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Hydroxyurea appears safe for African children with sickle cell anemia
Hydroxyurea did not increase the risk for malaria infection in children with sickle cell anemia who live in malaria-endemic regions of Uganda, according to the results of a randomized, double-blind clinical trial published in Blood.
“Hydroxyurea has proven laboratory and clinical efficacy for children and adults with sickle cell anemia living in the United States and Europe,” Russell E. Ware, MD, PhD, director of the division of hematology at Cincinnati Children’s Hospital Medical Center, told HemOnc Today. “However, there are virtually no data regarding its safety and toxicities in sub-Saharan Africa, which bears the greatest global burden of disease.”
Sickle cell anemia is a life-threatening inherited disorder characterized by abnormal red blood cells that collect in blood vessels and obstruct blood flow to organs, which may result in severe pain, organ failure, stroke or death. More than 300,000 affected babies are born worldwide each year, mostly in sub-Saharan Africa, where an estimated 50% to 90% of children with sickle cell anemia die by the age of 5 years, often without an established diagnosis.
Hydroxyurea helps reduce the production of sickle hemoglobin, thus increasing the amount of healthy fetal hemoglobin. Approved by the FDA for adults with severe symptoms and by the European Medicines Agency for affected adults and children aged older than 2 years, hydroxyurea has a low incidence of treatment-related toxicity and no serious long-term adverse events. Evidence-based guidelines published by the NHLBI strongly recommend wider usage of hydroxyurea, including offering treatment to infants as young as 9 months.
However, hydroxyurea is not widely prescribed in sub-Saharan Africa, partly because of a lack of data that hydroxyurea would be effective and safe in low-resource regions.
Additionally, research has suggested that hydroxyurea could make people with sickle cell anemia more susceptible to malaria — a serious and sometimes fatal disease spread by mosquitoes — which is common across sub-Saharan Africa.
“There are concerns that hydroxyurea might worsen the severity of malaria in young children with sickle cell anemia, so a clinical trial using hydroxyurea in a malaria endemic region of Africa was warranted,” Chandy John, MD, MS, professor of pediatrics, microbiology and immunology at Indiana University School of Medicine, told HemOnc Today. “Because hydroxyurea provides such positive outcomes for people in high-resource regions, we want to be sure that this drug is safe for children in low-resource, malaria-prone settings.”
To help make that determination, researchers from the United States and Uganda established the year-long randomized, placebo-controlled Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM) trial.
Led by Robert O. Opoka, MMED, professor at Makerere University in Kampala, Uganda, researchers recruited 213 children aged 1 to 4 years receiving care at Mulago Hospital Sickle Cell Clinic in Kampala, Uganda, between Sept. 24, 2014, and Oct. 2, 2015. Five children with severe malnutrition, known chronic medical conditions, or who received a blood transfusion within 30 days were excluded.
Researchers randomly assigned 208 children to either once-daily oral hydroxyurea — 1,000 mg scored tablets and 100 mg dispersible tablets — or a placebo for a full year. All patients also received standard care for sickle cell anemia — including folic acid, penicillin prophylaxis and pneumococcal vaccinations — along with insecticide-treated mosquito nets and antimalaria medication.
After trial completion, all participants could receive open-label hydroxyurea.
Researchers monitored children for clinical malaria and toxicities at 2 weeks and at 1, 2, 3, 4, 6, 8, 10 and 12 months.
Incidence of clinical malaria served as the primary endpoint. Secondary endpoints included sickle cell anemia-related adverse events, clinical adverse events and dose-limiting toxicities.
Three children assigned hydroxyurea experienced a total of five malaria episodes, and seven children receiving placebo had a total of seven malaria episodes. All 10 study participants with malaria recovered.
Malaria incidence did not differ between children prescribed hydroxyurea (0.05 episodes per child per year; 95% CI, 0.02-0.13) vs. placebo (0.07 episodes per child per year; 95% CI, 0.03-0.16). The hydroxyurea-placebo malaria incidence rate ratio was 0.7 (95% CI, 0.2-2.7).
