Primary Prevention of Strokes in Nigerian Children with Sickle Cell Disease (SPIN Trial): Final Results

Introduction: In children with sickle cell anemia (SCA) living in high-income settings, the routine use of transcranial Doppler (TCD) measurements, coupled with regular blood transfusion therapy for those with abnormal velocities (> 200 cm/sec) dramatically decreased the rate of strokes. Despite evidence of its beneficial effects in preventing strokes, regular blood transfusion therapy is not feasible for 99% of the children that are born with SCA living in low- and middle-income countries. To address this gap in care, we tested the hypothesis that moderate fixed dose of hydroxyurea (20 mg/kg/day) for primary stroke prevention was feasible in a low-income setting, Kano, Nigeria. Specifically, we previously demonstrated that families were willing to enroll at a 92% recruitment rate and were adherent to the study protocol with no missed monthly research visits (603 of 603 visits). We have extended the trial for approximately five years to test the hypotheses that moderate fixed dose hydroxyurea will: 1) not result in excess incidence rate of severe adverse events (death or stroke) when compared to a group of children with SCA and TCD measurements less than 200 cm/sec; 2) decrease the incidence rate of strokes to the level of children receiving regular blood transfusion for primary stroke prevention in the STOP Trial. We report the final results of the primary Stroke Prevention Feasibility Trial in Nigeria (SPIN Trial (NCT01801423). Methods: At trial entry, all eligible participants were screened with non imaging TCD to determine increased stroke risk; defined as two independent measurements of time-averaged maximum velocity (TAMV) ≥ 200cm/sec in the middle cerebral artery (MCA) or one measurement >219cm/sec. Families were offered moderate fixed dose hydroxyurea (~20mg/kg/day). The comparison group included individuals with SCA that have a TCD measurement less than 200 cm/sec and agreed to be followed as routine medical care. Serious adverse events including death or stroke in the treatment and comparison groups were defined based on WHO criteria. Results: A total of 29 children treated with hydroxyurea for primary stroke prevention, and 206 children in the comparison group, were included. The median age for the treatment and comparison groups were 7.0 and 8.2 years, respectively. No statistically significant difference was observed in age, sex, ethnicity, height and weight of the treatment and comparison groups. Table 1 The median time on therapy (follow up time) was 4.9years (IQR- 4.60, 5.2). After 3 months of starting hydroxyurea therapy, 65.5% of the participants had a drop in TCD measurement to below 200cm/sec, which was sustained through 12months of therapy (61.5% had a TCD measurement below 200cm/sec at 12 months). Figure 1 The stroke incidence rate among the participants on hydroxyurea was 0.76 per 100 person-years (95% confidence interval 0.11 to 5.24), which was not significantly different from the incidence rate of 0.32 per 100 person-years (95% confidence interval 0.10 to 0.99) for participants in the comparison arm (P = 0.489), and significantly lower than the reported rate of stroke in the standard care group for the STOP study (10.7 per 100 person-years, total of 102 patient years). A total of 20 deaths occurred, with no death in the treatment group. One death occurred in a child that was originally in the treatment group, but after the patient was withdrawn from the trial due to progressive renal disease unrelated to treatment. The death rate in the comparison group was 2.05 per 100 patient-years. There was no statistically significant difference in the death rate between treatment and comparison group (p = 0.082). The leading cause of death was suspected malaria occurring in 79% (15 of 19). As expected, we found a statistically significant higher incidence rate of pain in the comparison group (30.04 per 100 person-years) compared to the treatment group (15.28 per 100 person-years) (P <0.001). No difference in incidence rates of anemia, infection, malaria and transfusion rates between the two groups. Conclusion: The extended results of the SPIN trial provide clear evidence that initial treatment with fixed moderate dose hydroxyurea (20 mg/kg/day) will prevent strokes in children with abnormal TCD measurements in a low-resource setting. The results of the extended SPIN trial have established the first evidence based stand care strategy for primary stroke prevention for children with SCA in Africa. Disclosures No relevant conflicts of interest to declare.

