You are on page 1of 78

~

P"wn+6"n
OFFICE OF 0003 7-- SEP -4 A 8 41 Direct Dia L•
(908) 218 -3227
GENERAL COUNSEL Fa u : (908) 218-3084

August 31, 2007

Division of Dockets Management (HFA-305 )


U.S. Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852

Re : Docket No . 2006P - 0071

Dear Sir/Madam :

We submit this comment on behalf of Ethicon, Inc . and Closure Medical Corporation
("Ethicon and Closure"), subsidiaries of Johnson & Johnson, in opposition to the FDA's proposal to
reclassify tissue adhesives for the topical approximation of skin from class III to class 11 . 1 Closure
developed and manufactures DermabondTM Topical Skin Adhesive (2-octyl cyanoacrylate )
("Dermabond"), the first tissue adhesive to receive FDA approval, and Ethicon markets it . Johnson
& Johnson objects to the agency's proposed reclassification of tissue adhesives because the
companies firmly believe that the administrative record in this proceeding is inadequate to meet the
standards for reclassification, in particular, because it does not contain valid scientific evidence
either to characterize the generic type of device for reclassification or to define the device's
performance parameters and its risks . Importantly, the record is empty of evidence that the agency's
proposed controls will provide reasonable assurance of safety and effectiveness for topically applied
tissue adhesives . Indeed, the principal proposed controls, premarket notification and a special
controls guidance document, fail to address two of the relevant factors that are critical to ensuring
safety and effectiveness : device composition and manufacturing . Simply put, neither premarket
notification nor the proposed special controls will result in the composition and manufacturing
specifications or clinical data that are crucial to providing patients safe and effective tissue
adhesives .

As we explain later in greater detail, the formulation and manufacturing of tissue adhesives is
extremely complex. As a result, creating a safe and effective tissue adhesive product is very
difficult. Indeed, although the tissue adhesive technology was first discovered in 1951,2 it took 47
years for FDA to approve the first tissue adhesive in 1998 . Prior attempts to control the technolog y

1 See 72 Fed. Reg. 36398 (July 3, 2007) (FDA's proposal for reclassification of tissue adhesives for
the topical approximation of skin) .

2 See James V . Quinn, M.D., Tissue Adhesives in Clinical Medicine 19 (2nd ed . 2005) .

ZOO- a 07l

~
Docket No . 2006P - 007 1
August 31 ; 2007
Page 2

resulted in products that caused acute and chronic inflammatory reactions .3 Use of tissue adhesives
was limited because of the potential for thermal damage and tissue scarring and concerns regarding
histotoxicity .4 Even today, there are only three tissue adhesives approved by the FDA and they vary
significantly in technology, formulation, product characteristics and performance . To date, PMA
controls, including well-controlled clinical trials and pre-approval inspections, have been necessary
to ensure that new tissue adhesives that enter the market are safe and effective . Nothing has changed
since any of these PMA approvals to suggest that these comprehensive controls are unnecessary
now . Indeed, nothing in the administrative record supports a change in regulatory control . In other
words, the technology has not matured to a point where FDA knows enough to apply generic special
and general controls to provide reasonable assurance of safety and effectiveness .

For these reasons, and the fact that the agency failed to conform the reclassification process
or evidentiary record to the legal requirements for reclassification of tissue adhesives, FDA's
proposal for reclassification should be withdrawn and the reclassification petition should be denied .
The following comment makes the case that the proper procedures for reclassification were not
followed, thus biasing the process, and that the requirements to move a device from a class III,
premarket approval status to class II have not been met . In sum, we conclude that no basis exists in
the administrative record to reclassify topically applied tissue adhesives from class III to class I L

COMMENT IN OPPOSITION TO RECLASSIFICATION

1 . Legal Criteria And Data Requirements For Reclassificatio n

A. FDA Erred in Characterizing Tissue Adhesives As Transitional Devices And


Failed To Instruct The Panel On The Legal Standard For Reclassification A llowing
The Panel To Rely Heavily On Evidence That Cannot Legally Support Reclassification .

Johnson & Johnson objects to FDA's characterization of tissue adhesives as transitiona l


devices because the agency failed to demonstrate that the device meets the legal definition for
transitional devices, and thus, incorrectly applied the abbreviated transitional device reclassification
procedures to tissue adhesives . Additionally, the agency failed to properly instruct the panel on the
appropriate standards for reclassification . Importantly, the record clearly shows that the panel failed
to limit the considerations for its recommendation to valid scientific evidence, and instead, relied on
anecdotal information, e .g., Medical Device Reports ("MDRs") and personal experience, as the
mainstay for its recommendation . Johnson & Johnson thus believes the panel's recommendation
was biased and failed to conform to the legal requirements for reclassification .

L Tissue Adhesives For Topical Approximation Of Skin Do Not Meet The Legal
Definition For Transitional Devices.

3 See James V. Quinn, M.D., Tissue Adhesives in Wound Care 41 (lst ed . 1998) .

4 See Quinn, supra note 2, at 17.


~
~
Docket No . 2006P - 007 1
August 31, 2007
Page 3

FDA characterizes tissue adhesives as transitional devices, justifying its view by asserting
that after publication of a list of transitional devices in the Federal Register in 1977, see 42 Fed.
Reg. 63472 (Dec . 16, 1977), INDs and NDAs for products regarded as transitional devices were
transferred to CDRH and the transfer included some products, such as tissue adhesives, that were
absent from the 1977 published list.5 See 72 Fed. Reg. 36398, 36399 (July 3, 2007) . However, the
agency does not state whether the applications that were transferred were in effect or pending on
May 28, 1976, the date of enactment of the Medical Device Amendments of 1976 (hereinafter
"enactment date") .

We do not dispute that at least one tissue adhesive submission was made to FDA's drug
section prior to the enactment date ; however, if tissue adhesives do not meet the legal definition for
transitional devices in section 520(1) of the Federal Food, Drug, and Cosmetic Act ("FDCA" or "the
Act"), the product would not qualify as a transitional device . Under the FDCA, transitional devices
are those products :

A . For which an approved NDA was in effect on the enactment date ;


B . For which an NDA was "filed on or before the enactment date and with respect to which
application no order of approval or refusing to approve had been issued on such date" ;6
C . For which an IND was in effect on the enactment date ;
D . Which is within a type of device described in A, B, or C, and is substantially equivalent to
another device within that type;

5 During the panel meeting held on August 25, 2006, to discuss the reclassification of tissue
adhesives, Mr . Melkerson, Director of FDA's Division of General, Restorative and Neurological
Devices, stated that there were approximately 20 products, including tissue adhesives, that were not
in the 1977 Federal Register notice that were transferred to CDRH, and the only information
demonstrating the transfer was a memorandum to CDRH that identified the products being
transferred to CDRH . Transcript of General and Plastic Surgery Devices Panel Meeting at 12 4
(Aug. 25, 2006) [hereinafter "Panel Transcript"] . Although Mr. Melkerson stated that he may have a
pdf of the memorandum and the panel requested a copy of it at the meeting, this memorandum has
never been submitted to the record .

6 This criterion does not apply to NDAs that were submitted to FDA, but abandoned or withdrawn
before the enactment date . There is no suggestion in the legislative history of the Medical Device
Amendments of 1976 that this criterion was intended to apply to such NDAs, and the legislative
history indicates that Congress intended this criterion to apply to pending NDAs . For example,
Congress stated that for this criterion, the NDA would be considered a PMA and FDA would be
required to act on the application within the period in which it would have been required to act on an
NDA, thus indicating that this criterion applies to applications which required agency action, i.e.,
pending applications . See Conference Report, H .R. Rep. No . 94-1090, at 62-63 (1976) . Section
520(l)(2) included as transitional devices all devices that met the criteria of subparagraphs (E) and
(F), including those subject to withdrawn or abandoned NDAs, assuming FDA took the actions
specified in these subparagraphs to affirmatively declare such products drugs .
Docket No . 2006P - 0071
August 31, 200 7
Page 4

E . Which FDA in a notice published in the Federal Register before the enactment date has
declared to be a new drug subject to section 505 ; or
F . With respect to which on the enactment date an action was pending in court under section
302, 303, or 304 for an alleged violation of a provision of section 301 which enforces a
requirement of section 505 or for an alleged violation of section 505(a) .
FDCA §520(l)(1) .

The agency has provided no evidence, nor is there any evidence in the administrative record ,
to establish that tissue adhesives fall under any of these categories of transitional devices . Thus,
even if tissue adhesives were included in the list of INDs and NDAs that were transferred to CDRH
after the enactment date, any agency action after the enactment date would have no legal
significance for purposes of defining the product as a transitional device, unless an IND was in effect
or NDA was pending or approved on the enactment date . 7 Simply put, no legal basis exists to
support a transitional device status for tissue adhesives . Instead, tissue adhesives are "new" devices
(those automatically classified into class III under section 513(fl(1)) 8 subject to more detailed
reclassification procedures than transitional devices .

2. The Panel Was Not Instructed On The Appropriate Legal Standard for
Reclassification. As A Result, The Panel Improperly Relied On Evidence That Was Not
Valid Scientific Evidence .

Although every device reclassification must be supported by valid scientific evidence, the
reclassification regulation for "new" devices is explicit on this legal standard with regard to panel
recommendations . In particular, the regulation requires the panel in its review to consider, inter alia,
the factors in 21 CFR § 860 .7 relating to the determination of safety and effectiveness, and to
determine the safety and effectiveness of the device on the basis of valid scientific evidence.9 See 21

7 We are aware that an NDA for a tissue adhesive was filed in 1964, but the applicant decided to
abandon the NDA in 1970 because the agency required a long-term study to evaluate the possible
carcinogenicity of cyanoacrylates that would have been too costly, and there was no assurance that
the agency would not request additional studies . See James V. Quinn, Tissue Adhesives in Clinical
Medicine 19 (2d ed . 2005) (stating that an approval application for a cyanoacrylate tissue adhesive
("CTA") was submitted to the FDA in 1964, but further work on the CTA was abandoned in 1970
due to the failure to obtain FDA approval) . Because the NDA was abandoned in 1970, it was not
pending on the enactment date and we are not aware of any NDAs or INDs that were pending or in
effect on May 28, 1976 .
8
Because tissue adhesives do not meet the definition of a transitional device, and any preamendment
tissue adhesives were investigational, there were no tissue adhesives in commercial distribution prio
III rtohenacmd,usrltingheaomcsiftnueadhvsitocl
under section 513(f)(1) as not substantially equivalent to a preamendment device .

9 The definition of valid scientific evidence is set out in 21 CFR § 860 .7(c)(2) :

Valid scientific evidence is evidence from well-controlled investigations, partially


Docket No . 2006P - 0071
August 31, 200 7
Page 5

CFR § 860 .134(b)(4), 860 .84(c) . The reclassification regulation for transitional devices, however,
fails to specify the manner in which a panel should be instructed by FDA, and thus, the need for
valid scientific evidence. See 21 CFR §860 .136 .

Based on our review of the transcript of the panel meeting held on August 25, 2006, to
discuss the tissue adhesive reclassification petition, it appears that the panel in fact was not properly
instructed on the appropriate legal standard. Instead, in literal reliance on the truncated transitional
device reclassification regulation, FDA provided panel members with summary instructions without
informing the panel that valid scientific evidence is necessary to support a reclassification
recommendation . Further, FDA's briefing memorandum to the panel did not contain a valid
scientific evidence instruction, and the questions posed to the panel by FDA staff failed to inquire
whether valid scientific evidence supports all elements of a device reclassification from class III to
class II . See Section I.B, infra . However, assuming arguendo that the panel was properly instructed
privately by the FDA, nonetheless, the panel failed to follow such instructions, and importantly,
neither FDA staff nor the panel executive secretary "re-instructed" the panel when it discussed and
clearly relied upon evidence that was not valid scientific evidence and could not legally support
reclassification .

Specifically, the panel members relied heavily on personal experience and MDRs, and the
agency's own panel briefing memorandum relied on the MDR information .10 Personal experience
and MDRs are not valid scientific evidence . Not surprisingly, the panel completely failed t o
critically determine whether valid scientific evidence existed in the record to demonstrate that a
generic type of tissue adhesive device could be reclassified from class III to class II . In other words,
FDA's failure to properly instruct the panel on the correct legal standard tainted and biased th e

controlled studies, studies and objective trials without matched controls, well-
documented case histories conducted by qualified experts, and reports of significant
human experience with a marketed device, from which it can fairly and responsibly
be concluded by qualified experts that there is reasonable assurance of the safety and
effectiveness of a device under its conditions of use . The evidence required may vary
according to the characteristics of the device, its conditions of use, the existence and
adequacy of warnings and other restrictions, and the extent of experience with its use .
Isolated case reports, random experience, reports lacking sufficient details to permit
scientific evaluation, and unsubstantiated opinions are not regarded as valid scientific
evidence to show safety or effectiveness . Such information may be considered ,
however, in identifying a device the safety and effectiveness of which is questionable .

10 The petition "is based on a history of safe and effective use of these devices and the scarcity of
adverse events reports in the published medical articles, as well as the risks to health reported in the
FDA's Medical Device Reporting System ." FDA Summary Memo, General and Plastic Surgery
Devices Advisory Committee (Panel) Meeting On August 25, 2006, at 6[hereina$er "Panel Briefing
Memo"] . FDA's own review of its MDR database found "the risk of significant clinical adverse
events when using the device is low and consistent with events reported in the published literature ."
Id. at 8 .
Docket No . 2006P - 0071
August 31, 200 7
Page 6

panel's recommendation, inviting the panel to rely on anecdotal and other limited information for its
determinations.

B. Standards For Reclassification

To achieve reclassification of a generic type of device from class III to class II, there must be
valid scientific evidence in the administrative record demonstrating that class II controls, i.e., special
controls and general controls, will provide a reasonable assurance of safety and effectiveness . See
Contact Lens Mfrs. Assoc . v . Food and Drug Admin ., 766 F .2d 592, 599 (D .C. Cir. 1985) ; Ethicon,
Inc. v. Food and Drug Administration, 762 F . Supp . 382, 384 (D.D.C. 1991) ; see also 21 CFR §
860.3(c)(2), 860 .7(c)(1), 860.134(b)(4), 860 .84(c) . Indeed, "the absence of [valid scientific
evidence] may be the basis for classification of the device into Class III", see 43 Fed. Reg. 32988,
32991 (July 28, 1978) (final rule establishing FDA's classification regulations in 21 CFR Part 860)
and 21 CFR § 860 .7(g)(1), and likewise the basis to deny reclassification of a class III device into
class II or class I .

What is clear is that while the type of valid scientific evidence required may vary due to the
nature of a device, and its conditions of use and labeling, "[i]solated case reports, random
experience, reports lacking sufficient details to permit scientific evaluation, and unsubstantiated
opinions" cannot support a reclassification . 21 CFR § 860.7(c)(2) ; Contact Lens, 766 F .2d at 600 .
For example, professional testimonials and personal or general statements of experience with a
product or type of product are anecdotal information, and cannot constitute the type of valid
scientific evidence necessary to demonstrate a reasonable assurance of safety and effectiveness for a
generic type of device. See id. Similarly, MDRs, such as those relied upon in the reclassification
petition and by FDA in its panel briefing memorandum and proposed reclassification, 72 Fed. Reg.
at 36399, cannot provide detail or substantiation that permits scientific analysis . The absence of
such reports is a similarly unscientific measure of device safety and effectiveness, particularly
because of known underreporting .

For FDA to support reclassification, there must be sufficient valid scientific evidence of
safety and effectiveness in the administrative record (1) "for the agency to understand the device" in
order to determine the generic type being reclassified and its performance parameters and risks, and
(2) "to demonstrate that factors determining the device's safety and effectiveness are controllable",
i.e., to demonstrate that special controls can be identified that will address the identified performance
parameters and risks and provide a reasonable assurance of safety and effectiveness . Ethicon, 762 F .
Supp . at 388 . The Act's general controls, such as premarket notification, cannot compensate for the
lack of an adequately characterized generic type or lack of adequate special controls .

As the following shows, FDA's reclassification proposal for tissue adhesives fails to rely on
administrative record evidence that defines a coherent generic type of tissue adhesives, or valid
scientific evidence identifying the performance parameters and risks of tissue adhesives that must be
controlled to provide reasonable assurance of device safety and effectiveness . Additionally, the
administrative record falls far short of providing valid scientific evidence, or frankly any evidence at
all, that the proposed special controls and the Act's general controls will result in safe and effective
Docket No . 2006P - 0071
August 31, 2007
Page 7

tissue adhesives . To the contrary, the FDA, like the advisory panel it educated, relies upon anecdotal
information and assumptions about device performance to support its proposed reclassification .

In sum, the petition and the FDA's proposed reclassification, including the proposed special
controls, fail to meet the legal standards for a reclassification . The administrative record
demonstrates that tissue adhesives are too variable in composition, and the manufacturing
procedures for the device too critical to safety and effectiveness, for effective regulation at a class II
level . Additionally, the effect on tissue adhesive safety or effectiveness from subtle changes in
composition or the manufacturing process make the device too variable for the generic controls that
define class II. Moreover, even assuming an acceptable generic type of device that could be
reclassified into class II, FDA has failed to fully identify the device's performance parameters and
risks, and lacks valid scientific evidence in the administrative record to justify reclassification . In
other words, FDA lacks a legal basis to reclassify tissue adhesives into class II, see Ethicon, 762 F .
Supp . at 384 & 387-88 .

H. FDA's Proposed Reclassification is Unjustifiably Broad and Cannot Be Saved By Limiting


It to Cyanoacrylate Tissue Adhesives ("CTAs"), Because CTAs Are Too Dissimilar To
Constitute A Generic Type Of Device .

Without evidence in the administrative record, FDA's proposed reclassification broadly


encompasses all tissue adhesives, whether cyanoacrylate-based or not . Even if the reclassification
were limited to CTAs, trade secret, methods of manufacture, and product composition information
from PMAs could not be used to support reclassification, see FDCA §§ 520(c) and 520(h)(4), and
such information is unavailable in the published literature . Indeed, the administrative record in this
proceeding is devoid of such evidence, and there is no basis to support the conclusion that one tissue
adhesive will have the same performance characteristics or risk profile of any other .

Specifically, this lack of data on methods of manufacture and product composition in the
administrative record is particularly troublesome because the composition of CTA devices and their
manufacturing techniques are significantly variable, and formulation and manufacturing are directly
relevant to most of the risks and performance parameters identified by FDA in its Federal Register
reclassification proposal (and to those that FDA failed to identify, see Sections III .A.1 and III .B.l,
infra). Indeed, the differences among the CTAs are critical enough to product performance that
continuation of product-by-product review and approval is necessary to provide reasonable
assurance of safety and effectiveness . Simply put, FDA is lacking the formulation and
manufacturing information critical to understanding and establishing a generic type of device . On
this basis alone, the reclassification petition should be denied .

A . FDA's Proposed Reclassification Of "Tissue Adhesives For The Topical


Approximation of Skin" Fails to Identify A Meaningful Generic Device Type.

FDA identifies the device proposed for reclassification as follows :

Tissue adhesives for the topical approximation of skin are intended for topical closure
of surgical incisions, including laparoscopic incisions, and simple traumatic
Docket No . 2006P - 0071
August 31, 200 7
Page 8

lacerations that have easily approximated skin edges . Tissue adhesives for the topical
approximation of skin may be used in conjunction with, but not in place of, deep
dermal stitches .

General and Plastic Surgery Devices ; Reclassification of the Tissue Adhesive for Topical
Approximation of Skin Device, Proposed Rule, 72 Fed. Reg. 36398, 36401 (July 3, 2007) . Although
FDA states in the preamble that this device "may contain cyanoacrylate as the active ingredient", see
id. at 36399, this broad identification on its face covers products other than those containing
cyanoacrylate . Thus, although the panel believed the reclassification only pertained to products
based on the then approved CTAs, Dermabond and Indermil, FDA has proposed a reclassification
that encompasses many more products, potentially including products with technologies unknown to
the agency . Without even considering the lack of similarity in composition and manufacturing
among the approved CTAs, the proposed scope of reclassification raises the question of how can
there be a meaningful generic type of device when the proposed device type clearly exceeds CTAs in
breadth. While under the court's analysis in Ethicon, each reclassification effort is fact driven, the
proposed reclassification of CTAs is similar to the facts of Contact Lens, because the approved CTA
monomers cited in the petition as comprising the generic type of device for reclassification cove r
two chemically distinct legally marketed liquid adhesives (2-octyl and n-butyl), and FDA's proposed
generic type would be defined by the universe of tissue adhesives, including of course, those that
have yet to be formulated . In effect, like in Contact Lens, the so-called "generic type" would include
too many chemically different products to be meaningful .

B . Even Among CTA devices, FDA Fails to Describe a Generic Type of Device.

CTAs differ from one another to such an extent that stating the reclassification "may contai n
cyanoacrylate" is essentially a description without meaning . Indeed, CTAs differ so greatly that
similar regulatory controls cannot be identified that will provide a reasonable assurance of safety and
effectiveness for all cyanoacrylates . For example, Dermabond and Indermil have different basic
starting materials (butyl versus octyl cyanoacrylate), different chemical processing conditions and
controls during manufacture, different chemical stabilizers, and different systems that control
polymerization of the liquid adhesive during use . Indeed, differences in the products' stabilization
system and means of initiation are seen in how the products are stored : Dermabond is stored at room
temperature and used without further preparation, while Indermil requires refrigerated storage and
warming prior to use.

As pointed out by U .S . Surgical,ll the petition contradicts itself by attempting to create a


generic device type, yet at the same time recognizes the vast differences between octyl and butyl
cyanoacrylates . See RCRI Petition for Reclassification of Tissue Adhesive for Soft Tissu e
Approximation (Feb . 9, 2006) ("Petition") at 5 (stating "Butyl and Octyl cyanoacrylate tissue
adhesives differ in that butyl tissue adhesives, with their smaller molecular size provide higher
tensile strength but are less flexible than the lower tensile strength but more flexible octyl materials .

ll See U.S
. Surgical, Response to Petition for Reclassification of Tissue Adhesives for Soft Tissue
Approximation, Docket No. 2006P-0071/CCP 1 , at 2 (Aug . 9, 2006).
# 0
Docket No . 2006P - 007 1
August 31, 2007
Page 9

Butyl materials also polymerize faster than octyl cyanoacrylates .") . Even FDA's draft special
controls guidance recognizes that "formulations can be manufactured that vary in viscosity, setting
time, bond strength, degradation rate, and other physical and mechanical properties . . .[that] define
the adhesive performance and utility of the final product ." FDA Draft Guidance, Class II Special
Controls Guidance Document : Tissue Adhesive for the Topical Approximation of Skin at 7 (July 3,
2007) (hereinafter "Special Controls Guidance") . Despite this specific acknowledgement, the
agency is pressing forward with reclassification, even without access to publicly available
administrative record information that provides details of chemical formulation, chemical
engineering, and manufacturing processes that are critical to characterizing the biochemical
properties of the three approved devices, or to relate those properties to the device's performance
parameters and risks, see Section III, infra . 1 2

C . The Composition And Manufacturing Of The Approved CTAs Vary So Great1v


That A Generic Type Of Device Cannot Be Estab lished . In Particular, Even If Two
CTAs Have The Same Base Monomer, Differences In Trace Additives, Chemically
Transformed Trace Additives, And Impurities Can Significantly Affect Device
Characteristics .

Even had FDA limited the reclassification to CTAs, the generic type would be inadequately
characterized with regard to composition and manufacturing . As both Closure and U .S . Surgical
previously explained, because of the differences in proprietary formulations, each CTA can have
different "ingredients", i .e., stabilizers, plasticizers, levels of impurities, etc . As stated in the
administrative record, "While design verification testing may confirm the initial specifications, each
of these product attributes must be properly managed in order to ensure that the specifications are
met and that the risk of injury to the patient (in terms of exothermic reaction, dehiscence, and
cosmesis) is minimized ." U.S . Surgical, Response to Petition for Reclassification of Tissue
Adhesives for Soft Tissue Approximation, Docket No . 2006P-0071/CCP1, at 3 (Aug. 9, 2006) .
Even a representative of the petitioner, Mr . Stenton, acknowledged that the significant difference in
viscosity between Dermabond and Indermil "leads to the devices being more than just the monomer
themselves ." Panel Transcript at 85 .

Further, Dr . Anthony A . Parker's explanation of the extreme complexity of CTA


composition, which is part of the panel record, as well as comments from Polymer Synergies,1 3

12 Not only is FDA lacking the formulation and manufacturing information critical to establishing
the generic type of device, it can rely only on one of the three approved PMAs, Dermabond, for
safety and effectiveness information . As noted above, RCRI improperly used information from both
the Dermabond and Indermil PMAs to support its petition . See Petition at 17 (providing adverse
event reporting rates from clinical studies in both PMAs) . FDA also illegally relied on the Indermil
PMA in its panel briefing memorandum . See Panel Briefing Memo at 5 . Also, at the panel meeting,
Mr. Melkerson from CDRH informed the panel that the agency would "reclassify those products that
are currently in PMA approval" and "[t]he petition is only for those products that are currently
PMA-approved," suggesting that reclassification is based on both PMAs . Panel Transcript at 133 .
13
See complete comments in Closure Medical Corporation's Comments Regarding Petition for
Docket No . 2006P - 0071
August 31, 200 7
Page 1 0

discuss how minor variations in trace additives, chemically transformed trace additives, and
impurities can greatly affect the devices' performance characteristics, such as the polymerization
rate, shelf life and other attributes i.e ., the heat of reaction, green strength, cure rate, shear strength,
tensile strength, peel strength, burst strength, etc . The following briefly summarizes their comments .

These expert views establish in the record that to create a CTA, a manufacturer adds
initiators and inhibitors to control the overall rate of polymerization and the product's shelf-life, but
key ingredients such as monomers will already contain "trace additives," i.e., inhibitors and
stabilizers and other compounds which have been purposely added by the monomer supplier for in-
process stability to prevent premature radical polymerization reactions and for shelf stability . If a
key monomer ingredient is purchased from a different supplier, it might contain different levels and
types of these trace additives .

