NIH The Use of Prophylactic Antibiotic Therapy in Children With Sickle Cell Disease A Systematic Review and Meta-Analysis (2012) PDF

The Use of Prophylactic Antibiotic Therapy in Children With Sickle Cell Disease:
A Systematic Review and Meta-Analysis, 2012
Prepared for the National Heart, Lung, and Blood Institute

Prepared by the Knowledge and Evaluation Research Unit, Mayo Clinic Rochester
Tarig Elraiyah, M.B.B.S.
Mohammed Nabhan, M.D.
Ahmad Hazem, M.D.
Annie LeBlanc, Ph.D.
Larry Prokop, M.L.S.
Victor M. Montori, M.D., M.Sc.
M. Hassan Murad, M.D., M.P.H.
THE USE OF PROPHYLACTIC ANTIBIOTIC THERAPY IN CHILDREN WITH SICKLE CELL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS, 2012
Contents
Included Studies ................................................................................................................................................................................................................................................................................................................... 3
Table 1.
Table 2.
Table 3.
Table 4.
Baseline Characteristics of Included Studies ...................................................................................................................................................................................................................................................... 3

Quality of Included Randomized Controlled Trials .............................................................................................................................................................................................................................................. 4
Quality of Included Observational Study ............................................................................................................................................................................................................................................................. 4
Outcomes of Included Studies ............................................................................................................................................................................................................................................................................. 4
References ............................................................................................................................................................................................................................................................................................................................. 6
Appendix A: Study Selection Process ............................................................................................................................................................................................................................................................................... 7
Appendix B: Methods .......................................................................................................................................................................................................................................................................................................... 8
Appendix C: Data Sources and Search Strategies ........................................................................................................................................................................................................................................................... 9
Appendix D: Excluded Studies ......................................................................................................................................................................................................................................................................................... 14
Appendix E: Acronyms and Abbreviations ..................................................................................................................................................................................................................................................................... 15
Included Studies
Table 1. Baseline Characteristics of Included Studies
% of patients
with SCD in
total study
population
Design
Falletta,
1
1995
RCT
Children
Mean:
5.1 yr
400
To evaluate the
consequences of
discontinuing penicillin
prophylaxis at 5 yr of
age in children with
sickle cell anemia (SCA)
who had received
prophylactic penicillin for
much of their lives
2, patients with sickle cell

disease (SCD) who
continued penicillin
prophylaxis on 1 arm and
patients with SCD who
discontinued penicillin
prophylaxis on the other
Inclusion: Received prophylactic

penicillin for at least 2 yr immediately
prior to 5th birthday and the
23-valent pneumococcal vaccine
between 2 and 3 yr of age.
Exclusion: A history of documented
bacteremia or meningitis caused by
S. pneumoniae or H. influenzae,
known penicillin allergy, or surgical
splenectomy
54.5
HbSS
(95%)
HbS-thal
(5%)
NR
100
Mean:
38.4 mo
Gaston,
2
1986
RCT
Children
Range:
336 mo
215
To test whether the

regular, daily
administration of oral
penicillin would reduce
the incidence of
documented septicemia
due to S. pneumoniae in
children with SCA under
3 yr of age
2, patients with SCD taking

penicillin on 1 arm and
patients with SCD taking
placebo on the other
Inclusion: Children 36 mo old with

HbSS were eligible.
Exclusion: Children receiving longterm antibiotic or transfusion therapy
or penicillin allergy
50
HbSS
(100%)
0.5
100
Mean:
15 mo
John,
3
1984
RCT
Children
Range:
6 mo3 yr
242
To investigate the
efficacy of prophylactic
penicillin and of 14
valent pneumococcal
vaccine in preventing
pneumococcal infection
in homozygous sickle
cell disease (HbSS)
2, patients with SCD on

penicillin prophylaxis on 1
arm and patients with SCD
who are not on penicillin
prophylaxis on the other
Inclusion: Children with HbSS

diagnosis between 6 mo and 3 yr
attending sickle cell clinics of the
University Hospital of the West
Indies, Kingston.
Exclusion: Children with documented
pneumococcal infection or
splenectomy before the study
53
HbSS
(100%)
NR, but
10.3%
children
withdrew
from trial
100
NR, but
this interim
analysis
conducted
after
60 mo
Nkouwap,
4
1999
Observational
prospective
Children
Mean:
1.46 mo
Max:
4.27 mo
94
To compare the
frequency of
pneumococcal infections
that occurred in children
receiving penicillin or
spiramycin
2, Group 1: All children under

age 3 who received oracilline
between Jan. 1, 1999 and
March 1, 1996
Group 2: All children under
age 3 entering the study after
March 1, 1996 and receiving
Rovamycine
Inclusion: Children >3 yr, with SCD

seen in Guadeloupe and followed at
the sickle cell center
58.51
HbSS
(47%)
HbSC
(53%)
NR
100
Until the
children
reach 3 yr
old
Study
label
Patient age
Total N of
patients in
the study
% of
patients
lost to
followup
Patient
age
group
What is the objective of Description and number of

this study?
study arms
Inclusion/exclusion criteria
%
males
Genotypes
Followup
in mo
Table 2. Quality of Included Randomized Controlled Trials

