different antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. This is an update of a Cochrane Review first published in 2007, and most recently updated in 2015. OBJECTIVES: To determine whether an empirical antibiotic treatment approach (used alone or in combination):1. is effective for acute chest syndrome compared to placebo or standard treatment;2. is safe for acute chest syndrome compared to placebo or standard treatment;Further objectives are to determine whether there are important variations in efficacy and safety:3. for different treatment regimens,4. by participant age, or geographical location of the clinical trials. SEARCH METHODS: We searched The Group's Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the LILACS database (1982 to 23 October 2017), African Index Medicus (1982 to 23 October 2017) and trial registries (23 October 2017).Date of most recent search of the Haemoglobinopathies Trials Register: 10 July 2019. SELECTION CRITERIA: We searched for published or unpublished randomised controlled trials. DATA COLLECTION AND ANALYSIS: Each author intended to independently extract data and assess trial quality by standard Cochrane methodologies, but no eligible randomised controlled trials were identified. MAIN RESULTS: For this update, we were unable to find any randomised controlled trials on antibiotic treatment approaches for acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS: This update was unable to identify randomised controlled trials on efficacy and safety of the antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. While randomised controlled trials are needed to establish the optimum antibiotic treatment for this condition, we do not envisage further trials of this intervention will be conducted, and hence the review will no longer be regularly updated.

Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell disease: A SUSTAIN study analysis.

The cell adhesion molecule P-selectin plays a key role in the pathogenesis of a vaso-occlusive crisis (VOC) in patients with sickle cell disease (SCD). In the double-blind, placebo-controlled phase 2 SUSTAIN study, crizanlizumab (humanized, anti-P-selectin monoclonal antibody) 5 mg/kg significantly lowered the rate of VOC in patients with SCD by 45% vs placebo. In SUSTAIN, patients with SCD were randomized to crizanlizumab 2.5 mg/kg, crizanlizumab 5 mg/kg, or placebo intravenously 14 times over 52 weeks. The primary endpoint was the annual rate of VOC with crizanlizumab vs placebo. This post hoc descriptive analysis evaluated the proportion of patients who did not experience a VOC during the study in the following subgroups: VOCs in the year prior to study entry (2-4/5-10), SCD genotype (HbSS/non-HbSS), and concomitant hydroxyurea use (yes/no). More patients were VOC event-free in the crizanlizumab 5 mg/kg arm than in the placebo arm, including those with more frequent prior VOCs (ie, 5-10; 28.0% vs 4.2%), the HbSS genotype (31.9% vs 17.0%) and/or using concomitant hydroxyurea (33.3% vs 17.5%). Further analyses of secondary endpoints demonstrated that crizanlizumab treatment significantly increased time-to-first VOC vs placebo in these subgroups. The rates of treatment-emergent adverse events were similar between treatment arms across all subgroups. This post hoc analysis of SUSTAIN shows that in patients with a high number of prior VOCs, on concomitant hydroxyurea and/or with the HbSS genotype, crizanlizumab treatment increases the likelihood of patients being VOC event-free and delays time-to-first VOC.

Causes of death and early life determinants of survival in homozygous sickle cell disease: The Jamaican cohort study from birth.

Globally, the majority of persons born with sickle cell disease do not have access to hydroxyurea or more expensive interventions. The objectives were to estimate the survival in homozygous sickle cell disease, unbiased by symptomatic selection and to ascertain the causes of death in a pre-hydroxyurea population. The utility of early life biomarkers and genetically determined phenotypes to predict survival was assessed. A cohort study based on neonatal diagnosis was undertaken at the Sickle Cell Unit, a specialist clinic delivering care to persons with sickle cell disease in Jamaica. Screening of 100,000 deliveries detected 315 babies with homozygous sickle cell disease of whom 311 have been followed from birth for periods up to 43 years. Pneumococcal prophylaxis and teaching mothers splenic palpation were important, inexpensive interventions. Anticipatory guidance, routine care and out-patient acute care were provided. Each participant was classified as alive, dead, or defaulted (usually emigration). Causes of death were ascertained from clinical records and/or post-mortem reports. Survival was assessed using the Kaplan-Meier function. Sex-adjusted Cox semi-parametric proportional hazards and Weibull modelling were used to assess the effects on survival of biomarkers. Survival to 40 years was 55.5% (95% CI 48.7% to 61.7%). Acute Chest Syndrome (n = 31) and septicemia (n = 14) were significant causes of death at all ages. Acute splenic sequestration (n = 12) was the most common cause of early deaths. Survival was significantly shorter in those with lower hemoglobin at 1 year, high total nucleated count at 1 year, and a history of dactylitis ever. In these hydroxyurea naïve patients, survival into midlife was common. Causes of death were often age specific and some may be preventable. Early life biomarkers predictive of decreased survival in SS disease identify a patient group likely to benefit from close clinical supervision and potentially high risk therapies.

