 |
 |
On 27 May 2020, at 03:30, Kumara Mendis <[log in to unmask]> wrote:Hi BenThank you for your excellent short description of convincing a clinician.I think you have convinced me (this is because I believe in EBM with all its challenges). Hopefully I can convince some of my secondary care colleagues who will question and continue their was quoting “I have never seen the patient with harms due to XXX”Need a few clarifications1)Formally, this can be expressed as decision threshold (T) = RXharms /(RRR-RRR*RXharms)RRR - RRR will be 0 zero so the whole denominator will be 0?So T = RXharms?Is this correct?2)Benefits (effectiveness): The Lancet article also states that mortality was 9% in the control arm , and was 16.8% to 23.8% . So, RRR=0.How did you work this out?Apologies for questions and Thank you again for the explanation.KUmaraHi Kumara,
Perhaps an illustration can help.
Incidentally, your questions reminded me on my work on regret theory (I helped developed something called “acceptable regret” theory at which you will not regret being wrong) , which forces you to explicitly consider trade-off between the consequences of failing to provide potential benefits vs unnecessary harming patients. You may ask yourself question like this:
How many more times is worse not treating the patient whom I possibly can benefit comparing with treating unnecessary someone whom I can possibly harm (=RV)?
Formally, this can be expressed as decision threshold (T)=RXharms/(RRR-RRR*RXharms)
Where RRR= relative risk reduction of a given treatment.
The equation tells you that you should treat ONLY if morbidity/mortality without Rx is greater than T (note that morbidity/mortality ranges from 0 to 1; thus if it is 0, you should always treat, if it is 1, you should never treat)
[The equation for including RV and multiple harms is a bit more complicated but let’s stick to one harms only and assume RV=1]
Harms: Lancet article lists the % of De-novo ventricular arrhythmia in control at 0.3% and 4.3% to 8.1% in patients using HCQ in the various combination with antibiotics . Let’s assume it is about 5%.
Benefits (effectiveness): The Lancet article also states that mortality was 9% in the control arm , and was 16.8% to 23.8% . So, RRR=0.
(This would also mean that you would treat if T>9%).
If you replace these numbers in the equation above, T>>>1, which means you should NEVER treat the patient.
However, you believe that the Lancet article is at high risk of bias (although as Mohammed reminded us high risk for bias is not the same as risk of high bias). Nevertheless, highest risk of bias that I am aware in terms of distorting true effect of treatment is about 50-70% (but is typically in 10-20% range). Let’s then assume that harms=2%. How high RRR should be to satisfy you that you should treat your patient at T=9%?
Solving the equation above, you get that you need RRR~ 22% in order to justify giving HCQ.
Do you really believe that HCQ is so efficacious? If yes, you really need data to support this belief. If not, then you are really harming your patients. [Most people counter this argument with remark: “I have never seen the patient with harms due to XXX”. The problem is that in our individual practice we can never have enough patients to get personal experience such as the collective experience reported in the Lancet report, which reports 96,000+ patients. It is famously said 40 years of the experience with one drug for one disease cannot compete with one, well-designed large RCT]
Of course, this just an illustration but provides you with an explicit framework how one can replace or augment his/her intuition.
Hopefully this may convince you to discontinue using HCQJ
Best
ben
From: Evidence based health (EBH) [mailto:[log in to unmask]] On Behalf Of Kumara Mendis
Sent: Tuesday, May 26, 2020 10:09 AM
To: [log in to unmask]
Subject: Re: Re Critical Appraisal of Lancet paper
Dear all
Just heard BBC news that Brazil is using HCQ for all patients despite the warning from the WHO.
One possible reason is that the President of Brazil is a good friend of President Trump!
This is where politics gets into healthcare!
Now, getting back to my question, EBM has three elements as Sackett explains
a) Patients expectations, what they want and expect
b) Clinicians expertise
c) Best evidence that guides the decisions
A typical scenario from a LMI country physician who has only a few choices...
