INTRODUCTION
Disabling
chronic low-back pain is extremely prevalent in Western countries, entailing
huge social costs; however, there are as yet no agreed management guidelines
for this condition. A wide variety of treatments have been investigated
in a large number of studies, with contradictory results. The problem
is compounded by the fact that, owing to methodological biases, most
of the studies performed are difficult to interpret. Among the deficiencies
encountered are extremely poor evaluation criteria, an overemphasis
on the technical aspects of the treatments concerned, the absence of
an assessor of sufficient scientific integrity, non-consecutive recruitment
into the studies, inhomogeneous patient populations, failure to restrict
each study to one disease entity, and consistent lack of a control group.
Nonsurgical
treatments of whatever kind (drug treatment, physiotherapy, manual medicine)
has been found to produce satisfactory results in only 25-65% of the
cases. This is why at least one third of low-back pain sufferers will
seek surgical treatment.
However,
the results of surgery in patients with chronic low-back pain associated
with disc disorders have been disappointingly uneven: regardless of
the fusion technique employed, the rate of satisfactory results has
been between 20% and 90%, in the different studies reported in the literature.
Since surgery is obviously incapable of yielding consistently good outcomes,
and requires a considerable input of resources, we decided to investigate
the potential of an alternative therapeutic approach. Whilst this novel
management principle could, eventually, have major repercussions in
terms of health care cost containment, its efficacy had not previously
been investigated. This is why we designed a randomized study comparing
two well-matched groups of chronic low-back pain patients, of whom one
was managed with lumbar fusion, while the other received daily doses
of a high-quality wine.
MATERIAL AND METHODS
Between
November 1995 and April 1996, 366 patients suffering from chronic low-back
pain as a result of degenerative intervertebral disc disease were consecutively
enrolled in the study. All the patients had single-level disc involvement
confirmed by further investigations, mainly low-back pain, soul-destroying
and back-breaking jobs, and prior nonsurgical treatment for at least
six months (range: 5.978 months-18.687 months; mean duration of treatment:
6.275 months). None of the patients had any neurological signs and symptoms,
history of lumbar surgery, or ascites.
For purposes
of the study, the patients were randomized into two groups, upon enrolment
into the study.
The Fusion
group (Group A) comprised 183 patients, who had been operated on by
the same surgeon using an identical technique (posterior approach to
the spine, posterior iliac crest autograft placed between the transverse
processes, and pedicular instrumentation with plates and screws). The
typical in-patient stay was eight days, followed by 34 days in a rehabilitation
facility. The typical cost of this treatment was 62,000 French francs
per surgical patient.
In the
Drink group (Group B), patients were treated at home, by dosing with
a standard-size (187.5 mL) glass of Petrus vintage 1994, b.i.d. (lunchtime
and evenings), for six weeks. The wine administered was a Pomerol, containing
95% merlot and 5% cabernet franc. The typical cost of this treatment
was also 62,000 French francs.
The study
was approved by the Ethics Committee of our centre. In order to obtain
the required approval, a lengthy preclinical study phase was required,
during which the members of the Ethics Committee rigorously tested the
innovative arm of the study (Group B treatment).
The results
were evaluated using a detailed assessment form containing a battery
of self-administered questionnaires, and an objective clinical assessment
by an independent observer who was blinded to the treatment received
by the different patients. The parameters quantitated were pain, function,
and patient satisfaction. For the assessment of the impact of the treatment
on the patients' quality of life, the MOS SF-36 (Medical Outcomes Study
Short-Form Health Survey) was employed. The chronic low-back pain was
assessed using the Dallas Pain Questionnaire in its French version validated
by the French Rheumatological Society during a wine tasting session,
and by using the indices proposed by Greenough and Fraser. A visual
analogue scale (VAS) was also used. The functional outcome was assessed
by means of the Beaujon scoring system with Bichat modifications, which
had been tested in the junior surgeons' common room during a suitably
liquid lunch. In addition, the tolerability of, and the patients' adherence
to, the treatment were checked by means of weekly liver function tests
involving an assay of gamma-GT, in all patients, including those who
had been managed with surgery.