Additionally, they state the "same" monomer from a different supplier might contain
different "chemically transformed trace additives," i.e., trace compounds such as inhibitors that
undergo chemical transformations during the lifespan of the monomer . Because different
manufacturers employ different conditions during the production of a monomer, i.e., different
reaction temperatures, reaction times, atmospheric conditions, head space volumes, etc ., the
chemical nature of these transformed inhibitor species will vary among manufacturers . The
chemical transformation of post-addition inhibitors, which enhance the monomer's shelf life or
control an end user's induction period, occurs over longer periods of time, typically during the
storage of the monomer product. Thus, the chemical nature and concentrations of these transformed
inhibitors depend on the storage conditions (i.e., storage time, temperature, atmospheric exposure to
oxygen, atmospheric exposure to moisture, chemical nature of the storage container, shipping
conditions, etc.) . Here again, because storage conditions vary among manufacturers and facilities,
even a simple change can result in a finished formulation with different characteristics .

Importantly, a manufacturer generally cannot specify the chemical nature of inhibitors used
in monomers, because this knowledge is often considered to be proprietary and specific to a given
monomer manufacturer's process . Nor could a manufacturer specify the chemical compositions of
transformed additives, because the in-process chemical transformations will vary amon g
manufacturers . There are no analytical protocols for detecting trace additives that sufficiently detect
the chemically transformed additives because their identities and characteristics are typically
unknown and highly variable . Moreover, the monomer's trace additives may also undergo chemical
transformations after they have been incorporated into a finished adhesive formulation, which could
alter the adhesive's cure characteristics in potentially unpredictable ways .

Also, the "same" monomer purchased from a different supplier might contain different "trace
impurities," i.e., contaminates whose presence may or may not be known . Cross-contamination can
occur when a manufacturer transfers materials via pipes, hoses, or pumps from its inventory to a
reactor, or from a reactor to storage vessels, such as totes, drums, or a truck . If a single reactor is

Reclassification of Tissue Adhesives for Soft Tissue Approximate, Docket No . 2006P-0071, Att . 1
(Aug . 9, 2006).
Docket No . 2006P - 0071
August 31, 200 7
Page 1 1

used to produce multiple products, the potential for cross-contamination arises both before and after
each production changeover . Batch size also is an important factor in minimizing transfer
impurities . The capacity of the reactor, head space in the reaction vessel, and agitation efficiency
can contribute to impurity levels . Unfortunately, the manufacturers who purchase the monomers
may unknowingly end up formulating their products with monomers that contain varying levels and
types of cross-contaminates . Thus, the manufacturer may adjust the initiator or inhibitor levels to
compensate not only for the reaction chemistry of the monomer itself, but also for the effects created
by the cross contaminate, which may or may not be present in the next batch of monomer product
that is purchased .

In sum, minor variations in the composition of CTAs can affect the cure chemistry and the
final properties of a CTA . The "same" monomer from two different suppliers may produce finished
formulations with completely different rates of polymerization which would likely lead to
unanticipated variations in the clinical effectiveness of a formulated product . As Dr . Parker
explained :

Each supplier of a nominally identical product will have its own unique set of
manufacturing procedures, raw material sources, additives, storage conditions, and
shipping conditions . In turn, each of these factors has the potential to influence the
chemical structures and concentrations of minor compositional components,
including trace additives . . ., trace impurities . . ., and transformed trace additives . The
concentrations and chemical identities of these minor components will inevitably vary
from manufacturer to manufacturer, even when the primary components are
nominally the same . Moreover, even if a formulator were able to specify the tolerable
limits and structures of specific trace additives, it is unlikely that he/she would ever
have control over the compositions of chemically transformed additives, mainly
because the nature of these species will be specific to the monomer's process history,
and to the manufacturer's synthetic procedures, which are usually proprietary.

Closure Medical Corporation's Comments Regarding Petition for Reclassification of Tissue


Adhesives for Soft Tissue Approximate, Docket Na 2006P-0071, Att . 1(Dr . Parker's Report) at 9
(Aug . 9, 2006) (hereinafter "Closure Comments") .

Thus, the safety and effectiveness of the approved cyanoacrylate materials for wound closure
depend not on the generalizable characteristics of the materials, but on their specific composition
and manufacturing, which for the PMA approved products have been individually established
through substantial proprietary evidence demonstrating that process conditions and quality controls
will ensure a consistent material is produced and properly assembled into its applicator . As pointed
out by U .S . Surgical in its opposition to the reclassification petition, even the recently published
ASTM standards relied upon in the proposed special controls guidance emphasize the complexity of
and differences between these products, and direct an individualized decision about whether a
standard is an appropriate measure of strength properties of tissue adhesives . In short, the controls
of the PMA process are necessary for safe and effective tissue adhesives . If these devices were
reclassified as class II, 510(k) products, there could be no reasonable assurance of their safety and
~ .
Docket No . 2006P - 007 1
August 31, 2007
Page 12

effectiveness, because there would be no pre-approval inspection, no rigorous manufacturing review,


and companies would be able to modify design and manufacturing without FDA's premarket review .

III. FDA Failed To Fully Define Performance Parameters And Risks, And To Identify
Adequate Special Controls ; Moreover, The Administrative Record Lacks Valid Scientific
Evidence To Support FDA's Reclassification Proposal And Proposed Special Controls .

A review of the administrative record relied upon by FDA shows there is not enough valid
scientific evidence to support reclassification . The evidence does not provide an adequate basis to
identify the performance parameters and risks or to show that FDA's proposed special controls
guidance can control the parameters and risks to provide reasonable assurance of safety and
effectiveness in conjunction with the Act's general controls . FDA identified 17 articles as
representative of the published literature in the petition, but these articles do not constitute valid
scientific evidence to support the proposed reclassification . Almost half of the articles relate only to
Dermabond ;14 however, valid scientific evidence about one device cannot support reclassification of
a generic type that is comprised of more than one product, with varying compositions and differing
clinical expressions . There is very little information in the literature relating to any bench or animal
testing or other controls used in developing non-Dermabond CTAs . As the agency noted in its
briefing memorandum to the panel, "[a]n understanding of the methods to assess safety and
effectiveness is a central factor in the classification of medical devices ." FDA Summary Memo,
General and Plastic Surgery Devices Advisory Committee (Panel) Meeting On August 25, 2006, at
11 [hereinafter "Panel Briefing Memo"] .

The balance of the literature highlighted by the FDA as representative of the petition's
showing fails to provide adequate valid scientific evidence to support reclassification . For example,
three articles are not reports of prospective clinical trials . The first just provides a general discussion
of CTAs, focusing primarily on Dermabond .15 The second article provides a brief description of one
facility's six-month experience with CTAs without reference to any specific CTA .16 Thus, there is
no information on the specific product used at the facility and the information provided is anecdotal .
Finally, the third article is a retrospective review of eight different clinical studies, four on butyl-

14 Eight of the 17 articles relate to only Dermabond . Similarly, of the total number of articles cited
and actually reviewed by the petitioner (108), nearly half (44%) relate to Dermabond (octyl-
cyanoacrylate) . We assume that articles on octyl-cyanoacrylate relate to Dermabond because we are
not aware of any other octyl-cyanoacrylates that are marketed domestically or internationally .
Additionally, for 22 of the 108 articles, the petition does not identify the particular CTA that is
discussed ; thus, it is unclear whether the CTA in these articles relate to Dermabond or even to an
FDA approved CTA .
1 5 See
Dean M. Toriumi et al., Cyanoacrylate Tissue Adhesives for Skin Closure in the Outpatient
Setting, Otolaryngol . Clin . North Am . (Feb . 2002) 35(1) at 103-18 .
16
See Azize Kilic, M.D . & Emre Ozdengil, M .D ., Skin Graft Fixation by Applying Cyanoacrylate
WithoutAny Complication (July 2002) 110(1) at 370-1 .
0 0
Docket No . 2006P - 007 1
August 31, 2007
Page 1 3

cyanoacrylates and four on octyl-cyanoacrylatesl 7 in which the author states that "the validity of
these studies must also be taken into account including the general poor quality and small sample
size" and concludes that "there is insufficient evidence that using the tissue adhesive leads to lower
or higher levels of dehiscence, infection, satisfaction with cosmetic appearance, patient or surgeon
general satisfaction, than using sutures, adhesive tape or any other technique ."18 Because of the
limitations of the studies reported in these articles, this information cannot constitute valid scientific
evidence supportive of reclassification .

The FDA-designated representative articles, reporting the results of prospective clinical


trials, are also of limited value for purposes of reclassification . Specifically, the six articles that
discuss prospective clinical studies involve limited numbers of subjects with a total of 60 to 100
subjects in each study . Additionally, these are all comparative studies so the number of subjects
evaluated in the particular CTA group is about half of the total enrolled . Indeed, one author
qualified the results in a study stating, "the author recognizes the limitations of this study . . . and a
larger, more detailed study should be carried out should more information be required regarding
efficacy and wound closure ."19 Compared to the large, randomized, controlled clinical trials
required for approval of the Dermabond PMA (818 patients) and Indermil PMA (1,092 patients),
these small studies cannot provide the valid scientific evidence necessary to support reclassification
of tissue adhesives .20 Importantly, none of the representative literature bears on the ability of FDA's
proposed controls to provide reasonable assurance of device safety and effectiveness . Thus, the
articles which FDA identified as "representative" show the overall weakness of the petition's
purported scientific support . Importantly, had the panel been properly instructed on the
requirements of reclassification, its members would have considered the record evidence differently .

17 See P . Coulthard et. al., Tissue Adhesives for Closure of Surgical Incisions, Cochrane Database
Systematic Rev. (2002) 3(2) :CD004287 .
ls Id.
at 8-9 .
19 A
. Charters, Wound Glue : A Comparative Study of Tissue Adhesives, Accid . Emerg . Nurs . (Oct.
2000) 8(4) at 223-7 .

20 In addition to their small sample size, there were other limitations as well . For example, one study
had questionable validity due to the large number of patients who failed to complete the protocol ,
see Vance Brown, M .D., Laceration Repair with Tissue Adhesive in Children, J . Fam. Pract
. (May
1997) 44(5) at 445-6 ; and two studies did not have a follow-up period that was adequate to evaluate
cosmesis (3-month follow-up is standard for cosmesis evaluation as reflected in the clinical trials
conducted to support the Dermabond and Indermil PMAs), see E.D . van den Ende et al., Adhesive
Bonds or Percutaneous Absorbable Suture for Closure of Surgical Wounds in Children, Results of
. Pediatr . Surg. (Aug. 2004) 39(8) at 1249-51 (six-week follow-up)aProspectivRndmzTral,J ;
Thomas B . Bruns, M.D. et al., Laceration Repair Using a Tissue Adhesive in a Children's
Emergency Department, Pediatrics (Oct . 1996) 98(4 pt 1) at 673-5 (two-month follow-up) .
Docket No . 2006P - 0071
August 31, 200 7
Page 14

A. The Described Performanc e Parameters For Ti ssue Adhe sives Are Incomplete And
The Special Control s Proposed Inad equate To Control Them.

1. FDA Failed To Identify All Important Performance Parameters.

The petition cites the following benefits of CTAs : effective wound closure, faster closur e
time than conventional closing techniques, improved cosmesis, less-invasive, less-tissue trauma, no
secondary dressing, and no suture/staple removal. See Petition at 11, 13-17 . Moreover, FDA asserts
CTAs "may prevent extended bleeding in the repair of surgical incisions and traumatic lacerations,
promote healing of approximated wound edges, and reduce pain and recovery time ." 72 Fed. Reg. at
36400 (stating "there is reasonable knowledge of the benefits of the device") . There is no question
that the three products that have been subjected to rigorous PMA review offer these significant
benefits . However, FDA and the petitioner fail to consider many other performance parameters
considered critical in the CTA approval process, including (1) adherence and endurance (how long
the product will remain intact once applied) ; (2) the ability to not potentiate infection; (3) the ability
to maintain a microbial barrier; and (4) how the skin reacts to the stabilizing agents . See, e .g.,
Dermabond P960052 Summary of Safety and Effectiveness Data ("SSED") at 16 (stating the panel
believed the most important parameters to look at in evaluating the results of the clinical study
included wound dehiscence and infection rate) ; Dermabond labeling (identifying skin reactions as
adverse events) ; Indermil P010002 SSED at 12 (explaining the clinical trial assessed wound healing,
cosmetic appearance, general condition and wound healing complications (dehiscence, infection,
skin irritation)) ; Histoacryl P050013 SSED at 17 (stating the clinical studies evaluated dehiscence,
infection, redness/tenderness, swelling, and fever) .

Moreover, the petition incorrectly minimizes the significance of some of these performance
parameters, characterizing them simply as labeling claims, and ignoring the fact that FDA required
clinical validation for some of them . See Petition at 6 (noting there have been PMA supplements
approved for high viscosity formulations, modified applicator systems, and expanded labeling
claims, including greater application control and recognition that the polymerized tissue adhesive
provides a microbial barrier) . Nonetheless, the petition itself recognizes that CTAs create unique
challenges that can only be addressed by clinical use . See Petition at 14 (noting a learning curve
with CTAs and that variables such as type of surgery, size of wound, and surgeons' competence with
closure type used affect the results) . Historically, FDA has required clinical data to provide valid
scientific evidence for numerous parameters, including, for example, data on pediatric patients
presenting in the emergency room . See, e.g., P960052/S4 (approval for Dermabond's higher
viscosity formulation) . Because FDA and the petitioner have not fully identified these parameters, a
generic device type for these CTAs cannot be adequately defined by the agency .

Last, the publicly available scientific literature does not yield ranges of values that would
constitute acceptable performance on required tests to demonstrate performance parameters are met .
Similarly, as discussed in Section II, supra, the literature lacks information on product composition
and manufacturing technologies that is critical to understanding and defining performanc e
parameters . The published literature does not provide any information on whether the
manufacturing controls, standards, and testing for octyl-cyanoacrylates are the same as for butyl-
cyanoacrylates . Because octyl-cyanoacrylates have different formulations and properties compared
~ •
Docket No . 2006P - 007 1
August 31, 2007
Page 1 5

to butyl-cyanoacrylates, it is likely that different manufacturing controls, standards, and testing were
used. Without detailed information about a device type, such as its basic formulation and methods
of manufacture, there is no reliable way of knowing what critical characteristics must be controlled
to provide reasonable assurance of safety and effectiveness . This is particularly true for ne w
cyanoacrylate or non-cyanoacrylate tissue adhesives that would come before FDA in the future .

2. The Draft Special Controls Guidance Fails To Adequately Address Or Control Even
The Performance Parameters Identified In FDA's Proposed Reclassification.

The proposed controls do not adequately address the performance parameters addressed by
FDA in its reclassification proposal, and certainly do not compensate for the lack of characterization
of the type of device . As with the lenses at issue in the Contact Lens case, even if detailed
information about the marketed products' composition and manufacture could be gathered to
establish special controls, conformity with a special control would not guarantee that tissue
adhesives would function safely and effectively in human use . Clinical data are necessary because
there is "no substitute for human trials" at this stage in the development of the products FDA
proposes here to reclassify, see Contact Lens, 766 F .2d at 597 . As recently as the Histoacryl PMA
approved on February 16, 2007, which was the second n-butyl cyanoacrylate tissue adhesive
approved, FDA did not find that standards could substitute for clinical data . Numerous ASTM
standard methods, including one proposed in the special controls guidance were relied upon in the
Histoacryl PMA, yet substantial controlled clinical trial data were still required to obtain approval .
Below we discuss in more detail the deficiencies in the proposed special controls as they relate to
performance parameters for CTAs .

(a) Non-clinical testing methodologies do not effectively evaluate critical performance


parameters .

Because of the importance of composition to performance, tissue adhesives must be


thoroughly evaluated through testing, including clinical testing . Indeed, medical professionals who
use these products emphasize the need for controlled clinical investigations . For example, Dr.
William D . Spotnitz, Professor of Surgery and Director of the Surgical Therapeutic Advancement
Center at the University of Virginia, opines that clinical evaluation of tissue adhesives in well-
controlled studies is the only way to assure the performance and safety of these products . See Panel
Transcript at 120-121 ; see also Declaration of Adam J . Singer, M .D. (Attachment 1) (hereinafter
"Singer Declaration") at ¶ 5 & 19 (stating that clinical studies are necessary to ensure that tissue
adhesives with different characteristics will not adversely impact clinical performance or increase
the risk of harm to patients) . Specifically, these devices function by transitioning from a liquid to a
solid form after they are applied to the skin, and this transition is unique with a large number of
factors that can influence the polymerization reaction . Thus, new tissue adhesives need to clinically
demonstrate safety and effectiveness, not substantial equivalence, to validate the chemical
formulation of any specific tissue adhesive and delivery system employed to apply these unique
formulations to the skin .

Although FDA and the petition propose the use of ASTM standards, these standards do not
correlate to device performance . In other words, the measurements obtained by use of these
~ •
Docket No . 2006P - 007 1
August 31, 2007
Page 1 6

standards do not relate to the clinical performance of CTAs, and the petition does not provide
evidence, let alone valid scientific evidence, to show that the ASTM standards are validated
predictors of clinical performance . Indeed, in his testimony before the panel, Dr . West explained
that these-methods do not provide acceptance criteria for the measurements and are not intended to
correlate to or predict the clinical performance of the device . Panel Transcript at 117 . For example,
as previously discussed in our 2006 comments, ASTM F2458-05 is designed to use porcine skin as
the substrate for strength testing, and while this method comes closer to a true biomechanical test, it
only measures strength in one dimension, and does not address durability, thermal skin reaction, or
other potential effects of tissue adhesives on healing . Indeed, no standard methods exist to measure
these effects, including tissue adherence and the effect of the adhesive film on underlying microbial
growth or healing . We also point out that these ASTM standards are relatively new and in fact were
not used by the PMA holders for the two devices that have been on the market the longest . Indeed,
not all of FDA's proposed ASTM standards were used by the manufacturer of the most recently
approved product, Histoacryl . See P050013 SSED at 10-11 (citing testing on bond strength in
accordance with ASTM 2458, which is cited in FDA's proposed special controls guidance, and
citing other ASTM standards which FDA does not reference in the proposed special controls) .
Moreover, as pointed out by U .S . Surgical, the ASTM standards disclaim the suitability of those test
methods to reliably assess strength properties of tissue adhesives without "thorough analysis and
understanding of the application and adhesive behaviors" and/or using "great caution since different
adhesives may respond differently to varying conditions ." 2 1

In its discussion of bench testing for adhesive strength, FDA's proposed tests and methods
are performed using non-biological substrates that are not representative of the way topical skin
adhesives are actually used . In fact, non-biological substrates can provide misleading comparisons
between skin adhesive products . The ability of skin adhesive materials to adhere to metal surfaces is
not indicative of information on the brittleness, flexibility, or ability of these materials to conform to
a tissue surface . If in vitro tests are to be used for product comparison, they should measure
properties relevant to performance on a biological substrate such as film elongation, resistance to
abrasion, resistance to creep, tensile fatigue (cyclic test), and torsional fatigue (flexibility) . Ex vivo
or in vivo methods provide a more meaningful correlation to the way in which these devices are
used .

Additionally, for degradation rate, the proposed conditions for hydrolytic extraction (50° C
for 15 days) will not necessarily provide a viable test of the different materials that could potentially
be used as skin adhesives . Similarly, while the heat of polymerization study is appropriate for
cyanoacrylate-based adhesives, not all materials that will potentially be used for these devices set
through an exothermic polymerization reaction . Thus, the agency needs to consider other methods
for assessing setting performance for any device that relies on a non-exothermic curing mechanism
to achieve its final form . Also, the use of an analytical method to compare CTAs, or other materials
that undergo an exothermic curing reaction, is not necessarily appropriate if the threshold for thermal
safety is not considered . An upper limit needs to be established which ensures that no therma l

21 See U.S . Surgical, Response to Petition for Reclassification of Tissue Adhesives for Soft Tissue
Approximation, Docket No . 2006P-007 1 /CCP 1, at 3-4 (Aug . 9, 2006) .
Docket No . 2006P - 0071
August 31, 200 7
Page 1 7

damage is imparted by the exothermic reaction during setting . While a device may be generally
comparable in setting temperature to a predicate device, if the amount of heat generated in the
reaction exceeds the biological limit for preventing burn injury, the comparison is meaningless and
invalid.

For other mechanical testing, the guidance refers to the measurement of the "force to
express" as an attribute, but depending on the applicator design, this may not be a relevant test . A
more appropriate attribute to measure would be "applicator functionality" which should include all
relevant attributes that are essential to applicator/delivery device functionality . Additionally, FDA
should remove the requirement to perform moisture vapor transmission testing because there is no
correlation to a specific performance attribute .

The guidance fails to specify the use of worst-case conditions to test for biocompatibility .
These would include the maximum allowable concentrations of impurities in each formulation
component ; maximum allowable concentrations of each potentially reactive formulation component ;
maximum concentrations of curing initiators ; worst case extremes for levels of residual monomer in
the polymerized sample ; use of packaging components ; worst case exposure times for terminal
sterilization ; and aging of samples to the device expiration.

For animal testing, the guidance fails to include an evaluation of the ability of the test article
to maintain skin edge apposition without dehiscence over the test period . This ability to evaluate
apposition without dehiscence is a primary test of device functionality and should be evaluated over
an appropriate time period . Other quantitative analyses of wound closure strength should likewise
be considered; for example, in vivo strength testing as with a force gauge (tensile force/compression
force) provides quantitative data regarding wound closure strength in a biological model that
provides a more meaningful correlation to the anticipated performance of these devices as used to
approximate skin .

For shelf life testing, conditioning of samples used to establish device shelf life must include
cyclic temperature and humidity aging (environmental cycling) to truly reproduce the potential
storage and shipping conditions encountered during normal distribution of the device . Also, to
establish shelf life, the test requirements need to include all those identified in the material
characteristics section that are relevant to stability indicating tests, as well as tests to evaluate the
reliability of the delivery device/applicator after cyclic temperature and humidity aging and evaluate
the functional performance of the device packaging . Components of the device applicator and
packaging may be susceptible to change when exposed to the typical environmental conditions
encountered during normal distribution . The proposed tests need to be evaluated for samples stored
at recommended device storage conditions over the proposed shelf life of the device . All tests
conducted to determine material characterization, mechanical properties, and biocompatibility
should be tested over the device's established shelf life . Changes in these attributes are possible as
the device ages and therefore must be verified as part of the stability program .

Simply put, the proposed special controls are inadequate . Even if various changes are made
to the guidance's testing recommendations, well-controlled clinical studies are necessary to assuring
the safety and effectiveness of tissue adhesives .
• •
Docket No . 2006P - 007 1
August 31, 2007
Page 18

(b) Clinical trials are necessary to adequately evaluate performance and safety

Because animal models cannot provide an evaluation of potential discomfort associated with
burning, stinging, or skin reaction during application of a topical skin adhesive device, an evaluation
must be conducted for all new devices in an intact skin human model at a minimum . See Singer
Declaration at ¶ 13 . Only human studies can provide this type of information . Testing for the
durability of the device on human skin is the only way to definitively provide an assessment of the
ability of the device to stay on after application . This testing also provides a method of evaluating
potential skin irritation or contact dermatitis over the time the device is in place on the skin that
cannot be determined from other methods .

We reiterate Closure's 2006 comments related to the petition that FDA's proposed
mechanical tests to characterize tissue adhesives only measure individual aspects of mechanica
l lperfomancthdvirplao,netidcvofheralbimcn
performance of the device as it is used clinically . There are no standardized test methods available
to measure biomechanical strength of tissue adhesives that have been directly correlated to clinical
performance. Thus, the only way to evaluate these parameters is through rigorous clinical trials .
Similarly, while FDA recommends that biocompatibility testing be performed according to the FDA-
modified ISO-10993 standard, this set of tests is only one aspect of the safety assessment of a new
device and clinical evaluation is also required to confirm device safety .

Importantly, FDA previously recognized that many variables relative to clinical outcomes
cannot be adequately assessed by in-vitro and in-vivo methods . The agency identified the following
variables whose impact on safety and effectiveness can only be evaluated as part of a controlled
clinical study: anatomic location of wound; size of wound (length, width, and depth) ; age of wound ;
wound type and etiology ; wound classification (clean, clean-contaminated, contaminated) ; and signs
of infection and inflammation . See FDA's Guidance, Cyanoacrylate Tissue Adhesive for the Topical
Approximation of Skin - Premarket Approval Applications (PMA), at 11-12 (Feb . 13, 2004)
[hereinafter "PMA Guidance"] . We do not believe anything has changed since FDA's prior
identification of these factors . Evaluation of device performance with respect to these variables can
only be achieved through a well-controlled clinical study . For example, when the viscosity of
Dermabond was reformulated, we submitted clinical data, including data from pediatric patients that
ensured a worst case challenge for the device and because pediatric patients are representative of the
patients presenting in the emergency room with lacerations that are closed with topical skin
adhesives . Moreover, as Dr. Spotnitz explains ,

Because widespread clinical use of cyanoacrylates remains a new and recent


area of surgical use, the accumulation of data for safe and effective employment
remains important .

There are remaining clinical questions about the appropriate and most
efficacious uses of these materials . The specific clinical settings as well as the
methods of application are open to debate by even the most experienced clinicians .
These controversies still need resolution and can be best addressed by the
Docket No . 2006P - 0071
August 31, 200 7
Page 19

performance of rigorously controlled human clinical trials . Animal models are not
capable of simulating all clinical settings in which these materials will be used .

Spotnitz at 2 (Closure Comments, Att. 2) . For example, pairing the cyanoacrylate wit h
additional sutures depends on numerous factors that need to be evaluated in humans, including depth
of wound ; age of wound ; patient age; wound thickness ; skin strength and fragility ; sub-dermal
serous, lymphatic, or bloody fluid accumulations ; and soft tissue conditions including adipose
content and edema . Id.

(c) The record fails to reveal any new valid scientific evidence that demonstrates a
diminished need for clinical validation of CTAs .

