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The authors [1] are to be congratulated on demonstrating that, when
readers view radiographs at 2 time-points simultaneously, they observe the
relative change in JSN and/or erosions between the radiographs rather than
the absolute state of the joints. Thus, they assign separate scores to the
2 radiographs to reflect this observed change, rather than scoring the 2
radiographs independently. This truth is...
The authors [1] are to be congratulated on demonstrating that, when
readers view radiographs at 2 time-points simultaneously, they observe the
relative change in JSN and/or erosions between the radiographs rather than
the absolute state of the joints. Thus, they assign separate scores to the
2 radiographs to reflect this observed change, rather than scoring the 2
radiographs independently. This truth is evidenced in the smaller variance
of the ‘change’ data compared to that of the traditional ‘difference’ data
[2-4]. Distinct acronyms, SDC and SDD, for smallest detectable change and
smallest detectable difference, usefully distinguish cut-offs determined
from the two datasets.
But, when the precision of data is improved, the use of appropriate
statistics becomes critical.
In this paper, SDC is determined as 2.85 using two readers and
chronological scoring. In their earlier paper (5), SDC was determined as
1.7 and 2.4 using a single reader, chronological and paired scoring,
respectively. Historical estimates of SDD are in the range 4.7 to 11.0 [2-
4].
The validity of the statistics employed in the earlier paper [5]
caused us unease but there was no data or cumulative ‘probability’ plot
[6] against which to rationalise our concerns. In the present paper, the
situation is remedied by explicitly giving the data for the 10 patients
considered, Table 1, and, although the study size is small, it rather
neatly proves the point. For 3 of the patients (30%), the difference in
score change recorded by the 2 readers exceeds SDC, whereas statistically
this number should be around 5%. Further, 2 of the 10 patients (20%) would
have been differently assigned as progressors / non-progressors by the two
readers.
Hence, the authors rightly find variation in score change data more
appropriate than variation in individual score data, but extrapolation to
SDC requires more careful consideration of the data distribution and its
correlation to the underlying score change. For this non-normally
distributed data, the 97th percentile may be a more meaningful cut-off,
but the influences of patient population and different readers’
assessments of change should also be considered more thoroughly. From the
data, there is little justification for lowering the SDC (or SDD) cut-off
below 4.5.
References
(1). Bruynesteyn K, Boers M, Kostense P, van der Linden S, van der
Heijde D. Deciding on progression of joint damage in paired films of
individual patients: smallest detectable difference or change? Ann Rheum
Dis 2004; Published Online First 29/07/2004. doi:10.1136/ard.2003.018457.
(2). Bruynesteyn K, van der Heijde D, Boers M, Saudan A, Peloso P,
Paulus H et al. Determination of the minimal clinically important
difference in rheumatoid arthritis joint damage of the Sharp/van der
Heijde and Larsen/Scott scoring methods by clinical experts and comparison
with the smallest detectable difference. Arthritis Rheum 2002; 46:913-920.
(3). Lassere MN, van der Heijde D, Johnson K, Bruynesteyn K, Molenaar
E, Boonen A et al. Robustness and generalizability of smallest detectable
difference in radiological progression. Journal of Rheumatology 2001;
28:911-913.
(4). Landewé R, Boers M, van der Heijde D. How to interpret
radiological progression in randomized clinical trials? Rheumatology
(Oxford) 2003; 42:2-5.
(5). Bruynesteyn K, Landewé R, van der Linden S, van der Heijde D.
Radiography as primary outcome in rheumatoid arthritis: acceptable sample
sizes for trials with 3 months follow-up. Ann Rheum Dis 2004; Published
Online First 22/03/2004. doi:10.1136/ard.2003.014043.
(6). Landewé R, van der Heijde D. Radiographic progression depicted by
probability plots: presenting data with optimal use of individual values.
Arthritis Rheum 2004; 50:699-706.
I was surprised to find in the current issue of Annals of the
Rheumatic Diseases that the lead editorial (“Leader” in British English)
was written by the co-authors of one of the manuscripts reviewed in the
same editorial (1,2).
Traditionally, readers of the peer-reviewed
biomedical literature have come to expect that editorialists bring an
unbiased perspective to the papers or topics bei...
