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
First, thank you for highlighting our paper. However, I do want to take issue with this commentary.
Systematic reviews in postop analgesia have been done now for over 20
years, and there is considerable methodological research to substantiate
what is done. The results are robust and trustworthy.
Single trials, however well done, are not trustworthy because while
they may be powered t...
First, thank you for highlighting our paper. However, I do want to take issue with this commentary.
Systematic reviews in postop analgesia have been done now for over 20
years, and there is considerable methodological research to substantiate
what is done. The results are robust and trustworthy.
Single trials, however well done, are not trustworthy because while
they may be powered to show direction of effect (drug better than placebo,
for example), they are not powered to measure the magnitude of effect
accurately. That typically needs about 10 times more data, hence the value
of systematic reviews and overview reviews (see Cochrane Database Syst
Rev. 2015 Sep 28;9:CD008659). Overview reviews are where you can get
indirect comparison of efficacy.
I think the authors are making a point about speed of onset with
caffeine, and that is fair, though it took some time to work that out. And
if so I am not sure that the study by Raisian helps. Apart from being
small (fewer than 40 per treatment group), it was a multiple-dose study in
patients who did not have initial moderate to severe pain, so it was more
of a pre-emptive study than one that could measure speed of onset.
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.
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.
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?
We were pleased to read the commentary by Millar and Sanz(1)
regarding our publication on Tdap safety in pregnancy from the Vaccine
Safety Datalink.(2) We agree that policies regarding routine vaccination
should be made after careful review of the risks and benefits of
vaccination. For maternal vaccination, evaluations of risk-benefit
profiles are complex, as both maternal and infant outcomes must be...
We were pleased to read the commentary by Millar and Sanz(1)
regarding our publication on Tdap safety in pregnancy from the Vaccine
Safety Datalink.(2) We agree that policies regarding routine vaccination
should be made after careful review of the risks and benefits of
vaccination. For maternal vaccination, evaluations of risk-benefit
profiles are complex, as both maternal and infant outcomes must be
considered.
In our observational retrospective study of more than 25,000 women
with singleton pregnancies who received Tdap during pregnancy in
California, we found no increased risk of hypertensive disorders of
pregnancy, preterm or small for gestational age births associated with
maternal vaccination. We did observe a small, but statistically
significant increased risk of chorioamnionitis diagnosis among vaccinated
women. Chart review of a subset of women with a chorioamnionitis
diagnosis revealed that only half met case definitions for probable
chorioamnionitis. Furthermore, 95% of women with a chorioamnionitis
diagnosis had an epidural during labor, providing a potential alternative
explanation for fever during labor.(3)
Tdap vaccination during pregnancy remains the most effective
available strategy for promoting maternal transfer of pertussis-specific
antibodies and thus preventing severe disease in newborns. In a recent
case-control study in England, Dabrera and colleagues estimated the
effectiveness of maternal Tdap vaccination for preventing laboratory-
confirmed pertussis infection in infants to be 91%.(4)
In the United States, policies to routinely administer Tdap during
pregnancy came after widespread pertussis outbreaks, including 10 infant
deaths in California.(5) In 2014, California once again reported an
increase in pertussis cases. In both recent outbreaks, disease prevalence
and severity has been highest in infants under 4 months.(6) We agree with
Millar and Sanz that further monitoring of Tdap safety is important, with
particular attention to fetal outcomes potentially associated with
chorioamnionitis. However, given continued ongoing pertussis transmission,
and the high of risk of morbidity in newborns, we support current
guidelines from the Advisory Committee on Immunization Practices
recommending the routine administration of Tdap during pregnancy.
References
1. Millar MR, Sanz MG. The administration of pertussis vaccine to
pregnancy women was associated with a small increased risk of
chorioamnionitis, but not an increased risk fo hypertensive disorders or
preterm birth Evid Based Med. 2015 (in press).
2. Kharbanda EO, Vazquez-Benitez G, Lipkind HS, et al. Evaluation of the
association of maternal pertussis vaccination with obstetric events and
birth outcomes. JAMA 2014;312(18):1897-1904.
