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Comments
135
0 This entire section needs to be reconsidered. There is no discussion of non-pharmacological
interventions in patients with chronic pain. Cognitive and behavioral interventions, vocational
rehabilitation, occupational therapy, psychological interventions and many other therapies are
as important as chronic opioids in the management of chronic pain. Neuropathic pain has very
specific interventions that are not included. Formal psychological/psychiatric screening for
depression and other comorbid conditions that will exacerbate chronic pain and complicated
management. Goals of chronic pain treatment are not just pain control but increasing function
and quality of life.
Suggestions
Type
This section, at least the recommendations should Public
be completely rewritten. Although evidence is not
robust in sickle cell disease, recommendations from
chronic back pain, orthopedic problems, rheumatoid
disorders, diabetes, neuropathies can be utilized to
formulate some basic principles of approaching
chronic pain management.
Discussion
All of the items are covered in the document by the
American Pain Society. Rec. 9.1. A few sentences
should be added to the background.
Action/Recommendation
Revision subitted to this section. Done.
135
11 Could the panel comment on the difference between VOC and breakthrough pain episodes
among those with chronic pain syndromes?
Invited
136
11 concept of two types of pan is introduced but then nociceptive pain never defined, elaborated
Invited
Public
Will craft some wording about this. In the background. Revision subitted a revision to this section. Done.
140
141
143
7 The focus on pain relief is not consistent with most current chronic pain management
strategies which focus on improving function rather than pain relief
5 (expand cell for full contents) AVN: First, the recommendations of Ficat staging is outdated and We strongly recommend that decompression coring Public
has been replaced by MRI imaging using the ARCO or Ficat-Arlet classifications (ref: Am J
be an early consideration in the treatment of AVN
Orthopedics, Sept 2011 p. E188). These recommendations utilize MRI. Furthermore, the
since these patients progress irregardless of the
primary symptom in patients with AVN is often in the groin and knee, and not necessarily the
physical therapy and are often bilateral, which
hip. In addition, 40-80% of patients develop bilateral hip disease. This complicates therapy
minimizes non-operative approaches. (ref: Physical
and should be mentioned. Coring decompression is a safe and clinically beneficial procedure. therapy alone compared with core decompression
A meta analysis of 21 studies demonstrated that non-operative management results in less
and physical therapy for femoral head
than a 20% satisfactory outcome leading to THA and other salvage procedures (ref:
osteonecrosis in sickle cell disease. Results of a
Amanatullah et al. Current Management Options for Osteonecrosis of the Femoral Head: Part multicenter study at a mean of three years after
1, Diagnosis and Nonoperative Management. American Journal of Orthopedics. 2011). The
treatment. Neumayr LD, Aguilar C, Earles AN, et al.
orthopedic literature does not recommend passive physical therapy and activity modification as J Bone Joint Surg Am. 2006 Dec;88(12):2573-82.;
the primary treatments for AVN. Even in SCD, progression is inevitable. We were the principal also: Clinical evaluation of avascular necrosis in
investigators in the one randomized trial for AVN vs. aggressive physical therapy.
patients with sickle cell disease: Children's Hospital
This protocol actually incorporates aggressive daily physical therapy as a primary intervention. Oakland Hip Evaluation Scale--a modification of the
This protocol actually incorporates aggressive daily physical therapy as a primary intervention. Harris Hip Score. Aguilar CM, Neumayr LD, et al.
This type of aggressive physical therapy without research funding is rarely practical and is
Arch Phys Med Rehabil. 2005 Jul;86(7):1369-75.).
replaced inadequate activity limitation. Our study demonstrated that decompression coring
was totally safe.
Revision submitted to this section. References were added for (1) Ballas et al. 2010, "Definitions of
the phenotypic manifestations of sickle cell disease." American journal of hematology 85(1): 6-13; (2)
Steinberg, M. E., G. D. Hayken, et al. (1995). "A quantitative system for staging avascular necrosis."
J Bone Joint Surg Br 77(1): 34-41. (3) Steinberg, M. E. and D. R. Steinberg (2004). "Classification
systems for osteonecrosis: an overview." Orthop Clin North Am 35(3): 273-283, vii-viii. Done.
Comment: We got the two references mentioned in the comments. Reference part I does mention
40-80 % of cases with AVN of the hip (all cases not only SCD) could be bilateral. However, the
commentator said 40-80 % of patients with SCD develop bilateral AVN. There is a big difference
between what the comment says and what the reference says. It also seems that a similar confusion
probably by the same person thought that SCD and SCA are the same. Perhaps we should check
the accuracy of every reference mentioned in the public comments.
Reference part II, however, clearly mentions that core decompression should be done for Ficat stage
I or II. This is contrary to what the comment says that the Ficat classification is obsolete although it is
used for decision making by the references the commentator recommends. The references are listed
below.
Based on the above, recommend the following changes in the background: Page 141 line 6 add:
About 40% to 80% of cases of AVN of the hips are bilateral and, hence, evaluation of patients with
AVN should focus on both hips (Amanatullah, Strauss et al. 2011). Revised exhibit added on the
stages of AVN. Then, Page 141 after line 21 (which would be at the end of the revised exhibit with
the definitions of the stages of AVN) add: Most orthopedists consider core decompression most
beneficial for Ficat stage I and II of AVN of the hip (Amanatullah, Strauss et al. 2011). Editor: Done
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143
6 As worded this is of little use
145
149
Comments
Suggestions
Give a clearer guideline of who should be imaged.
21 In leg ulcers please consider a recommendation to consult with local wound care specialists for
expert assistance. Again this document will be the model for payment by payors and this is a
consultation that is often difficult to get covered but is vitally necessary in leg ulcers expecially
recurrent ones.
3 CKD is defined as either GFR<60 or evidence of kidney damage 3 months. Only proteinuria Use KDIGO classifications or provide rationale for
is listed as a marker of kidney damage. The KDIGO (Kidney Disease: Improving Global
not using.
Outcomes) classification of CKD includes albuminuria, proteinuria, and hematuria as markers
of kidney damage. (Ref: Levey et al. Kid Intern 2005)
Type
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Discussion
Action/Recommendation
Will review the background to see what needs to be I think this refers to page 143, line 6; the page number was missing in the original table received. No
added. Table, vocational therapy will be added to the change was made to Recommendation 1 in the AVN section.
background. Panel will weigh in on MRI/no MRI at a
later date. Consider a consensus rec.
Public
Public
149
17 Hypersecretion may occur many experts do state the need for microalbumin screening not just
dipstick see comments below on page 152.
Public
149
19 Cites prevalence of microalbuminuria to be 16% in children (Becton et al.) and 32.9% in adults incorporate additional information.
(Ataga et al.). Other studies show higher prevalence:
- Pediatrics: McPhersonYee 2011: 20.7% in HbSS/Sb0; 16.8% in HbSC/Sb+ (410 subjects)
- Adults: Guasch 2006: 68% in HbSS; 42% in other sickling hemoglobinopathies (300 subjects)
Public
p. 149, line 14: Added: "Finally, in a study of 300 adults with SCD, the prevalence of any
albuminuria in people with SCD was 68 percent, and the prevalence in other genotypes was 32
percent (Guasch 2006)." DONE
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Comments
150
1 In this section, renal disease in SCD is discussed. There are some notable omissions.
Suggestions
Please consider adding:
a) Type IV renal tubular acidosis
b) Papillary necrosis-in SCD or trait
c)The association of membranoproliferative
glomerularnephritis and membranous
glomerulopathy in SCD (therefore, the need for
biopsy in patients with significant, persistent
proteinuria.
Type
Public
Discussion
Action/Recommendation
Will consider adding a sentence in the background
On p. 150, line 14, add: There have not been any studies looking at the utility of renal biopsy in
about biopsy Other comments will also be considered individuals with SCD. One study that examined 18 renal biopsy specimens found four histopatholigc
and reviewed.
variants: focal segmental glomerulosclerosis (FSGS( (39%), membranoproliferative
glomerulonephritis (28%), thrombotic microangiopathy glomerulopathy (17%), and specific sickle cell
disease glomerulopathy (17%). (Medicine (Baltimore). 2010 Jan;89(1):18-27). The authors of this
study note that the long-term outcomes were not different according to the histologic lesions that
were identified, with 50% of cases having chronic renal failure after a mean followup of 28 months.
The decision to perform renal biopsy should be individualized for each patients. Editor: DONE
1/7/13 Note: I made this a new paragraph, as a line of text here at the end of line 14 about the
management of gout in individuals with SCD was also added. Editor: Done 1/7/13.
151
7 This is a misleading citation of the results. 191 children were screened but only 9 were treated consider rewriting the section and
with hydroxyurea and 9 with ACE inhibitors. Some patients appeared to get both. There was
also a high complication rate. 4 of 9 on ACE developed hyperkalemia therapy stopped in 3 of
the 4. Some received chronic transfusions. 3 progressed to endstage kideny disease.
Public
The following needs to be deleted pg. 151, line 7: "One observational study of 191 children (3-20
years of age) with HbSS demonstrated that microalbumin excretion normalized in 44 percent of
those treated with hydroxyurea and 56 percent of those treated with an angiotensin-converting
enzyme (ACE) inhibitor; in the analysis of this study, however, the investigators did not control for
other potential confounders that might have affected proteinuria (McKie et al. 2007)." Editor: Done
1/7/13
152
4 rather than renal complications here can you just say with microabuminuria, proteinura or Cr>1
- or are there other indications you would also use
Invited
Comment: Leave as is; we described above for what indications we would prescribe ACE.
152
11 I am surprised by the moderate recommendation to start an ACE-I in both children and adutls
with isolated microalbuminuria given the very low quality evidence, especially for children
153
136
4 The principles of treating chronic pain differ from those of acute pain Nothing is said about
how these principles differ. There is a discussion of differences in pathophysiology, but not in
treatment principles.
139
Public
Invited
Information on gout is in the background. No review Comment: Gout is already mentioned on p. 150, line 13. On p. 150, line 14 add: Diagnosis and
of evidence on gout. New treatments for gout may
management of gout in individuals with sickle cell disease is the same as in other populations.
not be applicable to gout in SCD. Do we have enough Editor: Done 1/7/13
information in the background to address these
comments. Do not put treatment into the background.
Done 1/4/13. Change necessitated changes in the second sentence of this recommendation, which
was revised to: "The partnership agreement should list the patient's rights" instead of "the agreement
form should list"
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Comments
139
15 Consider splitting this into more than 1 rec
140
140
141
5 This line with a 50% SS with AVN is in direct contradiction to line 3 with the prevalence of 10%.
Make it congruent.
141
7 HbS-alpha thalassemia
145
0 Refer to wound care clinic, some improvements have helped if engaged early or state may
need to adjust and live with the ulcers
145
Suggestions
HbSS-alpha thalassemia
Type
Invited
Discussion
CHANGE: remove second statement and make it a Done 1/4/13.
new recommendation. Leave the rest as the next
recommendation. New Rec: "Use long and short
acting opiods to manage chronic pain that is not
relieved by nonopiods." Same grade. Make it the new
#4 - needs to go after #3. Please add comment/query
- NEEDS PANEL REVIEW
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HbSS
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Public
Yes, make this change - add the S but use the "a" to Done.
represent alpha
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148
153
155
Done
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IND
Public
Done 1/6/13
Done 1/6/13
Done 1/6/13
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Action/Recommendation
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Comments
158
18 Should this be AVN or are bisphosphonates proposed as a treatment for cutaneous ulceration?
Suggestions
Type
IND
Discussion
CHANGE: Replace "chronic leg ulcers" with AVN
Done 1/6/13
Action/Recommendation
159
Public
Done 1/6/13
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Done 1/6/13
140
We acknowledge this is a big issues. Rec #11: coPer email received on 2/7/13: We discussed this comment in one of the conference calls. We agreed
morbid conditions...including pain due to co-morbid that no change in the recommendations should be made and that the goal of the guidelines is to
conditions...including mood disorders that may impact address complications of SCD and not to address co-morbid conditions. Nevertheless, there was a
pain. Use the word "addressed".
request to mention the co-morbid conditions reported in patients with SCD. To that end a sentence
was added in the introduction to the chronic chapter (p133 lines 6-7). In addition, another 2
sentences were added in the background section on chronic pain about anxiety, depression, despair
etc. that are associated with chronic pain ( p 136 lines 7-10).
Accordingly, no change is needed and sentences have already been added in the chapter
introduction and in the background section on chronic pain. DONE
146
12 Once again, this is the definition for pulmonary hypertension of which PAH is a subgroup.
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148
6 It is not clear what the authors mean by various levels of benefit. Clearly, there is a bias on the
part of the authors to present these studies as being not useful but for the uneducated reader,
it would be helpful to give more information of the actual data and what construes a positive
treatment response.
11 The L-arginine study was not outlined in Machado 2005. The correct reference for that study
is Morris CR AJRCCM 2003.
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2/19/13: Beyond the scope of the discussion to delineate specifics (e.g. reduced pressures, exercise
capatiy, too varied to easily summarize given varied definitons of PAH, groups that were studied, etc
- statement as written is neutral.
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This reference will be fixed as we review the evidence From Editor: Machado ref deleted and Morris reference added. 2/19/13.
section
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Comments
148
15 Is there a role for doing ECHO before referring for right heart cath? Should clinicians do an
ECHO when a pt has sx/sx possibly indicating the need for a work-up of Pulm HTN?
Suggestions
Discussion
Action/Recommendation
This needs to be fixed. Should read, have
2/19/13: Recommendations changed to reflect echo first, then referral for further evaluation. DONE
symptoms or signs suggestive of PH, refer them for
echocardiography for assessment of pulmonary
hypertension, such as elevated TRV. #2-Confirm all
diagnoses of PH with right heart catheritization.
Strong recommendation, moderate-quality evidence.
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155
2 Priapism is not an acute and separate chronic problem, it is a continum. This section is a
waste of space. Combine the sections and make one rational discussion. Chronic prolonged
priapism is a major source of impotence risk and you do not really address it.
Public
Expand section to make clear we are talking about a No Change - the language is clear that we are talking about stuttering priapsim, which the public
chronic condition and that it has adverse
comment acknowledges; the evidence and scope of the document do not support further discussion
consequences.
or elaboration. No change made. Done
135
12 it might be helpful to have a sense of types of pain meds and average doses used by people
with SCD at different ages (ie % adult pts on chronic opiods and average dosing with range). I
know this is highly variable but the breakdown could provide some context for docs not seeing
many of these pts.
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138
152
9 Is this what is supposed to happen to the peple who screen positive for proteinuria - see page
29. if these suggestions are linked, please indicate so in the report
Type
IND
Invited
Editor: The Recommendation was revised as follows: In men and boys with SCD and recurrent or
stuttering priapism, offer evaluation and treatment in consultation with a sickle cell disease specialist
and a urologist, especially when episodes increase in severity or frequency. DONE
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Comments
136
7 These are symptoms of PTSD (posttraumatic stress disorder), and should be acknowledged
as such by medical professionals. Life-long severe, unpredictable, acute episodes of pain,
along with repeated bouts of poor pain treatment, and stigmatization by medical professionals
are the primary causes of these symptoms in SCD patients. [Also noted as an SS patient and
Clinical Lab Scientist.]
Suggestions
Type
Public
Discussion
Group discussed adding language about the multiple
barriers for some patients in the
introduction/background section. Social services
should also be addressed very early on and should
be part of the care process. Assess the unmet needs
- identify barriers to patients participating in
care...Assess potential barriers, participation in care,
follow-up visits, ability to follow healthcare
recommendation or appointments, which may be
indicative of unmet needs beyond those addressed
by the health care system alone..."Change needed.
Add to research gaps - research on how
understanding of PTSD affects the lives of people
with SCD. Also recommendation #10 will be adjusted.
Action/Recommendation
Editor added gap to end of chapter. Revised rec. #11 as follows: Refer people with behavioral issues
for evaluation by a mental health professional such as a psychiatrist, social worker, or addiction
specialist if neededed to identify unmet needs. Perform neurocognitive testing to rule out underlying
neuropsychological deficits. (ConsensusAdapted). Done.
Public
Revision submitted to this section. A new research gap was also submitted: Clinical and natural
history research to clarify the onset, risk factors, and description of neuropathic pain occurring after
recurrent episodes of nociceptive pain related to SCD. Done
135
14 In a sense, chronic sickle cell pain is an extension of recurrent acute painful episodes.
This may need some rephrasing. As noted elsewhere, there are chronically painful
complications of sickle cell disease that probably aren't extensions of crisis, such as
avascular necrosis or other osteopathies. We may be more accurate if we think of chronic SCD
pain as a diagnosis of exclusion (though a common one). This encourages us to look for
sources of pain with more specific interventions first. Describing it as an extension of acute
pain also tends to direct us away from the dramatic strategic differences in the management of
chronic pain and acute pain; I think this is to be avoided we should probably be emphasizing
these differences rather than minimizing them.
136
139
15 Very difficult to manage this in many large hospital settings, especially clinics where many
Medicaid patients are seen, where they may not see the same physician each time. Nurse
practitioners are used more in clinics now, and they also may rotate. This is one of the
reasons SCD Day Hospital programs and SCD Clinics are needed, for continuity of care.
Additionally, it must be remembered that there are patients that are not in large urban centers
who will not get this level of care.
Public
138
18 Chronic Pain Recommendations - Why is the first recommendation in the list the "Weak
recommendation, Low Quality Evidence"? The least effective treatment should not be listed
first. It encourages medical professionals to make this the first priority in treatment of the pain.
The therapies listed in #1 are complementary therapies, and should probably be #3 or #4 in
the list. [Also noted as an SS patient and Clinical Lab Scientist.]
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Change
152
6 For this set of recommendations, provide in each recommendation statement the age limits or
clear definitions for children vs. adults
Fed
Change
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Comments
152
13 1. is this potentially unclear or misleading, given the suggestion to screen for proteinuria only?
2. doesn't microalbuminuria often spontaneously resolve in patients with SCD?
3. microalbiminuria found during an episode of illness, or while on nephrotoxic drugs be a false
positive?
4. therefore, for this recommendation to hold, wouldn't screening for microalbuminuria at well
visits also be required?
135
17 wasn't there some concern about validity of some of the diary studies - like pts filling out a
weeks worth of days at once? Sorry I do not know more about this but if true may deserve a
qualifying sentence
137
11 I'm not sure we should still be using the word adjuvant for nonopioid analgesics. In general,
they have independent and additive analgesic effects and don't require an opioid to work.
138
Suggestions
Type
Public
Discussion
Do testing in steady state; never make diagnosis with Change
one screening. Do the screening multiple times.
Health maintenance section will be changed to be
consistent with this section. Should this be a policy in
the document overall? i.e. should all similar
recommendations that are similar be modified to say
that positive results should be confirmed before
initiating treatment? Panel should decide if changes
should be made across-the board with attention to
the health maintenance chapter.
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No change
138
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138
17 Consider revising this set of recommendations. There is insufficient detail in an area that is
much needed in practice
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139
5 Revisit first sentence. It is inconceivable that a single annual visit would be sufficient to
manage chronic pain. The remainder of this recommendation should be moved to #1 for this
section
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No change
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140
7 Chronic Pain - Recommendation #9 should be first (#1) on the list. This should be the treating
medical professionals primary goal in chronic pain treatment of SCD patients. [Also noted as
an SS patient and Clinical Lab Scientist.]
No change
Action/Recommendation
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140
9 First, PTSD is a factor that should be acknowledged and treated. Second, transportation to
medical appointments has become a major problem for the elderly, disabled and chronically ill
in the US. Many SCD patients live in poverty, and are forced to use taxicabs to get to medical
appointments. Even if taxi vouchers are provided for the patient, this form of transportation is
not very reliable many times. Paratransit and ambulance systems are more reliable, but may
be cost prohibitive for many patients. This is a social services issue that is not given enough
attention for SCD patients, especially adults. This is partially due to lack of adequate medical
social workers assigned to service SCD patients, where as cancer patients are assigned plenty
of these services. [Also noted as an SS patient and Clinical Lab Scientist.]
Suggestions
Type
Public
Discussion
This was covered in a previous comment. Thank you No change
for this submission, language is being crafted to
address this in the Intro.
140
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140
9 Limiting the recommendation for mental health referral to mis-behavior issues is exceptionally This is a serious and potentially misleading
Public
short sighted
omission from these guidelines; psychologic
treatment stategies need to be included; there is
also a wealth of information on the efficacy of these
interventions in other chronic pain disorders
No change
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No change
140
10 CHANGE: Page 140, lines 10-12: change to "for evaluation by a psychiatrist, social worker,
psychologist, or addiction specialist if needed to identify unmet needs.Perform neurocognitive
testing or refer to a neuropsychologist, if needed, to rule out underlying neuropsychological
deficits."
SONAR: Psychologists are one of the specialty provider types most able and available to
evaluate and diagnose behavioral issues (Anie & Green, 2002). Neuropsychologists are
uniquely capable of evaluating, diagnosing, and recommending management strategies for
underlying neuropsychological deficits (Berkelhammer, 2007).
140
10 In many areas, providers consist of MD, Nurse and maybe specialist, can other options be
provided if do not have SW, psychiatrist, etc. Needed, what would be the impact of the
practice? May need to restate in regard to this
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No change
140
11 in this section it would be useful to include specific recs on ancillary treatments often used in
scd pain, ie antidepressants, NSAIDS, etc.. Which agents are most effective (gabapentin vs.
nortryptilline, etcc and at what doses). This would make this more practical and useful for daily
care. Possible place a table with ancillary drugs
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No change
140
11 I would separate the neurocognitive screening rec from the violating narcotic policy section and
also consider include depression, anxiety, sleep screening recs somewhere in this area as
these correlate strongly with chronic pain
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141
1 The "Risk factors" sentence reads as if these are independent factors one of which is SCD. Hb
leve and a-gene deletion by themselves and independent of SCD, are not risk factors for AVN.
Suggest rewording the sentence such as: "Risk factors for AVN of the femoral head in people
with SCD include...."
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No change
141
7 Assume "HbS--thalassemia" is to imply SS disease with alpha deletion. Need clarification for List both beta globin genes,ie SS, with alpha thal so Public
non-hematologists to minimize confusion.
not to confuse reader of description of different
globin genes.
No change
Action/Recommendation
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Comments
141
7 you have not prev mentioned HbS-alpha thal - want to include in initial table on genotypes?
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143
11 helpful to know
0 Avascular Necrosis: Very good chapter. In the
comprehensive care of patients with SCD routine xray of Hips and shoulders should be done
when patient first seen and thereafter when the patient complains of Acute pain in one hip. A
patient admitted or seen in the clinic for acute Hip pain should have an xray, and a hip MRI to
determine early AVN. Beside analgesic and PT, a consult with an orthopedic surgeon expert in
AVN for advice in management. More studies are needed for conservative management
versus Hip coring. But for patients with symptomatic stage III and with stage IV, Hip
Replacement is the procedure of choice but it has to be done in an Institution where PT is
available. Chronic pain from AVN can and should be avoided.
143
5 Individuals with AVN also need occupational therapy and vocational rehabilitation in many
cases because their occupations are not compatible with AVN such as construction workers,
plumbers, cooks, hair stylists, etc. where the prolonged standing and repetitive lifting
accelerate degeneration and intensify pain.
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11 implication of guidelines is that surgical intervention is limited to advanced stage disease and
arthroplasty, and does not discuss potential interventions for earlier stage disease
Suggestions
Type
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Discussion
This is covered in a previous change.
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No change
No specific change proposed. We believe this will be No change
adressed with the classification revision that is
forthcoming.
Action/Recommendation
No change
We have a rec for PT, rec #2. This is out side of the
scope of the evidence review for this section.
No change
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143
13 No studies of wound care products, tissue grafts, or tissue substitute grafts include SCD
patients. This is a major problem. Those physicians and researchers that perform these
studies typically do not want to include SCD leg ulcer patients in the studies because SCD leg
ulcers are the most difficult type of ulcer to heal [told to me as a patient by multiple
physicians, hematologist, dermatologist, surgeons], therefore, they would mess up our
numbers [told to me as a patient by vascular surgeon]. SCD patients should be included in
these studies, and SCD patient data can be kept separate from the primary data of studies that
usually include diabetic, arterial and vascular leg ulcer patients. Thus, we SCD patients would
not skew their data. There should be a push from NHLBI to Big Pharma for the inclusion of
SCD leg ulcer patients in their studies and clinical trials. [Also noted as an SS patient with 20
years of leg ulcer hx, and as Clinical Lab Scientist.]
Suggestions
Type
Public
Discussion
This would belong in the gaps section.We believe we No change
have addressed this concern about not including
SCD patients in many research studies in the gaps
section.
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Thank you
Acklowledged. It is beyond our scope to do more.
No change
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IND
No change
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16 Would include these references in the screening section as the literature for both sections
should match. Typically, prior to referral for a right heart catheterization, an echocardiogram
should be obtained. This should be included in this recommendation.
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No change
146
16 While this recommendation is in concordance with our recommendations in the ATS document,
it is impossible for the reader to understand how this conclusion was drawn from the
presentation of the literature in this section of the document.
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No change
146
16 Would include these references in the screening section as the literature for both sections
should match.
20 This is the prevalence of PH, not PAH. Please reference Parent F NEJM 2011, Mehari A
JAMA 2012, Fonseca 2011.
