We read with great interest the recent article written by William
Rogers et al on the Harms of CT scanning prior to surgery for suspected
appendicitis(1). It highlights the radiation risk of cancer while
routinely performing an abdominal
CT scan on an otherwise healthy patient with symptoms suggestive of
appendicitis. This radiation risk of cancer becomes all the more important
in patients with 'ne...
We read with great interest the recent article written by William
Rogers et al on the Harms of CT scanning prior to surgery for suspected
appendicitis(1). It highlights the radiation risk of cancer while
routinely performing an abdominal
CT scan on an otherwise healthy patient with symptoms suggestive of
appendicitis. This radiation risk of cancer becomes all the more important
in patients with 'negative' appendectomy.
However, relying purely on clinical judgment for diagnosis of
appendicitis can result either in increased 'negative' appendectomy or
diagnostic delay which may cause appendiceal perforation. There are
studies which show that negative appendectomy is associated with an
appreciable degree of morbidity and mortality, including a significant
increase in length of hospital stay, postoperative complications like
wound infection and death(2). Also, it can increase health care costs.
Perforated appendicitis is also related to increase in length of
hospital stay(3). In-house mortality is high for perforated
appendicitis(4).
During the last decade, there have been many advances in CT
technology
which have resulted in improved spatial resolution, rapid scan and
increased use
of multiplanar images enabling better visualization of appendix. Although
the effective dose value for CT scan of abdomen and pelvis is taken as 8 -
11 mSv(5) , studies comparing low-dose CT group with standard-dose CT
group have shown that low-dose CT was not inferior with regard to
diagnosis of appendicitis(6) and negative appendectomy rates(7) . Neither
the appendiceal perforation rate nor the diagnostic performance of CT for
appendicitis differed significantly between the two groups. A randomized
controlled trial, low-dose CT for appendicitis trial (LOCAT) is being
undergone comparing the clinical outcomes following low vs standard-dose
computed tomography as the first-line imaging test in adolescents and
young adults with suspected acute appendicitis, where the effective dose
of CT is reduced to 2 mSv(8). This greatly reduces the carcinogenic risk.
Study using non-contrast focused abdominal CT scan has also shown to have
a high sensitivity for diagnosis of appendicitis(9). Here, there is no
risk of contrast nephropathy.
Further research in this field will enable us to use very low dose CT
scan with significantly less radiation risk of cancer; at the same time
significantly reducing negative appendectomy rate without an increase in
the appendiceal perforation rate.
References
(1) Rogers, W., Hoffman, J., Noori, N. Harms of CT
scanning prior to surgery for suspected appendicitis. Evidence Based
Medicine 2015;20(1):3-4.
(2) Flum DR, Koepsell T. The clinical and economic correlates of
misdiagnosed appendicitis: nationwide analysis. Arch Surg 2002;137:799-804.
(3) Al-Omran M, Mamdani M, McLeod RS. Epidemiologic features of acute
appendicitis in Ontario, Canada. Can J Surg 2003;46:263-268.
(4) Wen SW, Naylor CD. Diagnostic accuracy and short-term surgical
outcomes in cases of suspected acute appendicitis. CMAJ 1995;152:1617-1626.
(5) Furlow B. Radiation dose in computed tomography. Radiol Technol
2010;81:437-50.
(6) Keyzer, C., Tack, D., De Maertelaer, V., et al. Acute Appendicitis: Comparison of Low-
Dose and Standard-Dose Unenhanced Multi-Detector Row CT 1. Radiology 2004;232(1):164-172.
(7) Kim, K., Kim, Y. H., Kim, S. Y., et al. (2012). Low-dose abdominal CT for evaluating
suspected appendicitis. New England Journal of Medicine 2012;366(17):1596-1605.
(8) Ahn S. LOCAT (low-dose computed tomography for appendicitis trial)
comparing clinical outcomes following low- vs standard-dose computed
tomography as the first-line imaging test in adolescents and young adults
with suspected acute appendicitis: study protocol for a randomized
controlled trial.Trials. 2014;15:28. doi:10.1186/1745-6215-15-28.
