|Major Variables Studied and
Measurement of Major Variables
|Strength of the Evidence (i.e., level of evidence + quality [study strengths and weaknesses])|
|Author, Year, Title||Sharef, S. W., Al-Hajri, M., Belshlawi, I., & Al-Sharabally, A. (2013). Optimizing Hydroxyurea use in children with sickle cell disease: low dose regimen is effective. European Journal of Haematology, 519-524.|
Age= 2 to16 years
Delivery; doses of 15-20 mg/kg/day with the possibility of increasing it to 35 mg/kg/day
IG (A): retrospective observation of patients from Sultan Qaboos University Hospital from 1998 to 2008.
IG (B): prospective observation of the same patients from 2009 to 2-11.
|IV= Hyroxyurea treatment
DV= sickle cell disease, prescription of myelosuppressive drugs.
|Observation of responses or side effects from the initial dose of Hu of 10-12 mg/kg/day.
Patients divided into two different groups based on the 10-15.9 mg/kg/day and 16 to 26 mg/kg/day doses of HU.
Mean of each groups
Wilcoxon singed rank test.
|19 patients dropped out of the program due to various Sid effects.
Recognisable reduction of admissions because of VOC in both groups. (P< 0.001 Wilcoxon signed-rank test.
Difference between groups was insignificant. (P> 0.05, Mann-Whitney U-test)
|Level of evidence: III
Limitation: Patients dropping out due to side effects.
Research was too generalised as it included information that developed over the years before the prospective follow-up.
Observed admissions using ACS or VOC instead of the duration or severity of admission.
Strength: data is critically analysed and statistically detailed.
↑ Applicability: requires expertise in the area and its observation period is extremely long. Needs yeas to be applied.
|Author, Year, Title||Harminder Singh, N. D. (2010). Effective control of sickle cell disease with hydroxyurea therapy. Indian J Pharmacol, 32-35.|
|No||Cross-sectional study||N: 27
IG: Patients with SCD were given a mean doe of Hu measuring at 22 mg/kg/day
IG2; analysis of baseline results against post treatment results after a duration of a year.
|IV: Hydroxyirea therapy
DV:Sickle cell disease
|Observation of Hb eltrophoresis with quantitative HbF%, CBC with reticulocyte and differential count, liver function tests, serum B-12 as well as folate.
Follow up visits every two months with key observation of Hb level, HbF, MCV, MCHC and WBC count on the 6th observation.
|Mean initial haemoglobin level measured at 9.15 g/dl with an increase after an year to 9.98 g/dl
Mean initial HbF was valued at 12.83% and later 19.7%after one year of HU therapy
The baseline WBC was 9.62 (* 109 L) and lowered insignificantly after one year to 8.33 (* 109 L)
|Level of evidence: I
Strength: observations were held frequently.
Effective treatment and testing methodologies
Limitation: small sample size.
↓applicable to hospitals with relevant treatment infrastructure.
|Author, Year, Title
|Lobo, C. L., Pinto, J., Nascimento, E., & Moura, P. (2013). The effect of hydroxcarbamide therapy on survival of children with sickle cell disease. British Journal of Haematology, 852-860.|
|Logistic regression models||Cohort||N= 1760
IG (A): 267 were given hydroxycarbamide measuring at 20.8 mg/kg/day for an average of 2 years
IG (B): Clinical/ laboratorial effects of hydroxycarbamide and mortality data of the first 9 years of the program was collected.
|IV: Hydrocabamide therapy
DV: children with sickle cell disease, mortality rate.
|Administrations were based on the Brazilian Ministry of Health Hdroxyurea Clinical Treatment Protocol.
The first dose was measured at 10mg/kg/day and administered once per day.
Patients who could not take tablets, 500 mg capsules were dissolved in sterile water as well as being constituted to a 100 mg/ml for small children.
Parents and guardians were also involved in administering the reconstitution. The doses were increased by 5 mg/kg/d every month with a monitoring of clinical benefits and laboratory information.
Monthly clinic visits during escalation of dose and every 3 months in a maintenance phase.
Complete blood counts and chemistries in every visit.
HbF was analysed through high performance liquid chromatography every second month visit and every 6 month visit.
|1760 patients with SCD at HEMORIO between 1st August 2000 and 31 December 2009.
267 met the laboratory criteria.
Hdroxycabamde working was not by recurrent pain events in 45.3% of them. > ACS event were in 25.1% of them. Hb concentration <60 g/l in 24.4%.