Transcranial Doppler velocity among Jamaican children with sickle cell anaemia: determining the significance of haematological values and nutrition.

This study investigated the association of nutritional and haematological variables with maximum time-averaged mean velocity (TAMV) measured by transcranial Doppler (TCD) velocity and the agreement of classification between two protocols. TCD categories included: normal (<170 cm/s), conditional (170-199 cm/s) and abnormal (≥200 cm/s) based on TAMV in distal internal carotid artery (dICA), middle cerebral artery (MCA), internal carotid bifurcation, anterior and posterior cerebral arteries. Of 358 children with sickle cell anaemia (SCA) examined, the mean age (±standard deviation) was 7·4 ± 2·7 years; 13·1% and 6·7% had conditional and abnormal velocities, respectively. Children with abnormal TCD velocities had higher prevalence of prior stroke (P = 0·006). Increased TAMV was associated with younger age (P = 0·001), lower weight (P = 0·001), height (P = 0·007) and oxygen saturation (P = 0·005). There was no association of TAMV with height-age or body mass index (BMI) z-scores. Adjusting for gender, BMI z-score, age, previous stroke and oxygen saturation, mean corpuscular volume (P = 0·005) and reticulocyte count (P = 0·013) were positively associated with TAMV, while haemoglobin concentration (P = 0·009) was negatively associated. There was good agreement [99%; weighted Kappa 0·98 (95% confidence interval 0·89-1), P = 0·0001] in TCD classification using data from five vessels versus two vessels (dICA and MCA). Haematological variables, rather than nutritional status, may be useful markers that identify high-risk children with SCA.

Factors associated with elevated blood pressure or hypertension in Afro-Caribbean youth: a cross-sectional study.

BACKGROUND: Although several studies have identified risk factors for high blood pressure (BP), data from Afro-Caribbean populations are limited. Additionally, less is known about how putative risk factors operate in young adults and how social factors influence the risk of high BP. In this study, we estimated the relative risk for elevated BP or hypertension (EBP/HTN), defined as BP ≥ 120/80 mmHg, among young adults with putative cardiovascular disease (CVD) risk factors in Jamaica and evaluated whether relative risks differed by sex. METHODS: Data from 898 young adults, 18-20 years old, were analysed. BP was measured with a mercury sphygmomanometer after participants had been seated for 5 min. Anthropometric measurements were obtained, and glucose, lipids and insulin measured from a fasting venous blood sample. Data on socioeconomic status (SES) were obtained via questionnaire. CVD risk factor status was defined using standard cut-points or the upper quintile of the distribution where the numbers meeting standard cut-points were small. Relative risks were estimated using odds ratios (OR) from logistic regression models. RESULTS: Prevalence of EBP/HTN was 30% among males and 13% among females (p < 0.001 for sex difference). There was evidence for sex interaction in the relationship between EBP/HTN and some of risk factors (obesity and household possessions), therefore we report sex-specific analyses. In multivariable logistic regression models, factors independently associated with EBP/HTN among men were obesity (OR 8.48, 95% CI [2.64-27.2], p < 0.001), and high glucose (OR 2.01, CI [1.20-3.37], p = 0.008), while high HOMA-IR did not achieve statistical significance (OR 2.08, CI [0.94-4.58], p = 0.069). In similar models for women, high triglycerides (OR 1.98, CI [1.03-3.81], p = 0.040) and high HOMA-IR (OR 2.07, CI [1.03-4.12], p = 0.039) were positively associated with EBP/HTN. Lower SES was also associated with higher odds for EBP/HTN (OR 4.63, CI [1.31-16.4], p = 0.017, for moderate vs. high household possessions; OR 2.61, CI [0.70-9.77], p = 0.154 for low vs. high household possessions). Alcohol consumption was associated with lower odds of EBP/HTN among females only; OR 0.41 (CI [0.18-0.90], p = 0.026) for drinking <1 time per week vs. never drinkers, and OR 0.28 (CI [0.11-0.76], p = 0.012) for drinking ≥3 times per week vs. never drinkers. Physical activity was inversely associated with EBP/HTN in both males and females. CONCLUSION: Factors associated with EBP/HTN among Jamaican young adults include obesity, high glucose, high triglycerides and high HOMA-IR, with some significant differences by sex. Among women lower SES was positively associated with EBP/HTN, while moderate alcohol consumption was associated lower odds of EBP/HTN.

