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Major research papers from NEJM in 2023

Posted in Uncategorized, tagged , , , , , , , , , , on January 25, 2024|

Here is a pleasant surprise, a collectors issue of NEJM year book 2023, is made available free (even for non subscribers, in its website) .It is fascinating to know how fast the Internal medicine has grown. For the busy cardiologists, this will a be refreshing reminder, that there are other important organs and specialties do exist in medicine , with equal breakthroughs and Innovations.

It is indeed an amazing , whirlwind tour of medicine for all those who see medical science as single holistic specialty. It has articles, ranging from from simple clinical studies on postpartum hemorrhage (E-MOTIVE study) from deep inside Africa by Melinda Gate foundation, to Dupilumab for COPD, a stunning monoclonal antibody inhibitor of IL-4 for COPD exacerbations. Shortening tuberculosis treatment with a strategy involving initial treatment with an 8-week Bedaquiline-linezolid regimen (TRUNCATE-TB study) is also a revelation.

Of-course, the mandatory cardiac topics do find a prominent place including the currently omnipresent drug GLP agonist Semaglutide for HFpEF (STEP-HFpEF study). Baxdrostat, an Aldosterone synthase antagonist for treatment-resistant Hypertension, appears promising (BrigHTN).

Final message

However, the crowning glory among all articles appear towards the end of the document, titled Combating misinformation as a core Function of Public Health.

Let me share the link to this PDF document here. Hope it allows open access and there are no copyright issues. Notable articles of 2023 from NEJM .

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Rosuvastatin or Atorvastatin , Which is good and safe ?

Posted in Uncategorized, tagged , , , , , , , , , , , , , , , on November 10, 2023|

Statins belong to a group of drugs, stolen and reengineered from the blueprint of natural Chinese red yeast rice (Monocoline K) in the late 1980s. The rest is the remarkable history in the pharma industry.

Statins directly interrupt the cholesterol synthesis by blocking HMG-CoA within the hepatocytes. It significantly lowers the LDL, fights human vascular atherosclerosis. It makes the plaque either regress, prevent progress, make it harder and in the process make them less vulnerable . There are innumerable studies that document the evidence. Statin has become a must-prescribe drug in any one with clinically established CAD or even in concealed CAD. Guidelines are available to prescribe statins various intensity, depending on the risk profile.

Which statin ?

There has been a long list of statins. Many of them have retired from the ring .Currently, the fight is between Atorvastatin, a Rosuvastatin. Like Pepsi vs. Coke.

Note the graphic ,A meteoric rise of one drug since 2005 . (Can you guess the reason ?)

ATRORVA or ROSUVA Which one should I choose ?

There is very little “one to one” comparison study between Rosuvastatin and Atorvastatin .The gap in the pros and cons are narrow. Following points are observed, without much dispute.

1.Rosuvaststin is more powerful.

2.Plaque stabilisation effect is not different((Satrun, study NEJM 2011 based on IVUS)

3.New onset diabetic risk is more likely with Rosuvastatin

4.Worsening of cataract is also more with Rosuvastatin

5.Atrovastatin has some additional benefits in lowering triglycerides. (Bakker-Arkema RG, JAMA. 1996)

No one is dare enough to give strong verdict . Surprised to find one this month. BMJ has come out with a possible answer. It is called LODESTAR trial (Ref 1)

Mechanism of new onset diabetes with statins (REF 3)

It can be 7% with Rosuvastatin (less with Atorvastatin). We think, statins act primarily within the hepatocytes where cholesterol synthesis takes place, but they also have an eye on the pancreatic β-cells as well. It down-regulates GLUT-4 in adipocytes, and results in compromised insulin signalling. Furthermore, statins’ impact on epigenetics may also contribute to statin-induced T2DM via differential expression of microRNAs.

