Keywords
dupuytren disease - faciectomy - collagenase - survey - treatment
Introduction
The survey sent by the Spanish Society for Surgery of the Hand (Sociedad Española
de Cirugía de la Mano, SECMA) regarding the treatment of Dupuytren's disease (DD),
included a series of clinical assumptions in which was posed the assessment of the
current trend of treatment, considering practical cases. Comparison with previous
data from the study of Muñoz-Peñin[1] is not strictly applicable in this case, since that study design is different from
this article, although we will refer to it when referring to the use of the different
techniques used by surgeons. In the current medical literature only one article,[2] recently done, performs an assessment using an international survey to assess current
perspectives of DD treatment in a similar way. This survey, based on clinical cases,
establishes a regional difference regarding the preference of hand surgeons for treatment
with DD, encompassing the most common treatments today for primary processes: partial
fasciectomy (PFSC), the needle aponeurotomy (NA) and treatment with Clostridium Histolyticum collagenase (CCH). The survey and the obtaining of results were carried out before
the suspension of the commercialization of the CCH in late 2019.
Our objective is to assess, by carrying out clinical cases in the survey promoted
by SECMA, and adapted to the most common therapeutic solutions today in our geographical
area, the trend of Spanish surgeons in the treatment of DD.
Material and Methods
Recruitment
This study has been approved by SECMA and is part of the SPAINCOL project for the
assessment of long-term CCH treatment. It was approved by the Institutional Ethical
Committee (code CEI m38/19) and the Spanish Association of Medicines and Health Products
(code AEMPS RSC-COL-2019–01).
The survey was tested on two members of the medical staff of the lead author's hospital;
their responses were not included in the results. After that, it was sent by email
to SECMA partners. A brief description of the survey, details of anonymity and the
intention to publish the identified data was made on the first page. Both the general
questions and the clinical assumptions were drawn up by the lead author and agreed
with various hand surgeons and the SECMA research committee. It should be borne in
mind that the survey was drafted, carried out and analyzed in the time before CCH
was withdrawn from the European market.
Instrument
The variables analyzed in this study correspond to the block of questions from the
survey provided by SECMA ranging from number 13 to 20. Of these eight questions, the
first four correspond to primary clinical cases and the following four to recurrences.
The questions were structured into five possible answers, leaving the last one open
for the introduction of other treatment alternatives, which was analyzed separately
but was considered unique for statistical analysis.
The results of these questions were analyzed in relation to the group of questions
(5,6,9–12,21–23 25–27) about the general opinion of DD treatment (Annex 1).
Interest groups
For the study of the primary cases, the characteristics selected as representative
were based on criteria of supposed severity or a higher rate of recurrence of the
patients, such as: age younger than 50 years as a factor of greater aggressiveness
present in cases of Dupuytren diathesis,[3] involvement of one or more fingers, involvement of the 5th finger, involvement of PIP and/or of the MCP and contracture less than or equal to
45° considered mild, and greater as severe. This last value has been considered based
on the severity criteria established in the CORD studies[4] to which was applied a variation of 5° for possible measurement errors.[5]
[6]
[7] The characteristics studied for each case are summarized in [Table 1].
Table 1
|
Case
|
Age >50 years
|
Number of affected fingers
|
Is the 5th finger affected?
|
More than 45° contracture (single joint or combined in only 1 finger)
|
Is PIP affected?
|
|
1 (p13)
|
Yes
|
One
|
Yes
|
Yes
|
No
|
|
2 (p14)
|
No
|
One
|
No
|
No
|
No
|
|
3 (p15)
|
N/A
|
Two
|
Yes
|
Yes
|
Yes
|
|
4 (p16)
|
No
|
One
|
No
|
No
|
Yes
|
For the study of recurrences, the analysis focused on the choice of technique, with
assumptions that included recurrences after treatment with CCH or FSC and with the
same variables as in primary cases. The definition of recurrence was made based on
Felici's criteria.[8]
Statistical Analysis
Statistical analyzes were carried out using SPSS v.22. The results were shown as absolute
and relative frequency. To assess whether there were differences between the number
of times each technique was chosen according to the group, an analysis of X2 was used. To assess the strength of association between the variables, the Odds ratio
(OR) was used for dichotomous variables and Cramer's V for ordinal variables. For
all analyzes, statistical significance was considered for p values less than 0.05.