For all the reasons detailed above, the laboratory tests proposed as special controls are an
insufficient substitute for clinical trials . The guidance's failure to require clinical trials for all tissue
adhesives is a complete turnaround from the PMA guidance that FDA published in 2004, and quite
simply, nothing has intervened in the past three years to change the need for clinical information to
demonstrate safety and effectiveness . Indeed, as Mr. Steinborn testified before the panel, 80% of the
literature references in the petition were published prior to the 2004 guidance document, and the
remaining 20% of the cited published literature describe studies similar to those published prior to
the guidance document.22 See Panel Transcript at 104 . Moreover, the agency states that it relied in
part on published literature in developing the 2004 guidance . See PMA Guidance at 2. Thus, the
agency was likely aware of most of the published literature cited in the petition at the time of the
2004 guidance . Because the literature published after the guidance merely repeats earlier
information, no obvious basis exists for why FDA believes special controls are now adequate, when
previously the agency believed that each change to a tissue adhesive's formulation, including a
change in viscosity, required clinical data to ensure safety and effectiveness .

B. The FDA, Petitioner, And The Panel Understated The Risks Of These Tissue
Adhesives, And Fail ed To Appreciate That The Risks Of Tissue Adhesives Have Been

22 Of the 119 articles cited in petition, only 24 articles were published during or after 2004, the year
FDA issued the PMA guidance document on CTAs . Of these 24 articles, 16 articles relate to
Dermabond (we assume that articles on octyl-cyanoacrylate relate to Dermabond because we are not
aware of any other octyl-cyanoacrylates that are marketed domestically or internationally) . Thus,
most of the new information FDA relies upon relates to the one PMA . For the remaining eight
articles : (a) two articles could not be located by the petitioner and thus, were not reviewed ; (b) four
articles discuss prospective clinical studies in a limited number of patients ; collectively, these studies
only represent 160 patients treated with a butyl-cyanoacrylate tissue adhesive (whether these are the
same or different butyl-cyanoacrylate product is unclear) ; (c) one article presents a review of
cyanoacrylates (petition does not specify the CTA type) ; and (d) one article presents a retrospective
review of eight different clinical studies, four on butyl-cyanoacrylates and four on octyl
-andi whic theauthorcnludesther is nuficent videnc regardingth e
devices' performance, see note 17 .
~ •
Docket No . 2006P - 007 1
August 31, 2007
Page 20

Minimized Because Of The Rigorous PMA Development And Review Process That
Currently Marketed Products Have Undergone.

L FDA Has Failed To Fully Identify The Risks Associated With Tissue Adhesives.

In its proposed rule, FDA stated based on "the information in the petition, the informatio n
presented at the panel meeting, the panel's recommendation, and Medical Device Reports, FDA has
evaluated the risks to health associated with use of the tissue adhesive for the topical approximation
of skin and determined that the following risks to health are associated with its use[ :]" (1)
unintentional bonding or product leaks into eyes which can lead to sealing the eyelids shut and can
require surgical intervention; (2) wound dehiscence, i.e., the subsequent separation of the edges of
the wound, which can cause complications such as re-sealing the wound and surgical revision of the
wound with adhesive or sutures and which can potentially delay the patient's recovery; (3) adverse
tissue reaction, including allergy, inflammation, foreign body reactions, erythema, granuloma, and
the exacerbation of asthma, and chemical bums such as those caused by fumes given off by the
adhesive before or during polymerization ; (4) infection, including that caused by the adhesive not
being properly sterilized ; (5) applicator malfunction, which can be caused by inadequate packaging
or user error when opening the package, and which can result in extended surgery including
additional time under anesthesia, or a delay in treatment, and can result in lacerations to the user or
patient ; and (6) delayed polymerization which results in compromising the wound, additional time
under anesthesia, or delayed treatment . 72 Fed. Reg. at 36399-400.

However, this list of risks fails to identify all the potential hazards that are associated with
these complicated devices . For example, patients can experience pain, stinging, or burning upon
application due to the polymer, solvent system, or other formulation components . See, e.g.,
Dermabond P960052 SSED at 3 (stating polymerization may cause a sensation of heat or discomfort
in some patients) ; Indermil PO 10002 SSED at 16 (stating discomfort due to heat generation may
occur) ; Histoacryl P050013 SSED at 9 (stating clinical experience outside the United States suggests
thermal discomfort during polymerization may occur) . Indeed, our review of CTA MDRs in FDA's
database after June 13, 2006 (cutoff point for MDRs in FDA's Panel Briefing Memo) indicates that
these are safety concerns : there were five MDRs on patients experiencing burning sensations or
pain, including "intense" or "unbearable" pain . Although MDR data are not valid scientific evidence
that can support reclassification, such data may be relied upon to identify "questionable" device
safety or effectiveness . See 21 CFR § 860 .7(c)(2) .

Additionally, patients can experience delayed wound healing or tissue toxicity depending on
the formulation used . It is already known that different versions of cyanoacrylates (methyls, butyls,
octyls) have differing effects on wound healing and cytotoxicity . CTAs potentially can be
formulated from a wide range of polymers and copolymers and require a variety of different
solvents, plasticizers, preservatives, etc . All of these ingredients may have widely differing effects
on tissues and on wound healing rate and quality . Indeed, the literature shows that even slightly
different formulations of the same product can have differential effects on wound healing depending
on purity, excipients, etc . See W .H . Eaglstein & P .M . Mertz, "Inert " Vehicles Do Affect Wound
Healing, J . Invest . Dermatol . (Feb 1980) 74(2) at 90-1 . Additionally, some patients may experience
chronic non-healing of a wound . See Indermil P010002 SSED at 16 ; Histoacryl P050013 SSED at 9 .
~
Docket No . 2006P - 007 1
August 31, 2007
Page 2 1

Other adverse effects discussed at the panel meeting included patients picking off the adhesive and
necrosis ; however, FDA failed to identify these risks . Panel Transcript at 46-47 (Aug . 25, 2006)
(comments of Dr. Norsted) .

The petition's discussion of benefits and risks was similarly deficient in that it failed to
identify adverse events that have been reported for tissue adhesives . Specifically, in comparing the
benefits of tissue adhesives versus sutures, the petition states that tissue adhesives "[d]o not
introduce foreign materials (i.e., by the suture itself, or contaminates drawn into the wound-site by
the suture) ." Petition at 15 . However, this statement suggesting that tissue adhesives do not cause
foreign body reactions contradicts the petition's MDR table, which identified a foreign body reaction
MDR. See Petition at Att . E, Table 9, #246 (identifying an Indermil MDR reporting "Foreign body
reaction" (received by FDA Oct . 7, 2003)) . Although the petition identifies only one MDR with a
foreign body reaction, other reports should have been identified as reporting foreign body
reactions .23 Indeed, Dermabond's labeling warns against use below the skin due to possible foreign
body reaction . See Dermabond Labeling in P960052 . Moreover, Closure has reported excessive
scarring, which the petition fails to identify . Additionally, Dr . West, consultant for Closure, testified
at the panel meeting that the petition failed to include literature that identifies numerous hazards and
risks encountered by other unsuccessful developers of CTAs, including allergic reaction, foreign
body reaction, potential for carcinogenicity, and risk of poor cosmesis . Panel Transcript at 116 .
Unfortunately, FDA failed to fully consider these risks in the context of its reclassification proposal .

The petition and FDA's review of MDR data is also inadequate to show the risks of tissue
adhesives because the MDR database contains information primarily on one CTA, which may be a
function of different companies' approaches to submitting MDRs . Closure has taken a conservative
approach to reporting MDRs for Dermabond, reporting all events relating to eye bonding, infection,
skin reaction, dehiscence and others . The company believes that this may account for the fact that
most of the MDRs on CTAs relate to Dermabond . Not only are there relatively few MDRs on other
CTAs, MDRs simply cannot be used as a basis for reclassification .

Also problematic is that the petition asserted that the risk of significant clinical adverse
events is low, without recognizing the role of current PMA controls in preventing adverse outcomes .
Petition at 11 (stating "the risk of significant clinical adverse events when using tissue adhesives is
low" and "the risk of field issues is extremely low") . Not surprisingly, the panel failed to appreciate
that the two CTAs in use only went to market after full clinical studies demonstrated their safety and
effectiveness, and each manufacturer was fully inspected prior to receiving FDA's device approval .
In contrast to statements by panel members describing the device as presenting little risk, FDA has

23 See Petition at Aft . E, Table 9 (at #284, identifying a Dermabond MDR received by FDA May 17,
2005 that was described by petitioner as "Granuloma & Fat Necrosis," but this should have been
characterized as a possible foreign body reaction because the manufacturer suspected it was a
sensitivity reaction, possibly a foreign body reaction ; and a Dermabond MDR (at #96, received by
FDA May 10, 2000) that was described by the petitioner as "Laceration swell after 4 days" but thi
t sMDRalohudvebncartizsfoegnbdyracti usehMDRat
swelling was the result of a foreign body reaction) .
0 0
Docket No . 2006P - 007 1
August 31, 2007
Page 2 2

considered tissue adhesives to be significant risk devices .24 See PMA Guidance at 8 ; Special
Controls Guidance at 12 .

The panel's view of these products as low risk devices appears also to be informed, in part,
by their personal experience. For example, Dr . Lewis has treated "at least 1,000 [wounds] with
some form of either Steristrips or tissue adhesive ;" yet, his comments that these products are used on
"very low end wounds" and that infection is "irrelevant" reflect a lack of understanding about the
broad application of these products and the risks concerning them . Panel Transcript at 135 . Indeed,
FDA identified infection as a risk related to tissue adhesives, and therefore, it clearly is a relevant
concern. See Special Controls Guidance at 6 . As reflected in the published literature cited by the
petitioner, tissue adhesives are used to close a variety of wounds (e .g., long surgical incisions,
excisional wounds, laparoscopic trocar wounds, head and neck incisions, and colmellular incisions)
in many different types of surgeries and procedures (e .g., abdominal surgery, circumcision, perineal
repair, skin grafting, hernia repair, and reconstructive surgery) . See Petition at Att. C. Individual
assessments by panel members represent information that FDA would not accept to establish safety
for a device, and are at odds with what is reported in the literature and the agency's historical and
consistent view of CTAs . Significantly, several panel members did not appear to appreciate the role
of PMA controls in providing the safe and reliable CTAs, and appear to have no idea of the type of
evidence that is permissible to support a device reclassification .

2. The Risks Identified Are Not Supported By Valid Scientific Evidence .

Although FDA identified the risks associated with tissue adhesives based on the petition, the
panel meeting and panel's recommendations and MDRs, most of this information is insufficient to
identify the risks for purposes of reclassification . MDRs are anecdotal information about adverse
events or malfunctions . They are tantamount to hearsay without substantiation or investigation or
scientific analysis . Moreover, the MDR system historically has been plagued with underreporting so
it is unlikely that many risks associated with the use of CTAs were reported to the agency . Indeed,
the panel acknowledged the limitations of MDRs . For example, Dr. Li stated :

In the orthopedic area where I spend most of my time, we estimate the reporting to
the MDR as something less than 1 percent . In my own institution . . . we did 300 to 400
revisions a year at our hospital, none of which were ever reported to the MDR . So I think the
MDR, like Mark [Melkerson] said, is a particularly bad number to use to try to assess the
number of bad events . It is pretty good at telling you the kinds of bad events, but it i s

24 A significant risk device : (1) Is intended as an implant and presents a potential for serious risk to
the health, safety, or welfare of a subject ; (2) Is purported or represented to be for a use in supporting
or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a
subject ; (3) Is for a use of substantial importance in diagnosing, curing, mitigating, or treatin g
disease, or otherwise preventing impairment of human health and presents a potential for serious risk
to the health, safety, or welfare of a subject ; or (4) Otherwise presents a potential for serious risk to
the health, safety, or welfare of a subject . 21 CFR. § 812 .3(m).
Docket No . 2006P - 0071
August 31, 200 7
Page 23

nowhere near telling you how many there are . So multiplying a number by 100 or in some
cases, 1,000 is really probably closer to the estimate, at least in orthopedics .

Panel Transcript at 56-7 . Similarly, Dr . Newberger, in expressing her concern that MDRs are
unlikely to capture sensitization events, stated, "I think that the reporting system is not as rigorous as
all of us would like. We know that MAUDE doesn't get that many reports ." Id. at 157-58 . Even
Dr. Hollander, representing the petitioner, acknowledged that the MDR data "obviously under
reports by some . . . significant factor ." Id. at 57 .

Even if MDRs qualified as valid scientific evidence, one cannot evaluate the prevalence of
risk from MDR data because FDA does not know the total number of uses of tissue adhesive
products, and it does not know the number of adverse events associated with them Indeed, FDA's
Mr. Melkerson acknowledged that the agency uses "the MDR database as an indication of the types
of adverse events or types of risk associated with [a device] and not necessarily a numerator and
denominator ." Panel Transcript at 55 .

Moreover, under FDA regulations, panel members' personal experience with CTAs is not
valid scientific evidence, and cannot stand in for the lack of valid scientific evidence . See 21 CFR . §
860.7(c)(2) . In sum, the agency's reliance on MDR data and panel members' anecdotal experience
for the proposed reclassification inappropriately lowers the threshold for reclassification, and is not
legally sustainable .

3. The Proposed Special Controls Are Inadequate To Eliminate Or Mitigate The Risks.

FDA's proposed controls are inadequate to mitigate or eliminate the risks of these tissu e
adhesives because, among other things, not all the risks are identified . However, even if the risks
identified represent all the risks associated with these devices, the proposed special controls and
general controls do not provide a reasonable assurance of safety and effectiveness .

For example, the agency asserts bench testing and labeling could adequately address
unintentional bonding or product leaks into eyes . This risk relates to product viscosity as well as
user error and issues of anatomical location and positioning . Only human use by surgeons in a
clinical setting would reveal the nature of such risks for any specific device . Thus, we strongly
believe only clinical trials could address this risk and identify any collateral measures necessary to
address it . Indeed, when Dermabond was reformulated to offer a higher viscosity product, extensive
clinical testing was required by FDA to ensure the higher viscosity product would perform as
intended . See P960052/S4 .

Similarly, FDA believes wound dehiscence can be addressed by bench testing, shelf-life
testing, animal testing, and labeling . To the contrary, wound dehiscence risks would not be
adequately predicted by any testing other than clinical trials . See Singer Declaration at ¶ 11
("clinically relevant dehiscence rates for a tissue adhesive can only be obtained in clinical trials .") .
Animal testing is inadequate because animals do not subject their wounds to the same stresses as
humans, for example, the stresses experienced from positioning, bathing, the effects of clothing, and
other activities of daily life . See id. at ¶ 9 . Dehiscence also may be related to product strength
relative to incision length, shape (curvature) and anatomical location/motions that are not easily
~
~
Docket No . 2006P - 007 1
August 31, 2007
Page 24

modeled in animals but best seen in human wounds or surgical procedures of different types . See id.
at ¶ 10 (discussing a clinical study which compared an octylcyanoacrylate with a butylcyanoacrylate
tissue adhesive and found that the octylcyanoacrylate tissue adhesive resulted in lower dehiscence
rates when applied to high tension wounds) . Dr . Spotnitz has noted that wound dehiscence remains
a concern depending on the methods of cyanoacrylate application . These controversies can only be
resolved by maintaining rigorous product standards and appropriate clinical trials . See Closure
Comments, Att. 2 at 1(explaining that the literature regarding CTAs for skin approximation still
suggests controversies over the proper clinical settings and application methods) .

For adverse tissue reaction and chemical burns, the agency claims biocompatibility and
animal testing will suffice . However, animal testing will not reveal any pain, stinging, or burning
sensations due to the polymer or solvent system . See Singer Declaration at ¶ 13 . These sensations
can only be reported by a conscious human, i.e., the patient is not under general anesthesia ;
therefore, only clinical testing in traumatic wounds such as lacerations will reveal this potential risk
and thus create the opportunity to address this risk . See id. ("Because animals have different skin
and do not express pain when under anesthesia, the data obtained from animal studies may not
reflect clinical experience . Therefore, clinical trials must be used to measure the amount of pain
resulting from adhesive application and whether the heat generated from adhesive polymerization
would result in burns.") . Indeed, as Dr . Spotnitz points out, the use of cyanoacrylates in topical
dermal application has been associated with unpleasant sensations of burning or discomfort in a
minority of patients . These effects can only continue to be evaluated and minimized through clinical
trials . Because a major advantage of CTAs is avoidance of pain associated with dermal suture
placement and removal, discomfort associated with cyanoacrylate use is not an insignificant issue
and still needs further evaluation. See Closure Comments, Att. 2 at 2 ; see also Dermabond SSED at
1 (stating expedited review was granted "based on the potential public health benefit from reducing
patient pain and anxiety related to the closure of low tension lacerations") .

Also, CTAs can cause hypersensitivity reactions or allergic reactions, because of potential
sources of variability in adhesive formulations . Some reactions to these ingredients might be related
to exposure/sensitization to similar compounds or polymers that animals would never have
experienced . Only clinical trials can adequately reveal these potential risks .

For infection, the proposed controls are bench and sterility testing, including establishing an
SAL for the device . However, the proposed tests do not address the product in use, where its unique
characteristics may directly relate to its infection potential . Specifically, most wound infections are
caused by local microbial flora of the skin or environmental pathogens that enter the wound after the
acute injury or surgery . These tests would not reveal any effects of the product, negative or
otherwise, on microbial populations of the skin around the wound site that could cause infection .

For delayed polymerization, FDA recommends bench testing and animal testing . However,
polymerization can be delayed by interactions with ancillary products present on the skin such as
surgical skin preparations or scrubs . There are a myriad of types and brands of ancillary products .
Moreover, such products sold for animal use can be different formulations and of differing purity
than those sold for human use . Thus, only actual clinical use would potentially reveal these sources
of delayed polymerization .
Docket No . 2006P - 0071
August 31, 200 7
Page 25

Finally, for the risk of patients experiencing delayed wound healing or tissue toxicity (risks
that FDA failed to identify), we point out that animal models of wound healing have certain inherent
inadequacies in predicting human response . See W.A. Dorsett-Martin, Rat Models of Skin Wound
Healing: a Review, Wound Repair Regen . (Nov/Dec 2004) 12(6) at 591-9 ("Developing an animal
model that has all the complexity of human chronic wounds may be an unattainable goal, because
nonhealing and delayed healing wounds in humans are often the result of combinations of impaired
circulation, inadequate nutrition, age, limited physical activity, and/or chronic physiological
imbalance .") . Here again, only clinical testing will suffice to adequately address these risks .

Additionally, we point out that even if we agree with the petitioner and panel's
characterization of the low risk attributed to the use of these CTAs, we firmly maintain that this
assessment is the result of the effective controls enforced through class III PMA requirements .
Specifically, the applications for the three approved products contained substantial evidence that
demonstrated that process conditions and quality controls will ensure a consistent material is
produced through the manufacturing processes . Similarly, the three devices were validated for their
intended use through well-controlled clinical studies which established safety and effectiveness . The
characteristics required for effective wound closure are not inherent in cyanoacrylate materials, and
it is only the rigorous PMA evaluations that have ensured the safety and effectiveness of these
devices . Without PMA controls, there is increased risk of adverse events due to the lack of
sufficient data to ensure safe, effective, and consistent clinica l
performance.

C . FDA's Proposed Special Controls Cannot Compensate For The Lack Of Record
Evidence, And Fail To Address Tissue Adhesive Composition Characterization and
Manufacturing Controls

In its special controls, while FDA appears to recognize the importance of the composition of
CTAs, it fails to require the detailed manufacturing descriptions necessary to fully understand the
composition of these devices . Specifically, the agency states in its proposed guidance :

Various formulations can be manufactured that vary in viscosity, setting time, bond
strength, degradation rate, and other physical and mechanical properties . Because
these properties define the adhesive performance and utility of the final product, your
description should discuss the molecular composition and structure of your
compound .

Special Controls Guidance at 7 . However, without a full understanding of the processing and
manufacturing controls in place to ensure that the composition of CTAs is what manufacturers
believe it should be, a discussion of "the molecular composition and structure of your compound" is
meaningless .

The guidance lacks meaning in this regard because even though the quality and purity of the
finished product are dependent on the specific process controls, the guidance does not require tissue
adhesive manufacturers to identify each impurity or additive and apply tight control to the
manufacturing processes to limit the levels of trace impurities or trace additives, such as inhibitors
~ •
Docket No . 2006P - 007 1
August 31, 2007
Page 26

and stabilizers, in every component used in the chemical process . Similarly, the guidance does not
require well established, scientifically justifiable specifications for the material characteristics of the
adhesive, including the chemical constituents and final formulation, to ensure consistent device
performance and biocompatibility/safety . Moreover, there are no requirements that the
specifications for the chemical constituents and device formulation take into account worst-case
conditions,25 nor any testing requirements that would consider the use environment at the time of
application, for example, the use of skin preparation products or other products/chemicals present in
the emergency room or operating room, even though such materials are known to affect the setting
performance, durability, and other characteristics of topical skin adhesive devices .

Also notably absent from the proposed special controls guidance is any discussion of
manufacturing details . Compare PMA Guidance at 2 to Special Controls Guidance . As discussed
above, because manufacturing controls are critical to ensuring that these devices perform as
anticipated, failing to require any description of these controls offers no assurance of device safety
and effectiveness . The 2004 guidance document directs that manufacturing systems adhere to
agency guidance, Quality System Information for Certain Premarket Application Reviews ; Guidance
for Industry and Staff. See PMA Guidance at 4 . We believe that complying with this Quality
System guidance and requiring premarket inspections is necessary for CTAs, because of the complex
nature of the manufacturing processes . Indeed, requiring PMA-related submissions for
manufacturing changes is the only way to provide a reasonable assurance of safety and effectiveness
for tissue adhesives . We fail to see what has changed in the manufacturing process of CTAs to
warrant the lesser showing of device safety and effectiveness suggested by the proposed special
control guidance . While in 2004, FDA required manufacturers to provide, among other things, the
quality control procedures used for the monomer production, cyanoacrylate formulation, ampoule
filling, and final packaging, the agency is now silent on these requirements in the context of fewer,
less rigorous controls ; and has provided no explanation why formulation and manufacturing are no
longer critical to the safety and effectiveness of the product, particularly, in light of its extremely
broad proposed classification .

In sum, the composition and manufacturing of these products are critical to defining the
device's performance parameters and risks, and thus, a generic type of device that could be
adequately regulated under class II controls . Because there is not adequate evidence in the
administrative record defining the composition and manufacturing processes that will yield a safe
and effective device, the proposed special controls cannot possibly contribute to assuring a safe and
effective device.

IV . General Controls Will Not Provide A Reasonable Assurance Of Safety And Effectiveness .

25 Worst-case conditions include : the maximum allowable concentrations of impurities in each


component, the maximum allowable concentrations of formulation components that are associated
with potential skin reaction or other biocompatibility concerns, packaging materials and how they
are affected by release agents, processing aids, or other factors . If the quality of the curing process
can affect the chemical profile of the final device, manufacturers need to consider this factor in
determining worse-case conditions appropriate for setting device specifications .
Docket No . 2006P - 0071
August 31, 2007
Page 27

The Act's general controls, in particular, premarket notification and routine good
manufacturing practice inspections under the Quality System Regulation do not provide a reasonable
assurance of safety and effectiveness for these complex individualized tissue adhesive formulations
e ,whicrequpsmanfctrigdpoesqualyirmntopedcablyu
devices, and clinical data to ensure the device formulation is safe and effective .

First, substantial equivalence determinations cannot be reliably made because, as we


discussed in Section II .C, supra, there is no defined variability of factors for composition and
manufacturing, and minor formulation or manufacturing changes can have significant effects on
device characteristics and performance. Simply put, there is not a coherent generic type of device
that would permit meaningful substantial equivalence comparisons and determinations .

Second, the 510(k) process, which does not afford the same level of manufacturing control as
the PMA process, and which allows manufacturing changes often without FDA review, cannot
guarantee the safety of these tissue adhesives . FDA has always been concerned with the safety of
CTAs with regard to impurities from the manufacturing process, the toxicity potential of stabilizing
agents and other additives, and the toxicity potential of degradation products, see, e .g., PMA
Guidance at 3 ("Degradation rate is an indicator of the possible toxicity of the adhesive .") ; id. at 4
(recommending the hydrolytic degradation study monitor the amounts of additives and monomer
impurities) . Only PMA controls are able to address these concerns prior to marketing . The panel
recognized the importance of manufacturing controls for these products :

It's more that you're putting a chemical on an open wound . I mean, you're trying to
close it, but essentially it is an open place in the skin, and if that material is
manufactured improperly, or is changed in some way, and then has a characteristic
that could injure the tissues . . . . if there were some other injury to the skin from the
exothermic reaction or anything like that, the question is, would those types of issues
be picked up in a Class II review ?

Panel Transcript at 143 (quoting Dr . Leitch) .

The 510(k) review does not include review of manufacturing controls and the absence of
such a rigorous review is critical here where manufacturing controls play such a vital role in the
safety and effectiveness of tissue adhesives . Indeed, premarket notification would not accommodate
the need for premarket inspections .26 Because such inspections can detect problems, identif y

26 Preclearance inspections "are not feasible nor are they appropriate, for a class TI device ." See
February 23, 2001 Letter from Bernard E . Statland, Director of the Office of Device Evaluation to
Drew Johnson, Advanced Neuromodulation Systems, denying reclassification of the Totally
Implanted Spinal Cord Stimulator for Pain Relief from class III to class II (pointing out that the
statute prohibits FDA from withholding decision on a 510(k) for failure to comply with good
manufacturing practice requirements unless there is a substantial likelihood that non-compliance will
potentially present a serious risk to health, and finding moreover that compliance with the quality
system regulation alone was insufficient to reasonably assure safety and effectiveness, particularly
with respect to device failure) .
Docket No . 2006P - 0071
August 31, 2007
Page 28

shortcomings and prevent inadequate devices from coming to market, the failure to require such
inspections creates a regulatory gap . Additionally, changes in design or manufacturing would
become of great concern in the 510(k) context, where there is greater flexibility to modify and
market devices without FDA's premarket review .

Finally, substantial clinical data are needed to adequately address device performance and
safety, because there are no established standards or tests that have been proven to correlate with
clinical performance. As Dr. Parker explained :

no quantifiable link has been established between cure rates, physical properties, and
clinical performance . No standardized methods are currently available to measure
biomechanical strength in ways that correlate directly to clinical performance . No
standard methods exist for directly measuring tissue adherence, durability, thermal
skin reaction, or the affect of the adhesive film on underlying microbial growth . The
methods listed in the FDA guidance for cyanoacrylate skin adhesives (such as those
for conducting overlap shear strength, flat-wise tensile strength, peel strength, and
burst strength) all measure mechanical strength in ways that are not directly indicative
of clinical performance . Thus, it follows that the windows of tolerance for cure rate
and degree cure (both of which affect mechanical properties) have not been
standardized and linked to clinical performance . Consequently, the tolerance for
compositional variations . . . (i.e., variations that affect cure rates) also remains
unknown .

