Abstract
Several factors are here enumerated and the early steps in the process are elucidated for elevating an apparent biologic marker, termed Response Consistency, to the level of a vital sign. The possibility became evident as a result of seeking a simple psychological process in order to augment expensive leading edge medical research methods of studying human pain.
Introduction
My old medical school Dorland’s, American
Illustrated Medical Dictionary 21st Edition copyright 1947,
definition of the term ‘vital’ is “pertaining to life”. It lists only “pulse, respiration and
temperature” for ‘Sign, vital’ among its almost 11 solid pages of what must be hundreds
of different medical terms referencing various human signs. Most of us often
use that term loosely to include some of the other biologic markers such as
blood pressure and even sometimes erythrocyte sedimentation rate. Now, in 2003,
the U.S. Patent Office lists some 1764 patents, back only to 1975, under the
term ‘marker, biologic‘ and 2253 under ‘marker, pain’ –my major area of
interest.
While
we have in the past always considered such signs, now more commonly termed
biologic markers, as being of paramount importance lately they seem to be of
even greater interest particularly if they point the way to clinical conditions
that are of known major medical significance for humans. Perhaps if we choose
to make a distinction between the older term and that of today we can limit the
former definition to only those markers or signs that actually are of a more
universal degree vital to what our, now also broader, term for human life may
actually be. Although only of anecdotal interest, I have admittedly not yet
uncovered how far back the term ‘vital’ can be traced for such a sign as the
pulse rate –perhaps to William Harvey himself.
Since my own interest in this larger panoply is
limited to the area of pain, I might mention that many clinicians now consider
blood pressure as the fourth vital sign. And lately, pain is allegedly being
given the exalted position of the fifth sign according to Marni Jackson’s book[1]
which is cited in Healthcare Inspirations2
covering the new requirement of the Joint Commission on Accreditation of Health
Care Organizations’ (JCAHO). It is now
required that a pain inquiry must be made and recorded when a patient’s medical
history is taken. In the strictest sense of a definition of the term ‘sign’ one
might better include an objectively visible phenomena of the pain rather than
simply a subjective complaint, which takes us to the body of the subject of
this presentation.
Response
Consistency as a Biologic Marker
Because almost all of the work in the past, where
both acute and chronic pain is concerned, has been dependent upon the subjects
own, mainly verbal, assessment of his or her perception of a noxious stimulus,
only limited interest in a more objective method of measurement has been
evident in the realm of actual
scientific physiologic studies until recently. That is to say that all methods
of depicting or documenting the patient’s interpretation of a stimulus, such as
that described by the broad term ‘pain’, have been based upon his or her
subjective assessment since there are few if any really objective methods like,
for example, now the recently introduced functional MRI, PET and SPECT scans
that are available. Thus we can say that the medical specialty termed Cranial
Nuclear Medicine is now showing us that there can be a clear picture of the
presence or absence of higher neurological levels of a stimulus rather than the
simple measurement of the nerve’s electrical conduction which can hardly be
traced beyond the level of its first synaptic juncture and certainly does not lend
itself well to in vivo study. True where lower animal studies are involved
there have been techniques that have been adapted to rigorous scientific
methods of studying the response to noxious agents: for example, the tail
twitch of rats when subjected to heat; terming it ‘pain’ while recognizing that
there may be almost no relationship to that experienced by the human. But here
again one is at a lose for something more adaptable that can truly, some day,
encompass all significant factors such as ethnic and gender origin or even
general well being which go into a subjective response when it comes to the use
of such a vague term as pain. Until
that is achieved we can not actually speak of a real pain threshold knowing
that a variability of the subject’s past or even immediate circumstances, such
as a recent meal prior to testing, can confound the result.
In pursuit of a suitable inexpensive biologic marker
to be used in selecting which patients would most economically lend themselves
to the study of chronic pain I have begun to recognize that there maybe an
underlying definable universal factor to the concept of its perception. This
was published in the electronic Journal
of the Chronic Pain Institute3 in some
detail using the StatView statistics computer software tool of SAS Institute
Incorporated. In there I tried to
clarifying that variances from the Mean of each individual’s aggregate test
readings, rather than simply taking the Average, is best used as an expression
of the significance of that subject’s consistency in arriving at a repeated
quantifiable judgment relative to a measurable stimulus in the form of skin
pressure. The testing was done in a way so as to sharply reduce such
confounding variables as inter-operator variation by having the subjects
actually apply the stimulus to themselves in order to judge the degree of skin
pressure; yet the interpretation of
their perception was read and recorded only by the technician who had no other
input or control ¾ in order to achieve a
double-blind single-subject result.