I was surprised to find in the current issue of Annals of the
Rheumatic Diseases that the lead editorial (“Leader” in British English)
was written by the co-authors of one of the manuscripts reviewed in the
same editorial (1,2).
Traditionally, readers of the peer-reviewed
biomedical literature have come to expect that editorialists bring an
unbiased perspective to the papers or topics being reviewed. It would
seem to be a fundamental violation of that implicit trust to permit
authors to report their own findings and then concurrently to submit an
editorial which compares their work with the other papers in the field.
An example of the bias that may result from this apparent conflict of
interest is that the importance of the findings may be inflated. Here,
for example, the editorial is entitled “A historic issue of the Annals:
three papers examine paracetamol in osteoarthritis,” thus implying that
these are epochal papers of profound historic gravity; close examination
of the material, however, leaves one substantially less enthusiastic that
major breakthroughs have occurred. Moreover, although in the body of the
editorial the authors mention the extremely short trial periods employed
by each of the positive paracetamol studies, they conclude that “…the
aggregated research data still support paracetamol as being more effective
than placebo in relieving pain of large joint OA.” As OA is a chronic
disease characterized by recurrent pain over years, findings of efficacy
at one week and 3 months can hardly be considered compelling evidence of
efficacy in relieving the pain of OA.
The point is not that paracetamol
is ineffective; rather, its efficacy for chronic pain relief remains
unstudied and unclear.
Reference
(1). Neame R, Zhang W, Doherty M: A historic issue of the Annals:
three papers examine paracetamol in osteoarthritis. Ann Rheum Dis 2004;
63:897-900.
2. Zhang W, Jones A, Doherty M: Does paracetamol (acetaminophen) reduce
the pain of osteoarthritis?: a meta-analysis of randomized controlled
trials. Ann Rheum Dis 2004; 63:901-907.
We thank Dr Chirinos for his interest in our article and appreciate
his comments [1].
We would disagree, however, with his suggestion that paired t-test is
only appropriately used to analyze repeated measurements before and after
an intervention in a single sample population. In our study the
statistical analysis by a paired t-test was determined before data
collection and based on the stu...
We thank Dr Chirinos for his interest in our article and appreciate
his comments [1].
We would disagree, however, with his suggestion that paired t-test is
only appropriately used to analyze repeated measurements before and after
an intervention in a single sample population. In our study the
statistical analysis by a paired t-test was determined before data
collection and based on the study design of cases and controls being
closely matched for five variables (sex, age, height, mean peripheral
blood pressure and heart rate).
We are very happy to provide the probability values for the
difference of the augmentation index between rheumatoid cases and healthy
controls, using paired/ unpaired statistical tests for normally and not
normally distributed data. These were 0.0284, 0.0245, 0.0422 and 0.0432
for paired t-test, Wilcoxon (matched pairs) test, unpaired t-test and Mann
-Whitney test, respectively.
The difference remains statistically significant and we would
therefore maintain that our study is the first to indicate that arterial
stiffness is indeed increased in patients with rheumatoid arthritis, a
finding which has recently been confirmed both in patients with rheumatoid
arthritis [2] and those with systemic vasculitis [3].
References
(1). Chirinos JA. Is arterial stiffness increased in rheumatoid
arthritis? Ann Rheum Dis 24 June 2004 (eLetter)
(2). Wong M, Toh L, Wilson A, Rowley K, Karschimkus C, Prior D, Romas
E, Clemens L, Dragicevic C, Harianto H, Wicks I, McColl G, Best J, Jenkins
A. Reduced arterial elasticity in rheumatoid arthritis and the
relationship to vascular disease risk factors and inflammation. Arthritis
Rheum 2003;48:81-89.
(3). Booth AD, Wallace S, McEniery C M, Yasmin, Brown J, Jayne DR,
Wilkinson IB. Inflammation and arterial stiffness in systemic vasculitis:
a model of vascular inflammation. Arthritis Rheum 2004;50:581-588.