Closure Comments, Att. 1(Dr . Parker's Report) at 9 .

In sum, because product-by-product class III PMA controls are necessary to ensure the safety
and effectiveness of tissue adhesives, particularly the requirements for well-controlled clinical
studies that demonstrate safety and effectiveness and compliance with GMPs before a device is
introduced to the marketplace for general use, premarket notification and other general controls
under the Act are inadequate to reasonably assure device safety and effectiveness . Moreover,
because so much more information is needed for FDA to fully evaluate these devices than what the
agency has proposed in its Special Controls guidance, we do not believe that FDA can effectively
review these devices through a 510(k) submission . A reclassification proceeding should not be used
as a mechanism to create a PMA-like review in the 510(k) context . Ethicon, 762 F . Supp . at 391
(stating that premarket notification cannot serve as a mini-PMA) . More importantly, doing so would
significantly diminish consumer protection, and would be contrary to the law .
Docket No . 2006P - 0071
August 31, 200 7
Page 29

V. Conclusion

For all of the foregoing reasons, Johnson & Johnson respectfully requests that the agency
withdraw its current proposal to reclassify tissue adhesives from class III to class II and deny RCRI's
petition .

Sincerely,

Dorothy J . Clarke
Assistant General Counsel
Office of the General Counsel
Johnson & Johnson
P .O, Box 151, Route 22 West
Somerville, NJ 0887 6
(908) 218-3227

Attachments

Regulatory Counsel :

Mark A. Heller
Melisa Moonan
Stephanie Philbin
Siyeon Lee
Goodwin Procter LL P
901 New York Avenue, NW
Washington, D .C . 20001
(202) 346-4107
Attachment 1 : Declaration of Adam J . Singer, M .D.
~ •
08/31/2007 11 :02 FAX 6314443319 EMERGENCY DEPT 1600 2

DECLARATION OF ADAM J . SINGER, M.D .

I, A.dam J . Singer, M .D ., declare as follows :

1 . I am presently Professor and Vice Chairman for Research in the Department of

Emergency Medicine at Stony Brook University . My curriculum vitae is attached. See

Attachment 2.

2 . I went to medical school in Israel where I grew up . I then served as a medical officer in

the Army for nearly five years and moved back to the U .S, where I did a general surgery

internship at Yale, Afterwards, I moved to Stony Brook in New York where I completed

a residency in emergency medicine and stayed on as a faculty member and attending

physician in the department of emergency medicine, My main areas of research are

wound healing and cyanoacrylate tissue adhesives .

3 . I have worked with Ethicon, Inc . and Closure Medical Corporation since 1998, mostly as

part of the companies' Speaker's Bureau . I am currently engaged by both companies as a

consultant in connection with a patent infringement lawsuit involving the campanies . I

have never testified on behalf of either compaz .y.

4 . 1 first used cyanoacrylate tissue adhesives to close wounds in 1980 when I worked as a

nurse in the emergency department in Israel . I have been involved in multiple clinical

trials on laceration repair and have investigated cyanoacrylate tissue adhesives in cell

culture, animal models and multi-center clinical trials . I have evaluated the use of tissue

adhesives for lacerations, incisions, abrasions, ulcers, burns, and even for nose bleeds .
0 8 / 3 1/ 2007 1 1 :03 FAX 6314443319 E MERG ENCY DEPT 1100 3

S . There are considerable differences among topFical tissue adhesives, such as the manner of

their application to the skin, e .g., Indermi[ is applied in a thin or dotted line along the

wound ; Dermabond is applied over the wound in multiple layers, but the most significant

differences relate to their physical characterisCics . For example, butylcyanoacrylate tissue

adhesives are more brittle, have less strength and cure faster than octylcyanaacrylate

tissue adhesives . Characteristics of tissue adhesives, such as their degree of flexibility,

adhesive strength and rate of polymerization, can affect clinical performance and raise

safety concerns that can only be adequately evaluated in clinical studies. Even tissue

adhesives with essentially the same formulaticm differ enough from a safety and

effectiveness perspective that the FDA rightfully required clinical studies before allowing

the slightly modified product to be used in patients outside of an investigational study ,

i.e., clinical studies were required to show the safety and effectiveness of Dermabond

HV, a more viscous version of the original Dermabond. Indeed, we did a clinical study

of Dermabond HV showing that when placed on the skin, it was less likely to migrate and

therefore would be less likely to result in bonding of the eyelashes .

. Unquestionably, there is significant variability in strength among the'6 different topica l

tissue adhesives . For example, a study comparing the wound breaking strength of rat

incisions closed with an octylcyanoacrylate (DERMABOND FiVD) and a

buCylcyanoacrylate (INDERMIL) demonstrated that the bursting strength of the

butylcyanoacrylate was considerably less than that of the octylcyanoacrylate (mean

difference= 243 mmHg ; 95% CI, 42-229 mmHg, P=0 .002).2 Another in vivo study found

that the bursting strength of an octylcyanoacrylate {low viscosity DERMABOND) was

three times greater than that of a butylcyanoacrylate (Histoacryl Blue) .3

2 of 7
08 /31/2007 1 1 :03 FAX 6314443319 EMERGENCY DEPT iM004

7 . The strength of a tissue adhesive affects the riak of wound dehiscence, which refers to the

separation of the wound edges . The most important function of the topical tissu e

adhesive is to ensure secure wound approximation until the wound is able to heal enough

to avoid dehiscence after device removal or sloughing . Wound dehiscence may delay

healing, and result in a wide scar . Wound dehiscence may also require re-treatment of

the wound with another wound closure device adding to patient suffering and

inconvenience.

8 . The likelihood of wound dehiscence is related to the bursting strength of the adhesive as

well as the static and dynamic tension on the wound. The wound bursting strength,

which is usually measured on animals such as pigs, is a better measure of the ability of

the adhesive to prevent premature wound separation because it measures the three-

dimensional forces in-vivo.

9. However, the static and dynamic tensions that apply to the back or flanks of experimental

animals are considerably less than those tlha# Ei pply to most areas of the human body, and

are therefore a poor reflection of the clinical performance of the adhesive and would not

adequately determine the risk of dehiscence ir, humans . The performance of a topical

tissue adhesive can only be accurately evaluated in human patients who continue to

function and perform daily activities such as bathing, sweating, ambulating, bending,

smiling, etc ., activities not replicated by an animal model .

10. Few clinical studies have directly compared the different topical skin adhesives for

wound closure . A study comparing wound closure with butylcyanoacrylate and

octylcyanoacrylate in 94 children with short (mean length, 1 .3 cm), low-tension, simpl e

3 of 7
0 8 /31/20 0 7 11 :03 FAX 6314443319 EMERGENCY DEFT Q 005

facial lacerations found similar short and longer term outcomes .4 However, difference
s

in dehiscence rates are observed when the adhesives are used on high tension wounds, A

study comparing wound closure with butylcyanoacrylate and octylcyanoacrylate in 167

children with groin incisions found lower dehiscence rates and higher parental

satisfaction with the octylapanoacryiate,S A recent study comparing wound closure using

a butylcyanoacrylate (Indermil) and sutures in children with groin incisionsalso suggests

that closure of these high tension wounds may result in a higher rate of wound dehiscence

for tissue adhesives following repair (26% vs . 0%) . 6

11 . Thus, clinical studies are not only necessary because animal models fail to factor in daily

human activities which affect product performance and risk of dehiscence, but the studies

above show that dehiscence rates can greatly differ based on the type of tissue adhesive

and wound . As a result, clinically relevant dehiscence rates for a tissue adhesive can only

be obtained in clinical trials .

12 . Tissue adhesives also vary in their rate of polymerization


. The polymerization of the

tissue adhesives results in the release of heat, which can cause not only patient discomfort

and pain but also burns, depending on the amount of heat generated as well as the patient

and skin characteristics . The amount of heat generated is a function of the rate of

polymerization, and the thickness of the adhesive . For example, the amount of heat

generated by the fast curing butylcyanoacrylates is greater than for the slower curin

. A prior clinical study of laceration repair demonstrated that whilgoctyleanrs e

there were no thermal burns noted, up to 40% of the patients felt a sensation of heat after

application of an octylcyanoacrylate . 7

4 of7
_ • _. _. a_ . . , . ._
~

08 /3112007 11 :04 FAX 6 319443318 EMERGENCY DEPT 9 00 8

13 . Animal models do not a ll ow for the measurement of pain or discomfort that may result

from adhesive polymerization . Furthermore, the likel ihood of thermal insults resulting in

burns i s dependent in part on the skin's thickness and degree of vascularity, which differ

among vari ous animal species an d humans . B ecause animals have di fferent skin and do

not express pain when under anesthesia, the data obta i ned from animal studies may not

reflect clinical experience . Therefore, clinical trials must be u sed to measure the amount

of pain resulting from adhesi ve appli cati on and whether the heat generated from adhesive

polymeri zation would result in bums .

1 4 . It is also impo rtant to evaluate the ability of the tissue adhesive to reduce the risk of

wound infection. Tissue adhes ives may reduce the ri sk of i nfecti on in several ways, for

example, the adhesive may have in h erent antin a crobial properties . However, I believe

the most relevant characterist ic to clinical pract ice is the adhesive's microbial barri er

function, i. e. , the ability of the adhesive to form an occlusive dressing that prevent s

introduction of pathogenic organisms from the external env ironment.

15 . Usually the microbial barrier functi on is determined in-vitro by


testing the ability of
bacteri a to penetrate through the adhesive film . However, the adhesive film
may only
func tion as a microbial barrier if it remains intact over time in a live, moving
and
sweating ani mal . The ability of the adhesive fi l -tn to remain intact on the skin over time is

not consistent across all tissue adhesives .

. 6 . A study comparing the surface characteristics oi' a butylcyanoacrylate (INDERMIL) and

octylcyanoacrylate (DERMABOND HVD) th at were used to close rat incisions found

that wi thin one hour the integrity of TIVI3ERNlII.., which is known to


be more brittle, was

tI
. . . . . .

5 of 7
..
~ ~

08/31/20 07 11 :04 FAX 6314443319 EMERGENCY DEPT QD00 7

compromised demonstrating exposed wound areas, while DERMABOND, which is

known to be more flexible, remained intact . $

17 . The ability of octylcyanoacrylate to function as a m i


crobial barrier over time and in-vivo
is further demonstrated by a porcine study of deep excisional
wounds . In this study the
wounds were covered wi th octylcyanoac rylate and then challenged
with an infecti ous
inoculum of Staphylococcus aureus once a day for three consecutive days
.9 None of the
octylcyanoacrylate covered wounds developed histological or evidence
of infection .
There is no simi lar st udy evaluating the in-vivo microbial
barrier function of

butylcyanoacrylate

. Because a tissue adhesive's


.18 ability to reduce th e risk of infection is dependent in part on

its ability to perform as a microbial barrier which it can only do if it rema


ins intact in-
vivo, animal studies and clinical studies which take
into account human activity and

movement are needed to evaluate a tissue adhesive's ab ility to maintain a microbial

barrier on the skin and reduce the risk of infections in repaired


lacerations and incisions .

19. Because tissue adhesives vary from product to product and certain
characteristics can
significantly impact performance or ri sks and can only be adequately assessed
i n humans,
each tissue adhesive must be evaluated in clin i cal studies
to ensure that the different
product characteristics will not adversely affect clinical
performance or incre ase the ri sk
of harm to patients .

: 'ursuant to 28 U .S .C . § 1746, I declare under


penalty of perj ury that the foregoing is true and
corr xt .

I ;xecuted on ~ ~ .
Ad.arn J . Singer, M . D .

6 of ?
08/31120 07 11 :05 FAX 6314443319 EMERGENCY DEPT QhO08

S nger AJ, Giordano P, Fitch JL, et al . Evaluation of a new high-viscasi#y actylcyanoacrylate tissue adhesive fo
r
lac :ration repair: a randomized, clinical trial . Acad Emerg
Mod 2043 ;30: 1 134-113 7 .
2S
ager AJ, Zimmerman T, Rooney J, et at . Comparison of woo ad
bursting strengths and surface characteristics of
FD k-approved tissue adhesives for skin closure. J Adhesion Sol Technol 2004;18 :19-28
.
' Pi rry LC . An evaluation of acute incision strength with Traumaseal surgical tissue adhesive wound closure
.
Dir tensional Analysis Systems, Leonia, NJ, 1995 .

"fl mond MH, Quinn -TV, Sutcliffe T, Jarmuske M, Klassen Tp, A randomized, clinical trial comparin
g
but 9cyanoacrylate with octylcyanoacrylate in the management of selected pediatric facial lacerations . Acad Emerg

Me. 11999,6:171-177.

S 3t =iner Z, Mogilner J . Histoacryl vs dercnabond cyanoacrylate glue for closing small operative wounds
. Harefuah
200);139 :4D9-411 .

6 va i den Ende ED, Vriens PWHE, Allema JH, Breslau PJ . Adhesive bonds or percutaneous absorbable suture fo

ire of surgical wounds in children . Results of a prospective randomized trial rcios


. J Pediatr Surg 2004 ;39:1249-51 .
7 Sit ger AJ, Giordano P, Fitch )L, et al ., supra note 1 .

Sit ger AJ, Zimmerman T, Rooney J, et al ., supra note 2.

9 Sir ger AJ, McClain SA. Persistent wound infection delays epid<
:rmal maturation and increases scarring in thermal
burn ;, Wound Repair and Regen 2002 ; 10:372-377.

7 of 7
Attachment 2 : Curriculum Vitae for Adam J. Singer, M.D.
July 23, 2007

Curriculum Vitae
State University of New York at Stony Brook
Health Sciences Center

Name : Adam J Singer, MD

Date and Place of Birth : November 30, 1961


Philadelphia, PA.

Mailing Address : 9 Lewis Street


East Setauket, New York 11733

Home Telephone : (631) 689-387 0

Office Telephone : (631) 444-7857

Higher Education
(Including internship, residency and other formal professional training)

From To Deree Institution Fiel d

1992 1995 Residency State University of New York Emergency Medicine


Stony Brook, NY

1991 1992 Residency Yale New Haven Hospital General Surgery


New Haven, C T

1985 1986 Internship Barzilai Medical Center Rotating


Ashkelon, Israel

1979 1986 M .D . Ben-Gurion University Medical Degree


Beer-Sheba, Israel

1
. ._ . . . . . ... . .. . :_. ,.. . .:-. ._ ..- .

.,'
.
~ . •
July 23, 200 7

Certification & Licensure


(ECFMG, FLEX , National & Professional Boards & Licenses)

Date Agenc y

12/96 Board Certified American Board of Emergency Medicine

Current Advanced Trauma Life Suppo rt

Current Adv anced Cardiac Life Support

Current Pediatric Advanced Life Support

Current BL S

Current New York State License

Appointments
(Academic Appointments)

From To Title Status Institution & Location

4/03 Present Professor of Emergency S Department of Emergency Medicine


Medicine State University of New York at Stony Brook

1/99 4/03 Associate Professor of S Department of Emergency Medicine


Clinical Emergency State University of New York at Stony Brook
Medicine

7 /95 1 /99 Assistant Professor of S Department of Emergency Medicine


Emergency Medicine State University of New York at Stony Brook

7 /94 6 /95 Chief Resident S Department of Emergency Medicin e


State University of New York at Stony Brook

7/92 6 /95 Clinical Assistant S Department of Emergency Medicine


Instructor of Emergency State University of New York at Stony Brook
Medicine

*Status : Volunta ry (V) , Salaried (S), Tenured (T)

2
July 23, 2007

Other Appointments

From To Title Status Institution & Locatio n

2003 Present Vice Chairm an for S Department of Emergency Medicine


Research State University of New York at Stony Brook

2001 Present Associate Residency S Department of Emergency Medicin e


Director State University of New York at Stony Brook

1997 Present Director of Clinic al S Department of Emergency Medicine


Research State Universi ty of New York at Stony Broo k

1996 Present Director of Resident S Department of Emergency Medicine


Research State University of New York at Stony Brook

Professional Practice & Service s

Date Activi Location Institutional Affiliation

7/95 A tt ending Emergency University Hospital ,


Department State University of New York at Stony Brook

2/ 87-5 /91 Medical Officer Israel Israel Defense Forces

Professional & Scientific Societie s

Orizanization Dates of Initial Leadershi p Position(s)


Membership and Dates

Society for Academic Emergency Medicine 1992 Member


Americ an College of Emergency Physicians 1992 Member
American Medical Association 1992 Member
International Society for Burn Injuries 2004 Member
Wound Healing Society 2004 Membe r

3
July 23, 2007

Academic & Professional Honor s

Date Honor

2006 American College of Emergency Physicians Award for Outstanding


Contribution in Research
1999 Young Investigator Award .
Society for Academic Emergency Medicine .
1998 1996 Outstanding Consultant .
Annals of Emergency Medicine .
1995 Award for Excellence in Research.
State University of New York at Stony Brook .
1995 Outstanding Resident Academic Achievement Awar d
1995 Council of Emergency Medicine Residency Directors, San Antonio, Texas .
1982 Rector's Award-for most outstanding student in the Faculty of Healt h
Sciences .
Ben-Gurion University, Beer-Sheba, Israel .
1983 Rector's Award-for most outstanding student in the Faculty of Health
Sciences .
Ben-Gurion University, Beer-Sheba, Israel .
1984 Dean's Award-for the most outstanding student in the Medical School .
Ben-Gurion University, Beer-Sheba, Israel .
1985 Dean's Award-for the most outstanding student in the Medical School
. .Ben-GurioUvsty,e-ShbaIrl
1981 Dean's List .
Ben-Gurion University, Beer-Sheba, Israel .
1980 Dean's List .
Ben-Gurion University, Beer-Sheba, Israel .

Research Support: Grants / Contracts

Sponsor Proje c

Intranasal Dilaudid for Trauma


Biosite MINDSE T
Eli-Lily Acute Coronary Syndrome (TIMI 38)
Co-Investigator

Ortho-McNeil Ankle Sprain Study

Aventis Rescue ACS


Co Investigator

Duke Clinical CRUSADE : Angina study

4
• ! July 23, 2007

Research Institute MAINTAIN : Medicine over tim e


(DCRI)

5
July 23, 2007

Spon s or Project

Millennium EARLY ACS

Scios ADHERE

Biosite REDHOT II

Biosite Shortness of Breath

Biosite Stroke

Biosite DVT Study

Biosite Triage Protein C : blood/plasma correlation


study
Biosite i-STAT

Biosite Abdominal Pain

Biosite Aortic Dissection

Biosite MIDAS : Myeloperoxidase and multi-markers


° In the Diagnosis of Acute coronary Syndrome

Ethicon Liquid Occlusive Dressing

Ethicon Microbial barrier functio n

Emergency Reduction of Medical Errors in the ER


Medicine
Foundation (EMF )

MGH/Abbott Labs Pneumonia

Schering-Plough IMPROVE I T

Auxagen Inc. Evaluation of a synthetic TGF-0 peptantagonist


for partial thickness burns and excisional
wounds

Scios, Inc . The effect of BNP on scar formation in a rat


incisional model

Scios, Inc . Role of Brain Natriuretic Peptide in Airway


Remodeling
Co-Investigator

6
July 23, 2 007

Courses Directe d

From To Institution Title Enrollment

2007 Society for Academic SAEM NY Regional Meetin g


Emergency Medicine
2005 State University of New York Management of Acut e
at Stony Brook Decompensated Heart Failure
2004 State University of New York Management and Evaluation of
at Stony Brook Acute Coronary Syndrome s
1997 present State University of New York Academic Associate Program Bi-weekly
at Stony Brook (Undergraduate Introduction t o
Emergency Medicine
Research)

1996 2003 Department of Emergency Journal Club Monthly


Medicine

1996 present Department of Emergency Introduction to Biostatistics Monthly


Medicine

1996 present Department of Emergency Regional Nerve Block Tri-annual


Medicine Laboratory

Other Academic Se rvice

Date To Activity

2007 Present SAEM Board of Directors


20005 Present SAEM Institute of Medicine Task Forc e

2005 Present Member, Clinical Trials Advisory Committee for the Stony Brook University
Hospital Medical Center

2005 Present Member, Journal of the Korean American Medical Association Editorial Board

2004 2004 Member, Membership Survey Task Force, Society for Academic Emergency
Medicine

2004 Present Member, Israeli Journal of Emergency Medicine Editorial Boar d

2003 2005 Member, Nominating Committee, Society for Academic Emergency Medicine
(SAEM)

2002 2003 Chair, Grants Committee, Society for Academic Emergency Medicine (SAEM)

7
July 23, 2007

2002 present Stony Brook University Task Force for Junior Faculty Development

2000 2001 Chair, Scientific Subcommittee, Society for Academic Emergency Medicine
(SAEM)

2000 present Surgical Hospital Quality Assurance Committe e

2000 present Member, American Heart Association Task Force on First Aid

1999 2002 Program Committee, Society for Academic Emergency Medicine (SAEM)

1999 present Associate Editor, Academic Emergency Medicine

1999 present Institutional Pain Committee, State University of New York at Stony Brook

1998 present Scientific Review Committee, American College of Emergency Physicians

1997 present Institutional Review Board, State University of New York at Stony Brook

1996 present Committee of Residency Directors, American College of Emergenc y


Physicians
(A CEP)

Editorial Board Positions and Reviews in Peer Reviewed Journals

From To Activi

2007 Present European Journal of Cardiology


2007 Present Editorial Board, Emergency Medicine

2007 Present American Journal of Cardiolog y

2007 Present Deputy Editor, Journal of the Korean American Medical Association (JKAMA)

1996 present Associate Editor, Academic Emergency Medicin e

1996 present Journal of Dermatological Research

1996 present Wound Repair and Regeneration

1996 present Annals of Emergency Medicine

1998 present American Journal of Emergency Medicine

2001 present Journal of the American Medical Association (JAMA)

8
July 23, 200 7
2002 present Editor, Israeli Journal of Trauma, Intensive Care and Emergency Medicine

2002 Present Annals of Surgery

2003 Present Journal of Postgraduate Medicine

2006 Present Pediatrics

2006 Present Journal of the European Academy of Dermatology and Venereology

Membershitr-Advisorv Boards

From To Activitv

2001 Present Glaxo-Smith Kline

2002 Present CEVAT (Centers of Excellence in Venous and Arterial Thrombosis)

2002 Present Johnson & Johnso n

2002 Present Ethicon, Inc .

2002 Present Essential Therapeutics, Inc.

2002 Present Encelle, Inc .

Steering Committee s

From To Activity

2004 Present ADHERE EM Module (Acute Decompensated Heart Failure Nationa l


Registry) [Scios, Inc .]

Invited Lectures

1 . Myths and Truths in Acute Wounds


. Grand Rounds, Stanford University, Palo Alto, CA .
June 13, 2007 .
2 . Myths and Truths in Acute Wound Care
. Grand Rounds, NY Hospital in Queens, NYC,
NY. June 6, 2007 .
3 . How to write an abstract? NYC, NY . March 28, 2007 .
4 . Emergency Medicine : What is it and who are we? Boston
, MA . March 27, 2007 .