Study label
Blinding
Allocation concealment
Reported baseline imbalances
% lost to followup
Source of study funding
Caregivers, patients
NR/unclear
None
NR
Combined
Patients
Yes, the main coordinating center generated the randomization sequence and directed patient
entry assignments by means of telephone contact. Sealed envelopes were available as backup
None
0.5
Combined
None/NR
NR/unclear
None
NR, but 10.3% of

children withdrew from
trial
Combined
Falletta, 1995
Gaston, 1986
John, 1984
Table 3. Quality of Included Observational Study

Study label
Nkouwap, 1999
Baseline imbalances
Blinding
Outcome ascertainment
Adjustment for confounders
% of children vaccinated 87% vs. 50%.

Length of followup was different in the 2 cohorts
No blinding
Similar ascertainment in the 2 cohorts
NR
Table 4. Outcomes of Included Studies

Study
label
Falletta,
1
1995
N of
patients
in
group A
201
Antibiotic
Penicillin V
potassium
N of patients
who had an
Administration infection
250 mg, twice
daily, orally, for
4 yr (mean)
4 children:
2 children had a
systemic
infection
caused by
S. pneumoniae;
2 children
developed
bacteremia
caused by other
organisms
(H. influenzae
and Salmonella)
N of
N of patients
patients
with adverse Mortality in
effects
rate
group B Control used
2, nausea
and vomiting
199
Identical
placebo tablet
N of patients who
Administration had an infection
Twice daily
N of patients
with adverse Mortality
effects
rate
Outcome
7 children: 4 children 1, nausea

and vomiting
had a systemic
infection caused by
S. pneumoniae;
3 children developed
bacteremia caused by
other organisms
(H. influenzae (2) and
Streptococcus (1)
2
children
died after
stroke
1,155 courses of nonstudy

antibiotics were required in group
A as compared to 1,278 in group
B over study period. Relative risk
of S. pneumoniae infection (95%
CI): 0.5 (0.1, 2.7) compared to
placebo
Study
label
N of
patients
in
group A
Antibiotic
N of patients
who had an
Administration infection
N of
N of patients
patients
with adverse Mortality in
effects
rate
group B Control used
N of patients who
Administration had an infection
Gaston,
2
1986
105
Penicillin V
potassium
125 mg, twice

daily, orally, for
15 mo (mean)
2 patients
developed
severe bacterial
infections
(pneumococcal
septicemia) due
to S. pneumoniae
110
Vitamin C
placebo
John,
3
1984
143
Penicillin +
vaccine
(pneumococcal
or
H. influenza B)
Penicillin: long
acting
benzathine
penicillin,
600,000
units/mo via
intramuscular
injection,
administered
until the age of
3 yr
7 patients
developed
pneumococcal
septicemia
None
0.8
89
Pneumococcal Single
6 patients developed
or
intramuscular
pneumococcal
H. influenza B dose of 0.5 mL septicemia
on admission
to the study
Nkouwap,
4
1999
76
Penicillin
(oracilline)
Pediatric
suspension
None
NR
58
Spiramycin
(Rovamycine)
N of patients
with adverse Mortality
effects
rate
Outcome
50 mg tablet of 13 patients developed 0

pneumococcal
vitamin C,
septicemia
twice daily,
orally, for 15
mo (mean)
In sachet
2, 1 with meningitis
(HbSS) and 1 with
septicemia (HbSC)
0.14
Reduction in the incidence of

septicemia was seen in the
children who received penicillin,
regardless of whether they had
received the vaccine. Trial
stopped 8 mo early for benefit.
3 patients developed
nonpneumococcal septicemia (1
in intervention, 2 in placebo).
70% of participating children had
received the pneumococcal
vaccine at or prior to study entry
Yes
Comparison of pneumococcal
vaccine with H. influenzae
vaccine, after allowance for
penicillin group and age group,
gave a chi-squared value of 1.16.
Comparison of penicillin with no
penicillin, after allowance for
vaccine group and age group,
gave a Mantel Haenszel value of
0.02. When analysis was
restricted to the age group below
3 yr (in which penicillin was
given), the value was 1.33. None
of these values were significant
at 5% due to small number of
isolates
NR
82% of group A subjects were