We read with interest the article by Shanahan et al [1] on
suprascapular nerve blocks and the accompanying editorial by Hall and
Buchbinder [2]. It is gratifying to know that in this context the indirect
method of needle placement produces a similar outcome to the
radiologically-guided method. However, we would like to point out an
important methodological flaw in the study.
We read with interest the article by Shanahan et al [1] on
suprascapular nerve blocks and the accompanying editorial by Hall and
Buchbinder [2]. It is gratifying to know that in this context the indirect
method of needle placement produces a similar outcome to the
radiologically-guided method. However, we would like to point out an
important methodological flaw in the study.
The patients who received injections via the landmark approach were
injected with 40mg of methylprednisolone and 10 mls of 0.5% bupivacaine,
whereas those who underwent CT-guided injection received 40mg of
methylprednisolone and 3 mls of 0.5% bupivacaine. Previous studies have
shown that suprascapular nerve blocks produce effective analgesia for a
variety of painful shoulder conditions, including frozen shoulder [3],
rotator cuff lesions [4], and rheumatoid arthritis [5]. Fundamentally,
however, in a double-blind study of 58 rheumatoid shoulders, suprascapular
nerve block with bupivacaine alone has been shown to be as effective as
bupivacaine plus methylprednisolone at improving pain, stiffness, and
range of movement [6]. The authors of this study concluded that the
addition of methylprednisolone conferred no additional benefit.
Thus, if one concludes from this that the local anaesthetic is the
active ingredient, Shanahan’s two patient groups were given different
doses of the same drug (10 mls compared with 3 mls). Consequently the
study may have underestimated the effect of the CT-guided approach.
References
(1). Shanahan EM, Smith MD, Wetherall M et al. Suprascapular nerve
block in chronic shoulder pain: are the radiologists better? Ann Rheum Dis
2004;63:1035-1040
(2). Hall S, Buchbinder R. Do imaging methods that guide needle
placement improve outcome? Ann Rheum Dis 2004;63:1007-1008
(3). Dahan TH, Fortin L, et al. Double blind randomized clinical trial
examining the efficacy of bupivacaine suprascapular nerve blocks in frozen
shoulder. J Rheumatol. 2000 Jun;27(6):1464-9.
We read with interest the article by Rudwaleit et al [1]. "How to
diagnose early spondyloarthropathy" and "Comment in leading" by Barkham et al
[2]. We agree that MRI, particullary with the special techniques, could be
very helpful in detecting signs of sacroiloiitis not yet visible on
standard radiographs.
MRI is most sensitive (95 %)and superior to
Quantitative SI scintigraphy...
We read with interest the article by Rudwaleit et al [1]. "How to
diagnose early spondyloarthropathy" and "Comment in leading" by Barkham et al
[2]. We agree that MRI, particullary with the special techniques, could be
very helpful in detecting signs of sacroiloiitis not yet visible on
standard radiographs.
MRI is most sensitive (95 %)and superior to
Quantitative SI scintigraphy (48 %) or conventional radiography (19 %)[3].
Although MRI scoring system for sacroiliac and spinal pathology have
developed still remains same concern about reliability and validity of
MRI, and its implications to prognosis and outcome. High costs and
availability of MRI are limiting factors for the widespread use.
Standard
radiographs, a single x-ray of the pelvis, or barsony technique still
remain common investigational method. A single AP film of the pelvis
showing inflammatory changes in the sacroiliac joints has a 55
sensitivity for spondyloarthropathy. Where changes are equivocal
additional techniques can increase sensitivity to 80 % [4]. Unfortunatelly
additional x-ray films increase the dose of radiation and costs.
In the
last 10 years we performed diascopy method in the standing position. With
this technique we can better visualis ventral and dorsal intraarticular
space and with the greater accuracy and lower degree of the radiation, the
diagnosis of the sacroiliitis can be made. In the follow up of the
patients it is possible to perform the same position [5].
References
(1). Rudwaleit M, van der Heijde D, Khan MA, Braun J, Sieper J. How to
diagnose axial spondyloarthritis early. Ann Rheum Dis 2004;63.535-543.
(2). Barkham N, Marzo-Ortega H, Mcgonagle D, Emery P. How to diagnose axial
spondyloarthropathy early. Ann Rheum Dis 2004;63:471-472.