Inhaled bronchodilators for acute chest syndrome in people with sickle cell disease.

BACKGROUND: Bronchodilators are used to treat bronchial hyper-responsiveness in asthma. Bronchial hyper-responsiveness may be a component of acute chest syndrome in people with sickle cell disease. Therefore, bronchodilators may be useful in the treatment of acute chest syndrome. This is an update of a previously published Cochrane Review. OBJECTIVES: To assess the benefits and risks associated with the use of bronchodilators in people with acute chest syndrome. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Additional searches were carried out on MEDLINE (1966 to 2002) and Embase (1981 to 2002).Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 11 July 2016. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials. Trials using quasi-randomisation methods will be included in future updates of this review if there is sufficient evidence that the treatment and control groups are similar at baseline. DATA COLLECTION AND ANALYSIS: We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease. MAIN RESULTS: We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS: If bronchial hyper-responsiveness is an important component of some episodes of acute chest syndrome in people with sickle cell disease, the use of inhaled bronchodilators may be indicated. There is need for a well-designed, adequately-powered randomised controlled trial to assess the benefits and risks of the addition of inhaled bronchodilators to established therapies for acute chest syndrome in people with sickle cell disease.

EXpanding Treatment for Existing Neurological Disease (EXTEND): An Open-Label Phase II Clinical Trial of Hydroxyurea Treatment in Sickle Cell Anemia.

BACKGROUND: Cerebral vasculopathy in sickle cell anemia (SCA) begins in childhood and features intracranial arterial stenosis with high risk of ischemic stroke. Stroke risk can be reduced by transcranial doppler (TCD) screening and chronic transfusion therapy; however, this approach is impractical in many developing countries. Accumulating evidence supports the use of hydroxyurea for the prevention and treatment of cerebrovascular disease in children with SCA. Recently we reported that hydroxyurea significantly reduced the conversion from conditional TCD velocities to abnormal velocities; whether hydroxyurea can be used for children with newly diagnosed severe cerebrovascular disease in place of starting transfusion therapy remains unknown. OBJECTIVE: The primary objective of the EXpanding Treatment for Existing Neurological Disease (EXTEND) trial is to investigate the effect of open label hydroxyurea on the maximum time-averaged mean velocity (TAMV) after 18 months of treatment compared to the pre-treatment value. Secondary objectives include the effects of hydroxyurea on serial TCD velocities, the incidence of neurological and non-neurological events, quality of life (QOL), body composition and metabolism, toxicity and treatment response, changes to brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), genetic and serologic markers of disease severity, and cognitive and pulmonary function. METHODS: This prospective Phase II trial will enroll children with SCA in Jamaica, between the ages of 2 and 17 years, with either conditional (170-199 cm/sec) or abnormal (≥ 200 cm/sec) TCD velocities. Oral hydroxyurea will be administered daily and escalated to the maximum tolerated dose (MTD). Participants will be seen in the Sickle Cell Unit (SCU) in Kingston, Jamaica monthly until achieving MTD, and then every 3 months. TCD will be performed every 6 months. RESULTS: Currently, 43 participants have been enrolled out of a projected 50. There was one withdrawal due to immigration, with no permanent screen failures. Of the 43 enrolled, 37 participants have initiated study treatment. CONCLUSIONS: This trial investigates the effects of hydroxyurea treatment at MTD in children with conditional or abnormal TCD velocities before transfusion therapy and may represent an important advance towards establishing a suitable non-transfusion protocol for stroke prevention in children with SCA. The trial outcomes will have profound significance in developing countries where the disease burden is highest. CLINICALTRIAL: ClinicalTrials.gov NCT02556099; https://clinicaltrials.gov/ct2/show/NCT02556099 (Archived by WebCite at http://www.webcitation.org/6k1yMAa9G).