21 this is probably an over-estimate of PAH prevalence, based on the best study to date in this
area, by Parent et al
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Action/Recommendation
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3 This statement is an argument to support echocardiographic screening.
Suggestions
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Discussion
No change
Action/Recommendation
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6 Would refer to Parent F NEJM 2011 and Mehari A JAMA 2012 for some clarity on these issues.
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No change
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148
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Remains is correct
Thank you for the comment, no change
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16 It seemed from earlier discusison on screening that maybe echo was sens but not specific in
detecting people with pulm HTN; can you describe why rec would not be echo in sx pts, then
RHC if abnormal? I doubt many people would get RHC without an echo.
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This is not the right chapter for this. This would be in No change
HM.
149
11 As above how much urine protein is too much. Probably 1+ but the panel needs to be explicit
if this is all they are willing to recommend. The microalbumin to creatinine ratio line 17 is what
most SCD renal experts recommend even with the creatinine hypersecretion issue.
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No change
150
5 This is an error in fact that hyposthenuria causes volume depletion n sickle cell disease . They consider changing to free water dehydration.
are more at risk for free water dehydration and hypernatemia more than volume depletion.
Most data in chronic anemia and sickle cell disease supports a normal blodd volume and
increased plasma volume. Sodium handling by the kidney is not impared.
Public
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150
152
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152
6 There is insufficient data for the recommendations made by the Panel on initiating ACE
inhibitor therapy. No recommendations on hematuria are made. No recommendation on
assessing the renal function is made, so that proper monitoring can be initiated.
Suggestions
Type
Patients with Hematuria, proteinuria or albuminuria Public
should have a comprehensive renal function testing
assessed or referred to a nephrologist so that
baseline is obtained before initiating ACEI therapy.
E.g., BP, GFR/Crt clearance, 24 hr urine alb,
lytes,uric acid esp K+ should be evaluated before
initiating ACEI therapy. Patients with SCD are
unable to excrete potassium adequately and are at
high risk of hyperkalemia. Patients with GFR<30
(and this norm may be higher in sickle patients
where GFR is higher than normal) cannot be given
ACEI. They are also at risk of hyperuricemia.
Discussion
Outside the scope of this document. Data is
considered sufficient for the recommendation but of
low quality
Public
Action/Recommendation
No change
152
7 The text on pages 29 and 36 suggests to screen for renal disease by checking urinalysis for
protein, including patients with hypertension. Yet, the only recommendations for treatment
pertain to patients with microalbuminuria. Proteinuria is not synonymous with microalbuminuria
since the former is a more crude analysis.
No change
152
7 The text recommends to assess 24 hour urine in patients with dipstick positive for protein.
152
7 If the panel will not consider microalbumin screening as a feasible recommendation, obtaining
a 24 hours urine before referral to nephrology is not realistic.
Public
152
7 need to reconcile this recommendation with earlier section. If the prior rec is to screen for
proteinuria, how would microalbuminuria be identified?
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152
11 recommendations 4 through 4 are premature and not evidence based because there are no
controlled long-termed studies that support the use of ACE inhibitors for proteinuria in sickle
cell disease. The McKie article is misquoted (See above)
152
Suggestions
Reconsider the recommendations
Type
Public
Discussion
Evidence is low-quality but based on two references. No change
We will be elaborating more on the recommendations
in the background. If change it would be in
background. Recommendations are evidence-based,
but low quality evidence.
No change
153
0 Page 153: RENAL COMPLICATIONS under recommendation #9, renal transplantation is listed
as an option that should be used in people with SCD if they need it, yet there is no mention of
when to intervene with HCT before they get ESRF.
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155
13 If you are going to mention finisteride for recurrent priapism you also have to include
lupron/leuprolide
0 Stuttering/Recurrent Priapism: The panel did not mention if any the role of transfusion. The
panel did not discuss either when prosthesis is indicated or other form of devices in the
management of patients with complications of priapism/complication of aspiration/shunt.
155
155
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0 Ophthalmologic Complications: From a practical experience, a patient with sickle cell disease
should be followed by a competent ophthalmologist on a yearly basis so proper referral to a
specialist in Retinal Disease can be done on a timely fashion. I saw 2 cases of retinal
hemorrhage in 2 adolescents with SC age 15 and 17, the former was diagnosed because of
sudden blurry vision, the second because of routine eye examination as a component of health
maintenance. THis chapter again emphasizes the severity of sickle cell disease which includes
particularly SC and SB+thalassemia.
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22 it would be useful to add sections on iron overload and how to follow and manage in chronic
section with empahsis on ferrtin, T-2 MRI and tx with new agents. It would also be sueful to
include a section on Vit D deficiency and tx in SCD
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158
158
0 Page 158: KNOWLEDGE GAPS AND OPPORTUNITIES FOR RESEARCH - again no mention
of HCT and listed as an opportunity on page 160 is "Studies to improve outcomes in people
with SCD undergoing renal transplant. Again this is a non-curative therapy.
12 Calls for a registry are controversial. Does the document address this controversy?
Action/Recommendation
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Comments
160
14 Duplicate recommendation from acute chapter.
Suggestions
Type
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Discussion
We are OK with that.
Action/Recommendation
No change
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Comments
0 The section on blood transfusion in the management of patients with SCD is well written for the most part and I would only
suggest a few additions. It seems on the summary of evidence regarding preoperative transfusion that the 10
observational studies were not given any weight. As stated (on page 202), these studies showed significantly lower
postoperative morbidity when compared to the one randomized trial where complication risks were not compared to those
not receiving any transfusions, which would have been the appropriate comparator. Therefore, I think recommendation
number 2 (page 203) should at least be moderate quality evidence and transfusion not be limited to high risk surgery.
Suggestions
Type
Discussion
Action/Recommendation
Sounds like this person wants a more strong rec for Change made
use of transfusions. This change is for rec #2. We
are unable to increase the quality of evidence for
consulting b/c there is no evidence. Change protocol
to "method" on page 203, line 16
203
9 The recommendations for pre-op transfusions do not address those patients who are on hydroxyurea (which should be
the majority of SCA patients, especially pediatric SCA patients, as is true in my practice). I am not aware of studies on
patients on hydroxyure with Hgb close to 10 and HgbF>20% undergoing anesthesia (this is the majority of my patients).
What is the expert panel's position on this? It does not make sense to exchange transfuse these patients for low or
moderate risk surgery.
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203
17 I am not sure the literature supports transfusion for SC and SB+ for all surgeries, as the low risk ones, even if a GA, were
not complicated, only the moderate risk.
0 exhibit9 - reduction of Hb by 1gm/dl does not match the previous advice I the guideliens on anemia, and comments on
page 95 also apply
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204
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Change made
205
205
3 The recommendation for recurrent acute splenic sequestration is not clear to me. Is this the recommendation is there is
not severe anemia/evidence of hypovolemia? I would still acutely transfuse a patietn with recurrent acute splenic
sequestration acutely until the spleen could be removed
InvitedThis section refers to a specific issue over time with Change made
Non
the spleen. It is not about pre-operative treatment.
Disclosed Consider to change wording to recurrent spenic
sequestration instead of acute. Take out the word
acute.
205
4 Line 4 of table recurrent acute splenic sequestration - somehow you have to indicate that you mean no CHRONIC
transfusion, simple transfusion IS indicated for recurrent acute sequestration during an episode with a hemoglobin below
baseline. Rephrasing needed
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205
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Change made
205
9 Would clarify that TCD reading is the time averaged mean maximal cerebral blood flow velocity
This is already defined in the document in the acute Need to add hyperlink or page referral or both to to
chapter. can hyperlink or page referral be done?
information about symptomatic anemia. DONE.
Added page referral.
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Comments
Suggestions
Type
0 General Transfusion:
There should be a sentence on page 219 (under
Public
Alloimmunization is an important complication of SCD. Alloantibodies responsible for significan transfusion reactions may "recommendations" to prevent transfusion complications) saying
evanesce and difficult to detect prior to subsequent transfusion(CA Tormey, Transfusion 2009 and Blood 2009), making an that it is critically important to obtain a transfusion history (including
adequate history essential for transfusion safety.
RBC alloimmunization/RBC autoimmunization history) on all
patients.
Discussion
Action/Recommendation
Consensus protocol is already included in chapter. Change made
Add to p. 209. First bullet point: Obtain patient tx
history to include locations of prior transfusions and
adverse effects . To blood bank bullet, add: ask the
blood bank to contact hospitals where patient
reported previous transfusion to obtain transfusion
information.
208
11 A missing recommendation: May seem obvious but clinicians should request blood that is Hb S negative when planning
transfusion for a patient with SCD. This is an extra and non-routine step for blood banks.
Invited
208
18 The transfusions may be at an interval other than monthly and this may not be clear to all providers. Suggest saying the
goal is to maintain a Hb S <30% immedaitely before the next transfusion.
IND
Change made
IND
Agreed.
Change made
210
210
13 An indirect coombs is not the test most blood centers use, instead it is an "ANTIBODY SCREEN" suggest changing
wording since that is what is charged for by most transfusion programs.
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210
19 Annual monitoring of ferritin for someone on chronic transfusions is not enough, especially if they are on a chelation
regimen (compliance assessment, increase in dose, stopping chelation)
Invited
Invited
Change bullet to insert such as "liver biopsy", MRI- Done. Changed to: Evaluation for iron overload
R2Please change this to look like p. 220 line 7.
every 12 years by validated liver iron
quantification methods such as liver biopsy, or
MRI- R2 or MRI T2*/ and R2 techniques." This
matches what is on page 220 line 7.
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Change made
Public
211
2 Iron quantification methods by MRI is not available everywhere and should not be required,
211
212
22
Done.
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Comments
17 Iron Overload and Chelation Therapy: Iron overload and chelation therapy for SCD are not necessarily equivalent to
thalassemia.
Suggestions
Type
The indication for initiating chelation in intermittently transfused
Public
patients should be indicated with recommendations about their
management or alternatively a specific document should be referred
to that is required reading for embarking on iron overload and
chelation management.
Sickle cell disease and thalassemia are not the same disease and
some statements about follow-up recommendations beyond iron
measurements should be made. Presently, Exjade is approved for
SCD. Deferiprone, which has been used in Europe, has not been
approved in the United States for SCD. Given the toxicities of the
medication, the document should briefly cover the baseline
monitoring tests required for their use such as audiology, renal, liver,
ophthalmology, and growth. Particular toxicities of chelators should
be mentioned such as neutropenia with Deferiprone and renal injury
with Exjade. Monitoring of patients for endocrine dysfunction, low
bone mass, and cardiac disease is necessary.
215
Discussion
Action/Recommendation
This is true- we do not have recommendations about Change made
chelation, and the different drugs. This is beyond the
scope of this project. We agree with the comments
of this contributor. We will add..."but a thorough
review of chelation dosing and management is
beyond the scope of these guidelines." Goes on 214,
line 8. "for chelation, but a thorough...
IND
217
1 Some DHTR (including some involving bystander hemolysis) don't have any new RBC alloantibodies associated with
them (de Montalembert et al, Haematologica 2011; Win et al, Transfusion 2008).
Public
217
9 I am not sure that the statement that jaundice is more common in extravascular hemolysis is correct (assuming the
comparison is to intravascular hemolysis).
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Change made
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Change made
IND
Change made
217
11
217
218
218
Page #
219
Line #
Comments
Suggestions
16 redundant to p208
Type
Invited
219
220
220
221
Discussion
Action/Recommendation
Editor review these 2 recs they should be identically Done. Revised 219 line 16 to read: RBC units that
worded.
are to be transfused to individuals with SCD should
include matching for C, E, and K antigens. This rec
is identical to the one on p. 208 of PDF of
guidelines.
MAKE THESE CONSENSUS
These are new recs #1 AND #2. Renumber
RECOMMENDATIONS ON PAGE 219. FIRST 2
remaining recs. Add Consensus? and a query to
RECS. First Rec: Obtain patient tx history to include the file. DONE
locations of prior transfusions and adverse effects .
Also add rec: Ask the blood bank to contact hospitals
where patient reported previous transfusion to obtain
transfusion information. Consensus - both.
3 Patients with low HbS levels can be transfused to > 10 g/dL, even if not on chronic transfusions - use of disjunction makes Would change "and" have low Hb S levels" to "or" have low Hb S
more sense than conjunction
levels
10 More specific recs would be useful to include agent, dose, how to titrate, toxicities and how to screen. Could also be
included under chronic complication section
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11
Change made
221
DONE
221
Done.
221
206
14
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199
Line #
Comments
11 should mention cutoff used to allow assessment of sensitivity and specificity of serum ferritin
Suggestions
Add cutoff used to text or otherwise explain
Type
Public
Discussion
Is a period missing here. Methodologist please
address this question. Panel will be submitting a
sentence. Methodologists need to provide the
references.
10
Public
Action/Recommendation
199
209
1 these defn are helpful along with the three listed advantages of exchange but does not seem to explain why simple recd
for certain conditions and exchange for others. A little bit more detail here might be good unless it gets too involved.
20 why is this recommendation only included under chronic transfusion therapy? Why would you not do this for any
transfusion? Many complications occur with episodic transfusions in SCD
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208
Line #
Comments
9
Suggestions
Type
Add paragraph 5: "For SCD patients who are only sporadically
Public
transfused, check serum for formation of new alloantibodies
(primary alloimmunization) 2 -3 months after each transfusion. At
this time the transfused RBCs are no longer in circulation so there is
no hemolysis even if a new antibody has been formed. Detecting
primary alloantibody formation at this time is crucial, since up to
40% of formed alloantibodies become serologically undetectable
about one year after the alloimmunizing transfusion. Undetected
primary alloimmunization results in delayed hemolytic transfusion
reactions when subsequent transfusions elicit a secondary,
anamnestic alloantibody response."
Discussion
This is a good point. This can be discussed in the
background. Will re-word this and submit it.
Public
Action/Recommendation
204
8 Table (Exhibit 9)
Public
204
Public
Public
204
Re: ACS with hypoxia recommendation: why is there no category for simple transfusion here in the case of ACS with
hypoxia?
197
0 Blood Transfusion in The Management of Sickle Cell Disease: This chapter is a good document from an extensive review
as well expert opinion of some Panel members. However, I want to stress 2 issues based on my review. The Transfusion
Guidelines needs to be simplified even for an expert in hematology. Recommendations should be simple, an Algorith
would be helpful. Exhibit 9 page 204/205 is clear and easy to follow. Except for simple transfusion for symptomatic
anemia, transfusion should be managed by the hematologist expert in SCD in consultation with the Blood Bank.
Public
197
1 Consider moving this section upfront, or provide references to the appropriate info in this section throughout the
guidelines where transfusions are recommended
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200
202
202
203
10 Regarding sentence to the effect that exchange transfusions may increase RBC alloimmunization risk. Although this is
logical, Wahl SK et al (Transfusion 2012) just published a manuscript showing lower rates.
9 Transfusion Recommendations
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203
203
203
203
203
203
204
204
Line #
Comments
10 Given the degree of evidence this recommendation is NOT WARRANTED. AS written it is phrased incorrectly "raise
hemoglobin to 10 g/dl" would be better. However the data are that 9 g/dl either by exchange or simple transfusion is
adequate so where does the 10 come from. Lower risk procedures especially MRIs should not require transfusion.
Suggest
the panel consider
stating Transfusion
to a hemoglobin
on 9-10g/dl
considered"
for all evidence
general that
10 The
recommendations
on transfusion
are very clear.
There is some
published"should
cases be
series
and emerging
anesthetics
and with
a decision
indivualized
procedure
and patient'sPE
history.
minor surgeries
GA in children
and based
adults on
(typcially
line placemnets,
tube placements, and similar
10 surgeries/procedures
Should specify more clearly
thatrequire
sickle transfusion.
negative ABO/D, C, E and Kell matched blood is preferred
may not
Suggestions
Type
Public
Discussion
The basis of this is the only randomized trial in
transfusion.
Action/Recommendation
No change
17 It is unclear why there is a strong recommendation for pre-operative exchange transfusion for Hb SC and Hb S+
thalassemia.
17 WHERE is the evidence for this? SS is not the same as SC and you have managed to suggest that for most of the
document yet here you subject SC and S beta plus thal to a partial exchange transfusion? Consider softening this
recommendation as well. The data does not support it.
17 No data exists to support this in SC and S Beta plus thal
1 I have had dozens of transfusions. Im at the point now where I need one every month. Im all for tranfusions when done
the right way. Many times drs will gie you one when you dont need it thinking that its the solution but it could actually do
as a resulthere
of getting
ive hadingallstones,
overload,
and i have so
antibodies
takes
1 Imore
thinkharm.
the information
re useso
ofmany
transfusion
SCD is veryiron
helpful.
I do co-manage
all many
my SCD
pts withthat
Hemit and
longer
theinaverage
time
to find
a match.
i had here
to beisonnew
steroids
because
defer tothan
them
this area.
A good
bitme
of what
was once
presented
information
for finding
me andaImatch
would was
needliterally
to learn
impossible,
that
lasted
for
months.
Transfusions
should
be
a
last
resort,,
not
primary.
Its
not
a
cure
even
if
you
get
more before being comfortable with making these decisions without hem guidance. That being siad, this information will
transfused
could
still partner
be in crisis
many
think
opposite.
make me ayou
more
helpful
and but
better
allow
methe
to ensure
that necessary monitoring is being done and that patients
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No change
204
205
205
9 I would recommend modifying the recommendations for stroke by subtype of stroke. The evidence is moderate that
chronic transfusion is the best therapy for the secondary prevention of ishcemic stroke in children with SCD (bone marrow
transplant may be better, but the data are very limited). The data include prospective cohort studies with a pre and post
design and studies looking at stopping transfusions in those transfused for secondary ischemic stroke. In addition, there
was an RCT (SWiTCH) comparing transfusion to hydroxyurea, the study was stopped early because of a higher
proportion of strokes in the HU arm. The evidence for adults is very limited and the risk of recurrence of subarrachnoid
hemorrage or intracererbal hemorrhage may be lower than that of ischemic stroke, but the published data are insufficient
to say at this time what the best rx is for hemorrhagic stroke.
No change
205
Invited
Already addressed
No change
206
I disagree that transfusion is not indicated in recurrent splenic sequestration, especially in the management of young
children.
0 As far as I can see, there is no mention at all of genotyping in this draft. Given the number of Rh variants in the sickle
cell community, genotyping has become quite important as a diagnostic option for patients with unexpected antibodies.
And in the future it will have an even bigger role, both on the donor and the recipient side of the equation.
Public
206
1 makes more sense to start the transfusion chapter with this section, or at least pages 206-209
Invited
207
0 Next on page 207, 212, the rates of alloimmunization are discussed and as I pointed out earlier, range from 3 to 29%. It
is also emphasized of those who had stricter cross-matching criteria had more favorable results. I believe this area
should be bolstered with the information showing that more attention to detail in cross matching the donor blood would
give you a much lower rate of alloimmunization. This could be transported to the earlier area that I mentioned rather than
putting just the high 18.6% rate.
From
Email?
No change
No change
No change
Page #
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Comments
0 Finally, there is no information I can find on the use transfusion in pregnant women. The literature is replete with cohort
control studies, but there is only one randomized clinical trial (Koshy). This trial did not really reach the numbers needed
in their power calculations, but was nevertheless termed a negative study. When one reads the study carefully however,
over 85% of the non-transfusion group, received transfusions sometime during the pregnancy due to VOC. In the
transfusion group there was less morbidity, although because of small numbers, it did not reach statistical significance.
While this is not the number one treatment modality, it should be at least mentioned in compared and contrasted to the
cohort within the frame work of the report.
Suggestions
Type
From
Email?
Discussion
We do not discuss pregnancy because pregnancy
management is not discussed in these guidelines.
We appreciate this comment. This topic is beyond
the scope of this project.
Action/Recommendation
No change
208
Invited
208
12 Matching should be for RH and Kell, which is usually stated as CcDEe and Kell since C and c as well as E and e antigens
are codominant not dominant and recessive.
Public
208
12 It is interesting that the quality of evidence for C/E/K matching is "low quality"----there are a few papers not referenced
that potentially should be, including LaSalle-Williams M et al, Transfusion 2011.
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208
14 Why would this recommendation not apply to all genotypes of SCD? A patient with SCD-SC and acute anemia faces the
same risk of hyperviscocity if transfused to too high a level of Hb. (Also applies to p220-line1)
Invited
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208
18 How about goals in adults. When or if is it safe to drop Hb S targets to below 50% in adults with chronic exchange
Invited
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208
18 Chronic transfusion as discussed above indicates that you can decrease to < 50% S after a period of time (reference
Cohen 1992) yet here you just state 30%. Need to account for the change in parameters that many experts use.
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208
18 This recommendation for children implies that the practice of allowing Hb S level to rise to < 50% after 3 years of
neurologic stability in prior stroke patients is not recommended. Also, patients on chronic RCT for indications other than
stroke should be maintained at Hb S < 30%. Are these really intended?
3 refer people to p212 for more detail on alloimmunization
Invited
No change
Invited
No change
Invited
No change needed
No change
6 ? Need for monthly retic counts. How does this change management
10 ? Need for monthly hb electrophoresis. This is costly and levels will likely not change that much month to month. Would
suggest Q 3-4 motnhs.
13 consider removing references to monthly
19 THIS is NOT a frequent enough monitoring of ferritin. Yes ferritin is a poor measure of iron burden as a single value, but
as a trend does indicate what is happending to a patient and does correlate in a specific patient with MRI or biopsy based
measurements of iron. SO suggest monthly or quarterly measurement of ferritin. Otherwise patients will be denied by
insurers one of the best re-enforcements of how iron burden is trending and of course something required for safe
monitoring of chelation per the FDA with deferisirox or deferiprone. This is not correct and should be rediscussed by the
panel.
Invited
Invited
No change
No change
IND
Public
19 Blood Transfusion-Suggested Periodic Evaluations Ferritin should be done more than semi-annually in a chronically
transfused patient, especially if on iron chelation. This assists in monitoring compliance with chelation therapy, and
effectiveness of the chelator and dosage.
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209
209
210
210
210
210
210
7 thank you!
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Comments
19 serum ferritin once or twice a year seems inadequate to me to evaluate adherence to chelation
211
211
2 I'm not convinced monitoring hepatic iron in patients prescribed a maximum chelator dose is worth the risk/expense if
ferritin is over 2-3000
214
9 I would recommend commenting that proper deferoxamine SC administration is 18-24 hours as some physicians
misunderstand and believe a 2 hour bolus dose is effective. The longer administration times are required due to short
half-life of deferoxamine
214
10 I take exjade and I absolutely hate it. I dont know anyone who disagrees with me. Its so bad everyone I know who was on
the other medicaton first, chooses to stay with that verses having to drink some horrible gritty mess that they say has no
taste. Its the worst. I was just wondering if there was any other option. Is there a pill you can simply swallow, anything
would be better than drinking that horrid medicine.
215
18 I would recommend commenting that proper deferoxamine SC administration is 18-24 hours as some physicians
misunderstand and believe a 2 hour bolus dose is effective. The longer administration times are required due to short
half-life of deferoxamine
218
Suggestions
Type
IND
Discussion
Change covered in previous comment.
No change
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Action/Recommendation
219
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220
5 Is there really outcomes study to study that suggest pateints do better using MRI results as compared to ferritin. In my
expereince both are usally abnormal and you titrate your therapy as needed. This was given strong rec with mod quality
of evidence, but I am unaware that studies really show improvment in iron overload using MRI ( but I am y not be up-to10 date)
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220
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220
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Comments
3 STRONGLY suggest that this research opportuinity be pursued especially with reference to the need for transfusion for
low risk procedures (lines, ear tubes, hernias and imaging).
Suggestions
Type
Public
Discussion
This section is being revised
Action/Recommendation
No change
Page # Line #
Comments
81
14 I'm not sure "prompt" imperic therapy requires gm neg coverage;
Suggestions
Type
I would emphasize providing urgent treatment to kill Public
pneumococcus
Discussion
Action/Recommendation
Simplify these recommendations with a statement about
Editor: Changed to: 2. Promptly administer ongoing empiric parenteral antibiotics
how they address the initial stages of fever. Wording for the that provide coverage against Streptococcus pneumoniae and gram-negative
background to be submitted.
enteric organisms. Subsequent outpatient management using an oral antibiotic
is feasible in people who do not appear ill. (ConsensusPanel Expertise) 12-1212 Done
92
0 Worsening Anemia - Background: On the first black book published by NIH, we had
a table showing hematologic features of the different types of SCD. I modified it and I
will be happy to send it to the expert panel for their review. I feel that it would be a
good addition to the guidelines .
Public
Helpful to have ranges of values by SCD genotype to give Editor: Background Revised per panel. Added: Baseline values are typically 7
sense of baseline. Keep simple hemoglobin concentration 10 gm/dL for people with SCA, 912 gm/dL for people with HbSC, and 1013
for 4 main genotypes. Add that these are the most common gm/dL for people with HbS+-thalassemia. Done.
genotypes. Sentences will be drafted and they will be
passed by panel.