3. Abramovici A, Szychowski JM, Biggio JR, et al.
Epidural Use and Clinical Chorioamnionitis among Women Who Delivered
Vaginally. Am J Perinatol. Apr 4 2014.
4. Dabrera G, Amirthalingam G, Andrews N, et al. A case-control study to
estimate the effectiveness of maternal pertussis vaccination in protecting
newborn infants in England and wales, 2012-2013. Clin Infect Dis 2015;60(3):333-337.
5. Winter K, Harriman K, Zipprich J, et al. California pertussis epidemic,
2010. J Pediatr 2012;161(6):1091-1096.
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.
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 read with great interest the recent article by Dr. Windish [1]
reviewing a number of Evidence-Based Medicine (EBM) smartphone apps.
Immediate access to brief summaries of the literature is essential in
bringing EBM knowledge to the bedside, as physicians are often busy and
are presented with frequent interruptions which hinder their ability to
perform detailed searches or read complete articles dur...
We read with great interest the recent article by Dr. Windish [1]
reviewing a number of Evidence-Based Medicine (EBM) smartphone apps.
Immediate access to brief summaries of the literature is essential in
bringing EBM knowledge to the bedside, as physicians are often busy and
are presented with frequent interruptions which hinder their ability to
perform detailed searches or read complete articles during the workday.
Indeed, we note the success of the randomized trial by Pastori, et al.
[2], where in the intervention group they provided a physician whose sole
purpose was collecting relevant EBM evidence from the literature. This
resulted in better patient outcomes, as assessed by ICU transfers and
hospital readmissions.
We would like to highlight an EBM database of diagnostic accuracy that we
have developed, entitled GetTheDiagnosis.org
(http://www.getthediagnosis.org). This website, which has a mobile version
suited to smartphones as well, contains a database of sensitivity and
specificity of history questions, physical examination findings, and
laboratory and imaging tests for nearly 300 diagnoses. The data is culled
from primary literature and is maintained by physician-users, who can
submit new entries or edit existing entries in the same manner as
Wikipedia. The site displays citations and links to the literature for
each entry, and the data is highly structured and allows for searching by
diagnosis or finding. By using structured data, we can provide a post-test
probability calculator based on the data for each diagnosis.
In this way, we have attempted to marry successful features of apps such
as EBM Tools or MedCalc 3000 EBM with an actual database of EBM data from
the literature. We hope that physicians will find our website helpful and
easy to use while in the clinic, and we hope that many of them will help
build the database by adding articles from the primary literature.
References
1. Windish D. EBM apps that help you search for answers to your clinical
questions. Evid Based Med 2014;:ebmed-2013-101623. doi:10.1136/eb-2013-
101623
2. Pastori MM, Sarti M, Pons M, et al. Assessing the impact of
bibliographical support on the quality of medical care in patients
admitted to an internal medicine service: a prospective clinical, open,
randomised two-arm parallel study. Evid Based Med 2014;19:163-8.
doi:10.1136/ebmed-2014-110021
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,
First, thank you for highlighting our paper. However, I do want to take issue with this commentary.
Systematic reviews in postop analgesia have been done now for over 20 years, and there is considerable methodological research to substantiate what is done. The results are robust and trustworthy.
Single trials, however well done, are not trustworthy because while they may be powered t...
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,
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,
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,
We were pleased to read the commentary by Millar and Sanz(1) regarding our publication on Tdap safety in pregnancy from the Vaccine Safety Datalink.(2) We agree that policies regarding routine vaccination should be made after careful review of the risks and benefits of vaccination. For maternal vaccination, evaluations of risk-benefit profiles are complex, as both maternal and infant outcomes must be...
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,
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...
Dear Editor,
We read with great interest the recent article by Dr. Windish [1] reviewing a number of Evidence-Based Medicine (EBM) smartphone apps. Immediate access to brief summaries of the literature is essential in bringing EBM knowledge to the bedside, as physicians are often busy and are presented with frequent interruptions which hinder their ability to perform detailed searches or read complete articles dur...
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