(9) Akhtar, W., Ali, S., Arshad, M., Ali, F., Nadeem, N. (2011).
Focused abdominal CT scan for acute appendicitis in children: can it help
in need. Journal of the Pakistan Medical Association 2011; 61(5):474-6.
We share your enthusiasm for the current efforts to reduce radiation
exposure associated with the use of CT scanning and agree with your
assertion that performance of appendectomy without scanning will
inevitably lead to more negative appendectomies. We are confident though
based on the NHS laparoscopic appendectomy statistics reviewed by Omar and
Clark in the Annals of Surgery that those negative appendectomies are
asso...
We share your enthusiasm for the current efforts to reduce radiation
exposure associated with the use of CT scanning and agree with your
assertion that performance of appendectomy without scanning will
inevitably lead to more negative appendectomies. We are confident though
based on the NHS laparoscopic appendectomy statistics reviewed by Omar and
Clark in the Annals of Surgery that those negative appendectomies are
associated with essentially no risk. In the NHS series 234,402 patients
underwent laparoscopic appendectoy without a single death or major
morbidity. CT scanning these 234 thousand patients on the other hand will
cause more than 100 fatal cases of cancer.
Dr Rogers et al have astutely pointed out the dangers of routine CT
assessment of right iliac fossa pain in the paediatric population. I agree
wholeheartedly that the role of clinical judgement, alongside observation
and serial examination remain critical. Ultrasonography and MRI are
additional valuable diagnostic adjuncts that do not incur a radiation dose
to patients.
Dr Rogers et al have astutely pointed out the dangers of routine CT
assessment of right iliac fossa pain in the paediatric population. I agree
wholeheartedly that the role of clinical judgement, alongside observation
and serial examination remain critical. Ultrasonography and MRI are
additional valuable diagnostic adjuncts that do not incur a radiation dose
to patients.
I would question the data the authors have used to calculate the risk
of CT induced cancer. The estimates from the BEIR V data are based on a
radiation exposure of 10mSv. Contemporary CT-appendix protocols expose
patients to around 2mSv or less, but have equivalent accuracy to a CT scan
of the abdomen and pelvis. Would it not be more appropriate to calculate
the risk of cancer based on these figures?
You are correct that protocols and improved technology have led to
reductions in radiation exposure from CT scanning at some hospitals. I
would suggest though that the resultant reduction in the risk of fatal
cancer due to imaging does not affect the conclsion of the paper. If a
laparotomy on a healthy young patient carries no risk of death and CT
scanning imposes a risk of death the decision to perfor...
You are correct that protocols and improved technology have led to
reductions in radiation exposure from CT scanning at some hospitals. I
would suggest though that the resultant reduction in the risk of fatal
cancer due to imaging does not affect the conclsion of the paper. If a
laparotomy on a healthy young patient carries no risk of death and CT
scanning imposes a risk of death the decision to perform a CT scan on a
young healthy person before proceeding to the operating room poses an
ethical dilemma for the ordering physican.
Mazar and Ariely's recent paper [1] reinforces the concepts and
suggestions discussed in our recent publications: dishonesty is a human
universal, and there is no one-size-fits-all solution [2,3]. Education,
moral reminders and changing how researchers are rewarded are important
tools [1]. Most importantly, we need to reclaim the integrity, dedication
and code of honor Sir Austin Bradford Hill consider...
Mazar and Ariely's recent paper [1] reinforces the concepts and
suggestions discussed in our recent publications: dishonesty is a human
universal, and there is no one-size-fits-all solution [2,3]. Education,
moral reminders and changing how researchers are rewarded are important
tools [1]. Most importantly, we need to reclaim the integrity, dedication
and code of honor Sir Austin Bradford Hill considered essential to the
practice of Medicine [4].
References
1. Mazar N, Ariely D. Dishonesty in scientific research. J Clin Invest
2015; Nov 2; 125(11):3993-6.