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Feasibility Trial for Primary Stroke Prevention in Children with Sickle Cell Anemia in Nigeria (SPIN Trial)

Blood ◽

10.1182/blood.v128.22.122.122 ◽

2016 ◽

Vol 128 (22) ◽

pp. 122-122 ◽

Cited By ~ 1

Author(s):

Najibah Aliyu Galadanci ◽

Shehu Umar Abdullahi ◽

Leah Danielle Vance ◽

Musa Tabari ◽

Shehi Abubakar ◽

...

Keyword(s):

Treatment Group ◽

Sickle Cell ◽

Stroke Prevention ◽

Comparison Group ◽

Controlled Trial ◽

Preliminary Evidence ◽

Feasibility Trial ◽

Transfusion Therapy ◽

Comparison Groups ◽

Hydroxyurea Therapy

Abstract Background: In children with sickle cell anemia (SCA), the routine use of transcranial Doppler (TCD) measurements and regular blood transfusion therapy for those with elevated velocities > 200 cm/sec, has dramatically decreased the rate of strokes. However, blood transfusion therapy for primary stroke prevention is not an option for most children in Africa. In preparation for a phase III trial of hydroxyurea therapy (20 mg/kg/day vs 10 mg/kg/day) for primary prevention of strokesin children with SCA in Africa, we conducted a single site, single-arm feasibility trial of hydroxyurea therapy for primary stroke prevention in children with SCA. Participants were between 5 and 12 years of age, attending the pediatric sickle cell disease clinic of Aminu Kano Teaching Hospital, in Kano, Nigeria. The main objectives of the feasibility trial were to determine the acceptability rate of a hydroxyurea therapy trial to families, and to obtain preliminary evidence of hydroxyurea safety in Africa. Methods: All eligible participants were screened with TCD, non-imaging technique, to determine increased stroke risk; defined as time-averaged maximum velocity (TAMV) greater than or equal to 200cm/sec in the middle cerebral artery (MCA). Families were offered moderate fixed dose hydroxyurea (~20mg/kg/day) for initially 2 years. Primary outcome measures of acceptability were based on three key components required for phase II randomized controlled trial: recruitment rate, retention rate and adherence to the study medication. To determine the expected background rate of adverse events and serious adverse events in this population, children with TCD velocities less than 200cm/sec who were not on hydroxyurea therapy were enrolled. Results: A total of 375 families were approached to be screened for elevated TCD measurements, of which 90% (330 of 375) enrolled; 8% (27 of 330) had two consecutive elevated TCD measurements; and 92% (25 of 27) participated in the trial. A total of 210 participants were identified with TCD velocities less than 200 cm, signed informed consents, and agreed to be followed prospectively in a comparison group. The median age for the trial participants and comparison group were 8 and 6.8 years, respectively. No statistically significant difference was observed in age, sex, ethnicity, height and weight of the treatment and comparison groups. The median time on therapy was 2.1 years (range: 0 to 2.8 years), and the average mean cell volume increased from 85 fl at baseline to 101.3 fl at 2 years. As per protocol, all patients were expected to attend monthly research visits and none were missed (n=total 603 visits). No participant in the treatment group dropped voluntarily from the trial, though one participant was withdrawn due to development of progressive renal failure. After follow up visits, participants in the comparison group with subsequent TCD measurements, were given the option to receive hydroxyurea therapy, and the only 2 with elevated TCD values elected to do so. No stroke occurred in the treatment group and 1 stroke occurred in the comparison group. Hospitalization rates in treatment and comparison groups were 35.1 and 48.0 per 100 patient years respectively, (p=0.06). A total of 9 deaths occurred, 1 death in the treatment group, but after participant withdrew from the trial because of progressive renal disease (1.76 per 100 patient-years) and 8 deaths in the comparison group (1·88 per 100 patient-years) p = 0.94. No participants that died received any PCV-13 vaccinations and only 2 received Hib vaccinations. At the time of death, all participants were prescribed malaria prophylaxis, and 8 of 9 participants were prescribed penicillin prophylaxis. Conclusion: In Nigeria, participants in SPIN Trial with elevated TCD measurements treated with moderate dose of hydroxyurea, showed high rates of successful recruitment, retention and adherence rates to trial medication. Importantly hydroxyurea therapy did not reveal any evidence of excessive toxicity when compared to those not treated with hydroxyurea. Our results provide strong preliminary evidence supporting the current multi-center randomized controlled trial comparing hydroxyurea therapy (20 mg/kg/day vs 10 mg/kg/day) for preventing primary strokes in children with SCA living in Nigeria (1R01NS094041-01;clinical trials.gov NCT 02560935). Disclosures No relevant conflicts of interest to declare.