A Retrospective Analysis of the Significance of Haemoglobin SS and SC in Disease Outcome in Patients With Sickle Cell Disease and Dengue Fever.

BACKGROUND: Little is known about the significance of haemoglobin genotype in dengue fever severity. This study was undertaken to determine the case fatality ratio and the impact of genotype in patients with sickle cell disease and confirmed dengue fever. METHODS: This retrospective analysis included 40 patients with confirmed dengue and sickle cell disease, during the study period (2010-2012). FINDINGS: There was a significantly higher case fatality ratio, 12.5% among patients with either haemoglobin SC disease or homozygous SS disease when compared to that of the general population 0.41% (p < 0.0001). The unadjusted odds of dying among those with haemoglobin SC disease compared with the group with homozygous SS disease was OR = 4.4 (95% CI 0.6 to 31.7). The predictors of mortality independent of sickle cell disease genotype were haemoglobin concentration at presentation OR = 0.57 (95% CI, 0.35 to 0.94) and the change in haemoglobin concentration from steady state OR = 0.59 (95% CI, 0.37 to 0.94). Adjusting for haemoglobin concentration at presentation increased the risk of death for the SC genotype relative to SS genotype OR = 13.4 (95% CI 1.1 to 160.3). INTERPRETATION: The risk of fatal dengue may be higher among patients with a relatively mild genotype (haemoglobin SC).

Antibiotics for treating acute chest syndrome in people with sickle cell disease.

BACKGROUND: The clinical presentation of acute chest syndrome is similar whether due to infectious or non-infectious causes, thus antibiotics are usually prescribed to treat all episodes. Many different pathogens, including bacteria, have been implicated as causative agents of acute chest syndrome. There is no standardized approach to antibiotic therapy and treatment is likely to vary from country to country. Thus, there is a need to identify the efficacy and safety of different antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. This is an update of a Cochrane review first published in 2007, and previously updated in 2013. OBJECTIVES: To determine whether an empirical antibiotic treatment approach (used alone or in combination):1. is effective for acute chest syndrome compared to placebo or standard treatment;2. is safe for acute chest syndrome compared to placebo or standard treatment;Further objectives are to determine whether there are important variations in efficacy and safety:3. for different treatment regimens,4. by participant age, or geographical location of the clinical trials. SEARCH METHODS: We searched The Group's Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the LILACS database (1982 to 23 February 2015), African Index Medicus (1982 to 23 February 2015). and the World Health Organization International Clinical Trials Registry Platform Search Portal (23 February 2015).Date of most recent search of the Haemoglobinopathies Trials Register: 20 January 2015. SELECTION CRITERIA: We searched for published or unpublished randomised controlled trials. DATA COLLECTION AND ANALYSIS: Each author intended to independently extract data and assess trial quality by standard Cochrane Collaboration methodologies, but no eligible randomised controlled trials were identified. MAIN RESULTS: For this update, we were unable to find any randomised controlled trials on antibiotic treatment approaches for acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS: This update was unable to identify randomised controlled trials on efficacy and safety of the antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. Randomised controlled trials are needed to establish the optimum antibiotic treatment for this condition.

Birth weight and maternal socioeconomic circumstances were inversely related to systolic blood pressure among Afro-Caribbean young adults.

OBJECTIVES: In this study, we examined the effects of birth weight (BWT) and early life socioeconomic circumstances (SEC) on systolic blood pressure (SBP) and diastolic blood pressure (DBP) among Jamaican young adults. STUDY DESIGN AND SETTING: Longitudinal study of 364 men and 430 women from the Jamaica 1986 Birth Cohort Study. Information on BWT and maternal SEC at child's birth was linked to information collected at 18-20 years old. Sex-specific multilevel linear regression models were used to examine whether adult SBP/DBP was associated with BWT and maternal SEC. RESULTS: In unadjusted models, SBP was inversely related to BWT z-score in both men (ß, -0.82 mm Hg) and women (ß, -1.18 mm Hg) but achieved statistical significance for women only. In the fully adjusted model, one standard deviation increase in BWT was associated with 1.16 mm Hg reduction in SBP among men [95% confidence interval (CI): 2.15, 0.17; P = 0.021] and 1.34 mm Hg reduction in SBP among women (95% CI: 2.21, 0.47; P = 0.003). Participants whose mothers had lower SEC had higher SBP compared with those with mothers of high SEC (ß, 3.4-4.8 mm Hg for men, P < 0.05 for all SEC categories and 1.8-2.1 for women, P > 0.05). CONCLUSION: SBP was inversely related to maternal SEC and BWT among Jamaican young adults.