vaccinated as opposed to 50% in
group B (p<.0001). The
2 reported cases of infection
occurred in nonvaccinated
subjects. 40 patients in group A
had to change to the other group
because medication was not
available anymore
References
1.
Falletta JM, Woods GM, Verter JI, Buchanan GR, Pegelow CH, Iyer RV, et al. Discontinuing penicillin prophylaxis in children with sickle cell anemia. Prophylactic Penicillin Study. J
Pediatr. 1995;127(5):685-90.
2.
Gaston MH, Verter JI, Woods G, Pegelow C, Kelleher J, Presbury G, et al. Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. N Engl J Med.
1986;314(25):1593-9.
3.
John AB, Ramlal A, Jackson H, Maude GH, Sharma AW, Serjeant GR. Prevention of pneumococcal infection in children with homozygous sickle cell disease. Br Med J (Clin Res Ed).
1984;288(6430):1567-70.
4.
Nkouwap I, Diara JP, Noyon I, Etienne-Julan M, Merault L. Is there any alternative to oral penicillin in antibioprophylaxis for children with sickle cell disease?. [French] Y a-t-il une
alternative a la penicilline orale dans l'antibioprophylaxie chez les enfants drepanocytaires? Medecine et Maladies Infectieuses. 1999;29(2):111-6.
Appendix A: Study Selection Process
Evidence Selection
Study selection started by screening abstracts for eligibility followed by screening of full-text articles. Both steps followed an a priori established protocol. Study selection and data extraction
were performed using piloted online reference management software (Distiller SR). Abstracts were reviewed in duplicates until adequate interviewer agreement was observed (kappa
statistic 0.90). Data extraction was done by one reviewer and confirmed by a second reviewer. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation)
approach was used to evaluate the quality of the evidence.
Appendix B: Methods
The Critical Question of the Systematic Review (PICOS)*

Patients:
Children with SCD
Intervention/comparison:
Prophylactic antibiotic therapy/placebo, no prophylactic antibiotic therapy
Outcomes:
Incidence of relevant infections
Incidence of relevant mortality
Incidence of adverse effects of prophylactic antibiotics
Study design:
Randomized or nonrandomized studies with original data
*PICOS = patient, intervention, comparison, outcomes, and study design.
Appendix C: Data Sources and Search Strategies