For the assessment of preferences in cases of recurrence we have not performed a statistical
analysis, considering the descriptive analysis sufficiently representative.
Results
Sample
The survey was sent to a total of 332 members of the Society. Of these, 127 (38.2%)
answered the survey, of which 79 (62.2% of the respondents) had experience with the
use of CCH and were chosen to assess preferences in primary cases. For the final evaluation
of the primary clinical cases, only the surveys in which the CCH or FSC options had
been selected were considered, since the number relative to the other options was
marginal and not relevant for the analysis ([Table 2]). Thus, 61 (48%) of the surveys were analyzed.
Table 2
|
Clinical case
|
N
|
CCH
|
FSC
|
DFSC
|
NA
|
Other
|
|
13
|
120
|
24 (19.4)
|
95 (76.6)
|
4 (3.2)
|
4 (3.2)
|
10 (8.1)
|
|
14
|
124
|
56 (45.5)
|
54 (43.9)
|
1 (0.8)
|
8 (6.5)
|
4 (3.3)
|
|
15
|
123
|
23 (19)
|
91 (75.2)
|
1 (0.8)
|
1 (0.8)
|
5 (4.1)
|
|
16
|
121
|
27 (22.5)
|
80 (66.7)
|
2 (1.7)
|
5 (5.0)
|
5 (4.2)
|
Results of Individual Preferences in Primary Cases
When we analyze the influence of the characteristics of the surgeon and the treatment
used, we find an association between this and the time he has been practicing the
specialty since he finished his residency (X[2] p = 0.027), however that association has been weak (V = 0.16). ([Table 3])
Table 3
|
Treatment selected in each case
|
|
Variable
|
Group (N = 61)[θ]
|
CCH[*]
|
FSC[*]
|
p (X
2)
|
OR
|
CI
|
p (V Cramer)
|
V Cramer
|
|
Surgeon's age
|
< 30 years (21)
|
34 (40.5%)
|
50 (59.5%)
|
0.976
|
–
|
–
|
0.977[**]
|
0.01
|
|
30–40 years (18)
|
30 (41.7%)
|
42 (58.3%)
|
|
40–50 years (22)
|
37 (42%)
|
51 (58%)
|
|
How many years have you been practicing your specialty since your residency ended?
|
< 3 years(2)
|
0 (0.0%)
|
8 (100%)
|
0.027
|
–
|
–
|
0.098[**]
|
0.16
|
|
3–6 years(8)
|
12 (37.5%)
|
20 (62.5%)
|
|
6–15 years (21)
|
36 (42.9%)
|
48 (57.1%)
|
|
>15 years (30)
|
53 (44.2%)
|
67 (55.8%)
|
|
And as a surgeon dedicated to hand surgery?
|
< 3 years (2)
|
2 (25%)
|
6 (75%)
|
0.816
|
–
|
–
|
0.686[**]
|
0.08
|
|
3–6 years (9)
|
15 (41.7%)
|
21 (58.3%)
|
|
6–15 years (27)
|
48 (44.4%)
|
60 (55.6%)
|
|
> 15 years (18)
|
28 (38.9%)
|
44 (61.1%)
|
|
General Orthopedic/Plastic surgeon (5)
|
8 (40%)
|
12 (60%)
|
|
In Dupuytren's disease, which of the following treatments do you use most frequently?
|
CCH (23)
|
62 (67.4%)
|
30 (32.6%)
|
<0.001
|
6.0
|
3.3–10.6
|
–
|
–
|
|
FSC (38)
|
39 (25.7%)
|
113 (74.3%)
|
|
Regardless of frequency, what is your preferred treatment?
|
CCH (30)
|
75 (62.5%)
|
45 (35.7%)
|
<0.001
|
–
|
–
|
–
|
–
|
|
FSC (30)
|
23 (19.2%)
|
97 (80.8%)
|
|
NA (1)
|
3 (75%)
|
1 (25%)
|
The treatment used also corresponded to the frequency of use of the treatment options
and their preference. Surgeons who reported higher frequency of CCH use (67.4% vs.
25.7%) were up to 6 times more likely to indicate such treatment in primary cases.
([Table 3])
When the patients were 50 years old or younger (53.3% vs. 23%), the 5th finger was
free of disease (53.3% vs. 29.5%) and contracture was less than 50° (53.3% vs. 29.