2. Seshia SS, Makhinson M, Phillips DF, Young GB. Evidence-informed person
-centered healthcare part I: do 'cognitive biases plus' at organizational
levels influence quality of evidence?. J Eval Clin Pract 2014;
Dec;20(6):734-47.
3. Seshia SS, Makhinson M, Young GB. 'Cognitive biases plus': covert
subverters of healthcare
evidence. Evid Based Med 2015; Nov 26;. doi: 10.1136/ebmed-2015-
110302.[Epub ahead of
print].
4. Hill AB. Medical ethics and controlled trials. Br Med J 1963; Apr
20;1(5337):1043-9.
I am very grateful to Ken Uchino for amplifying and clarifying the
detail of some of the points I was trying to make within the word limits
of a 'Perspectives' paper. I suggest there are four key elements:
1. The epidemiology is indeed complex and I am neither an academic
nor an epidemiologist. However, it would appear that we can agree that
there is indeed a difference between 'younger old'...
I am very grateful to Ken Uchino for amplifying and clarifying the
detail of some of the points I was trying to make within the word limits
of a 'Perspectives' paper. I suggest there are four key elements:
1. The epidemiology is indeed complex and I am neither an academic
nor an epidemiologist. However, it would appear that we can agree that
there is indeed a difference between 'younger old' (i.e. 65-75) and 'older
old' (i.e. 80+), both in relative and absolute risk - albeit in opposite
directions. The key point here is not the strength of the associations
with age, but the magnitude of impact of treating the risk factor at any
given age. This is where interventional trials come in.
2. As I pointed out in my paper, the data about treating hypertension
in 80+ year olds accumulated prior to HYVET were very suggestive of
benefit; they predicted HYVET would give a definitive answer. HYVET - by
far the largest trial looking at patients aged 80+ - failed to live up to
this promise. Sadly, the premature termination of the trial (because of
excess mortality in the placebo group) arguably raised more questions
about the clinical applicability of its results, than the trial answered.
3. The PROSPER trial examined the use of statins in European patients
initially aged 70-82 (mean 75), and followed up for an average of 3.2
years. Nearly 20% of patients entered into the 4-week single-blind
placebo lead-in period failed to proceed to the randomised period (either
for using <75% or more than 120% of placebo, or because they refused to
participate). This raises questions as to generalisability. Whilst
reducing cardiovascular events, the intervention failed to show a
reduction in stroke. I fully accept that absence of evidence is not
necessarily evidence of absence, but this must surely raise questions as
to the magnitude of any true effect.
4. None of these trials looked into the patients' preferences and
priorities re outcomes. I argue that these change significantly with
advancing frailty and incapacity (which in turn increase
disproportionately with, but are not confined to, increasing age).
If we cannot even be certain of the ostensibly simple quantitative
aspect of the decision (the certainty of the magnitude of the treatment
effects), how can we properly weigh that up against the much more
difficult to define qualitative aspects (the beliefs, values, and
priorities of my patient)?
My central point is that without robust evidence applicable to the
patient in front of me - usually over 80, and often very frail - how can I
help the patient to reach truly informed consent? I may well have some of
the estimates of magnitude wrong, but the principle still stands. A
treatment decision is only as strong as its weakest link. I suggest that
there are so many weak links in this particular evidence chain that it is
almost impossible to reach a decision that all doctors would support.
Suggesting that a simple 'one size fits all' (i.e. algorithmic guideline-
based) solution would be appropriate is simplistic. Without more data we
cannot be sure.
For all these reasons I strongly urge that we undertake randomised
trials of withdrawals of treatment in real life elderly patients (both
frail and robust). This has the potential to find out how much impact
these interventions have in clinical practice, as opposed to in the
rarefied environment of scientific clinical trials.
In the UK NHS we arguably should have a real opportunity to use 'big
data' in real life in this way to find out if there are any signals there
amongst the noise. A simple pragmatic trial involving tens of thousands
of people would surely have a good chance of giving us the information we
need? If the NHS funded this with the money currently earmarked for
hitting treatment targets in those over 80, it would not take long to
answer this question.