Children receiving hydroxyurea also had lower rates of pain crises and hospitalizations.
Fewer children assigned hydroxyurea experienced a composite of sickle cell anemia-related adverse events that included vaso-occlusive painful crisis, dactylitis, acute chest syndrome, splenic sequestration or blood transfusion (45% vs. 69%; P = .001). Incidence of serious adverse events, sepsis and dose-limiting toxicities was comparable between the arms.
“In this setting, the incidence and severity of malaria was no greater in the hydroxyurea arm, compared to the placebo arm,” Chandy said. “Laboratory and clinical benefits of hydroxyurea were observed, suggesting that hydroxyurea therapy is safe and effective in this low-resource setting.”
Six of the 12 malaria episodes required hospitalization and four episodes had concomitant vaso-occlusive pain crisis (n = 3) or pneumonia (n = 1). Two children in the hydroxyurea arm died, one from presumed sepsis and the other from unknown sudden death. One child in the placebo arm died, presumably of sepsis.
“Because the children prescribed hydroxyurea experienced significantly better outcomes without any increase in malaria risk, we were incredibly encouraged to further explore the drug’s use in sub-Saharan Africa,” Ware said.
Researchers are recruiting additional participants in malaria-prone regions of sub-Saharan Africa to assess how sickle cell anemia-related adverse events and hematological responses compare for children receiving fixed-dose treatment vs. dose-escalation regimens.
“The incidence of malaria in the NOHARM trial was lower than predicted; accordingly, our conclusions of safety for hydroxyurea treatment may not be applicable to regions with higher malaria rates,” Ware said. “Another area for further investigation is the optimal dosing and monitoring scheme for hydroxyurea in sub-Saharan Africa, given the costs of both the drug itself and periodic blood tests in areas with limited resources. Before hydroxyurea can be recommended for wide use across sub-Saharan Africa, partnerships are needed to develop and implement effective, affordable, and sustainable models of treatment delivery.” – by Chuck Gormley
New RFP Announcement: Sickle Cell Disease Association of America, Inc. (SCDAA)
Request for Proposal: SCDAA-HRSA Newborn Screening Follow-up Program
The Sickle Cell Disease Association of America, Inc. (SCDAA) is seeking to provide support for up to 17 Sickle Cell Disease Community Based Organizations (CBO’s) to work with state collaborators that will improve the care and reduce the number of individuals with sickle cell disease (SCD) who are “lost to follow-up” by supporting efforts of sickle cell disease education and service coordination. This program will ensure that individuals diagnosed with sickle cell disease receive appropriate follow-up services including counseling, education, access to a medical home, and other support services. This effort will be overseen by SCDAA as the National Coordinating Center.
To view and download a full copy of the RFP and instructions please click here or log on to the SCDAA website at www.sicklecelldisease.org.
Important Dates:
- RFP Release Date: October 1, 2017
- Webinar/Teleconference: Tuesday, October 10, 2017
A pre-submission technical assistance webinar for all prospective applicants will be held:
- Time: 2:00 p.m. EST – 4:00 p.m. EST
- Dial In: 1-240-454-0879
- Passcode: 662 468 533
- Web Link: https://sicklecelldisease.webex.com/sicklecelldisease/onstage/g.php?MTID=ed89f253219538c6dad3928f4d0d03317
Proposal Due Date: November 13, 2017, by 11:59 p.m. EST
CONTACT: Sonya Ross, Project Director ● PHONE: 410-528-1555 ● 800-421-8453
WEBSITE ADDRESS: www.sicklecelldisease.org ● E-MAIL ADDRESS: SCDAARFP@sicklecelldisease.org
Articles in the Medical Literature
Indian J Med Res. 2017 Jun;145(6):705-707. doi: 10.4103/ijmr.IJMR_1208_17.
World Sickle Cell Day: Lessons for India.
Author information:
1 Sickle Cell Trust (Jamaica), Kingston 6, Jamaica.
Free Article
PMID: 29067968
Am J Hematol. 2017 Oct 25. doi: 10.1002/ajh.24953. [Epub ahead of print]
Pediatric to adult care Co-location transitional model for youth with sickle cell disease.
