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Posts Tagged ‘jama’

                                            The growth of medical science has been phenomenal .It is estimated , the quantum of break throughs  and development  in the  last  50 years  is   nearly equal  to  2000 years of evolution of our  knowledge  put together.  Along with this growth , came the  unavoidable misuse , and abuse of medical science. This  is mainly due to contamination of medicine with commerce . Federal drug authority (FDA) and it’s variants  were formed in all countries to monitor the proper usage of  these technologies for the benefit of mankind. It has an authority to ban a drug or device  , if it is found to bring more injury or side effects  than benefit !

But , unfortunately there is no legal authority to ban an  an  investigation  which is  potentially  or (really  harmful )

or  used  extensively without any valid purpose .

The list of such investigation is increasing in every speciality 

In  cardiology

  • Doing a Troponin assay in patients wuth classical STEMI
  • MDCT in general population
  • Pro BNP in all suspected cardiac  failure
  • Routine C reactive protein for CAD
  • Central venous catheters for all pateints with shock.

Is there a case for banning an investigation (Like banning a drug) for the benefit of  our patients ?

Looking superficially , it  may seem  ironical. But we realise many seemingly  innocuous investigations are responsible for uncontrolled misery for many patients.

This especially true in people who throng the wellness clinic (Also called master health check up)

A incidentally high C – reactive protein   can lead on to forearm blood flow assessment of endothelial dysfunction and carotid intimal plaque  that could  lead onto carotid stents ! and life long anticoagulation , and an  excess INR and sudden cerebral bleed and death !

This is one sample story  in one particular speciality

There is a definite case for banning ( Either total or partial)  some of the questionable investigations  which are done routinely !

Just because these investigation do not have any  physical , visible , adverse reactions like a drug , it should not be allowed to be abused  .The consequence of  false positive results of these investigations could be terrible and worse than the real disese itself !

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The irony of medicine is unlimited !  100 years of active clinical  research   failed  to find a specific cure for the rhino virus mediated common cold.In fact  US Govt stopped funding for this .

While ,   complete cure is possible  for many of the cancers, especially hematological ones !

Message 

In medicine there are thousands  of disorder  which have no cure ! 

Cancers ,  constitute  only a  fraction of  them !

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Let us not forget the basics !

  • HT management has been made  easier with the availability of  many  good drugs , at the same time it has become a complex  issue with as many classification and guidelines.
  • The management of HT has evolved over the decades. Now we have realised  HT  is not a simple number game . Reducing the blood pressure to target levels is not  sufficient and is not the primary aim !.
  • In fact we now know controlling the numbers alone is never going to work  , combined risk factor reduction is of paramount importance.
  • HT per se is less lethal but when it combines with hyperlipidemia and diabetes or smoking  it becomes  aggressive.The blood lipids  especially the LDL molecule  enjoy the high pressure environment  ,   penetrate and invade the vascular endothelium.
  • ASCOT  LLA  study has taught us,   for blood pressure reduction to  be effective and reduce CAD  events one has to reduce thier  lipid levels also.So , for every patient with HT there is not only a target BP but also a target LDL level .

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Final message

The tip for better vascular  health is  , all  hypertensive patients should keep their lipids to optimal levels and all hyperlipidemia patients should keep their BP as low as possible .

“Keep your LDL  as low as  your diastolic blood pressure  and  let us  keep it around 70 -80

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                                                 It is now mandatory for all  journals  to declare the  conflict  of interest by the authors  who are involved in medical research .The purpose apparently is to make all transactions or links  between the researchers and their funding agencies transparent .Even major journals  do not go beyond this . Some ensure it , to appear in the first page of  the article.

 What does the the journals tend to  convey to the reader by publishing the conflicts of interest ?

  •  Does it  mean the article in question  may have a bias or indeed have a bias  ?  and readers are warned  hereby !
  •  Do they send across a message  that the  article may not be really a genuine one and the judgement is left to the the consumers of the articles ?

How often a journal article is rejected purely on the basis of  conflicts of interest ?

Most of  journal articles are rejected  for poor methodology, statistical analysis and so forth .We don’t know how often a paper is rejected  due to a conflict issue per se.If this could happen ,bulk  of drug trials would face a torrid time from the editors.

Why , even the leading scientific  journals never indulge in grading the significance of the conflict ?

Here is an example .

accomplish

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The much hyped drug trial on Hypertension “ACCOMPLISH”  was published in the  world’s most prestigious medical journal recently .It  left  it to the readers to  have their  own assessment  on the conflict issue.