5%), participating surgeons preferred CCH treatment. The age of patients under 50
years was the variable with the strongest association with the choice of CCH as treatment
(OR = 3.8; CI95% 1.9–7.6) ([Table 4]).
Table 4
|
Selected treatments in each case
|
|
Variable
|
Group
|
CCH[*]
|
%
|
FSC[*]
|
%
|
p
|
OR
|
CI
|
|
Age
|
Less than or equal to 50 years
|
65
|
53.3
|
57
|
46.7
|
<0.001
|
3.8
|
1.9–7.6
|
|
Over 50 years
|
14
|
23.0
|
47
|
77.0
|
|
Number of affected fingers
|
One finger
|
79
|
43.2
|
104
|
56.8
|
0.37
|
1.3
|
0.7–2.4
|
|
Two or more fingers
|
22
|
36.1
|
39
|
63.9
|
|
Is the 5th finger affected?
|
No
|
65
|
53.3
|
57
|
46.7
|
<0.001
|
2.7
|
1.6–4.6
|
|
Yes
|
36
|
29.5
|
86
|
70.5
|
|
Does it have more than 45° of contracture?
|
No
|
65
|
53.3
|
57
|
46.7
|
<0.001
|
2.7
|
1.6–4.6
|
|
Yes
|
36
|
29.5
|
86
|
70.5
|
|
Is PIP affected?
|
No
|
58
|
47.5
|
64
|
52.5
|
0.069
|
1.6
|
0.9–2.7
|
|
Yes
|
43
|
35.2
|
79
|
64.8
|
Results of Recurrence Preferences
In all cases, the preferred response by surgeons was FSC, ranging from 54.8% (question
# 20) to 83.7% (question # 17). The predominant response was FSC in cases with involvement
considered severe and patients over 50 years of age, as well as in those with combined
involvement of the metacarpophalangeal joint (MCP) and the proximal interphalangeal
joint (PIP). Question 19, which presented by a 72-year-old patient with combined involvement
(MCP + PIP) of the 5th finger, was the only one in which the dermophasciectomy (DFSC)
has had a considerable response rate (8.7%) as well as other alternatives (6.1%),
including amputation among free field responses. Treatment with CCH was considered
as an alternative in cases of recurrence in those cases of young patients, with isolated
involvement of the MCP and central radius mild contracture, independently of the treatment
previously performed with FSC (31%) or CCH (29.3%). The results are consistent with
the subjective opinions of the surgeons, in which 82.2% (88) preferred FSC as the
technique of choice. ([Table 5]).
Table 5
|
CASE
|
Age
|
Finger
|
Severity
|
Joint
|
Previous Treatm
|
CCH[*]
|
FSC[*]
|
DFSC[*]
|
NA[*]
|
Other[*]
|
|
17
|
>50
|
5
|
>45
|
MCP + PIP
|
CCH
|
6.8
|
83.8
|
0.9
|
3.4
|
5.1
|
|
18
|
<50
|
4
|
≤45
|
MCP
|
CCH
|
29.3
|
63.8
|
0.9
|
3.4
|
2.6
|
|
19
|
>50
|
5
|
>45
|
MCP + PIP
|
FSC
|
12.2
|
70.4
|
8.7
|
2.6
|
6.1
|
|
20
|
<50
|
4
|
≤45
|
MCP
|
FSC
|
31
|
54.9
|
8
|
3.5
|
2.7
|
Discussion
Our results indicate that the preferred and most used treatment for DD continues to
be FSC. However, we have defined that CCH has been established as a second treatment
option. There is also a clear decrease in DFSC.