Interventions for treating leg ulcers in people with sickle cell disease.

BACKGROUND: The frequency of skin ulceration makes it an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease. OBJECTIVES: To assess the clinical effectiveness and safety of interventions for treating leg ulcers in people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.We searched LILACS (1982 to August 2012), the African Index Medicus (up to August 2012), ISI Web of Knowledge (1985 to August 2012), and the Clinical Trials Search Portal of the World Health Organization (August 2012). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 21 July 2014; date of the last search of the Cochrane Wounds Group Trials Register: 18 September 2014. SELECTION CRITERIA: Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data. MAIN RESULTS: Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl(®) cream, RGD peptide dressing, topical antibiotics). Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, RGD peptide matrix significantly reduced ulcer size compared with a control group, mean reduction 6.60cm(2) (95% CI 5.51 to 7.69; very low quality of evidence). Three trials reported on the incidence of complete closure (isoxsuprine, arginine butyrate, RGD peptide matrix; ranging between low and very low quality of evidence). None reported a significant effect. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; or incidence of amputation. There was no reported information on the safety of these interventions. AUTHORS' CONCLUSIONS: There is evidence that a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants compared to controls. This evidence of efficacy is limited by the generally high risk of bias associated with these reports.We planned to analyse results according to general groups: pharmaceutical interventions (systemic and topical); and non-pharmaceutical interventions (surgical and non-surgical). However, we were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the unit of randomisation and the unit of analysis. This heterogeneity, along with a paucity of identified trials, prevented us performing any meta-analyses.This Cochrane review provides some evidence for the effectiveness of one topical intervention - RGD peptide matrix. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having a high risk of bias. We recommend that readers interpret the trial results with caution. The safety profile of the all interventions was inconclusive.

Inhaled bronchodilators for acute chest syndrome in people with sickle cell disease.

BACKGROUND: Bronchodilators are used to treat bronchial hyper-responsiveness in asthma. Bronchial hyper-responsiveness may be a component of acute chest syndrome in people with sickle cell disease. Therefore, bronchodilators may be useful in the treatment of acute chest syndrome. OBJECTIVES: To assess the benefits and risks associated with the use of bronchodilators in people with acute chest syndrome. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Additional searches were carried out on MEDLINE (1966 to 2002) and Embase (1981 to 2002).Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 17 March 2014. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials. Trials using quasi-randomisation methods will be included in future updates of this review if there is sufficient evidence that the treatment and control groups are similar at baseline. DATA COLLECTION AND ANALYSIS: We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease. MAIN RESULTS: We found no trials investigating the use of bronchodilators for acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS: If bronchial hyper-responsiveness is an important component of some episodes of acute chest syndrome in people with sickle cell disease, the use of inhaled bronchodilators may be indicated. There is need for a well-designed, adequately-powered randomised controlled trial to assess the benefits and risks of the addition of inhaled bronchodilators to established therapies for acute chest syndrome in people with sickle cell disease.

Gangrene of the digits of the right lower limb in a patient with homozygous sickle cell disease and ulcerative colitis.

Thrombosis may play an important role in the pathophysiology of certain complications of sickle cell disease (SCD). While the association between SCD and ulcerative colitis (UC) is still debatable, inflammatory bowel disease is known to be associated with an increased incidence of thromboembolic disease. We report a case of a 16-year old girl known to have homozygous SCD and also diagnosed with UC who presented with digital ischemia of her right lower limb. This led to gangrene and subsequent amputation of the first, second and third digits of that limb. This case highlights that patients with both UC and SCD may have an increased risk of thromboembolism and raises the question as to whether patients with UC and SCD should be screened for thrombophilia.