  The consequence of not , grading and investigating  about the conflicts could have  serious  global health  implications both financially and academically .

This study was designed, formulated, completed and published  with a single hidden aim of neutralising the land mark trial  of ALLHAT which recommended diuretics as a first line drug in HT.Apparently diuretics are very  cheap  , effective  generic drugs.

 Is it a scientific rule  that  the  latest evidence  ,  should always prevail over the older evidence ?

No. Science can never have such a rule ! The question is how good and genuine is the evidence.
Just because an evidence is current , it does not  attain a scientific sanctity !

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One of the important principles of medicine  is  “Diagnosis should  always precede treatment”

This quote , though appear reasonable , can not be practiced always especially in emergencies,  where we  have to first stabilise the patient   without a  prior diagnosis  .(Like administering IV fluids in hypotension , acetaminophen for fever , etc)

Modern medicine  considers treating a patient without a diagnosis as unscientific.

But,  it is a well recognised fact ,  millions  of decision in everyday medical practice is not based on scientific diagnosis  but on clinical acumen and empirical therapy . There are many  instances  wherein , we are never near the  diagnosis  even after exhaustive investigations. 

prescription3

                       Ironically , in this era of evidence based medicine , when  we are  unable to  conclude ,  we are forced  to do the most  funniest  thing , namely converting patient’s symptom itself as disease entity and  be happy  in labelling them. Like , Motion sickness ,  poly-arthritis, , chronic fatigue syndrome, adult respiratory distress syndrome ,  pre mature ejaculation, fever of unknown origin  , attention deficit disorder , etc (The list is endless . . .)

               This happens because physicians always feel guilty if they are unable to label a patient with a disease entity.

Is the guilt  justified ?  Not necessarily so !  Symptomatic treatment without  diagnosis  is the most dominant theme even today (Fever, pain etc ).So don’t feel unduly negative* when one is not able to fit a patent’s  symptom into a disease entity  but ensure  he  gets relief from his symptom.

 *Except of course , one has to rule out a serious disorder.

 Comments welcome

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                                Hypertension is the most common clinical  cardiovascular entity.Left ventricular hypertrophy (LVH) is  an important consequence of  HT.In fact, it is considered as a end organ effect or damage. Others being brain, kidney, and peripheral vascular disease.Knowing about LVH is important because it has been linked to increased cardiovascular events.

lvh-4

                              Though LVH is considered  as a close companion of  HT  it is  surprising  only a minority (15-30%)  show evidence of LVH .Some  experienced clinicians (Level C evidence)  quote even lower < 10 %  .Traditionally LVH was detected by ECG and now it is replaced by echocardiography.

What determines the LVH ?

It will be suprising to note , answer to this question  is  still not  clear .

  • Is it the duration of elevated blood pressure ?
  •  Is it the absolute level of blood pressure ?
  • If so , is it  the systolic BP  , diastolic BP or the mean BP ?
  • Or is it related to the etiology of HT ?
  • There has been no significant correlation between the above parameters

When we don’t know  the answer to a question in medicine , the answer will  generally will be inside the genes !

So in HT also the major determinant of LVH is in the genes that determine the myosin heavy chain  response .

and also ACE gene polymorphism.ACE genes are involved in the expression of growth factors within the myocardium.

An excellent study  on the issue http://www.nature.com/jhh/journal/v17/n3/full/1001523a.html#tbl1

It implicates , gender, age, race etc in the genesis of LVH

Final message

So , the  myocardium does not respond with LVH   in all patients with HT.It happens only in a minority* .Duration of HT can be an important determinant , but  the major factor is  the alteration of genetic switches  within the myocytes How this switches are going to  behave ,  is largely inherited .Regression of LVH is also not uniform again implying lesser role for hemodynamics. (Some studies revealed ACEI have maximum regression  of LVH , later disputed )

*LVH is more consistently seen  in hypertension due to reno vascular  or parenchymal disorders .It is also an observed fact , a  combination of diabetes and HT is more likely to result in  LVH.

The other major issue  that needs explanation in HT/LVH  is   , how much of LVH is due to  myocyte hypertrophy perse  and how much is contributed by interstitial cell hypertrophy(Non myocytic hypertrophy)

This issue will be discussed soon

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                                            The science of medicine has evolved over 2000 years since the stone age days.It has  currently reached  a glorious era with  cutting edge  scientifc  technology .Today  one can map the entire human genetic blue print and intervene in the  disease  even before they manifest .One can   keep dying people alive for years with multi organ transplantation. Modern medicine has taught us  how human sufferings can be prevented and life can be prolonged (with or without purpose !)