While I agree with Dr Byatt that it is important to discuss with
patients the choices of treating risk factors to prevent disease, the
basis for the discussion needs to be clarified and fine-tuned.
Epidemiology: The attributable risk of hypertension in stroke
decreases in the elderly. This phenomenon may be partly because other
factors such as atrial fibrillation become more dominant factor....
While I agree with Dr Byatt that it is important to discuss with
patients the choices of treating risk factors to prevent disease, the
basis for the discussion needs to be clarified and fine-tuned.
Epidemiology: The attributable risk of hypertension in stroke
decreases in the elderly. This phenomenon may be partly because other
factors such as atrial fibrillation become more dominant factor.
Framingham Study quoted in the paper is only one study. Pooling data from
multiple studies, Prospective Studies Collaboration has reported that that
higher risk of stroke mortality is observed with higher systolic and
diastolic blood pressures across blood pressure ranges into age 80s.[1]
The relative risk conferred with higher blood pressure diminish with age,
but still in age 80s, 20 mm Hg increase in systolic blood pressure (SBP)
is associated with ~1.5 fold increase in stroke. That compares with ~2.8
fold increase in risk of stroke in age 40s. But the absolute risk
difference with increase in SBP or DBP is greater in old age.
Even if Dr Byatt's reading of epidemiologic data is correct, a lack
of observed association disease (stroke) with a risk factor (hypertension)
does not necessarily translate that intervening on the factor would not
reduce disease. This was clearly shown in case of cholesterol, where no
consistent association with stroke risk has been shown in multiple
studies.[2] Yet, clinical trials using statin class of cholesterol
lowering medications have shown that stroke is indeed reduced if the study
size is large enough in both primary and secondary prevention settings.[3,
4] We cannot assume that because the contribution of hypertension is
smaller as one gets older, that treatment would not reduce stroke.
Trial data: There is a consistent finding from clinical trials of
blood pressure reduction comparing different targets or regimens that SBP
reduction of 10-20 mm Hg confer a relative reduction stroke by about 30-
40%. Most studies confirm that stroke is very sensitive to blood
pressure.[5] The finding of the HYVET study mentioned consistent in
relative risk reduction of fatal and nonfatal stroke by 30% (p=0.06) with
SBP difference in 15 mm Hg between the groups. The study may have be
underpowered to reach statistical significance.
One needs to keep in mind that the risk of stroke is low in the
relatively healthy elderly individuals in clinical trials that mostly
consists of persons free of cardiovascular disease. HYVET study with 80
years of age or older and found a rate of stroke of 1.7% per year in the
placebo group. Active treatment results in a number needed to treat of 94
over 2 years to prevent one stroke. For comparison, in ALLHAT, with the
mean age of 67, the annual stroke rate was ~1% per year.[6]
Primary prevention is a challenge because the event rate and absolute
risk reduction by intervention is low, even if relative risk reduction is
large. In the elderly, the risk of events is higher, but the time horizon
is also shorter. The discussion should not necessarily focus on the
absolute risk reduction and the number needed to treat, but put the
context of the outlook of the elderly individuals into the next several
years, some of whom are living into elderly age in relative good health.
Prioritizing may be important. What are the important diseases to prevent,
screen, treat? While Dr Byatt focuses on stroke, treatment of hypertension
reduces strokes, congestive heart failure, and myocardial infarction.
While I agree with the recent JNC 8 recommendation to question the same
blood pressure target across ages, hypertension cannot be simply viewed as
over treated.[7]
References
1) Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to
vascular mortality: a meta-analysis of individual data for one million
adults in 61 prospective studies. Lancet 2002;360(9349):1903-13.
2) Lewington S, Whitlock G,
Clarke R, et al. Blood cholesterol and vascular mortality by age, sex, and blood
pressure: a meta-analysis of individual data from 61 prospective studies
with 55,000 vascular deaths. Lancet 2007;370(9602):1829-39.
3) Taylor FC1, Huffman M, Ebrahim S. Statin therapy for primary
prevention of cardiovascular disease. JAMA 2013;310(22):2451-2.