Nolan VG1, Anderson SM2,3, Smeltzer MP1, Porter JS4, Carroll YM2, Brooks IM5,6, Elmagboul N3, Gurney JG1, Hankins JS2,3.
Abstract
Among youth with sickle cell disease (SCD), morbidity and mortality substantially increase following departure from pediatric care. The purpose of this study was to investigate the efficacy of co-location transitional model by comparing the rate of health care utilization pre- and post-transfer to adult care and to evaluate the relation between disease specific knowledge and the co-location model. All patients transferring from pediatric to adult care between October 2011 and December 2013, opting for the co-location model to transition from pediatric to adult care in Memphis, TN were included in the analysis. Overall utilization, comprised of both acute care visits and hospitalizations, and health-maintenance visits were compared pre- and post-transfer. Additionally, the association between patient understanding of pain and all health care utilization were assessed. There were 59 participants who established adult care using the co-location transitional model. We found an increase in acute care visits, but a decrease in hospitalizations, that resulted in no change in overall utilization (IRR: 1.11; (95%CI: 0.76, 1.63) comparing pediatric to adult care. The overall utilization rate during adult care was below those previously reported (3.61 vs. 1.65 per person-year, p<0.001). Additionally, we found a significant decrease in hospitalizations and an increase in health-maintenance visits associated with higher pain knowledge after transfer. The co-location model for pediatric to adult care transition seems to provide benefits among youth with SCD by increasing disease knowledge and reducing health care utilization to levels below those seen at the national level. This article is protected by copyright. All rights reserved.
© 2017 Wiley Periodicals, Inc.
PMID: 29067725
Biol Blood Marrow Transplant. 2017 Oct 20. pii: S1083-8791(17)30799-1. doi: 10.1016/j.bbmt.2017.10.030. [Epub ahead of print]
Rangarajan HG1, Abu-Arja R1, Pai V2, Guilcher GMT3, Soni S4.
Abstract
Unrelated donor (URD) hematopoietic cell transplants (HCT) in children with sickle cell disease (SCD) is associated with a high incidence of rejection and graft versus host disease. We report on first four patients with severe SCD who underwent URD HCT using a novel myeloablative and immunosuppressive regimen comprising of busulfan, fludarabine and anti-thymocyte globulin with a single dose of post-transplant cyclophosphamide along with tacrolimus and mycophenolate mofetil for graft versus host disease prophylaxis. Three patients engrafted and remain disease free after a median follow-up period of 2.5 years. One patient had primary graft failure attributed to low stem cell content of the graft. Of interest, none of the engrafted patients developed acute or chronic graft versus host disease. This preparative regimen along with the use of post-transplant cyclophosphamide offers a promising approach for unrelated donor transplants in patients with sickle cell disease and needs further corroboration in larger number of patients.
Copyright © 2017. Published by Elsevier Inc.
PMID: 29061531
J Stroke Cerebrovasc Dis. 2017 Oct 19. pii: S1052-3057(17)30491-3. doi: 10.1016/j.jstrokecerebrovasdis.2017.09.020. [Epub ahead of print]
Adegoke SA1, Macedo-Campos RS2, Braga JAP3, Figueiredo MS4, Silva GS5.
Abstract
BACKGROUND AND OBJECTIVES:
Hydroxyurea (HU) was recently described as a substitute for chronic transfusion for children with sickle cell disease (SCD) and abnormal transcranial Doppler (TCD) velocities who have received at least 1 year of transfusions. However, the role of HU in reverting elevated TCD velocities in patients not treated with transfusion is still debatable. The objective of the study was to examine whether HU influences the progression of TCD velocities in children with SCD.
PATIENTS AND METHODS:
Children with SCD with at least 2 TCDs not less than 6 months apart were evaluated over 51 months. Time-averaged maximum mean (TAMM) velocities for the initial and the last transcranial Doppler examinations were noted and differences compared between HU and HU-naive groups.