The term conservative management  conveys two different

meanings for medical professionals.

conservativ-3

For other group of physicians

 

conservative-4

                         

                             Ever since the days of  application of leech over the  head for treating migraine and a crude knife abdominotomy for emergency exit of babies from  pregnant mothers in distress  , healer’s   mind has always  perceived “something  has to be done  urgently when some body suffers”  this sort of  reaction is probably  inherited  and is related to  the primitive flight or fight response .

This may be true in  some of the emergencies but it is untrue in many of the non emergencies.

                                          Unfortunately ,  our mind  finds it difficult   to differentiate  between these  situations . With constant exposure to dramatic medical breakthroughs , modern day physician is made to believe   “Some thing  is always  better than nothing  when illness strikes. Human body is a wonderful machine which has it’s own service station ! in the form autoregulation  and the meticulous  homeostatic mechanisms. Only if the disease process overwhelms,  it needs intervention.( Typical example:In the routine viral fever , you don’t adminster Acyclovir or other antiviral  for all of them !

                                        The problem with early aggressive approach is,  it fails to give an oppurtunity  for the body’s natural defence forces  to respond. Further , we will  never ever know how the administered treatment is going to fare vis a viz the natural response.( With due respects to RCTs).   While the field of medicine   has  so much  evolved , our thought process,  especially  the  aspect of clinical  reasoning  has always been lagging behind .It is now considered  as inferior or even unscientific  treatment  if  some one follows a conservative approach to a problem even if  it  provides   same outcome of that of an invasive or aggressive approach ( The classical example is PCI for chronic stable angina The COURAGE study).

The other major issue is the hazards of unwarrnted  invesitigations , drugs and procedures

Classical example:No one knows how much morbidity or mortality the routine Swan ganz catheter  caused when it was rampantly used for over two decades to monitor central venous pressure .It is estimated  that in modern medicine  there are at least  few  drugs or devices  in each speciality waiting  for the same fate  as that of  the swan ganz catheter.

No body knows when it will be exposed .Our EBM will take it’s own time . . .Till that time humanity need to suffer.

This thinking is not new  The concept  “First do no harm is over 2000 years old”

hippocrates-primum-non-nocere

Questions in search of answers

 Does law of conservation of energy applicable to human body and medicine  ? 

 Can we defy death with modern medicine ?

Final message

  • Conservative management is still  a great medical concept  in many situations  and one should not allow it to die  by the whims and fancies of the modern scientific forces.
  • Whatever you do on the patent’s body  do it ,  only if it is going to helpful for him /her. If you are unsure  Whether a given  treatment  is going to help or not ask this question to an expert .
  • The widely prevailing  dogma  of aggression is always better than  non aggression  has absolutely no evidence.
  • So approach a clinical issue disease by disease ,  individual by individual.
  • Now , in this era  high tech  medicine  ,  It is lot more tougher to choose a conservative path as the pressure to do more and more  looms  larger ! It is easier to follow the crowd  than a path of your own .
  • Always remember it needs a  stronger  mind to  act according to our conscience !

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                    circulatory                                                                            A normally  functioning  circulatory system is vital for our survival . We have about 6000 ml of  blood, circulating  all over the  body in an  approximate time of 15-20 seconds.The pressure at which this blood moves across the body is called the blood pressure . Hypertension  or simply , high blood pressure is an undesirable  hemodynamic disturbance  in human circulatory system.Systemic hypertension is the most common type of hypertension. The blood pressure is primarily  dependent  on the status of the blood vessel(vascular resistance)  and cardiac contractility. This regulation is under  many neural and hormonal factors.Further  the blood pressure varies depending  upon the blood vessel calibre, and the local milieu.There is a progressive drop in blood pressure from major arteries to the small arteries .The pressure drop is maximum  across the arterioles to reach the venules .The venous circulation has the lowest pressure, it ends up at right atrium with a mean pressure of 0- 5mmhg.

Importance of regional variation of blood pressure.

It should be realised  ,  each organ has it’s own regulated blood pressure.The brain  perfuses by the  intracerebral pressure .The lungs decide how much should be the pulmonary arterial pressure.The kidney not only controls it’s own pressure but also  has a major regulatory role in  systemic pressure by rennin angiotensin system.The examples are numerous, portal system has it’s unique pressure controlling hepatic hemodynamics. The  retinal blood vessels regulate  intra ocular pressure. While the human  circulatory system has a wide variation of blood pressure  across the breadth and length of vascular system,  it is ironical a single snap shot BP with a brachial cuff is used  to define the normality and if it is normal every thing is thought to be  hunky dory !