(3). Blum U, Buitrago-Tellez C, Mundinger A et al. Magnetic resonance
imaging (MRI) for detection of active sacroiliitis- a prospective study
comparing conventional radiograph, scintigraphy, and contrast enhanced
MRI. J Rheumatol 1996;23:2107-2115.
(4). Yelland M. Diagnostic imaging for back pain. Aus Fam Physician
2004;33:415-419.
(5). Potoèki K, Æurkoviæ B, Babic-Naglic D. Advantage of diascopy of the
sacroiliac joints versus barsony x-ray views. J Rheumatol
1998;25(suppl.54):42 (abst.)
We would like to thank Dr. Kumar for his interest in our report. He
was very correct to point out the possibility of chronic subdural hematoma
based on the CT appearance. In fact, chronic subdural effusion was the
top differential diagnosis raised by our radiologist at that juncture.
Simultaneous and subsequent follow-up MRI scans of the brain in our
patient confirmed significant and diff...
We would like to thank Dr. Kumar for his interest in our report. He
was very correct to point out the possibility of chronic subdural hematoma
based on the CT appearance. In fact, chronic subdural effusion was the
top differential diagnosis raised by our radiologist at that juncture.
Simultaneous and subsequent follow-up MRI scans of the brain in our
patient confirmed significant and diffuse loss in brain volume, together
with a small rim of effusion in the subdural space, being more prominent
on the right side. Thus, the CT appearance was not mainly contributed by
subdural effusion alone.
The etiology and significance of this subdural
effusion was unclear and it failed to resolve after 12 months and despite
immunosuppressive therapy. However, the main focus and interest of our
case report was the progressive atrophy of the brain and the spinal cord,
which has hitherto been undescribed in Chinese patients with systemic
lupus erythematosus.
We read with interest the report of the WOSERACT trial [1] that
compared the addition of 7 mg daily prednisolone or placebo to
sulfasalazine in early rheumatoid arthritis (RA). There are a number of
important aspects of the trial which have been dealt with well: the sample
size is adequate; appropriate attention has been paid to confounders; two
separate and independent readers scored the radiograph...
We read with interest the report of the WOSERACT trial [1] that
compared the addition of 7 mg daily prednisolone or placebo to
sulfasalazine in early rheumatoid arthritis (RA). There are a number of
important aspects of the trial which have been dealt with well: the sample
size is adequate; appropriate attention has been paid to confounders; two
separate and independent readers scored the radiographs; the two year
trial was of adequate length and there was satisfactory completeness of
the data. Given these strengths, it is all the more disappointing that the
results of the main outcome, radiographic damage, cannot be adequately
interpreted as they are reported. Indeed, the validity of these results is
open to serious doubt. We feel there is a real possibility of a Type II
statistical error (missing a true difference between treatment arms).
There are two (possibly three) reasons for this.
First, there is an absolute difference between the x-ray scores of
the two readers of about 40 Sharp points. This raises strong doubts over
the proficiency of either or both readers. In early RA Sharp scores are
typically very low, with most patients scoring 0 and only a few with
higher scores. Scores of 80, let alone 159 after one year of RA are
without precedent in the literature, and even the baseline medians of 6
and 8 recorded for the conservative reader are quite high. In contrast to
the authors, we cannot be ‘reassured’ by their assertion that ‘the change
in x-ray score was consistent between the two readers’: these data are
simply not provided in the report. All we have is an unsatisfactory
correlation of absolute scores between readers of 0.8 (where in most
trials the intra-class correlation coefficient [the recommended and more
severe test of reliability between readers] exceeds 0.9), and the
comparison between readers of differences between the median start and end
scores in the two study groups. Unfortunately the difference between
medians at baseline and endpoint is not the same as the median change.
Second, most trials choose two readers that read either with sequence
known or unknown (the jury is still out which is the preferred method),
and report the mean of these two readings. This report has two readers
each of whom uses a different one of these options and this makes it
impossible to pool the results. Also, even with sequence unknown films
should be read as sets (all films belonging to one patient assessed
simultaneously), not totally at random. Reading totally at random strongly
decreases the signal-to-noise ratio [2]. Which method did the ‘random’
reader apply exactly?