A comprehensive search of several databases (from 1970 to January 2011, English language, any population) was conducted. The databases included Ovid Medline In-Process & Other NonIndexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials, and Scopus. The search strategy
was designed and conducted by an experienced librarian with input from the Guideline methodologist. Controlled vocabulary supplemented with keywords was used to search for the topic:
sickle cell disease and efficacy of antibiotic prophylaxis in children. Additional references were identified by consulting with experts in the field.
OVID 20102011
Database(s): EMBASE 1988 to 2011 Week 04, Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) 1948 to Present, EBM ReviewsCochrane Central
Register of Controlled Trials 4th Quarter 2010, EBM ReviewsCochrane Database of Systematic Reviews 2005 to January 2011
Search Strategy
#
Searches
Results
exp Antibiotic Prophylaxis/
(antibiotic* or "anti-biotic*" or "antimycobacterial agent*" or "anti-mycobacterial agent*" or "antibacterial agent*" or "anti-bacterial agent*" or bacteriocid*).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, ps, rs, nm, ui, kw, tx,
ct]
exp Anti-Bacterial Agents/
exp antibiotic agent/
or/1-4
exp prophylaxis/
440,345
(prophyla* or (disease adj2 prevent*) or (health adj2 protect*) or (infection adj2 prevent*) or (infection adj2 protect*) or (prevent* adj2 therapy) or (prevent* adj2 treatment*)).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, ps,
rs, nm, ui, kw, tx, ct]
432,896
6 or 7
771,384
23,456
666,848
1,787,233
571,021
1,935,567
exp Anemia, Sickle Cell/
29,718
10
(sickle cell or "hemoglobin s" or drepanocytemia or "drepanocytic anemia" or drepanocytosis or "hemoglobin ss" or meniscocytosis or "sickle anemia" or "ss disease" or "hemoglobin sc").mp.
34,094
11
9 or 10
34,095
12
5 and 8 and 11
523
13
remove duplicates from 12
441
14
limit 13 to yr="2010 -Current"
15
exp controlled study/
16
exp evidence based medicine/
486,862
17
evidence-based.mp.
157,489
44
3,457,636
Searches
Results
18
((controls or randomized) adj2 (study or studies or trial or trials)).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, ps, rs, nm, ui, kw, tx, ct]
4,408,041
19
meta analysis/
20
meta-analysis.mp.
21
exp "systematic review"/
38,015
22
systematic reviews.mp.
84,573
23
exp Guideline/ or exp Practice Guideline/
24
guidelines.ti.
25
or/15-24
4,882,856
26
exp case study/
1,486,651
27
exp Cohort Studies/
1,224,739
28
exp longitudinal study/
817,790
29
exp retrospective study/
575,350
30
exp prospective study/
493,750
31
exp observational study/
32
exp comparative study/
2,098,600
33
exp clinical trial/
1,420,655
34
exp evaluation/
1,017,547
35
exp twins/
37,089
36
exp validation study/
24,790
37
exp experimental study/ or exp field study/ or exp in vivo study/ or exp panel study/ or exp pilot study/ or exp prevention study/ or exp quasi experimental study/ or exp replication study/ or exp theoretical study/ or
exp trend study/
6,509,371
38
((clinical or evaluation or twin or validation or experimental or field or "in vivo" or panel or pilot or prevention or replication or theoretical or trend or comparative or cohort or longitudinal or retrospective or
prospective or population or concurrent or incidence or follow-up or observational) adj (study or studies or survey or surveys or analysis or analyses or trial or trials)).mp.
5,418,263
39
("case study" or "case series" or "clinical series" or "case studies").mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, ps, rs, nm, ui, kw, tx, ct]
40
or/2639
41
14 and (25 or 40)
42
from 14 keep 3435
43
limit 42 to (clinical trial, all or clinical trial, phase i or clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or clinical trial or comparative study or controlled clinical trial or evaluation studies or
guideline or meta analysis or multicenter study or practice guideline or randomized controlled trial or twin study or validation studies) [Limit not valid in EMBASE,CCTR,CDSR; records were retained]
44
from 14 keep 3644
45
41 or 43 or 44
29
46
limit 45 to human [Limit not valid in CCTR,CDSR; records were retained]
26
47
limit 46 to humans [Limit not valid in CCTR,CDSR; records were retained]
26
78,675
123,010
257,286
79,886
17,879
138,554
12,008,042
29
10
Searches
48
limit 47 to (editorial or letter or news) [Limit not valid in EMBASE,CDSR; records were retained]
49
from 48 keep 1-2
50
47 not 49
Results
11
2
24
11
OVID 19702009
Database(s): EMBASE 1988 to 2011 Week 04, Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) 1948 to Present, EBM ReviewsCochrane Central
Register of Controlled Trials 4th Quarter 2010, EBM ReviewsCochrane Database of Systematic Reviews 2005 to January 2011
Search Strategy
#
Searches
Results
exp Antibiotic Prophylaxis/
(antibiotic* or "anti-biotic*" or "antimycobacterial agent*" or "anti-mycobacterial agent*" or "antibacterial agent*" or "anti-bacterial agent*" or bacteriocid*).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, ps, rs, nm, ui, kw, tx, ct]
exp Anti-Bacterial Agents/
exp antibiotic agent/
or/1-4
exp prophylaxis/
440,345
(prophyla* or (disease adj2 prevent*) or (health adj2 protect*) or (infection adj2 prevent*) or (infection adj2 protect*) or (prevent* adj2 therapy) or (prevent* adj2 treatment*)).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, ps,
rs, nm, ui, kw, tx, ct]
432,946
6 or 7
771,434
exp Anemia, Sickle Cell/
29,728
10
(sickle cell or "hemoglobin s" or drepanocytemia or "drepanocytic anemia" or drepanocytosis or "hemoglobin ss" or meniscocytosis or "sickle anemia" or "ss disease" or "hemoglobin sc").mp.
34,095
11
9 or 10
34,096
12
5 and 8 and 11
523
13
remove duplicates from 12
441
14
exp controlled study/
15
exp evidence based medicine/
486,934
16
evidence-based.mp.
157,572
17
(controls adj2 (study or studies or trial or trials)).mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, ps, rs, nm, ui, kw, tx, ct]
18
meta analysis/
19
meta-analysis.mp.
20
exp "systematic review"/
38,015
21
systematic reviews.mp.
84,601
22
exp Guideline/ or exp Practice Guideline/
23
guidelines.ti.
23,468
667,042
1,787,512
571,021
1,935,837
3,457,636
4,297,592
78,733
123,061
257,299
79,901
12
Searches
Results
24
or/14-23
4,781,503
25
exp case study/
1,487,438
26
exp Cohort Studies/
1,225,907
27
exp longitudinal study/
818,513
28
exp retrospective study/
575,818
29
exp prospective study/
494,056
30
exp observational study/
31
exp comparative study/
2,099,419
32
exp clinical trial/
1,421,183
33
exp evaluation/
1,018,573
34
exp twins/
37,096
35
exp validation study/
24,790
36
exp experimental study/ or exp field study/ or exp in vivo study/ or exp panel study/ or exp pilot study/ or exp prevention study/ or exp quasi experimental study/ or exp replication study/ or exp theoretical study/ or
exp trend study/
6,510,907
37
((clinical or evaluation or twin or validation or experimental or field or "in vivo" or panel or pilot or prevention or replication or theoretical or trend or comparative or cohort or longitudinal or retrospective or prospective
or population or concurrent or incidence or follow-up or observational) adj (study or studies or survey or surveys or analysis or analyses or trial or trials)).mp.
6,427,541
38
("case study" or "case series" or "clinical series" or "case studies").mp. [mp=ti, ab, sh, hw, tn, ot, dm, mf, ps, rs, nm, ui, kw, tx, ct]
39
or/25-38
40
13 and (24 or 39)
41
from 13 keep 327-424
98
42
limit 41 to (clinical trial, all or clinical trial, phase i or clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or clinical trial or comparative study or controlled clinical trial or evaluation studies or
guideline or meta analysis or multicenter study or practice guideline or twin study or validation studies) [Limit not valid in EMBASE,CCTR,CDSR; records were retained]
18
43
40 or 42
261
44
limit 43 to yr="1970 - 2009"
232
45
from 44 keep 1-224
224
46
limit 45 to (book or book series or editorial or letter or note or addresses or autobiography or bibliography or biography or dictionary or directory or duplicate publication or interactive tutorial or interview or lectures or
legal cases or legislation or news or newspaper article or patient education handout or periodical index or portraits or video-audio media or webcasts) [Limit not valid in EMBASE,Ovid MEDLINE(R),Ovid
MEDLINE(R) In-Process,CCTR,CDSR; records were retained]
47
45 not 46
48
from 44 keep 225-232
49
47 or 48
17,879
138,618
12,147,963
261
12
212
8
220
13
Appendix D: Excluded Studies