While working with the first group of 113 subjects I
recognized that there is a rather finite degree of consistency of perception in
terms of each students ability to blindly (only the technician having access to
the response) return to the same measurement reading in judging 5 episodes of
skin pressure, which I termed Response Consistency (RC). It seems to underlie
all of their perception, at least to skin pressure because there was a rather
tightly grouped Mean covering the total of the 113 dental students who each
self-judged 20 pressure points of their own skin pressure as can be noted in
greater detail when read in that publication.
The Mean of this population sample of 113 dental
students is demonstrated in the Descriptive Statistics of Fig. 1 below along
with its Frequency Distribution.
Figure 1.
This resultant high degree of consistency in the
overall group as well as in most of the individuals does not seem to me to be
completely explainable on the basis of a possible sample bias of dental
students relative to the geographic general population as such. A bias which
could be the result of the rigorous training that all dental students are
involved with due to their experience with dental instruments and the like when
it comes to the perception and interpretation of many different forms of skin
pressure. The concept, of there being a fixed baseline degree of consistency
throughout the population at large, is born out further by the fact that there
was a smaller, but statistically significant subgroup (Past Unus. Pn) of the
cited population sample made up of individuals who had experienced at least one
episode of more than minor pain in their background. These had a greater degree
of variance (2.112 kg/cm2) as opposed to the total student sample
Mean (1.403 kg/cm2). This may be due to a mechanism of memory that
was pointed out by Gazzaniga4, termed
the attentional system. Of note is that when, the Past Unus. Pn subgroup (n=22)
was compared, by Unpaired t-test with the 113 student Mean it showed a a
significant difference giving a P-Value of .0011 by using Fisher’s PLSD. Rather conversely the Present
Pn subgroup (n=28), who were actually experiencing some degree of what they
termed pain, such as a headache or backache during the time of testing, showed
only a P-Value of .2596 by Unpaired t-test relative to the Mean of the same
sample 113 dental student population.
The Possible
Universality of Response Consistency
In the Facial Pain Clinic at the School of Dentistry
of the University of the Pacific, we recently performed another, but somewhat
differently designed experiment, which lends itself sufficiently to comparison
on the basis of being a second sample from the broad geographic general
population because it incorporated the testing principles cited above. Taking
that study as a second sample of a dental student population we get some
insight into what could in the future be considered a wide ranging Response
Consistency baseline at least for skin pressure in certain groups such as
dentists. We also can get a glimpse of the possibility that there may be more
universality here than would simply be reflected in using the term ‘biologic
marker’.
Here, we had 94 more dental students utilizing the same techniques in the first part of a similar sequence of test performance as that of the earlier sample of 113 dental students. However for this experiment an electronic skin pressure measuring device, the Commander algometer of JTech Instruments, was used which could account for the group’s Mean of all the Variances (Var 4T) this time being 1.837 giving a P-Value of .5595 when a Paired t-test was done to compare this 94 student population sample to the earlier 113 student sample (Var 4RC) as shown in Fig. 2 below.
Figure 2.
For the above Paired t-test of the two different
student samples, the 113 student sample was reduced randomly using the Simple
Random Sample technique of blindly dropping one of every 6 student cases
thereby providing only 94 students for a better comparison analysis. Their Bivariate Scattergram, in Fig. 2
above, demonstrates fairly good grouping of both samples, but the better
linearity of the RC group, in red, suggests that the repetition of a more
identical study, to avoid all factors of unfamiliarity with the different type
of testing equipment, will reveal greater sampling uniformity which could well
provide added insight from the
standpoint of the Response Consistency concept. All statistical analyses for
both samples was done with the StatView program, version 5.0.1
of SAS
Institute Incorporated.
A detailed publication of this study will follow
later, but where this presentation is concerned I am here pointing up only the
relevant portion pertaining to Response Consistency Testing. It gives further
encouragement to the idea of now seeking comparison to a few samples from the
general geographic population at large.
The
Bigger Picture
One might well be tempted to
say that since these two samples do compare somewhat favorably despite having
been achieved using two different types of algometers, that they can be taken
as reflective of the human population at large, however there are several
important points that must now be considered:
First, in all seriousness,
can we really take two admittedly good-sized samples as being reflective of a
population of millions or even billions of people? Hardly. Never-the-less, back
when the concept of using the term ‘vital sign’ to reflect the universality of
certain clinical findings was first established, and that may not be so long
ago, likely no really major world wide sampling procedures were used to reach
those conclusions. Rather they were based upon logic, which is the mainstay of
almost all of our medical knowledge even to this day. Since when are humans
actually considered to be infallible and why then can we not arrive at a rather
finite quantification of our human fallibility? Using this form of reasoning it
should be clear that we must recognize even human infallibility, in the form of
total consistency, should be discernable given a certain degree of ingenuity in
deriving ways of measuring it.