A third concern is with the analysis, although this may only be a
question of the way the data are presented. Although the authors state the
main outcome measure is the change in radiographic damage, they only
report medians and ranges of the absolute scores in the groups. From our
reading of the report, we fear the analysis has (statistically) compared
the distributions of these absolute scores rather than their changes.
This is an important study, and has the potential to add valuable
information to our understanding of the best way to treat RA, but in its
present form the radiographic results are more likely to cloud the issues
than clarify them. We suggest that the radiographs are made available to
be re-read by two new, experienced readers with either the sequence known
or unknown to both. We also suggest that the analysis should present the
median, range etc. of the changes in each group, and the test of the
difference between these. (If they have a skewed distribution, then either
transformation before parametric analysis or the use of non-parametric
methods would be the best way to compare the groups.)
There are other difficulties with the study, although these are less
important than the essential concerns noted above. For example, we are
baffled by the statement in the introduction that the COBRA combination
[3] ‘showed radiological advantage over sulfasalazine alone but the study
was not powered to detect differences in x-ray change’. In fact, the
differences in x-ray change were among the COBRA study’s key findings, and
have since been shown to increase over time [4]. So the study was not only
adequately powered but also showed an unexpectedly large effect.
The authors diminish the value of the report by inappropriate
interpretation of their secondary data, especially on the adverse effects.
In the discussion they comment, ‘While observed toxicity from
corticosteroids in terms of hypertension, weight gain, and osteoporosis
could be reduced by active assessment and prompt intervention, there is no
room for complacency’. However, in their results section they report that,
‘Low dose aspirin and treatment for ischaemic heart disease remained
similar, whereas the use of anti-hypertensive agents increased in both
groups, as did prescription of lipid lowering agents. The use of any
treatment for osteoporosis also increased in both groups’. In fact there
was no difference between the groups and thus there was no observed
toxicity from glucocorticoids in their study. Further, the authors make no
comment on their observation that (many) more patients stopped
sulfasalazine treatment due to side effects in the placebo than in the
glucocorticoid group.
In relation to weight gain, inappropriate attention to within-group
changes leads the authors to conclude body weight ‘increased
significantly’ in the glucocorticoid group (median gain, 4 kg), with only
a ‘borderline increase’ in the placebo group (median gain, 3 kg). Body
mass index is handled in the same way. However, the only really relevant
comparisons, those between groups, do not even show a trend to
significance (all p values at or above 0.10). As with the radiographic
findings, the presentation of the table suggests endpoint results were
compared rather than change scores.
Our interpretation of the clinical results contradicts that of the
investigators, and we conclude that the effects on symptoms are in line
with previous reports of limited and temporary advantages for disease
activity, blunting of sulfasalazine toxicity, and extremely limited side
effects when appropriate caution is applied. It is not possible to
adequately assess the main results on x-ray progression, which are at
variance with several previously published studies [3-8] and we urge the
authors to allow a second read of the radiographs so that their important
dataset can be added to the existing evidence.
References
(1). Capell HA, Madhok R, Hunter JA, et al. Lack of radiological and
clinical benefit over two years of low dose prednisolone for rheumatoid
arthritis: results of a randomised controlled trial. Ann Rheum Dis 2004;
63: 797–803.
(2). Van der Heijde D, Boonen A, Boers M, Kostense P, van Der Linden S.
Reading radiographs in chronological order, in pairs or as single films
has important implications for the discriminative power of rheumatoid
arthritis clinical trials. Rheumatology (Oxford) 1999; 38: 1213-20.
(3). Boers M, Verhoeven AC, Markusse HM, van de Laar MA, Westhovens R,
van Denderen JC, et al. Randomised comparison of combined step-down
prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in
early rheumatoid arthritis [see comments] [published erratum appears in
Lancet 1998 Jan 17;351(9097):220]. Lancet 1997; 350: 309-18.
(4). Landewe RB, Boers M, Verhoeven AC, Westhovens R, van De Laar MA,
Markusse HM, et al. COBRA combination therapy in patients with early
rheumatoid arthritis: Long-term structural benefits of a brief
intervention. Arthritis Rheum 2002; 46: 347-56.