Mechanism of cataract with statins (Ref 2)

The cells lining that line the lens are dynamic and require cholesterol on a day-to-day basis. Statins inhibit proper epithelial cell development within the crystalline lens, where cholesterol biosynthesis is critical to maintain transparency and structure of the lens.

Final message

So, is it Atorvastatin or Rosuvastatin? It is left to you.

Mind you, “no statin at all” is the best option if circumstances and risk profile allows. Statins are never considered life-saving staple drugs in our fight with CAD and atherosclerosis. We, along with our scientists might may make you feel like that. Lipids can be controlled within desirable means exclusively with diet and exercise in most of the population* .

(*Forget about statins in the last 5000 years of known human existence, so many great people have lived a long and successful life in this world, without even knowing there is an organ called the heart that is responsible for the circulatory system)

Reference

1.Lee YJ, Hong SJ, Kang WC, Hong BK, Lee JY, Lee JB, Cho HJ, Yoon J, Lee SJ, Ahn CM, Kim JS, Kim BK, Ko YG, Choi D, Jang Y, Hong MK; LODESTAR investigators. Rosuvastatin versus atorvastatin treatment in adults with coronary artery disease: secondary analysis of the randomised LODESTAR trial. BMJ. 2023 Oct 18;383:e075837. doi: 10.1136/bmj-2023-075837. PMID: 37852649; PMCID: PMC10583134.

2.Leuschen J, et al Association of statin use with cataracts: a propensity score-matched analysis. JAMA Ophthalmol. 2013 Nov;131(11):1427-34.)

3.Carmena R, Betteridge DJ. Diabetogenic Action of Statins: Mechanisms. Curr Atheroscler Rep. 2019 Apr 30;21(6):23. doi: 10.1007/s11883-019-0780-z. PMID: 31037345.

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Extreme “Knowledge + Skill” is a powerful stress test for our Intelligence

Posted in Uncategorized, tagged , , , , , on October 22, 2023|

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“World heart day” : Two conflicting messages

Posted in Uncategorized, tagged , , , , , , , on September 29, 2023|

World heart day is being celebrated every year on September 29th ,Initiated by the World heart federation with a genuine purpose, vision & goal. It has become big hit in recent times. In India, the theme has captured the imagination of the main stream media . Every one wants to propogate a message. I am not an exception. Please bear with this skewed message “One for the patients and the other for the self” !

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A potential new face of “Ethical dysfunction” is waiting to unfold !

Posted in bio ethics, Medical education, Medical ethics, medical satistics, tagged , , , , , , , , , , , , , , , , on September 8, 2023|

Postamble

This quote is being sent for the annual meet of “Right care movement” I know ,this can sound outrageous, permissble limits of abuse ? Up to 2% or 5% ? Let it be anything . Meanwhile try to enlighten yourself , the key differences between misuse & abuse.

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Be happy with the “H” Index of Hippocrates

Posted in Cardiology quotes, cardiology-ethics, Uncategorized, tagged , , , , , , , , , , , , , , , , , , , on March 5, 2022|

“Publish or perish “

This sound bite is regularly uttered by all academic leads in any university or medical school. I don’t know, why this bothers me. Looking back, many of our mentors & professors never had any great publications. Still, they were extraordinary teachers and wonderful clinicians with great wisdom. They created generations of high-quality doctors who are present all over the globe now. Is scientific publication that important in a doctor’s life? After pondering for quite some time, got a hazy answer to that query in one of my sleepless early morning academic dreams.

Hippocrates was one of the applicants for the post of professor of medicine at Harvard medical school.His application was rejected for a dismally low H index. The reluctant father of medicine tried to impress the authorities, by telling them that his experience was vast and used to teach medicine 2000 years ago, well before their country USA was discovered. The father of medicine almost begged to reconsider their decision.The miffed Harvard academic office ridiculed the old man and insisted nothing will work, except a minimum H index of  50 or atleast 10 papers as first author in a peer reviewed high Impact  factor journal. A dejected Hippocrates returned to Kos islands and asked his new generation fellows, what is this H index and Impact  factor stuff ? His students were worried about their guru’s ignorance. They some how convinced the greatest ever medical teacher to urgently subscribe for a platinum membership of a premium medical authourship services located in the Boston suburb and fixed a 30 day deadline for his first manuscript.