92
2 What is a "sickle cell expert"? What certification or credentials does this expert have?
Invited-Non
Disclosed
92
9 Choice of the term "Worsening Anemia" suggests a time dependent process requiring
multiple measurements. This is a new term and does not adequately describe the
often precipitousand life-threatening drop in Hb level detected in a single Hb
measurement. The term "Acute Anemia" was coined by the CSSCD and the term
"Acute exacerbation of anemia" was used in the definitions of SCD phenotypes
(Ballas et al, 2009) by the Comprehensive SC Centers - both programs funded by
NHLBI. "Acute" is the keyword as suggested by the recommendations.
Invited
93
3 The panel comments on having a high reticulocyte count during a delayed hemolytic
trahsfusion reaction. Usually a delayed hemolytic transfusion reaction is associated
with low reticulocyte count.
Invited
Good - thank you. Line 3 will change. Count will not always Delete the parenthetical statement per panel -AH. Editor: Done.
be elevated.
94
Invited
Editor: Paragraph about acute aplastic crisis was moved up and revised to read:
An aplastic episode or crisis is a common feature of SCD, especially in children
with HbSS (Smith-Whitley et al. 2004; Serjeant et al. 1981). The usual clinical
picture is gradual onset of fatigue, shortness of breath, and sometimes syncope.
Fever is quite common as well. Physical examination may reveal lethargy, rapid
heart rate, and occasionally frank heart failure. The hemoglobin value (typically
36 g/dL) is usually far below the persons baseline level, and the reticulocyte
count is reduced or even zero. Done
94
Invited
94
Public
Editor: per panel, changed to: The usual clinical picture is gradual onset of
fatigue, shortness of breath, and sometimes syncope. Done
94
Public
Editor: Per panel: changed to: Physical examination may reveal lethargy, rapid
heart rate, and occasionally frank heart failure. Done
94
Public
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Comments
94
14 I think Steinberg showed G6PD has no impact on hemolysis
Suggestions
Type
A modest drop in Hb is frequently seen in acute pain Public
and chest episodes
Discussion
Agreed. Delete sentence starting with word concomitant
and ending in circumstances. Line 14-15, page 94. other
causes are (List them). Incorporated into other sentences.
Action/Recommendation
Editor: Sentence deleted. DONE
Editor: P. 92, line 17: Added definition of acute anemia to Background section as
follows: Acute anemia, ordefined as a decline by 2.0 g/dL or more in hemoglobin
concentration below the patients baseline value, is often sudden and can have
diverse causes. Done.
95
Public
95
13 symptomatic is not well defined and 2gm/dl below baseline seems very arbitary. If
their Hb is normally 9, then 7 is not necessary a suitable threshold for transfusion.
Conversely if normally 6, then 4 may be too low. Inappropriate transfusion is a huge
problem in community hospitals and these guidelines do not adequate mitigate this
risk, and could potentially worsen it through lack of firm guidance on this issue.
95
Invited
Editor: Recs. 3-5 revised as follows: 3. Use simple transfusion in people with
SCD and acute anemia whose symptoms are due to anemia. (Consensus
Panel Expertise)
4. Perform a CBC and reticulocyte count promptly and again 7 to 10 days later in
siblings and others with SCD who are exposed to a person with an aplastic
episode. (ConsensusPanel Expertise)
5. Manage aplastic events with immediate red blood cell transfusion aimed at
restoring the hemoglobin to a safe (not necessarily baseline) value. Isolation of
hospitalized patients (droplet precautions) is required to prevent spread of the
parvovirus B19 to pregnant women and others with SCD or compromised
immunity. (ConsensusPanel Expertise). Done
95
14 I believe this may be a typo and <2 g/dL should read >2 g/dL
Public
95
14 THIS IS WRONG. You mean > or GREATER THAN 2 grams below baseline
Public
95
14 MAJOR CONCERN that stating a hemoglobin more than 2 grams below baseline
requires transfusion. IN SC this could mean that a child with a hemoglobin of 9.5 is
transfused not because of oxygen carrying capacity or problem but because they are
below their baseline of 11.5. Consider suggesting that the fall from baseline is ONLY
one part; concomitant oxygen requirements, falling reticulocyte count etc should also
be evaluated.
Public
95
Invited
95
18 It is not clear why (slow) is listed without mention reason for slow transfusion and
what qualifies for slow. In a patient with Hb of 1.5 or 2 this recommendation maybe
misleading.
Invited
Editor: Rec. 5 revised to: 5. Manage aplastic events with immediate red blood
cell transfusion aimed at restoring the hemoglobin to a safe (not necessarily
baseline) value. Done
95
Invited
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Comments
96
5 Modify the sentence to read----because both the red cells and the platelets are
trapped in the spleen.
96
6 Toddlers not a precise term
97
2 modify the sentence to read as the sequestered erythrocytes.
97
97
Suggestions
Type
Invited
Discussion
" Both red cells and" at the end of line 6.
Done
Public
Invited
Done
Done
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Public
Done.
Editor: Revised to: Most people with chronic splenic sequestration accompanied
by local pain and hypersplenism are also managed with splenectomy.
Splenectomy for splenic sequestration does not further increase the risk of death
or bacteremia (Wright et al. 1999) since most patients are already functionally
asplenic. Done.
Public
Invited
Done.
Public
Public
Done.
Public
Invited
change the word people to adults in line 19. Reference will Sentence deleted. Mallouh & Hamdan 1989 reference deleted. Done
be checked
Public
5 older people?
9 Throughout the document the authors need to be careful about declaritive statements
based on studies with large potential for B error. Thus, and for example, on page 97
"Splenectomy for splenic sequestration does not increase the risk of death or
bacteremia (Wright 1999)" seems highly improbable. The study was likley
underpowered to identify even large increases in clinically relevant outcomes. Why
would splenectomy for this indication be not associated with sepsis and yet is for othe
indications for splenectomy. There are numerous similar examples throughout the
text.
97
10 This statement is misleading and not supported by the other literature regarding risk
of overwhelming infection in patients with splenectomy.
97
10 consider adding "bc pts with SCD are already functionally asplenic"
97
98
98
9 The reference cited documented occurrence of splenic sequestration in pts on chronic Clarify wording and conclusions.
transfusions. The goal of temporary transfusions is to prevent severe or fatal
sequestration until splenectomy can be performed. A transfused pt with Hb 10 drops
to 7.5 with enlarging spleen is better off than a pt with Hb 5.5 who has recurrence and
drops to 3. So this conclusion misses the point.
98
98
Delete sentence.
99
0 The ACS background is poor. There is National ACS study was not mentioned.
Invited
99
0 This section on ACS does not differentiate between ACS and simple pneumonia in
this population. If this is your intention, I suggest adding one or two sentences to this
effect for clarification.
Public
99
1 On p96-line21, the acuity of splenic sequestration in infants and the potential for
hypovolemic shock are mentioned however, fluid management is not included in the
recommendations. It may take hours in most settings to initiate blood transfusion; fluid
recuscitation may be the first life-saving intervention.
Invited
99
2 Why transfuse to increase Hgb by 2-3 versus to a stable level. I get not bringing to
baseline but if they present with Hgb of 3, do you bring up only to 6?
Action/Recommendation
Page # Line #
Comments
99
2 The issue is the hemoglobin that defines severe anemia, not necessarily the amount
of transfusion to be given although the discussion of do not overtransfuse is a good
one.
99
Suggestions
3 The recommendation to transfuse people with "severe anemia" is not very clear. The
recommendations on page 95 were to transfuse if symptoms and drop greater than 2
in Hgb. Can you make this recommendation fit with that one?
Type
Public
Discussion
Rewording will be provided for this.
Action/Recommendation
Revised. See comment immediately above. Done
Invited
99
14 Clarify definition of ACS. Onset is not always sudden. Do you really want to require Have a less specific definition for ACS.
signs and symptons and infiltrate? Need acknowledgement of the various definitions
used in the literature.
Public
99
14 concern here that it is not mentioned that the onset of ACS can be insidious, and the the subtley of presentation and expectant
S/S can be very subtle in a patient. The medical professional needs to be aware that investigation/management needs to be mentioned
a patient with ACS can look fairly good, and have only a mildly increased RR or mild
cough, and be very ill the next day with ACS; the CXR changes may also lag, so that
the initial CXR is normal.
Public
99
15 Chest retractions are only seen in children. Need to emphasize the importance of
hypoxemia as a physical sign.
16 In Vichinsky EP NEJM 2000, the largest study of ACS to date, the etiology of ACS
was unknown in 45.7%. This needs to be clarified in the text as ACS is often not
infectious, particularly in adults.
Public
Public
16 The Cooperative Study identified Chlamydia as the most common infectious agent
actually.
4 Would refer to table 3 of Vichinsky EP NEJM 2000 where predictors of a more severe
course included multi-lobar disease, the presence of a pleural effusion and
thrombocytosis.
Public
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Invited
99
99
100
100
100
11 Add reference for sPLA2. Some mention of C-reactive protein as a surrogate marker
may be useful since it is more readily available than sPLA2
101
14 We note that there is no discussion of the risk of anesthesia in children with SCD,
who may have a greater than usual incidence of post operative hypoxemia and
atelectasis, and who are at increased risk of VOC and ACS following surgery.
Panel will draft some language to address this. For the ACS Out of scope. This is dealt with in Transfusion chapter.
background.
Page # Line #
Comments
105
6 Paragraph discussing secondary stroke prevention does not cite results of SWiTCH
trial, now reported.
Suggestions
incorparate additional reference.
Type
Public
Discussion
Submitting a revision to this.
Action/Recommendation
Revision received 2/4/13: On p. 105, paragraph 1, add the following at the end
of the paragraph: These preliminary single-institution findings were then tested in
the prospective Stroke With Transfusions Changing to Hydroxyurea (SWiTCH)
multicenter phase 3 clinical trial. Children with previous stroke and iron overload
were randomized to receive either continued transfusions with iron chelation
(standard arm) or hydroxyurea with phlebotomy (alternative arm). The SWiTCH
trial had a noninferiority design, with a composite primary end point consisting of
recurrent stroke and liver iron concentration (Ware et al. 2011). At interim data
analysis, there were seven strokes on the standard arm (10 percent) and none
on the alternative arm; this was still within the noninferiority stroke margin, but
equivalent liver iron content between treatment arms, indicating futility for the
composite study end point. Accordingly, the study was closed, and the authors
concluded that transfusions and chelation remain a better way to manage
children with SCA, stroke, and iron overload (Ware and Helms 2012). Also add
2 new references: Ware RE, Schultz WH, Yovetich N, Mortier NA, Alvarez O,
Hilliard L, Iyer RV, Miller ST, Rogers ZR, Scott JP, Waclawiw M, Helms RW.
Stroke With Transfusions Changing to Hydroxyurea (SWiTCH): a phase III
randomized clinical trial for treatment of children with sickle cell anemia, stroke,
and iron overload. Pediatr Blood Cancer. 2011 Dec 1;57(6):1011-7. AND Ware
RE, Helms RW; SWiTCH Investigators. Stroke With Transfusions Changing to
Hydroxyurea (SWiTCH). Blood. 2012 Apr 26;119(17):3925-32.
105
19 Do all patients with rule out stroke really require CT if MRI is emergently available?
NO. ALSO what is the role of MRA. You do not mention. Since this document will be
used by payors to determine what is reasonable to pay for, this is one place that you
must indicate the need for MRI/MRA to evaluate thrombotic stroke especially in
children.
Public
107
Public
Updating text. Same as page 99, line 14. This is for 106,
line 20, not page 107.
71
10 A VOC by definition requires parenteral medical therapy? Since 80% of pain episodes
are managed at home in the US, in effect, your definition considers only 20% of pain
episodes qualify as VOC. In much of the world people with SCD in severe pain never
receive "parenteral medical therapy."
Invited
On line 10, page 71 change wording to "and bone marrow Done 12-11-12
and usually requiring parenteral medical therapy." Consider
adding to chronic chapter.
71
10 Delete "and requiring parenteral therapy". Many patients with VOC may not even get
oral analgesic therapy.
Invited
72
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Comments
72
4 add to relieve pain before mention of mortality.
72
73
Suggestions
Type
Invited
Discussion
To address comment, add the word morbidity to read
"treatment to reduce morbidity and mortality"
Done 12-11-12
Action/Recommendation
Invited
Done 12-11-12
Public
Done 12-11-12
73
Public
Done 12 -11-12
73
Invited
Same as above
73
17 Change the sentence to read--there are no tests to confirm or rule in the diagnosis of
VOC.
19 however, there is great variation and some individuals with other genotypic forms
such as HbSC can have frequent crises as well. (comment: Hb SO Arab has the most
severe biological and clinical form of disease).
73
19 Often, primary care physicians think SC and SB+ thalassemia are benign
Public
Done 12-13-12
73
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73
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Done 12-11-12
76
Invited
Done 12-11-12
Invited
We do not believe there is a single protocol that would apply Done 12-11-12
to all patients in all settings. There are a lot of comments
about this issue. This is an implementation tool that could be
deferred to the NBDP. Add the following: Substitute
"use" with "develop and use" in the recommendation
Public
Done 12-11-12
Invited
Done 12-11-12
Public
77
77
6 This suggests not taking both long and short acting. Reads as never give long and
short. Or is this stopping short acting orals and adding parenteral? Regardless it
must be clarified.
77
78
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Comments
79
0 In Exhibit 5 (Acute Pain Algorithm) should "Triage as high priority" include a specific
recommendation for ESI level?
79
2 Last box8/13/2012 Avoid "SC" for subcutaneous, since this is considered a
"forbidden" abbreviation
79
2 Figure central diamond states APLASTIC ANEMIA when I believe aplastic crisis is
meant.
80
2 Splenic impairment may occur by age 3 months in infants with HbSS, but usually is
later
80
Suggestions
7 Change the sentence to read---Even though the incidence of sepsis and meningitis
has declined .. (the sentence at this time implies the incidence of febrile illnesses
has declined).
Type
Invited
Discussion
After "high priority" add in parens (ESI 2) in the box.
Done 2/13/13
Action/Recommendation
Invited
Done 2/13/13
Public
Done 2/13/13
IND
Done 12-11-12
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Done 12-13-12
80
10 Change the sentence to read --Serious infections can also affect persons with
Invited
Done 12-12-12
80
80
81
Invited
Invited
Invited
Done 12-12-12
Yes. Done. 12-12-12
Switched order so that 101.3 F occurs first and 38.5 C is in parens. Done. 12-1212
81
Done 12-12-12
81
11 Would recommend adding differential to the CBC and a reticulocyte count to the
evaluation-also urinalysis/urine cx in younger children and CXR in children, especailly
if they will not be admitted based on studies finding ACS in children with respiratory
findings initially
Invited-Non
Disclosed
Done 12-12-12
81
81
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Disclosed
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Done 12-12-12
81
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Done 12-12-12
82
0 The section Acute Kidney Injury (pgs 82-84) does not distinguish papillary necrosis Distinquish betweeen papillary necrosis and acute
from acute renal insufficiency (defined by decrease in GFR). The distinction between renal insufficiency and include guidelies for both
these 2 acute complications is important, and guidelines as to how to manage
complications.
papillary necrosis are needed.
Public
Re-name this section to Acute Renal Failure. Definitions are DONE 12-13-12 added comment to Word file requesting missing
needed up front. AKI needs to be replaced with Acute Renal definition
Failure (or ARF) in all cases.
82
9 change to read (e.g. renal papillary necrosis)--delete glomerular from within the
parenthesis since papillary necrosis does not involve glomeruli and sickle cell
nephropathy is generally not acute.
Invited
Done 12-12-12
Invited
Done 12-12-12
Done 12-12-12
82
12 "obstruction of the blood supply to the vasa recta" suggestes that the occlusion
occurs pre-vasa recta and not in the vasa racta themselves. Not sure whether that is
accurate statement
82
18 In a discussion of acute kidney injury (AKI), the text does not mention the vulnerability Consider adding: "Children with SCD often display a Public
of patients with SCD to develop pre-renal AKI due to sub-optimal ability to develop a relative inability to maximally concentrate the urine,
maximally concentrated urine.
resulting in increased vulnerability to pre-renal
azotemia".
82
21 Change the sentence to read since the serum creatinine levels are generally low in
individuals with SCD, the values in AKI in SCD may still be within normal limits even if
they have doubled from baseline.
Line 21: Change to read, "Since the serum creatinine levels Done 12-12-12
are generally low or low-normal in individuals with SCD, the
values in ARF may still be within normal limits even if they
have doubled from baseline.
Invited
Page # Line #
Comments
83
14 Delete acute before renal---the complications listed in the parenthesis include both
acute and chronic renal problems.
84
0 Acute Kidney Injury: Recommendations - I feel this chapter needs to be more
organized. Different kidney injuries In SCD are mentioned and this will be confusing
for a primary care and even a hematologist. An immediate renal consult is necessary.
Chapter on chronic renal failure should follow.
84
11 Modify the sentence to read ---unless there are complications involving other organs
that necessitate transfusion therapy (such as ACS or multiple organ failure). This
sections should also have a recommendation for seeking consultation with a SCD
expert and Nephrologist.
87
89
89
91
93
95
Suggestions
delete?
Type
Invited
Discussion
Action/Recommendation
Agreed
Done 12-12-12
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Done 12-12-12
Done 12-13-12
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11 Include statement that lack of reticulocytosis with worsening anemia favors aplastic
episode as the cause
6 this statement may be misleading because it seems to suggest that the spleen should remind the reader of the basic principles re:
immediately be removed after one transfusion given to reach Hb or 8. The child
preparation for surgery in patients with sickle cell
should be allowed to get over the acute illness and stabilze, which may require
disease, especially infants and small children.
several transfusions (short-term), appropriately speced.
Invited
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100
11 The link between ACS and chronic pulmonary disease has become less clear since
1995. Would suggest familiarizing yourselves with some of the literature on this
subject published in the 21st century.
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Done 12-12-12
103
10
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104
106
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99
106
106
6 Are there anectodal data for avoiding lytics/anticoagulants in ischemic stroke-especially in adults?
remove comma
Done 12-12-12
Done 12-12-12
made change and added comment about needing panel review. DONE
12-12-12
Page # Line #
Comments
106
8 I dont see a discussion of the panel's rationale for not using tpa in adults with scd
and acute stroke. I agree there is no reason to use anticoagulation
Suggestions
Type
Include some discussion of pro and con for tpa,
Public
given the lack of evidence I dont support this strong
a recommendation to avoid tpa. Also this section
should mention PRES which is often confused with
ischemic stroke.
Discussion
Rec #5 - "...stroke, initiate a program of monthly simple or
exchange transfusions."
Action/Recommendation
Done 12-12-12
106
106
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Done 12-12-12
Done. Note: Added comment to file to confirm that change was made
correctly.
106
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Done 12-12-12
107
107
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108
14
108
111
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Done
111
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113
11 RCT - studies related to CVA in adults should include at what age (if ever) to d/c
chronic transfusions if they began transfusion tx as a child.
IND
Done 12-12-12
Done 12-12-12
Public
Done 12-12-12
92
7 non severe IHC did well in the St Jude review and in Dallas (children)
Done 12-12-12
Add a line: Summary of the Evidence section, on page 110, done 12-12-12
line 17 - remove "exchange transfusion" from parens. Add
on line 18 after OCS: There was not enough evidence to
make a recommendation about using transfusion to manage
these acute complications.
Page # Line #
Comments
95
18 Should the phrase "packed red blood cell" be changed to just "red blood cell" since
they are no longer "packed"?
Suggestions
Type
Invited-Non
Disclosed
Discussion
Eliminate the word packed. Panel will also make changes in Done 12-12-12
this section
Action/Recommendation
101
Public
Can methodolgists provide more detailed information about done; see revisions to line 102-6 below
transfusion and the use of antibiotics and other supportive
care from the evidence in the summary?
102
1 This sentence mentions the term---"symptomatic ACS"---I thought all ACS was
symptomatic. This recommendation should be modified to say all patients with ACS
requiring oxygen supplementation (Fio2 >40% or whateve) or those with hypoxia
despite oxygen supplementation without mechanical ventilation. I would personally be
more liberal and recommend transfusino with anybody with decreasing Hb or hypoxia
that does not correct rapidly.
Invited
Ask methodologists for a better synthesis of this topic. Then for panel to decide
take to panel for further review. Look at evidence tables,
look at literature, possibly.
102
3 10cc per kg is simple, but not ideal for patient care, plus it is not clear where this
Have a target, such as baseline and rounding to
comes from. So if this is 1.25 units would you really just give a small fraction of a unit nearest unit without raising hgb too high. Have a
a expose the patient to another donor? If it were 1.75 units, wouldn't you give 2 full
comment about what to do if intial Hgb is high
units as long as the final HCT wasnt too high? I worry that this simple
recommendation will result in exposing patients to additonal donor units, and may
waste some potential benfits with little addioanl risk. Also, what if the intial Hgb is 9.5,
you wouldnt give 10cc/kg, you would exchange.
Public
Ask methodologists for a better synthesis of this topic. Then Transfusion team please review and OK recommendations. Then editor change
take to panel for further review. Look at evidence tables,
comments assigned to methodologists to 'no change.
look at literature, possibly.
102
3 the instructions starting here may cause a transfusion to be given that would result in put in the caution re: not to transfuse to Hb higher
a Hb greater than10.5 (if the pt's baseline Hb is 10, and is now 9 and 10 ml/kg is
than 10.5/11
given, the end Hb could be 12, with concern re: increased viscosity
Public
Ask methodologists for a better synthesis of this topic. Then Transfusion team please review and OK recommendations. Then editor change
take to panel for further review. Look at evidence tables,
comments assigned to methodologists to 'no change'."
look at literature, possibly.
102
Public
Ask methodologists for a better synthesis of this topic. Then Transfusion team please review and OK recommendations. Then editor change
take to panel for further review. Look at evidence tables,
comments assigned to methodologists to 'no change'.
look at literature, possibly.
102
3 Should the phrase "packed red blood cell" be changed to just "red blood cell" since
they are no longer "packed"?
Invited-Non
Disclosed
Ask methodologists for a better synthesis of this topic. Then Editor: Per panel, deleted "packed."
take to panel for further review. Look at evidence tables,
look at literature, possibly.
102
3 Partial exchange transfusion is a viable option here that may prevent increases in
viscosity that are detrimental
Public
Ask methodologists for a better synthesis of this topic. Then Transfusion team please review and OK recommendations. Then editor change
take to panel for further review. Look at evidence tables,
comments assigned to methodologists to 'no change'.
look at literature, possibly.
102
3 no more packed cells (Adsol)-can give more. Worsening resp status is more
important indication than a 1 gm drop in Hb.
Ask methodologists for a better synthesis of this topic. Then Transfusion team please review and OK recommendations. Then editor change
take to panel for further review. Look at evidence tables,
comments assigned to methodologists to 'no change'.
look at literature, possibly.
Page # Line #
Comments
Suggestions
102
3 "Give simple blood transfusion .. with symptomatic ACS and a Hgb concentration
Base recommendation for simple blood transfusion
>1gm/dl below baseline."
on maximum and minimum Hb targets rather than
Simple blood transfusion may be dangerous (hyperviscosity) in SC or S B thal with Hb specific Hgb drop.
over 10-11. The threshold for transfusion may vary among patients, and might be
Consider separate recommendations for adults and
inappropriate for some (e.g., SC patient with baseline Hgb of 11). The decison to
children.
transfuse and whether to use simple or exchange depends BBOTH od severity and
rate of progression of ACS as well as the hemoglobin at time transfusion ordered.
Further, some management decisions may be different for children and adults.
Type
Public
Discussion
Action/Recommendation
Ask methodologists for a better synthesis of this topic. Then Transfusion team please review and OK recommendations. Then editor change
take to panel for further review. Look at evidence tables,
comments assigned to methodologists to 'no change'.
look at literature, possibly.
102
Public
Ask methodologists for a better synthesis of this topic. Then Transfusion team please review and OK recommendations. Then editor change
take to panel for further review. Look at evidence tables,
comments assigned to methodologists to 'no change'.
look at literature, possibly.
102
6 Where is data for urgent exchange? With what O2 support? Does this imply
intubation or nasel prongs. Where is data for exchange versus direct?
Public
Ask methodologists for a better synthesis of this topic. Then add to page 101, line 13: Studies that evaluated antibiotics did not demonstrate
take to panel for further review. Look at evidence tables,
a significant effect on patient important outcomes. Multiple observational studies
look at literature, possibly.
evaluated opiates in ACS. In one, nalbuphine hydrochloride reduced the
incidence of ACS compared to morphine (12% vs 29%) and also reduced
hospital stay (buchanan). In the remaining studies opiates clearly reduced pain
but without other effects on the clinical course of ACS. Transfusion studies in
ACS showed conflicting results. In one study, length of hospital was similar
between simple transfusion and exchange transfusion. ICU stay was longer in
the exchange group, (5.6 days vs 2.6 days). (King) Another study found
significant correlation between exchange transfusion and fewer days of
hospitalization and oxygen requirement. (Liem). In these and other transfusion
studies, sicker patients were more likely to receive exchange transfusion; which
indicates a clear selection bias. Editor: Done 3/7/13. Also added refs: King et al.
1996, Liem et al. 2004, and Buchanan et al. 2005. Done.