So....patients wants a drug to cure or shorten the COVID-19 disease
As a clinicians who has treated maybe 10-50 or more patients with HCQ, may be 1-2 had only had heart problems and many have been discharged home. In addition CLQ has been known and used for decades to treat malaria....
The evidence so far is on the fence...(This is why I was asking for a critical appraisal of the Lancet paper....can anyone do this as critical appraisal is one aspect of what you do when you find evidence?)
So as a clinician I keep on treating patients (without doing clinical trials as I do not have time or funds...)
Also the alternative drug Remdesivir which is promoted by USA & NEJM is expensive, and seems not any better.
I cannot find any articles on comparison between HCQ and Remdesivir
What to do?
Thanks all
Kumara
On Tue, May 26, 2020 at 9:27 PM K Hopayian <[log in to unmask]> wrote:
Dear Vivek,
Yes, I can understand why those are all powerful arguments. But still insufficient evidence.
A priori reasoning that it works come from in vitro studies. But a priori reasoning it may do harm also exists - QT interval.
Yes, safety profile when used in rheumatological conditions and malaria is good but when used in people who have myocarditis from SARS-2??? Don’t have enough evidence yet
Kev
On 26 May 2020, at 15:59, Vivek Podder <[log in to unmask]> wrote:
Hello respected everyone,
Today, I was watching an Indian press brief, where the concerned person briefed that the biological plausibility, evidence from in-vitro studies, and experience over the time of using hydroxychloroquine in malaria along with relative safety profile from local studies have prompted to use it as prophylaxis. A similar thought is running in my country where such indications go viral in social media and people start using it on their own. On the other hand, hardly any data come out about the effectiveness and safety from local patients to support the guideline recommendations. At times, it becomes very difficult to discuss evidence as common statements are "something is better than nothing during a pandemic." It further influences me to think "What would I do if I was that COVID-19 positive patient in the hospital ICU, would I opt to take it?"
Best,
Vivek
On Tue, May 26, 2020 at 8:37 PM Bewley, Susan <[log in to unmask]> wrote:
All medical interventions cause anxiety & harm, using up time & resources - whether that's our tests, labels, poisons (aka drugs) or assaults (aka surgery). Old heuristics https://en.wikipedia.org/wiki/Vis_medicatrix_naturae and
https://en.wikipedia.org/wiki/Medicus_curat,_natura_sanat still have a place. The beauty of science lies in its many explanatory stories, and the wonderful findings that some interventions cure disease, prolong life and diminish human suffering. Surely, with our unedifying past examples, we know by now that it is unethical to guess rather than test?
Susan
From: Evidence based health (EBH) <[log in to unmask]> on behalf of Benjamin Djulbegovic MD <[log in to unmask]>
Sent: 26 May 2020 15:04
To: [log in to unmask] <[log in to unmask]>
Subject: Re: Re Critical Appraisal of Lancet paper
Hi Kumara,
Let’s assume the Lancet study is flawed, does this really justify giving Rx with unknown benefits and well known harms? That is, regardless if the study described in the Lancet is credible or not, what EBM has taught us is that the probability of harming patients when giving them not well tested treatments is much higher than benefited them (+ lead to waste of resources). On my last count, there are 30+ different treatments that have been claimed to have effect against SARS-CoV2 (from vitamin C to HCQ to plasma of patients who recovered from COVID19). Should we use them all?
This urge “to do something”, to “treat ourselves rather than patients”, or even to provide false hope is , unfortunately, characteristic of all physicians regardless where we practice. But, we ought to resist it. Or, better, we should use the opportunities like these to formally test the effects of these Rxs. For example, perhaps you have enough patients treated with HCQ that you can analyze and we all can learn from you. This is not criticism of your practice- tendency for overRx dominates the current practice of medicine all around the world- but I am sad to see that after more than quarter century EBM is still In its infancy.