RESULTS:
Overall, 68.8% of the HU-group with elevated TCD velocities compared with 40.0% of the HU-naive experienced TCD reversal (P = .047). A higher proportion of the HU-naive group, 7 (14.3%) versus 9.8% of the HU group experienced TCD conversion. Those with initial conditional velocities in the HU-group experienced a significant reduction in TAMM velocities (from 176.8 ± 5.3 to 162.7 ± 13.9 cm/s, difference of 14.1 cm/s; P = .001) unlike those in the HU-naive group (176.3 ± 5.3 to 170.0 ± 18.6 cm/s, difference of 6.3 cm/s; P = .148). The change in the TAMM velocities was also significantly higher among the HU-group (14.1 ± 12.4 cm/s versus 6.3 ± 18.5 cm/s, P = .015).
CONCLUSION:
Our data suggest a beneficial role of HU in TCD velocity reduction in patients not treated with chronic transfusions, particularly among those with initial conditional TCD velocities.
Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.
PMID: 29056404
Blood. 2017 Oct 19. pii: blood-2017-06-788935. doi: 10.1182/blood-2017-06-788935. [Epub ahead of print]
Opoka RO1, Ndugwa CM1, Latham TS2, Lane A2, Hume HA3, Kasirye P1, Hodges JS4, Ware RE5, John CC6..
Abstract
Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA) living in high-resource malaria-free regions, but its safety and efficacy in malaria-endemic sub-Saharan Africa, where the greatest sickle cell burden exists, remain unknown. In vitro studies suggest hydroxyurea could increase malaria severity, and hydroxyurea-associated neutropenia could worsen infections. NOHARM was a randomized, double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda, comparing hydroxyurea to placebo at 20 ± 2.5 mg/kg/day for 12 months. The primary outcome was incidence of clinical malaria. Secondary outcomes included SCA-related adverse events, clinical and laboratory effects, and hematological toxicities. Children received either hydroxyurea (N=104) or placebo (N=103). Malaria incidence did not differ between children on hydroxyurea [0.05 episodes/child/year, 95% CI (0.02, 0.13)] versus placebo [0.07 episodes/child/year (0.03, 0.16)]; the hydroxyurea/placebo malaria incidence rate ratio was 0.7 [(0.2, 2.7), p=0.61]. Time to infection also did not differ significantly between treatment arms. A composite SCA-related clinical outcome (vaso-occlusive painful crisis, dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion) was less frequent with hydroxyurea (45%) than placebo (69%, p=0.001). Children receiving hydroxyurea had significantly increased hemoglobin concentration and fetal hemoglobin, with decreased leukocytes and reticulocytes. Serious adverse events, sepsis episodes, and dose-limiting toxicities were similar between treatment arms. Three deaths occurred (two hydroxyurea, one placebo, none from malaria). Hydroxyurea treatment appears safe for children with SCA living in malaria-endemic sub-Saharan Africa, without increased severe malaria, infections, or adverse events. Hydroxyurea provides SCA-related laboratory and clinical efficacy, but optimal dosing and monitoring regimens for Africa remain undefined.
Copyright © 2017 American Society of Hematology.
PMID: 29051184
J Pediatr Psychol. 2017 Sep 26. doi: 10.1093/jpepsy/jsx120. [Epub ahead of print]
Psihogios AM1, Daniel LC1,2, Tarazi R3,4, Smith-Whitley K1,5, Patterson CA1,5, Barakat LP1,5.
Abstract
Background:
Informed by the Pediatric Self-Management Model, the present study tested relationships between parent and family functioning, sickle cell disease (SCD) self-management, and health outcomes for children with SCD.
Method:
83 children with SCD and a parent completed baseline data as part of a larger investigation of a family-based, problem-solving intervention for children with SCD (M age = 8.47). Youth and parents completed a measure of child health-related quality of life (HRQOL), and parents completed measures of family efficacy, parenting stress, and SCD self-management. SCD pain episodes and urgent health utilization information over the past year were obtained via medical chart review.
Results:
SCD self-management mediated the relationship between parent-reported family efficacy and parent proxy HRQOL, as well as the relationship between parenting stress and child and parent proxy HRQOL. Mediation models were nonsignificant for outcomes beyond HRQOL, including SCD pain episodes and urgent health utilization.