9
July 23, 2007
5 . Topical Skin Closures . Boston, MA, January 23, 2007 ,
6 . Controversies in wound managements . Maui, HI, December 7 .
7 . Use of topical skin adhesives . Bangor, ME, November 16, 2006 .
8 . Cyanoacrylate topical skin adhesives . Lexington, KY, October 235, 2006.
9 . Wound update . Rochester, NY, October 24, 2006 .
10. Wound closure . Miami, FL, October 11 ; 2006 .
11 . Tissue Adhesives . Lexington, KY, October 25, 2006 .
12 . Comparison of tissue adhesives . Tampa, FL, September 13, 2006 .
13 . Topical skin adhesives . Chicago, IL, September 7, 2006 .
14. Wound closure update . Minneapolis, MN, September 6, 2006.
15 . Advances in wound closure in correctional medicine . Office of Continuing Medical
Education, University of Texas . Galveston, TX, August 18, 2006 .
16 . Update on wound closure devices . Osage Beach, MO, August 9, 2006 .
17 . Wound healing . Norfolk, VA, August 3, 2006 .
18 . Evaluation and management of traumatic lacerations . Philadelphia, PA, July 27, 2006
.
19 . Advances in the prevention of wound contamination . New York, NY, July 20, 2006 .
20 . Tissue Adhesives . Beaufort, SC, July 18, 2006 .
21 . Wound closure . Charlotte NC, June 29, 2006 .
22 . Comparison of tissue adhesives . San Antonio, TX, June 15, 2006 .
23 . Topical skin adhesives . Columbus, OH, June 7, 2006 .
24 . Evaluation of skin lacerations . Indianapolis, IN, June 1, 2006
25 . Traumatic lacerations . Omaha, NB, May 31, 200 6
26 . Topical skin adhesives . St Louis, MO, May 25, 2006
27 . Evaluation and management of traumatic lacerations . Pittsburgh, PA, May 25, 2006
28 . Closure devices for wound repair . Derby, CT, May 23, 200 6
29 . Would closure update . Austin, TX, May 4, 2006
30 . Tissue adhesives . Lansing, MI, April 26, 2006
31 . Topical skin adhesives . Anaheim, CA . March 30, 2006
32 . Topical skin closure . Baton Rouge, LA . March 29, 2006 .
33 . Wound closure update . Tampa, FL . March 29, 2006 .
34. Traumatic lacerations : Evaluation and management . Portland, ME . March 23, 2006
.
35 . Comparison of tissue adhesives . Association of Operating Room Nurses Annual Meeting .
Washington, DC . March 21, 2006 .
36 . Evaluation of skin lacerations . Cincinnati, OH . March 15, 2006 .
37. Advantages in wound repair . Miami, FL . March 2, 2006 .
38 . Topical skin adhesives . Washington DC . March 2, 2006 .
39 . Evaluation and management of traumatic lacerations . Stony Brook, NY
. January 31, 2006 .
40 . Topical skin adhesives . Charlotte, NC . January 26, 2006 .
41 . Wound closure update-2006 . Jackson, MS . January 19, 2006 .
42 . Wound update . Louisville, KY . January 18, 2006 .
43 . Evaluation and management of traumatic lacerations . Memphis, TN
. January 16, 2006 .
10
0 ~
July 23, 2007
44 . Closure devices for wound repair . San Diego, CA . January 12, 2006 .
45 . Advances in wound healing . Chicago, IL . January 11, 2006 .
46. Evaluation and management of burns . Maui, HI. Dec 8 2005.
47 . Tissue adhesives. Fort Wo rth, TX. Dec 1, 2005 .
48 . Grand Rounds : Wound controversies . Parkl and Memori al Hospital, Dallas, TX
. Dec 1,
2005 .
49 . Wound management. Milwaukee, WI, Nov . 30, 2005 .
50. Evaluation of traumatic lacerations . Knoxville, TN, Nov 28, 200 5
51 . Evaluation and m an agement of burns . Stony Brook, NY . Nov 23 , 2005.
52 . Evaluation and m anagement of lacerations . Salt Lake City, UT . Nov 17, 2005
.
53 . Wound management . Naples, FL . Nov 16, 2005 .
54 . F all update on wound closure . Baltimore, MD . Nov 15, 2005 .
55 . The role of adhesives in wound repair . Portsmouth, NH . Nov 10, 2005 .
56 . Tissue adhesives and wound closure. S an Jose, CA. Nov 9, 2005 .
57 . Would Updates . Po rt Jefferson, NY. Nov 8
58 . Tissue adhesives . Boston, MA . Nov 3, 2005 .
59 . Wound closure devices and tissue adhes ives . Houston, TX. Nov 2, 2005 .
60 . Use of point of care testing in the ED . Chicago, IL . Nov 2, 2005 .
61 . Improving the flow of patients with ACS in the ED . Urgent Matt
ers Regional Conference,
Las Vegas, NV . Oct 28, 2005 .
62 . ED m anagement of ADHF in the ED . Rockville Centre, NY
. Oct 26, 2005
63 . Wound closure . Melbourne, FL . Oct 25, 2005 .
64 . Wound closure update. Phoenix, AZ Oct 19, 2005
65 . Grand Rounds : Wound controversies . North Shore University Hosp
., Manhasset, NY Oct
19, 2005
66 . Wound closure and tissue adhesives . Virginia Beach, VA . Oct 18, 2005 .
67 . Wound updates . Dall as, TX. Oct 17, 2005 .
68 . Controversies in wound management . Tulsa, OK. Oct 14, 2005 .
69 . Improving the flow with patients with ACS in the ED . Urgent Ma tters Regional
Conference . Atlanta, GA . Oct 13, 2005 .
70 . Evaluation and management of heart failure in the ED . Oyster Bay, NY
. Oct 11, 2005 .
71 . Update on wound closure devices . Shrevepo rt, LA. Oct . 10, 2005 .
72 . Wound updates . Washington DC . September 27, 2005 .
73 . Skin adhesives . Richmond, VA . September 21, 2005 .
74 . Controvers ies in wound care . Jacobi Medical Center, NY, NY . September 21 ,
2005 .
75 . Management of acute decompensated heart failure. NY, NY.
September 15, 2005.
76 . Tissue Adhesives . West Virginia. September 14, 2005 .
- 77 . Proper wound closure . Pittsburgh, PA . September 13, 2005 .
78 . Wound closure . Monroe, LA . September 12, 2005 .
79 . Controversies in wound management . Oklahoma City, OK
. August 18, 2005 .
80 . Wound closure and would healing . Oklahoma City, OK . August 17 ,
2005.

11
i r July 23, 2007
81 . Grand Rounds : Acute Decompensated heart failure . Our Lady of Mercy Hospital, Bronx,
NY . August 17, 2005 .
82 . Wound closure in the emergency room . Chevy Chase, MD . July 20, 2005 .
83 . Topical skin adhesives in the ER . Washington, DC . July 20, 2005 .
84 . Advances in wound closure . Hackensack, NJ, July 8, 2005 .
85 . Wound closure & wound healing . Seattle / Spokane, WA, June 9, 2005 .
86 . Wound healing. North Brunswick, NJ, June 8, 2005 .
87 . Topical skin adhesive ; practical & cosmetic . Del Mar, CA, May 26, 2005 .
88 . State of the art science in wound healing . Glenview, IL, May 19, 2005 .
89 . Advances in wound closure in the emergency room . Oak Park, IL, May 18, 2005 .
90 . Acute decompensated heart failure . Boston, MA, May 17, 2005 .
91 . Topical skin adhesives . New York, NY, May 12, 2005 .
92 . Proper wound closure protocol . Kansas City, MO, May 5, 2005 .
93 . Wound controversies . Orlando, FL, March 9, 2005 .
94 . Tissue Adhesives : Pearls, Pitfalls, and Misconceptions . Boston, MA, February 24, 2005
.
95 . Grand Rounds : Wound Controversies . Christiana Medical Center, Newark, DE, February
16, 2005 .
96 . Heart Failure Management . Garden City, NY, February 16, 2005 .
97 . Wound Management . Stony Brook University, Stony Brook, NY, February 7, 2005 .
98 . Grand Rounds : Management of Acute Decompensated Heart Failure in the ED
. Lennox
Hill Hospital, NY, NY, February 4, 2005 .
99 . ED management of acute decompensated heart failure . New York, NY, February 2, 2005
.
100 . Multi-center research . ACEP Practice Management Symposium, New York, NY, January
28, 2005 .
101 . Managing heart failure . Washington, DC, January 27, 2005 .
102 . Wound Controversies . Stony Brook, December 17, 2004 .
103 . Wound Controversies . Maui, HI, December 5, 2004 .
104 . Wound Management . Dallas, TX, November 10, 2004 .
105 . Heart failure management, Grand Rounds, Queens, NY, November 3, 2004 .
106 . Wound healing . Las Vegas, October 28, 2004 .
107 . Topical skin adhesives in the ER . New York, NY, October 27, 2004 .
108 . ED management of acute decompensated heart failure
. ADHERE Registry, San Francisco,
CA, October 16, 2004 .
109 . Topical skin adhesives in the ER . ACEP, San Francisco, CA, October 15, 2004
.
110 . Wound Controversies, Grand Rounds, Metropolitan Hospital, New York, NY, September
29, 2003 .
111 . Wound Management and tissue adhesives, Atlanta, GA, September 21, 2004
.
112 . Use of tissue adhesives : pearls, pitfalls and misconceptions
. Portland, OR, September 16,
2004.
113 . Wound Controversies, Grand Rounds, McGill University, Montreal, Canada, September
15, 2004 .

12
• ~
July 23, 200 7
114 . ED Management of acute decompensated heart failure . Huntington, NY, September 9,
2004.
115 . Tissue adhesives and wound closure. El Paso, TX, September 7, 2004
.
116 . Wound Controversies, Grand Rounds, Medical College of Pennsylvania
. Philadelphia, PA,
August 10, 200 4
117 . Tissue Adhesives . San Diego, CA, August 5, 2004 .
118 . DVT Prophylaxis . East Meadow, NY, July 15, 2004 .
119. Laceration management . Columbus, OH, July 8, 2004 .
120 . Laceration Management . Waverly, WV, July 8, 2004 .
121 . Laceration Management . Pittsburgh, PA, July 7, 2004 .
122 . Laceration Management . Little Rock AR, June 28, 2004 .
123 . Laceration Managements . Minneapolis, MN, June 21, 2004 .
124 . Comparison of Tissue Adhesives . Somerville, NJ, June 17, 2004 .
125 . Comparison of Tissue Adhesives . Somerville, NJ, June 15, 2004 .
126 . Controversies in Wound Management . Grand Rounds, New York Presbyterian Hospital,
New York, NY, June 14, 2004 .
127 . Pain management . New York, NY, June 10, 2004 .
128 . Wound closure . Sacramento, CA, May 27, 2004 .
129 . Tissue adhesives . Orlando, FL, May 24, 2004 .
130 . Wound controversies . Augusta, GA, May 21, 2004 .
131 . Wound controversies . Omaha, NB, May 12, 2004 .
132 . Tissue adhesives . Tampa, FL, May 6, 2004 .
133 . Tissue adhesives . Philadelphia, PA, May 5, 2004 .
134 . Pain management . Washington DC, April 20, 2004 .
135 . Deep vein thrombosis prophylaxis . Larchmont, NY, March 18, 2004
.
136 . Deep vein thrombosis prophylaxis . Bay Shore, NY, March 4, 2004
.
137 . Wound controversies . Grand Rounds . Mt Sinai Hospital, New York, NY, Feb 11, 2004
.
138 . Wound controversies . Grand Rounds, Barnes Jewish Hospital, St
. Louis, MO, Feb 3, 2004 .
139 . Laceration management . St Louis, MO, Feb 2, 2004.
140. Wound closure . Grand Rounds at UC Davis . Jan 13, 2004 .
141 . Wound update 2003 . 27th annual CAPA Conference . Oct 24, 2004
.
142 . Wound closure . Cincinnati, OH, Oct 22, 2003 .
143 . Wound Controversies . Yale New Haven Hospital . Grand Rounds
. New Haven, CT, Oct
l, 2003 .
144 . Designing prospective research in your Emergency Department
. Barcelona, Spain, Sep 16,
2003
145 . Wound update 2003 . Kansas City, MO, Aug 27, 2003 .
146 . The biology of wound healing . Somerville, NJ, Aug 4, 2003 .
147 . Wound update 2003 . St . Luke's Hospital
. Grand Rounds, Bethlehem, PA, July 31, 2003 .
148 . Update on wound healing . Chaim Sheba Medical Center, Tel-Aviv University, Tel
Hashomer, Israel : Grand Rounds, July 17, 2003 .

13
July 23, 2007
149 . Wound closure . Chicago, IL, June 13, 2003 .
150 . Wound closure . Cincinnati, OH, June 17, 2003 .
151 . Kaiser Permenente . Sacramento, CA, May 22, 2003 .
152 . Wound closure . Downstate Grand Rounds, Brooklyn, NY, May 14, 2003 .
153 . Wound closure and tissue adhesives . Wellesley, MA, May 13, 2003 .
154. Wound closure . Raleigh, NC, Mar 13, 2003 .
155 . High viscosity tissue adhesive . Barbados, Jan 27, 2003 .
156 . High viscosity tissue adhesive . Baltimore, MD, Dec 11, 2002 .
157. Wound closure . Johnson & Johnson, Boston, MA, Oct 20, 2002 .
158 . Wound closure. West Orange, NJ, Sep 18, 2002 .
159 . Community Acquired Pneumonia . West Orange, NJ, Sep 17, 2002 .
160 . Wound closure . Raleigh, NC, July 30, 2002 .
161 . Bum management . Grand Rounds, Morristown Memorial Hospital, Morristown, NJ, June
26, 2002 .
162 . Wound closure . Los Angeles, CA, June 11, 2002 .
163 . Wound closure . Anaheim, CA, June 10, 2002 .
164 . Wound closure and tissue adhesives . Somerville, NJ, May 14, 2002 .
165 . Evaluation of LOD for donor sites . Wound Healing Symposium, Baltimore, MD,
Apr 29, 2002 .
166 . Evaluation of LOD for partial thickness wounds . Department of Dermatology, Miami
University, Mar 2002.
167 . Burn evaluation and management / Research in wound healing, Emergency Grand Rounds,
University of Pittsburgh, Pittsburgh, PA, Feb 28, 2002 .
168 . Wound Management and use of Tissue Adhesive . Brown Medical School, Providence, RI,
Nov 19, 2001 .
169 . Wound Care and Tissue Adhesives . South Carver, MA, June 21, 2001 .
170 . Grand Rounds Lecture, Northwestern Memorial Hospital, Chicago, IL, Mar 28, 2001
.
171 . Wound Healing Research Overview, Ortec International, Inc ., New York, NY, Mar 22,
2001 .
172 . Wound Care and Tissue Adhesives . Chicago, IL, Feb 23, 2001
. Wound Care Workshop . Sedona, AZ, Feb 17-18, 2001 . .173
174 . Tissue Adhesives . Dutch Surgical Meeting. Rotterdam, Netherlands, Oct 20, 2000 .
175 . Wound Care and Tissue Adhesives . Brookhaven Memorial Hospital, Sep 22, 2000
.
176 . Wound Care and Tissue Adhesives . Rhode Island Chapter ACEP, Newport, RI, July, 2000
.
177 . New Advances in Wound Closure . Biomaterials of the Future . San Francisco, CA, June
2000 .
178 . Clinical Outcomes . Preventive Medicine. SUNY, Stony Brook, June 13, 2000 .
179 . Tissue Adhesives . North Shore University Hospital, Manhasset, NY, June 13, 2000
.
180 . Wound Management . Family Medicine 26th Annual Seminar
. SITNY, Stony Brook,
June 2, 2000.
181 . Wound Healing . Brookhaven Memorial Hospital . June 2, 2000.
182 . Wound Care. Chirurgendagen, Amsterdam, Netherlands, May 17 and May 18, 2000
.
14
July 23, 2007
183 . Wound Care and Tissue Adhesives . Somerville, NJ, May 16, 2000 .
184 . Wound Care and Tissue Adhesives. London, England, Apr 26, 2000 .
185 . Wound Care and Tissue Adhesives . Southampton, England, Apr 25, 2000 .
186 . Emergency Medicine Week in Israel-2000 . 7th Annual Scientific Assembly . Herzliya,
Israel, Mar 26-Apr 2, 2000 .
187 . Wound Care and Tissue Adhesives . Charlotte, NC, Mar 2000 .
188 . Wound Care and Tissue Adhesives . Newark, NJ, Mar 2000.
189 . Wound Care and Tissue Adhesives . Denver, CO, Mar 2000 .
190 . Wound Care and Tissue Adhesives . Birmingham, AL, Feb 2000 .
191 . Wound Care and Tissue Adhesives . Boston, MA, Dec 1999 .
192 . Wound Care and Tissue Adhesives . Los Angeles, CA, Dec 1999 .
193 . Wound Care and Tissue Adhesives . Portland, OR, Dec 1999 .
194 . Wound Care and Tissue Adhesives . Somerville, NJ, Dec 22, 1999 .
195 . Wound Care and Tissue Adhesives . Dallas, TX, Nov 1999 .
196 . Wound Care and Tissue Adhesives. Minneapolis, MN, Nov 1999 .
197 . Wound Care and Tissue Adhesives. Chicago, IL, Nov 1999 .
198 . Wound Care and Tissue Adhesives . Charlotte, NC, Oct 1999 .
199 . Wound Care and Tissue Adhesives . New Orleans, LA, Oct, 1999 .
200 . Wound Care and Tissue Adhesives . New York, NY, Sep, 1999 .
201 . Advances in Wound Care . New York American College of Emergency Medicine, New
York, NY, July 1999 .
202 . Advances in Wound Care . Family Practice Update 1999 . SUNY at Stony Brook, Stony
Brook, NY, June 1999 .
203 . Research in Wound Care . Harvard Medical School . Boston, MA, June 1999 .
204. Emergency Medicine Week in Israel-1999 . Wound care workshop : Tel-Aviv, Israel,
Mar 1999 .
205 . Advances in Wound Management . Huntington, New York, NY, Jan 1999 .
206 . Wound Care and Tissue Adhesive . St . Louis, MO, 1998 .
207 . Wound Care and Tissue Adhesive . Cleveland, OH, 1998 .
208 . Tissue Adhesives . International Conference on Emergency Medicine
. Vancouver, Canada,
May, 1998.
209 . Emergency Medicine Week in Israel-1998 . Advanced concepts in emergency medicine :
"Wound Controversies ." Jerusalem, Israel, Mar, 1998 .
210. Evaluation and Management of Bums . Department of Emergency Medicine, University of
Pennsylvania, Philadelphia, PA, Sept 1997 .
211 . Grand Rounds : "Wound Management" North Shore University Hospital, Manhasset, NY,
Aug 1997 .
212 . Evaluation and management of bums . Department of Family Medicine, SUNY at Stony
Brook, NY, July 1997 .
213 . Emergency Medicine Week in Israel-1997 . Advanced concepts in emergency medicine
:
"Wound Management ." Jerusalem, Israel, Mar 1997 .

15
July 23, 2007
214. Grand Rounds : "Wound Management ." Morristown Memorial Hospital, Morristown, NJ,
Nov 1996 .

16
~ •
July 23, 2007

Publications

Peer Reviewed Publications :

Cutaneous Wounds

1 . Singer AJ, Quinn JV, Hollander JE . The cyanoacrylate tissue adhesives


. Am J Emerg Med
2007 ;14 : in press.
2 . Singer AJ, Arora B, Dagum A, Valentine S, Hollander JE
. Development and validation of
a novel scar evaluation scale . Plastic & Reconstr Surg 2007 ; in press.
3 . Singer AJ, Jurukovski V, Simon M, Ma J-Y, Protter A, Arora B, Soroff HS
. The presence
of BNP in bums and the responsiveness of fibroblasts to BNP : Proof of Principle. Acad
Emerg Med 2007 ; in press .
4 . Singer AJ, Lee CC . Management of minor thermal injuries
. Am J Emerg Med 2007 ; in
press;
5 . Singer AJ, Wang Z, McClain SA, Pan Y . Optical coherence tomography
: A non-invasive
method to assess wound reepithelialization : Acad Emerg Med 2007 ; 14 : 387-391 .
6 . Singer AJ, McClain SA . Development of a porcine incisional wound model and novel
scarring scales . Wound Repair & Regen 2006 ;14 :492-497 .
7 . Soroff HS, Singer AJ . The initial management of minor bums
. J Korean Am Med Assoc
2006 ;12:64-71 .
• 8 . Carleo C, Singer AJ . Effect of frequent soaking on the rate of tissue adhesive sloughing
:
A randomized study . Can J Emerg Med 2005 ;7:391-395 .
9 . Chale S, Singer AJ, Marchini S, McBride MJ, Kennedy D
. Digital versus local anesthesia for
finger lacerations : A Randomized Controlled Trial . Acad Emerg Med 2006 ;13
:1046-1050.
10 . Singer AJ, McClain SA, Hacht G, Botchkina G, Simon M
. Semapimod enhance s
reepithelialization of partial thickness bums in swine. J Bum Care & Rehab 2006 ;27 :40-
49 .
11 . Singer AJ, Friedman B, Modi P, Soroff HS
. Effects of a commercially available cooling
blanket on core temperatures in volunteers . Acad Emerg Med 2006 ; 13 :686-690 .
12 . Singer AJ, Thode HC Jr, Hollander JE . National trends in Emergency Departmen
. Am J Emerg Med 2006 ;24 :183-188 . tlacerionsbw192-0
13 . Singer AJ, Arora B . Topical skin tissue adhesives
. J Korean Am Med Assoc 2005 ;11 :92-
96 .
14 . Soroff HS, Singer AJ . Initial management of minor bums
. Israeli J Emerg Med 2005 ;4:7-
16.
15 . Singer AJ, Soroff HS, Brebbia J . Octylcyanoacrylate for the treatment of small,
superficial, partial-thickness bums : A pilot study . Acad Emerg Med 2005 ;12
:900-904.
16 . Singer AJ, Gulla J, Hein M, Marchini C, Chale S, Arora B
. Single vs double layer closure of
facial lacerations : A randomized control trial . Plast & Reconstr Surg 2005
;116 :363-368 .
17 . Singer AJ, Specht J, Henry MC
. Self-inflicted injuries in adolescents presenting to a
suburban emergency department . J Forensic Nurs 2005 ; 1 :20-22 .
18 . Singer AJ, Blanda M, Cronin K, Lo-Giudice-Khwaja M, Gulla J, Bradshaw J
. Comparison
of nasal tampons for the treatment of epistaxis in the Emergency Department : A
randomized control trial . Ann Emerg Med 2005 ;45 :134-139 .
19 . Tarsia V, Singer AJ, Cassara GA, Hein MT
. Percutaneous regional compared with local
anaesthesia for facial lacerations : A randomized controlled trial . Emerg Med J
2005 ;22 :37-40 .

17
July 23, 2007
20 . Rosenberg L, Lapid 0,
Bogdanov-Berezovsky A, Glesinger R, Krieger Y, Silberstein E ,
Sagi A, Judkins K, Singer AJ . Safety and efficacy of a proteolytic enzyme for enzymatic
burn debridement : A preliminary report . Bums 2404 ;843-850.
21 . Singer AJ, Gulla J, Thode HC Jr, Cronin KA
. Pediatric first aid knowledge among
patients . Pediatr Emerg Care 2004;20 :808-811 .
22 . Singer AJ, McClain SA, Katz A . A porcine epistaxis model
: Hemostatic effects of
octylcyanoacrylate . Otolaryngol Head Neck Surg 2004 ; 130 :553-557 .
23 . Singer AJ, Zimmerman T, Rooney J, Cameau P, Rudomen G, McClain SA
. Comparison of
wound bursting strength and surface characteristics of FDA approved tissue adhesive for
skin closure . J Adhesion Sci Technol 2004 ; 18 :19-27 .
24 . Singer AJ, Thode HC Jr . A review of the literature on octylcyanoacrylate tissue adhesive
.
[Review] Am J Surg 2004 ;187 :238-248 .
25 . Singer AJ, Mynster CJ, McMahon BJ . The effect of intramuscular Ketorolac
Tromethamine on bleeding time : A prospective interventional controlled study . Am J
Emerg Med 2003 ;21 :441-443 .
26 . Singer AJ, McClain SA . Development of a porcine excisional wound model
. Acad Emerg
Med 2003 :10 :1029-1033 .
27 . Singer AJ, Giordano P, Fitch JL, Gulla JM, Ryker D, Chale S
. Evaluation of a new high-
viscosity OCA tissue adhesive for laceration repair . A randomized clinical trial . Acad
Emerg Med 2003 ;10 :1134-1137 .
28 . Singer AJ, Nable M, Cameau P, Singer DD, McClain SA
. Evaluation of a new LOD for
excisional wounds . Wound Repair & Regen 2003 ;11 :181-187 .
29 . Mittra ES, Singer AJ, Bluestein D, Hollander JE
. Simulated wound irrigation impact
pressures . Israeli J Emerg Med 2003 ;3 :9-16 .
30. Singer AJ, McClain SA . Persistent wound infection delays epidermal maturation and
increases scarring in thermal burns . Wound Repair and Regen 2002 ;10 :372-377.
31 . Singer AJ, Thode HC Jr . National analgesia prescribing patterns in Emergency
Department patients with burns . Bum Care & Rehab 2002 ;23 :361-365 .
32 . Singer AJ, McClain SA . The effects of a high potency topical steroid on cutaneous healing
of burns in pigs . Acad Emerg Med 2002 ;9 :977-982.
33 . Singer AJ . Hair apposition for scalp lacerations [Editorial] Ann Emerg Med 2002
;40 :27-29 .
34 . Singer AJ, Quinn JV, Thode HC Jr ., Hollander JE
. Determinants of poor outcome after
laceration and surgical incision repair . Plastic & Reconstruc Surg 2002 ;110 :429-435 .
35 . Singer AJ, Quinn JV, Hollander JE, Clark RE
. Closure of lacerations and incisions with
Octylcyanoacrylate : A multi-center randomized clinical trial . Surgery 2002 ;131
:270-276 .
36 . Hollander JE, Singer AJ, Valentine SM, Shofer FS
. Risk factors for infection in patient s
with traumatic lacerations . Acad Emerg Med 2001 ;8:716-720 .
37 . Singer AJ, Stark MJ . LET vs EMLA
for pretreating lacerations-A randomized trial .
Acad Emerg Med 2001 ;8 :223-230.
38 . Singer AJ, Thode HC Jr, McClain SA
. Effects of Octylcyanoacrylate on scarring after
burns . Acad Emerg Med 2001 ;8 :107-111 .
39 . Singer AJ (Contributing Editor) . Part 5 : New First Aid Guidelines
: Guidelines 2000 for
Cardiopulmonary Resuscitation and Emergency Cardiovascular Care . Circulation
2000;1 02(8) :177-I85 .
40 . Berrutti LE, Singer AJ,1VIcClain S . Histopathological effects of cutaneous tape striping in
pigs . Acad Emerg Med 2000 ;7 :1349-1353.
41 . Singer AJ, Thode HC Jr, McClain SA
. Development of a histomorphologic scale to
quantify cutaneous scars after burns . Acad Emerg Med 2000;7 :1083-1088 .

