I read the article by Hua et al.1 that was published in this journal with great interest. The authors provided an excellent review of the literature regarding the clinical efficacy and toxicity of glucocorticoids (GCs) in rheumatoid arthritis (RA). The review included comprehensive discussion about the efficacy of GCs as a bridging therapy in addition to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) based on the rapid onset of action of these drugs.1 The authors advocate that because even low-doses of GCs might have adverse effects, administration of these drugs should be restricted to the lowest dose for the shortest time.1 The first part about the effectiveness of GCs was well documented and convincing; however, the second part about the safety of these drugs seemed a little less convincing. This might be attributed to the fact that a small number of studies on the safety of GCs have been published. In particular, little evidence regarding bone-related adverse effects has been presented. We have obtained very preliminary data in our hospital about the effects of GCs on bone health, including fractures and osteoporosis, and would like to contribute these as a comment.
We retrospectively reviewed the medical records of 883 patients with RA who visited our hospital in 2018. Of these, 364 patients (41.2%, Figure 1A) were prescribed GCs. At the last visits in 2018, appro...
I read the article by Hua et al.1 that was published in this journal with great interest. The authors provided an excellent review of the literature regarding the clinical efficacy and toxicity of glucocorticoids (GCs) in rheumatoid arthritis (RA). The review included comprehensive discussion about the efficacy of GCs as a bridging therapy in addition to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) based on the rapid onset of action of these drugs.1 The authors advocate that because even low-doses of GCs might have adverse effects, administration of these drugs should be restricted to the lowest dose for the shortest time.1 The first part about the effectiveness of GCs was well documented and convincing; however, the second part about the safety of these drugs seemed a little less convincing. This might be attributed to the fact that a small number of studies on the safety of GCs have been published. In particular, little evidence regarding bone-related adverse effects has been presented. We have obtained very preliminary data in our hospital about the effects of GCs on bone health, including fractures and osteoporosis, and would like to contribute these as a comment.
We retrospectively reviewed the medical records of 883 patients with RA who visited our hospital in 2018. Of these, 364 patients (41.2%, Figure 1A) were prescribed GCs. At the last visits in 2018, approximately 80% of the patients who were receiving GCs used 5 mg/day or less of GCs; the mean dosage was 4.1 mg/day (Figure 1B). Vertebral fractures were more frequently observed in patients who were receiving GCs than in those not receiving them (p = 0.028, Figure 1C). The incidence of non-vertebral fractures was the same regardless of GC use (Figure 1D). Osteoporosis, defined as <80% of the young-adult mean bone mineral density of the lumber spine or left femoral neck, was diagnosed in 195 patients (22.1%). The incidence of osteoporosis was twice as high among patients who were receiving GCs compared with those who were not receiving them (Figure 1E). The effect of GCs on osteoporosis was observed in both male and female patients (Figure 1F).
Figure is available upon request.
Patients with RA are at a high risk of fracture, and the use of GCs for more than 3 months is associated with an increased risk of vertebral fracture regardless of the dosage.2,3 Our data were very preliminary, and thus, it had several limitations. For example, we did not consider differences in patient backgrounds. However, this simplified retrospective study supports, at least in part, the concept that GCs should be used at minimal dosage and for the shortest duration possible.1
References
Hua C, Buttgereit F, Cobe B. Glucocorticoids in rheumatoid arthritis: current status and future studies. RMD Open 2020;6(1):e000536.
Xue AL, Wu SY, Jiang L, Feng AM, Guo HF, Zhao P. Bone fracture risk in patients with rheumatoid arthritis: A meta-analysis. Medicine (Baltimore) 2017;96:e6983.
Ozen G, Pedro S, Wolfe F, Michaud K. Medications associated with fracture risk in patients with rheumatoid arthritis. Ann Rheum Dis 2019;78:1041–1047.
Acknowledgments
The study protocol was approved by the Ethics Committee of the Osaki Citizen Hospital (No. 20190822-25) and performed in accordance with the Declaration of Helsinki.
This survey demonstrated that a significant proportion of clinicians
use smartphones to share clinical information. While this rightly raises
concerns over confidentiality and makes headlines in the press it is
important to question why this situation has arisen. As Mobasheri and
colleagues demonstrated, ownership is near ubiquitous among medical staff
and this affords availability and immediacy of access. It is hardly...
This survey demonstrated that a significant proportion of clinicians
use smartphones to share clinical information. While this rightly raises
concerns over confidentiality and makes headlines in the press it is
important to question why this situation has arisen. As Mobasheri and
colleagues demonstrated, ownership is near ubiquitous among medical staff
and this affords availability and immediacy of access. It is hardly
surprising that medics should choose to use tools which improve their
efficiency and the care they deliver to their patients. If there is a
faster or easier way to answer a clinical question than using the legacy
IT systems and software that many trusts provide then many will use it.