Conclusion:
Fostering family efficacy and reducing parenting stress may be meaningful intervention targets for improving SCD self-management and child HRQOL among school-aged children. Although findings were consistent with the Pediatric Self-Management Model in terms of HRQOL, the model was not supported for pain episodes or urgent health utilization, highlighting the need for multi-method, longitudinal research on the SCD self-management behaviors that are linked to preventable health outcomes.
PMID: 29048590
J Pediatr Psychol. 2017 Sep 18. doi: 10.1093/jpepsy/jsx115. [Epub ahead of print]
Downes M1,2, Kirkham FJ2, Telfer PT3, de Haan M2.
Abstract
Objective:
Sickle cell disease (SCD) is a genetic red blood cell disorder that often leads to stroke and executive dysfunction in school-age children and adults. This study aimed to characterize the development of the neural correlates of selective attention, an early component of executive function, in preschool children with SCD.
Methods:
Auditory event-related potentials (ERPs) were recorded while children attended to a story stream in one ear and ignored a second story in the other ear interchangeably. In total, 12 patients (mean age = 5.5, 7 males) and 22 typically developing children (mean age = 4.4, 10 males) were included in the final analyses.
Results:
By 100 ms, more positive ERP amplitudes were observed for attended relative to unattended stimuli in typically developing children but not those with SCD, suggesting deficits in the ability to focus attention. Reduced attention effects were associated with lower performance intellectual quotient.
Conclusion:
There are deficits in early attention modulation in young children with SCD.
PMID: 29048550
Br J Haematol. 2017 Oct 19. doi: 10.1111/bjh.14969. [Epub ahead of print]
Haymann JP1,2,3, Hammoudi N4,5, Stankovic Stojanovic K6, Galacteros F7, Habibi A7, Avellino V6, Bartolucci P7, Benzerara Y1, Arlet JB8, Djebbar M1, Letavernier E1,2,3, Grateau G6, Tabibzadeh N1, Girshovich A1, Chaignon M1, Girot R6, Levy P9, Lionnet F6.
Abstract
The management of sickle cell nephropathy (SCN) at an early stage is an important issue to prevent renal and cardiovascular morbidity and mortality. This study aimed to evaluate in this population, whether angiotensin converting enzyme inhibitors (ACEIs) treatment could exert a cardio-renal protection in a SCN cohort. Forty-two SCN patients (urine albumin:creatinine ratio (ACR) > 10 mg/mmol) were treated with ACEIs for 6 months, then evaluated for ACR, measured glomerular filtration rate (mGFR) together with haematological and cardiovascular parameters. A 1-month washout was also performed in order to differentiate short- and long-term ACEIs effects. A decrease in ACR baseline value (>30%) was detected in 62% of cases (mean ACR: 46·4 ± 7·6 and 26·4 ± 3·9 mg/mmol at baseline and 6 months respectively; P = 0·002), whereas mGFR values were unchanged. ACR decrease was detected at 1 month following ACEI initiation (32·9 ± 6·9, P = 0·02) with a persistent trend after withdrawal (P = 0·08). ACEIs also decreased diastolic blood pressure (P = 0·007), pulse wave velocity (P = 0·01), tricuspid regurgitation velocity (TRV; P = 0·04), asymmetric dimethyl arginine (ADMA: P = 0·001) and haemoglobin (P = 0·01) while conventional haemolytic biomarkers were unchanged. Our data suggest that ACEIs are safe and effective at decreasing albuminuria in sickle cell patients with a beneficial effect on specific mortality risk factors, such as TRV and asymmetric dimethyl arginine.
© 2017 John Wiley & Sons Ltd.
PMID: 29048108
CJEM. 2017 Oct 17:1-8. doi: 10.1017/cem.2017.413. [Epub ahead of print]
Binding A1, Ward R1, Phua C2, Naessens V3, O’Brien T4, Bhatia S4, Baranek H4, Marani H4, Mukerji G4.