If we compare our results with those previously published in Spain[1] ([Table 6]), FSC is considered the treatment of choice today in even more cases. A curious
fact from the 2011 study is that almost 12% of surgeons advocate the use of a radical
FSC, a technique little used today and not without serious complications[9]
[10]
[11]
[12] for primary cases. The trend of our surgeons seems to guide the current preference
towards minimally invasive techniques in the treatment of DD, since they allow a quick
recovery of the patient with the minimum impact, leaving only the most demanding techniques
for those severe cases and pronounced recurrences, as various authors have sustained.[13]
[14]
Table 6
|
Year
|
parcial FSC
|
radical FSC
|
DFSC
|
NA
|
CCH
|
|
2011
|
51.70
|
11.80
|
12.20
|
12.20
|
N/A
|
|
2019
|
73
|
N/A
|
0.8
|
2.4
|
23
|
Regarding primary cases, we have observed that the participating surgeons with more
time as specialists in hand surgery tend to choose CCH as treatment for DD. Similarly,
those who report higher frequency of its use in routine practice are more likely to
select CCH as the treatment method. The baseline characteristics of the patients influence
this choice, the most important being age. In the USA, a survey sent to members of
the American Society for Surgery of the Hand (ASSH),[15] indicates that for simple primary cases, the technique preferred by surgeons is
CCH, leaving FSC for more complex cases with combined involvement of MCP and PIP,
and seeing how minimally invasive techniques are predominant in cases of primary involvement
and with the consideration of “best treatment,” results similar to the trend that
we are observing in Spain. In Switzerland,[16] CCH use has also been increasing in recent years, especially by younger surgeons,
unlike what happens here, although FSC is still the treatment of choice.
Observing our results, it is curious that in those young patients (under 50 years
of age in our study), CCH is increasing as a technique of choice in both primary and
secondary cases. Although it is true that the clinical cases presented in both primary
and recurrence situations represent relatively simple cases, with the predominant
involvement of a central and major finger of the MCP, young age has been classically
considered as one of the factors of poor prognosis in DD, with more aggressive techniques
being endorsed due to the possibility of recurrences due to the concept of Dupuytren
diathesis established by Hueston.[11] All these regional variations are influenced by regulatory, political, economic
or logistical factors[17]
[18] therefore the data shown in our study cannot be extrapolated to other populations.
The only reference to an article that bases its conclusions on clinical assumptions
and that includes CCH as an alternative treatment is established by McMillan.[2] In his case, the variables analyzed are the thickness of the cord, the severity
of the contracture, the age, and the affected joint. Although this is a study covering
surgeons from various countries, the number of respondents is relatively small (36
surgeons with expertise in hand surgery), so the results may not show the reality
of treatment worldwide. As it is the only study at the international level, in its
discussion it mentions how CCH is most used in the USA and Australia, indicating a
certain predisposition of surgeons in northern Europe to use NA. We agree in his statement
that there is little consistency in the DD treatment recommendations, and the lack
of consensus among the scientific community and our results support this.
Currently the assessment of the need for treatment is often based on the decision
of the patients' need or not,[19] leaving aside the classic assessment of the degree of contracture and making those
assessments for treatment planning, as we saw in the results of the global survey
carried out in Spain. Proof of this is the assessment of pre and post treatment states
with tools such as PROM (Patient Reported Outcome Measures) and PREM (Patient Reported Experience Measures),[20]
[21]
[22]
[23] although like everything with DD there is inconsistency in terms of results and
consensus.[24]
In the recurrences section, the preferred technique in all cases is FSC by far. Drawing
conclusions with the results of four standardized clinical cases is somewhat risky,
but in our opinion we see how the more aggressive techniques are detrimental in favor
of performing a new FSC in the event of recurrence and that CCH is an alternative
in those cases in which it has demonstrated its efficacy, that is, isolated involvement
of the MCP with non-severe contraction in the central radius. Although it is true
that more and more treatment is individualized for the patient, recurrence tends to
be valued as another primary disease (whenever conditions allow), not neglecting any
therapeutic alternative if its use is possible. Recurrence as a workhorse of DD, and
the prospect of maintaining viable tissues in the face of the possibility of new future
involvement, is a determining factor at the time of determining the treatment of recurrences.
As for the limitations of our study, they are the same as those presented in the gross
results of the general survey, that is: the results of a survey that shows only the
subjective opinions of the participants, the lack of uniformity of the responses presented
allows only a partial comparison of the results obtained, fatigue in conducting the
survey, biases produced by unanswered responses, and sample error produced with the
recruitment of participants.
In conclusion, we can say that FSC is still the most used treatment for DD in Spain
based on clinical assumptions. In primary cases, CCH has displaced other techniques
as a second treatment option for DD. The selection of CCH as the primary treatment
was associated with a longer time as a specialist in hand surgery, with choosing CCH
as the most frequently used treatment, and with the age of the patient being less
than 50 years. In recurrences, FSC is, without a doubt, the most widely used technique.
Annex 1 Surveys sent to SECMA partners
SURVEY ON TREATMENT TECHNIQUES FOR DUPUYTREN'S CONTRACTURE
-
1-. How long have you been practicing in your speciality area (not counting residency
period)?