4) Amarenco P, Labreuche J. Lipid management in the prevention of
stroke: review and updated meta-analysis of statins for stroke prevention.
Lancet Neurol 2009;8(5):453-63.
5) Staessen JA1, Wang JG, Thijs L. Cardiovascular protection and
blood pressure reduction: a meta-analysis. Lancet. 2001;358(9290):1305-15.
6) ALLHAT Officers and Coordinators for the ALLHAT Collaborative
Research Group. Major outcomes in high-risk hypertensive patients
randomized to angiotensin-converting enzyme inhibitor or calcium channel
blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to
Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:2981-2997
7) James PA, Oparil S, Carter BL, et al. 2014
evidence-based guideline for the management of high blood pressure in
adults: report from the panel members appointed to the Eighth Joint
National Committee (JNC 8). JAMA 2014;311(5):507-20.
Andrea Giaccari asserts that I wrote in my editorial that sitagliptin in the TECOS trial "caused" 20% increase in the secondary outcome of congestive heart failure. That is not what I wrote. I wrote that "the study data remain consistent with" a 20% increase in this adverse outcome. While the wide confidence interval is also consistent with a reduction in heart failure risk, the primary goal of the TECOS tr...
Andrea Giaccari asserts that I wrote in my editorial that sitagliptin in the TECOS trial "caused" 20% increase in the secondary outcome of congestive heart failure. That is not what I wrote. I wrote that "the study data remain consistent with" a 20% increase in this adverse outcome. While the wide confidence interval is also consistent with a reduction in heart failure risk, the primary goal of the TECOS trial was to assess the safety of DPP4 inhibitors. Hence, the upper bounds of the confidence interval are of particular interest to practicing physicians interested in drug safety.
I read with interest the comments of Dr. Fenton. In his editorial (Evid Based Med. 2016 Jun;21(3):81-2) Dr Fenton stated that sitagliptin caused in TECOS "a 20% increase in the secondary outcome of congestive heart failure (intention-to-treat HR 1.00, 95% CI 0.82 to 1.20, p=0.98)". This is really misleading. With exactly the same numbers Dr. Fenton could state that sitagliptin caused an 18% reduction in hos...
I read with interest the comments of Dr. Fenton. In his editorial (Evid Based Med. 2016 Jun;21(3):81-2) Dr Fenton stated that sitagliptin caused in TECOS "a 20% increase in the secondary outcome of congestive heart failure (intention-to-treat HR 1.00, 95% CI 0.82 to 1.20, p=0.98)". This is really misleading. With exactly the same numbers Dr. Fenton could state that sitagliptin caused an 18% reduction in hospitalizations for heart failure. Obviously, both affirmations are false, since the real risk decrease/increase with sitagliptin is 1.00. That is, no effect at all.
I am really surprised how a journal named "Evidence Based Medicine" can publish such a "Subjective Data Interpretation".
Conflict of Interest:
Speaker's fee from Astra Zeneca, Boehringer, Sanofi
This article brings into light the upcoming ways in which medical
health care knowledge is disseminated between general population and the
various pitfalls such an approach can have. Although such issues are in
nascent stage in a developing country like India but its climbing up the
ladder at a brisk rate. The new generation of physicians is media savvy
but can get easily influenced by media based...
This article brings into light the upcoming ways in which medical
health care knowledge is disseminated between general population and the
various pitfalls such an approach can have. Although such issues are in
nascent stage in a developing country like India but its climbing up the
ladder at a brisk rate. The new generation of physicians is media savvy
but can get easily influenced by media based propaganda's.
There is no doubt Evidence based Medicine is the future of way medicine is
going to be practiced be it in a developed country or a developing
nation, but scientific and regulating authorities need to keep a keen and
watchful eye on ways, quality and standard of literature that is being
published and distributed to practitioners and public.
There needs to be a healthy and interactive communication between
journalists and scholars so that the message intended reaches the public
and students in a clear, concise and undisputed way.