102
6 lines 8 and 9 could be used as the indication for simple transfusion above. A drop in
Hb certainly is not an indication for exchange
Ask methodologists for a better synthesis of this topic. Then Transfusion team please review and OK recommendations. Then editor change
take to panel for further review. Look at evidence tables,
comments assigned to methodologists to 'no change'.
look at literature, possibly.
102
6 Page 102 - exchange transfusion "(with)... decline in hemoglobin concentration" should be quantified or at least a range provided - what if the fall is 0.1 g per
decilitre ? Should a HbS be measured before exchange since it seems to me that
many patients have sufficient transfusions during the "resuciation phase" to cause
their HbS levels to be very low.
Public
Ask methodologists for a better synthesis of this topic. Then Transfusion team please review and OK recommendations. Then editor change
take to panel for further review. Look at evidence tables,
comments assigned to methodologists to 'no change'.
look at literature, possibly.
102
6 recent systematic review failed to identify any studies comparing methods for
transfusion in ACS. This should not be a recommendation but should instead be
moved to the section on knowledge gaps/needs for research
Invited
Ask methodologists for a better synthesis of this topic. Then up to the panel: they can consider removing this recommendation or
take to panel for further review. Look at evidence tables,
downgrading it. It certainly should be downgraded as reviewer suggested.
look at literature, possibly.
Page # Line #
Comments
Suggestions
Type
84
5 In a discussion of acute kidney injury (AKI), the text mentions that a serum creatinine Please consider that in SCD, many patients exhibit Public
level of 0.7 is elevated.
increased secretion of creatinine (and high GFR).
Also, applying a cutoff level for AKI of 0.7 does not
take into account the influence of body habitus on
serum creatinine (lower levels in smaller children).
Suggest changing the definition of AKI to: "An acute
fall in glomerular filtration rate, defined by an
absolute increase in sedrum creatinine of greater
than or equal to 0.3 mg/dl or percentage increase in
serum creatinine of greater than or equal to 50%.
86
20 From the description of the evidence, there did not seem like there was high quality
evidence for any of the recommendations.
IND
Discussion
Action/Recommendation
This needs to be cross-walked with the Chronic section and Changed lines 6 and 7 to read: "1. In the setting of an acute rise in serum
adjustments may be needed.
creatinine by greater than or equal to 0.3 mg/dl:" DONE 2/13/13
86
20 YOU MUST consult the AFUD (American Foundation for Urologic Disease) that is the
policy making group of the Americal Urologic Association AUA's recommendations for
PRIAPISM IN ANYONE. They clearly have recommended to their members the
experts in the management of priapism that any erection lasting longer than 4 hours
be relieved with intracavernosal injections of dilute phenyephrine. To be less explicit
here is simply WRONG. That this recommendation can also be applied to children is
also published by the Dallas group. AT LEAST mention ASPIRATION AND
IRRIGATION for prolonged priapism!
Public
98
Invited
71
7 The term crisis to describe manifestations of SCD for instance is problematic and
has been for some time. It lacks specificity and this colloquialism instead connotes
circumstances that are unpredictable, catastrophic, difficult to control and scientifically
poorly understood. These guidelines should embrace a more progressive approach
to the discussion of SCD that uses more clear and less stigmatizing descriptors,
much in the same way that manifestations of other significant illnesses are described,
starting with a change in nomenclature. Terms such as vaso-occlusive 'event' or
'episode' carry far less "baggage" than crisis.
Invited
71
8 Avoid the term crisis. It is emotional , doesn't represent how many patients are able
to deal with it, and can be demeaning and hard on pateints sense of self (especially
teens)
Public
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71
8 Prior to this definition, various terms had been used to describe pain episodes in
SCD; you might go back to bring uniformity your pain terminology
Suggestions
Type
Invited
Discussion
Deferred to panel because scope of change would affect
entire document.
Public
71
73
Invited
76
3 1. Should the exclusion of "cold packs" and ice therapy be specifically mentioned?
2. Should specific alternative agents, such as methadone, or adjunct medications
such as muscle relaxants be mentioned?
Public
77
Invited
77
9 This is an extremely dangerous recommendation without concurrent discussion about Ask the panel to carefully reconsider this
close monitoring for side-effects and complications and recommendation as to when recommendation.
to get input from an expert in pain management. This recommendation is going out to
the general medical community and one needs to know the patient well and have
significant experience in managing acute pain to avoid getting patients into trouble
with such recommendations without well defined limits.
Public
78
10 There are other routes available - did the authors consider intranasal opioids?
Invited
81
Invited
81
13 It is more typical for children than adults to receive empiric antibiotics while fever is
being evaluated. Is your intention to extend the same practice to adults?
Public
81
15 I know there was a study using oral antibiotics after discharge, but why not return in
24 hours for a recheck and another IM dose of antibiotics. Some practitoners have a
24 hour return and if cultures are negative and patient is afebrile, stop antibiotics. I
think the written Panel expertise recommendation needs to be softened to allow for
other treatment regimens that are not necessarily less effective.
Invited
81
18 This article by Morris et al. suggests that obtaining a CXR should be empiric for
Would modify recommendation to include all febrile
febrile patients with SCD and not based on respiratory symptoms. Ann Emerg Med. patients
1999 Jul;34(1):64-9. Clinician assessment for acute chest syndrome in febrile patients
with sickle cell disease: is it accurate enough? Morris C, Vichinsky E, Styles L.
Public
81
18 Very young children with ACS may not demonstrate signs of respiratory illness initially.
Evaluation with chest xray for children < 3yr has become routine in fever management
Invited
17 You really must include the results of the SWiTCH trial on this issue, published by
WARE et al in early 2012.
Public
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Action/Recommendation
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Comments
71
1 Change the statement regarding pathophysiology to read---"Unlike HbA that remains
dissolved and liquid whether or not oxygen is present, HbS has a tendency to become
gel-like under low oxygen concentration. The gelling, also called polymerization, can
change the flow of red cells in the blood, change their shape to crescent or sickle
form, and cause occlusion of blood vessels leading to tissue ischemia, pain crises
and organ damage. Red cells with HbS break down faster and the release of free Hb
may lead to changes in the blood vessel that cause vasculopathy, large vessel
disease and complications such as stroke and pulmonary hypertension. Leukocytes,
coagulation and inflammatory processes contribute to complications of SCD." This
statement can be improved upon but would be more inclusive of other elements of
pathophysiology of SCD than the current statement. The modified statement should
replace all other repetitions of this statement in the guidelines.
81
71
73
Suggestions
Type
Invited
Discussion
Defer to panel because making a change would require
changes to entire document. Therefore scope of change
requires panel.
13 ? If all adult SCD patients with fevers really need a dose of iv abx (if very stable,
outpatient, etc
0 The section on vaso-occlusive crisis (VOC), page 71-78 is very well written.
Although, there are no specific tests to diagnose VOC, I would suggest a list of
symptoms which accompany crisis and the percentage or frequency could be gleaned
from the literature (noted on page 72) and put in a table. Also, while the
recommendations and studies support using opiates for the control of pain, recent
work and national and state level suggest that oral/parenteral opiates be withheld
from all patients other than those having cancer. VOC and other acute/chronic
conditions such as, osteoporosis, and other degenerative diseases have strong
evidence that opiates are helpful versus placebo or non-steroidal but these studies
are being over looked. Perhaps a stronger statement in one sentence would be
helpful, so opiate would be available to the SCD patients.
Invited
18 Add a sentence--finding another cause such as pneumonia on chest x ray does not
rule out the presence of a concomitant VOC of ribs, sternum or vertebral column.
Invited
Action/Recommendation
Changed to: There are no tests to rule in or to rule out a VOC; there
are only tests that potentially rule out other causes of pain. DONE
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Comments
Suggestions
74
3 This belittles the role of reversing triggers of pain episodes (e.g. hydration or warmth), Need to state role in non-analgesia management of
distraction, comfort measures, biofeedback or meditation, etc
pain
Type
Public
Discussion
Action/Recommendation
Add another sentence to say the role of hydration and
Prior to start of line 3, add: "Pain management must be guided by
nonpharm interventions are important. They can be used in patient report of pain severity. No biomarkers or imaging studies can
the context of appropriate management. Hydration is not validate pain or assess its severity." Then, after "analgesic treatment,"
always needed, however. General statement can be added add "typically with opioids. No empiric data exist to indicate that rapid
analgesic administration results in better outcomes. However, as
patients with VOC present with severe pain and are at risk for other
complications, best practice suggests that rapid triage, placement,
and administration of analgesics should be encouraged. The
Emergency Severity Index Version 4 triage system, which is used by
more than 50 percent of emergency departments in the United States,
suggests persons with SCD be triaged as ESI level 2, a very high
priority, and rapid placement be facilitated (Gilboy et al. 2011). Many
specific recommendations for acute VOC management are included in
this section. A recommendation is included to guide providers in
managing persons who take both long- and short-acting opioids to
manage pain at home. There are no empirical data to guide whether
or not to continue long-acting opioids when ordering continuous
opioids via patient-controlled analgesia (PCA). The decision to
continue long-acting oral opioids should be made on an individual
basis. For example, in most circumstances, it is advisable to continue
methadone therapy even when ordering continuous opioids via PCA.
Finally, hydration and nonpharmacologic therapy are also very
important as is concurrent treatment of itching caused by histamine
release.
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74
5 Key Question - there were no comments on the use of oxygen when a pt is admitted
with VOC. Should there at least be a comment to check the pt's O2saturation given
the possibility of ACS or other pulmonary complication during the admission. This
would give clinicians the pt's baseline on admission.
74
Suggestions
Type
Invited-Non
Disclosed
Discussion
Action/Recommendation
Not enough evidence on the use of oxygen to make
Added new Rec #17: In adults and children with SCD and a VOC with
evidence-based recommendation. Agree to incorporate a
an oxygen saturation <95 percent on room air, administer oxygen.
new line in concensus statements regarding oxygen.
(ConsensusPanel Expertise) 1/17/13 DONE
Concensus-based recommendations will be added by panel.
Panel will draft a sentence to be reviewed by panel.
Invited
Public
Revision submitted: before p. 74, line 16, revised as: "One study
evaluated the effectiveness of meperidine versus placebo or other
opioids and found meperidine more effective than placebo in reducing
pain. Also, Rec. #8 added: In adults and children with SCD and a VOC,
do not use meperidine unless it is the only effective opioid for an
individual patient. (ConsensusAdapted) DONE
74
16 You clearly do not want to recommend the use of meperidine. The sentence however
leaves doubt about the panel's position. Suggest restructuring to state BECAUSE OF
NEUROTOXICITY CONCERNS MEPERIDINE SHOULD NOT BE USED TO TREAT
PAINFUL CRISIS.
74
76
Invited
Will revise recommendation and submit. Need to add a 30- Editor: Revised Rec #2 to read as follows: 2. In adults and children
minute goal timeframe.
with SCD and a VOC,
Determine characteristics, associated symptoms, location, and
intensity of pain based on patient self-report and observation. If the
VOC pain is atypical, investigate other possible etiologies of pain.
(ConsensusAdapted)
Rapidly assess the patients recent analgesic use (opioid and
nonopioid). (ConsensusAdapted)
Rapidly initiate analgesic therapy within 30 minutes of triage or
within 60 minutes of registration. based upon pain assessment,
associated symptoms, and prior analgesic use. (Consensus
AdaptedPanel Expertise)
Base analgesic selection on pain assessment, associated symptoms,
outpatient analgesic use, patient knowledge of effective agents and
doses, and past experience with side effects. (ConsensusAdapted)
DONE
76
17 clarify if these recs are specific for inpatient vs. outpatient vs. day staty, etcc..here
and throughout this section
Invited
Team discussed clarifying the text to address this comment. Editor: on p. 76, line 6, added: These recommendations are intended
Pg. 76, line 4: "These recommendations are intended to be to be for all settings where patients present with VOC.
for all settings where patients present with VOC." Algorithm
may be adjusted as well.
Public
Line 15 on page 77, regarding use of antihistimes and non- Editor: changed Rec. #9 to: In adults and children with a VOC,
steroidals. panel will revise.
administer oral NSAIDS as an adjuvant analgesic in the absense of
contraindications (Consensus--Adapted). DONE 2/13/13
77
5 The role of NSAIDS as adjunctive therapy in addition to opioids in severe VOC needs
to be clarified. This should be included in Exhibit 5 as well.
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Comments
77
15 Should you explicitly state that ANTIHISTAMINES are not needed for each dose of
opioid? That would be a big help in clinical management.
Suggestions
Type
Public
Discussion
Action/Recommendation
Editor: changed Red. #10 to: 10. In adults and children with a VOC
who require antihistamines for itching secondary to opioid
administration, prescribe agents orally, and do not re-administer with
each dose of opioid in the acute VOC management phase. Readminister every 4 to 6 hours if needed. (ConsensusPanel Expertise)
DONE
77
15 I am not clear why consultation with hem needed for antihist, antiemetics
Invited
77
15 Consult with a sickle cell expert regarding use of antihistamines or starting other
Please provide dosing recommendations for
adjuvant agent categories: Not useful in majority of settings where sickle cell experts frequently used medications, including Benadryl,
are not available.
Atarax, and low dose Narcan for pruritis; and antiemetics such as Zofran.
Public
Editor: changed rec. #13 to: In euvolemic adults and children with
SCD and a VOC who are unable to drink fluids, provide intravenous
hydration at no more than maintenance rate to avoid over-hydration.
(ConsensusAdapted) DONE
78
78
ACS is not VOC but will be addressed in the ACS portion of Editor: revised Rec. #11 to: To reduce the risk of acute chest syndrome
the guidelines. A sentence will be drafted and it will go to the in adults and children hospitalized for a VOC,
panel for review.
Encourage use of incentive spirometery while awake. (Strong
Recommendation, Moderate-Quality Evidence)
Encourage ambulation and activity as soon as possible.
(ConsensusPanel Expertise). DONE
78
78
13
78
21 No mention of use of oxygen for simple painful event; this should be addressed - I
believe that no data exists validating its usefulness in this setting.
Invited-Non
Disclosed
Panel will look at the background and see about making an Editor: a logical place to address this comment was not found. Editor:
adjustment
comment added to master file.
Public
Added new rec 17. In adults and children with SCD and a VOC with an
oxygen saturation <95 percent on room air, administer oxygen.
(ConsensusPanel Expertise). Does this address this?
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79
Figure: there is no evidence cited for the 30 minute time to begin analgesic
administration. Given the lack of evidence, it might be more accurate to say "as soon
as possible" Same comment about alternate routes of pain administration for figure why not intranasal pain meds?
Suggestions
Type
Invited
Discussion
There is no evidence, but a comment is needed to make
done 2/13/13
sure the figure matches the change we made in the
recommendations about timing of initial analgesic. Panel will
submit changes to the figure.
Action/Recommendation
100
8 While there is no reason not to suggest incentive spirometry, the data to support its
use is quite limited and to say that it prevents ACS is a bit of an over-statement.
Public
New sentence will be added to the background. Ballas 1995 pg 100, line 8 and 9, replace the sentences and reference Belllet,
reference.
1995. Use of incentive spirometry in hospitalized patients with acute
chest pain has been found to prevent atelectasis and pulmonary
infiltrates. Have panel ok. DONE
100
Invited
101
14 The guidance on management of ACS seems appropriate, but fails to make mention 1. We recommend the addition of a statement
Public
of additional modalities of treatment which, in the opinion of experienced clinicians in indicating that there is some support in the literature
our group, appear to be effective adjuncts to the more traditional treatments indicated for the efficacy of incentive spirometry in preventing
here. We recognize that the the evidence for these treatment modalities is small, but the evolution of ACS in children who present with
we submit that they are in widespread use, and should be addressed here in order to VOC. As this modality is inexpensive, safe, and can
raise awareness of the need for further objective evaluation of outcomes. In particular, be performed easily by patients outside the hospital
we would like to see mention of incentive spirometry and non-invasive ventilation in
setting, its benefit would seem to far outweigh any
the setting of ACS.
risk or expense associates with its use.
I would simply add that the children with recurrent ACS predispose towards increasing 2. We recommend a brief discussion of the potential
airway obstruction (J Pediatr 2006;149:17-22), a fact that often goes unnoticed until use of non-invasive ventilation, particularly of BiPAP,
multiple episodes of ACS eventually produce the chronic restrictive pattern that many in treatment of children with severe or rapidly
of us see in advanced SCD. Also would emphasize the co-pathologies often seen in progressive ACS.
SCD, ie sleep disordered breathing and asthma, both contributing to hypoxemia and
sickling promotion. Thus the need for a good
database to generate long term data.
Editor: p.78, add new Rec. #13. 13. In euvolemic adults and children
with SCD and a VOC who are unable to drink fluids, provide
intravenous hydration at no more than maintenance rate to avoid
over-hydration. (ConsensusAdapted)
A recommendation to be written about incentive spirometry. Editor: revised p. 78 to include new Rec. #11: To reduce the risk of
acute chest syndrome in adults and children hospitalized for a VOC,
Encourage use of incentive spirometery while awake. (Strong
Recommendation, High-Quality Evidence)
Encourage ambulation and activity as soon as possible.
(ConsensusPanel Expertise) DONE.
73
8 consider adding a reference for this statement about pain during the lifetime
Invited
71
0 All the recommendations in the Managing Acute Complications of Sickle Cell Disease
needs to reformated for the emergency department. Many of the recommendations
are not appropriate nor appropriate in the emergency department.
Invited-Non
Disclosed
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outside of scope
No change
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4 Vaso-Occlusive Crisis
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Comments
5 Change the sentence to read--"VOC occur with variable frequency in individuals with
SCD and the first crises can occur during early infancy".
14 at the Florida meeting in 2012, there was dentist who presented data on increased
rate of hosp when VOC was accompanied by dental pain/infection. Wondered if you
considered including dental abscess in this list
Suggestions
Type
This section should consider adding requirements for Public
incentive spirometry, stool softeners, specific tools to
assess pain, and at least discuss the complicating
issues of tolerance, withdrawal, and pseudoaddiction.
Discussion
Suggestions are beyond the scope of this document. Issues No change
will be dealt with at the dissemination stage.
Recommendations should not be changed at this point.
Invited
No change
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no change
74
5 I have sickle cell anemia and I know from experience that treatment for this disease is
in desperate need. Plenty could be avoided if doctors and nurses would listen to the
patient. Usually te patient knows whats best for them. Im my experience the pca
works much better than on demand. Theres a high risk of delay and thats part of the
reason it doesnt work, mostly nurses dont have time to run back and forth pushing
meds and it helpd more when the patient is in charge of teir own dosing. It saves time
and it actually works. I only wish that hospitals would start pca treatment in the er.only
one hospital i know of does it. when you strt with giving push doses ifyou dont stay on
top of if and do it about every 20 or 30 minutes it doesnt work. with the pca the patient
is in control and can push every few minutes to get a small dose but the consistency
is what makes the treatment a success. when the pca is given in the er theres a
strong chance the pain will b under control and there will be no need for admission,
but if there is it most likely will be a short one because the pain is being controlled in a
successful manor.
Public
no change
74
5 Key Question - no guidance on dosage was given other than using the pt's protocol or
their home regimen. If this document is to be useful to a broad base of clinicians,
some additional information eluding to higher doses than what other pts with pain may
require is necessary.
Invited-Non
Disclosed
Do not agree with change because not in the scope of the no change
document. Also not possible to change key question at this
stage of document development.
Also comments on biases against pts who know what they need as being "drug
seekers" should be made. Similar to pts with CF who kow what antibiotic works or pts
with DM who know their insulin response - pts with SCD usually are knowledgeable
about pain control. Many of us who treat pts with SCD are aware of this but
sometimes get pressure from other clinicians and nursing staff about the doses we
prescribe.
74
8 other interventions apparently have been limited to medical interventions; no mention Include non-pharmacologic management strategies; Public
is made of or psychological, physical, or supportive management strategies for acute there is a large body of clinical and research
pain
experience describing the psychologic component of
pain experience that is being conformed by brain
imaging studies
No change
Action/Recommendation
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9 It is not clear that any non-pharmacologic studies were included in this review, or that This is a serious and potentially misleading omission Public
psychological expertise was included on this panel
from these guidelines; psychologic and nonpharmacologic treatment stategies need to be
included; there is also a wealth of information on the
efficacy of these interventions in other acute pain
disorders
75
Discussion
Recommendations are included for nonpharmacologic
interventions. Agree that psychological expertise was
missing, but can't change now.
Action/Recommendation
no change
Invited
No change
75
Invited
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75
Public
No change
76
3 In general, this section seems vague. Specific recommendations are not given as to
initial diagnostic workup, recommendations for opioid dosing. SCD-specific protocols
are referenced but not given.
Invited
No change
76
Invited
No change
76
8 Need more specific information that are clinically relevant with these
recommendations. Need to start with rapid assessment of pain - how/with what
tools?
Invited
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76
12 Atypical pain is misleading, do you wish to clarify as "atypical" for this patient?
Public
No change
76
12 by "if VOC pain is atypical" do you for that pt or in general for VOC?
Invited
No change is needed
No change
76
14 Words such as "rapidly" are vague and difficult to implement, particularly if building
computer-based clinical decision support systems that depend on explictly-defined
triggers. If the vagueness is intentional, would state that explicitly and/or provide
parameters to help guide implementers.
Fed
No change
76
16 Meaning of "prior analgesic" use is unclear. Both "analgesics used as outpatient for
current VOC and past history of analgesic efficacy and side effects" are important.
Clarify wording.
Public
No change
76
Public
No change
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No change
76
77
It would be quite useful in this section to give more specific recs on pain management
ie PCA dosing recs, agents of such orally and IV and dose equivalence tables. This
would be very practical and make the document more applicable to daily care
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5 We recommend continuation of long acting home opiates at HALF the home dose. If continue long acting opiates at half the home dose
long acting opiates are continued at full dose, patients baseline home doses tend to while inpatient.
escalate with each admission. By cutting long acting dose in half, as short acting
opiates are titrated down during the hospital admission, the patient will eventually go
below their home long-acting dose.
Type
Public
Action/Recommendation
No change
77
5 For acute pain, page 77, lines 5-6, is discontinuing short acting and using long acting
opioids the appropriate recommendation?
77
77
Public
77
7 Please use other drugs beside morphine as an example. Such as Fentyl, didlauded
etc. When given examples of the dose that is recommended please consider patients
that are already on high levels of opioid For an example when I am admitted I am
given 100 mcg of Fentyl to start then depending on the pain the dosage is escalated
up.
Public
No change
77
7 I thinkour adult providers are beeing punitive by withholding IV opioids. I gather the
panel thinks SC (IM?) is OK?
7 consider adding equianagesic dosing table here; you hope people know that but
Public
No change
Invited
No change
77
11 by what % over what period of time with what period of assessment? I know you have
said there is insufficient evidence to know but as long as you're giving expert
consensus, be more specific
Invited
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77
11 Gradually titrate down parenteral opioids as VOC resolves: Too vague for nonsickle cell experts to use as guideline.
No change
77
14 If not familiar at all, do not need to ask the question of time medication was taken and
the amount to prevent over sedation?
Invited
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77
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77
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77
20 not clear what diffference is bw first and third option in this list - protocol written by pt
SCD provider and individual protocol
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77
Public
Discussion
Yes, it is.
No change
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78
3 Additional comment for VOC
Comments
Suggestions
Type
Please include dosing recommendations for
Public
commonly used opiates in the acute care setting, as
many patients receive inadequate doses of pain
medications
Discussion
This was addressed in a previous comment.
No change
Action/Recommendation
78
No change
78
No change
78
Public
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8 another place where more specifics, sample protocols would be helpful; obviously
these need vary by pt, but in absence of knowing the pt or having indiv protocol,
people need recd on where to start with agent choice and dosing
Suggestions
Type
Invited
Discussion
This has been discussed in a previous comment
Action/Recommendation
No change
78
78
Fed
Public
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78
9 Here parenteral means IV? parenteral /prntrl/ Show Spelled[pa-ren-ter- say intravenous if that is what is meant
uhl] Show IPA
adjective Anatomy, Medicine/Medical, Physiology .
1. taken into the body in a manner other than through the digestive canal.
2. not within the intestine; not intestinal.
Public
No change
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78
78
78
13 same as above
21 maybe IS is somwhere else?
Invited
9. All patients hospitalized for pain, especially those Public
receiving opioids and/or experiencing pain in the
chest, back or abdomen, should be provided
incentive spirometry 10 puffs every two hours while
awake.
79
0 Since sickle patients can be medicated at triage, making sickle cell patients a high
priority may not be practical in busy emergency department.
Invited-Non
Disclosed
No change, this has been discussed and is out of the scope No change
of the document
79
Invited-Non
Disclosed
No change
79
0 Many Eds are not equiped nor experienced in giving PCA in the ED.
Invited-Non
Disclosed
No change
79
79
0 Exhibit 5 - Given many hospitals are trying to improve "thru-put" (i.e. decrease time in
ED, implement rapid assessment of need for in-pt care), this protocol should include
"consider arranging a direct admission for pt". We attempt to do this when possible if
it is clear that the pt is experiencing a VOC w/o complications. Our pts (adults) HATE
going through the ED. Since we have an IM Residency program, we often arrange for
a direct admission & have the residents see the pt aa soon as they arrive on the floor.
When we follow this process pts express increased satisfaction with pain control and
overall hospital experience.