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Low- Versus Moderate-Dose Hydroxyurea for Secondary Stroke Prevention in Children with Sickle Cell Disease in Sub-Saharan Africa: Final Results of a Randomized Controlled Trial, Sprint Trial

Blood ◽

10.1182/blood-2020-142896 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 5-6

Author(s):

Shehu Umar Abdullahi ◽

Surayya M. Sunusi ◽

Mohammed Sani Abba ◽

Saifuddeen Sani ◽

Aisha Galadanci ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Blood Transfusion ◽

Incidence Rate ◽

Stroke Prevention ◽

Low Dose ◽

Controlled Trial ◽

Secondary Stroke Prevention ◽

Moderate Dose ◽

Transfusion Therapy ◽

Randomized Controlled

Introduction Strokes are a preventable cause of neurological morbidity and premature death, particularly in children with sickle cell anemia (SCA) living in low-resource countries. If untreated, 50% of children with SCA their first overt ischemic stroke will have a recurrent stroke within two years of the event. In high-income countries, ASH 2020 guidelines recommend indefinite regular blood transfusion therapy for secondary stroke prevention (Blood Adv. 2020). Unfortunately, regular blood transfusion therapy is not a feasible option for children with SCA in sub-Saharan Africa due to the high cost of monthly blood transfusion, limited blood supply, and unsafe transfusion practices. Also, children who receive regular blood transfusions will ultimately require daily iron chelation at a cost that is prohibitive to most families in low-income settings. One randomized controlled trial provided evidence that HU therapy may be an effective therapy for secondary prevention of strokes when compared to no therapy (Blood. 2012;119(17):3925-3932). In the SWiTCH trial, the incidence rate of stroke recurrence in the group randomly allocated to receive maximum tolerated dose HU therapy was significantly higher than the group randomly assigned to receive blood transfusion therapy (5.6 and 0 events per 100 person-years, respectively, but considerably lower when compared to children not treated with any treatment, approximately 28 events per 100 person-years (Niger Postgrad Med J. 2013;20(3):181-187). Given the practical limitations for regular blood transfusion therapy, we tested the hypothesis that for secondary stroke prevention among children with SCA and acute overt ischemic stroke, fixed moderated dose HU therapy (~20 mg/kg/day) results in 80% relative risk reduction when compared to fixed low-dose HU therapy (10 mg/kg/day) in a randomized controlled trial (SPRINT Trial; NCT02675790). Methodology In phase III controlled trial, partially blind d controlled trial, we randomly assigned children 1 - 16 years of age with SCA and a new-onset of ischemic stroke (within 1 month) to receive fixed moderate-dose HU therapy at 20 mg/kg/day or fixed-low dose HU therapy at 10 mg/kg/day) with a monthly follow-up for at least 36 months. The primary endpoint was a recurrence of overt stroke or transient ischemic attack. Myelosuppression was assessed with monthly CBCs. Adherence to hydroxyurea was based on an increase in MCV from baseline and monthly pill count return, as a percent of dispensed pills. Results A total of 101 children with SCA were randomly assigned to fixed low- (~10 mg/kg/day) or moderate- (~20 mg/kg/day) dose hydroxyurea. The mean age was 6.6 years; 55.4% were males, and the median follow up was 1.6 years (IQR 1.0 - 2.3). The DSMB stopped the trial early due to the futility of the primary endpoint. In the fixed low- and moderate-dose groups, the incidence rates of recurrent strokes per 100 person-years were 7.1 and 6.0, respectively, incidence rate ratio of 0.85 (95% CI: 0.20 - 3.34), p=0.999. The incidence rates of mortality per 100 person-years in the fixed low dose and moderate- fixed-dose groups were 2.38 and 3.63, respectively, with an incidence rate ratio of 1.53 (95% CI: 0.18 - 18.30), p=0.98. No participant had hydroxyurea therapy stopped because of myelosuppression. As a measure of adherence, MCV from baseline to endpoint increased 6.2 fl and 13.3 fl in the fixed low- and moderate-dose groups, respectively, p=0.025; returned pills during the trial were 3.3% and 3.5% in the fixed low- and moderate-dose groups, respectively, p= 0.76. Conclusion For secondary stroke prevention, in a randomized controlled trial in children with SCA and new onset of ischemic strokes, fixed low-dose, when compared to fixed moderate-dose hydroxyurea therapy, demonstrated no difference in the incidence rate of stroke recurrence. Fixed low-dose hydroxyurea for secondary prevention of strokes in Nigeria provided similar stroke recurrence rate, when compared to the SWiTCH Trial (Blood. 2012;119(17):3925-3932) with the maximum tolerated dose of hydroxyurea of 7.0 and 5.7 events per 100 person-years, respectively. For secondary stroke prevention, in low-income settings without access to indefinite regular blood transfusion therapy, fixed low-dose hydroxyurea of at least 10 mg/kg/day with biannual CBC is a new evidence-based strategy to prevent strokes and minimize unnecessary laboratory testing. Disclosures DeBaun: Global Blood Therapeutics (GBT): Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: fixed low and moderate dose hydroxyurea for primary stroke prevention in sickle cell