(What is this H index ?)  Why is it so popular?)    Ref : J. E. Hirsch  An index to quantify an individual’s scientific research output Proceedings of the National Academy of Sciences Nov 2005, 102 (46) 16569-16572; 

Off to Kos Islands 

Now, let us travel back in time,2000 years ago to this picturesque nation, Kos islands in the Aegean sea,. This is where Hippocrates taught lessons under his favorite tree. No teaching apps, No 4k audiovisuals, The humble noise from within his lips became great wisdom thoughts. All that students had were set of ears to hear him. Hippocrates became the celebrated father of medicine for two reasons. He was the first to dispute the then-prevailing thoughts about human health and disease. He first proposed for every illness there is a hidden reason ie the beginning scientific basis. He insisted and negated the idea that diseases are bestowed upon by evil forces and spirits. The second one is more important. He realized knowledge, skill, and power are a deadly mix for the healing industry if they lack responsibility. He foresaw non-academic factors that will try to challenge the integrity of medical professionals and the health care delivery systems. It is astonishing to note how he could predict this 2000 years ago and wrote the behavior code for medical professionals which has become immortal.

How to grade the quality of medical professionals?

Scientific publication is just one of the indices of quality assessment for medical professionals. Grading them based on a few manufactured rating systems is beginning to look like an academic comical. There are many more visible and invisible, quantifiable and non-quantifiable quality assessment parameters that deserve attention.

Research  & Innovations are indeed the pivotal pillars that take us to newer frontiers of medicine. But, It is explicitly clear now, the prime purpose of research is definitely not aimed at the growth of science. It is more of a survival tool, intertwined with commerce, status symbol, pride, peer pressure, self-esteem, rivalry, or just a filler for CV. 

Final message 

Blanket statements like Publish or perish at any cost could be a dangerous doctrine to adopt in medical education which is essentially about healing and caring (& whenever possible, curing). In one sense, medical teaching is little to do with research. Many of the great professors in our country never published a single paper. Unfortunately, research and teaching have been made to look inseparable. Beware, history has repeatedly taught us medical professionals need not be hyper-intelligent. They need to be just wise, men /women of integrity, enriched with sincerity, righteousness. Proper consumption of knowledge is much more important than the creation of it. Let us hope the future will be at least as perfect as the past. 

Postamble

My  H index stands at 15, I must confess I am confused a lot. Should I bother for more, or be just be happy to reach the H index of our mentor and father of medicine, which is numero Zero, and propagate his work. 

Reference 

1  Grzegorz Kreiner The Slavery of the h-index—Measuring the Unmeasurable..Front. Hum. Neurosci., 02 November 2016

2.Academic excellence does not always require publication  Ernest L Boyer argued in his 1990 book, Scholarship Reconsidered: Priorities for the professoriate,(BoyerScholarshipReconsidered)

3.Too much academic research is being published https://www.universityworldnews.com/post.php?story=20180905095203579 

 

 

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Testing times for EBM : NEJM gets ready & begins a new journey

Posted in Uncategorized, tagged , , , , , , , on January 19, 2022|

The New England Journal of Medicine (NEJM) the premier journal in medicine originated two centuries ago, in 1811, when  John Collins Warren, a Boston physician, along with James Jackson, submitted a formal prospectus to establish the New England Journal of Medicine and Surgery and Collateral Branches of Science as a medical and philosophical journal. 

Subsequently, the Massachusetts Medical Society (MMS) purchased the Journal for US$1 and, in 1928, renamed it to The New England Journal of Medicine.