Public
No change
Invited-Non
Disclosed
No change
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Comments
79
0 Exhibit 5 - Although meperidine should be avoided per recommendations, can a
comment on its occaisional use be included. Annecdotally, we have a few pts that we
use it with.
Suggestions
Type
Invited-Non
Disclosed
Discussion
Action/Recommendation
No change
As a person living with SCD (HbSS) & as a physician caring for pts with SCD, I chose
to "convert" myself from meperidine to hydromorphone due to recommendations
(trying to be an adherent pt). My pain control with hydromorphone (or morphine) has
never matched that of meperidine & the side effects I experience from the preferred
agents are significant. I had no untoward side effects from meperidine including no
euphoria. The primary reason my pain is inadequately controlled on the preferred
agents is that I choose to tolerate the pain over enduring their adverse side effects.
Perhaps this can be the subject of another study. I would be curious to know the
impression of persons with SCD who "grew up on" meperidine versus their current
management.
79
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79
Invited-Non
Disclosed
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79
2 having an algorithm such as this is much more likely to be used clinically than prose
above however it is not specific enough as to dx, disp criteria for setting (clinic vs day
hosp vs ER) and tx; also think there may be a word missing in the top line of the box
on the bottom - maybe add "or" between possible and within?
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80
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10 emergency room care is terrible. The waits are long and the staff act like they dont
care about you. They dont bother to listen to you, most of the time they think youre
just there for the drugs. Half the time they gie you a shot and send you have without
even examining you or asking any questions, they dont even do a blood test
sometimes. If they do and it looks good to them, u cant be in pain, but blood results
do not always justify if you should be in pain or not. Many times I have been judged to
the point where if they hear my name they just send me home. It needs to come to a
hault its rediculous. I had a fever of 103+ and i had to wait in the er for 3 hours before
I was seen, then when I was finally seen I was so ba off i was uncontious for the next
few days. I woke up in icu in the worst shape of my life, I had pneumonia on top of a
crisis . i stayed for a month. theres no way my care shold have been delayed that
long. they wouldnt even give me oxygen.
Suggestions
Type
Public
Discussion
Action/Recommendation
This is commentary
No change
81
81
Fed
Invited
No change indicated
Urinalysis has been addressed with a change. No further
change is being made.
No change
No change
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81
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81
14 I question the use of oral antibiotics. I'm concerned that antibiotic overuse will lead to
increased resistance and that antibiotic use gives a false sense of security to
caregivers and healthcare providers. Also, there are no recent studies that I'm aware
of to support antibiotic use in this setting.
Public
81
15 possible to be more specific than not appearing ill? Like maybe not meeting SIRS
criteria
16 Any consideration to recommend admission for very young patients with HbSS (ie,
patients < 1 year age who are not fully immunized with PCV13 and HIB vaccines)?
Invited
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No change is needed.
No change
81
81
16 per Willimas
I would use 40 deg C
16 Feel that no strong data exists in regards to how high fever is and risk of sepsis;
Believe statement should be "consider hospitalization for fever greater than or eqial to
39.5"
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4 As written AKI is not sufficiently distinct from MSOF or renal problems described
under chronic complications, consider consolidating
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9 RE: "(e.g. glomerular injury such as renal papillary necrosis or sickle cell
nephropathy.)" renal papillary necrosis is not a glomerular injury. Furthermore, renal
papillary necrosis often does not meet the panels definition of AKI (rapid rise in Cr
and reduction in GFR)
Suggestions
Clarify wording.
19 helpful to know
8 key question should relate to diagnosis or management of AKI not to ESRD
Type
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The panel disagrees that this should be consolidated.
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11 Rec. 2 - "Do not give RBC transfusions to treat AKI unless there is evidence of acute Add to recommendation: "...or a significant
multisystem organ failure." This recommendation ignores an imporant potential
exacerbation of anemia."
indication: acute exacerbation of anemia.
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12 Suggest omitting SEVERE PAIN here as one of the components of MSOF; above the
panel concludes correctly I believe that there is no data for transfusion in painful crisis
yet here it appears that they are endorsing transfusion for "severe pain" when in
reality it is for the MSOF.
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0 Consider consolidating all the priapism information here since prolonged priapism is
the organ function risk, but recurrent stuttering priapism also needs management.
Recurrent prolonged priapism needs chronic management as well and you omit it
from the chronic chapter.
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1 We are strong proponents of early aspiration/irrigation. I'm not sure I would rely on
urologists to do it without urging
8 Given the real possibilityconcern that a SCD patient could die while the provider is
wading through all the information in this sub-chapter, I would suggest the various
complications be listed in outline form with respective S&S and for possible AHS or
AIC an indication in BOLD that this is an Emergency situation.
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20 In priapism section it would be much more helpful if doses and recs were given for
medical management of priapism ( ie terbutaline, pseudo-ephedrine
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20 There is no rationale for waiting 4 hours to treat an episode of priapism.
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Recommend treatment be initiated as soon as the
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patient presents for medical evaluation and therapy.
Patient who have repeated episodes should have a
treatment plan so they can also initiate treatment
immediately when they recognize an episode is
beginning.
Discussion
There is no evidence for waiting less than 4 hours either.
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1 Surprised that oral pseudoephedrine was not presented as option here prior to/in
conjuction with caling urology
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1 consultation should be with a urologist who is familiar with SCD. Consider adding
consensus recommendations on specific medical interventions, including irrigation
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6 There are several places where consultation with "experts" is recommended, but I see
no recommendations for those experts. As an example, for priapism recommendation 3 - consult with a hematologist - as a hematologist I would find this
unhelpful.
87
8 Hepatobiliary Complications: Cirrhosis and liver failure are growing causes of death in This should be mentioned somewhere in the
Public
SCD.
document. Screening for cirrhosis and appropriate
liver transplantation is often delayed in SCD.
Patients can be cured from liver failure and should
be referred appropriately (Ref: Hurtova, et al.
Transplantation for liver failure in patients with sickle
cell disease: Challenging but feasible. 2011).
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15 When I was a patient at the childrens hospital I never had to wait because of my
illness I was always pushed to the front. It we were treated that way as children what
was the point if when we got older we would be tossed to the side like theres nothing
wrong with us at all.People should start listening to the patients. I complained of
stomach pain for months, because i was on tranfusions my dr would turn me away
every time i showed up. i got a second opinion and turned out that i had gallstones, a
result of what was supposed to be helping me, transfusions. no one even told me
about the risk. But there really was something wrong and it was totally ignored and
had a chance to keep getting worse. i needed surgery. Ive had a blood clot because
no one bothered to find out what was wrong. Its got to stop. I hae been deemed a
drug seeker even, like most of us, but if thats all you can offer what else am i
supposed to expect. when youre in pain the only treatment is to be relieved, does that
make you a drug addict, dont think so. the last thing i want to do is pump my body full
of drugs on a regular basis but if thats the only thing that helps you just dont have a
choice.
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20 Do not find the data convincing that surgical intervention has better long-term
outcomes than medical management.
alogorithm good, but need to have more dirtion aobut what can be done in PCP office,
may divert staff away from regular office duties; thus, making it too expensive for the
bottom line.
3 compare with baseline population
19 Modify the sentence to read (AIC)---also called sickle cell hepatopathy, can occure in
individuals with SCD.
0 There are a few patients that we have taken care of that have chronic intrahepatic
cholestasis, as well as a couple of case reports to support this rare complication
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delete?
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4 order LFT, coags, cbc, retic, RUQ US
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5 This recommendation is redundant and should be deleted or changed.
Suggestions
change to getting a consultation from a
gastroenterologist with expertise in hepatic sickle cell
complications.
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9 This is a mismash of many causes of anemia and actually confuses the many issues
in transfusion of patients. Restructure and make it make some sense. Your discuss
ASSC and ACS here before you present and discuss them in full.
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1 Add acute blood loss as with renal papillary necrosis or from another site as a cause
for worsening anemia.
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21 Add sentence about risks of parvovirus B19 to pregnant personnel, other patients
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0 Page 99: ACUTE CHEST SYNDROME - A key question might be "when to consider
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4 Does this recommendation extend to children <age 2 years
6 Disagree with this recommendation, particularly with very young children
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6 Strongly disagree with this oversimplified rec. Short-term transfusion may be very
appropriate to reduce risk of death until splenectomy can be performed.
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6 "Avoid" is too strong based on clinical experience and antedotal reports that 6 month Clarify wording.
period of transfusions have a 50+ % chance of sparing splenectomy (ie successful
second chance)
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8 The Section on ACS suggests that incentive spirometry during VOC hospitalizations is
preventive. This should be noted elsewhere (e.g., in the prevention section)
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14 Acute Chest Syndrome
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Specific antibiotics should be recommended with
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dosing. Treatment for broncho-reactive lung disease
is indicated. Bronchospasm is difficult to detect
clinically. There is significant published data
documenting broncho-reactive lung disease during
acute chest syndrome. Relying on clinical detection
alone is not reliable. Techniques including peak
expiratory flow are warranted if available. Otherwise,
bronchodilators should be included. Patients should
be evaluated for acute pulmonary embolism if
appropriate symptoms exist. Patients are often
under or over treated for pulmonary embolism.
Recommendations concerning this and its therapy
should be included.
Discussion
This will be addressed in the Acute Pain section
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20 macrolides can be given IV. Why cephalosporin? If additional antibiotics are needed, ACS with a macrolide and additional antibiotics as Public
ampicillin, unasyn, zosyn, vanco might be reasonable. Or a quinolone instead of a
indicated
macrolide?
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20 "recommendation to start IV cephalosporin and oral macrolide":
Choice of antibiotics should be determined by local microbiological patterns and
individual needs.
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Suggestions
We recommend editing to add "start IV
cephalosporin or other broad spectrum antibiotic
along with an oral macrolide."
Type
Public
Discussion
Panel working on revsions to this section. This will be
covered in the revision.
21 The rationale for a goal O2 sat of >95% is not supported by the literature or common
pulmonary physiology management.
21 Why does it have to be an oral macrolide? Can it be IV if necessary due to patient
condition? I might change this to a macrolide, oral if possible.
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21 Oxygen to increase o2 sat to 95% may suppress reticulocytosis, and this risk should
be considered. Many authors feel 90-92% is sufficient.
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0 Page 102: ACUTE STROKE - A key question might be when to consider HCT.
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6 Poorly worded
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6 Would suggest modify the statement -people of all ages with HbSC and HbSB+thal
rarely have overt CNS events as HbSC and HbSBthal is associated with increased
stroke risk in middle age adults-rare to see in children and young adults (age <35 to
40)
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9 there are data now from the NIS that show hospitalizations for stroke among kids with example is Ovbiagele and Adams 2011
scd have falled in the Post STOP era
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16 The fact that data are limited does not suggest that TCD is not suggestive of stroke in Revise sentence
adults, as this sentence implies
2 There is a typo here are well. I think you mean goal of < 50% after a period of years
with a goal of <30%. At least that is what was published by Cohen. As it is now you
suggest that <30%=<50% and it is not.
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18 Acute Stroke
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Transplantation is effective therapy for patients who Public
have had stroke. The data is very convincing. All
patients who have had a CNS event should have
HLA studies done, and families should be offered
sibling-matched transplantation.
There is increasing data available using
encephaloduroarteriosynangiosis (EDAS). EDAS
has been studied in several diseases, and appears
beneficial. It should be discussed in the
management section for stroke patients with
moyamoya.
Discussion
This is beyond the scope of this chapter
Action/Recommendation
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18 It is worth mentioning that the most effective strategy at least in children is prevention
by annual screening with TCD and primary prophylactic transfusions
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19 Not all emergency departments have neurologic consultation available for emergency
consultations.
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0 Beyond these comments its a good review of basically a data free zone.
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really in adults
0 there are several case reports when I search multiorgan failure and sickle cell.
Search pubmed using 'multiorgan failure' and 'sickle Public
cell'
1 Modify the recommendation. Some individuals with stroke who have very low Hb can
Invited
be managed by simple transfusion alone. In other patients, a simple transfusion
should be performed first while exchange is being arranged. These recommendations
have medicolegal impact, hence caution is necessary.
This is not the appropriate section for this and is dealt with in No change
research gaps.
So noted.
No change
Add to line #1 "Perform simple or exchange transfusion"
INSERT COMMENT THAT THIS REQUIRES PANEL
REVIEW.
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6
Comments
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anticoagulant agents regarding aspirin, since aspirin
is recommended in patients with MoyaMoya disease.
Discussion
Change covered in previous comment
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106
6 Would not recommend avoiding anticoagulant therapy in patient with SCD and
ischemic stroke if they have clear indication-such as atrial fibrillation or another cause
of embolic stroke or cerebral sinus thrombosis
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10 In children and adults who have had a stroke, initiate hydroxyurea therapy if
transfusion therapy cannot be provided. (Moderate Strength, Low-Quality Evidence)
I do not think this recommendation should be given. Maybe this is the panel expert
recommendation, but I do not think there is evidence for this.
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10 There is no mention of the strokes that occurred in the Hydrea arm in patients on the Please mention the evidence of recurrent strokes in Public
SWITCH study. Even though the primary endpoint of the study was not stroke, only
the SWITCH study and make recommendations
patients switched to hydroxyurea had recurrent strokes and no patients on the chronic keeping that trial in mind.
transfusion arm had a stroke recurrence. The panel has ignored this important RCT,
upon which a strong recommendation should have been based.
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10 very limited data to support this recommendation, including SWiTCH study results.
Why not consider stem cell transplant?
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11 Wording is confusing/ambiguous.
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In children and adult who have had a stroke, initiate Public
hydroxyurea therapy if transfusion therapy is not an
option due to other medical complications
Discussion
This is already revised based on earlier comments
No change
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8 Would consider separating the recommendations for children and adults for regualr
transfusions and hydroxyurea as almost all of the evidence is in children/pediatric age
group for first stroke and also ischemic and hemorrhagic stroke may differ
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16 Any patient with multi-organ system failure needs to be seen by a critical care
specialist and be in an ICU setting.
17 The transfusion and exchange should be moved up to the 2nd or 3rd
recommendation.
17 MSOF should be managed in a hospital setting equipped with an intensive care unit.
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14 helpful to know
3
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After "nerves III and V." add: "Medical management Public
should include prompt transfusions or exchange
transfusions to prevent further orbital ischemia,
which in SCD can occur along with an infective
etiology of the orbital syndrome."
No change
Recommendations are not apporpriate in this section. There No change
was not enough evidence to make a recommendation about
using transfusion to manage these acute complications.
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The team has covered this issue as much as possible in the No change
chapter. Additional content is out of the scope of the chapter.
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Thank you
This is beyond the scope of this chapter.
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3 Is it ethical to do a study of open vs. laparoscopic cholecystectomy today?
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This has been addressed in a previous comment
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1 from a primary care standpoint, I wonder if there was any SCD specific evidence on:
1)nutritional concerns or recommendations, 2) exercise limitations/adaptations given
AVN, issues of temperature disturbance triggering VOC 3) dental management given
risk of infection, ?exacerbation of VOC 4) sleep assessment, recommendations given
increased risk/impact sleep apnea 5) mental health assessment/management given
high prevalence chronic pain. I know these may not all fit into the chronic
management section - some better for health maintenance
INV
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1 Does each chapter need to repeat of the general introduction and methodology-It
makes the entire guidelines longer and more challenging to read
IND
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10 Would add reticulocyte count to the CBC for diagnosis of transient red cell aplasia
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3 What "clinical outcomes" are you referring to---pain? ACS? I'm assuming these two because that's what you started
the chapter with.
9 Why limit the use of hydroxyurea for other disorders to the 1980s? Typo?
6 Please reference the "exhibit 8" table in the text about evidence of harm--make it clear that you review potential
adverse side effects.
17 I could not follow this statement, as BABY HUG was a clinical trial and did not require 3 crises per year as an entry
criterium
4 The strong recommendation with high quality evidence for treatment of infants and children with hydroxyurea is
overstated and not consistent with the opinion of most pediatric hematologists. The BABY HUG study was designed
to demonstrate a reduction of organ system damage, and failed in its primary objective, which was chosen to provide
strong evidence for the use of hydroxurea, and which was felt to be a demonstration necessary for a definitive
outcome. The duration of treatment (2 years) was not sufficient to guarantee the safety or efficacy of long term
treatment and is based on less than 100 patients treated with hydroxyurea for two years. This makes a broad and
strong recommendation very tenous. The BABY HUG Lancet paper recommended that treatment be offered to all
patients, a more reasonable conclusion. We recently obtained expert opinion from 17 pediatric hematologists at 17
centers, which indicated that 15 of 17 (88%) did not agree with treatment of all children with hydroxyurea at an early
age. This opinion was obtained in April 2012 at the SIT Trial investigator's meeting, well after publication of the BABY
HUG results and with the purpose of assessing the effect of the results on this opinion. This indicates that the
majority of the pediatric hematologists in the SIT Trial do not agree with universal treatment of all infants and children
with hydroxyurea.
Suggestions
Clarify statement
Type
Invited
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Discussion
"...outcomes, especially pain and ACS, Done
..."
Change 1980's to "for several decades Done
prior to its use in SCD"
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Change recommendation to
Public
"hydroxyurea should be offered to all
infants and children with SCA."
Recommendation would be considered
Moderate, evidence as well.
Done
This is about recommendation #5 on Done, but grading is not the same for both age groups. One is
page 187. We will recommend to offer strong rec, high, the other is mod rec, mod. Added query to
treatment, but keep as
file requestijng clarification.
moderate/moderate. Combine the age
groups since the grading is the same.
Change recommendtation first
statement to "In infants 9 months of
age and older, children and
adolescents with SCA"
The recommendation for treatment of infants appears to be stronger than for adults, which seems odd. There is also
a disconnect in childhood, with a weaker recommendation for children over the age of 42 months. Should the reader
consider discontinuation at 42 months?
The following is a more elaborate discourse on this issue that I shared with the BABY HUG investigators in responding
to Letters to the Editor in Lancet, and may be of help:
"I do think that there are two issues that we should separate:
1) What does BABY HUG tell us, critically evaluated; and
2) What is the most reasonable course of action for our patients, given the present level of evidence
186
... During the deliberations on the design of BABY HUG, I remember several feelings that were expressed by many
people:
1) Simply demonstrating that events could be reduced by HU would not be a convincing endpoint, as this was almost
assumed from previous studies in adults and children. It was the low-hanging fruit, but not a convincing endpoint.
2) The endpoints were chosen to show that organ systems could be protected, which was felt to be necessary to
provide further evidence that the drug should be used early in life.
3) Demonstrating safety was of tantamount importance.
19 Definition for severe ACS. IS one recurrence enough to recommend HU?
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189
9 "Give maximum of 35 mg/kg/day or until mild myelosuppression is achieved. This dose can be considered maximum
tolerated dose." It is unclear whether doses higher than 35 mg/kg/day are recommended until there is mild
myelosuppression. Also MTD deserves a clearer definition separated from the proposed maximum dose . Are you
implying that the MTD is the dose above 35 mg/kg/day at which there is mild myelosuppression or any dose at which
there is mild myelosuppression? First, MTD was originally thought of as a dose above which there is REPEATED
myelosuppression, not just once. Second, MTD is NOT a fixed characteristic for all patients; some children who had
repeatedly been intolerant of doses lower than the maximum dose have been able to tolerate increases above their
presumed MTD when challenged months later. (this may reflect the concomitatnt effect of other causes of
myelosuppression, e.g., viral suppression that may take several weeks to resolve. Third, why is the MTD defined in
terms of mild but not moderate or severe myelosuppression?
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12 Need for hydroxyurea monitoring every 8 weeks seems excessive- in "real life", it will not happen! Toxicity is usually
evident early, but once patient arrives at therapeutic dosing, cytopenias are uncommon and rarely require dose
adjustments.
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Done
189
12 "Stable effective dose": What is the meaning of effective? A weakness in HU therapy in SCD is the lack of definition of
a therapeutic goal. If an intermediate goal such as Hb level were used to guide the treatment, clinicians could easily
use that to adjust doses until the goal is reached. For example, if Hb 10 were selected as a "surrogate" therapeutic
goal, clinicians would increase the dose until Hb 10 or the maximum dose was achieved, then assess the clinical
benefit over time as that Hb level is maintained with dose adjustments. That Hb goal will be achieved at different
doses of HU for different patients; the lowest dose at which that Hb level is achieved would be defined as the lowest
effective dose (LED), a potentially useful safety feature in HU therapy. Waiting for decreases in frequency of pain or
ACS in an individual patient is a very imprecise definition of "effectiveness" since these events may not occur that
frequently. This is especially important since HU therapy is being recommended for ALL infants and children. In an
infant without a long history of complications, how would the clinician assess the value or effectiveness of the therapy?
Treatment or no treatment, frequency of dactylitis decreases over time. I suggest a revision of the dosing protocol to
base it on an easily demonstrated effect such as Hb level.
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190
190 5-6
191
0 more important than monitoring CBC for neutropenia is pt education around febrile illness.
Use of Hydroxyurea - Recommendation states "For the patient who has a clinical response, Hydroxyurea therapy
should be continued indefinitely."
15 panel sttes "data are needed concerning the effects of hydroxyurea therapy during pregnancy". Is that ethical to do subject an unborn child to potential harm of a known chemotherapeutic agent?
Public
Done.
191
18 It seems an important factor to study would be impact of the way HU is presented to the pt esp in terms of
risks/benefits; what is most effective communication in terms of discussion and written materials
174
3 The two introductory paragraphs seem out of place here--you discuss pain and then respiratory complications/ACS.
But the chapter is about hydroxyurea. How do these topics relate? I'm assuming that the reason these two
paragraphs are in here is because there is evidence to support the use of hydroxyurea in these two
instances/outcomes. But need to make this clear. If this is true, then at very minimum consider including
subheadings that clearly indicate why these two first paragraphs are in here....
175
7 Hsieh
reference
182
1 The table "exhibit 7" is very helpful, but need to reference it in the appropriate section in the text
178
186
12 General question: Is there any reason that universal education on hydroxyurea should not be recommended to all
patients with sickle cell anemia?
186
12 In this HU section it would be nice to comment and give recs on 1.)need to monitor electrolytes and LFTs If any 2.)any
worrisome drug/drug interactions to know about 3.) use or non use in patients on transfusion protocols 4.)efficacy or
nonefficacy to decrease stroke recurrence, priapism, pulm HTN etc...
190
8 The format of this future research section is different from that in the other chapters. It should be reformatted with
bullet points.
Missing in
list
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Done
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Public
Hsieh MM, Kang EM, Fitzhugh CD, Link MB, Bolan CD,
Kurlander R, Childs RW, Rodgers GP, Powell JD, Tisdale
JF. Allogeneic hematopoietic stem-cell transplantation
for sickle cell disease.
N Engl J Med. 2009 Dec 10;361(24):2309-17.
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Public
Interesting suggestion for a consensus 10/4: The following will be the first recommendation
statement. Agreement on this.
with renumbering of the others: "Educate all patients
with SCA and family members about hydroxyurea
therapy. (Consensus Panel Statement)." DONE
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18 neuts >2.0 is a generous cut-off and may limit dose escalation unecessarily. Many hem amd hem-onc physicians are
comfortable with neuts 1.5.
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183
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Disclosed
179
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Good catch.
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13 Could mild to severe pain events be defined for clinicians using these guidelines?
183
6 Should rash be mentioned? Increased skin pigmentation is a fairly frequent, though mild, AE
Invited Not
Disclosed
We could add it as another side effect. No change needed. Mild skin pigmentation is not a patient
WE need to back and look at what the important outcome in this content and we typically do not
evidence is.
include it in evidence profiles (only serious side effects are the
ones considered as tradeoffs for stronke/mortality/pain crises.
181
174
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Public
Good catch.
Will address this statement in the
appropriate section of the comment
file.
175
7 Editor Note: No line and page number provided. Used line and page number of commenter's previous comment.
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Skip, no page/line
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19 Need to include a subheading to this paragraph about HbF---why do you talk about HbF? IF this is tied to the
mechanism of action of HbF, then include a subheading here
Should we not
include HbSC?
176
177
179
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7 Overall costs were not statistically different between the two groups, so why is it relevant to just inlcude costs for pain
hospitalizations
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Disclosed
Keep as is.
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6 Is there really moderate evidene that hydroxyurea does not cause cutaneous ulceration in adults or children? The
RCTs were not powered to show a differnce in cutaneous ulceration rates and there is a rate of 1% or so in other
populations treated with HU
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8 The reproductive effects of hydroxyurea are not adequately addressed. There are reports on azoospermia with long
term use, and it should not be given to pregnant women, unless there is evidence that hydroxyurea has no
teratogenicity. I am a big proponent of hydrozyurea since its benefits outweigh the risks. However, we should not
become incognizant of the harmful effects or ignore mentioning them.
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12 Hydroxyurea Recommendations: This is a detailed, well-developed review of hydroxyurea and its recommendations.
We are in agreement with these recommendations.