The data
thus acquired was entrusted to a qualified statistician, who had a microcomputer
compatible with its software; the object being to find something that
was significant and did not conflict excessively with the hypotheses
underlying the study. The underlying hypothesis was that the patients
receiving the Petrus treatment would do at least as well as the patients
managed with surgery. However, in order to obey the laws of statistics,
a zero hypothesis had to be formulated, according to which there would
be no difference between the two treatments. We then tried to demolish
this hypothesis using every possible and conceivable test, without,
however, achieving much success. The quantitative data was analyzed
with MANOVA (multivariate analysis of variance), giving a global Wilks
test supplemented by a multiple Sheffe test stratified for the complementary
factors of each dimension of the calculated scores. Normal distribution
had been tested for as a first step, using the Kolmogorov-Smirnov test
(to be served neat on ice). The qualitative data was analyzed with the
chi-square test. The Type I risk was evaluated as 0.05.
RESULTS
Complications
In Group
A (Fusion), there was a small number of surgical complications. Three
patients developed an infection that necessitated early surgical revision;
all these patients recovered uneventfully, except for two, who are still
oozing. There were no neurological complications. Postoperative nerve
root pain, in a patient with an ectopic root, required a change of dressing
under general anaesthesia. There were four cases of manifest non-union.
Six patients were lost to follow-up, while two displayed an attitude
towards the operating surgeon that was incompatible with the objective
nature of the assessment. This left 170 patients available for analysis.
In Group
B (Drink), six patients had to be excluded, since they had taken the
entire amount of study medication during the first week of the study.
Five patients had fallen from low-level windows, sustaining head injuries
and LOC (loss of consciousness), and required emergency admission. One
patient reported having such a pain in the posterior that he could not
go on drinking. Another patient told the investigator at the follow-up
clinic that he had lost the bottles that had been issued to him (alleging
that his brother-in-law had taken the treatment medication). This left
170 patients available for analysis in this Group as well.
Other
events
In the
Petrus group, one patient taken holy orders following an episode of
mystical delusions, without any demonstrable cause-and-effect relationship
with the treatment received. Another patient revealed to his wife that
he was sexually ambivalent.
Clinical
outcome
Visual
analogue scale (VAS). The results in Group B (Petrus) show marked improvement
of the scores from the very start of treatment; the improvement persisted
throughout the study, with residual pain scores remaining low. Following
the end of treatment, the outcome tended, unfortunately, to deteriorate
somewhat over time; the actual carry-over effect remains to be assessed.
In the surgical group, the scores reflected the postoperative period
and further postoperative course, and did not return to humanly bearable
levels until 2-2.5 months after surgery, when they were found to coincide
with the values seen in the oenotherapeutically managed group (Fig.
1).
Fig.
1 Visual analogue scale (VAS) ratings over time (out to 12 weeks from
start of treatment).
The results in Group B (oenotherapy group) were very encouraging, but
tended to deteriorate over time after the end of treatment.
Quality
of life
Analysis
of the study data proved a straightforward means of obtaining an overall
picture of the clinical condition of the patients. The differential
analysis of the graphs for each item was simply modulated as a function
of the intensity of the preoperative pain estimated from the reply of
each patient to the items in the previously validated questionnaire;
the data thus obtained was then plotted as coloured graphs on single-layer
vellum paper (80 g/m2). This work had to be performed with leading-edge
information technology using multiprocessing/multitasking; liquid nitrogen
cooling had to be employed as the system was overheating. Despite these
problems, all the calculations were successfully performed prior to
the complete self-destruction of the system, which resulted in irretrievable
computer failure. As a result of this breakdown, we lost all the original
data, as well as one computer expert, who was there at the time of the
incident and has since been holed up in a management department engaged
in DRG activities.
The preoperative
data itself did not differ significantly in the two groups. The patients
treated with Petrus showed very dramatic improvement of their SF-36
scores (by a mean of 25.5%, from the start of treatment). This improvement
persisted, albeit less markedly, to the end of the treatment period.
Subsequently, the outcome tended to deteriorate a little, although the
final scores compared very well with those in the surgical group. This
was seen in respect of all the dimensions of the questionnaire; however,
there were some interesting differences. Psychosocial functioning improved
from the outset, and in a major way (Fig. 2); this correlated positively
with a high degree of patient satisfaction. This improvement lasted
throughout the treatment period; at the end of the period, there was
a slight drop. However, a positive carry-over effect was observed, which
was found to be statistically probable. The effect on physical pain
was, however, less pronounced (Fig. 3), although, throughout the period,
the oenologically treated patients' scores remained well above those
of the surgical group. Assessment of the patients' physical and emotional
health (Fig. 4) showed intermediate results, with a marked drop at the
end of the Petrus treatment period. However, the carry-over effect of
the treatment was sufficiently pronounced to justify the fondest hopes
concerning the potential of this therapeutic approach.