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COMMUNITY BELONGING THROUGH THEATER: CREATIVE ARTS INTERVENTION FOR LOW-INCOME OLDER ADULTS

Innovation in Aging ◽

10.1093/geroni/igz038.714 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S198-S198

Author(s):

Ruth E Dunkle ◽

Laura Sutherland ◽

Garrett T Pace ◽

Ariel Kennedy ◽

Patricia Baldwin

Keyword(s):

Older Adults ◽

Treatment Group ◽

Social Exclusion ◽

Social Isolation ◽

Sense Of Community ◽

Low Income ◽

Comparison Group ◽

Creative Arts ◽

Significant Difference ◽

Community Belonging

Abstract Creative arts can promote social contact and possibly reduce isolation. A professionally run theater group comprised of low-income older adults met for 12 weeks to learn basic skills and perform a play. Using a pre-post questionnaire, data were gathered from the treatment group (n=14) who participated in the class and a non-participating comparison group (n=5) to identify potential program effects on measures of social isolation, community belonging, and social exclusion. Participants were African American living in low-income housing in an urban area. The average age of the sample was 65 years, 21% were men, 83% had at least high school degree, 71% reported good to excellent health, and 58% reported at least one ADL. Regression analyses showed that a sense of community belonging was significantly greater for the treatment group than the comparison group at time 2.This was not the case when considering social isolation or social exclusion. When controls were added (age, health, and previous theater experience), the significant difference remained with higher age predicting a sense of community belonging. The greater number of class sessions attended was also associated with a greater sense of community belonging for the treatment group. Through the shared experience of theater, participants can gain a sense of community, but this activity does not seem to be related to social isolation or social exclusion. It could be that theater participation fosters a sense of belonging due to group dynamics but is not a significant enough activity to reduce a sense of isolation or exclusion.

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Moderate Effects of Low-Intensity Behavioral Intervention

Behavior Modification ◽

10.1177/0145445518796204 ◽

2018 ◽

Vol 44 (1) ◽

pp. 92-113 ◽

Cited By ~ 5

Author(s):

Amin D. Lotfizadeh ◽

Ellie Kazemi ◽

Paula Pompa-Craven ◽

Sigmund Eldevik

Keyword(s):

Treatment Group ◽

Comparison Group ◽

Adaptive Skills ◽

Vineland Adaptive Behavior Scales ◽

Response Relationship ◽

Dose Response Relationship ◽

Low Intensity ◽

Intervention Intensity ◽

Comparison Groups ◽

Vineland Adaptive Behavior

We compared clinical outcomes in a treatment group of 98 individuals who received between 8 and 15 weekly hours ( M = 10.6; SD = 1.7) of applied behavior analysis (ABA) intervention with a comparison group of 73 individuals who received another provision, including some ABA, (between 1.4-8 weekly hours, M = 5.7; SD = 1.6). After 2 years, the treatment group made greater gains than the comparison group on language and social skills, and other areas assessed by the Verbal Behavior Milestones Assessment and Placement Program (VB-MAPP). We evaluated the outcome on adaptive skills for a smaller sample of participants using the Vineland Adaptive Behavior Scales II (VABS), but found no significant differences between the treatment ( n = 17) and comparison groups ( n = 11). Although the treatment group made important and clinically meaningful gains, the gains were moderate. These findings underline the importance of intervention intensity and provide further support for a dose–response relationship between ABA intervention hours and outcomes.