-
A) Less than 3 years
-
B) 3–6 years
-
C) 6–15 years
-
D) More than 15 years
-
2-. And how long have you been working as a hand surgeon?
-
A) Less than 3 years
-
B) 3–6 years
-
C) 6–15 years
-
D) More than 15 years
-
3-. Which autonomous community do you do most of your work in?
-
4-. How old are you?
-
A) Less than 30
-
B) 30–40
-
C) 40- 50
-
D) More than 50
-
5-. Which of the following treatments do you use most in Dupuytren's contracture?
-
A) Collagenase injection
-
B) Partial open fasciectomy
-
C) Dermofasciectomy
-
D) Percutaneous Needle Aponeurotomy
-
E) Other techniques, please specify: _______________
-
6-. Do you have experience using collagenase clostridium histolyticum (CCH) to treat
Dupuytren's contracture?
-
7-. In your opinion, what is the main advantage of CCH? You can choose more than one
option.
-
A) Cost-effective for the healthcare system
-
B) Few treatment-related complications
-
C) Rapid recovery and return to normal life
-
D) Surgical convenience
-
E) All of the above
-
F) None of the above
-
8-. And the main disadvantage(s)?
-
A) Recurrence rate
-
B) Need for more than one dose in patients with multiple cords or several affected
fingers
-
C) Not being able to bill for this procedure in certain hospitals
-
D) Need to see the patient on two separate days
-
E) All of the above
-
F) None of the above
-
9-. Regardless of how often you use different treatments, which treatment do you prefer?
-
A) Collagenase injection
-
B) Partial open fasciectomy
-
C) Dermofasciectomy
-
D) Percutaneous Needle Aponeurotomy
-
E) Other techniques, please specify: _______________
-
10-. Do you use any of these approaches to treat special cases? You can choose more
than one.
-
11-. Has your approach to treating Dupuytren's contracture changed in the last 5 years?
-
12-. In general, how has the approach to treating Dupuytren's contracture changed?
You can choose more than one option.
-
A) CCH is being used more.
-
B) Needle aponeurotomy is being used more.
-
C) Radical surgical approaches are being used less.
-
D) Other: ______________________
-
13-. In routine practice, what would be your preferred treatment for a 75-year-old
patient with a contracture >70° in the proximal interphalangeal joint (PIP) of the
little finger and an uninvolved metacarpophalangeal (MCP) joint?
-
A) Collagenase injection
-
B) Partial open fasciectomy
-
C) Dermofasciectomy
-
D) Percutaneous Needle Aponeurotomy
-
E) Other techniques, please specify: _______________
-
14-. In routine practice, what would be your preferred treatment for a 45-year-old
patient with a 40° contracture in the MCP joint of the middle finger and an uninvolved
PIP joint?
-
A) Collagenase injection
-
B) Partial open fasciectomy
-
C) Dermofasciectomy
-
D) Percutaneous Needle Aponeurotomy
-
E) Other techniques, please specify: _______________
-
15-. In routine practice, what would be your preferred treatment for a patient with
contractures affecting the ring and little finger in which the total angle is >45°
counting the MCP and PIP joints (MCP, PIP or MCP + PIP)?
-
A) Collagenase injection
-
B) Partial open fasciectomy
-
C) Dermofasciectomy
-
D) Percutaneous Needle Aponeurotomy
-
E) Other techniques, please specify: _______________
-
16-. In routine practice, what would be your preferred treatment for a 45-year-old
patient with a nodule in the first phalanx of the middle finger and a contracture
of 30° in the MCP joint and 15° in the PIP joint?
-
A) Collagenase injection
-
B) Partial open fasciectomy
-
C) Dermofasciectomy
-
D) Percutaneous Needle Aponeurotomy
-
E) Other techniques, please specify: _______________
-
17-. In routine practice, what would be your preferred treatment for a 72-year-old
patient previously treated with CCH presenting with a 20° contracture in the MCP joint
and a 40° contracture in the PIP joint of the fifth finger?
-
A) Collagenase injection
-
B) Partial open fasciectomy
-
C) Dermofasciectomy
-
D) Percutaneous Needle Aponeurotomy
-
E) Other techniques, please specify: _______________
-
18-. In routine practice, what would be your preferred treatment for a 50-year-old
patient previously treated with CCH presenting with a 40° contracture in the MCP joint
of the ring finger?