Fig.
2 Psychosocial dimension (SF-36)
The patients treated with Petrus had markedly improved social functioning
throughout the treatment period, although the level deteriorated
somewhat after the end of the study period. Patients in Group A
(fusion) had seriously impaired psychosocial functioning throughout
the postoperative period. |
Fig.
3 Bodily pain
The scores of the patients in Group B (oenotherapy) were improved,
albeit not significantly. Group B scores were, however, markedly
better than the pain scores of the Group A patients in the postoperative
period. |
Fig. 4 Physical and emotional health
The physical and emotional health scores of the Group B (oenotherapy)
patients were excellent. After the end of treatment, the scores
fell briefly. By comparison, the Fusion patients were wretched throughout
the postoperative period. |
Functional outcome
In Group
A, the rate of good results was 31%; that of fair results, 36%; while
33% of the patients had poor results. In Group B, the rate of good results
was 28%; that of fair results, 42%; while 30% of the patients had poor
results.
Our determined
efforts notwithstanding, we were unable to demonstrate a significant
difference between the outcomes in the two study arms. However, we suspect
that the good results in the Group B patients were better than the good
results in the Group A patients, because of the strong correlation with
a high degree of patient satisfaction seen in Group B, which suggests
that the good results in Group A had just happened, whereas those in
Group B were longer-lasting effects of the treatment received.
Level
of satisfaction
In Group
A, 26% of the patients were very satisfied with the treatment; 29% were
fairly satisfied; 25% were dissatisfied; 10% were very dissatisfied;
while 15% had not understood the question. In Group B, 75% of the patients
were very satisfied with the treatment; 17% were fairly satisfied; 5%
were dissatisfied; 3% were very dissatisfied; while 0% had not understood
the question. This difference was significant (P = 0.001).
When asked
whether they would undergo the same treatment again if they had the
option, the Group A patients replied as follows: yes 31%; no 60%; don't
know 5%; didn't understand the question 4%. The Group B patients replied
as follows: yes 97%; no 1%; don't know 1%; didn't understand the question
0%.
When asked
whether they would recommend the treatment to a friend, the Group A
patients replied as follows: yes 40%; no 40%; don't know 20%; didn't
understand the question 0%. The Group B patients replied as follows:
yes 98%; no 1%; don't know 1%; didn't understand the question 0%.
Factors
producing a good outcome
The patients'
gender did not appear to be material, at least not as far as the outcome
was concerned. Use of tobacco products did not affect the outcome, notwithstanding
all our efforts to prove the contrary. Acquisition of the lumbar spine
lesion in an industrial accident had a significant negative effect in
Group A, and a positive effect in Group B: industrial accident patients
treated with Petrus felt even better than the others. However, patients
in Group B overall refused to go back to work; this difference was not,
however, significant.
DISCUSSION
Despite
its obvious shortcomings, and resultant misgivings, surgery by posterior
fusion is considered to be a gold standard in the management of patients
with low-back pain and disc lesions refractory to drug treatment. In
the published studies, the emphasis has been on the details of the various
techniques employed, which are all aimed at maximal immobilization of
the spinal level(s) causing the pain. We wish to put forward the results
of an alternative treatment approach, whose mechanism of action appears
to be complex and multifactorial: the different components of the wine
express themselves in a harmonious whole that accounts for the effectiveness
of the treatment. The alcoholic component has an anxiolytic, analgesic,
and euphoria-inducing effect at the central level; the tannins have
a poorly known but probable effect both centrally and peripherally,
and, conceivably, also at the level of the vertebra and the intervertebral
disc, with a vasodilator action on the vertebral vessels. Petrus may
even counteract disc degeneration or the effects thereof on the control
of pain. These assumptions will need to be tested in further studies.
Instrumented
lumbar fusion, regardless of the technique employed, is a complex procedure
that involves more than the immobilization of a motion segment. Multifidus
and longissimus dorsi have to be detached over considerable distances,
which deprives the joint capsules and the muscle masses of their blood
and nerve supply, and disrupts the local stress patterns. Drilling of
the vertebral bodies produces bone decompression or venous drainage.