NEJM’s New Journey

It is 2022, after 200 years of providing explosive knowledge in medical science, MMS  starts a new journal, fresh and bold. It is called NEJM Evidence. Can you guess, what is the need for such a journal now? I think the most battered word in science in current times is probably “ evidence”.  It has a unique character of appearing most sacred as well as scandalous at the same time.

NEJM has remained the torchbearer of almost all advances in the medical field seen in the last two centuries.  It is heartening to note the newborn is named as NEJM evidence. It has come at a critical juncture. I am sure, everyone will acknowledge that we are at difficult crossroads. Overwhelmed with unregulated scientific discoveries and publications, struggling to deal with self-inflicted knowledge pandemic. In the process, we have lost “not only” the ability to ignore trivial health issues “but also” failed to provide simple, cost-effective care to the real patients who desperately need it.

Let us hope, (& wish,) NEJM’s new prodigy will guide medical science towards a successful, meaningful, and ethically fulfilling journey for mankind. Meanwhile, let us pray for every medical scientist to be blessed with the required strength and courage to steer in the right direction, weeding off both academic and non-academic contaminants.

 

 

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FAME 3 fails to defame CABG, cardiologists need not worry though !

Posted in Cardiology -Therapeutic dilemma, Cardiology -unresolved questions, Ethics in Medicine, fame study ffr, Fracional flow reserve, tagged , , , , on November 5, 2021|

News: Series of clinical trials fail to clear the ongoing confusion in the business of cardiac revascularization.FAME 3 is the new addition. 

Caution: A non-academic journal review

There is no secret, about this cold war happening in an incognito mode for territorial rights between cardiologists and cardiac surgeons in glamorous cardiac suits for the past two decades. Of course, we keep believing this is a friendly fight in the overall interest of CAD patients. The ultimate winner should be the patient, not anyone else. Will that happen? Will anyone will allow that to happen? I am not sure.

The FAME3 is a stunning large study from 50 centers FFR guided multivessel PCI, that failed to dethrone CABG (or at least it wanted to sit along with it) I am not a seasoned statistician but definitely can’t understand the logic behind the methodology* and the choice of words in the conclusion from a paper published from a renowned journal.

 

 

(*I can recall an article about Non-inferiority trial  from Lancet (Ref 1) )

FAME 3 aftermaths: A dizzy Interpretation

Before accepting the fact that, FFR guided PCI wasn’t able to show its superiority or to unable to prove its non-Inferiority, while CABG was clearly found to be non-inferior, (rather superior) to PCI, we should take into account an important caveat in the concept of FFR itself, which has at least half a dozen serious hyperemic and non-hyperemic flaws that demanded a more superior,non-hyperemic indices like iFR, RFR, qFR, etc.

Those of you who still believe PCI would be an undisputed modality in multivessel CAD  should take up the challenge and disprove the superiority of CABG by doing the same FAME 3 subset with iFR and other stuff. (Eagerly waiting for the hypothetical iFAME 4 trial)

One more way to Interpret FAME 3: How can we accept FFR guided multivessel PCI as inferior, unless we have an FFR guided CABG (FAME 3 didn’t do this) to compare? Can you guess if only pre-CABG FFR was mandatory criteria, that would have excluded or included important grafts, what would have been the impact of CABG? This is a more dramatic suggestion, that will say sorry to FFR,( the old physiological friend,) and label it as a new villain.

Final message 

Multivessel PCI still has a long way to go before trying to dethrone CABG.  But, strictly scientific cardiologists need not worry much and they can continue to indulge multivessel PCI without FFR, which is no longer unscientific ! Thanks to FAME 3. I think one of the Important indirect consequences (?purpose) of FAME 3 would be, playing the end game for FFR.

Reference

https://doi.org/10.1016/S0140-6736(07)61604-3

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Discontinuing medical education : Why current medicine is often not the correct medicine ?