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13 In Voskaridou et al 2010 paper, hydroxyurea was shown to increase survival of the more symptomatic SCA patients
In all patients with SCA, treat with
over those patients not put on hydroxyurea because their symptoms were considered mild. This argues that adult SCA hydroxyurea.
patients should be on hydroxyurea regardless of symptom severity. From the BabyHUG study, we know that
symptoms of SCA begin early in life, even if the symptoms are not clinically obvious. I believe it can be stated that
there are no SCA patients who are asymptomatic. Therefore, why restrict the use of hydroxyurea to adult patients who
have severe symptoms? The guidelines do not place restrictions on the use of hydroxyurea in children, why restrict
adult usage of hydroxyurea when survival benefit was demonstrated not once, but twice, in adult patients? Limiting
hydroxyurea therapy in adults also contradicts guideline on p. 190 line 5 "For the patient who has a clinical response,
hydroxyurea therapy should be continues indefinitely."
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4 1. If this recommendation is intended to suggest that all children should receive HU regardless of disease severity"
then this should be emphasized.
2. Would recommend specifically stating patients with SS disease if that is what is intended.
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4 I would recommend modifying the force and strength of this recommendation as the BABYHUG study that serves as
the evidence did not demonstrate statistically significant findings either of its primary endpoints. The acute
complications were all secondary endpoints (threshold for significaince set at p<0.01 in the analytic plan for the study).
Only dactylitis, all pain events, and pain only events were below this threshold. Approximately 2 children would be
need to be treated for a year to prevent one pain event. Also is this recommendation for fixed HU dosing (20
mg/kg/day as used in BABYHUG) or dose escalated HU based on hematologic parameters?
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4 Do you include adolescents here? If so need to specify (confusing because you mention the strength of evidence for
specific ages and adolescents right below)
4 This recommendation is premature and misleading for asymptomatic infants and young children and should not be
included at this time
4 I do not agree with the strong recommendations for infants, treat with hydroxyurea regardless of complications
5. In children with SCA, treat with
nor that the evidence is high quality for 9 - 42 month olds. The infant data is primarily comprised of the HU-SOFT (21 hydroxyurea regardless of clinical
patients, 11 who had up to 6 years of therapy) and BABY HUG trials (67 on HU, 2 years of therapy). I dont think that severity
this amount of experience is equivalent to the decades of work and long-term monitoring of the MSH and do not
believe that NIH should be making such a strongly worded guideline based on this small body of research. I also dont
think that the FDA would find this level of evidence convincing for the approval of HU for infant use.
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4 As a comparison, even though the STOP study showed that RBC transfusions reduce stroke incidence in children with Clincal registries of children with SCA Public
high TCD velocities by an impressive 90%, there were many critics who were concerned about over-treatment of the treated with hydroxyurea should be
roughly 50% of individuals with high TCD velocity who might not ever get a stroke and it took another 5+ years before developed and maintained to be able to
TCD screening and transfusion therapy became more mainstream in clinical practice. In the case of universal HU
adequately monitor efficacy and longtherapy for all infants, how many of the potential patients have high risk for severe outcomes, what outcomes can we term safety.
be confident in knowing HU will help, and what are the potential risks of lifetime HU therapy beginning in infancy?
187
4 The lack of published reports about potential toxicities in the infant group is not equivalent to the demonstration of
long-term safety. I am concerned that infants, with their rapid rate of growth, will be at increased risk of malignant
transformation beyond what has been observed in children > 5 years and adults. Of course, none of this has been
documented yet, due to lack of sufficient long-term follow-up studies. At the current time, I believe that treatment of
asymptomatic infants with SCA is still in the experimental phase, and fully agree with having a BABY-HUG follow-up
study, and the newly funded R34 study of the effects of HU on the development of CNS complications in infants with
SCA. I strongly agree with the Opportunities for Research that a national registry would be invaluable to fully
understanding the effectiveness and safety of HU, and I believe that this should be a funding priority. In addition,
more basic-translational research is needed to better understand the mechanisms of HUs beneficial actions are
there direct effects on inflammation, vascular remodeling, ischemia-reperfusion, the hallmarks of SCA
pathophysiology?
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4 While a 50% reduction in painful episodes in BABY-HUG is impressive, it is unlikely that SCA infants in the general
population will experience the same high rate of treatment adherence that was observed in a well-organized clinical
trial environment. Something as simple and indisputably life-saving as penicillin therapy has been reported to have
adherence rates as low as 40%. I am concerned that universally treating asymptomatic infants with SCA with HU will
lead to a (1) significant drain on the healthcare system, in terms of monitoring and tracking of adherence, toxicity and
efficacy, and social service interventions for non-adherent children, (2) early treatment adherence burn-out of
children and caretakers if there is not an obvious benefit for all children, and (3) exposure of many more children and
families to a potentially toxic medication (pregnant family members, sibs, healthcare workers, etc.). I also think that it
is very important to have a better understanding of HU knowledge, attitudes and acceptance of the patients and
families as we embark on the new era of possibly giving HU to all.
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7 The change in recommendation at age 42 months may be confusing-will this encourage some providers to stop HU at
42 months?
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13 You mention use of an established "protocol"--where are we to find these? Need to make reference to them or
resources available to find. This otherwise would be a big barrier for any PCP in a busy clinic.
1 this section and the section above on recommendation are both very clear and would be manageable to follow for
primary care physicians. Specific rec on starting dose, protocol for escalation and recd lab testing is all very helpful.
Interesting to think about techniques to ensure adherence with lab monitoring at the population level. I assume easiest
method would be to tie monthly refills to lab testing, but do not know if this has been studied.
188
188
188
12 The difficult question of what to do when they WANT to have a child with their partner is being dodged. How long
should they stop HU therapy? Or should they stop contraception, continue to use HU and stop at the earliest suspicion
of pregnancy?
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18 SCD in U.S. primarily affects African Americans who may already run low wbc. Can goal ANC be any more lenient
than 2000?
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18 ANC of 1250/mm3 was used in BABY HUG, not 2000/mm3 - higher cutoff of 2000/mm3 will limit therapy
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18 What is the rationale for using ANC >2000 as a cutoff? In other heme-onc situations, ANC>1000 is considered safe.
Even in early data on fever and neutropenia cancer patients, increase in infections was noted for ANC<1000.
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8 rationale for 8 week interval in dosing change not understood. What was the reasoning for this?
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12 Page 189 - is there evidence for testing counts every 8 weeks on hydrea ? This seems unneccessarily frequent in
patients who are stable on chronic therapy
13 Are there data to support the monitoring with CBC and differential every 8 weeks (vs. a shorter interval)-also would
consider adding a reticulocyte count to this monitoring
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13 For patients with a stable effective dose, I have spaced monitoring visits to every 3 months, simply because 3 month
intervals coincide with administration of Depo-provera.
No change
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0 no recommendation given on monitoring any biochemistry whilst on drug. Does this never need checking?
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190
0 What is the impact if receive transfusion while on HU should this be addressed to prevent confusion
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0 Question (1) Are results from non-clinical trial long-term "use" of Hydroxyurea going to be the data used to determine no recommendation
whether there are adverse effects?
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0 Question (2) Should "Monitoring Therapy" include organ function after the initial 6 months use and then annually?
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5 Seems to contradict benefit in MSH follow up study of reduced mortality even in patients who stopped HU
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7 Are there any times that HU should be stopped in the hospital-severe infections?
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1 Is there any reason severe chronic anemia alone cannot be declared an indication by itself? This definition includes
symptoms which many patients underscore or over time accommodate quite well.
187
1 Is ANY level of anemia, as long as symptomatic, appropriate to consider treatment with HU?
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9 Folate should be given while on hydroxyurea, as MCV will not longer be indicator of folate deficiency and could mask
treatment effect
14 What age cutoff do you consider adult--18 or 21?
13 Discrepancy between adult and pediatric recommendations should be further explained, possibly eliminated- why start
ALL children on HU at 2 years, while waiting for adults to have 3 hospital admissions/year? I understand the data
sources, but this discrepancy makes no sense clinically.
no recommendation
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Consider severe anemia as indication Public
alone due to known disadvantages of
chronic anemic state. Many patients do
not report symptoms but have made
lifestyle changes (some they are not
even aware) that are due to the effects
of anemia were they challenged to
those tasks/activities.
No change
No change at this time
188
184
186
6 thank you!
13 Are the events in this recommendation linked with admissions as in the MSH study?
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Clarify if pain events mean hospitalized Public
events as many patients deal with
significant pain at home.
Answer is no.
No change needed
No change.
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0 the boxed area does not add anything to the document. I do not know why remove boxed text from each section
it has been duplicated at the start of each section,
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0 Boxed introduction should not start each chapter of the report. It should
only be in once at most, and again should not be necessary in this type of
document.
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Action/Recommendation
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0 Figure
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1 Consider using the box at the beginning of each section to summarize the
key findings of the chapter instead of stating the same intro over and over
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1 The first line suggests that sickle trait meets the definition of SCD as sickle SCD encompasses a group of disorders
Public
hemoglobin is present.
characterized by the presence of the sickle
hemoglobin mutation on one allele, and a
second abnormal beta-globin allele
allowing the sickle hemoglobin to
polymerize.
21
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Discussion
Definition is needed as a reference in each chapter in case they No change
are used in isolation.
Need to add something to the definition. Add a sentence. There Definition has been updated.
are other less common genotypes such as Hemoglobin S/D or
hemoglobin arab.
No clarification is needed here.
No change
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1 The explanation of rationale for screening (p22 1-5) is probably
unnecessary and can refer to standard texts. The specific items are
redundant and not clear
22
8 What is "Mayo-KER"?????
22
22
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1 I'm not sure that adding the narrative or diagram with Healthy People 2020
objectives really adds much here, on the heels of talking about evidence
based guidelines. IF you keep this in, need to clarify whether or not
Healthy People 2020 objectives are evidence based or not, and/or
describe WHY you include them, where they come from?
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4 This is a very nice Exhibit. Well written, comprehensive and commendable. No suggestions.
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Action/Recommendation
No change
We cannot change the HP 2020 objective wording.
No change
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16 delete "extremely high" for the sentence to read "have a very high risk of
septicemia in absence of appropriate prophylaxis"
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Comments
17 Inapprpriate Ref." Gaston et al".: this important intervention study was
based on previous studies reporting high incidence of these infections Barrett-Connor (1971), Seeler (1977), Pearson (1977), Overturf (1977),
and Zarkowsky (1986).
Suggestions
Type
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Discussion
This needs to be verified with the evidence report for this
chapter. Change is TBD
Action/Recommendation
DONE. Retained the Gaston et al. 1986 reference and added
Zarkowsky HS, Gallagher D, Gill FM, Wang WC, Falletta JM,
Lande WM, Levy PS, Verter JI, Wethers D. Bacteremia in sickle
hemoglobinopathies. J Pediatr. 1986 Oct;109(4):579-85.
Additional changes: Pg. 24, line 12, after "In some cases, a
literature search was not conducted" add "due to low anticipated
yield." p. 24, line 15: Change title of section to "Prevention of
Invasive Pneumococcal Infection." p. 24, line 16: after "Young
children with SCA have" delete "an extremely" and add "a very." P.
24, line 17, after Gaston et al. 1986 ref, add Zarkowsky HS et al. J.
Pediatr 1986; 109:579-85 ref. p. 24, line 19: after "with HbSS" add
"early in the first year of life" and delete "before 3 months of age."
Note: Panel also wanted to add "in the absence of appropriate
preventive strategies" prior to Gaston et al. and Zarkowsky
references, but I did not make this change since the comment
above proposed making the final sentence: "Young children with
SCA have a very high risk of septicemia and meningitis in the
absence of appropriate prophylaxis (Gaston etc.)."
24
18 "result from defective or absent splenic function that typically has its onset
in people with HbSS before 3 months of age"-the age of onset is usually
later in most-Median age of decreased splenic function was 13 months in
CSSCD
No change
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24
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This is not what the literature says, but we respect that it is the No change
person's experience.
25
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Need to delete the whole sentence, "Prevention is effective.is Done 1/10/13 However, pls note that a handwritten edit was
low"
submitted to change this sentence to read, "Preventive strategies
are effective, so currently" Since the sentence was deleted, I did
not make this change.
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Comments
13 Pen V K 125 mg BID between 2/3 months BID until 3 years
of Age and 250mg BID from 3 years of age to 5 years of age
unless specific indications.
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No change suggested here.
Action/Recommendation
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25
20 "Do not administer regular penicillin prophylaxis to people with HbSC and
HBSB+ unless they have had a splenectomy". I do not think that lack of
evidence in the PROPS study is enough to give this recommendation.
Invited
This is a controversial topic and is debatable. This is a weak rec No change made after all. The background clearly states low risk
with mod quality evidence for this reason. This is a good point. of invasive infection in HbSC and HbSB+. No data support use of
Would like to use the word "consider discontinuing" Team would prophylactic penicillin in these genotypes, as indicated in the
like to work on wordsmithing this. Wording will be drafted for
Summary of the Evidence. DONE
background.
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20 I do not understand when it is said that PROPS has low evidence because
of "imprecisions". Please define what these imprecisions are.
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4 Why not add the numbers for the statistically significant decrease in
pneumococcal morbidity instead of just the non-statistically significant
difference in mortality? This would provide demonstrable support for the
recommendation to give prophylaxis...
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15 Clarify that the dosages for penicillin are per dose, not total daily dose.
Fed
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16 Clarify whether 5 year olds should receive penicllin or not (i.e., should
penicillin prophylaxis end at the 5th birthday or the 6th birthday?)
Fed
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16 Use of PenVK prophylaxis for all sickling genotypes is a common practice Clarify wording.
in many centers. Until prevalence of IPD morbidity and mortality becomes
equal to general population, a sentence to acknowledge use of PenVK
use in other non HbSS patients may be used.
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Discussion
We are not saying that they cannnot do it.
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18 Basis for discontinuation of penicillin is weak and may still leave older
children with SCD at risk of peumococcal infection higher than that of
healthy children. PROPS II compared children with SS with each other.
The rates for pneumococcal bacteremia or meningitis, 0.33 per 100 pr-yrs
for penicillin group and 0.67 per 100 pr-yrs for the placebo group far
exceeded the rates in the healthy childhood population. The increased risk
faced by children with SCD was not completely eliminated even in the
Penicillin group in PROPS I. Err on the side of caution without causing
unintended harm.
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Comments
18 see line 45 above - need similar clarification
Throughout the document there is lack of clarity about SS vs SS and S
B0thal. These 2 recs are example, "SS" should read "SS and S B0thal"
There are numerous other instances of this inconsistency throughout.
Suggestions
Clarify wording.
Type
Fed
Public
Discussion
This will be covered with a previous change.
No change
We will have to look at this throughout the document. Take this Change
back to panel to ensure consistency.
26
Clarify wording.
Public
We will have to look at this throughout the document. Take this Change
back to panel to ensure consistency.
26
Clarify wording.
Public
We will have to look at this throughout the document. Take this Change
back to panel to ensure consistency.
Action/Recommendation
27
0 The section is not clear in distinguishing renal tubular/medullary injury from See below for specifics
glomerular injury. Although it has been postulated that ischemic damage
in the medulla leads to glomerular hyperfiltration (the first stage of
glomerular injury) via prostaglandin and NO release, there is no direct
evidence to support that tubular/medullary injury is associated with or
results in glomerular damage. The statement Renal abnormalities can
start with defects in urine concentration and process with age to
microalbuminuria (pg 27, lines 16-18) is misleading, since there is no
direct evidence that urine concentration defects result in glomerular
defects. References and statements regarding prevalence of ESRD and
death due to ESRD are not accurate. (see below for specifics)
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27
27
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Comments
4 All children are immunized with Prevnar and H inf vaccine within first two
years of life. What evidence is there to support giving meningococcal
vaccine early and what is the risk of meningococcal infection before 13
years of age? What evidence is there to support the recommendation for
Pneumovax over and above penicillin prophylaxis at 2 years of age and
again at 5 years. These recommendations are made without any
evaluation of proof.
Suggestions
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Action/Recommendation
27
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27
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Done 1/10/13
27
27
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Needs to be clarified
27
10 The sections Screening for Renal Disease and Acute Kidney Injury are The panel should not suggest a causal link Public
not clear in distinguishing renal tubular & medullary injury from glomerular between tubular and glomerular injury, as
injury.
this has not been established.
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10 The recommendations and definitions are not consistent with the KDIGO Annual screening for albuminuria by spot
(Kidney Disease: Improving Global Outcomes) position statement in 2005 urine albumin/creatinine ratio should be
(Levey et al. Kidney International, 2005; 67:2089-2100).
included in the recommendation.
This position paper recommends albuminuria, as assessed by spot urine
albumin/creatinine ratios, as a marker for kidney disease. The rationale
for testing for albuminuria includes the fact that higher levels are the
earliest marker of kidney damage due to diabetes, glomerular diseases,
and hypertension, higher levels are associated with adverse outcomes,
including progression of kidney disease, and therapies that reduce
albuminuria are associated with slowing the progression or diabetic and
nondiabetic kidney disease.
This paper also defines the classification of chronic kidney disease (CKD),
stages 1 -5. Stage 1 CKD has normal or high GFR with a marker of
kidney damage (markers include albuminuria, proteinuria, and hematuria).
Screening for albuminuria is therefore required in order to diagnose Stage
1 CKD.
Type
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Discussion
Need to review what the Acute section states so that we are
consistent. Will see if we need to clarify/add anything here.
Action/Recommendation
Revision to this section submitted.
27
10 The section Screening for Renal Disease (pgs 27-29) recommends urine Annual screening for albuminuria by spot
dipstick only, which may detect gross proteinuria, but is insensitive and
urine albumin/creatinine ratio should be
also is unable to detect albuminuria. The later section Renal
included in the recommendation.
Complications (pgs 149-153) gives recommendations on further testing
and treatments when microalbuminuria is identified; however it cannot be
identified if not recommended as a routine screening test.
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27
14 The Statement that renal blood flow and glomerular filtration are elevated
in childhood normalize in adolescents and declines in adults is incorrect.
They are elevated in early life and decline throughout life.
27
14 The statement GFR and renal plasma flow are increased in childhood, Clarify wording.
normalize during adolescence, and decline with age
is incorrect. GFR and RPF are declining in adolescence due to ongoing
loss of renal function, not normalization of renal function.
27
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19 RE: "When significant proteinuria or azotemia is present, approx of
Correct reference and clarify interpretation. Public
individuals with SCD will progress to ESRD in less than 2 years (Herrera
2002). This is the wrong reference. Herrera et al. is a study of tubular
function in SCD pts with normal/supra-normal GFR. Herrera references
Bakir (Am J Nephro 1987) when stating when significant proteinuria or
azotaemia are present, approx half of the pts with SCA will go onto ESRD
in less than 2 years [Bakir 1987] however this quote is inaccurate. The
paper by Bakir examined 22 patients with biopsy-proven glomerulopathy
and showed that 11/22 died in 2 yrs (10/11 who died had renal failure vs.
5/11 who lived had renal failure). This is a small study of selected patients
with nephrotic-range proteinuria and shouldnt be used to claim that half of
patients with proteinuria (of any degree) progress to either ESRD or death
in 2 yrs.
Discussion
Will review and clarify this.
Action/Recommendation
A revision to this section was submitted. This sentence was
modified and the Herrera et al. 2002 reference was deleted and
replaced by Alvarez et al. 2006.
21 RE: Renal failure may occur in as many as 18% of individuals with SCD Correct references and interpretation.
[ref: Falk NEJM 1992]. This is the wrong reference. Falk et al.
screened 381 with SCD and showed 7% had elevated serum Cr. Falk
references Causes of death in SCD in Jamaica by Thomas et al. (Br Med
J 1982) when stating renal failure may occur in as many as 18%... Other
more recent studies have shown a lower prevalence of renal failure:
Powars et al, Ann Int Med 1991: Renal failure 4.2% in HbSS (median
age 23.1 yr) and 2.4% in HbSC (median age 49.9 yr)
Powars et al, Medicine 2005: Renal failure 11.6% in HbSS (median age
37 yr).
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0 The section on screening for renal disease (p 28-9) would benefit from at
least a brief sentence or reference summarizing non-SCD literature on the
ability of preventive interventions to slow the progress of progression of
ESRD. This wasn't clear to me.
Public
Will review
28
5 The screening question should not be limited to Cr and urine protein. The Include urine albumin/creatinine ratio in
utility of albuminuria must also be included, as this is a recognized marker key question.
of early kidney disease.
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Will review
28
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Will review
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28
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29
Comments
Suggestions
7 Additional information to include:
Include additional data in summary.
- Guasch et al. (Kid Intern 1997) compared albumin excretion rates in
HbSS adults with normal GFR and with renal insufficiency; he showed
albuminuria was significantly higher in the renal insufficiency group,
supporting the role of albuminuria as a screening test for renal disease.
- Albuminuria is prevalent in pediatric and adult SCD populations (shown in
numerous observational studies), and the prevalence increases with age
(McPherson Yee et al. CJASN 2011; Guasch JASN 2006). Albuminuria
detected in 1st 2nd decades of life; for HbSS: albuminuria in 7% aged 26yo; 20% aged 7-12yo; 35% aged 13-19yo. (McPherson Yee)
Type
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18 delete people
3 not clear if this statement includes Baby HUGS data on renal disease
Discussion
Will review this to make sure we used this reference.
ok
data not validated
Action/Recommendation
A revision to this section was submitted. The Guasch et al. 1996
refrence was included: Guasch A, Cua M, Mitch WE. Early
detection and the course of glomerular injury in patients with sickle
cell anemia. Kidney Int. 1996 Mar;49(3):78691. This is not the
same as the 2 references noted in the comment.
29
Invitedrewrite needed for entire section. Entire panel should weigh in. Submitted
Non
Evidence insufficient but still need to come to concensus. Will
Disclosed gather data and present to panel
29
9 "Screen all people beginning at age 10 for proteinuria using standard urine Add urine albumin/creatinine ratio to
dipsticks. When negative, repeat annually."
recommended annual screening and
- Proteinuria is not defined (what concentration is considered abnormal?) define threshold per KDIGO guidelines.
- The KDIGO (Kidney Disease: Improving Global Outcomes) position
statement for defining CKD states: Retain albuminuria as a marker for
kidney damage. They recommend spot urine albumin/creatinine ratio,
with a threshold for abnormal at >30mg/g. (Ref: Levey et al. Kid Intern
2005).
- In the later section on managing chronic renal complications (page 152),
recommendations are given for treating patients with microalbuminuria and
macroalbuminuria, therefore the screening recommendation should assist
in detecting albuminuria.
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29
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Comments
10 SAME COMMENT as above. URINE PROTEIN here is very difficult to
interpret. This entire section needs to be carefully reread to be sure that
the intent of the panel is clear. A sentence or two to discuss the ways
urine protein may be measured IS VITAL. Specifically while the
recommendation is understandable the exclusive use of dipstick rather
than urine microalbumin to creatinine ratios should be discussed here as
well as in the chronic disease chapter at the end.
Suggestions
Type
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Discussion
same as above items on this topic. Panel to assess after
research is done.
Action/Recommendation
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Submitted
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Submitted
29
10 NEED to also state the level of postive dipstick that should be considered
postitive. THAT is should trace protein be considered positive (no
probably not) but the panel needs to state. ALSO the further evaluation of
patients with 1+ protein should be listed here as well as in the chronic
disease chapter at the end.
29
29
10 Screen all people with SCD with urine dipsticks. Urine dipsticks is not a
very accurate method. Urine protein or urine albumin measureaments
over creatinine are more accurate.
29
29
10 I am not clear why the rec is for urine dip when later under renal disease
management you rec initiating therapy if microalbuminuria is present
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10 How did you come up with age 10? This seems arbitrary to me
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Comments
10 The recommendation for screening for proteinuria seems very weak.
There is nothing to address false positives, but more importantly, there is
nothing that tells the provider what to do if there is protein in the urine. I
would add a recommendation about what to do if a urine test is positive - is
it refer to a renal specialist? If no recommendation, then why screen. This
is very vague and therefore not very helpful.
Suggestions
Type
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29
29
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29
Discussion
same as item 85. Left vague so provider will seek consultation Submitted
with specialist
New renal revisions submitted. This issue not resolved. Editor please insert comment re: starting screening at age 2-5 yrs.
Submitted
Submitted
11 You have described here what to do if the screen is negative, but what do
you do if positive? Send them to a nephrologist?
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Submitted
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Comments
14 Point of clarification - Pulmonary hypertension is defined as stated above
by a mean PAP > 25 mmHg. At the 4th World symposium of Pulmonary
Hypertension at Dana Point in 2008, Pulmonary Hypertension was subclassified into 5 different groups based upon similarities in histopathology
and pathogenesis. Pulmonary arterial hypertension (PAH) is Group 1
Pulmonary Hypertension and accounts for approximately 50% of cases of
SCD related PH. The remaining patients have hemodynamics consistent
with pulmonary venous hypertension (PVH), also called Group 2
Pulmonary Hypertension. Both PVH and PAH are risk factors for mortality
in this population. The use of the terms PAH and PH interchangeably in
this document is incorrect, particularly since half of the patients with SCD
related PH do not have PAH at all.
Suggestions
Type
wouldchange the sentence "The remaining Public
patients have PVH or "mixed" PH
defined as mPAP 25 mm Hg, inceased
PCWP wtih an increased PVR."Would
reference the numerous guidelines
documents published in 2009 devoted to
the subject of diagnosis and treatment of
pulmonary hypertension so that the NHLBI
guidelines are reflective of them.
Discussion
This will be covered in the previous comment. Changes being
made.