Second, we should recognize
that the point made earlier, concerning the suspected group bias, in terms of
the ability in young dentists to interpret
the perception of skin pressure, must be taken seriously enough to argue for
the broader undertaking of geographic population sampling methods using randomly chosen individuals rather than
homogeneous groups. If we then see the probable long-term value to be achieved
by such a task, it seems quite evident that the recognition and subsequent
measurement of this form of central nervous system physiology now termed
Response Consistency will provide great dividends in the study of various
mental mechanisms. I am presently undertaking to bring together funding for
such an endeavor under the Federal Internal Revenue Services’ income tax
exemption letter that the Chronic Pain Institute holds. This should allow us to
set up further testing of more public samples. Should one wish to view those
credentials in more detail they can be found by choosing the selection ‘References and Credentials’ at:
http://www.ChronicPainInstitute.org
.
Third, one must keep in mind
that we are actually interested in finding a meaningful sign to inexpensively
point to certain mental conditions in the future which at the moment are being
studied by the very expensive techniques just mentioned. As a consequence we
are not simply looking only for universality of a human characteristic. Such
can be any type of minor attribute of which by far the majority do not
have any clearly defined medical uses when it comes to the day to day maladies
of patients compared to the level of importance of pulse, respiration and temperature. Therefore there would seem to
be little if anything gained by an expenditure of a large portion of our
medical financial resources solely for testing of the population at large in
order to define the universality of RC alone. To the contrary, it is important
to also show its applications to real medical needs.
In order to embark on such a
broad quest as identifying the medical need for the observation of Response
Consistency as above defined, both this described experiment as well as the one
already published carried with them the identical set of 72 questions many of
which as yet, time and money, have not permitted the important task of
submission to data mining procedures. However the difference in statistical
significance of the two groups already mentioned: that is, Past Unusual and
Present Pain, is a good start in this direction of establishing specific
medical needs for this concept. As can be recognized in more detail when the
previously cited electronic publication3 is read, these two
subgroups contain adequately large enough samples to allow for comparison of
their Means relative to the general public. When one studies further the
notable difference in the aggregate responses of the reasonably good sized subgroup labeled Past Unusual Pain, this
could be expected to provide new insight into the physiology of the central
nervous system’s perception mechanism for specific types of stimuli: namely, in
this instance skin pressure.
In the 72 questions of each
subject’s response, made up of multiple choice answers, there are quite a few
additional ones for future analysis such as: an inquiry concerning previous
virus infections and others that are relative to various physical complaints of
the subjects. Thus the response to those questions is expected to point the way
further to the medical significance of all of the data gathered in both
studies.
Conclusion
It will likely take many
other experiments before one can clearly make the connection of Response Consistency
with what has been described as the ‘attentional system’, mentioned above.
However, at this point, I am confident that at least a similar explanation will
sooner or later become apparent, relative to some form of a subject’s memory of
a past painful event, which will
account for a measurable difference in Response Consistency in most humans.
Then what will remain to be seen is
whether certain individuals
actually demonstrate a difference from the Norm of the geographic population at
large in terms of its comparison with the Mean of that subject’s aggregate
readings when it comes to conditions like Past or even Present Pain and other
human mental conditions such as Mania and Depression.
*August L. Stemmer, MD, DMD, FACS is an Adjunct Clinical Professor in the Basic Sciences Department of the School of Dentistry at the University of the Pacific
and is the
President, CEO of the Chronic Pain Institute
References
1 Marni
Jackson, Pain: The Fifth Vital Sign, Random House of Canada
2 Healthcare Inspirations, http://www.HealthcareInspirations.com/hci_pain_assessment_tool.html
3 August L. Stemmer and Peter F. Chase, Response Consistency Testing, the electronic Journal of the Chronic Pain Institute Vol. 1 Issue 1, at: http://www.ChronicPainInstitute.org
4 Gazzaniga, M. S., (1998) The Split Brain Revisited, Scientific American, July 1998 pg 51-55
Key Words:
Biologic Marker, Response Consistency, Pain
Contact Information
August L. Stemmer, M.D., D.M.D., President
Chronic
Pain Institute
1280 Lynwood Dr
Novato, California 94947
email: August@ChronicPainInstitute.org
or to: CPI@mainStem.net
Original Presentation Made
by August L. Stemmer, M.D., D.M.D
to the 11th Annual Conference of the Western Users of SAS Software, Inc. at the Hotel Nikko in San Francisco, California on November 5, 2003