Antibiotics for treating acute chest syndrome in people with sickle cell disease.

BACKGROUND: The clinical presentation of acute chest syndrome is similar whether due to infectious or non-infectious causes, thus antibiotics are usually prescribed to treat all episodes. Many different pathogens, including bacteria, have been implicated as causative agents of acute chest syndrome. There is no standardized approach to antibiotic therapy and treatment is likely to vary from country to country. Thus, there is a need to identify the efficacy and safety of different antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. OBJECTIVES: To determine whether an empirical antibiotic treatment approach (used alone or in combination): 1. is effective for acute chest syndrome compared to placebo or standard treatment; 2. is safe for acute chest syndrome compared to placebo or standard treatment;Further objectives are to determine whether there are important variations in efficacy and safety: 3. for different treatment regimens, 4. by participant age, or geographical location of the clinical trials. SEARCH METHODS: We searched The Group's Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the LILACS database (1982 to 19 October 2012), African Index Medicus (1982 to 3 November 2012). and the World Health Organization International Clinical Trials Registry Platform Search Portal (19 October 2012).Date of most recent search of the Haemoglobinopathies Trials Register: 29 October 2012. SELECTION CRITERIA: We searched for published or unpublished randomised controlled trials. DATA COLLECTION AND ANALYSIS: Each author intended to independently extract data and assess trial quality by standard Cochrane Collaboration methodologies, but no eligible randomised controlled trials were identified. MAIN RESULTS: For this update, we were unable to find any randomised controlled trials on antibiotic treatment approaches for acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS: This update was unable to identify randomised controlled trials on efficacy and safety of the antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. Randomised controlled trials are needed to establish the optimum antibiotic treatment for this condition.

Relationship between acute chest syndrome and the sympatho-vagal balance in adults with hemoglobin SS disease; a case control study.

The present study evaluated the relationship between acute chest syndrome (ACS) and autonomic nervous system (ANS) activity in patients with hemoglobin SS disease (Hb SS). Nine patients had suffered ACS were matched by age and gender to patients who had not suffered ACS and ANS activity, pulmonary function and history of painful crisis were compared. Correlations between number of episodes of ACS suffered and these variables were determined. The results demonstrated that 1) patients with a history of ACS ever had lower parasympathetic nervous system (PNS) activity and lower global ANS activity than patients with no ACS ever (p < 0.05), 2) the number of ACS episodes ever negatively correlated (p < 0.05) with PNS activity and global ANS activity and 3) There were no significant associations between lung function or a history of painful crisis in these patients. In conclusion, a history of ACS was associated with ANS dysfunction in adults with Hb SS disease.

Mortality, asthma, smoking and acute chest syndrome in young adults with sickle cell disease.

PURPOSE: Sickle cell disease (SCD) patients with asthma have an increased risk of death. Acute chest syndrome (ACS) is a major cause of mortality in patients with SCD, and ACS may be more common in SCD patients who smoke. The purpose of this study was to test the hypothesis that mortality in young adults with SCD would be greater than that of controls during a 10-year period and to determine whether asthma, reduced lung function, ACS episodes, and/or smoking predicted mortality during the follow-up period. METHODS: The outcomes during a 10-year period were ascertained of SCD patients and race-matched controls who had taken part in a pulmonary function study when they were between age 19 and 27 years. Smoking and asthma status and whether they had had ACS episodes were determined, and lung function was measured at the initial assessment. RESULTS: Seventy-five subjects with SCD were followed for 683 patient years. There were 11 deaths with a mortality rate of 1.6 deaths per 100 patient years, which was higher than that of the controls; one death in 47 controls was observed for 469 patient years with a mortality rate of 0.2 per 100 patient years (p = 0.03). There were no significant associations of body mass index, recurrent episodes of acute chest, steady state haemoglobin, or gender with mortality. Adjusting for baseline lung function in SCD patients, "current" asthma [hazard ratio (HR) 11.2; 95 % confidence interval (CI) 2.5-50.6; p = 0.002] and smoking [HR 2.7; (95 % CI 1.3-5.5); p = 0.006] were significantly associated with mortality during the 10-year period. CONCLUSIONS: Our results indicate that young adults with SCD should be discouraged from smoking and their asthma aggressively treated.