 

 

It is widely acknowledged now , aging of humanity  is nothing but aging of our vascular system

                                    So we should have new parameters to assess individual organ’s vascular health as well as the currently popular systemic vascular health.The single important factor that determine coronary endothelial damage is the intra coronary pressure.It is never taken into account in any of the cardivascular mortality studies. This is the prime reason for  the widely prevalent conflict in the cardiology literature , namely : Controlling systemic  blood pressure has poor correlation with  cardiovascular outcome. Many of the so called normotensive individuals  have serious hemodynamic injury in their  coronary arteries.This was made apparent in the  ASCOT LLA  study , in which patients with  near normal blood pressure also benefited from statin therapy , implying  endothelial damage could occur at any level of systemic blood pressure.

What is the normal intracoronary pressure  ? When do you diagnose intracoonary hypertension?

The normal intracoronary pressure is around 40mmhg . Intra coronary hypertension as a clinical entity  is yet to be  recognised . There is no defintion available for intracoronary HT  , intracerebral hypertension as well. 

It’s still a  long way to  go , for the cardiology and neurology  community to assess non invasively  intracoronary pressures and  intra cerebral arterial pressure to prevent  coronary events ant strokes.

Final message

Simple risk prediction using brachial cuff blood pressure is a grossly unscientific method (Sorry, i really mean it ) to assess one’s vascular health.There has been  few attempts like vascular endothelial health assessment by fore arm blood  flow , central aortic pressure (Instead of brachial cuff pressure) as an  index for risk predictment and  assessment for hypertension is suggested.

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                                        Angina pectoris , classically occur on exertion and gets relieved on rest .This is called typical chronic stable angina as described by Heberden (CSA ) .  Unstable angina(UA), the term originally described by Noble O Fowler in early 1970s. ( Also being referred as  intermediate coronary syndrome , preinfarction angina etc).The definition for unstable angina has evolved  over the years  and currently  refers to .

 1.All new onset angina of any degree* Some include severe angina only ! New onset angina of very mild degree on exertion could be the onset of the first episode of  stable  angina. 

 2.Rest angina of more than >30 mts not relieved by taking sublingual nitroglycerine.

 3.All Post MI angina

 4.Any angina in patients who have been stented by PCI.

How to recognise a patient  who is shifting from  stable angina to  UA ? 
UA is  to be suspected when  a patient develops. 
5.More frequent episodes than usual
6.Angina occurring at lesser level of exertion than before 
7.Angina radiating to new site ( Example : Chest pain radiating  to jaw rather than to the usual left arm or vice versa)

Why the first episode of angina is given a special status and often considered critica ?

Angina is the  clinical expression of   myocardial ischemia.The course of  the  first  episode of angina , can not be predicted.It could be a the beginning of a chronic disease process, or it could be a progressive coronary occlusion as in unstable angina /NSTMEI , or the onset of even a STEMI.
In contrast a patient with chronic stable angina  has a predictable chest pain , at a particular level of exertion, radiation to same site, same character, and the patient knows for sure the pain  would promptly dissappear  when he takes rest or nitroglycerine  tablets.

What is the underlying pathology in UA ?  

Generally it is very rare for  a stable plaque to produce a  serious episode of unstable angina .It  requires  an unstable plaque* to  precipitate an unstable angina !
Unstable plaque refers to any plaque which is eroded, fissured, ruptured or  hanging  eccentrically ,  with
an active thrombus.

What is the significance of post PCI angina?

It is an irony, any angina following PCI is to be considered unstable as sudden occlusion of stent is quiet common.This is a paradox of sorts as one would wonder in a patient  with CSA who undergoes PCI with stenting  of left anterior descending coronary artery  (LAD)  all his subsequent episodes of angina  will be labelled as UA  even if a stable angina occur in his other coronary artery.And these patients would go for early invasive approach and potentially inappropriate interventions even if they are at low risk !

Is all angina at rest can be termed as unstable angina ?

No, but many times ,  rather most of the times  cardiologist believe all rest angina to be unstable.

What are the situations where stable angina can occur at rest?

An episode of angina during mental stress, or post prandial* state are very common in patients with CSA. This gets relieved after the stress. Some times  patients with CSA during episodes of fever may get angina at rest .These are considered variants of stable angina.
Post prandial angina , may be considered by some as unstable

How often a diagnostic confusion occur between CSA and UA ?