(5). Kirwan JR, Arthritis and Rheumatism Council Low Dose Glucocorticoid
Study Group. The effect of glucocorticoids on joint destruction in
rheumatoid arthritis. N Engl J Med 1995; 333: 142-146.
(6). Hickling P, Jacoby RK, Kirwan JR. Joint destruction after
glucocorticoids are withdrawn in early rheumatoid arthritis. Br J
Rheumatol 1998; 37: 930-936.
(7). Rau R, Wassenberg S, Zeidler H. Low dose prednisolone therapy
(LDPT) retards radiographically detectable destruction in early rheumatoid
arthritis--preliminary results of a multicenter, randomized, parallel,
double blind study. Z Rheumatol. 2000;59 (Suppl 2): II/90-6.
(8). van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, Bijlsma JW.
Low-dose prednisone therapy for patients with early active rheumatoid
arthritis: clinical efficacy, disease-modifying properties, and side
effects: a randomized, double-blind, placebo-controlled clinical trial.
Ann Intern Med. 2002; 136(1): 1-12.
Feletar and colleagues have reported an interesting study concerning
treatment with infliximab of refractory psoriatic arthritis.[1]
They
found a high incidence of liver toxicity, that occurred in 4/16 patients
and led to discontinuation of infliximab in three patients. These data are
rather surprising as to date hepatic toxicity has not been found to be a
major concern with infliximab and ot...
Feletar and colleagues have reported an interesting study concerning
treatment with infliximab of refractory psoriatic arthritis.[1]
They
found a high incidence of liver toxicity, that occurred in 4/16 patients
and led to discontinuation of infliximab in three patients. These data are
rather surprising as to date hepatic toxicity has not been found to be a
major concern with infliximab and other anti-TNF agents. However, there
are some doubts about the causative role of infliximab in liver
disturbances observed in patients treated by Feletar et al. Firstly, two
of them were concomitantly treated with methotrexate and one of these two
had also a significant alcohol intake. Methotrexate hepatotoxicity is a
well known problem, that is more frequently observed in psoriatic patients[2] and may be enhanced by excessive alcohol consumption. Secondly, the
negativity of viral hepatitis serology is reported only for one patient
and we have no data concerning the other three patients. This could be a
significant point as a high prevalence of HCV infection has been reported
in patients with psoriatic arthritis [3] and although there are some
encouraging data on the safety of anti-TNF agents in patients with chronic
viral hepatitis,[4,5] this item is still debatable.[6] In conclusion, it
is not possible to rule out that liver disturbances observed by Feletar et al. could be due to other factors than infliximab therapy. Moreover,
baseline screening for chronic hepatitis B or C infection should probably
be reccomended before starting therapy with infliximab and other anti-TNF
agents.
References
1) Feletar M, Brockbank JE, Schentag CT, et al. Treatment of refractory
psoriatic arthritis with infliximab: a 12 month observational study of 16
patients. Ann Rheum Dis 2004; 63: 156-61.
2) Whiting-O'Keefe QE, Fye KH, Sack KD. Methotrexate and histologic
hepatic abnormalities: a meta-analysis. AM J Med 1991; 90: 711-16.
3) Taglione E, Vatteroni ML, Martini P; et al. Hepatitis C virus
infection: prevalence in psoriasis and psoriatic arthritis. J Rheumatol
1999; 26: 370-2.
4) Peterson JR, Hsu FC, Simkin PA, et al. Effect of tumour necrosis factor
alfa antagonists on serum transaminases and viraemia in patients with
rheumatoid arthritis and chronic hepatitis C infection. Ann Rheum Dis
2003; 62: 1078-82.
5) Oniankitan O, Duvoux C, Challine D, et al. Infliximab therapy for
rheumatic diseases in patients with chronic hepatitis B or C. J Rheumatol
2004; 31: 107-9.
6) Michel M, Duvoux C, Hezode C, et al. Fulminant hepatitis after
infliximab in a patient with hepatitis B virus treated for an adult onset
Still's disease. J Rheumatol 2003; 30: 1624-5.