18
July 23, 2007
42 . Singer AJ, Mach C, Thode HC Jr ., Hemachandra, Shofer, Hollander JE
. Patient priorities
with traumatic lacerations . Am J Emerg Med 2000 ;18(6) :683-686 .
43 . Singer AJ, Stark MJ . Pretreatment of lacerations with LET at triage
: A randomized trial .
Acad Emerg Med 2000 ;7:751-756 .
44 . Singer AJ, Mohammad M, Thode HC Jr, McClain SA
. OCA vs polyurethane for treatment
of burns in swine : A randomized trial . Bums 2000 ;26:388-392 .
45 . Singer AJ, Mohammad M, Tortora G, Thode HC, Jr ., McClain SA
. Octyl-cyanoacrylate
for the treatment of contaminated partial thickness bums in swine . A randomized
controlled study . Acad Emerg Med 2000 ;7 :222-227 .
46 . Singer AJ, Thode HC Jr ., McClain SA . The effects of epidermal debridement of partial
thickness bums on infection and reepithelialization in swine . Acad Emerg Med
2000 ;7 :114-119 .
47 . Singer AJ, Berrutti L, Thode HC Jr, McClain SA
. Standardized bum model using a multi-
parametric histological analysis of bum depth . Acad Emerg Med 2000 ;7:1-6.
48 . Singer AJ, Berruti L, McClain SA . Comparative trial of octyl-cyanoacrylate and silver
sulfadiazine for the treatment of full-thickness skin biopsies . Wound Repair and Regen
1999 ;7 :356-361 .
49 . Singer AJ, Coby CT, Singer AH, Thode HC Jr, Tortora GT . The effects of low frequency
ultrasound on staphylococcus epidermidis . Curr Microbiol 1999 ;38 :194-196 .
50 . Hollander JE, Singer AJ . Laceration management . Ann Emerg Med 1999
;34 :356-367 .
51 . Singer AJ, Clark RAF . Advances in Cutaneous Wound Healing
. New Eng1 J Med
1999 ;341 :738-746.
52 . Singer AJ, Berrutti L, Thode Jr HC, McClain SA
. Octyl-cyanoacrylate for the treatment of
partial thickness bums in swine . A randomized controlled trial . Acad Emerg Med
1999 ;6:668-692 .
53 . Singer AJ . Clinical wound evaluation scales [editorial] . Acad Emerg Med 1998
;5 :564-566 .
54. Singer AJ, Hollander JE, Valentine SM, Turque TW, McCuskey CF, Quinn JV
. Prospective,
randomized, controlled trial of a new tissue adhesive (2-Octyl Cyanoacrylate) versu s
standard wound closure techniques for laceration repair . Acad Emerg Med 1998 ;5 :94-99.
55 . Hollander JE, Valentine SM, Turque T, Singer AJ . Long-term evaluation of cosmetic
appearance : Validation of telephone assessment . Ann Emerg Med 1998 ;31 :92-98 .
56 . Hollander JE, Richman PB, Werblud M, Miller T, Huggler J, Singer AJ
. Irrigation in facial
and scalp lacerations : Does it alter outcome? Ann Emerg Med 1998 ;31 :73-77.
57 . Hollander JE, Singer AJ, Valentine SM . Comparison of wound care practices in pediatric and
adult lacerations repaired in the emergency department . Ped Emerg Care 1998 ;14 :15-18 .
58 . Hollander JE, Singer AJ . Application of tissue adhesives
: Rapid attainment of proficiency .
Acad Emerg Med 1998 ;5 :1012-1017.
59 . Singer AJ, Shallat J, Vallentine S, Doyle L, Thode HC
. Cutaneous tape stripping to
enhance topical drug absorption . A randomized controlled trial . Acad Emerg Med
1998 ;5 :1051-1056 .
60. Singer AJ, Homan CS, McClain SA, Church AL . Low frequency sonophoresis
:
Pathologic and thermal effects in dogs . Acad Emerg Med 1998 ;5:35-40 .
61 . Singer AJ, Hollander JE, QuinnJV . Evaluation and management of traumatic lacerations
.
New Engl J Med 1997 ;337 :1142-1148 .
62 . Singer AJ, Church AL, Forrestal K, Werblud M, Hollander JE
. Comparison of patient and
practitioner satisfaction with wound appearance after traumatic wound repair . Acad Emerg
Med 1997 ;4 :133-137 .

19
July 23, 2007
63 . Brogan GX, Singer AJ, Hollander JE, Giarrusso E . Comparison of wound infection rates
using plain versus buffered lidocaine for anesthesia of traumatic wounds . Am J Emerg
Med 1997 ;15 :25-28 .
64 . Singer AJ, Hollander JE, Valentine SM, Thode HC, Henry MC
. Association of training
level and short term cosmetic appearance of repaired lacerations . Acad Emerg Med
1996 ;3:378-383 .
65 . Hollander JE, Blasko B, Singer AJ, Thode HC, Henry MC
. Poor correlation of short- and
long term cosmetic appearance of repaired lacerations . Acad Emerg Med 1995 ;2 :983-987.
66 . Hollander JE, Singer AJ, Valentine S, Henry MC . The wound registry
: Development and
validation . Ann Emerg Med 1995 ;25 :675-685 .
67 . Singer AJ, Hollander JE, Cassara G, Valentine SM, Thode HC Jr, Henry MC
. Level of
training, wound care practices, and infection rates . Am J Emerg Med 1995 ; 13 :265-268 .
68 . Singer AJ, Hollander JE, Subramanian S, Malhotra AK, Villez PA
. Pressure dynamics of
irrigation methods commonly used in the emergency department . Ann Emerg Med
1994;24 :36-40 .
69 . Singer A, Sagi A, Ben-Meir P, Rosenberg L . Chemical bums
: our ten year experience .
Bums 1992 ;18 :250-252.
70 . Singer AJ, Hollander JE . Infiltration pain and local anesthetic effects of buffered vs plain
1% diphenhydramine . Acad Emerg Med 1995 ;2:884-888 .
71 . Hauben D, Carmi R, Singer A . Reconstructive surgery for Down syndrome
. QuartMed
Rev 1989 ;1(1) :20-22 .

Pain Assessment and Managemen t

72 . Lee CC, Golub R, Singer AJ, Cantu R, Levinson H


. Routine versus selective abdominal
computed tomography scan in the evaluation of right lower quadrant pain . A RCT . Acad
Emerg Med 2007 ;14 :117-123 .
73 . Singer AJ, Weeks R, Regev R . Laser assisted anesthesia reduces the pain of venous
cannulation in children and adults : A RCT . Acad Emerg Med 2006 ; 13 :623-628 .
74 . Singer AJ, Singer D, McClain S, Tortora G
. Histologic effects of laser assisted topical
anesthesia in a porcine model . Acad Emerg Med 2005 ; 12 :1148-1152.
75 . Singer AJ, Regev R, Weeks R, Tlockowski D
. Laser assisted anesthesia prior to
intravenous cannulation in volunteers : A randomized controlled trial . Acad Emerg Med
2005 ; 12 :804-808 .
76 . Lovell SJ, Wackett A, Gulla J, Singer AJ
. Comparison of Valdecoxib and an oxycodone
acetaminophen combination for acute musculoskeletal pain in the ED . A randomized
controlled trial . Acad Emerg Med 2004 ;11 :1278-1282 .
77 . Siderias J, Gaudio F, Singer AJ
. Comparison of topical anesthetics and lubricants prior to
urethral catheterization in males : A randomized controlled trial . Acad Einerg Med
2004 ;11 :703-706 .
78 . Nelson B, Cohen D, Lander 0, Crawford N, Viccellio A, Singer A
. Mandated pain scales
improve frequency of ED analgesia administration . Am J Emerg Med 2004 ;22:582-585 .
79 . Singer AJ, Gulla JM, Thode HC Jr . Parents and practitioners are poor judges of youn
g
children's pain severity . Acad Emerg Med 2002;9 :609-612 .
80 . Singer AJ, Kowalska A, Thode HC Jr . Ability of patients to accurately recall the severity
of acute painful events . Acad Emerg Med 2001 ;8:292-295.
81 . Dickinson R, Singer AJ, Carrion W
. Etomidate for pediatric sedation prior to fracture
reduction . Acad Emerg Med 2001 ;8 :74-77 .

20
July 23, 2007
82 . Singer AJ, Richman PB . Comparison of patient and practitioner assessment of pain from
commonly performed emergency department procedures . Ann Emerg Med 1999 ;33 :652-658 .
83 . Singer AJ, Konia N . Comparison of topical anesthetics and vasoconstrictors versu
s
lubricants prior to nasogastric intubation . A randomized controlled trial . Acad Emerg Med
1999 ;6:184-190.
84 . Richman PB, Singer AJ, Flanagan M . The effectiveness of ice as a topical anesthetic for
the insertion of intravenous catheters . Am J Emerg Med 1999 ;17:255-257 .

Cardiovascular

85 . Singer AJ, Shembekar A, Visram F, et al


. Emergency department activation of an
interventional cardiology team reduces door-to-balloon times in STEMI . Ann Emerg Med
2007 ; in press .
86 . Chaudry A, Singer AJ, Chohan J, Russo V . Inter-rater reliability of hemodynamic profiling
of heart failure patients in the emergtency department . Am J Emerg Med 2007 ; in press .
87 . Singer AJ, Visram F, Shembekar A, Khwaja M, Viccellio A
. Telemetry monitoring during
transport of low-risk chest pain patients from the ED : Is it necessary? Acad Emerg Med
2005 ; 12 :965-969 .
88 . Singer AJ, Ardise J, Gulla J, Cangro J
. Point of care testing reduces length of stay in ches t
pain patients. Ann Emerg Med 2005 ;45 :587-59 1 .
89 . Engelberg S, Singer A, Moldashel J, Sciammarella J, Thode HC Jr ., Henry MC
. Effects o f
prehospital nitroglycerine on vital signs and chest pain intensity . Prehosp Emerg Care
2000 ;4:290-293 .
90. Singer AJ, Kahn SR, Thode HC Jr, Hollander JE
. Comparison of forearm and upper ar
. Pre Hosp Emerg Care 1999 ;3 :123-126. mblodpresu
91 . Singer AJ, Brogan GX, Valentine SM, McCuskey C, Khan S, Hollander JE
. Effect of
duration from symptom onset on the negative predictive value of a normal ECG for
exclusion of acute myocardial infarction . Ann Emerg Med 1997 ;29 :575-579.
92 . Singer AJ, Hollander JE . Blood pressure : Assessment of interarm variability
. Arch
InternalMed 1996 ;156 :2005-2008 .
93 . Hollander JE, Todd KH, Green G, Heilpern KL, Karras DJ, Singer AJ, Brogan GX, Funk
JP, Strahan JB . Chest pain associated with cocaine : An assessment of prevalence in
suburban and urban emergency departments . Ann Emerg Med 1995 ;26:671-676.

Research Methodology

94 . Hollander JE, Singer AJ . An innovative strategy for conducting clinical research


: The
Academic Associate Program . Acad Emerg Med 2002 ;9 :134-137 .
95 . Singer AJ, Thode HC, Jr, Hollander JE . Research Fundamentals
: Selection and
development of clinical outcomes . Acad Emerg Med 2000 ;7(4) :397-401 .
96 . Singer AJ, Homan CS, Brody M, Thode Jr HC, Hollander JE
. Evolution of abstracts
presented at the annual scientific meetings of Academic Emergency Medicine . Am J
EmergMed 1999 ;17 :638-641 .
97 . Singer AJ, Thode HC Jr
. Determination of the minimal clinically significant difference on
a patient visual analogue satisfaction scale. Acad Emerg Med 1998 ;5:1007-1011 .

21
July 23, 200 7
98 . Singer AJ, Homan CS, Stark MJ, Werblud MS, Thode HT, Hollander JE
. Comparison of
published research in emergency medicine and non-emergency medicine journals . Acad
Emerg Med 1997 ;4:1153-1158 .
Other

99 . Singer AJ, Singer AH, Halpern P, Caspi G, Assaf K . Medical lessons from recent terror
attacks in Israel . J Emerg Med 2007 ;32:87-92 .
100 . Lee CC, Hwang SO, Im MJ, Kim TM, Singer AJ . The current status of emergency medical
system in Korea . Am J Emerg Med 2006 ; in press.
101 . Lee CC, Singer AJ . Respiratory failure due to subglottic stenosis from relapsing
polychondritis . Am J Emerg Med 2006 ;24 :750-752.
102 . Fischer TF, Singer AJ, Gulla J, Garra G, Rosenfeld R . Reaction toward a new treatment
paradigm for acute otitis media . Pediatric Emergency Care 2005 ;21 :170-172.
103 . Singer AJ, Lampel M, Lewis L, Schafemeyer RW, O'Neil B, Camargo C, Nowak R
.A
call for expanding the role of the emergency physician in the care of asthmatic patients .
Ann Emerg Med 2005 ;45 :295-298 .
104 . Singer AJ, Chretien J, Viccellio AW, Schiavone F, Thode HC Jr . Insertion of IVs by
residents : Does it save time . Am J Emerg Med 2002 ;20:385-387.
105 . Gaspari R, Singer AJ . Magnetically-guided orotracheal intubation . Acad Emerg Med
2001 ;8 :285-287 .
106 . Singer AJ. Alternative medicine : Why should we care? Acad Emerg Med 2001 ;8 :65-67 .
107 . Singer AJ, Sauris E, Viccellio A . Ceruminolytic effects of docusate sodium
:A
randomized trial . Annals Emerg Med 2000;36 :228-23 1 .
108 . Singer AJ, Gulla J . Use of alternative therapies among emergency department patients
.
Ann Emerg Med 2000 ;35:226-228.
109 . Fischer TFX, Singer AJ . Comparison of the palatability of standard and superactivated
charcoal in toxic ingestion . Acad Emerg Med 1999 ;6:895-899 .
110 . Harrow C, Singer AJ, Thode HC . Facilitating the use of the erythrocyte sedimentation rate
in the emergency department . Acad Emerg Med 1999 ;6:658-660.
111 . Singer AJ, Nestle M . Improvements are needed in hospital diets to meet dietary guidelines
for health promotion and disease prevention . J Am Dietetic Assoc 1998 ;98(6) :639-64 1 .
112 . Homan CS, Singer AJ, Thomajan C, Henry MC, Thode HC Jr . Thermal characteristics of
neutralization therapy and water dilution for strong acid ingestion : An in vivo canine
model . Acad Emerg Med 1998 ;5:286-292.
113 . Singer AJ, Migdal PM, Oken J, et al . Clostridium perfringens septicemia with massive
hemolysis in a patient with Hodgkin's lymphoma . Am J Emerg Med 1997 ; 15 :152-154 .
114 . Homan CS, Singer AJ, Henry MC, Thode HC
. Thermal effects of neutralization therapy an d
water dilution for acute alkali exposure in canines . Acad Emerg Med 1997 ;4:27-32.
115 . Singer AJ . Hospital diets and nutrition . The Experts Speak 1997
: The Role of Nutrition in
Medicine. IT Services, Sacramento, 1997 :80.
116. Singer AJ, McCracken G, Henry MC, Cobahug C . Correlation between clinical,
laboratory, and hepatobiliary scanning findings in patients with suspected acute
cholecystitis . Ann Emerg Med 1996;28 :267-272 .
117 . Henry MC, Wheeler J, Mofenson HC, Carraccio TR, Marsh M, Comer GM, Singer AJ
.
Hydrogen peroxide 3% exposures . J Tox & Clin Toxicology 1996 ;34 :323-327.
118 . Singer AJ, Mofenson HC, Caraccio TR . Temporal profile of elevated transaminases in
patients with acetaminophen induced hepatic dysfunction . Ann Emerg Med 1995 ;25 :49-
53 .

22
! 0
July 23, 2007
119 . Singer AJ, Mofenson HS, Caraccio TR, Il asi J . Mercuric chlo ri de poisoning due t
o
ingestion of a stool fixative . J Toxicol and Clin Toxicol 1994 ;32:577-582.
120 . Singer AJ, Tichler T, Orvieto R, Finestone A, Moskovitz M . Testicular carcinoma
: a study
of knowledge, awareness, and practice of testicular self-examination in male soldiers and
military physicians . Mil Med 1993 ;158 :640-643 .
121 . Phillip M, Chaimovitz C, Singer A, Golinsky D . Urine osmolality in nursery school
children in a hot climate . Israel J Med Sci 1993 ;29 :104-106 .
122 . Phillip M, Singer A, Tal A . Copper deficiency in an infant with giardiasis fed with cow's
milk . Israel J Med Sci 1990 ;26:289-290.
123 . Singer A, Ben-Yehuda 0, Ben-Ezra Z, Zaltzman S . Multiple identical stress fractures in
monozygotic twins . Case report . J Bone Joint Surg (Amer) 1990 ;72 :444-445 .
124. Singer A, Phillip M, Hermoni D, Abelson M, Moses SW . Correlation between C-reactive
protein and throat culture results in patients with pharyngitis . Israel J Med Sci
1989 ;25 :235-236.

Letters / Non-Peer Reviewed Publications

Cutaneous Wounds

125 . Singer AJ. The cyanoacrylate tissue adhesives . Surgical Techniques International . 1999
.
126 . Singer AJ, Hollander JE. Tissue adhesives for laceration repair [letter] . JAMA
1997;278 :703-704.
127 . Singer AJ, Hollander JE, Quinn JV . Management of traumatic lacerations [letter] . New
Engl J Med 1998 ;338 :475-476.

Pain Assessment and Managemen t

128 . Singer AJ, Thode JC Jr. Pain from urethral and intravenous catheterization [letter] . Am J
Emerg Med 1998 ;16 :327 .
129. Singer AJ . Intranasal Midazolam in pediatric conscious sedation [letter] . Ann Emerg Med
1995 ;25:851-852 .

Other

130 . Lee CC, Singer AJ . Case of relapsing polychondiritis in the Emergency Department
. [case
report] Am J Emerg Med 2006 ; in press.
131 . Singer AJ . Providing quality asthma care in the Emergency Department
. Physician's
Weekly. 2005 ;Vo1 . 22, No. 13.
132. Singer AJ, Sanders TB, Kowalska A, Stark MJ, Mohammad M, Brogan GX
. The effect of
introducing bedside TV sets on patient satisfaction in the ED . [letter] . Am J Emerg Med
2000;18:119-120 .
133 . Gaspari R, Singer AJ . Magnetically-guided orotracheal intubation [letter] . Acad Emerg
Med 2001 ;8:1010-1011 .
134 . Singer AJ, Thode HC Jr ., Homan CS, Hollander JE . Letter to the Editor
: The State of
Emergency Medicine Research [In reply] . Acad Emerg Med 1998 ;5:745 .

23
~ 0
July 23, 2007
135 . Hollander JE, Singer AJ, Brogan GX . ECG abnormality in acute myocardial infarction
[letter] . Ann Emerg Med 1998 ;31 :137 .
136 . Singer AJ, McCracken G, Henry MC, Cobahug C . Correlation between clinical,
laboratory, and hepatobiliary scanning findings in patients with suspected acute
cholecystitis . Year Book of Emergency-Medicine 1998 .
137 . Singer AJ, McCracken G, Henry MC, Cobahug C . Utility of HIDA scans in patients with
suspected acute cholecystitis . Medical Updates on Therapy, Diagnosis and Prevention . 1998
.
138. Singer AJ. Corticosteroids and asthma in children [letter] . Ann Emerg Med 1997 ;30:355-356
.
139. Singer AJ . Prevention of Bacterial Endocarditis : American Heart Associatio n
Recommendations . JAMA [letter] . 1997 ;278 :1232.
140 . Singer AJ, Werther K, Nestle M . The nutritional value of hospital diets
: A multicenter
survey [letter] . New Engl J Med 1996 ;335 :1446-1447.
141 . Singer A, Berner Y, Winkler W . Hospital diets : how nutritious are they? [letter] Arch
Internal Med 1991 ;151 :1240.
142 . Hollander JE, Singer AJ . Blood pressure : Assessment of interarm variability [letter] .
Arch Internal Med 1997 ;157 :818 .

Books:

143 . Singer AJ . Contributing Author . Chameides L, Ed . Heartsaver First Aid with CPR an
d
AED . American Heart Association, 2005 .
144 . Singer AJ . Contributing Author . Chameides L, Ed. Heartsaver First Aid with CPR and
AED . American Heart Association, 2002 .
145 . Singer AJ, Hollander JE (Editors) . Lacerations and acute wounds . An evidence-based
guide. Philadelphia :FA Davis, 2002 .
146 . Singer AJ, Burstein J ., Schiavone F . Emergency Medicine Pearls, second edition :
Guidelines and hints for the resident and student . Philadelphia :FA Davis, 2001 .
147 . Singer AJ, Burstein J, Schiavone F . Emergency medicine pearls
: Guidelines and hints for
the resident and student . Philadelphia:FA Davis, 1996 .

Book Chaaters:

148 . Singer AJ . Neuropathic Pain . In


149 . Ackerman J, Singer AJ . Burn Pain. In
150 . Singer AJ, Simon M . Wound healing and skin substitutes . In : Stem cell and gene-based
therapy : Frontiers in regenerative medicine, Battler A, Leor J (eds), London :Springer-
Verlag, 2006, pp . 375-393 .
151 . Singer AJ, Hollander JE . Wound preparation . In Emergency Medicine -A comprehensive
Study Guide, 6th Ed., Tintinalli JE, Ruiz E, Krome RL (eds), In Press .
152 . Singer AJ, Hollander JE. Methods for wound closure. In Emergency Medicine-A
comprehensive Study Guide, 6th Ed., Tintinalli JE, Ruiz E, Krome RL (eds), In Press .
153 . Hollander JE, Singer AJ . Postrepair wound care . In Emergency Medicine -A
comprehensive Study Guide, 6th Ed ., Tintinalli JE, Ruiz E, Krome RL (eds), In Press .
154 . Singer AJ, Hollander JE. Wound preparation. In Emergency Medicine -A comprehensive
Study Guide, 5th Ed., Tintinalli JE, Ruiz E, Krome RL (eds), 2003 .

24
0 ~
July 23, 2007
155 . Singer AJ, Hollander JE . Methods for wound closure . In
Emergency Medicine -A
comprehensive Study Guide, 5th Ed., Tintinalli JE, Ruiz E, Krome RL (eds), 2003 .
156 . Hollander JE, Singer AJ. Postrepair wound care. In Emergency Medicine -A
comprehensive Study Guide, 5th Ed ., Tintinalli JE, Ruiz E, Krome RL (eds), 2003 .
157 . Singer AJ, McClain SA . A porcine bum model . In Methods in Molecular Medicine
:
Wound Healing . Methods and Protocols . DiPietro L, Burns-Harring A (editors) Totowa,
NJ :Humana Press, 2003, pp . 107-119.
158 . Singer AJ, Clark RAF . The biology of wound healing . In Laceration and acute wounds
.
An evidence-based guide . Philadelphia :FA Davis, 2002, pp . 1-8 .
159 . Singer AJ, Hollander JE . Wound preparation . In Laceration and acute wounds
. An
evidence-based guide . Philadelphia :FA Davis, 2002, pp . 13-22 .
160 . Singer AJ . Adhesive tapes. In Laceration and acute wounds . An evidence-based guide
.
Philadelphia :FA Davis, 2002, pp . 64-72 .
161 . Singer AJ . Surgical staples . In Laceration and acute wounds
. An evidence-based guide .
Philadelphia :FA Davis, 2002, pp . 73-82 .
162 . Singer AJ, Quinn JV . Tissue adhesives . In Laceration and acute wounds
. An evidence-
based guide . Philadelphia :FA Davis, 2002, pp . 83-97 .
163 . Hollander JE, Singer AJ . Selecting sutures and needles for wound care . In
Laceration and
acute wounds. An evidence-based guide . Philadelphia :FA Davis, 2002, pp . 98-107.
164 . Singer AJ, Rosenberg L . Basic suturing and tissue handling techniques . In
Laceration and
acute wounds . An evidence-based guide . Philadelphia :FA Davis, 2002, pp
. 108-132 .
165 . Hollander JE, Singer AJ. Wound management . In
The Clinical Practice ofEmergency
Medicine . Harwood-Nuss A, Wolfson AB, Linden CH, Shepherd SM, Stenklyft PH
(editors) Philadelphia : Lippincott, Williams and Wilkins 2001, pp . 449-459.
166. Clark RA, Singer, AJ . Wound repair : Basic biology to tissue engineering
. In Principles of
tissue engineering, second edition . Lanza R, Langer R, and Vacanti J, (editors) San
Diego :Academic Press, 2000, pp . 857-878 .
167 . Singer AJ, Hollander JE . Joint Aspiration, Major Joint Reduction, and Intraosseous
Infusion. In Review and self-assessment to accompany Emergency Medicine .
Howell JM,
Linden J, Barton D, Givre S (Editors) Philadelphia :WB Saunders Company 1999, pp . 389-
390
. Singer.168 AJ, Hollander JE. Percutaneous Central Venous Catheterization an
d
Pericardiocentesis . In Review and self-assessment to accompany Emergency Medicine .
Howell JM, Linden J, Barton D, Givre S (Editors) . Philadelphia :WB Saunders Company
1999, pp . 387-388.
169 . Hollander JE, Singer AJ . Cricothyroidotomy and Percutaneous Transtracheal Ventilation
and Peritoneal Lavage . In Review and self-assessment to accompany Emergency Medicine
Howell JM, Linden J, Barton D, Givre S (Editors) . Philadelphia:WB Saunders Company
1999, pp . 383-384 .
170. Hollander JE, Singer AJ . Lumbar Puncture and Gastrostomy Tubes . In
Review and self-
assessment to accompany Emergency Medicine . Howell JM, Linden J, Barton D, Givre S
(Editors) Philadelphia :WB Saunders Company 1999, pp . 385-386 .
171 . Singer AJ . Thyroid Hormones . In Handbook of Medical Toxicology .
Viccellio P ., editor.
Boston: Lippincott-Raven Publishers, 1998, pp . 799-805 .
172 . Singer AJ, Fischer W, Sauter D, Viccellio P . Antihistamines
. In Handbook of Medical
Toxicology. Viccellio P ., editor. Boston : Lippincott-Raven Publishers, 1998, pp
. 731-739 .