It would appear that the NHS lags behind the private sector in having
the appropriate software tools and as a result many individuals find their
own solutions. There is an abundance of software available, much of it
free, which enhances productivity. Rather than limiting staff to safe but
basic tools, hospital IT departments would do well to explore these
available options and facilitate the use of modern collaborative software
to optimise workflow and improve patient care.
Thank you for your interest in our work. Your letter allows us to
further explain aspects that could possibly be misunderstood. We stressed
in the title and in the conclusion that depression was a predictor of the
"risk to consider applying for work disability pension". The key messages
could, however, be interpreted differently.
Firstly, we decided to use a composite endpoint of obtaining work
disability pens...
Thank you for your interest in our work. Your letter allows us to
further explain aspects that could possibly be misunderstood. We stressed
in the title and in the conclusion that depression was a predictor of the
"risk to consider applying for work disability pension". The key messages
could, however, be interpreted differently.
Firstly, we decided to use a composite endpoint of obtaining work
disability pension plus considering to apply for a disability pension due
to peculiarites of the German health insurance system: Before receiving a
work disability pension, chronically ill persons usually receive sick
leave compensation for up to 78 weeks. The patients in our cohort had less
than six months symptoms at inclusion. Therefore, only a minority of them
had a chance to have already completed the application process of work
disability pension at two years of follow-up. However, considering to
apply for work disability leads to definite work disability in the vast
majoritiy of cases. In our data, only 12 patients who had considered
disability pension changed their minds during follow-up.
Secondly, we reported that depression was a stronger predictor than
disease activity. Choing and Attia are right that this statement cannot be
made by means of the comparison of odds ratios referring to different
scales. Our statement was based on the comparion of models by means of the
likelihood score statistic which is not scale dependent.
When areas under the ROC curve were compared, the model including age,
FFbH, days of sick leave and PHQ-9 had an area under the curve of 0.80.
The model including age, FFbH, days of sick leave and DAS28 had an area
under the curve of 0.77 (p-value for comparison: 0.09).
Thirdly, the numbers presented in the baseline table are percent
values. In fact, 5% of all patients in the analysis and 22% of the
patients who did consider applying for (or had already applied) disability
pension had severe depression. These numbers are large enough to calculate
an odds ratio. We would like to point out that the lower margin of the 95%
confidence interval of this odds ratio was 3.4 which is still a
considerable effect.
We read with interest the article by Johanna Callhoff and colleagues
regarding depression being a stronger predictor of the risk of work
disability in early arthritis than disease activity or response to
therapy. On reviewing the article, we thought it is important to highlight
3 caveats in interpretation of this article.
Firstly, the outcome was not just those who had applied for or
obtained...
We read with interest the article by Johanna Callhoff and colleagues
regarding depression being a stronger predictor of the risk of work
disability in early arthritis than disease activity or response to
therapy. On reviewing the article, we thought it is important to highlight
3 caveats in interpretation of this article.
Firstly, the outcome was not just those who had applied for or
obtained a work disability, (n=27) but also those who were considering
applying for a work disability pension (n=42). The inclusion of this
group has the potential to create a spurious association between
depression and work disability, in that those who are depressed are more
likely to consider leaving work, even if they do not follow through on
this intent. The factors influencing a person with chronic disease to
consider applying for work disability are numerous and subjective and is a
strong potential confounder.
Secondly, the data were interpreted to say that depression is a
stronger predictor than disease activity or response to treatment simply
on the basis of the magnitude of the respective odds ratios. This is not
a valid interpretation since the odds ratio is the risk per category of
the co-variable, i.e. the odds ratio for depression is compared to the "no
depression" category, whereas the odds ratio for age is per 1 year
increase. These differences in scale mean that the odds ratios are
"apples and oranges" and cannot be directly compared. To do this, one
needs to ascertain the contribution of each factor to the prediction model
using the area under the receiver-operator characteristic (ROC) curve, and
unfortunately this was not provided.
Thirdly, the finding of depression as a strong risk factor should be
seen in the context of the low numbers of people with this condition.
Despite the large size of the study, only 5 people had severe depression
in the control group compared to 22 in the case group and the OR of 8.09
must be seen in the light of these small numbers, despite the significant
p-value, i.e. type I error is possible.
After reading the entire review, I would agree with the authors and I
feel there must be areas and specialities to defined and considered where
this system can be used. For example, using it for pharmacy practice in
few places will bring in a high potential of false prognosis as per lesser
knowledge of individuals.
I would suggest a more wider studies with a summarised meta-analysis,
where the use of this system...
After reading the entire review, I would agree with the authors and I
feel there must be areas and specialities to defined and considered where
this system can be used. For example, using it for pharmacy practice in
few places will bring in a high potential of false prognosis as per lesser
knowledge of individuals.
I would suggest a more wider studies with a summarised meta-analysis,
where the use of this system can be seen in different areas and their
potential towards its successful use as per outcomes achieved.
Dr. Sharma: You've hit upon multiple issues that certainly
complicate the innovation process. Subjectivity, bias, conflicting
interests, and stakeholder resistance can all prevent worthwhile needs
from being addressed and valuable solutions from reaching the market. Our
hope is that by taking a systematic approach to medtech invention,
innovators will at least be able to anticipate these potential roadblocks
and more...