-
A) Collagenase injection
-
B) Partial open fasciectomy
-
C) Dermofasciectomy
-
D) Percutaneous Needle Aponeurotomy
-
E) Other techniques, please specify: _______________
-
19-. In routine practice, what would be your preferred treatment for a 72-year-old
patient previously treated with partial fasciectomy presenting with a 20° contracture
in the MCP joint and a 40° contracture in the PIP joint of the little finger?
-
A) Collagenase injection
-
B) Partial open fasciectomy
-
C) Dermofasciectomy
-
D) Percutaneous Needle Aponeurotomy
-
E) Other techniques, please specify: _______________
-
20-. In routine practice, what would be your preferred treatment for a 50-year-old
patient previously treated with partial fasciectomy presenting with a 40° contracture
in the MCP joint of the fourth finger?
-
A) Collagenase injection
-
B) Partial open fasciectomy
-
C) Dermofasciectomy
-
D) Percutaneous Needle Aponeurotomy
-
E) Other techniques, please specify: _______________
-
21-. Which is the most important factor for you when planning a new treatment for
a patient with recurrent disease?
-
A) Degree of contracture in affected area
-
B) Functional outcome
-
C) Presence of palpable pretendinous cord
-
D) Condition of skin due to previous surgeries
-
22-. Generally speaking, which treatment do you use most for recurrent cases?
-
A) Collagenase injection
-
B) Partial open fasciectomy
-
C) Dermofasciectomy
-
D) Percutaneous Needle Aponeurotomy
-
E) Other techniques, please specify: _______________
-
23-. Supposing that you have performed a partial fasciectomy in a patient with recurrent
disease following initial treatment with CCH, how would define the anatomy of the
surgical area?
-
A) Completely normally
-
B) Altered, making surgery more complicated
-
C) Completely abnormal, with no resemblance to a typical Dupuytren cord
-
D) Variable depending on the case, but with an atypical cord
-
E) I have not seen any cases like this
-
24-. Personally, how would you rate CCH treatment?
-
A) Satisfactory, I use it as a routine procedure.
-
B) Satisfactory, but I still mostly use other techniques.
-
C) I think that CCH has its indications, but personally I don't use it.
-
D) I don't believe that CCH offers any advantages in the treatment of Dupuytren's
contracture.
-
E) Completely unsatisfactory. CCH should be eliminated as an option for Dupuytren's
contracture.
-
25-. In your experience, which treatment offers patients the best satisfaction in
terms of short-term outcomes?
-
A) Collagenase injection
-
B) Partial open fasciectomy
-
C) Dermofasciectomy
-
D) Percutaneous Needle Aponeurotomy
-
E) Other techniques, please specify: _______________
-
26-. And long-term outcomes?
-
A) Collagenase injection
-
B) Partial open fasciectomy
-
C) Dermofasciectomy
-
D) Percutaneous Needle Aponeurotomy
-
E) Other techniques, please specify: _______________
-
27-. How do you normally assess treatment outcomes? (You can choose more than one
option)
-
A) I measure improvements in finger extension.
-
B) I measure improvements in Tubiana classification.
-
C) I use a specific questionnaire (DASH, QuickDASH, MHS, BriefMHS, URAM…)
-
D) I evaluate the patient's subjective satisfaction
-
28-. The landmark CORD studies recommended using up to three CCH injections to achieve
full extension. Nonetheless, for reasons mainly related to cost-effectiveness and
availability, several authors have published reports on the use of single doses, regardless
of outcomes. In light of the above, what is your position on this?
-
A) I started out using the recommended CORD protocol, but no longer use it.
-
B) I started out using the recommended CORD protocol and still use it.
-
C) I have never used the CORD protocol.
-
29-. Have any of your patients developed complications that you would classify as
serious as a result of CCH treatment?
-
30-. There have been several recent reports of authors using doses higher than the
recommended dose of 0.58 mg for CCH injections? Do you ever alter the recommended
dose? You can choose more than one option.
-
A) No, I always use the standard dose and dispose of any remaining liquid.
-
B) I normally use a higher dose, i.e., I use the full vial.
-
C) I have sometimes injected two doses into the same finger or hand to complete the
treatment in one session.
-
D) I have sometimes administered injections in both hands in patients with bilateral
involvement.