Abstract
OBJECTIVES:
Patients with sickle cell disease (SCD) with vaso-occlusive crises (VOC) often visit the emergency department (ED) for management of painful episodes. The primary objective of this pilot study was to evaluate the acceptability of a short-stay model for treatment of VOC in SCD outside of the ED in Toronto, Canada. Secondary objectives were to assess patient satisfaction of this model, barriers to its use and comparison of clinical outcomes to a historical control.
METHODS:
Adult SCD patients with symptoms of an uncomplicated VOC between October 2014 to July 2016 were managed according to best practice recommendations in a short-stay unit as an alternative to the local emergency room. Primary outcome of time to first analgesia, and secondary outcome of discharge rate were compared to a historical control at a local ED from 2009-2012. Satisfaction and barriers to use of the ambulatory care delivery model were assessed by patient survey.
RESULTS:
Twenty-one visits were recorded at the short-stay unit during the study period. Average time to first opiate dose was 23.5 minutes in the short-stay unit compared to 100.3 minutes in the ED (p<0.001). Discharge rate from the short-stay unit was 84.2%. Average patient satisfaction with this model of care was high (>4/5 on Likert scale) except for geographic accessibility (85% response rate, n=18).
CONCLUSION:
This study demonstrated high patient satisfaction and acceptability of a short-stay model for treatment of uncomplicated VOC in adult SCD patients in Toronto, the first of its kind in Canada.
PMID: 29039292
Pain Med. 2017 Sep 26. doi: 10.1093/pm/pnx214. [Epub ahead of print]
Predictive Ability of Intermittent Daily Sickle Cell Pain Assessment: The PiSCES Project.
Smith WR1, McClish DK2, Levenson J3, Aisiku I4, Dahman B5, Bovbjerg VE6, Roseff S7, Roberts J8.
Abstract
Background:
Pain diary assessment in sickle cell disease (SCD) may be expensive and impose a high respondent burden.
Objective:
To report whether intermittent assessment could substitute for continuous daily pain assessment in SCD.
Design:
Prospective cohort study.
Setting:
Academic and community practices in Virginia.
Patients:
A total of 125 SCD patients age 16 years or older in the Pain in Sickle Cell Epidemiology Study.
Measurements:
Using pain measures that summarized all diaries as the gold standard, we tested the statistical equivalence of four alternative strategies that summarized diaries only from the week prior or the month prior to study completion; one week per month; or one day per week (random day). Summary measures included percent pain days, percent crisis days (self-defined), mean pain (0-9 Likert scale) on all days, and mean pain on pain days. Equivalence tests included comparisons of means, regression intercepts, and slopes, as well as measurement of R2.
Results:
Compared with the gold standard, the one-day-per-week and one-week-per-month strategies yielded statistically equivalent means of six summary pain measures, and the week prior and month prior yielded equivalent means as some of the measures. Regression showed statistically equivalent slopes and intercepts to the gold standard using one-day-per-week and one-week-per-month strategies for percent pain days and percent crisis days, but almost no other equivalence. R2 values ranged from 0.64 to 0.989.
Conclusions:
It is possible to simulate five- to six-month daily assessment of pain in SCD. Either one-day-per-week or one-week-per-month assessment yields an equivalent mean and fair regression equivalence.
PMID: 29036363
Cochrane Database Syst Rev. 2017 Oct 10;10:CD003427. doi: 10.1002/14651858.CD003427.pub4. [Epub ahead of print]
Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease.
Rankine-Mullings AE1, Owusu-Ofori S.
Author information:
Abstract
BACKGROUND:
Persons with sickle cell disease (SCD) are particularly susceptible to infection. Infants and very young children are especially vulnerable. The ‘Co-operative Study of Sickle Cell Disease’ observed an incidence rate for pneumococcal septicaemia of 10 per 100 person years in children under the age of three years. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population. This is an update of a Cochrane Review first published in 2002, and previously updated, most recently in 2014.
OBJECTIVES:
To assess the effects of antibiotic prophylaxis against pneumococcus in children with SCD in relation to:1. incidence of infection;2. mortality;3. drug-related adverse events (as reported in the included studies) to the individual and the community;4. the impact of discontinuing at various ages on incidence of infection and mortality.