It was interesting to read the recent report of systemic lupus
erythematosus associated with atrophy of brain and spinal cord.[1]
However, I would like to make certain observations.
Computerised tomography (CT) of brain presented in the report showed
bilateral hypodense lesions in the frontal and parietal regions. Though
Mok et al attribute this CT appearance to diffuse cerebral atrophy; othe...
It was interesting to read the recent report of systemic lupus
erythematosus associated with atrophy of brain and spinal cord.[1]
However, I would like to make certain observations.
Computerised tomography (CT) of brain presented in the report showed
bilateral hypodense lesions in the frontal and parietal regions. Though
Mok et al attribute this CT appearance to diffuse cerebral atrophy; other
possibilities too need to be considered in this setting. Chronic subdural
haematoma (SDH) is the foremost among these. In a recent report, all
chronic SDH appeared hypodense on CT, and were predominantly located in
the parietal and frontal regions,[2] which is similar to the case
presented by Mok et al. Hypodensity in chronic SDH could occur due to
gradual absorption of erythrocytes from the haematoma, typically with
haemoglobin concentration falling below 15 mg/dl.[3] Another mechanism
responsible for differing densities of acute and chronic SDH could be
related to their varying compositions. In a pathological study, hyperdense
picture on CT resulted with haematomas predominantly consisting of
erythrocytes and erythrocyte-fibrin component, whereas hypodense picture
resulted with haematomas consisting of fibrin and inflammatory cells.[4]
It should also be noted that bilateral chronic SDH is a recognized
complication of vasculitic syndromes and could even be a presenting
symptom.[5] Moreover, SLE too could produce focal angiitis of a cerebral
artery with secondary aneurysm formation, rupture of which leads to SDH.[6]
In conclusion, though I agree with Mok et al. that cerebral atrophy is
a known finding in patients with SLE, chronic SDH is a distinct
possibility in patients with bilateral fronto-parietal hypodense lesions
on CT.
References
1. Mok CC, Mak A, Tsui EYK. Shrinking central nervous system in
systemic lupus erythematosus. Ann Rheum Dis. 2004; 63:603-4.
2. Agunloye AM, Adeyinka AO, Obajimi MO, Malomo A, Shokunbi MT.
Computerised tomography of intracranial subdural haematoma in Ibadan. Afr
J Med Med Sci. 2003; 32:235-8.
3. Ito H, Maeda M, Uehara T, Yamamoto S, Tamura M, Takashima T.
Attenuation values of chronic subdural haematoma and subdural effusion in
CT scans. Acta Neurochir (Wien). 1984; 72:211-7.
4. Poljakovic Z, Petrusic I, Kalousek M, Brzovic Z, Jadro-Santel D.
Correlative pathology of subdural hematoma with computerized tomography.
Neurol Croat. 1991; 41:21-32.
5. Shiotani A, Mukobayashi C, Oohata H, Yamanishi T, Hara T, Itoh H,
et al. Wegener's granulomatosis with dural involvement as the initial
clinical manifestation. Intern Med. 1997; 36:514-8.
6. Sakaki T, Morimoto T, Utsumi S. Cerebral transmural angiitis and
ruptured cerebral aneurysms in patients with systemic lupus erythematosus.
Neurochirurgia (Stuttg). 1990; 33:132-5.
We read with interest the recent article of Jonsdottir and
colleagues,[1] in which the authors describe an increase in the rate of
ACLA in RA patients who received any anti-TNF therapy; a potentially very
interesting finding. However, this article commits multiple errors in
scientific methodology and we are concerned that the presumed apparent
correlations of ACLA are actually the result of inherent b...
We read with interest the recent article of Jonsdottir and
colleagues,[1] in which the authors describe an increase in the rate of
ACLA in RA patients who received any anti-TNF therapy; a potentially very
interesting finding. However, this article commits multiple errors in
scientific methodology and we are concerned that the presumed apparent
correlations of ACLA are actually the result of inherent bias in study
design, flawed analyses and an overinterpretation of a limited registry
database.