Duration of therapy was two years.
Median dose was 4.8 mg/kg/d.
Majority of hydroxycabamide-treated patients had HbSS genotypes.
Children with a younger ate group of median age 5.4 had a higher content of HbSS at 91% in comparison to those of median age of 7.2 years who had 73% concentration. P-value < 0.0001.
|Level of evidence: IV
Limitation: the clinical qualification is strict.
Applicability to international programs in a broader research perspective. Best suited for children under the age of 5.
|Author, Year, Title
|Fitshugh, C., Hsieh, M., Allen, D., & Coles, W. (2015). Hydroxyurea-Increased Fetal Hemoglobin Is associated with less organ damage and longer survival in adults with sickle cell anemia. Kingston: Crossmark.|
|No||Case Control||N= 383
IG: echocardiographic, laboratory and clinical evaluations between 2001 and 2010.
Mortality data was updated in a two year duration.
Sickle cell disease phenotypes were distributed based on DNA sequencing and performance liquid chromatography.
Outpatient studies had their results from the time of first visit to those of their most recent visit. Mean corpuscular volume was measured.
|IV: Hydroxyurea-increased fetal Haemoglobin
DV: sickle cell anaemia, mortality,
| Dosing treatment and decisions were made by the primary provider of o the patient.
The NIH Biometric Translational Research Information System screened notes for the term hydroxyurea from 20, 00 documents.
Wilcoxon rank sum tests
Cox proportional hazard regression
Sixty percent had been treated with hydroxyurea.
Comparison of deceased subjects indicates that majority of them were older at enrolment (41.8 versus 32.5 years, p=0.0067) and had a lower maximum HbF. P=0.0044.
They also were less likely to have used hydroxyurea (56% in comparison to 68% with p=0.040, hazard ratio was 0.58, 95% confidence interval 0.34, 0.97).
They also had a lower proportion prescribed hydroxyurea in the prescribed doses (29% in comparison to 46% with p=0.0067)
|Level of the evidence: I
Limitation: all the information is secondary and historical.
Strength: collection of information on the treatment of over the last decade.
|Author, Year, Title
|Al-Nood, H., Al-Khawiani, M., & Al-Akwa, A. (2010). FETAL HEMOGLOBIN RESPONSE TO HYDROXYUREA IN YEMENI SICKLE CELL DISEASE PATIENTS. Haemoglobin, 15-21.|
|No||Randomised control trial study||N= 100
IG: patients were sourced from Al-Thawra Hospital, Al Sabina Hospital, Yemen Society for Thalassemia and genetic blood disorders in Sana City in Yemen. They were divided into three groups, the first comprising 21 patients for short term follow up. 26 were set for long term and the third remained untreated.
|IV: fetal haemoglobin response, hydroxyurea.
DV: sickle cell disease
|Samples collected from correspondents were analysed by the Haemoglobin Research Laboratory, Kuwait University, and Faculty of medicine.
Detection of HbF levels with the application of high functional liquid chromatography.
Paired samples t-test
Independent sample t-test
Analysis of variance (ANOVA).
|Eighteen patinets responded to treatment, Hb F went up by 1.04-17 from the base line.
The mean was significant with p=0.05
Decrease in WBC count with p=0.05.
The Hb level of second group wias significantly higher that the thierd.
|Level of evidence: I
Limitation: Strict qualification criteria.
Some of the results were not dependable such as the reduction of WBC for cases where the treatment worked.
Al-Nood, H., Al-Khawiani, M., & Al-Akwa, A. (2010). Fetal Hemoglobin Response To Hydroxyurea In Yemeni Sickle Cell Disease Patients. Haemoglobin, 15-21.
Fitshugh, C., Hsieh, M., Allen, D., & Coles, W. (2015). Hydroxyurea-Increased Fetal Hemoglobin Is associated with less organ damage and longer survival in adults with sickle cell anemia. Kingston: Crossmark.
Harminder Singh, N. D. (2010). Effective control of sickle cell disease with hydroxyurea therapy. Indian J Pharmacol, 32-35.
Lobo, C. L., Pinto, J., Nascimento, E., & Moura, P. (2013). The effect of hydroxcarbamide therapy on survival of children with sickle cell disease. British Journal of Haematology, 852-860.
Sharef, S. W., Al-Hajri, M., Belshlawi, I., & Al-Sharabally, A. (2013). Optimizing Hydroxyurea use in children with sickle cell disease: low dose regimen is effective. European Journal of Haematology, 519-524.