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The influence of plastic techniques in surgery of primary skin melanoma on patient survival

Russian Journal of Oncology ◽

10.18821/1028-9984-2020-25-1-27-36 ◽

2020 ◽

Vol 25 (1) ◽

pp. 27-36

Author(s):

S. A. Yargunin ◽

Y. N. Shoyhet ◽

A. F. Lazarev

Keyword(s):

Plastic Surgery ◽

Distant Metastasis ◽

Comparison Group ◽

Progression Free Survival ◽

Control Group ◽

Skin Melanoma ◽

Early Stages ◽

Significant Difference ◽

Comparison Groups ◽

Defect Repair

Objective. To analyze the feasibility of performing plastic surgery in patients with primary skin melanoma (SM). Material and methods. We studied patients with primary MK treated in our institution in 2013 (n = 333), who were randomized to a group of 2 blind selection methods to the main one (n = 168), in which the tumor removal operation in patients ended with a tissue defect repair and a comparison group ( n = 165) (after removal of the tumor, simple linear suturing of the wound was performed). A statistically significant difference was found in the comparison groups in the occurrence of negative dynamics (ND), progression-free survival (PFS) and overall survival (OS) in patients with MK 0-IIA st during the follow-up period up to 36 months. Results. It was found that patients with 0-IIA st who underwent plastic surgery to close the defect when removing primary SM have a statistically proven advantage in ND, PFS, and OS compared with patients without plastic surgery for up to 36 months. In general, the use of plastics has a statistical tendency towards the dynamics of an increase in PFS and OS in the early stages of SM. Discussion. In the early stages (0-IIA) up to 36 months, cases of negative dynamics (4.2%) were observed 2.3 times less frequently than in the comparison group (9.7%) (p = 0.048), and fatal outcomes in the main group (1.8%) were observed 3.7 times less than in the comparison group (6.7%) (p = 0.028). The analysis also shows that in patients who underwent surgery using plastic surgery statistically significantly reduces the risk of distant metastasis by 3 times (p = 0.05), but significantly more often (in every third patient) (p = 0.022) than in the control group (without plastic surgery) met transient metastases. The appearance of ND, as well as an increase in PFS, OS depended on the plastic replacement of the defect after excision of the primary SM in patients with SM 0-IIA st during the observation period up to 36 months. Conclusion. The use of plastic methods for closing a wound defect reduces the risk of distant metastasis by 3 times compared with linear suturing, provides a reduction in mortality in patients with SM 0 IIA st for 60 months, prolongs the patients life by an average of 10 months and is the operation of choice in this category.

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Neurobehavioral Effects of Organic Solvents Exposure Among Wood Furniture Makers in Ile-Ife, Osun State, Southwestern Nigeria

Journal of Health and Pollution ◽

10.5696/2156-9614-9.22.190604 ◽

2019 ◽

Vol 9 (22) ◽

Cited By ~ 1

Author(s):

Patrick Ayodeji Akinyemi ◽

Caleb Aderemi Adegbenro ◽

Temitope Olumuyiwa Ojo ◽

Olanrewaju Elugbaju

Keyword(s):