Of particular concern, without specification of the selection criteria, a
subgroup of patients on TNF-á antagonists in STURE was analyzed. A small
group of 121 patients has been extracted from a much larger registry
experience - not to suggest a hypothesis generating observation – but to
support a very far reaching headline and conclusion. The increase in the
rate of ACLA in the reported patients who received any anti-TNF therapy
appears to be real and quite interesting. However, following that
observation, this article commits a variety of serious errors in
scientific methodology and reporting. As of March 2004, the Swedish
Rheumatology Registry had entered 2334 patients treated with biologics,
including 1715 treated with infliximab.– it is not explained how the
subgroup of 121 patients was selected. Only a subgroup of this
subgroup, i.e. 44 of the 64 infliximab-treated patients, is then utilized
to begin exploring the relationship of ACLA formation to other clinical
outcomes, such as ACR response and infusion reactions. No explanation is
provided as to why 20 of the 64 patients were not utilized in the
analysis. No information is given regarding other known predictors of
these outcomes, nor whether a proper analysis was done to determine if
this was a major independent risk factor. What was done to adjust for
baseline variables? Why wasn’t a proper regression analysis done? Why is
there no disclaimer stating that the presence of ACLA cannot be assumed to
have a causal relation to these outcomes based on these exploratory
analyses?
Of greater concern, comparative statements are made throughout the
article regarding the comparable effects in etanercept-treated patients –
but the data to support these statements are not shown! This is
remarkable and it is hard to understand how an article could be published
without such information being provided. How many of the 57 etanercept-
treated patients had this information available? Why is their data not
presented? How was the subset of 57 etanercept-treated patients selected
from the much larger number in the registry? Importantly, there is no
mention made that this registry does not randomize patients to infliximab
vs. etanercept and no attempt is made to discuss their comparability. The
presumed, not displayed, differences between infliximab and etanercept
could have been caused by imbalances in baseline, and confounding
variables between the infliximab-treated and etanercept-treated group. As
just one observation, there is a great imbalance in the use of
methotrexate at baseline in infliximab and etanercept groups (90% vs. 50%,
respectively), possibly indicating differences in the disease severity of
the two groups. Therefore, it is of particular concern that definitive
statements are made throughout the article regarding the comparable
effects in etanercept-treated patients – but the data to support these
statements are not shown, nor do the baseline data shown support their
comparability.
A registry database can potentially provide certain data very well,
e.g. large real world safety outcomes. It can also be a good source for
hypothesis generating exploratory observations. However, registry data is
rarely able to answer questions in the way a well designed randomized
trial can. This report appears to represent the worst type of data
dredging- a concern that makes people wary of the use of registry data
for mischief making. In this case that concern is warranted.
Referenc
1. Jonsdottir T, Forslid J, Van Vollenhoven AM, Harju A, Brannemark
SA, Klareskog L, et al. Treatment with TNF-{alpha} antagonists in patients
with rheumatoid arthritis induces anticardiolipin antibodies (ACLA): ACLA
predict worse clinical outcome with infliximab and more frequent treatment
limiting infusion reactions. Ann Rheum Dis 2004.
Dear Editor,
The authors [1] are to be congratulated on demonstrating that, when readers view radiographs at 2 time-points simultaneously, they observe the relative change in JSN and/or erosions between the radiographs rather than the absolute state of the joints. Thus, they assign separate scores to the 2 radiographs to reflect this observed change, rather than scoring the 2 radiographs independently. This truth is...
Dear Editor,
I was surprised to find in the current issue of Annals of the Rheumatic Diseases that the lead editorial (“Leader” in British English) was written by the co-authors of one of the manuscripts reviewed in the same editorial (1,2).
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Dear Editor,
We thank Dr Chirinos for his interest in our article and appreciate his comments [1].
We would disagree, however, with his suggestion that paired t-test is only appropriately used to analyze repeated measurements before and after an intervention in a single sample population. In our study the statistical analysis by a paired t-test was determined before data collection and based on the stu...
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Dear Editor
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Dear Editor
We read with interest the recent article of Jonsdottir and colleagues,[1] in which the authors describe an increase in the rate of ACLA in RA patients who received any anti-TNF therapy; a potentially very interesting finding. However, this article commits multiple errors in scientific methodology and we are concerned that the presumed apparent correlations of ACLA are actually the result of inherent b...
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