Annual stroke incidence in Nigerian children with sickle cell disease and elevated TCD velocities treated with hydroxyurea

Lagunju, Ikeoluwa; Bj, Brown; Oyinlade, Alexander Opebiyi; Asinobi, Adanze Onyenonachi; Ibeh, J.; Esione, A.; Sodeinde, Olugbemiro

doi:10.1002/pbc.27252

Cited by 34 publications

(35 citation statements)

References 28 publications

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“…Further, in a prospective feasibility clinical trial (SPIN) in Nigeria, hydroxyurea urea therapy resulted in significant decrease in TCD velocities >170 cm/s as well as improvement in the hematological profile of children with SCA . Hence, hydroxyurea may provide an effective approach to primary stroke prevention, thus providing a feasible substitute for primary stroke prevention in low‐income countries . Recently, results of two pivotal trials in SSA have been published.…”

Section: Strategies To Decrease the Burden Of Sickle Cell Diseasementioning

confidence: 90%

Sickle cell disease: Reducing the global disease burden

Mburu

Odame

2019

Int J Lab Hematology

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Sickle cell disease has been largely an invisible global health issue, especially in regions of high incidence mainly due to lack of awareness among both the local health policy makers and the public. Public health interventions, such as screening of newborns, provision of prophylaxis against bacterial infections, and immunizations against pneumococcal infections can have the greatest impact. Family education on assessment of spleen size and subsequent detection of splenic sequestration and promptness to seek medical attention for a febrile child is also important in the control of the morbidity and mortality of children with SCD living in resource‐poor countries. In addition to these affordable interventions, hydroxyurea therapy is necessary to decrease both the acute and chronic complications of sickle cell anemia. Sickle cell disease has been recognized to have global health significance by key institutions including the World Health Organization in 2006 and the United Nation is 2008. In 2010, the WHO released national health care management goals and set targets to be achieved by the countries in sub‐Saharan Africa for the control and management of SCD. These are yet to be translated into action. To do, this would require active and sustainable public‐private partnerships for sustainable program development in these regions. Effective interventions should be integrated into existing health systems, the best examples linking primary healthcare facilities to specialized sickle cell disease centers in regional and tertiary healthcare institutions.

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Section: Strategies To Decrease the Burden Of Sickle Cell Diseasementioning

confidence: 90%

Sickle cell disease: Reducing the global disease burden

Mburu

Odame

2019

Int J Lab Hematology

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“…Emerging data demonstrate that hydroxyurea is an effective therapeutic option for primary prevention of stroke in those children with sickle cell anemia (SCA) who are at increased risk of stroke as assessed by transcranial Doppler (TCD) measurements . In this issue of Pediatric Blood & Cancer , Lagunju et al present data from an observational cohort study of high‐risk children treated with hydroxyurea at maximum tolerated dose (mean (SD) of 25 (3.4) mg/kg) and followed for a minimum of 1 year (range 1‐8 years) at a single hospital center in Nigeria to ascertain the annual incidence of strokes. In this carefully conducted cohort study, the authors report one stroke, yielding an incidence of 0.27/100 person years, and one transient ischemic episode among the cohort.…”

mentioning

confidence: 99%

“…Within this context, there is clearly more need for clinical trials and carefully conducted research in these high burden regions to facilitate the bidirectional flow of translational medicine with the attendant improved care and clinical outcomes of children residing in these regions. In deference to some these factors, some investigators have opted to test moderate fixed dose of hydroxyurea for primary stroke prevention and as such the dose escalation to maximum tolerated dose approach of Lagunju et al in this study is novel.…”

mentioning

confidence: 99%

“…Additionally, the exact timing for start of hydroxyurea is unclear, whether at 6 months of age or when screen positive. Nevertheless, the data emerging suggest that hydroxyurea use in Africa is safe and that for primary prevention of stroke, escalating to maximum tolerated dose is practical and efficacious …”

mentioning

confidence: 99%

“…Similar to chronic transfusion therapy, hydroxyurea therapy is not a perfect primary prevention strategy and the one case of stroke in the paper by Lagunju et al illustrates this. Additionally, there remain concerns about its long‐term safety.…”

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confidence: 99%

See 2 more Smart Citations

Hydroxyurea for Primary Stroke Prevention: The time draweth nigh

Reid

2018

Pediatric Blood & Cancer

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Hydroxyurea to prevent brain injury in children with sickle cell disease (HU Prevent)—A randomized, placebo‐controlled phase II feasibility/pilot study

Casella,

Furstenau,

Adams

et al. 2024

American J Hematol

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Central nervous system (CNS) injury is common in sickle cell disease (SCD) and occurs early in life. Hydroxyurea is safe and efficacious for treatment of SCD, but high‐quality evidence from randomized trials to estimate its neuroprotective effect is scant. HU Prevent was a randomized (1:1), double‐blind, phase II feasibility/pilot trial of dose‐escalated hydroxyurea vs. placebo for the primary prevention of CNS injury in children with HbSS or HbS‐β0‐thalassemia subtypes of SCD age 12–48 months with normal neurological examination, MRI of the brain, and cerebral blood flow velocity. We hypothesized that hydroxyurea would reduce by 50% the incidence of CNS injury. Two outcomes were compared: primary—a composite of silent cerebral infarction, elevated cerebral blood flow velocity, transient ischemic attack, or stroke; secondary—a weighted score estimating the risk of suffering the consequences of stroke (the Stroke Consequences Risk Score—SCRS), based on the same outcome events. Six participants were randomized to each group. One participant in the hydroxyurea group had a primary outcome vs. four in the placebo group (incidence rate ratio [90% CI] 0.216 [0.009, 1.66], p = .2914) (~80% reduction in the hydroxyurea group). The mean SCRS score was 0.078 (SD 0.174) in the hydroxyurea group, 0.312 (SD 0.174) in the placebo group, p = .072, below the p‐value of .10 often used to justify subsequent phase III investigations. Serious adverse events related to study procedures occurred in 3/41 MRIs performed, all related to sedation. These results suggest that hydroxyurea may have profound neuroprotective effect in children with SCD and support a definitive phase III study to encourage the early use of hydroxyurea in all infants with SCD.

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Annual stroke incidence in Nigerian children with sickle cell disease and elevated TCD velocities treated with hydroxyurea

Cited by 34 publications

References 28 publications

Sickle cell disease: Reducing the global disease burden

Sickle cell disease: Reducing the global disease burden

Hydroxyurea for Primary Stroke Prevention: The time draweth nigh

Hydroxyurea to prevent brain injury in children with sickle cell disease (HU Prevent)—A randomized, placebo‐controlled phase II feasibility/pilot study

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