SEARCH METHODS:
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and also two clinical trials registries: ClinicalTrials.gov and the WHO International Registry Platform. Additionally, we carried out handsearching of relevant journals and abstract books of conference proceedings.Date of the most recent search: 19 December 2016.
SELECTION CRITERIA:
All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with SCD with placebo, no treatment or a comparator drug.
DATA COLLECTION AND ANALYSIS:
Both authors independently extracted data and assessed trial quality. The authors used the GRADE criteria to assess the quality of the evidence.
MAIN RESULTS:
Five trials were identified by the searches, of which three trials (880 children randomised) met the inclusion criteria. All of the included trials showed a reduced incidence of infection in children with SCD (SS or Sβ0Thal) receiving prophylactic penicillin. In trials which investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% confidence interval 0.16 to 0.86) (two trials, 457 children) (low-quality evidence), while for withdrawal the odds ratio was 0.49 (95% confidence interval 0.09 to 2.71) (one trial, 400 children) (low-quality evidence). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five.Overall, the quality of the evidence for all outcomes was judged to be low. The results from the risk of bias assessment undertaken identified two domains in which the risk of bias was considered to be high, these were incomplete outcome data (attrition bias) (two trials) and allocation concealment (selection bias) (one trial). Domains considered to have a low risk of bias for all three trials were selective reporting (reporting bias) and blinding (performance and detection bias).
AUTHORS’ CONCLUSIONS:
The evidence examined suggests that prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous SCD, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin.
PMID: 28994899
Blood Cells Mol Dis. 2017 Sep 21. pii: S1079-9796(17)30330-3. doi: 10.1016/j.bcmd.2017.09.006. [Epub ahead of print]
Yee ME1, Lane PA2, Archer DR2, Joiner CH2, Eckman JR3, Guasch A4.
Author information:
Abstract
Sickle cell nephropathy begins with hyperfiltration and microalbuminuria and may progress to renal failure. The aim of this study was to determine the effects of losartan on glomerular function and albumin excretion in sickle cell anemia (SCA). Individuals with SCA on hydroxyurea with persistent albuminuria were enrolled in a 1-year study of losartan. Glomerular filtration rate (GFR) measured by iohexol clearance, albumin excretion rate (AER), and fractional clearance of dextran were assessed at baseline, short-term (1-2month), and long-term (≥12month) intervals. Twelve subjects (6 microalbuminuria, 6 macroalbuminuria) completed short-term studies; 8 completed long-term studies. Baseline GFR was 112ml/min/1.73m2 (71-147ml/min/1.73m2). AER decreased significantly at the short-term (median decrease -134 mcg/min, p=0.0063). GFR was not significantly-different at short-term or long-term intervals. Dextran clearance improved for diameters smaller than albumin (<36Å) but not larger sizes. Losartan therapy for ≥1year in sickle nephropathy results in lower albumin excretion with stable GFR. Filtration of neutral molecules ≥36Å was not changed by losartan, suggesting that the effect of losartan is a mechanism other than alteration of glomerular filtration size-selectivity.
Copyright © 2017 Elsevier Inc. All rights reserved.
PMID: 28951038
Sickle Cell Conferences and Events
Please join the sickle cell team at Children’s National Medical Center for our 8th Annual Family Education Symposium: Living Well with Sickle Cell. All are welcome to this free event!
Saturday November 4th, 2017
9:00am-1:30pm
Sheikh Zayed Campus for Advanced Children’s Medicine
Children’s National Health System
111 Michigan Ave NW
2nd Floor, Auditorium
Washington, DC 20010
We will have a speaker from Shady Grove Fertility to discuss pre-implantation and sessions on topics including Bone Marrow Transplant, Hydroxyurea, Pain and the ongoing opioid crisis, social security, and transition to adult care. Breakfast will be served. Please register at: https://www.surveymonkey.com/r/5MYGT2L or call Alexandra Hollman, LICSW at 202-476-1333.