Author
Yr
Title
Reason for Exclusion
Brown
1989
Care of infants with sickle cell disease
Not original research
Desposito
1996
Health supervision for children with sickle cell diseases and their families
Diop
2011
Sickle cell disease and Malaria: evaluation of seasonal intermittent preventive treatment with sulfadoxine-pyrimethamine in Senegalese patients
A randomized placebo-controlled trial
Irrelevant outcome
Fukuda
2005
Acquisition of mutans streptococci and caries prevalence in pediatric sickle cell anemia patients receiving long-term antibiotic therapy
Not comparative study
Hirst
2010
Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease
Holzmann
1998
Bacteremia in children with sickle cell disease: A twelve year single institutional experience
No prophylactic antibiotic use
Hord
2002
Streptococcus pneumoniae sepsis and meningitis during the penicillin prophylaxis era in children with sickle cell disease
Knight-Madden
2001
Invasive pneumococcal disease in homozygous sickle cell disease: Jamaican experience 19731997
Lee
1995
Improved survival in homozygous sickle cell disease: Lessons from a cohort study
Nakibuuka
2009
Presumptive treatment with sulphadoxine-pyrimethamine versus weekly chloroquine for malaria prophylaxis in children with sickle cell anemia in
Uganda: A randomized controlled trial
Irrelevant outcome
Patel
2004
Cell disease in Central India
Pegelow
1991
Experience with the use of prophylactic penicillin in children with sickle cell anemia
Rahimy
2003
Effect of a comprehensive clinical care program on disease course in severely ill children with sickle cell anemia in a sub-Saharan African setting
Rogers
1995
Bacteremia in children with sickle hemoglobin C disease and sickle beta(+)-thalassemia: Is prophylactic penicillin necessary?
Steele
1996
Colonization with antibiotic-resistant Streptococcus pneumoniae in children with sickle cell disease
Swanson
1996
Penicillin-resistant Aerococcus viridans bacteremia in a child receiving prophylaxis for sickle cell disease
Telfer
2007
Clinical outcomes in children with sickle cell disease living in England: A neonatal cohort in East London
Warren
2010
Adherence to prophylactic antibiotic guidelines among Medicaid infants with sickle cell disease
14
Appendix E: Acronyms and Abbreviations

Numbered
3TC
32P
51Cr-EDTA
6MWD
lamivudine
radioactive phosphorous
chromium-51 labeled ethylenediaminetetraacetic acid; see
Cr-EDTA
6-minute walk distance
-thal
-thalassemia
AA
AB
Ab
ABC
ABG
A/C
ACE
ACEI
ACS
AE
AER
AHR
AI
ALT
ANC
ara-c
ARV
ASA
ASPEN
ASSC
AST
alpha, first letter of the Greek alphabet

See -thalassemia
alpha-thalassemia
African American
blood group AB
antibody
abacavir
arterial blood gas
albumin to creatinine ratio
angiotensin converting enzyme
angiotensin-converting enzyme inhibitor
acute chest syndrome
adverse event
per each
albumin excretion rate
airway hyperresponsiveness
augmentation index
alanine aminotransferase
absolute neutrophil count
arabinosylcytosine (cytarabine)
antiretroviral
acetylsalicylic acid (aspirin)
Association of Sickle Cell Disease, Priapism, Exchange
Transfusion and Neurological Events
acute splenic sequestration crisis
aspartate aminotransferase
atm
AUC
avL
atmospheric
area under the curve
automated volt left, EKG lead
-thal
-thalassemia
0-thal
BABY HUG
B cell
beta
b.i.d.
BM
BMI
BMT
BP
B-TI
B-TM
beta, second letter of the Greek alphabet