No change
Action/Recommendation
29
15 The definition of PH was changed in 2009. The new definition is a mean Change this so that it is reflective of
PAP > or equal to 25 mm Hg at rest, the exercise part of the definition was current definitions
removed.
Public
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18 consider defining elevated TRV; proxy used by some but not = PAH. Often
very confusing to providers outside of the field
Invited
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Public
In this case, there is no change. Howerver, there needs to be a Is this done satisfactorily?
section in each chapter and in the Methods section and in
Introduction clarifying the evidence review periods.
30
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8 Would use the term dyspnea instead of the colloquial shortness of breath
Public
Done 1/10/13
30
10 The medical term for "passing out suddenly" is syncope. In PH, typically it
is exertional syncope. Most importantly, many SCD patients are
asymptomatic despite having abnormal echos (see Klings ES AJH 2008)
and many SCD patients have symptoms such as dyspnea but do not have
an elevated TRV. Many of the symptoms of PH are non-specific in SCD
patients and this underlies why screening all patients regardless of
symptoms is warranted.
Public
Done 1/10/13
30
10 The medical term for "passing out suddenly" is syncope. In PH, typically it Would also include in the PAH definition,
is exertional syncope. The key thing to point out in your description of
PCWP 15 mmg and increased PVR
symptoms is that many SCD patients are asymptomatic despite having
abnormal echos (see Klings ES AJH 2008) and many SCD patients have
symptoms such as dyspnea but do not have an elevated TRV. Many of
the symptoms of PH are non-specific in SCD patients and this underlies
why screening all patients regardless of symptoms is warranted.
Public
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Comments
14 This section needs to be updated with current references including Parent
F NEJM 2011 and Mehari A JAMA 2012. Additionally Gladwin MT NEJM
2004, Ataga et al., Br J Haematol 2006; De Castro et al., Am J Haematol
2010; Lorch et al., Acta Haematol, 2010. need to be added to support the
concept that an elevated TRV predicts mortality.
Suggestions
Discussion
The background will need to be revised to address some of
these issues and clarify the panel's recommendations about
screening.
Action/Recommendation
Rrevision to the PH section was submitted. This included
additional references, including Parent et al. 2011; Gladwin et al.
2004 among others.
Public
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30
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31
Public
Public
Agreed
We agree that the correct term is PH not PAH.
Done 1/10/13
No change
Public
No change here.
No change
31
5 83 studies are mentioned in this report, yet the quality of the data is felt to
be very low. While studies that directly compare the effects of screening
with no screening on clinical outcomes are lacking, we hold that screening
identifies a high-risk group of patients for whom SCD-specific therapies
(e.g., hydroxyurea, chronic transfusion, supplemental oxygen, anticoagulation therapy) may be indicated because they improve clinical
outcomes in patients with SCD-related co-morbidities, including mortality,
quality of life, and the frequency of vasoocclusive crises (VOC) or acute
chest syndrome (ACS). As part of the American Thoracic Society funded
Clinical Guidelines for the Diagnosis and Treatment of PH of SCD, our
group of 24 hematologists, pulmonologists and cardiologists felt that
screening was the only method of identifying this high risk patient group
who may be asymptomatic at presentation but still at risk for morbidity and
mortality.
Type
Public
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12 6% of the 30%?
14 Would use the reference McLaughlin VV from Circulation which was the
official guidelines document. Additionally, an inclusion of their
recommendation to pursue further workup for a PASP > 40 mmHg as well
as the use of echocardiogram to evaluate RV size/function and assess for
a pericardial effusion would be a more balanced presentation of the
literature and reflective of the use of echocardiography in PH assessment
clinically.
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Comments
14 Would use the reference McLaughlin VV from Circulation which was the
official guidelines document. Additionally, an inclusion of their
recommendation to pursue further workup for a PASP > 40 mmHg as well
as the use of echocardiogram to evaluate RV size/function and assess for
a pericardial effusion would be a more balanced presentation of the
literature and would be more reflective of the true use of echocardiography
in PH assessment clinically.
Suggestions
Type
Public
Discussion
This is beyond the scope of this chapter.
Action/Recommendation
No change
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31
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31
16 The median survival in the Castro study was 25.6 months not 2.6.
Public
Done 1/10/13
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21 Would include Ataga KI BJH 2006 which showed that 13% of those with a
normal echo develop an elevated TRV over 3 yrs.
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Comments
5 There have been a multitude of studies published since 2000 describing
echocardiographic abnormalities observed in SCD. Yes, a reduced
ejection fraction is observed in a small percentage of SCD patients (Klings
ES AJH 2008), but the majority of patients with pulmonary venous
hypertension actually have diastolic dysfunction. Sachdev V JACC 2007
and Circulation 2011 should be referenced here.
Suggestions
Type
Public
Discussion
Action/Recommendation
This could be addressed in the background. Will be considered This section revised.
in revision.
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No change
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Public
The team discussed changing the word "dangerous." Should be This section revised.
more specific - "at risk for x". Will consider a revision.
32
The team discussed changing the word "dangerous." Should be This section revised.
more specific - "at risk for x". Will consider a revision.
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Comments
11 Echocardiogram Screening and PHT
Suggestions
Type
Recommendations for screening for
Public
pulmonary hypertension: The ATS clinical
practice guidelines which includes a
diverse, multi-disciplinary committee of
adult and pediatric experts, concluded that
screening echocardiograms are indicated.
We support the ATS recommendations and
believe their document, which you have
received, justifies this. The
recommendations section asks, "Do not
perform echocardiography to screen
asymptomatic sickle cell patients." We are
not really sure how you define
asymptomatic for PHT in sickle cell
disease. The NIH website states
"Symptoms of PAH include shortness of
breath with exercise, tiredness, episodes
of chest pain, a racing heart, decreased
appetite, and light-headedness with
exercise. These are common symptoms in
sickle cell disease that many adults have
intermittently, and can be due to PAH as
indicated on the NIH web site. If patients
have some of these symptoms, would
these be classified as asymptomatic or
symptomatic?
Discussion
Action/Recommendation
In the background, will reference the NIH list. Also will take this This section revised.
comment into consideration in the revision of the background.
32
11 For patients who are symptomatic & PAH is in the differential dx, should
screening begin with ECHO? Why go directly to right heart cath given how
invasive the procedure is?
Invited
These recs are being revised for clarification. This issue will be No change
addressed in the revision.
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Comments
12 I am trying to bring attention to the effect of PAH on SCD patients. I had a
patient bouncing for years between EDs for repeated VOC because of her
sickle and when we ran echo we go a TRV of 3.2 m/s. When we asked her
about her SOB she mentioned shed been complaining about it for ever.
For years she is unable to climb stairs or even walk a block without
running out of breath and having to rest. She gets SOB at rest so
technically she is class IV FC on the WHO classification. My argument is
that there is no recommendation for PAH screening in SCD patients
despite the high mortality and morbidity that has been reported already in
different papers. Thalassemia patients on the other hand are routinely
screened for PAH.
12 Do not agree with not performing echos routinely (data are missing to
decide one way or another, but by recommending not to do it, insurance
companies will not pay for it!). If we wait for symptoms to occur, patient
may already have chronic heart damage. Would rephrase and mention
that routine echos should be done (every other year after age 10? And
should include assessment of TRV
Suggestions
Type
Since you mention in your argument that Public
increased TRV>2.5 increases two years
mortality, why don't you accept the fact that
screening for TRV instead of PAH is
advised? We are talking about 40%
mortality which is huge. Our patient is SOB
at rest and we didn't even need a right cath
to confirm the dx although I admit we need
it for staging and NO challenge testing and
to get a baseline for PAP. Nevertheless, A
simple ECHO test is able to tell if the
patient is going to have increased
mortality/morbidity so that we take it
seriously and be more aggressive in our
management. Moreover, many physicians
are swayed by the preaching that "if the
SOB/hypoxia is unexplained then search
and or screen for PAH." While this might
hold true to other diseases, SCD gives a
good excuse for the already prevalent
hypoxia and SOB. In our institute for
example, the patient has seen different
physicians and none was able to identify
the cause of repeated VOC and took it for
granted that it is the SCD that is bad and
not the concomitant PAH that is making
the SCD worse and the SCD that is
making the PAH worse. It is this synergistic
relation between those two pathologies
that we must break by primary preventive
medicine and not wait and hold off our
cheapest tools to put a full stop, an early
stop to the progression of this heinous
Invited
Discussion
Thank you for this input. We are also trying to raise awareness No change
of this issue.
No change
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Comments
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Type
12 I respectfully disagree with the recommendation not to screen for PAH in Recommend to screen for PAH by TTE all Public
HbSS disease. Almost all patients with HbSS disease have some level of adult patients with HbSS.
exertional dyspnea by virtue of their severe anemia, PAH or other
cardiopulmonary disease with the exception possibly being those with
HPFH of alpha thal, and most of them develop hypoxemia at some stage
of their illness or in crisis. Thus, it is hard to imagine a scenario of an
asymptomatic SCD patient for PAH, and the recommendation not to
screen asymptomatic patients becomes a moot point. Early signs of PAH
are easily missed and an echo is done almost invariably at some stage of
their care anyhow, so it would make sense to obtain it as a screening test
in steady state. Although there is no proven effective therapy for PAH in
SCD, it is intuitive that maximization of medical therapy with an attempt to
achieve disease control may be beneficial. Considering the mortality and
burden of PAH in SCD, I believe that to wait for a RCT before making a
recommendation of maximizing medical therapy in patients with suspected
or confirmed PAH is a risky approach. Moreover, finding of PAH should
prompt a workup for chronic thromboembolic lung disease, PFTs, OSA and
other pulmonary comorbidities and presence of PAH is a risk factor for
sudden death. This is an important piece of information during VOC
therapy in the hospital, when PA pressures may increase acutely and place
the patient at increased risk of pulmonary failure, particularly when IV
opiates are administered. Knowledge of the patients PAH may increase
the level of alertness in the staff and prompt more aggressive
cardiopulmonary monitoring.
Discussion
The team does not believe a change is warranted.Thank you
for the comment.
No change
12 data concerning echo is very controversial and may meet with criticism
Thank you.
No change
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Comments
12 After our guidelines group did a comprehensive assessment of the entire
body of literature concerning PH of SCD, a survey of was performed to
determine what each member thought was the most important
recommendation to emerge from the entire document. The overwhelming
first choice was universal screening of SCD adults. Our rationale for this is
as follows: 1) An elevated TRV predicts mortality and a significant number
of patients will not have symptoms early in their disease (Klings ES AJH
2008); 2) Although treatment of PAH has not been shown to improve
mortality, we would argue that no randomized controlled trial of PAH
therapy has been successfully completed in this population. This rationale
for not screening limits the ability to accurately assess and define the true
natural history of this disease. 3) While there is no clear established
specific therapy for PAH of SCD, identification of this patient group with an
increased mortality risk is an indication for a) intensification of treatment
for SCD with hydroxyurea and possibly chronic transfusions and b)
increased assessment of other conditions with known treatments which
increase cardiopulmonary risk such as venous thromboembolism,
obstructive sleep apnea, etc.
Suggestions
Type
Public
Discussion
We adapted a recommnendation that acknowleges screen in
adults with SS. Appreciate the comment.
Action/Recommendation
No change
No change
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Comments
12 Our guidelines group did a comprehensive assessment of the entire body
of literature concerning PH of SCD in the process of assembling our
guidelines. When a survey of our group was performed to determine what
each member thought was the most important recommendation to emerge
from the entire document, the overwhelming first choice was universal
screening of SCD adults. Our rationale for this is as follows: 1) An
elevated TRV predicts mortality and a significant number of patients will
not have symptoms early in their disease (Klings ES AJH 2008); 2)
Although treatment of PAH has not been shown to improve mortality, we
would argue that no randomized controlled trial of PAH therapy has been
successfully completed in this population. This rationale for not screening
limits the ability to accurately assess and define the true natural history of
this disease. 3) While there is no clear established specific therapy for
PAH of SCD, identification of this patient group with an increased mortality
risk is an indication for a) intensification of treatment for SCD with
hydroxyurea and possibly chronic transfusions and b) increased
assessment of other conditions with known treatments which increase
cardiopulmonary risk such as venous thromboembolism, obstructive sleep
apnea, etc.
Suggestions
Further, identification of these patients is
reaonable to consider for future clincal
drug trials, in SCD patients whose SCD
conventional treatment has already been
optimized, e.g. HU and/or transfusion
regimen.
Type
Public
Discussion
This suggested change is beyond the scope of this chapter.
Also, the comment appears to be a duplicate.
No change
Action/Recommendation
No change
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This recommendation has been re-written and will better define. No change
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12 I disagree that routine echos not be performed on adults with SCD: The Suggestion: Yearly echocardiogram should Public
controversy with TRV and its low predictive value in PH should not jade the not performed in children, since there is no
Panel in making the pendulum swing the complete opposite way. The
evidence of what this means in the
published evidence shows that (a) TRV elevation (>2.5m/s) is present in pediatric population as yet. However,
30% of adults with SCD. (b) Amongst those with elevated TRV, 25-33% of echocardiography should be performed at
the patients have cath-proven PH. (c) Elevated TRV, whether there is PH 1-2 year interval in adults. If TRV>2.5m/s,
or no PH, portends a poor prognosis (~8-15 fold higher mortality). (d) tthe and this finding is reproducible on a
cause of the elevation in TRV in 2/3rds of the patients is not known but the second echo, a cardiopulmonary
poor prognosis is universally seen in all studies. Therefore, even if cardiac evaluation should be done and the patient
cath proven PH is present only in a third to a fourth of the patients with
monitored more closely with a 6 minute
elevated TRV>2.5m/s, echocardiography still helps us identify patients at walk test and more frequent clinic visits. If
high risk of death, where more intense monitoring can be instigated, and elevated TRV is associated with a
measures like hydroxyurea, transfusions or a BMT can be offered. For the worsening 6 minute walk distance and/or
Panel to make a strong recommendation to stop a non invasive screening symptoms of PH, a cardiac catheterization
test in a third of adults that are at high risk of death does not seem ethical. should be performed to rule out PH.
Discussion
The team does not think further changes are needed - the
background and recommendation are being revised.
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32
14 Incomplete recommendation
Agreed.
No change
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Discussion
A change is being made to address this comment.
Public
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34
10 ECG screening pag e34 line 10seems as though this should be a strong
or at least moderate negative recommendation to parallel the D rating from
USPSTF.
Public
2/2/1900
1/10/1900 Do not agree with not performing routine ECG screening. Prolonged QT is
not uncommon and, if unrecognized, might lead to potentially lethal
arrhythmias. Patients and their physicians need to know about the
potential risk if they have prolonged QT and take certain common drugs,
such as macrolide antibiotics, methadone, certain anti-histamines or antiemetics
Invited
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33
Comments
15 We agree with this recommendation, but think it needs to read that right
heart catheterization is required to confirm PH and to distinguish PAH from
PVH. This reflects the correct use of right heart catheterization.
Suggestions
Action/Recommendation
No change
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no change
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12 do not recommend routine ECG screening":
We agree that screening ECGs are not necessary in the asymptomatic
patient, however it is important to note that many patients with SCD have
prolonged or borderline-prolonged QTc intervals (Liem et at, Pediatr Blood
Cancer. 2009; 52:842). ECGs they should be obtained prior to
medications at risk for to be harmful in pts with prolonged QTc intervals:
methadone, macrolides, tricyclic antidepressants and continuous albuterol
Suggestions
Acknowledge the frequency of
prolongation of QTc in SCD and include
recommendations for ECG screening as
indicated.
Type
Public
Discussion
will be addressed in the background section
Public
Invited
no change
Public
No change
36
15 Do both the systolic and the diastolic blood pressures need to exceed the
levels indicated, or is it sufficient that either elevated systolic or diastolic
blood pressure should lead to treatment (issue also applies to the next
recommendation)? Also, the method by which renal disease should be
screened is absent in this recommendation statement but indicated in the
next recommendation statement.
Fed
Revision submitted.
36
Revision submitted.
34
35
36
36
36
Action/Recommendation
no change
no change
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Comments
15 Recommendations 2 and 3 appear slightly inconsistent: parameters for
screening for renal disease are stated for BP > 120/80 but not for the for
BP > 140/90; also, for those with BP > 120/80, there is no
recommendation to initiate lifestyle modification but it is recommended that
"treatment" be considered. "Treatment" may be miscontrued as
pharmacologic therapy only.
36
36
36
15 in this sentence/guideline to you recommend "screen for renal disease"-but need to be more specific--using what test? Serum creatinine? Urine
microalbumin?
36
15 The text (Recommendation #2) states "In people with SCD with BP>
140/90."
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36
36
37
1 No action listed
Suggestions
Type
Invited
Discussion
agree confusing. Possible to make one recommendation?
Submitted
Consider treating at the next bp level. Use consider when the
evidence is weak. Use the word consider very carefully. Needs
to stay as recommendation, but some disagreement on this.
May have to go to panel
Invited
clarify for inpatient versus office visits, change narrative instead Submitted
of recommendation. Follow JNC recommendations. Clarify. 2
or more separate office viisits with hypertenstion per JNC.
Public
Submitted
Invited
No change
Invited
Consider modifying text to: "In patients
Public
with SCD and BP> 95th percentile for age,
gender and height, or >120/80 mmHg,
assess urinalysis for protein and measure
serum creatinine.
Invited
Action/Recommendation
do not have appropriate data and rec 3 does address this issue No change
no change
no change
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Suggestions
Type
Would include a frequency for screening of Public
BP; otherwise, this is confusing.
Discussion
make annual screening change already made
Action/Recommendation
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Please clarify
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Comments
3 Comments on "Screening for Retinopathy section in Health Maintenance
ch., cont.: In regards to age at screening commencement, it must be
emphasized that children develop vision from birth to age 7 or slightly
beyond. During the period of visual development, any insult to the retina
has the potential to interfere with this process and may have lasting effects
on vision, such as amblyopia or strabismus, that would interfere with visual
development and cause a child to be permanently visually impaired.
Therefore, any non-proliferative sickle cell retinopathy can be considered
an important finding in a child, despite the low rate of vision loss from nonproliferative retinopathy. In the publication by Rosenberg (2011), the
youngest patient with sickle cell retinopathy was 6 years old. As such,
screening from age 6 may be warranted.
Suggestions
Type
Public
Discussion
This section being updated
Action/Recommendation
Revision submitted
38
3 References
Clarkson J. The ocular manifestations of sickle-cell disease: a prevalence
and natural history study. Trop Amer Ophth Soc, 1982; 90:481-504.
Clarkson JG. The ocular manifestations of sickle-cell disease: a
prevalence and natural history study. Trans Am Ophthalmol Soc. 1992;90:
481504
Rosenberg JB, Hutcheson KA. Pediatric sickle cell retinopathy: correlation
with clinical factors. J AAPOS 2011 Feb;15(1):49-53.
Public
This section being updated. Adding Rosenberg. Dr. L will check Revision submitted
other references, as needed.
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Public
38
Public
This is a good suggestion. Acute vision loss, pain,the things Done. Added new rec. #1 on 1/10/13.
we usually try to tell patients. Maybe we can say "Screen for
and educate" NEW REC #1: Educate all patients about the
signs and symptoms of retinopathy. Consensus Panel Expertise
38
Invited
refer to an opthalmologist for dialated eye exam (add this Done 1/10/13
to the current #1, new #2. Delete "perform or" Just have "refer
to an opthalmologist"
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38
neonatal retinal screening is done with little InvitedThe recs are being revised
problems and should be use in 2-5 yr age Non
Disclosed
Invited
Revision submitted
Revision submitted
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Comments
0 Screening for risk of stroke using neuroimaging: ( Line 14
Recommendation) This is a strong personal statement based on clinical
practice experience : Young adults with history of abnormal TCD should
have a brain MRA to rule out severe vasculopathy with moyamoya. Adults
with no history of CVA or TIA who give a history of headache or "migraine
headache" should have an MRI/no contrast and a MRA to rule out cerebral
vasculopathy or cerebral aneuriym.
Suggestions
Type
Public
Discussion
There is no change based on this comment, the commenter is No change
not talking about asymptomatic individuals. We are addressing
screening of asymptomatic individuals.
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Fed
39
39
39
18 The sentence should start with "In those who have had one stroke, stroke
recurs"
Action/Recommendation
No change
No change
No change
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Comments
Suggestions
Type
21 The section on TCD screening and prevention of stroke is very short given The STOP study NeJM 1998 is not even Public
the massive high quality data--I cant believe more background and
referenced and must be. There are also
information cannot be provided here.
several other studies beyond the CHOP
clinic that show there has been a major
reduction in stroke almost certainly due to
TCD and Transfusion. This section should
be strengthened and amplified,
emphasizing the need to get ALL kids
regularly screened. --given the amount and
quality of the data, the numerous spin off
papers and teh $ 25,000,000 investment of
nhlbi.
Discussion
Will review the background and see if additional detail would
benefit the chapter. Consider indicating the quality of the
evidence by describing the number of RCTs.
Action/Recommendation
Rewritten as follows: Transcranial Doppler (TCD) imaging of large
intracranial blood vessels to detect increased velocities secondary
to stenosis is now employed to can predict risk of stroke in children
with SCA (Adams 1992)(Adams et al. 1992). Primary stroke
prevention using regular blood transfusions in children with such
elevated velocities proved successful in the NIH-funded STOP trial
(Adams et al. 1998 ). This approachtransfusions for an
abnormal TLD velocity (>200 cm/sec)has resulted in a declining
incidence of primary overt stroke in children with SCD (EnninfulEghan et al. 2010 ). Unfortunately, discontinuation of such
transfusions was shown in the STOP-2 trial to result in a high rate
of reversion to increased TCD velocities or to overt stroke (Adams
et al. 2005 ). Therefore, such transfusions may be necessary
indefinitely. DONE 2/14/13
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No change
CHANGE: Page 40, line 9: Add a new paragraph following this section
that acknowledges the growing body of research on neuropsychological
outcomes, and the role of neuropsychological testing, in identifying,
diagnosing, describing, and precisely guiding management of
neurocognitive or psychosocial compromise among individuals with SCD
(see, for example, Berkelhammer 2007, Wang et al. 2001, and Wills 2011).
Acknowledge that the present review considered neuroimaging
technologies but did not evaluate the role of psychological or
neuropsychological testing as a screening tool or for clinical evaluation of
patients with SCD.
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40
Comments
10 Screening for Risk of Stroke Using Neuroimaging: The key question is "In
asymptomatic individuals with SCD, what is the effect of screening on risk
of stroke with neuroimaging tests (CT scan, MRI or TCD)?" The
recommendations are to screen children with SS below 16 years of age
with TCD and not to do any testing in adults. These recommendations do
not address the complexity and risk categories in SCD. There are not 2
groups of patients totally asymptomatic who are under 16 years of age and
patients with overt symptoms over 16. The TCD and MRI are synergistic
and complimentary in several specific instances, and in many cases, the
MRI has specific indications.
Suggestions
Type
The recommendations section should
Public
define what asymptomatic means. Are
patients with headaches, deteriorating
school performance, severe sleep hypoxia,
neurologic soft signs, memory loss,
seizures, abnormal neurocognitive testing,
or IEPs in school asymptomatic or
symptomatic? There should be detailed
recommendations concerning when MRI
testing would be indicated.
In our opinion, there is sufficient evidence
to support screening for silent cerebral
infarction in general. However, in patients
with any soft signs, the data is even
stronger. Silent infarctions are correlated
with cognitive deficits and behavioral
problems that can be identified and allow
for additional educational resources and
assistance. In addition, close monitoring
and therapeutic options can be reviewed.
Discussion
Yes, we agree. Panel members will dicuss the extend that we
need to define asymptomatic.
Action/Recommendation
Per revision, Background section revised to include: "transfusions
for an abnormal TCD velocity (>200 cm/sec). DONE 2/14/13
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11 This is far from the "key question" as the effect of screening is clearly to
The key questions really are why these
Public
decimate the rate of first stroke, albeit at the price of tranfusions.
particular children develop vasculopathy
Neuroimaging is secondary to TCD and will likely always be as the first test and how it can be interupted with more
to establish treatment is often hard to improve upon with good evidence as discrete or small molecule approaches
the high risk individuals are no longer having outcomes nearly as often
short of transfusion. The other major issue
and surrogate measures, beyond TCD are not valid. TCD is easy to do
is the complete dearth of data on adults
and cheap but in cases where tcd cannot be done MRA or CTA should be with SCD and stroke and stroke risk. unlike
recommended.
in kids this risk is rising not falling and
there is no stategy even in the pipeline for
this.
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Comments
1 Would consider "elevated cerebral blood flow velocity (CBFV >200
cm/sec) as an alternative to abnormal, sicne the strog evidence is just for
that group
Suggestions
Type
Discussion
InvitedChange to "elevated" instead of "abnormal" on line 17
Non
Disclosed
10 Change from Dr. Lottenberg and Joylene received 11/30/12 via e-mail
Action/Recommendation
Done 1/10/13
Done 1/11/13
need rationale
Public
Invited
No change
Done 1/10/13
Public
41
15 This contrasts with the above text about doing it until age 10
need to be consistant
41
15 Should include information that some patients can not have a meaningful
TCD evaluation because of closure of bony windows, that this is more
common in older adolescents and adults. Also if known an estimate of this
number.