Posted in Cardiology - Clinical, cardiology -Therapeutics, cardiology innovation, cardiology-ethics, history of cardiology, tagged , , , , , , , , , , , , on May 16, 2011| Leave a Comment »

One of the greatest medical sermon of our times  is   “Doctors must   constantly update their knowledge , Continuing medical  education is as sacred as their profession  !  If you are not updating your knowledge you cease to a doctor “

It is fashionable , but true  to state  modern medicine lacks humane  care . Modern medicine  is  challenged by a huge  technological ,  commercial  onslaught  where common sense takes  the back seat

Hence , doctors need to renew not only  their  academic competence   but also  their ethical  fitness  every  year !

Aggression  could be the other  name for  modern medical care . For every  new  invention , treatment   or guideline that  is  approved  an equal number  is shelved after few months or years  for safety reasons.

Bulk of  medical updates  for  current age physicians  is nothing , but asking   them to forget  all those wrong things that has been meticulously uploaded in their brains in the recent past  ( Recall the classical story of drug eluting stents )

If this is the  case . . . then  . . .  what for  we  are  updating ?   and  for what  we are  learning and forgetting  ?  and  . . . how frequent we need to forget ?  Of course  , there is a big chunk of   human tribe  who  can never master the art of forgetting ! Some mistakes are permanently etched in their terra byte hard disks .

Is there a place  for backdating and discontinuing  medical  education  ?

What  man- kind needs  at times of  medical  crisis  ,  is  not  the current  treatment  but the correct  treatment    .It is our duty  to  find  all those  trustworthy  drugs  & treatment modalities  that were  sent  to  the gallows by the modern medical forces   for various reasons !

If  some of  the gems in  medicine are  left behind in  past  “time domain”  ,  it is  mandatory  for us  to go  back in time and   catch it , adopt it and disseminate it !

Further ,  whenever  the  hyped   “medical updating sessions ”  turns out to be  synonymous with adding nonsense (It is  becoming all too common these days   !) we should resist   it by all means !

For many . . . Hippocrates and his medicine sounds dirty now !

If  only we back-date  our knowledge   .  .  .

Todays  youngsters  can learn a secret that liver enlargement can be diagnosed easily  with their  hands ,  without  waiting for a  CT scan report !

If only we back-date  our   knowledge  . . .

We can realise  Aminophylline can save so many  lives of cardiac  failure  , which  our newer inotropic agents are struggling to accomplish .

If only we  back- date  our knowledge  . . .

We can calmly manage  acute MI with lignocaine  even in a country side  .  Amiodarone unfairly replaced  this  efficient  anti  VT  molecule  for no academic reasons !

If only we back- date  our knowledge  . . .

We  can  advice simple non pharmacological intervention for  stage 1 HT   than prescribing the  glamorous  sartan molecules  form a  multinational  ARB shoppe.

If only we back- date our knowledge  . . .

We can  promptly recognise  cardiac failure  without  ordering  for the error prone   BNP . Back dating also  helps us to under stand  that post infarct angina is a  glaring sign  for presence of   viable myocardium  and prevent us from undertaking a  2000 $ PET  excursion !

If only we back- date our knowledge  . . .

We can  send  all our uncomplicated , asymptomatic   STEMI  patients ( in class 1 )  straight to  their  home rather than to cath lab  play grounds !

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This article from mayo clinic is a real shocker ! . . . for all those interventional cardiologists !

Posted in Cardiology - Clinical, Cardiology -Interventional -PCI, cardiology -Therapeutics, tagged , , on February 12, 2011| Leave a Comment »

The review published in the prestigious NEJM seems to suggest

PCI  , the most  commonly  performed  therapeutic cardiac intervention  may  result in  more  myocardial  infarction in the community  than  the deadly atherosclerosis itself.


Can it be true in any  stretch of imagination ?

Yes , it seems so . But the only issue  is the  criteria   used to define MI  .

Comments are welcome on this article .

You won’t get the full text article free  .Try to get it from your library .It is worth the time spent  !

http://www.nejm.org/doi/full/10.1056/NEJMra0912134

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