See -thalassemia
beta-thalassemia
beta zero-thalassemia
Pediatric Hydroxyurea Phase III Clinical Trial
type of lymphocyte or immune mediator cell
See
bis in die, twice a day
Black male; bone marrow; bowel movement [see context]
Body Mass Index
bone marrow transplant
blood pressure
beta thalassemia intermedia
beta thalassemia major
C
C
Ca
CAD
CAR
CBD
CBFv
CBT
CCNU
CCT
CH
CI
cm
cm2
Celsius
calcium
coronary artery disease
Central African Republic haplotype
cortical bone density
cerebral blood flow velocity
cognitive behavioral therapy
1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (Iomustine)
clinically controlled trial
chronic hepatomegaly
confidence interval
centimeter
square centimeter
15
cm3
CML
cMRI
CMV
CNS
cP
CrCl
Cr-EDTA
Cross
CRP
CSSCD
CT
CTA
CTX
CUI
CV
CVA
CVD
CXR
cubic centimeter
chronic myelogenous leukemia
conventional magnetic resonance imaging
cytomegalovirus
central nervous system
centipoise
creatinine clearance
chromium 51-labeled ethylenediaminetetraacetic acid; see 51CrEDTA
cross-sectional study
C reactive protein
Cooperative Study of Sickle Cell Disease
computed tomography
computed tomographic angiography; concurrent treatment with an
antisickling agent
chronic transfusion therapy
cumulative incidence
cardiovascular
cerebrovascular accident
cardiovascular disease
chest x ray
D
d
d4T
DAT
DBP
ddI
DFO
DH
DHTR
DHTR/H
dL
DLCO
DM
DPI
DTPA
DW
day
didehydrodeoxythymidine
direct antiglobulin test
diastolic blood pressure
didanosine, dideoxyinosine
deferoxamine
day hospital
delayed hemolytic transfusion reaction
delayed hemolytic transfusion reaction/hyperhemolysis
deciliter
diffusing capacity of lung for carbon monoxide
diabetes mellitus
dynamic pressure index
diethylenetriamine pentaacetate
dry weight
dyn
dx
dyne
diagnosis
E
E
E wave
E/A
ECG
ECHO
ECMO
ED or ER
EDD
EF
EFV
EPO
ESD
ESSm
ET
E antigen; HbE/-thalassemia [see context]

electromagnetic wave
Doppler ratio of early (E) to late atrial (A) transmitral flow velocity
electrocardiogram
echocardiogram, echocardiographic, echocardiography
extracorporeal membrane oxygenation
emergency department or emergency room
end diastolic diameter
ejection fraction
efavirenz
erythropoietin
end systolic diameter
end-systolic wall stress
essential thrombocytopenia; exchange transfusion [see context]
F
F
F
f/u
FEF
FEV1
fL
FS
ft
FVC
female
Fahrenheit
follow up
forced expiratory flow
forced expiratory volume at 1 second
femtoliter
fractional shortening
feet
forced vital capacity
G
g
G
GFR
GI
GMP
Gp
gram
gauge
glomerular filtration rate; mL/min/1.73 m2
gastrointestinal
granule membrane protein
group
16
H
h
H1N1
H6CS
Hb
HbA
HbAA
HbAS
HbF
HbH
HbI
HBM
HbS
HbS+-thal
HbS-thal
HbS0-thal
HbS+-thal
HbSC
HbSD
HbSDLA
HbS/O-Arab
HbSS
Hct
HES
Hg
HIV
HLA
HPRT
HR
HRQOL
HSCT
HTN
HTR
HU
HUG KIDS
HUSOFT
hx
I
hour
respiratory virus, a variety of influenza A
Harvard Six Cities Study
hemoglobin
hemoglobin A
hemoglobin AA
hemoglobin AS
hemoglobin F; fetal hemoglobin
hemoglobin H
hemoglobin I
health belief model
hemoglobin S; sickle cell hemoglobin
hemoglobin S alpha plus-thalassemia
hemoglobin S beta-thalassemia
sickle hemoglobin beta zero-thalassemia
sickle hemoglobin beta positive-thalassemia
hemoglobin SC disease; sickle hemoglobin C disease
hemoglobin SD disease
hemoglobin SD disease, Los Angeles; also known as D-Punjab
hemoglobin SO-Arab
homozygous sickle cell disease
hematocrit
Health Examination Survey
mercury
human immunodeficiency virus
human leukocyte antigen
hypoxanthine phosphoribosyl transferase
heart rate
health-related quality of life
hematopoietic stem cell transplantation
hypertension
hemolytic transfusion reaction
hydroxyurea
Phase I-II trial of the safety of HU in children by the Pediatric
Hydroxyurea Group
The Hydroxyurea Safety and Organ Toxicity trial
history
IAT
IDV
IFN
i.m.
iNO or INO
INR
IQR
IR
IU
i.v. or IV
IVIG
IVS
indirect antiglobulin test

