UHM 2018, Vol. 45, No.
1 – LETTERS: REGULATOR PERFORMANCE; DAMO2CLES STUDY
LTE Para. 4: As stated above, the current authors’ work
was a controlled study, as well as any field study can be
controlled. Pollock’s implication that some regulators
were subjected to more rigorous conditions than others,
thus somehow accounting for our observation of a bi-
modal response, is unsupported by the facts, which are
too numerous to enumerate here, other than to say all
dives were conducted from heated huts.
In unmanned regulator testing by the U.S. Navy, where
conditions are even better controlled than in the field,
the identification of “acceptable” versus “unacceptable”
regulators is common. The acceptable ones are pub-
lished on the NAVSEA “Approved for Navy Use” list,
which currently has three regulators listed for cold-
water diving. The Sherwood Maximus is not one of
them.
LTE Para. 5: Although paragraph 5 asserts that it
expounds upon a “critical problem” with the Lang/
_____________________________________________________________________________________________________________________________________________________________________
Hyperbaric oxygen therapy in the
treatment of ischemic lower extremity ulcers in patients with diabetes:
Results of the DAMO2CLES multicenter randomized clinical trial.
Commentary on article in Diabetes Care [1]
Santema, et al. compared hyperbaric oxygen (HBO2)
therapy plus standard care to standard care alone for
wound healing and limb salvage in patients with
diabetes and concluded that HBO2 offered no advantage
[1]. Several aspects of this work beg address.
Lesions in 52% of enrollees were modest enough
(Wagner Grade 2) to not commonly represent a
hyperbaric treatment indication. As a significant limb
salvage difference favored HBO2 in per-protocol
analysis A, it would have been valuable to analyze
intention to treat outcome in lesions representing
accepted referral indications (Grades 3/4).
When electing to recalculate power secondary to low
recruitment, the authors chose to essentially double
effect size. If power is recalculated for the initial 12%
effect with the reported sample size, it drops to about
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Clarke paper, we’re not sure what his point is. The
present authors’ choice of descriptors is clearly
arbitrary, and meant simply to describe the bimodal
distribution of regulators. Regarding Pollock’s
comments about the “best” regulator, the governing
agency’s decision as to which regulators will be
approved for polar service are based on many factors,
not just the lowest incidence of freeze up in both
manned and unmanned testing. The assertion that only
one regulator is “the best,” is an over-simplification,
and is soundly rejected by the U.S. military.
Michael A. Lang, PhD
University of California San Diego, Department
of Emergency Medicine, San Diego, California
m4lang@ucsd.edu
John R. Clarke, PhD
Navy Experimental Diving Unit, Panama City, Florida
john.r.clarke@navy.mil
0.50. Further to this point, adjusting effect size so that
power “appears” to reach a desired level is misleading
at best, as one can choose an arbitrary effect size to
achieve any desired power. A recalculation of power
using the original 12% effect size should have been
reported.
The authors state that protocol analysis A “should
show the maximum attainable effect of HBOT.”
From an intent-to-treat perspective, perhaps this is true.
However, when protocol B and SC groups are com-
bined, distinction between groups becomes less clear,
more so when placing four subjects who received HBO2
of their choice into the SC group. To truly assess maxi-
mum attainable effect, one should compare protocol A
group with SC only, excluding the four noted subjects.
Despite all of this, protocol A group analysis reached
Pollock NW vs. Lang MA, Clarke JR; Clarke R, Hussey JR
 UHM 2018, Vol. 45, No. 1 – LETTERS: DAMO2CLES STUDY
statistical significance for limb preservation, so it is
unfortunate that this result is not reflected in the
abstract conclusion.
The authors argue that conclusions from the two
previous efficacy studies [2,3] are of limited value due
to short follow-ups, methodological weaknesses and
small numbers of participants. In fact, both study
designs involved the identical 12-month follow-up
reported here, with Fedorko’s group yet to publish
long-term data; their protocol reported within reference
17 [3]. Methodologic rigor employed in these studies
was superior to the current study as each involved a
double-blind sham controlled arm, and neither per-
mitted non-HBO2 assigned subjects to receive HBO2
upon request, a highly irregular research practice.
That stated, Fedorko’s research did suffer several study
execution flaws [4]. The argument for not including
sham exposure/double-blinding is likewise flawed.
Effective patient blinding in the absence of potential
to “dilute any demonstrated therapeutic effect” is
reported [5]. Sample sizes in the Fedorko and Londahl
studies were 94 and 107, respectively. At 120 subjects,
the current study can hardly be argued as a significant
order of magnitude increase.
Marked local hypoxia per tcpO2 testing was evident,
suggestive of underlying microangiopathy. As no data
were presented to demonstrate its reversibility per
provocative (oxygen inhalation) testing, one wonders
how many subjects underwent HBOT in the setting
of irreversible local hypoxia and, therefore, unlikely
to benefit.
In summary, we believe this paper is supportive of
HBO2 therapy for limb preservation in appropriately
selected patients.
Richard Clarke, CHT*
National Baromedical Services, Columbia, South Carolina
dick.clarke@palmettohealth.org
James R. Hussey, PhD
Associate Clinical Professor, Department of Epidemiology
and Biostatistics, University of South Carolina
Columbia, South Carolina
jhussey@mailbox.sc.edu
* Corresponding author
Clarke R, Hussey JR
Acknowledgments
Potential conflict of interest disclosure
Richard E. Clarke provides wound care and hyperbaric
medicine training, education and consulting services
James R. Hussey has no conflicts of interest to report
Funding: None
References
1. Santema K, Stoekenbroek R, Koelemay M, et al.
Hyperbaric oxygen therapy in the treatment of ischemic
lower extremity ulcers in patients with diabetes: results of
the DAMO2CLES multicenter randomized clinical trial.
Diabetes Care. 2018 Jan; 41 (1): 112-119. Epub 2017 Oct 26.
2. Londahl M, Katzman P, Nilsson A, et al. Hyperbaric
oxygen therapy facilitates healing of chronic foot ulcers in
patients with diabetes. Diabetes Care. 2010; 33 (5): 998-1003
3. Fedorko L, Bowen JM, Jones W, et al. Hyperbaric
oxygen therapy does not reduce indications for
amputation in patients with diabetes non-healing ulcers of
the lower limb: a prospective double-blind, randomized
controlled clinical trial. Diabetes Care. 2016; 39: 392-399.
4. Ledez KM. Serious concerns about the Toronto
Hyperbaric Oxygen for Diabetic Foot Ulcer Study.
Undersea Hyperb Med. 2016; Sept-Oct; 43 (6): 737-742.
5. Clarke D. Effective patient blinding during hyperbaric
trials. Undersea Hyperb Med. 2009; Jan-Feb; 36 (1): 13-17.
✦
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