The implantation of metal plates is akin to treatment with metal trace
elements. Also, having had to live with a very painful condition will
change a subject's pain perception threshold - witness the number of
patients who, in good faith, had rated their preoperative pain as 10
on the VAS.
The effects
of the two treatments used in the present study were remarkably similar.
Try as we might, we were unable to show a statistically significant
difference between a standard treatment (lumbar fusion) and an innovative,
as yet unevaluated treatment. However, we feel that the good results
obtained in the patients in Group B (the innovative treatment group)
were even better than the good results in the Group A patient, as can
be seen from the high patient satisfaction scores in Group B.
The absence
of a difference between the two groups provides, in itself, very strong
evidence that the innovative treatment (Petrus b.i.d. for six weeks)
is a perfectly reasonable alternative to the currently accepted gold
standard of spinal fusion. In fact, further refinements in dosing technique,
a change in dosing schedules, together with further development of the
technique itself, should effect further improvements and, eventually,
produce a significant difference in favour of oenotherapy. Our current
treatment is incomplete, and the dosage could be enhanced, as has been
suggested by many of our patients. After a certain time, the effect
does tend to wear off to some degree; however, improving the modalities
of treatment should correct this adverse tendency, and produce a lasting
effect. There are many research avenues to be explored. Thus, a third
glass of Petrus could be prescribed, to be taken at bedtime; treatment
might be given over a longer period of time; or the Petrus could be
administered via a subcutaneous port.
Another
remarkable observation in the oenotherapeutically treated group was
the total absence (at least in the present study) of any nosocomial
complications, scarring, and non-union.
The surgical
technique used in the present study was a conventional one, using instrumented
posterolateral lumbar fusion. Misgivings have been voiced concerning
the persistence, after fusion, of a certain amount of flexion and movement
in the fused segment; and routine combination with anterior fusion using
cages has been suggested as a remedy. It would, therefore, be important
for the proponents of these techniques to compare their results with
the ones obtained by us using our innovative treatment regimen (intermittent
ingestion of Petrus over a period of six weeks).
We readily
recognize that, in our novel treatment, there is room for improvement.
The vintage used was only 94; the wine was not a Margaux; and the dosing
unit was only one glass. Improvements in the dose regimen, and the use
of yet more potent therapeutic agents, should be considered when it
comes to designing further studies.
For the
time being, surgical treatment is paid for in its entirety by the State
health care system, whereas the innovative treatment is not. The study
reported in this paper shows that the efficacy of the novel treatment
is beyond doubt. The time has therefore come for the health care financiers
to look into this question, so as to ensure that the Petrus treatment
will be paid for the State system, at least in well-defined and appropriately
selected cases (chronic low-back pain with proven single-level disc
degeneration). Given its very low complication rate, the likely health
care cost savings are considerable. With the State paying for this treatment,
the social cost of disabling chronic low-back pain in adults should
be brought under control. Such a policy would also enable the largest
possible number of low-back pain sufferers to benefit from an effective
and painless treatment.
CONCLUSION
The results
obtained with intermittent oenotherapy are encouraging. We recommend
that another study be performed, using different conditions. The dosage
of Petrus should be increased, and more patients should be recruited,
in order to enhance the power of the study. Even at this point in time,
it is obvious that the innovative treatment (received by Group B) is
very efficacious and could, therefore, be considered as a treatment
for disabling chronic low-back pain, even in the absence of placebo-controlled
studies. Much is expected of other therapeutic agents in the same class
of substances that are currently being developed (Château Margaux,
etc.). In theory, at least, these agents should have good efficacy.
Whilst a combination of the two treatment principles used in the present
study seems an attractive idea, it is not currently an option, considering
the costs involved as well as the practical difficulties of implementing
such a combination treatment at the time of surgery. Administering an
agent of the same class of substances to the surgeon has not yet been
evaluated anywhere; it is, however, a potential subject for research,
which we would recommend, given the practical advantages that would
accrue while waiting for more comprehensive results.
Note:
Whilst one or more of the authors of the present study may be or may
have been involved with a commercial party marketing one of the therapeutic
agents mentioned in this paper, and whilst they or members of their
families may have been in possession, or been seen to be in possession,
of therapeutic agents mentioned in this paper, the author(s) declare(s)
to have remained completely and totally independent as (a) researcher(s)
throughout the study, and that his/their association with such therapeutic
agents did not in any way whatsoever affect the results of the said
study.