Generally, this issue is rarely addressed in cardiology literature , for the  simple reason it is never considered an  issue at all !
According to Canadian cardiovascular society grade 4 stable angina  is almost similar to unstable angina , as it denotes angina occurs with minimal effort or even at rest. In fact CCSC grade 4 should be termed as UA.

Can ECG be useful to identify stable angina from unstable angina ?

                                    ECG will some times  come to our rescue when one is confused between stable and unstable angina even though resting ST depression can occur in both stable and unstable angina . Statistically , if ST depression is noted during an episode of angina it is more likely to be UA rather than CSA. . Apart  from ECG , Troponin T or I levels may be elevated in some of the patients with unstable angina. Rarely stable angina can also show elevated troponin.

In patients with systemic hypertension and LVH or cardiomyopathy resting ST depression may not indicate UA 

So differentiation between, stable and unstable angina even though appear simple and  straight forward, it requires a diligent appraisal of history , physical examination (Aortic stenosis /HCM  may cause stable angina)  and ECG, enzyme evaluation.

Final message

In any coronary care unit ,  admissions with initial diagnosis of  ACS/UA/NSTEMI , subsequently turn out to be simple stable coronary artery disese . This error happens because the chest pain  or ECG changes  are aggravated by non cardiac factors like a mental stress or a post operative stress  or fever etc.
There could  be another school of thought, that is to err on the side of  safety, and manage all  rest angina as UA  .But the hazards of unwarranted therapy might exceed the risks of leaving these patients alone.
In this context ,there is a need for a new definition for unstable angina .
One ideal version could be . . .
  • Any angina , of any degree  which is caused  mainly by the supply side defect (By a acute thrombotic /disruptive plaque   occluding the  coronary lumen  with a imminent danger of myocardial infarction is to termed as real UA.
  •  All post MI and post PCI angina are unstable angina
  •  Rest angina which occurs due to increased demand situations need not be  labelled  as unstable angina for the simple reason  there is neither an active plaque nor a  fresh thrombus likely  in these patients. They rarely develop  recurrent angina or MI . The mechanism of angina at rest here is most often due to a tachycardia and resultant increase in MVO2 .(myocardial oxygen consumption) .Currently they are called as secondary unstable angina.In fact , anti thrombotic drugs are misused in these situations as they satisfy the criteria of UA/NSTEMI.

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          During CABG arterial grafts are always preferred over venous grafts , for the simple reason the grafted vessel has to carry arterial blood and not the venous blood. Saphenous veins are tuned to carry venous blood at low pressure.The mean coronary arterial pressure is around 40mmhg and this will damage the saphenous venous endothelium more quickly. The reocculsion rate at 10 years for venous grafts  can reach  60%.


                                                    Left internal mammary artery (LIMA) is the most commonly used arterial graft. This is usually anastamosed with LAD. The lumen of LAD &  LIMA are more or less equal and they match well in character also !

The other advantage  of  LIMA graft  is ,   blood    tends to  flow  both during systole and diastole in a smooth fashion.. Since the venous graft which  hangs from the root of aorta , the  ostium  of venous graft lacks the  hemodynamic benefits of   coronary sinus . (We know the coroanry sinus acts like a  reservoir for  the smooth release of  blood flow into coronary arteries.)

Finally ,  the most important feature of LIMA is

  It is a live graft

LIMA’s proximal origin from subclavian is left intact, so LIMA acts as a live vessel with it’s  vasa vasorum intact ,  which means the endothlium derived relaxing factor (EDRF-Nitric oxide) secretion is not interrupted.This makes the LIMA  an excellent graft , self protected against reocclusion.One may call it a drug eluting graft !

 What is the patency rate for LIMA ?

LIMA patency rates at 10 years is nearly 90 %  .But the graft patency depends on many factors , like diabetes, age, gender, surgical technique ,(Now , beating heart CABG is very popular , where the LIMA patency is said to be slightly lower than conventional CABG) Sequential LIMA grafts, free LIMA graft ( Which  loses the advantage of being  a live graft) have relatively lower patency rates.

What are the other arteries used in CABG ?

Other arteries that could be used are radial artery, right internal mammary artery, and gastro epiploic artery.The patency rates of all these arteries far less than LIMA .

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A surgeon testing LIMA flow before Anastomosing it to LAD.

Image courtesy Dr.Mannoj Aggny .You tube

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