25
July 23, 2007

Papers Presented(*) and Publish ed in Abstract Form:

1 . Albino H, Garra G, Singer AJ, Thode HC . Communication barriers in the Emergency


Department and their impact on diagnostic confidence and ancillary testing . Presented at
the Society for Academic Emergency Medicine (SAEM) annual meeting . Chicago, IL,
May 18, 2007 .
2. Schiller J, Singer AJ, Thode HC, Hollander J, Sinert R . Comparison of abstract
submissions and oral presentations at a regional SAEM . presented at the Society for
Academic Emergency Medicine (SAEM) annual meeting . Chicago, IL, May 18, 2007 .
3 . Singer AJ, McClain S, Romanov A, Rooney J, Zimmerman T . Curcumin reduces bu
. Presented at the Society for Academic Emergency Medicine (SAEM mprogesinat
. Chicago, IL, May 18, 2007 . )anulmetig
4. Singer AJ, McClain S, Zimmerman T, Romanov A, Rooney J . The effect of N-Acetyl
Cysteine on burn progression in rats . Presented at the Society for Academic Emergency
Medicine (SAEM) annual meeting. Chicago, IL, May 18, 2007 .
5 . Singer AJ, Viccellio P, Niegelberg E, Thode HC, Henry MC . Introduction of a stat
laboratory reduces ED length of stay . Presented at the Society for Academic Emergency
Medicine (SAEM) annual meeting . Chicago, IL, May 18, 2007 .
6 . Singer AJ, Huang JS, McClain S, Romanov A, Rooney J, Zimmerman T, Huang SS . A
novel TGF-(3 antagonist speeds reepithelialization and reduces scarring of partial thickness
porcine bums . Presented at the Society for Academic Emergency Medicine (SAEM)
annual meeting. Chicago, IL, May 18, 2007.
7 . Singer AJ, Chohan JK, Dickinson D, Troxell RG, Thode HC . Physical fitness cannot be
used to predict the likelihood of acute coronary syndromes in ED patients with chest pain .
Presented at the Society for Academic Emergency Medicine (SAEM) annual meeting .
Chicago, IL, May 18, 2007 .
8. Garra G, Singer AJ, Bamber D, Chohan JK, Troxell R . Pretreatment of patients requiring
abdominal CT with oral contrast with anti-emetics : A RCT . Presented at the Society for
Academic Emergency Medicine (SAEM) annual meeting . Chicago, IL, May 18, 2007 .
9 . Singer AJ, McClain S, Romanov A, Rooney J, Zimmerman T . Validation of an ischemic
comb bum model in swine . Presented at the Society for Academic Emergency Medicine
(SAEM) annual meeting. Chicago, IL, May 18, 2007 .
10. Baer A, Singer AJ, Byers AM, Perkins C . Automated activation of a stroke team and
radiology reduces time to evaluation and brain imaging . Presented at the Society for
Academic Emergency Medicine (SAEM) New York Regional meeting . March 28, 2007,
Manhattan, NY.
11 . Schiller J, Singer AJ, Thode HC, Hollander J, Sinert R. Comparison of abstract
submissions and oral presentations at a regional SAEM . Presented at the Society for
Academic Emergency Medicine (SAEM) New York Regional meeting . March 28, 2007,
Manhattan, NY.
12. Singer AJ, McClain S, Romanov A, Rooney J, Zimmerman T . Curcumin reduces bu
. Presented at the Society for Academic Emergency Medicine (SAEM) mprogesinat
New York Regional meeting . March 28, 2007, Manhattan, NY .
13 . Kwak M-J, Kim K, Lee C, Shin J-H, R J-E, Suh G-J, Chung W-Y, Singer AJ . The effect of
direct communication between emergency physicians and interventional cardiologists on door

26
July 23, 200 7

to balloon times in STEMI . Presented at the Society for Academic Emergency Medicine
(SAEM) New York Regional meeting . March 28, 2007, Manhattan, NY .
14 . Singer AJ, McClain S, Zimmerman T, Romanov A, Rooney J . The effect of N-Acetyl
Cysteine on burn progression in rats . Presented at the Society for Academic Emergency
Medicine (SAEM) New York Regional meeting . March 28, 2007 . Manhattan, NY .
1 5 . Garra G, Wackett A, McCormack JE, Singer AJ, Shapiro MJ, Thode HC . Incompatibility
between RRC requirements and actual number of emergent procedures in trauma patients .
Presented at the Society for Academic Emergency Medicine (SAEM) New York Regional
meeting . March 28, 2007, Manhattan, NY .
16. Fischer T, Singer AJ, Lee C, Thode HC . National trends in ED antibiotic prescribing fo
. Presented at the Society for Academi c rchildenwtauosmi,196-204
Emergency Medicine (SAEM) New York Regional meeting . March 28, 2007, Manhattan,
NY.
17 . Singer AJ, Thode HC, Lee CC . National epidemiology of cutaneous abscesses : 1996-
2004 . Presented at the Society for Academic Emergency Medicine (SAEM) New York
Regional meeting . March 28, 2007, Manhattan, NY .
18 . Singer AJ, Huang JS, McClain S, Romanov A, Rooney J, Zimmerman T, Huang SS . A
novel TGF-0 antagonist speeds reepithelialization and reduces scarring of partial thickness
porcine burns. Presented at the Society for Academic Emergency Medicine (SAEM) New
York Regional meeting . March 28, 2007, Manhattan, NY .
19 . Singer AJ, Chohan JK, Dickinson D, Troxell RG, Thode HC . Physical fitness cannot b
eusdtoprichelk odfacuteornysdomeinEDpateswihctpan .
Presented at the Society for Academic Emergency Medicine (SAEM) New York Regional
meeting . March 28, 2007, Manhattan, NY .
20 . Garra G, Singer AJ, Bamber D, Chohan JK, Troxell R . Pretreatment of patients requiring
abdominal CT with oral contrast with anti-emetics : A RCT . Presented at the Society for
Academic Emergency Medicine (SAEM) New York Regional meeting . March 28, 2007,
Manhattan, NY .
21 . Chohan JK, Singer AJ, Carman M . Risk of venous thromboembolism in patients with
borderline quantitative D-dimer levels . Presented at the Society for Academic Emergency
Medicine (SAEM) New York Regional meeting . March 28, 2007, Manhattan, NY .
22 . Tarsia V, Thode HC, McCormack JE, Schiller J, Henry MC, Singer AJ . Trends in injury
severity scores and mortality rates after motor vehicle collisions . Presented at the Society
for Academic Emergency Medicine (SAEM) New York Regional meeting . March 28,
2007, Manhattan, NY .
23 . Singer AJ, McClain S, Romanov A, Rooney J, Zimmerman T . Validation of an ischemic
comb burn model in swine . Presented at the Society for Academic Emergency Medicine
(SAEM) New York Regional meeting . March 28, 2007, Manhattan, NY .
24. Schiller JG, Tarsia V, McCormack 7E, Singer AJ, Huang E, Thode H, Henry MC, Brebbia
JS . Improvement of trauma related mortality with implementation of additional helicopter
transport . Presented at the Eastern Association for the Surgery of Trauma (EAST), January
17, 2007, Sanibel, FL .
25 . Singer AJ, Peacock FF, Emerman CL, Char DM, Heywood JT, Kirk JD, Hollander JE,
Summers RL, Lee C . Bronchodilator therapy in ADHF patients without a history of
COPD . Presented at the American College of Emergency Physicians (ACEP) annual
meeting, New Orleans, LA, October 2006 . Ann Emerg Med 2006 ;48 :510 [30] .

27
~ .
July 23, 2007

26 . Singer AJ, Lee C, Thode HC Jr . Trends in ED antibiotic prescribing for upper respiratory
tract infections 1996-2003 . Presented at the American College of Emergency Physicians
(ACEP) annual meeting, New Orleans, LA, October 2006 . Ann Emerg Med 2006 ;48 :[154] .
27 . Singer AJ, Arora B, Dagum A, Valentine S, Hollander JE . Development of a long-term
scar evaluation scale . Presented at the American College of Emergency Physician s
(ACEP) annual meeting, New Orleans, LA, October 2006 . Ann Emerg Med 2006 ;48 :5102
[342] .
28 . Shembekar A, Visram F, Schiller J, Russo V, Lawson W, Viccellio P, Henry MC, Singer
AJ . Activation of an interventional cardiology code reduces time to catheterization in ED
STEMI patients . Presented at the Society for Academic Emergency Medicine (SAEM)
annual meeting, San Francisco, CA, May 18, 2006 . Acad Emerg Med 2006 ;13 :S15 [#18] .
29. Singer AJ, Jurukovski V, Simon M, Protter A, Arora B, Soroff HS . The role of BNP in
cutaneous wound healing : Proof of principle . Presented at the Society for Academic
Emergency Medicine (SAEM) annual meeting, San Francisco, CA, May 19, 2006 . Acad
Emerg Med 2006 ;13:580 [#185] .
30 . Arora B, Singer AJ, Simon M, McClain SA, Dagum A . Correlation between clinical and
histological assessments of wound reepithelialization . Presented at the Society for
Academic Emergency Medicine (SAEM) annual meeting, San Francisco, CA, May 19,
2006. Acad Emerg Med 2006 ;13:S80[#186]
. Singer AJ, Wang Z, McClain SA, Pan Y . A non-invasive
.31 method to assess wound healing :
Optical coherence tomography . Presented at the Society for Academic Emergency
Medicine (SAEM) annual meeting, San Francisco, CA, May 19, 2006 . Acad Emerg Med
2006 ;13 :S81 [#187] .
32 . Chale S, Singer AJ, McBride MJ . Digital vs local anesthesia for finger lacerations : A
randomized clinical trial . Presented at the Society for Academic Emergency Medicine
(SAEM) annual meeting, San Francisco, CA, May 19, 2006 . Acad Emerg Med
2006;13 :S92 [#215] .
33 . Chaudry A, Singer AJ . The reliability and validity of rapid hemodynamic profiling of heart
failure patients in the ED . Presented at the Society for Academic Emergency Medicine
(SAEM) annual meeting, San Francisco, CA, May 20, 2006 . Acad Emerg Med
2006 ;13 :5108 [#258] .
34 . Diercks DB, Kirk JD, Peacock WF, Wynne J, Fonarrow G, Singer A, Emerman C .
Mortality in patients with acute decompensated heart failure presenting to the emergency
department : risk stratification analysis by gender . Presented at the Society for Academic
Emergency Medicine (SAEM) annual meeting, San Francisco, CA, May 21, 2006 . Acad
Emerg Med 2006 ;13 :5119 [#288] .
35 . Fischer TFX, Singer AJ, Chale S . Observation option trial for acute otitis media in the ED .
Presented at the Society for Academic Emergency Medicine (SAEM) annual meeting, San
Francisco, CA, May 21, 2006 . Acad Emerg Med 2006 ;13 :5171 [#422] .
36 . Shembekar A, Visram F, Schiller J, Russo V, Lawson W, Viccellio P, Henry MC, Singer
AJ . Activation of an interventional cardiology code reduces time to catheterization in ED
STEMI patients. Presented at the SAEM 2006 New York State Regional Meeting ,
Syracuse, NY, April 8, 2006 .
37. Leavens J, Garra G, Gulla J, Thode HC, Singer AJ . Do parents follow the CDC
recommendations on immunization records? Presented at the SAEM 2006 New York State
Regional Meeting, Syracuse, NY, April 8, 2006 .

28
July 23, 200 7

38 . Singer AJ, Singer DD, McClain SA . Histomorphologic effects of a hand held laser device
or assisting topical anesthesia in a porcine model . Presented at the American College of
Emergency Physicians (ACEP) annual meeting, Washington DC, September 27, 2005 .
(Ann Emerg Med 2005 ;46 :S68 [241] .
39 . Singer AJ, Wang Z, McClain SA, Pan Y . Optical coherence tomography : A non-invasive
method to assess wound healing . Presented at the American College of Emergency
Physicians (ACEP) annual meeting, Washington DC, September 27, 2005 . (Ann Emerg
Med 2005 ;46 :S68 [242] .
40 . Singer AJ, Friedman B, Modi P, Soroff HS . The effect of a commercially available bum
cooling blanket on core temperature in volunteers . Presented at the Society for Academic
Emergency Medicine (SAEM) annual meeting, New York, NY, May 23, 2005 . Acad
Emerg Med 2005 ;12 :75 [#199] .
41 . Singer AJ, Visram F, Khwaja M . Lack of utility of telemetry monitoring during transport
of low-risk chest pain patients from the ED . Presented at the Society for Academic
Emergency Medicine (SAEM) annual meeting, New York, NY, May 23, 2005 . Acad
Emerg Med 2005 ;12:77 [#207] .
42. Khwaja M, Singer AJ, Gulla J . Comparison of Ibuprofen, Cyclobenzaprine, or both, for
acute cervical strain : A RCT . Presented at the Society for Academic Emergency Medicine
(SAEM) annual meeting, New York, NY, May 24, 2005 . Acad Emerg Med 2005 ;12 :115
[#316] .
43 . Regev R, Singer AJ, Weeks R, Tolckwoski D . Laser assisted anesthesia prior to
intravenous cannulation in volunteers : A RCT . Presented at the Society for Academi
(SAEM) annual meeting, New York, NY, May 25, 2005 . Acad cEmergnyMdi
Emerg Med 2005 ;12 :155 [#432] .
44 . Weeks R, Singer AJ, Regev R . Use of a laser device to enhance anesthesia prior to IV
cannulation in ED patients . Presented at the Society for Academic Emergency Medicine
(SAEM) annual meeting, New York, NY, May 25, 2005 . Acad Emerg Med Z005 ;12:155
[#433] .
45 . Singer AJ, Soroff HS, Brebia JS . OCA for treatment for bums . A pilot study. Presented at
the 12th International Congress of the Society for Bum Injuries, Yokohama, JAPAN,
August 23, 2004 .
46 . Singer A7, Singer AH, Thode HC Jr . Reassessment of the emergency physician workforce
demands . Presented at the Society for Academic Emergency Medicine (SAEM) annual
meeting, Orlando FL, May 16, 2004 . Acad Emerg Med 2004 ; 1 1 :464 [86] .
47 . Singer AJ, Lovell SJ, Wackett A, Gulla J . Comparison of Valdecoxib and an oxycodone
acetaminophen combination . Presented at the Society for Academic Emergency Medicine
(SAEM) annual meeting, Orlando FL, May 17, 2004 . Acad Emerg Med 2004 ;1 1 :489
[161] .
48 . Ardise J, Singer AJ, Gulla J, Cangro J . Point of care testing reduces length of stay in chest
pain patients . Presented at the Society for Academic Emergency Medicine(SAEM) annual
meeting, Orlando FL, May 17, 2004 . Acad Emerg Med 2004 ;11 :504[204] .
49 . Singer AJ, McClain SA, Rogers KE . Development of a porcine incisional wound model
and novel scarring scales . Presented at the Society for Academic Emergency Medicine
(SAEM) annual meeting, Orlando FL, May 17, 2004 . Acad Emerg Med 2004 ;11 :518
[244] .

29
0 •
July 23, 2007

50 . Singer AJ, Blanda M, Cronin K, LoGiudice-Khwaja M, Gulla J, Bradshaw J . Evaluation of


a new nasal tampon for Epistaxis : A randomized controlled trial . Presented at the Society
for Academic Emergency Medicine (SAEM) annual meeting, Orlando FL, May 18, 2004 .
Acad Emerg Med 2004 ;11 :557 [359] .
51 . Singer AJ, Gulla J, Hein M, Marchini S ; Chale S . Arora BP . Single vs double layer closure
for facial lacerations . Presented at the Society for Academic Emergency Medicine
(SAEM) annual meeting, Orlando FL, May 19, 2004 . Acad Emerg Med 2004 ;11 :561
[372] .
52 . Singer AJ, Gulla J . Knowledge of herbs, indications and side effects . Presented at the
American College of Emergency Physicians (ACEP) annual research forum, Boston, MA,
October 12, 2003 . Ann Emerg Med 2003 ;42 :S25 [#88] .
53 . Singer A7, Niegelberg E . Relation of patient transfers to insurance status . Presented at the
American College of Emergency Physicians (ACEP) annual research forum, Boston, MA,
October 12, 2003 . Ann Emerg Med 2003 ;42 :S33 [#121] .
54 . Singer AJ, Chisum E, Stark MJ . An educational intervention to reduce oligoanalgesia in
the ED . Presented at the American College of Emergency Physicians (ACEP) annual
research forum, Boston, MA, October 12, 2003 . Ann Emerg Med 2003 ;42:541 [#148].
55 . Singer AJ . First aid knowledge among children . Presented at the American College of
Emergency Physicians (ACEP) annual research forum, Boston, MA, October 12, 2003 .
Ann Emerg Med 2003 ;42 :S52 [#190] .
56 . Singer AJ, McClain SA, Botchkina G, Buyuk A, Zimmerman T, Cameau P, Simon M .
CNI-1493 enhances reepithelialization of second degree bums in swine . Presented at the
Society for Academic Emergency Medicine (SAEM) annual meeting, Boston, MA, May
30, 2003 . Acad Emerg Med 2003 ;10 :464 [#125] .
57 . Siderias J, Gaudio F, Singer AJ . Comparison of topical anesthetics and lubricants prior to
urethral catheterization in male patients . A randomized controlled trial . Presented at the
Society for Academic Emergency Medicine (SAEM) annual meeting, Boston, MA, May
30, 2003 . Acad Emerg Med 2003 ;10:468 [#136] .
58 . Singer AJ, Zimmerman T, Rooney J, Silberstein C, Cameau P . Wound bursting strength
and surface characteristics of new tissue adhesives . Presented at the Society for Academic
Emergency Medicine (SAEM) annual meeting, Boston, MA, May 30, 2003 . Acad Emerg
Med 2003 ;10:498 [#224] .
59 . Singer AJ, Nable M, Bonner R, Soroff HS . Bum outcomes : Patient priorities and
agreement with practitioner assessments . Presented at the Society for Academic
Emergency Medicine (SAEM) annual meeting, Boston, MA, May 30, 2003 . Acad Emerg
Med 2003 ;10 :498 [#225] .
60 . Singer AJ, Giordano P, Fitch JL, Gulla J, Ryker D, Chale S . Evaluation of a new high
viscosity Octylcyanoacrylate tissue adhesive for laceration repair : A randomized
controlled trial . Presented at the Society for Academic Emergency Medicine (SAEM)
annual meeting, Boston, MA, May 30, 2003 . Acad Emerg Med 2003 ;10:499 [#226].
61 . Singer AJ, McClain SA . Development of an excisional wound model . Presented at the
Society for Academic Emergency Medicine (SAEM) annual meeting, Boston, MA, May
30, 2003 . Acad Emerg Med 2003 ;10:499 [#227] .
62 . Singer AJ, LoGiudice M, Khwaja IS, Kelly RF . Development of a computerized system to
reduce medical errors : A pilot study . Presented at the Society for Academic Emergency

30
0 .
July 23, 2007

Medicine (SAEM) annual meeting, Boston, MA, May 30, 2003 . Acad Emerg Med
2003 ;10:538 [#343] .
63 . Cordiale AJ, Hynes EM, Gulla J, Singer AJ . Effect of healthcare provider gender and
profession on patient interactions . Presented at the American College for Emergency
Physicians (ACEP) Annual Meeting, Seattle, WA, October, 2002 .
64. Gulla J, Singer AJ, Thode HC Jr . Characterization of migraine headaches . Presented at the
American College for Emergency Physicians (ACEP) Annual Meeting, Seattle, WA,
October, 2002 .
65 . Singer AJ*, Gulla J, Schiavone FM, Viccellio AW . Inclusion of alternative therapies in
Emergency Medicine Residency Curriculums . Presented at the American College for
Emergency Physicians (ACEP) Annual Meeting, Seattle, WA, October, 2002 .
66 . Specht J, Singer AJ*, Thode HC Jr. How good is the standard urinalysis? Presented at the
American College for Emergency Physicians (ACEP) Annual Meeting, Seattle, WA,
October, 2002 .
67 . Huang C, Koulouris M, Singer AJ* . Accuracy of automated triage vital signs . Presented at
the American College for Emergency Physicians (ACEP) Annual Meeting, Seattle, WA,
October, 2002.
68 . Singer AJ, Viccellio AW, Thode HC Jr, Garra G, Henry MC . Abdominal pain in the ED :
Work-up and diagnosis . Presented at the American College for Emergency Physicians
(ACEP) Annual Meeting, Seattle, WA, October, 2002 .
69 . Garber B, Garra G, Singer AJ . Characteristics of pediatric patients with acute appendicitis .
Presented at the American College for Emergency Physicians (ACEP) Annual Meeting,
Seattle, WA, October, 2002 .
70 . Singer AJ, Gulla J . Pain relief in the ED . Presented at the American College for
Emergency Physicians (ACEP) Annual Meeting, Seattle, WA, October, 2002 .
71 . Singer AJ*, Thode HC Jr . National epidemiology of lacerations . Presented at the
American College for Emergency Physicians (ACEP) Annual Meeting, Seattle, WA,
October, 2002.
72 . Henry MC, Singer AJ, Viccellio AW . Mode of arrival and presenting symptoms for
patients with Myocardial Infarctions and strokes . Presented at the American College for
Emergency Physicians (ACEP) Annual Meeting, Seattle, WA, October, 2002 .
73 . Singer AJ*, McClain SA. The addition of a potent topical steroid does not reduce bum
depth . Presented at the Society for Academic Emergency Medicine (SAEM) Annual
Meeting, St . Louis, MO, May 19-22, 2002 . Acad Emerg Med 2002 ;9:397 .
74 . Singer AJ*, Thode HC Jr. National analgesia prescribing patterns in patients with bums
.PresntdahSociyfrAemEgncyMdie(SAE)nualMtig,S .
Louis, MO, May 19-22,2002 . Acad Emerg Med 2002 ;9:397.
75 . Singer AJ*, McClain SA, Nable M, Cameau P, Singer DD . Evaluation of a liquid
occlusive dressing (LOD) for excisional wounds . Presented at the Society for Academic
Emergency Medicine (SAEM) Annual Meeting, St . Louis, MO, May 19-22, 2002 . Acad
Emerg Med 2002 ;9 :449 .
76 . Tarsia V, Singer AJ . Comparison of regional and local anesthesia for facial lacerations .
Presented at the Society for Academic Emergency Medicine (SAEM) Annual Meeting, St .
Louis, MO, May 19-22, 2002 . Acad Emerg Med 2002 ;9 :449 .
77 . Singer AJ*, Viccellio AW, Henry MC . Adherence to practice guidelines for ED
management of myocardial infarction . Presented at the Society for Academic Emergency

31
0 • July 23, 200 7

Medicine (SAEM) Annual Meeting, St . Louis, MO, May 19-22, 2002 . Acad Emerg Med
2002;9:493 .
78 . Arya, R, Hansen AM, Singer A7 . Oral contrast : What taste's best. Presented at the
Society for Academic Emergency Medicine (SAEM) Annual Meeting, St . Louis, MO, May
19-22, 2002 . Acad Emerg Med 2002 ;9:502 .
79 . Fischer TFX, Singer AJ, Gulla JM, Garra G . Physician comfort with withholding
antibiotics in children with acute otitis media . Presented at the Society for Academic
Emergency Medicine (SAEM) Annual Meeting, St . Louis, MO, May 19-22, 2002 . Acad
Emerg Med 2002 ;9:520 .
80 . Fischer TFX, Singer AJ, Gulla JM, Garra G, Rosenfeld R. Parental comfort with
withholding antibiotics for acute otitis media in children . Presented at the Society for
Academic Emergency Medicine (SAEM) Annual Meeting, St. Louis, MO, May 19-22,
2002 . Acad Emerg Med 2002 ;9:520 .
81 . Singer AJ*, Gulla JM . Evaluation of a pain VAS and the minimal clinically significant
difference in children ages 4-7 . Presented at the Society for Academic Emergency
Medicine (SAEM) Annual Meeting, St . Louis, MO, May 19-22, 2002 . Acad Emerg Med
2002 ;9:521 .
82 . Singer AJ*, Gulla J, Thode HC Jr . Lack of correlation between practitioner and parental
assessments of infants' and toddlers' pain . Presented at the Society for Academic
Emergency Medicine (SAEM) Annual Meeting, Atlanta, GA, May 6, 2001 . Acad Emerg
Med 2001 ;8:426 .
83 . Singer AJ*, Mynster CJ . Effect of intramuscular Ketoralac on bleeding times . Presented at
the Society for Academic Emergency Medicine (SAEM) Annual Meeting, Atlanta, GA,
May 6, 2001 . Acad Emerg Med 2001 ;8 :429 .
84 . Singer AJ*, Gulla J, Gaspari R . Herbal use in Emergency Department patients . Presented
at the Society for Academic Emergency Medicine (SAEM) Annual Meeting, Atlanta, GA,
May 6, 2001 . Acad Emerg Med 2001 ;8 :450 .
85 . Singer AJ*, Gulla J, Thode HC Jr . Parents and practitioners are poor judges of young
children's pain severity . Presented at the Society for Academic Emergency Medicine
(SAEM) Annual Meeting, Atlanta, GA, May 7, 2001 . Acad Emerg Med 2001 ;8 :484 .
86 . Singer AJ, Cohen D, Crawford N, Viccellio AW . Effects of mandated pain scales on
frequency and timeliness of analgesic administration . Presented at the Society for
Academic Emergency Medicine (SAEM) Annual Meeting, Atlanta, GA, May 7, 2001 .
Acad Emerg Med 2001 ;8:485 .
87 . Singer AJ*, McClain SA . Persistent wound infection delays epidermal maturation and
increases scarring . Presented at the Society for Academic Emergency Medicine (SAEM)
Annual Meeting, Atlanta, GA, May 8, 2001 . Acad Emerg Med 2001 ;8:519 .
88 . Singer AJ*, McClain SA, Simon M, Soroff HS . Evaluation of topical collagenase for
second degree burns . Presented at the Society for Academic Emergency Medicine (SAEM)
Annual Meeting, Atlanta, GA, May 8, 2001 . Acad Emerg Med 2001 ;8 :519 .
89 . Singer AJ*, McClain SA, Soroff HS . The effects of Santyl and infection on burn healing in
swine. Presented at the Society for Academic Emergency Medicine (SAEM) Annual
Meeting, Atlanta, GA, May 8 2001 . Acad Emerg Med 2001 ;8 :520 ,
90 . Singer AJ*, Botchkina G, McClain SA, Simon M . CNI-1493 reduces local production of
tumor necrosis factor-a in urns . Presented at the Society for Academic Emergenc y

32
0
July 23, 2007

Medicine (SAEM) Annual Meeting, Atlanta, GA, May 8, 2001 . Acad Emerg Med
2001 ;8:520.
91 . Singer AJ*, Carleo C . Effect of frequent soaking on durability of Octylcyanoacrylate .
Presented at the Society for Academic Emergency Medicine (SAEM) Annual Meeting,
Atlanta, GA, May 8, 2001 . Acad Emerg Med 2001 ;8:537 .
92 . Singer AJ*, Quinn JV, Hollander JE . Comparison of Octylcyanoacrylate and standard
wound closure methods for lacerations and incisions : A multi-center trial . Presented at the
Society for Academic Emergency Medicine (SAEM) Annual Meeting, Atlanta, GA, May 8,
2001 . Acad Emerg Med 2001 ;8:538 .
93 . Singer AJ*, Quinn JV, Thode HC Jr ., Hollander JE . Determinants of poor outcome after
laceration and incision repair . Presented at the Society for Academic Emergency Medicine
(SAEM) Annual Meeting, Atlanta, GA, May 8, 2001 . Acad Emerg Med 2001 ;8:538 .
94 . Singer AJ*, Botchkina G, McClain SA, Simon M . CNI-1493 reduces local production of
tumor necrosis factor-(x in burns . Presented at the New York State SAEM (Society for
Academic Emergency Medicine) Regional Meeting, Rochester, NY, March 12, 2001 .
95 . Carleo C, Singer AJ* . Effect of frequent soaking on durability of Octylcyanoacrylate .
Presented at the New York State SAEM (Society for Academic Emergency Medicine)
Regional Meeting, Rochester, NY, March 12, 2001 .
96 . Singer AJ*, Gulla J, Thode HC Jr . Parents and practitioners are poor judges of young
children's pain severity . Presented at the New York State SAEM (Society for Academic
Emergency Medicine) Regional Meeting, Rochester, NY, March 12, 2041 .
97 . Cohen D, Crawford N, Singer AJ*, Lander 0, Nelson B, Viccellio A . Effects of mandated
pain scales on frequency and timeliness of analgesic administration . Presented at the New
York State SAEM (Society for Academic Emergency Medicine) Regional Meeting,
Rochester, NY, March 12, 2001 .
98 . Singer AJ*, Quinn J, Thode HC Jr., Hollander JE. Determinants of poor outcome after
laceration and incision repair . Presented at the New York State SAEM (Society for
Academic Emergency Medicine) Regional Meeting, Rochester, NY, March 12, 2001 .
99 . Singer AJ*, Quinn J, Hollander JE. Comparison of Octylcyanoacrylate and standard
wound closure methods for lacerations and incisions : A multi-center trial . Presented at the
New York State SAEM (Society for Academic Emergency Medicine) Regional Meeting,
Rochester, NY, March 12, 200 L
100 . Singer AJ*, Bauch B, Thode HC Jr, McClain SA . Predicting healing potential of bums
using early histological findings . Presented at the ACEP (American College of Emergency
Physicians) annual meeting in Philadelphia, PA, October, 2000 . Annals of Emerg Med
2000 ;36 :S24 .
101 . Singer AJ*, Coleman D, Gulla J, Thode He Jr . A survey of physician diagnostic testing
and admitting habits in patients with seizure . Presented at the ACEP (American College of
Emergency Physicians) annual meeting in Philadelphia, PA, October, 2000 . Annals of
Emerg Med 2000 ;36:S36
. Specht J, Singer AJ, Henry.102 MC . Adolescent rage : An under-reported epidemic . Presented
at the ACEP (American College of Emergency Physicians) annual meeting in Philadelphia,
PA, October, 2000 . Annals of Emerg Med 2000 ;36 :S48 .
103 . Gaspari R, Singer AJ . Emergent intubations : Where and by whom? . Presented at the
ACEP (American College of Emergency Physicians) annual meeting in Philadelphia, PA,
October, 2000. Annals of Emerg Med 2000 ;36 :S51 .