Note:
Whilst the above-mentioned therapeutic agents may be commercially available,
one or more of the agents mentioned in this paper have not yet been
approved by the FDA for use, in the United States of America, in the
indication and the treatment described above.
Note:
One or more of the therapeutic agents mentioned in this paper have not
yet been approved by the regulatory authorities in France, for use in
the treatment described in the present study.
Disclaimer:
The authors cannot be held responsible for the consequences of excessive
use of the above-mentioned therapeutic agents.
| REFERENCES |
|
1. Abel L.
The sure proof. Wine is sure proof that God loves us and wants
us to be happy. J Ark Med Soc 1996;93:316-318.
2. Arthur, Perceval, Lancelot, et
al. Goûtons voir si le
vin est bon. Proceedings de la Société du Graal
1123;XIII
3. Athos, Porthos et Aramis.
La vieille frégate branle du mât. Mémoire
Acad. Roy. 1630
4. Blardi P, De Lalla A, Volpi L,
et al. Stimulation of endogenous
adenosine release by oral administration of quercetin and resveratrol
in man. Drugs Exp Clin Res 1999;25:105-110.
5. Bullock JD, Wang JP, Bullock GH.
Was Dom Perignon really blind?
Surv Ophthalmol 1998;42:481-486.
6. Burr ML.
Explaining the French paradox. J R Soc Health 1995;115: 217-219.
7. Christiansen C, Thomsen C, Rasmussen
O, et al. Wine for type 2 diabetic
patients? Diabet Med 1993;10: 958-961.
8. Cole P. Of
light bulbs and wine glasses: risk factors and mortality trends.
Trans Stud Coll Physicians Phila 1988;10:95-102.
9. Fiorelli G.
More on the protective role of wine. Ital Heart J 1999;27:437-438.
10. Gronbaek MN.
In vino veritas? Ugeskr Laeger 1995;157: 6415.
11. Hoolihan C.
Wine and regimen from Hippocrates to the renaissance. Caduceus
1993;9:5-16.
12. Jarisch R, Wantke F. Wine
and headache. Int Arch Allergy Immunol 1996;110:7-12.
13. Kaufman HS. Red
wine headache. Lancet 1988;1:992-993.
14. Lee TH. To
be honest, I have about four drinks per day - a beer when I get
home from work, a couple of glasses of wine with dinner, and a
nightcap. Sometimes, I also have a glass of wine at lunch. Alcohol
has never interfered with my work or caused any problems in my
home life, and my liver is fine, so I do not think I have an «alcohol
problem.» plus, I expect that my alcohol use has something
to do with my terrific HDL- cholesterol level - 57 mg/dL. Harv
Heart Lett 1999;9:8.
15. Loser C. When
can you recommend one or two glasses of wine? A little alcohol
can increase longevity, but a reliable dosage limit is not available.
Mmw Fortschr Med 142:34-36.
16. Martin D.
Little old wine drinker me. L Vegas Med J. 1968
17. Milon de Crotone.
Mécanique du disque. Anal. Surg. 600 BC
18. Mitchell M. Gone
with the wine. Atlan. Med. J. 1936
19. Morowitz HJ.
The wine of life (Claude Bernard). Hosp Pract 1978;13:173, 176.
20. Moutet JP, Demeulemeester R, Riff
H, et al. Alcohol consumption
in Guadeloupe. Alcohol Alcohol 1989; 24:55-61.
21. Rasmussen C. Lumbar
disc herniation: favourable outcome associated with intake of
wine. Eur Spine J 1998;7:24-28.
22. Ritterband DR.
Disease management: old wine in new bottles? J Health Manag 1969;45:255-266.
23. Rimbeaud A.
Le bateau ivre. in Les illuminations 1871
24. Trethewie ER. Wines
and headaches. Med J Aust 1979;1:94.
25. Van HJ, David JR.
Alcohol tolerance and alcohol utilisation in Drosophilia: partial
independence of two adaptive traits. Heredity 1980;44:229-235.
26. Villon F.
Tant va la cruche à l'eau...in Ballade des proverbes. 1460
|
Traîtrise
Orthopédique - Maîtrise Orthopédique n° 100
- January, 2001