Organic Solvents ◽

Comparison Group ◽

Verbal Learning ◽

Small Scale ◽

Exposure Index ◽

Total Volatile ◽

Solvent Exposure ◽

Significant Difference ◽

Volatile Organic ◽

Comparison Groups

Background. Furniture making industries are small scale businesses that commonly use organic solvents. There has been minimal focus on the health effects of this chemical hazard on the nervous system among furniture makers in Nigeria. Objectives. The present study aimed to assess the association between organic solvents exposure and neurobehavioral status of furniture makers, using electronic technicians as a comparison group. Methods. A comparative cross-sectional study design was employed. A sample size of 108 was calculated for each group. A semi-structured interviewer-administered questionnaire was used to obtain data on the socio-demographic variables and use of personal protective equipment (PPE). A proforma was developed to collect neurobehavioral assessment data. A checklist was used to assess the furniture makers' workshops. Air was sampled from all of the workshops in both the study and comparison groups to determine the concentration of total volatile organic compounds (TVOCs). Results. The use of PPE was poor in both the study and comparison groups, with no significant difference between them (34.4% and 37.7% respectively). Total volatile organic compound and formaldehyde (HCHO) concentrations were significantly higher at the furniture makers' workshops compared with electronic technicians (p<0.001) for both chemicals. The 8-hour time-weighted average of TVOC was also higher in the furniture makers' workshops (4.4±0.6 mg/m3) compared with the control group (0.3±0.3 mg/m3). The neurobehavioral symptoms score was significantly higher among the study group relative to the comparison group (p<0.001). There was a significant difference in the outcome of the auditory verbal learning test, total recall (p=0.005), and delayed recall (p=0.003). There was no significant association between solvent exposure index and findings from the simple reaction time test Conclusions. Poor compliance with the use of PPE among furniture makers may increase their exposure to organic solvents. There were more neurobehavioral changes in the furniture makers with a higher exposure index. Measures are needed to educate artisans about workrelated chemical hazards and ensure compliance with basic occupational safety and hygiene standards. Participant Consent. Obtained Ethics Approval. Ethics approval was obtained from the Health Research and Ethics Committee of the Institute of Public Health, Obafemi Awolowo University (IPH/OAU/12/1049). Competing Interests. The authors declare no competing financial interests.

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Evaluation of Adherence, Virology and Imunology Response in HIV Patients Treated with a Once Daily Fixed Dose Combination (FDC) and a Free Combination of Antiretroviral

Advanced Science Letters ◽

10.1166/asl.2018.12656 ◽

2018 ◽

Vol 24 (8) ◽

pp. 6143-6146

Author(s):

N Mariana ◽

V Lisdawati ◽

S Maemun ◽

A Sucahyo ◽

P Debby ◽

...

Keyword(s):

Viral Load ◽

Treatment Group ◽

Treatment Strategy ◽

Fixed Dose ◽

Combination Group ◽

Similar Proportion ◽

Hiv Patients ◽

Cross Sectional ◽

Once Daily ◽

Significant Difference

A once daily FDC is a treatment strategy to reduce both the pill burden and the dosing frequency. This study to evaluate the adherence, virology and immunology response in patients treated with a once daily FDC (single pill) and free combination of antiretroviral (more than one pill). A cross sectional study on adults HIV–infected (aged >18 years old) in Sulianti Saroso Hospital, ARV–naïve patients for 12 months of treatment, receiving the first line ARV bases on Tenovofir and Efavirenz in the form of once daily FDC and a free combination of ARV. Ninety eight patients (a once daily FDC group consist of 78 patients and a free combination group consist of 20 patients) were recruited during the period of July to October 2017. The proportion of patients with good adherence (≥95%) after 12 months of once daily FDC treatment group was 98,7%, and a free combination group was 100%. The proportion of patients with an undetectable viral load to a once daily FDC treatment group was 80%, and a free combination group was 85,5%. The viral load and adherence were not significantly different statistically in two groups (Fisher Exact, p value >0,05) at 12 months of treatment and there was no significant difference in the increase in CD4 cell count at 6 months between those 2 groups at 6 months of treatment (Chi-Square p = 0,723). A once daily FDC treatment strategy and a free combination of ARV have the same benefits toward adherence, immunology response at 6 months therapy and virology response in HIV patients during 12 months of therapy. Confirmatory studies with similar proportion of patients between the two groups are needed to clarify the benefits of adherence, immunology and virology response.

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Silent cerebral infarcts occur despite regular blood transfusion therapy after first strokes in children with sickle cell disease

Blood ◽

10.1182/blood-2010-01-261123 ◽

2011 ◽

Vol 117 (3) ◽

pp. 772-779 ◽

Cited By ~ 154

Author(s):

Monica L. Hulbert ◽

Robert C. McKinstry ◽

JoAnne L. Lacey ◽

Christopher J. Moran ◽

Julie A. Panepinto ◽

...