33
0 0
July 23, 2007

104 . Singer AJ*, Chretien J, Viccellio AW, Schiavone F, Thode HC Jr ., Henry MC . Insertion of
IVs by residents : Does it save time? Presented at the ACEP (American College of
Emergency Physicians) annual meeting in Philadelphia, PA, October, 2000 . Annals of
Emerg Med 2000 ;36 :S75 .
105 . Singer AJ*, Sauris E, Viccellio A . Ceruxninolytic effects of cerumenex and docusate
sodium. A randomized controlled trial . Presented at the Society for Academic Emergency
Medicine (SAEM) Annual Meeting, May 22-25, 2000 . Acad Emerg Med 2000 ;7 :471 .
106 . Singer AJ*, Nelson B . Digital versus analog radiography in the evaluation of cervical
spine injuries . Presented at the Society for Academic Emergency Medicine (SAEM)
Annual Meeting, May 22-25, 2000 . Acad Emerg Med 2000;7:494 .
107 . Singer AJ*, Kowalska, A . Do assessments of the severity of acute painful episodes change
over time? Presented at the Society for Academic Emergency Medicine (SAEM) Annual
Meeting, May 22-25, 2000 . Acad Emerg Med 2000 ;7:530 .
108 . Dickinson R, Singer AJ . Etomidate for pediatric sedation prior to fracture reduction .
Presented at the Society for Academic Emergency Medicine (SAFM) Annual Meeting,
May 22-25, 2000 . Acad Emerg Med 2000 ;7 :584 .
109 . Singer AJ*, Cruz JJ, Thode HC Jr ., Soroff HS . Burn appearance scale : Correlation
between patient and physician assessments and determination of the minimal clinically
significant difference . Presented at the Society for Academic Emergency Medicine
(SAEM) Annual Meeting, May 22-25, 2000 . Acad Emerg Med 2000 ;7 :584 .
110 . Singer AJ*, McClain S . Effects of supplemental topical steroids on bums : A randomized
trial . Presented at the Society for Academic Emergency Medicine (SAEM) Annual
Meeting, May 22-25, 2000 . Acad Emerg Med 2000 ;7:594 .
111 . Singer AJ*, Stark MJ . Pretreatment of lacerations with LET or EMLA at triage : A
randomized trial . Presented at the Society for Academic Emergency Medicine (SAEM)
Annual Meeting, May 22-25, 2000 . Acad Emerg Med 2000 ;7 :594.
112 . Mittra ES, Singer AJ, Stark MJ . Effects of distance on wound irrigation pressures .
Presented at the Society for Academic Emergency Medicine (SAEM) Annual Meeting,
May 22-25, 2000 . Acad Emerg Med 2000 ;7:594 .
113 . Singer AJ*, McClain SA . The effect of epidermal debridement on reepithelialization and
infection in porcine burns treated with Octyl-cyanoacrylate and dry gauze . Presented at the
American College of Emergency Physicians (ACEP) Research Forum, October, 1999 . Ann
Emerg Med 1999 ;34 :S4 .
114 . Singer AJ*, Jeong C . Vaginal bleeding : Documentation and frequency of coagulopathy .
Presented at the American College of Emergency Physicians (ACEP) Research Forum,
October, 1999 . Ann Emerg Med 1999 ;34 :S63 .
115 . Singer AJ, Gulla J . Have ED patients used or are willing to use alternative medicine ?
Presented at the American College of Emergency Physicians (ACEP) Research Forum,
October, 1999 . Ann Emerg Med 1999 ;34 :S64.
116 . Singer AJ*, McClain SA . Long term effects of Octyl-cyanoacrylate on scarring after
partial thickness burns in pigs : A randomized trial . Presented at the American College of
Emergency Physicians (ACEP) Research Forum, October, 1999 . Ann Emerg Med
1999 ;34 :512 .
117. Singer AJ*, Sanders B, Simman R, Soroff HS . Development of a scale to assess the
clinical outcome after cutaneous burns . Presented at the Society for Academic Emergency
Medicine, Boston, MA, May, 1999 . Acad Emerg Med 1999 ;6 :467 .
118 . McClain SA, Singer AJ*, Thode HC Jr . Development of a histomorphologic scale to
measure scarring after cutaneous injury . Presented at the Society for Academic Emergency
Medicine, Boston, MA, May, 1999 . Acad Emerg Med 1999 ;6 :467.
34
July 23, 200 7

119. Singer AJ*, Hatch G, Simon M . The direct effects of Octyl-cyanoacrylate on keratinocyte
cultures . Presented at the Society for Academic Emergency Medicine, Boston, MA, May,
1999 . Acad Emerg Med 1999 ;6 :468 .
120 . Singer AJ*, Mohammed M, McClain SA . Octyl-cyanoacrylate versus Tegaderm for
treatment or bums in swine : a randomized trial . Presented at the Society for Academic
Emergency Medicine, Boston, MA, May, 1999 . Acad Emerg Med 1999 ;6 :468 .
121 . Singer AJ, Mach C, Hemachandra S, Hornig S, Shofer FS, Hollander JE . Treatment of
traumatic lacerations : What are the patient's priorities? Presented at the Society for
Academic Emergency Medicine, Boston, MA, May, 1999 . Acad Emerg Med 1999 ;6:468-
469.
122 . Singer AJ, Stark MJ . Feasibility of triage nurse application of topical anesthesia for
lacerations . Presented at the Society for Academic Emergency Medicine, Boston, MA,
May, 1999 . Acad Emerg Med 1999 ;6 :469 .
123 . Singer AJ, Mittra E, Hollander JE . Comparison of impact pressures using common ED
wound irrigation methods . Presented at the Society for Academic Emergency Medicine,
Boston, MA, May, 1999 . Acad Emerg Med 1999 ;6 :469 .
124 . Singer AJ*, Wayrich G, Kowalska A, Henry MC . Sildenafil in the prehospital setting :
Frequency of use and awareness of adverse drug interactions . Presented at the Society for
Academic Emergency Medicine, Boston, MA, May, 1999 . Acad Emerg Med 1999 ;6:473-474.
125 . Singer AJ*, Mohammed M, Tortora G, McClain SA . Evaluation of Octyl-cyanoacrylate
for contaminated bums in swine : an experimental trial . Presented at the Society for
Academic Emergency Medicine, Boston, MA, May, 1999 . Acad Emerg Med 1999 ;6 :495 .
126 . Hollander JE, Singer AJ . Factors affecting the cosmetic appearance of lacerations repaired
in the ED . Presented at the Society for Academic Emergency Medicine, Boston, MA, May,
1999 . Acad Emerg Med 1999 ;6:495-496.
127 . Singer AJ*, Kowalska A, Thode HC Jr . Determination of the significance of pain severity
and the minimal clinically significant difference on pain scales . Presented at the Society
for Academic Emergency Medicine, Boston, MA, May, 1999 . Acad Emerg Med
1999 ;6 :513.
128 . Singer AJ*, Kowalska A, Thode HC Jr . Comparison of pain scales and determination of
the most patient friendly scale . Presented at the Society for Academic Emergency
Medicine, Boston, MA, May, 1999. Acad Emerg Med 1999 ;6:51 4.
129 . Gaspari RI, Singer AJ . Comparison of magnetic and standard orotracheal intubation in
inexperienced students and interns . Presented at the Society for Academic Emergency
Medicine, Boston, MA, May, 1999 . Acad Emerg Med 1999 ;6 :515.
130 . Engleberg S, Singer AJ, Moldashel JG, Sciammarella J, Thode HC, Henry MC . Effects of
prehospital nitroglycerine on vital signs and chest pain intensity. Presented at the Society
for Academic Emergency Medicine, Boston, MA, May, 1999 . Acad Emerg Med
1999 ;6 :491 .
131 . Singer AJ*, Thode HC, McClain SA . To debride or not to debride? The effect of
epidermal debridement on rates of infection and re-epithelialization in a swine burn model .
Presented at The Annual Scientific Meeting of the Israeli Association for Emergency
Medicine, Tel-Aviv, Israel, March, 1999 .
132 . Singer AJ*, Mohammed M, Tortora G, McClain SA . Evaluation of octyl-cyanoacrylate for
contaminated bums in swine: An experimental trial . Presented at The Annual Scientific
Meeting of the Israeli Association for Emergency Medicine, Tel-Aviv, Israel, March, 1999 .
133 . Singer AJ*, Konia N . Comparison of topical anesthetics and vasoconstrictors versus
lubricants prior to nasogastric intubation . A randomized controlled trial . Presented at The

35
0 0 July 23, 2007

Annual Scientific Meeting of the Israeli Association for Emergency Medicine, Tel-Aviv,
Israel, March, 1999 .
134 . Hollander JE, Reinhard SS, Singer AJ, Eskin B, Shofer F . The use of students to assist
with clinical research : feasible in a variety of emergency department settings . Presented at
the American College of Emergency Physicians Research Forum, San Diego, CA, October
1998 . Annals of Emergency Medicine 1998 ;32 :S43 (suppl) .
135 . Singer AJ*, Kowalska A, Sanders BT, Stark M, Mohammad M, Brogan GX . Does the
presence of a television effect patient satisfaction in the ED? Presented at the Society for
Academic Emergency Medicine, Chicago, IL, May 1998 . Acad Emerg Med
1998 ;5(5) :416 .
136 . Harrow C, Singer AJ*, Kube B . The ability of the 30 minute erythrocyte sedimentation
rate to predict normal values at one hour . Presented at the Society for Academic
Emergency Medicine, Chicago, IL, May 1998 . Acad Emerg Med 1998 ;5(5):499 .
137 . Khan SR, Singer AJ* . Comparison of forearm and upper arm blood pressures . Presented
at the Society for Academic Emergency Medicine, Chicago, IL, May 1998 . Acad Emerg
Med 1998 ;5(5) :485 .
138 . Fischer TF, Singer AJ . Prospective randomized double blinded controlled trial of the
palatability of standard and superactivated granular charcoal in patients with toxic
ingestions . Presented at the Society for Academic Emergency Medicine, Chicago, IL, May
1998 . Acad Emerg Med 1998 ;5(5) :467 .
139 . Turban JW, Singer AJ* . Can health care workers estimate blood loss in rectal bleeding?
Presented at the Society for Academic Emergency Medicine . Chicago, IL, May 1998 .
Acad Emerg Med 1998 ;5(5):530.
140 . Singer AJ*, Homan CS, Brody M, Hollander JE, Thode Jr HC . Evolution of SAEM
abstracts ; a twenty-five year perspective . Presented at the Society for Academic
Emergency Medicine, Chicago, IL, May 1998 . Acad Emerg Med 1998 ;5(5) :433 .
141 . Richman PB, Singer AJ, Flanagan M, Thode Jr HC . The effectiveness of ice as a topical
anesthetic for the insertion of intravenous catheters . Presented at the Society for Academic
Emergency Medicine, Chicago, IL, May 1998 . Acad Emerg Med 1998 ;5(5) :518 .
142 . Singer AJ*, Shallat JE, Valentine SM . Tape stripping to speed the absorption of EMLA
cream prior to intravenous catheterization . Presented at the Society for Academic
Emergency Medicine, Chicago, IL, May 1998 . Acad Emerg Med 1998 ;5(5):517 .
143 . Singer AJ*, Kowalska A, Richman PB, Thode Jr HC . Gender and racial differences in pain
assessment after intravenous catheterization . Presented at the Society for Academic
Emergency Medicine, Chicago, IL, May 1998 . Acad Emerg Med 1998 ;5(5) :535 .
144 . Singer AJ*, Kowalska A, Richman PB, Thode Jr HC . Gender differences in pain
associated with urethral catheterization . Presented at the Society for Academic Emergency
Medicine. Chicago, IL, May 1998 . Acad Emerg Med 1998 ;5(5) :534 .
145 . Singer AJ*, Coby C, Singer AH, Thode Jr HC, Tortora G . In-vitro evaluation of the
bacteriostatic effects of low frequency ultrasound . Presented at the Society for Academic
Emergency Medicine . Chicago, IL, May 1998 . Acad Emerg Med 1998 ;5(5) :536 .
146 . Singer AJ*, Berrutti L, McClain SA . Histopathologic effects of low frequency ultrasound
in swine . Presented at the Society for Academic Emergency Medicine, Chicago, IL, May
1998 . Acad Emerg Med 1998 ;5(5) :536 .
147 . McClain SA, Berrutti L, Thode Jr HC, Singer AJ* . A new scale for the assessment of
cutaneous bum depth . Presented at the Society for Academic Emergency Medicine,
Chicago, IL, May 1998 . Acad Emerg Med 1998 ;5(5) :475 .
148. Singer AJ*, McClain SA, Berrutti L, Thode Jr HC . Healing rate of partial thickness bums
treated with octyl-cyanoacrylate versus silver sulfadiazine in swine ; an experimental trial .

36
0 • July 23, 2007

Presented at the Society for Academic Emergency Medicine, Chicago, IL, May 1998 .
Acad Emerg Med 1998 ;5(5) :467 .
149 . Hollander JE, Valentine S, Turque T, Singer AJ . Application of tissue adhesives : rapid
attainment of proficiency . Presented at the Society for Academic Emergency Medicine,
Chicago, IL, May 1998 . AcadEmerg Med 1998 ;5(5) :465 .
150 . Hollander JE*, Valentine S, Singer AJ . Characteristics of traumatic lacerations and their
influence on post-repair infection rate . Presented at the Society for Academic Emergency
Medicine, Chicago, IL, May 1998 . Acad Emerg Med 1998 ;5(5):466 .
151 . Hollander JE*, Valentine S, Singer AJ . Emergency physician wound care practices differ
between children and adults . Presented at the Society for Academic Emergency Medicine,
Chicago, IL, May 1998 . Acad Emerg Med 1998 ;5(5) :385 .
152 . Singer AJ*, Berrutti L, McClain SA . A study of the histopathologic effects of cutaneous
tape stripping. Presented at the Society for Academic Emergency Medicine, Chicago, IL,
May 1998 . Acad Emerg Med 1998 ;5(5) :535 .
153 . Singer AJ*, Thode Jr HC . Determination of the minimal clinically significant difference
on patient satisfaction scales . Presented at the Society for Academic Emergency Medicine,
Chicago, IL, May 1998 . Acad Emerg Med 1998 ;5(5) :402 .
154 . Singer AJ*, Berrutti L, McClain SA, Bookbinder MK . Comparison of octylcyanoacrylate
and silver sulfadiazine for the treatment of full thickness cutaneous defects . Presented at
the Society for Academic Emergency Medicine, Chicago, IL, May 1998 . Acad Emerg Med
1998 ;5(5) :532 .
155 . Hollander JE, Giarrusso E, Singer AJ . Comparison of staples and sutures for closure of
scalp lacerations . Presented at the Society for Academic Emergency Medicine .
Washington, DC, May 1997 . Academic Emergency Medicine 1997 ;4:460 .
156 . Hollander JE, Richman PB, Werblud M, Miller T, Huggler J, Singer AJ . Irrigation in facial
and scalp lacerations : Does it alter outcome? Presented at the Society for Academic
Emergency Medicine . Washington, DC, May 1997 . Academic Emergency Medicine
1997 ;4:474 .
157 . Singer AJ*, Richman PB, La Vefre R, McCuskey CF, Thode HC . Comparison of patient
and practitioner's assessment of pain from commonly performed emergency department
procedures . Presented at the Society for Academic Emergency Medicine . Washington,
DC, May 1997 . Academic Emergency Medicine 1997 ;4 :404 .
158 . Singer AJ*, Homan CS, Stark MJ, Werblud MS, Thode HT, Hollander JE . Comparison of
types of research publications in emergency and non emergency medicine journals .
Presented at the Society for Academic Emergency Medicine . Washington, DC, May 1997 .
Academic Emergency Medicine 1997 ;4:501 .
159 . Singer AJ*, Hollander JE, Valentine SM, Turque TW, McCuskey CF, Quinn JV .
Prospective, randomized, controlled trial of a new tissue adhesive (2-Octyl Cyanoacrylate)
versus standard wound . Washington, DC, May 1997 . Academic Emergency Medicine
1997 ;4 :475 .
160. Homan CS, Singer AJ, Henry MC, Thode HC . Thermal effects of neutralization therapy
for acute alkali exposure in an in vivo canine model . Presented at the Society for
Academic Emergency Medicine . Denver, Colorado, May 1996 . Academic Emergency
Medicine 1996;3 :417 .
161 . Singer* AJ, Hollander JE. Blood pressure : Assessment of interarm differences . Presented
at the Society for Academic Emergency Medicine . Denver, Colorado, May 1996 .
Academic Emergency Medicine 1996 ;3 :484-485.
162 . Singer* AJ, McCracken G, Henry MC, Cobahug C . Correlation between clinical,
laboratory, and hepatobiliary scanning findings in patients with suspected acute

37
July 23, 2007

cholecystitis . Presented at the Society for Academic Emergency Medicine . Denver,


Colorado, May 1996 . Academic Emergency Medicine 1996 ;3 :542 .
163 . Singer* AJ, Brogan GX, Valentine SM, McCuskey C, Khan S, Hollander JE . Predictive
value of a normal ECG : Is it affected by duration of time from onset of chest pain?
Presented at the Society for Academic Emergency Medicine . Denver, Colorado, May
1996 . Academic Emergency Medicine 1996 ;3 :427 .
164. Mofenson HC, Caraccio T, Wheeler J, Marsh M, Comer G, Singer AJ, Henry M . Toxicity
of 3% hydrogen peroxide . Presented at the North American Congress of Clinical
Toxicology. Rochester, New York, September 1995 . Journal of Toxicology Clinical
Toxicology 1995 ;33 :488 .
165 . Homan CS, Singer AJ, Henry MC, Thode HC . Thermal effects of neutralization therapy
for acute alkali exposure in an in vivo canine model . Presented at the Society for
Academic Emergency Medicine . San Antonio, Texas, May, 1995 . Academic Emergency
Medicine 1995 ;2:397 .
166 . Blasko B, Hollander, JE, Singer* AJ, Thode HC, Henry MC . Lack of correlation between
the short term and long term cosmetic appearance of lacerations repaired in the emergency
department. Presented at the Society for Academic Emergency Medicine . San Antonio,
Texas, May, 1995 . Academic Emergency Medicine 1995 ;2:467 .
167 . Todd K, Hollander JE, Heilpern K, Green G, Singer AJ, Brogan GX, Karris D, Shahan JB .
Prevalence of the use of cocaine in patients with chest pain . Presented at the Society for
Academic Emergency Medicine . San Antonio, Texas, May, 1995 . Academic Emergency
Medicine 1995 ;2:463 .
168. Singer* AJ, Hollander JE, Henry MC, Valentine S, Brogan GX, Thode HC . Cosmetic
appearance of lacerations repaired by Emergency Medicine practitioners of various levels
of training . Presented at the Society for Academic Emergency Medicine . San Antonio,
Texas, May, 1995 . Academic Emergency Medicine 1995 ;2:414 .
169 . Singer* AJ, Hollander JE . Buffering of diphenhydramine does not reduce the pain of
infiltration . Presented at the Society for Academic Emergency Medicine . San Antonio,
Texas, May, 1995 . Academic Emergency Medicine 1995 ;2:463 .
170 . Singer* AJ, Hollander JE, Cassara G, Henry MC, Cassara G, Valentine S, Thode HC .
Wound infection rates are not affected by practitioner level of training . Presented at the
American College of Emergency Physicians Research Forum . San Francisco, California,
February, 1995 . Annals of Emergency Medicine . 1995 ;25 :159-160.
171 . Singer* AJ, Hollander JE, Subramanian S, Malhotra AK, Villez PA . Pressure dynamics of
various irrigation techniques commonly used in the emergency department . Presented at
the Society of Academic Emergency Medicine . Washington DC, May, 1994 . Academic
Emergency Medicine 1994 ;1 :A48-49 .
172 . Singer AJ, Mofenson HC, Caraccio TR . Temporal profile of elevated transaminases in
patients with acetaminophen poisoning . Presented at the North American Congress of
Clinical Toxicology, Salt Lake City, Utah, September, 1994 . Veterinarian and Human
Toxicology 1994 ;36 :367 .
173 . Brogan GX, Hollander JE, Singer* AJ, Giarrusso E . Comparison of infection rates using
plain lidocaine versus buffered lidocaine in anesthetizing wounds . Presented at the Society
of Academic Emergency Medicine . Washington DC, May 1994. Academic Emergency
Medicine 1994 ;1 :A46.
174. Hollander JE, Henry MC, Singer AJ . Evaluation and treatment of traumatic wounds : The
wound registry. Presented at the American College of Emergency Physicians Research
Forum. San Diego, California, March, 1994 . Annals of Emergency Medicine .
1994 ;23 :609 .

38
July 23, 200 7

175 . Singer A, Margalit B . The quality of data documentation in hospital records of multiple
trauma patients in Israel . Is retrospective quality assurance currently feasible? Presented at
the Israel Medical Week . Jerusalem, Israel, May, 1991 .
176 . Singer A, Sagi A, Rosenberg L . Chemical burns : A retrospective review . Presented at the
Jerusalem Burn Conference . Jerusalem, Israel, March, 1990 .

Onstoing Participation in Multicenter Trials :

Early ACS-Evaluation of GPIIBIIIA inhibitors in AC S

CRUSADE-Can Rapid risk stratification of Unstable angina patients Suppress ADverse


outcomes with Early implementation of the ACC/AHA Guidelines : The CRUSADE national
quality improvement initiativ e

MAINTAIN-Medication Applied and Sustained over tim e

ADHERE/ADHERE EM-Acute Decompensated heart failure national registry Emergency


Medicine module .

TIMI-38 : A Comparison of CS-747 and Clopidogrel in Acute Coronary Syndrome Subjects who
are to Undergo Percutaneous Coronary Intervention .

IMPROVE-IT-IMProved Reduction of Outcomes : Vytorin Efficacy Intervention Trial

Media Reports
Newspaper Reports

Emergency Medicine News : Troponin bedside testing shrinks ED stays.


Prevention . Hair Appositio n
Parents Magazine . Children's pain during medical procedures
The New York Times . Hair apposition
Reuters News . Pain assessment in children .
Scripps Howard News Agency (400 newspapers throughout the United States) . Hospital Diets
West Gadsen Times, West Gadsen, AL. Hospital Diet s
Washington Post, Washington DC . Hospital Diets
Miami Herald, Miami, Florida . Hospital Diets
Dallas Morning News, Dallas, Texas . Hospital Diets
New Haven Register, New Haven, Connecticut . Hospital Diet s
Tufts University Diet and Nutrition Letter, Boston, Massachusetts . Hospital Diets
Prevention Magazine, Emmaus, Pennsylvania . Hospital Diets
Nation's Restaurant News . Hospital Diets
Emergency medicine. Temporal profile of acetaminophen induced hepatotoxicity .
Newsday, New York . Tissue Adhesives .
Prevention Magazine, Emmaus, Pennsylvania . Comparison of patient and practitioner pain
assessments .

39
July 23, 2007

Radio Interviews

WCBS, New York, NY . Hair apposition


WABC, New York, NY . Hospital Diets
WBBM, Chicago, IL. Hospital Diets
WDEL, Wilmington, DE . Hospital Diets
Columbia Radio, Columbia . Hospital Diets

Television Reports

Channel 9, New York, NY . Ice Related Injuries . Winter 2007 .


WPIX, Channel 11, New York, NY (over 150 television channels nationwide) : Summer Hazards
for Children .
CBS This Morning, New York, NY : Hospital Diets
ABC Evening News, San Diego, CA : Hospital Diets
Fox Evening News, New York, NY : Hospital Diet s
Fox News Network, Health Report, New York, NY : Tissue Adhesives

Adam J. Singer, MD

40