Public
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41
41
No change
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Invited
No change
No change
41
15 what about sickle beta zero thal? May be better to consistently use
terminology that covers both SS and s-beta zero (?SCA)
Invited
No change
41
16 "at least age 16" is vague. If the statement is intentionally vague, please
state that explicitly. If there are known considerations for whether
screening should continue or discontinue starting with the 16th birthday,
please state those.
Fed
Panel members will discuss to determine if a change is needed Section revised. No change to this language.
41
17 what about imaging TCD (TCDi)? May need modifications of STOP cutoffs
Invited
42
1 please expand or clarify that Sbzero and SOarab are at increased stroke
risk. Screening should follow recommendation for HbSS
42
Before the parens, or hemoglobin S beta zero thalassemia (in Done 1/10/13
correct format).
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Comments
1 How can a strong recommendation be made against screening, with very
low quality evidence? Is there a better way to word this-there is limited
evidence that screening is not effective/necessary/cost effective?
42
42
42
42
42
42
Suggestions
Clarify recommendation.
Type
Discussion
InvitedThe panel is comfortable with the grading of this
Non
recommendation. Should this be addressed in the Intro - what
Disclosed strong/very low means?
Action/Recommendation
Yes, this will be revised in the Intro.
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No change
No change
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Comments
6 Screening for Respiratory Disorders in SCD (Asthma, PFTs)
Suggestions
Type
Asthma is a critical problem and needs to Public
be included in the document. Relying on
the physician to obtain history of asthma
symptoms is unreliable and
underestimates the magnitude of the
problem. Given the morbidity of this
complication, this section underestimates
the importance of early diagnosis and
treatment of broncho-reactive lung
disease. A high degree of suspicion is
warranted for testing. Rather than exclude
pulmonary functions as an entire category,
we would recommend an expanded
section that outlines those patients who
should be tested if not all. In addition,
since so many of the patients with acute
chest syndrome have a broncho-reactive
component, the issue of treatment of acute
chest syndrome with broncho-reactive
medications needs to be included
somewhere in the text.
42
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43
8 Should another key question be "Screening for asthma in all chidlren (+/-)
adutls with SCD?
44
44
Discussion
Asthma guidelines have this information. Some of that
information might be helpful here. This could be in the
background. Asthma will be further addressed in the
background. We will review what has been included in ACS
specific to what has been addressed in broncho-reactive lung
disease.
Action/Recommendation
Revised recommendations submitted for this section.
No change
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44
Comments
4 Question: did not have clarity what asymptomatic means: several only
have headaches without any other neurological problesms and MRI shows
an anerysm. Where does the PCP go with this from such a blanket
statement?
17 There is no discussion here of asthma in SCD, other than to mention that
the prevalence is increased. There are no recommendations in this
document for the appropriate surveillance and treatment of asthma in
children with SCD; there is not even a reference to the standard NHLBI
guidelines for asthma care. Children with asthma are at increased risk of
vaso-occlusive episodes and ACS, particularly if the asthma is
inadequately controlled.
Suggestions
Type
Invited
Discussion
This is out of scope fo this chapter
Action/Recommendation
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Comments
17 We are frankly dismayed by the lack of information regarding pulmonary
complications of SCD in this guideline. It is clear that nobody with a clinical
or research interest in this aspect of sickle cell care was asked to
participate in the generation of this report. While we concede that, again,
there is mostly poor quality evidence for any specific monitoring or
intervention for pulmonary complications of SCD in children, we absolutely
reject the defeatist tone that is implied in the single recommendation
provided in this document. Adult pulmonologists are increasingly familiar
with sickle cell chronic lung disease, an entity which is surely evolving
during childhood whether or not we recognize it. As the report indicates,
any number of observational studies have noted abnormalities of lung
function, both obstructive and restrictive in nature, in otherwise
asymptomatic children with SCD.
Suggestions
Type
1. We recommend that the Expert Panel
Public
Report call for the establishment of a
broad based registry for pulmonary
outcomes in children with SCD, which can
serve as the foundation for the urgently
needed prospective investigations of
clincial interventions for the treatment and
prevention of pulmonary complications.
Further, we recommend that this registry
be used for the institution of hypothesisdriven clinical investigation of therapies
and intervention to prevent many of the
pulmonary complications mentioned here.
2. Based on the recommendations of Drs.
Strunk and DeBaun in Kendig's textbook of
pediatric pulmonology, we believe that
children with SCD should have an
assessment of lung function by spirometry
annually after 6 years of age. Children with
asthma and SCD should have spirometry
with every visit, up to 4 times annually. A
bronchodilator challenge should be
performed for children who have an
obstructive pattern on baseline spirometry
(FEV1/FVC < 80%, or less than 95% CI).
3. Children with SCD should have an
assessment of possible defects in lung
function by lung volumes with
plethysmography starting at 6 years of age
(or first age at which they are able to
complete the test), and every 5 years
Discussion
This can be incorporated into the gaps section.
Action/Recommendation
Revised Recommendations submitted. The gaps section was not
modified.
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44
Comments
17 Page 44, line 17 Cont'd - Our members do not believe that lack of proven
efficacy for treatment justifies recommendations against regular
surveillance with PFTs in children with SCD. Pulmonary complications
remain one of the leading causes of mortality and morbidity in this
poulation, and simple screening tests like spirometry may allow us to
identify those patients at particular risk for poor pulmonary outcomes.
Ongoing assessment of basic lung function is an essential prerequisite to
the urgently required evaluation of therapies commonly used in SCD
patients, including hydroxyurea, bronchodilators, inhaled steroids and
combinations of these drugs. In addition, we often identify patients who
lack (or fail to perceive) clinical signs of asthma, but who have reversible
bronchoconstriction which may respond to asthma medications. If we do
not look, we will not learn to identify signs of early lung damage in these
children.
Twenty-five years ago, there was almost no evidence to support
interventions that were used to treat cystic fibrosis, and most children died
in their teens. It was only through continued, aggressive observation of
interventions informed by expert clinical opinion that the current broad
base of knowledge was acquired, leading to rapid and dramatic changes in
CF care. Now the median age of survival for CF patients is 37-38 years,
but this would not have happened were clinicians advised to stop
screening for complications since there were then no available
interventions. Evidence based medicine is only an effective guide in the
presence of quality evidence. Where it does not exist, there needs to be a
strong call for MORE clinical observation, and more research, until this
type of evidence is acquired. In this setting, the input of clinicians with
experience and expertise in the area should weigh heavily in any
recommendations disseminated to the general medical community.
Suggestions
Type
Public
Discussion
The reference provided will be reviewed and work with panel
members on this (and previous) comment. This may be
covered better in the revised recommendations that are
forthcoming. Research gaps may also be modified to address
this issue.
Action/Recommendation
Revised recommendations for this section were submitted. The
Gaps section was not modified.
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Comments
17 "Do not screen (asymptomatic) children and adults with SCDwith PFTS."
This recommendation is inconsistent with the cited data on pulmonary
dysfunction in SCD, and seems to be based on paucity of studies
evaluating "the utility of screening." However there are numerous studies
showing a high rate of reactive airway disease in the SCD population and
significant compromise of pulmonary function and decline with age in SCD
patients. Substantial restrictive lung disease is reported in adults with
SCD. Routine PFT screening is noninvasive and may guide therapies, in
particular, identifying reactive airway disease that may be amendable to
conventional standard of care asthma management. Indeed there are
clear guidelines (NIH) for asthma management. Given the difficulty in
defining "asymptomatic" in this population, the lack of sensitivity of
"symptoms" to predict abnormal PFT, and the critical role of pulmonary
function in the pathophysiology of SCD, it seems prudent and consistent
with good medical practice to assess pulmonary function in this group of
patients.
Suggestions
Type
Acknowledge the high incidence of lung
Public
disease in SCD and utility of routine PFT
screening in detecting dysfunction and
guiding therapy, especially for asthma.
Consider reference to NIH guidelines for
asthma management until more
information is available and asthma
studies specifically to SCD are performed.
Invited
Discussion
Will do some searching for review articles on this topic.
Action/Recommendation
This is a closed issue - the group did not think a change was
warranted.
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44
No change
44
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44
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44
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Comments
17 Add "asymptomatic" after "do not screen.." and before
".children"
17 I am surprised that the panel has reviewed the high incidence of airway
hyperreactivity, abnormal PFT, and studies have shown the associaiton of
asthma with mortality and ACS, and yet recommend not doing PFT. If
patients have airway hyperreactivity, they can be treated for asthma.
Asthma in SCD has been shown to be associated with increased mortality,
increased incidence of acute chest syndrome.
Suggestions
Type
Invited
Discussion
This is being addressed in a revision to the recommendations.
No change
Action/Recommendation
No change
44
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No change
44
Invited
No change
44
Invited
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EM
EM
45
0 The only area I did not see covered (and it would be easy to miss amongst
the 225 pages of text) was men and women with sickle cell disease using
gene therapy. It seems to me a section on this area, similar to hydroxyurea
therapy and blood transfusion therapy, would be appropriate.
45
45
45
10 Would add "if their partners have SCD, B-thalassemia,or HbS, HbC, or
thalassemia trait.
45
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Comments
16 The practical lack of access to PGD and CVS for patients because of
insurance limitations (especially public insurance), a restriction that also
pertains to recommendations for genetic counselling by genetic
counsellors should be so stated. Recognition that this is not possible for
financial reasons or that this is costly should be included.
Suggestions
Type
Public
Discussion
This is outside the scope of this document
Action/Recommendation
No change
47
EM
Panel will draft a statement and revise the section: "There is no EDITOR: Insert this statement at the end of line 10: There is no
evidence of increased risk" into page 49, line 9.
evidence that IUDs pose an increased risk for women with SCD.
47
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47
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Invited
"Thinking about your goals for having or not having children and EDITOR INSERT ON Page 45, line 4 (after CDC 2010) They
how to achieve those goals is called a reproductive life plan."
recommend that women and couples think about their golas for
Figure out where this language can go - background?
having or not having children and how to achieve these goals,
known as a "reproductive life plan."
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47
Fed
No change
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Comments
11 I would strongly suggest adding "or refer for risk assessment" in addition to
providing risk assessment and educational counseling. Most PCPs, even
if they had the time to devote to this single facet of counseling, probably do
not feel adequately prepared to counsel individuals with SCD on
reproductive issues. So if they don't want to/won't, then it is reasonable to
at least ask them to refer for this.
Type
Invited
Discussion
YES, change to "provide or refer to individuals with expertise in Done 1/17/13
these disciplines"
11 should this say all men and women or otherwise should this rec be listed in
the next section?
11 Consider adding clearer and more direct language to provide
contraceptive counseling, if desired, to prevent unintended pregancy, and
if pregnancy is desired, provide pre-conception counseling to reduce risks.
This could be connected to the subsequent section on contraception.
Invited
This is a very good suggestion and would have the consent of EDITOR - YES, CHANGE TO ALL WOMEN AND MEN.
the group.
We can insert the following between lines 12-13 on page 47.
Editor - change as indicated.
"Provide contraceptive counseling, if desired, to prevent
unintended pregancy, and if pregnancy is desired, provide
preconception counseling." However, I'm not sure it adds much.
Public
47
47
47
Suggestions
Fed
Action/Recommendation
Fixed by comment on page 47/11 "should this say all men and No change
women"
Here is how the sentence has been reworded this statement
Editor - change as indicated
without straying from our consensus, "If the partner of a man or
woman with SCD has unknown SCD or thalassemia status,
refer the partner for hemoglobinopathy screening. (Consensus
Adapted)" The Expert Panel did not discuss or develop
consensus around carrier screening and, therefore, we cannot
such make recommendations.
Invited
The group did not discuss or develop consensus around carrier No change
screening and, therefore, we cannot such make
recommendations.
Public
Public
The Expert Panel agreed an this is why the section does not
specify by whom the genetic counseling should be performed.
No change
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Comments
Suggestions
18 There is no statement of the burden of raising a young child and its
Add such a recommendation.
potential to reduce the ability of a young mother to care for her self and her
sickle cell disease. That she should have identified support systems
available before she becomes pregnant so she can take care of her own
health needs and so she has options for her child's care when she is
receiving health care for her sickle cell disease.
Type
Public
Discussion
This is an excellent point, but we actually found no literature
that supported our making such a recommendation.
18 there are recs for men in here too - confusing to have two sections here
that overlap
Invited
Invited
This document does not address the care of the woman once No change
she becomes pregnant. It would be appropriate to comment on
that in the introduction of the document.
Invited
Yes, but this document does not address the care of the woman No change
once she becomes pregnant.
48
13 should pregnant women with SCD be referred to high risk Obs or MFM
specialists based on these complication risks?
48
48
49
49
50
Action/Recommendation
No change
No change
InvitedWe make the statement that women should be counseled prior No change
Non
to pregnancy that, "For women who require chronic opioid
Disclosed therapy during pregnancy, there is an increased risk of neonatal
withdrawal in their newborns," however, this document does not
address the care of the woman once she becomes pregnant, let
alone the neonatal care of the infant after delivery
Invited
Invited
Invited
Yes, but this document does not address the care of the woman No change
once she becomes pregnant.
No data.
No change
No change
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Comments
6 The sentence on lines 6-8 is a duplicate from the paragraph above and
should be omitted.
Suggestions
Type
Public
Discussion
The sentence in line 4 should read, "There were no episodes of Done 1/17/13
deep vein thrombosis (DVT) in women with SCD using
progestin-only contraceptives or IUDs" This will make the
sentence more explicit and should eliminate the confusion.
Public
50
10
50
17 In non-SCD women with risk factors such as high VWF and ADAMTS13,
oral contraceptives increase MI and stroke risk (Blood 2012;119:1555). It
would be more prudent, in my opinion, to assume that SCD also
represents a risk factor to women exposed to oral contraceptives. Safer
alternatives to avoid pregnacy should be chosen: fertility-awareness
methods, which are as effective in preventing pregnancy as hormonal
contraceptives (Hum Reprod 2007;22:1310), would seem ideal for SCD
women.
No change
50
17 Risk of venous thrombosis with progesterone containing contraceptives the conclusion that thrombosis is not increased is surprising and not
consistent with my understanding as there are a lack of comparative trials
with no intervention. There is reasonable evidence the risk is lower with
progesterone alone compared with combined.
Public
No change
50
Fed
No change
50
Invited
No change
50
20 should there be an exception excluding patients with prior stroke (or VTE)
from this rec as estrogens are not typically recommended with prior stroke
or VTE
Invited
No change
50
Invited
No change
50
Invited
No change
Action/Recommendation
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Comments
1 Change to, "United States Preventive Services Task Force (USPSTF)
Recommendations" (This whole section inc. Exhitibit 4 should be in
accompanying Methodology/Reference volume.)
Suggestions
51
1 What does USPSTF stand for? Please spell out the complete name.
51
51
3
3 The USPSTF's report to Congress describes its recommendations as
"screening tests, counseling services and preventive medications"
51
4 The document uses the phrase "the average person" to describe the
population of interest for the Task Force. It might be more accurately
described as persons without signs or symptoms of the target condition.
However, recognizing how that might be confusing in this document could
you just say "children and adults" instead of "average person?" Or even
"general population" might capture the notion a little better.
51
5 Most primary care doctors do not test for trait in their patients who are in
childbearing years. Recent immigrants may never have been tested.
No change
51
5 Most primary care doctors do not test for trait in their patients who are in
childbearing years. Recent immigrants may never have been tested.
No change
51
13 Using the term "strong recommendations" may not be exactly right. Of all
its A and B recommendations the word "strongly" is only included in eight.
In addition, a few of the recommendations you listed include some C
recommendations. Could you use the term "positive recommendations?"
This would be more accurate. (As a reminder, the grade encompasses the
TF's assessment of both the magnitude of the potential net benefits and
certainty about the strength of evidence.) Another approach would be to
say, "We have only included A and B recommendations from the
USPSTF..." This is consistent with the ACA's approach as well.
Fed
51
Fed
Done 1/17/13
51
Fed
Define USPSTF
Type
Invited
Discussion
Spell out USPSTF in subheader
Action/Recommendation
Changed to U.S. Preventive Services Task Force 1/17/13. The
USPSTF does not spell out "U.S."
Invited
DONE
Public
Fed
Fed
No change
No change
Will look up exact wording and submit with her previous revision DONE
to first 1-2 lines of section.
No change
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Comments
Suggestions
Type
17 What do we do about the numbers of people who don't have a primary
Encourage hospital staffs to go through
Public
care provider. They go to the emergency room where they are unlikely to mandatory training in treatment of SCD in
find a well-trained doctor.
order to be accredited.
Discussion
Training is beyond the scope of this panel.
Action/Recommendation
No change
52
InvitedDelete this statement (in the Adults section). It is with the Lipids Done 1/17/13. Note: This change was not part of revised Exhibit 4
Non
bullet. Please change BP to Blood Pressure. Add: "For Blood
received as separate Word file on 1/8/13.
Disclosed Pressure screening recommendations, see page X" (this is in
the HM chapter - currently p. 34, line 13, "Screening for
Hypertension in Individuals with SCD" ALSO: DELETE the
parens "(diabetes, lipids, and BP)
52
Fed
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Public
Without evidence, it is difficult to address this here. This should DONE -resubmitted
go into the gaps - specific to SCD. Also, check with Chronic
chapter on how this is handled in their gaps.
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Fed
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Comments
0 Exhibit 4 - Newborns section: There are three positive TF
recommendations for newborns that you might consider adding: screening
for congenital hypothyroidism, screening for phenylketonuria, and
screening for hearing loss.
Suggestions
Type
Fed
Discussion
Action/Recommendation
We can add hearing loss. Also will re-visit the recommendations Done 1/11/13. Revised Exhibit 4 submitted
to see if any further additions are needed. Also, remove
redundant language (see parens).
52
Fed
52
Fed
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Fed
This is an update from when we did it. We will refer back to the Query from Editor: Pls clarify instruction in "discussion" column.
guidelines and ensure that this table is accurate.
Should we add, "for more information, please refer to the CDC"s
HIV screening guidelines at URL"? Or does it mean that we will
confirm that our recommendation is correct before these
guidelines are published by checking the CDC's guidelines to see
if they've changed?
52
Fed
Editor added a footnote with this information, with the date TBD.
Page #
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Type
Fed
Discussion
Will review and revise to include all applicable
recommendations.
Action/Recommendation
Done. Revised Exhibit 4 submitted
Fed
Fed
52
Fed
52
0 Exhibit 4 - Adults: For alcohol misuse, the TF says "provide screening and
behavioral counseling interventions to reduce alcohol misuse." Not just
screening. Also, this might be included in the section for pregnant women
making the parenthetical redundant.
Fed
52
52
52
Comments
0 Exhibit 4 - Adolescents: There are four additional positive
recommendations for adolescents that you might consider adding to the
table (they may help emphasize the Panel's point about general
prevention):
Screen for chlamydial infection for all sexually active non-pregnant young
women aged 24 and younger.
Counsel children, adolescents and young adults aged 10-24 years who
have fair skin about minimizing their exposure to ultraviolet radiation to
reduce risk for skin cancer.
Offer high intensity behavioral counseling to prevent sexually transmitted
infections (STIs) for all sexually active adolescents at increased risk for
STIs.
Screen adolescents (12-18 years of age) for major depressive disorder
(MDD) when systems are in place to ensure accurate diagnosis,
psychotherapy (cognitive-behavioral or interpersonal), and follow-up.
Suggestions
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52
Comments
0 Exhibit 4 - Adults: The obesity screening text seems both too vague and
too specific. The language from the TF is "screen all adults for obesity, and
offer or refer patients with a body mass index of 30kg/m*2 or higher to
intensive, multicomponent behavioral interventions. They do not specify a
periodicity for screening. "Diet and counseling" is too vague a description
of the intervention recommended by the TF.
Suggestions
Type
Fed
Discussion
Will review and revise as needed
Action/Recommendation
Revised Exhibit 4 submitted. Done
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Fed
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Fed
Page #
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52
Comments
0 Exhibit 4 - Adults: Genetic risk assessment for breast and ovarian cancer The TF recommends that "women whose family history is associated with
an increased risk for deleterious mutations in BRCA1 or BRCA2 genes be
referred for genetic counseling and evaluation for BRCA testing." The TF
does not provide an age at which to begin assessing family history. It is
important to include first and second degree relatives on both maternal
and paternal side, in addition the TF notes several high risk patterns.
Suggestions
Type
Fed
Discussion
Will review and revise as needed
Action/Recommendation
Revised Exhibit 4 submitted. Done
52
Fed
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Fed
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52
Comments
0 Exhibit 4 - Pregnant women: The TF recommends that clinicians "screen
all sexually active women, including those who are pregnant, for gonorrhea
infection if they are at increased risk for infection." You might add the part
about increased risk.
Suggestions
Type
Fed
Discussion
Will review and revise as needed
Action/Recommendation
Revised Exhibit 4 submitted
52
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Invited
So noted.
No change
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No change
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Comments
0 Exhibit 4 - General comment 2: There are several recommendations that
are currently being updated, however, we can only provide the existing
approved language. For other recommendations it may be better to refer
to the guidelines of other organizations which might be more current, like
JNC8 for BP, ATP4 for lipids or the CDC for HIV screening. We will note
that in the specific comments on those recommendations below. Finally,
often for completeness sake we have added positive recommendations
excluded from the table. We offer them up for the Expert Panel's
consideration on whether to include them or not.
Suggestions
Type
Fed
Discussion
Action/Recommendation
No change
52
Fed
52
Fed
52
Fed
The panel feels that adding the word "all" is reduntant and not
needed.
No change
52
1 colon ca risk - unless FMH then 10yrs before age of onset - think this is in
USPFT
1 bottom of table where discusses CV risk screening - duplicate entry of BP
Invited
Invited
No change
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2 Table: for adolescents and adults, would be helpful to include ages (ie do
you count adolescents from ages 13 to 18 or 13 to 21??)
Invited
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No change
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Comments
2 Good idea to summarize in a table but would expand beyond USPSTF or
make a second table to include the recommendations across the lifespan
recommended in the guidelines. Under newborn, should clarify screening
versus disease confirmation; the PCP needs to follow up screening with
appropriate confirmatory testing in most states (some are reflexive). All
other SCD-specific preventive measures at every age should be
incorporated (Newborn: start penicillin, get immunizations, etc)
Suggestions
Type
Invited
Discussion
Will review and revise as needed
Action/Recommendation
Revised Exhibit 4 submitted
Public
Public
Invited
Will work on this. The link will be included in the text for
updates.
54
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Invited
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4 Known by some physicians and patients that Influenza vaccine may cause
VOC in some sickle cell patients (significant numbers of people Ive polled
in our support group, approx 30%). This needs immediate RCTs. [Noted
as an SS patient and Clinical Lab Scientist.]
Public
54
4 addtl sentence specifying that adults with SCD qualify as high risk group
for pneumovax and mening due to functional asplenia (included in ACIP
recs but worth calling out)
Invited
No change
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No change
This is done.
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Comments
Suggestions
7 Need clarification of when to give boosters (or not). Reccomendations are Need a summary table of normal
changing
immunization needs including boosters
Type
Public
Discussion
The table in the chapter is being updated.
No change
54
Invited
No change
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Invited
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Invited
54
10 2nd Pneumovax has historically been given age 5 years in patients with
sickle cell disease, but most recent ACIP Dec 2010 recommendation is to
give 2nd dose 5 years after the 1st dose for children with sickle cell
disease. I personally have had some health departments not give 2nd
Pneumovax until age 7 years due to this. Based on the above mentioned
articles and ACIP guidelines, I've started continuing penicillin prophylaxis
beyond 5 years age and giving 2nd Pneumovax age 7 years. Since I'm
continuing penicillin, I don't feel as nervous having an unprotected gap
between 5 and 7 years age. Also, I think recommendation should be
made to give PCV13 to children age 6-18 years who've not been
previously vaccinated? This is also discussed in the ACIP 2010
recommendation.
Public
Please see the URL that will be provided. No further change will No change
be needed.
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10 second dose of PPV should be given 5 years after 1st dose per recent
AAP and CDC guidelines
0 I agree that studies are needed for pulmonary hypertension,
TCD in adults, renal disease, screening for asthma, natural history of
sickle cell retinopathy, Hypertension, needs of PFTs, natural history of
osteopenia and osteoporosis in SCD. However, one has to be cautious
regarding optimal management of pain crisis in pregnancy. Transfusion
should the treatment of choice. Avoidance of dependency or addiction is
important. In my experience the few patients with pain difficult to manage
are patients on habit forming opiates prescribed by theirs providers in
huge amount for years. The use of adjunctive non pharmacologic
approaches including psychosocial support are important.
Public
Public
Please see the URL that will be provided. No further change will No change
be needed.
This is beyond the scope of this chapter.
No change
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Clarify recommendation.
Action/Recommendation
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Comments
15 Adult TCD trials. Should be omitted because of issues about ability to
screen all adults due to closed bone windows. See above.
Suggestions
Type
Public
Discussion
TCD in adults should be addressed. Neuroimaging.
Neurocognitive testing. This could be combined. Neuroimaging
and neurocognitive evaluationNeurocognitive assessment
Action/Recommendation
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No change
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Invited
No change