Keyword(s):

Magnetic Resonance ◽

Sickle Cell Disease ◽

Blood Transfusion ◽

Sickle Cell ◽

Stroke Prevention ◽

Secondary Stroke Prevention ◽

Cell Disease ◽

Cerebral Infarcts ◽

Eligibility Criteria ◽

Transfusion Therapy

Abstract Children with sickle cell disease (SCD) and strokes receive blood transfusion therapy for secondary stroke prevention; despite this, approximately 20% experience second overt strokes. Given this rate of second overt strokes and the clinical significance of silent cerebral infarcts, we tested the hypothesis that silent cerebral infarcts occur among children with SCD being transfused for secondary stroke prevention. A prospective cohort enrolled children with SCD and overt strokes at 7 academic centers. Magnetic resonance imaging and magnetic resonance angiography of the brain were scheduled approximately every 1 to 2 years; studies were reviewed by a panel of neuroradiologists. Eligibility criteria included regularly scheduled blood transfusion therapy. Forty children were included; mean pretransfusion hemoglobin S concentration was 29%. Progressive cerebral infarcts occurred in 45% (18 of 40 children) while receiving chronic blood transfusion therapy; 7 had second overt strokes and 11 had new silent cerebral infarcts. Worsening cerebral vasculopathy was associated with new cerebral infarction (overt or silent; relative risk = 12.7; 95% confidence interval, 2.65-60.5, P = .001). Children with SCD and overt strokes receiving regular blood transfusion therapy experience silent cerebral infarcts at a higher rate than previously recognized. Additional therapies are needed for secondary stroke prevention in children with SCD.

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The Effects of Teach Back Method on Caregivers’ Strain in Handling Patients with Prolonged Immobilization

African Journal of Health, Nursing and Midwifery ◽

10.52589/ajhnm-iynvjnmh ◽

2021 ◽

Vol 4 (6) ◽

pp. 139-153

Author(s):

Weizheng Zhang

Keyword(s):

Treatment Group ◽

Experimental Design ◽

Assessment Tool ◽

Comparison Group ◽

Traditional Health ◽

Significant Difference ◽

Before And After ◽

Quasi Experimental ◽

Prolonged Immobilization ◽

Immobilization Method

Background: Caregivers’ strain mainly comes from lack of relevant care knowledge and nursing skills. Traditional health education is just a one-way information transmission mode without evaluation and feedback. Objective: To help caregivers’ memory, the researcher utilized a quasi-experimental design to measure the effectiveness of the teach-back method on caregivers’ strain in handling patients with prolonged immobilization. Method: A total of forty caregivers were averagely assigned into treatment (Teach-Back) and comparison group (traditional). Participant’s Data Sheet, The Zarit Burden Interview and Teach Back Assessment Tool was used to gather data. Results: There was a significant difference in caregivers’ strain before and after the Teach-Back Method in treatment (p<0.001) and comparison group (p <0.001). Likewise, a significant difference existed after the Teach-Back Method in the treatment group (p <0.001). Conclusion: The Teach-Back Method is an effective intervention in reducing caregivers’ strain in handling patients with prolonged immobilization.

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Randomized Controlled Trial of Fixed Low-Vs Moderate-Dose Hydroxyurea for Primary Stroke Prevention in Sub-Saharan Africa: Final Results of the Spring Trial

Blood ◽

10.1182/blood-2020-141436 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 4-5

Author(s):

Shehu Umar Abdullahi ◽

Binta W. Jibir ◽

Halima Bello-Manga ◽

Safiya Gambo ◽

Hauwa Inuwa ◽

...

Keyword(s):