indinavir
interferon
intramuscular
inhaled nitric oxide
international normalized ratio
interquartile range
index of rigidity
International unit
intravenous
intravenous immunoglobulin
interventricular septal thickness
K
K
kg
kJ
kPa
Kell
kilogram
Kilojoule
kilo-Pascal
L
L
LA
LACA
LDH
LFT
LIC
LMCA
LOS
Lp(a)
LPCA
LQTS
LV
LVDD
LVEDD
LVEF
LVESD
liter
left atrium, left atrial
left anterior cerebral artery
lactate dehydrogenase
liver function test
liver iron content; liver iron concentration [see context]
left main coronary artery
length of stay
lipoprotein (a)
left posterior cerebral artery
long QT syndrome
left ventricle; left ventricular
left ventricular diastolic dimension
left ventricle end-diastolic dimension
left ventricular ejection fraction
left ventricular end-systolic dimension
17
LVH
LVPWD
LVPWT
left ventricular hypertrophy

left ventricular posterior wall dimension
left ventricular posterior wall thickness
m
m
m2
MAP
MCA
MCT
MCV
MedAd
MF
mg
MI
min
mL
mm
mm3
mmHg
mmoL
mo
mol
mPAP
MPD
MPI
MRA
MRI
ms
MSH
MTD
Greek letter mu; micromilli-; moles per liter [see context]

meter
square meter
mean arterial pressure
middle cerebral artery
methacholine challenge test
mean corpuscular volume; mean cell volume
median study medication
myelofibrosis
milligram
myocardial infarction
minute
milliliter
millimeter
cubic millimeter
millimeters of mercury
millimolar
month
mole
mean pulmonary artery pressure
myeloproliferative disorder; maximal permissible dose [see context]
myocardial performance index
magnetic resonance angiography
magnetic resonance imaging
millisecond
Study of Hydroxyurea for Sickle Cell Anemia
maximum tolerated dose
N
n
n
N
nano
sample size
population size
NA or N/A
NC
ng
ng/mL
NHANES
NHLBI
NIH
nmol
NO or NOx
NR
NR/NC
NS
ns
not applicable
not clear
nanogram
nanograms per milliliter
National Health and Nutrition Examination Survey
National Heart, Lung, and Blood Institute
National Institutes of Health
nanomole
nitric oxide
not reported
not reported/not clear
not significant; normal saline [see context]
nanosecond
O
Obs
OCP
Od or o.d.
Op
OR
observational
oral contraceptive pill
omni die, every day
Operation; opioid [see context]
odds ratio
P
p
P, Obs
PAH
PaO2
PASP
PCA
pcMV
Pcr
PCV
PCWP
PEF
PFT
pg
PH, PHT, PHTN
PICU
PLC
probability
prospective observational
pulmonary arterial hypertension
symbol for partial pressure of oxygen in arterial blood
pulmonary artery systolic pressure
patient-controlled analgesia
pressure-controlled mechanical ventilation
plasma creatinine
packed cell volume
pulmonary capillary wedge pressure
peak expiratory flow
pulmonary function test
picogram
pulmonary hypertension
pediatric intensive care unit
propionyl-L-carnitine
18
plt
PMN
pmol
pO2 or PO2
POD
postop
ppm
PRBC
preop
Prn
PSR
PT
PTT
PV
PVR
PWV
platelets
polymorphonuclear leukocytes
picomole
partial oxygen pressure
postoperative day
postoperative
parts per million
packed red blood cells
preoperative
as needed
proliferative sickle retinopathy
prothrombin time
partial thromboplastin time
polycythemia vera
pulmonary vascular resistance
pulse wave velocity
Q
Q
Q wave
QID or q.i.d.
QOD
QTc
quality
the initial downward deflection of the QRS complex
quater in die; 4 times a day
every other day
corrected QT interval
R
R wave
R, Obs
R-P, Obs
RACA
RAD
RBC
rCBF
RCT
RE
retic
Rev.
RGD
RHC
the initial upward deflection of the QRS complex

retrospective, observational
retrospective-prospective observational
right anterior cerebral artery
reactive airway disease
red blood cell
regional cerebral blood flow
randomized controlled trial
right extremity; right eye [see context]
reticulocytes
reviewer
arginyl-glycyl-aspartic acid (peptide)
right heart catheterization
RMCA
RPCA
RR
rTPA
RV
RVEDD
RVEF
RVESD
RVP
right middle cerebral artery