We agree with the authors that development of such web based facilities is
an inevitable need of the hour even from the point of view of a developing
country. Such acts will bring about greater understanding of complex
medical issues and practices followed in patient care thereby avoiding
unnecessary litigation and panic created by outbreak of an infectious
diseases, a prime example being epidemic of dengue fever and assumption of
direct correlation of decreasing platelet count with hemorrhage and
mortality which is absolutely not true as shown by number of studies.
The article brings about the required amalgamation of media and scientific
community in a cohesive way to produce comprehensible medical knowledge
and its dissemination in public domain.
Dear Editor,
We read with great interest the recent article written by William Rogers et al on the Harms of CT scanning prior to surgery for suspected appendicitis(1). It highlights the radiation risk of cancer while routinely performing an abdominal CT scan on an otherwise healthy patient with symptoms suggestive of appendicitis. This radiation risk of cancer becomes all the more important in patients with 'ne...
We share your enthusiasm for the current efforts to reduce radiation exposure associated with the use of CT scanning and agree with your assertion that performance of appendectomy without scanning will inevitably lead to more negative appendectomies. We are confident though based on the NHS laparoscopic appendectomy statistics reviewed by Omar and Clark in the Annals of Surgery that those negative appendectomies are asso...
Dear Editor,
Dr Rogers et al have astutely pointed out the dangers of routine CT assessment of right iliac fossa pain in the paediatric population. I agree wholeheartedly that the role of clinical judgement, alongside observation and serial examination remain critical. Ultrasonography and MRI are additional valuable diagnostic adjuncts that do not incur a radiation dose to patients.
I would question the da...
Dear Editor,
You are correct that protocols and improved technology have led to reductions in radiation exposure from CT scanning at some hospitals. I would suggest though that the resultant reduction in the risk of fatal cancer due to imaging does not affect the conclsion of the paper. If a laparotomy on a healthy young patient carries no risk of death and CT scanning imposes a risk of death the decision to perfor...
Dear Editor,
Mazar and Ariely's recent paper [1] reinforces the concepts and suggestions discussed in our recent publications: dishonesty is a human universal, and there is no one-size-fits-all solution [2,3]. Education, moral reminders and changing how researchers are rewarded are important tools [1]. Most importantly, we need to reclaim the integrity, dedication and code of honor Sir Austin Bradford Hill consider...
Dear Editor,
I am very grateful to Ken Uchino for amplifying and clarifying the detail of some of the points I was trying to make within the word limits of a 'Perspectives' paper. I suggest there are four key elements:
1. The epidemiology is indeed complex and I am neither an academic nor an epidemiologist. However, it would appear that we can agree that there is indeed a difference between 'younger old'...
Dear Editor,
While I agree with Dr Byatt that it is important to discuss with patients the choices of treating risk factors to prevent disease, the basis for the discussion needs to be clarified and fine-tuned.
Epidemiology: The attributable risk of hypertension in stroke decreases in the elderly. This phenomenon may be partly because other factors such as atrial fibrillation become more dominant factor....
Dear Editor,
Andrea Giaccari asserts that I wrote in my editorial that sitagliptin in the TECOS trial "caused" 20% increase in the secondary outcome of congestive heart failure. That is not what I wrote. I wrote that "the study data remain consistent with" a 20% increase in this adverse outcome. While the wide confidence interval is also consistent with a reduction in heart failure risk, the primary goal of the TECOS tr...
Dear Editor,
I read with interest the comments of Dr. Fenton. In his editorial (Evid Based Med. 2016 Jun;21(3):81-2) Dr Fenton stated that sitagliptin caused in TECOS "a 20% increase in the secondary outcome of congestive heart failure (intention-to-treat HR 1.00, 95% CI 0.82 to 1.20, p=0.98)". This is really misleading. With exactly the same numbers Dr. Fenton could state that sitagliptin caused an 18% reduction in hos...
Dear Editor,
This article brings into light the upcoming ways in which medical health care knowledge is disseminated between general population and the various pitfalls such an approach can have. Although such issues are in nascent stage in a developing country like India but its climbing up the ladder at a brisk rate. The new generation of physicians is media savvy but can get easily influenced by media based...
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