Incidence Rate ◽

Stroke Prevention ◽

Low Dose ◽

Controlled Trial ◽

Maximum Velocity ◽

Incidence Rates ◽

Moderate Dose ◽

Advisory Committees ◽

Transfusion Therapy ◽

Hydroxyurea Therapy

Introduction: In children with sickle cell anemia (SCA) without transcranial Doppler (TCD) screening, the incidence rates of ischemic strokes is approximately the same among children living in low- and high- low-resource settings (Pediatr Neurol. 2019;95:73-78.) with a prevalence of ~ 11%. However, in high-income settings, the standard use of TCD ultrasonography, coupled initially with monthly blood transfusion therapy has dropped the stroke prevalence to < 1%. In a low-income setting, such as Nigeria, where 50% of children in the world with SCA are born (150,000 per year), initial monthly blood transfusion therapy is not practical for most children. In the Stroke Prevention in Nigeria (SPIN) Feasibility Trial (NCT01801423), fixed moderate-dose hydroxyurea was associated with a decreased rate of strokes in children with SCA and abnormal time-averaged mean of the maximum velocity (TAMMV) TCD measurements (≥200cm/sec) when compared to no treatment in the STOP Trial, 0.76 and 10.7 strokes per 100 person-years, repsectively (Am J Hematol. 2020). Based on the success of the SPIN trial, plus the challenges of real-world implementation of a government-supported primary stroke prevention programs for estimated 40,0000 children with SCA in three states in Nigeria, we tested the hypothesis that fixed-moderate dose (~20 mg/kg/day) hydroxyurea therapy for primary stroke prevention results in a 66% relative risk reduction (9 to 3 events per 100 person-years) when compared to fixed low-dose hydroxyurea (~10 mg/kg/day) therapy in a randomized controlled trial (The SPRING Trial; NCT02560935). Methods: In this partial-blind controlled phase III trial, we randomly assigned children between 5 and 12 years of age with SCA and a TCD time-averaged mean of the maximum velocity (TAMMV) ≥ 200 cm/sec measured independently twice or TAMMV ≥220 cm/sec once at study screening to receive fixed low-dose or fixed moderate-dose hydroxyurea. The primary endpoint was a clinical stroke or a transient ischemic attack (TIA). Myelosuppression was assessed with monthly complete blood counts (CBCs). Adherence to hydroxyurea was primarily based on an increase in MCV from baseline and monthly pill count return as a percent of dispensed pills. Hemoglobin F levels were measured at baseline, annually and upon trial exit. To evaluate the safety of hydroxyurea in the trial, children attending the same SCA clinics with TCD (TAMMV) <200 cm/sec at study screening were prospectively followed with biweekly phone calls and annual research visits. Results: A total of 220 children (mean age: 7.5 years, 51.8% female) were randomly assigned to fixed low- (10 mg/kg/day) or moderate- (20 mg/kg/day) dose hydroxyurea, and were followed for a median of 2.4 years (IQR 2.0-2.8). NINDS Clinical Trials leaders stopped the trial early because of futility for the primary outcome. In the fixed low- and moderate-dose hydroxyurea groups, the incidence rates of strokes per 100 person-years were 1.19 and 1.92 respectively, with an incidence rate ratio of 1.60 (95% CI: 0.31-10.34), p = 0.768. The incidence rate ratio of mortality when comparing the children treated with low- and moderate- fixed-dose hydroxyurea to the non-elevated TCD group (no hydroxyurea therapy, n= 211) was 1.97 (95% CI: 0.64-6.02) and 0.47 (95% CI: 0.05-2.38), p = 0.265 and 0.545, respectively. Returned pills during the trial was 5.4% and 4.8% in the fixed low- and moderate-dose groups, respectively, p= 0.144. MCV from baseline to endpoint increased 1.5fl and 7.2 fl in the fixed low- and moderate-dose groups, respectively, p<0.001. Upon exit from the trial 29.4% and 66.7% of the fixed- low and moderate -dose groups, respectively, had either hemoglobin level ≥ 9.0 g/dl, or a fetal hemoglobin level ≥ 20%. Conclusions: For primary stroke prevention in children with SCA, fixed low-dose, when compared to fixed moderate-dose hydroxyurea therapy, demonstrated no difference in the incidence rate of strokes. Both fixed low- and moderate -dose hydroxyurea doses are superior to no treatment for primary stroke prevention with abnormal TCD values. In partnership with Katsina, Kano, and Kaduna health department's leaders in Nigeria, 9 distinct SCA and primary stroke prevention clinics have been established, with the provision of free fixed low-dose hydroxyurea therapy (Bond Chemical, Nigeria; $0.15 per 500 mg) for abnormal TCD values, and biannual CBCs as standard care ,for over 40,000 children with SCA. Disclosures DeBaun: Global Blood Therapeutics (GBT): Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: fixed low and moderate dose hydroxyurea for primary stroke prevention in sickle cell

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