right posterior cerebral artery
relative risk
recombinant tissue plasminogen activator
right ventricle; right ventricular
right ventricular end-diastolic dimension
right ventricular ejection fraction
right ventricular end-systolic dimension
right ventricle pressure
S
s
S/O
S/O-Arab
SA
SBP
SCA
SCD
SD
SEM
SF
SLE
SPT
STOP
sx
seconds
hemoglobin SO Arab
hemoglobin SO-Arab
substance abuse
systolic blood pressure
sickle cell anemia
sickle cell disease
standard deviation
standard error of the mean
serum ferritin
systemic lupus erythematosus
service perception test
Stroke Prevention Trial in Sickle Cell Anemia
symptom
T
T wave
TACO
TAMMV
TCD
TENS
thal
TIA
t.i.d.
TLC
TNF-
the first deflection in the electrocardiogram following the QRS

complex
transfusion-associated circulatory overload
time-averaged mean of the maximum velocity
transcranial Doppler
transcutaneous electrical nerve stimulation
thalassemia
transient ischemic attack
ter in die; three times a day
total lung capacity
tumor necrosis factor alpha
19
TRF2
TRV, TRJV
TScr
tx
telomeric repeat-binding factor 2

tricuspid regurgitant velocity, tricuspid regurgitant jet velocity
tubular secretion of creatinine
therapy
U
U
UAE
g
l
ULN
m
mol
unit
urinary albumin excretion
microgram
microliter
upper limit of normal
micrometer
micromole
UNTH Enugu
US
UTI
University of Nigeria Teaching Hospital at Enugu

ultrasound; ultrasonography
urinary tract infection
V
V/Q
V1, V2, V3, V3V6
VAS
VC
VCFc
VOC
Vrft
vs.
visual analogue scale

Vital capacity
velocity of circumferential fiber shortening
vaso-occlusive crisis
velocity of regurgitant flow of tricuspid
versus
W
walk-PHaSST
WBC
wt
Pulmonary Hypertension and Sickle Cell Disease with Sildenafil

Therapy
white blood cell; white blood cell count
weight
Y
yr
year
Z
ZDV
zidovudine
ventilation-perfusion scan
unipolar electrocardiogram lead (16)
20

NIH The Use of Prophylactic Antibiotic Therapy in Children With Sickle Cell Disease A Systematic Review and Meta-Analysis (2012) PDF

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NIH The Use of Prophylactic Antibiotic Therapy in Children With Sickle Cell Disease A Systematic Review and Meta-Analysis (2012) PDF

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The Use of Prophylactic Antibiotic Therapy in Children With Sickle Cell Disease:

A Systematic Review and Meta-Analysis, 2012

Prepared for the National Heart, Lung, and Blood Institute

Baseline Characteristics of Included Studies ...................................................................................................................................................................................................................................................... 3

2, patients with sickle cell

Inclusion: Received prophylactic

To test whether the

2, patients with SCD taking

Inclusion: Children 36 mo old with

2, patients with SCD on

Inclusion: Children with HbSS

2, Group 1: All children under

Inclusion: Children >3 yr, with SCD

What is the objective of Description and number of

Table 2. Quality of Included Randomized Controlled Trials

Reported baseline imbalances

Source of study funding

NR, but 10.3% of

Table 3. Quality of Included Observational Study

Adjustment for confounders

% of children vaccinated 87% vs. 50%.

Similar ascertainment in the 2 cohorts

Table 4. Outcomes of Included Studies

7 children: 4 children 1, nausea

1,155 courses of nonstudy

125 mg, twice

50 mg tablet of 13 patients developed 0

Reduction in the incidence of

82% of group A subjects were

Appendix A: Study Selection Process

The Critical Question of the Systematic Review (PICOS)*

Appendix C: Data Sources and Search Strategies

exp Antibiotic Prophylaxis/

exp Anti-Bacterial Agents/

exp antibiotic agent/

exp Anemia, Sickle Cell/

remove duplicates from 12

limit 13 to yr="2010 -Current"

exp controlled study/

exp evidence based medicine/

exp "systematic review"/

exp Guideline/ or exp Practice Guideline/

exp case study/

exp Cohort Studies/

exp longitudinal study/

exp retrospective study/

exp prospective study/

exp observational study/

exp comparative study/

exp clinical trial/

exp validation study/

14 and (25 or 40)

from 14 keep 3435

from 14 keep 3644

limit 45 to human [Limit not valid in CCTR,CDSR; records were retained]

limit 46 to humans [Limit not valid in CCTR,CDSR; records were retained]

from 48 keep 1-2

exp Antibiotic Prophylaxis/

exp Anti-Bacterial Agents/

exp antibiotic agent/

exp Anemia, Sickle Cell/

remove duplicates from 12

exp controlled study/