Dr. Sharma: You've hit upon multiple issues that certainly
complicate the innovation process. Subjectivity, bias, conflicting
interests, and stakeholder resistance can all prevent worthwhile needs
from being addressed and valuable solutions from reaching the market. Our
hope is that by taking a systematic approach to medtech invention,
innovators will at least be able to anticipate these potential roadblocks
and more effectively manage them. Thank you for your comments.
Having recently completed the Singapore Stanford Biodesign programme, I found your piece particularly timely Paul. I would fully agree that the selection of an appropriate need is paramount with regards to the innovation process. If the disease in question is not a marketable burden, in terms of morbidity and mortality so to speak, then a need in this regard is not likely to attract potential investment from a stakeholder perspect...
Having recently completed the Singapore Stanford Biodesign programme, I found your piece particularly timely Paul. I would fully agree that the selection of an appropriate need is paramount with regards to the innovation process. If the disease in question is not a marketable burden, in terms of morbidity and mortality so to speak, then a need in this regard is not likely to attract potential investment from a stakeholder perspective. However based on my experience thus far, I would like to highlight the potential concern of subjectivity which appears to muddy the process.
As a medical trainee, subjectivity is rife. Patient care, although evidence based in the vast majority of cases, may have alternative slants depending on experience and this experience varies from individual. Secondly, in an academic setting, some potential areas of exploration may be regarded as plausible whereas others may not; again this is to a large extent subjective. I am of the mindset currently that without translation of lab based science to a clinical setting, there really is little impact in reality, yet the clash in opinion between scientists and clinicians is one that is unlikely to dissolve anytime soon, despite my interest in unison induction. Similarly during my innovation based exposure, I was met with alternative agreements from a solution perspective. Despite the need being strong, clinicians contested the potential solution. Some were all for it whilst others were hesitant. It was clear that experience may have played a huge part. Doctors generally tend to stick to what they know and what they are most comfortable with from a practical standpoint; hence a reluctance to adapt to novelty may hinder the true value in a solution. My gravest concern in this regard is that successful innovation is really pot luck. Some solutions will conquer, but other potential ones may never reach the frontline. Without an objective conclusion to a solution, a well formalized need will still suffer to rise.
To the Editor,
I read the article by Hua et al.1 that was published in this journal with great interest. The authors provided an excellent review of the literature regarding the clinical efficacy and toxicity of glucocorticoids (GCs) in rheumatoid arthritis (RA). The review included comprehensive discussion about the efficacy of GCs as a bridging therapy in addition to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) based on the rapid onset of action of these drugs.1 The authors advocate that because even low-doses of GCs might have adverse effects, administration of these drugs should be restricted to the lowest dose for the shortest time.1 The first part about the effectiveness of GCs was well documented and convincing; however, the second part about the safety of these drugs seemed a little less convincing. This might be attributed to the fact that a small number of studies on the safety of GCs have been published. In particular, little evidence regarding bone-related adverse effects has been presented. We have obtained very preliminary data in our hospital about the effects of GCs on bone health, including fractures and osteoporosis, and would like to contribute these as a comment.
We retrospectively reviewed the medical records of 883 patients with RA who visited our hospital in 2018. Of these, 364 patients (41.2%, Figure 1A) were prescribed GCs. At the last visits in 2018, appro...
Show MoreThis survey demonstrated that a significant proportion of clinicians use smartphones to share clinical information. While this rightly raises concerns over confidentiality and makes headlines in the press it is important to question why this situation has arisen. As Mobasheri and colleagues demonstrated, ownership is near ubiquitous among medical staff and this affords availability and immediacy of access. It is hardly...
Thank you for your interest in our work. Your letter allows us to further explain aspects that could possibly be misunderstood. We stressed in the title and in the conclusion that depression was a predictor of the "risk to consider applying for work disability pension". The key messages could, however, be interpreted differently.
Firstly, we decided to use a composite endpoint of obtaining work disability pens...
Dear Editor,
We read with interest the article by Johanna Callhoff and colleagues regarding depression being a stronger predictor of the risk of work disability in early arthritis than disease activity or response to therapy. On reviewing the article, we thought it is important to highlight 3 caveats in interpretation of this article.
Firstly, the outcome was not just those who had applied for or obtained...
After reading the entire review, I would agree with the authors and I feel there must be areas and specialities to defined and considered where this system can be used. For example, using it for pharmacy practice in few places will bring in a high potential of false prognosis as per lesser knowledge of individuals.
I would suggest a more wider studies with a summarised meta-analysis, where the use of this system...
Dr. Sharma: You've hit upon multiple issues that certainly complicate the innovation process. Subjectivity, bias, conflicting interests, and stakeholder resistance can all prevent worthwhile needs from being addressed and valuable solutions from reaching the market. Our hope is that by taking a systematic approach to medtech invention, innovators will at least be able to anticipate these potential roadblocks and more...