Thanks for openly engaging about your practice - only by sharing our experience we can learn from each other
Best
Ben
Sent from my iPad - excuse typos and brevity
On May 25, 2020, at 11:56 PM, Kumara Mendis <[log in to unmask]> wrote:
Hi Ben
I guess when you have no treatment at all fir Covid and you have a lots of experience with using Chloroquine for Malaria you want to do something fir your patients
Patients will also be happy to know that they are getting some specific medications
This is exactly the situation in most of the LMI countries
Isn’t it not how most of the treatments for diseases have come about?
But now with this Lancet study things take a different turn
We have done evidence of the efficacy of the treatment
My question is how good is the study to inform us and can it be generalized ?
Thanks
Kumara
On Tue, May 26, 2020 at 8:38 AM, Benjamin Djulbegovic MD <[log in to unmask]> wrote:
The question is, Kumara
Why would you administer HCQ with or without macrolides to begin with? [Just because there is no effective Rx is not good reason “to try something”. ]
Ben
Sent from my iPad - excuse typos and brevity
On May 25, 2020, at 7:15 PM, Kumara Mendis <[log in to unmask]> wrote:
[Attention: This email came from an external source. Do not open attachments or click on links from unknown senders or unexpected emails.]
Dear all
In Sri Lanka everyone who is admitted to the designated hospitals with PCR+ COVID gets at least Chloroquine /HCQ
The Lancet has published a study
Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
The findings are :
We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.
Has anyone done a critical appraisal of this paper?
My question if you are a clinicians would you give HCQ and or macrolide to each and every person (I will add my own criteria after taking an ECG and if there is no abnormal changes of rhythm or other ischaemic changes)
Would much value your comments
Thank you
Kumara
Truth, wisdom, learning, and good sense—these are worth paying for, but too valuable for you to sell.
Proverbs 23:23
To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link:
https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1
------------------------------------------------------------
-SECURITY/CONFIDENTIALITY WARNING-
This message and any attachments are intended solely for the individual or entity to which they are addressed. This communication may contain information that is privileged, confidential, or exempt from disclosure under applicable law (e.g., personal health information, research data, financial information). Because this e-mail has been sent without encryption, individuals other than the intended recipient may be able to view the information, forward it to others or tamper with the information without the knowledge or consent of the sender. If you are not the intended recipient, or the employee or person responsible for delivering the message to the intended recipient, any dissemination, distribution or copying of the communication is strictly prohibited. If you received the communication in error, please notify the sender immediately by replying to this message and deleting the message and any accompanying files from your system. If, due to the security risks, you do not wish to receive further communications via e-mail, please reply to this message and inform the sender that you do not wish to receive further e-mail from the sender. (LCP301)
--------------------------------------------------------------
Kumara Mendis
MBBS, MD (Family Medicine), MSc (Medical Informatics), FCGP, FACHI
Chair Professor of Family Medicine
Faculty of Medicine
University of Kelaniya
Sri Lanka
Tel: +942961245 | Mobile: +94776794423 | Web link
Associate Professor
School of Medicine
Western Sydney University
Australia
Web link
Truth, wisdom, learning, and good sense—these are worth paying for, but too valuable for you to sell.
Proverbs 23:23
To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link:
https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1
To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link:
https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1
--
Vivek Podder
Medical Student | Tairunnessa Memorial Medical College and Hospital
Student Editor | International Journal of Medical Students (IJMS)
Scientific Writer | Joanna Briggs Institute
Visiting Lecturer, School of Public Health | The University of Adelaide
"Wherever the art of medicine is loved, there is also a love of humanity" - ― Hippocrates
To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link:
https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1
To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link:
https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1
To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link:
https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1--Kumara MendisMBBS, MD (Family Medicine), MSc (Medical Informatics), FCGP, FACHIChair Professor of Family MedicineFaculty of MedicineUniversity of KelaniyaSri LankaAssociate ProfessorSchool of MedicineWestern Sydney UniversityAustraliaWeb linkTruth, wisdom, learning, and good sense—these are worth paying for, but too valuable for you to sell.Proverbs 23:23
To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link:
https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1
To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link:
https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1
