GOOD NEWS, AN ALTERNATIVE TO WARFARIN

Warfarin is a very old drug, almost as old as myself. It was approved for use in 1950 in the US for the treatment of Deep Venous Thrombosis ( DVT ) other forms of peripheral vascular thromboembolism, use following artificial valve rerplacements and also in atrial fibrillation. For the many good that it does, there are also many problems, primary of which is bleeding. Warfarin is a very fussy drug and has a low therapeutic index. It is affected by many foodstuff, making its use and control difficult. Patient have to undergo routine blood test, so that as clinicians we can guage its strength and so prescribe a correct dose. With too hign a dose, we of bleeding and with too low a dose, we run the risk of thrombosis ( clot formation ). It also takes a fews days for its action to come on.
Yesterday ( 30th Aug ) at the European Society of Cardiology Congress, now going on in Barcelona ( A H1N1 or not ), Dr Micheal Ezekowitz presentaed a paper entitled " Randomised Evaluation of Long-Term Anticoagulation Therapy" or Re-Ly for short. This is a study comparing the use of a new drug called Dabigatran Etexilate ( Boerhingher I ) versus Warfarin in the management of chronic atrial fibrillation. It came out that Dabigatran E at either 110mg BD or 150mg BD is better then warfarin. 951 centers in 44 countries enrolled 18,113 patients. So this is a very large study. There was a 35% reduction in in peripheral embolism and strokes, and a 74% reduction in bleeding . However, it is important to note that this is not a blinded study. It is what we call an open probe design, meaning that the investigators and patients know who is taking what, thus giving us a potential possibility of biaseness and error. Be that as it may, the results are also encouraging. There are however two notes of caution. Firstly, the mean followup period is two years. There is a slightly increase ( though not significant ) in Myocardial Infarction rates. and also the previous member of this group of drug, ximelgatran, had a nasty, serious side effects of liver necrosis. Perhaps we have to observe longer. Dabigatran is an anti-thrombin, which means that it binds to the thrombin and prevents it from cleaving off to trigger the clotting cascade. It is an anticoagulant and so the slight increase in heart attack rates must be carefully observed. It would appear that in some patients instead of blocking, it may infact stimulate the cascade. I suppose there is no perfect drug. However, we are assured that after two years, the rate of that happening is rare.
Well, on the positive note, there looks like a possible alternative to the " rat poison " warfarin that we now prescribe to our patients. The last note to observe with these new designer drugs is that it cannot be cheap. Warfarin on the other hand is dirt-cheap.

HAPPY MERDEKA. LET US PRAY FOR UNITY FOR OUR COUNTRY AND WISDOM FOR OUR LEADERS.

A H1N1 PANDEMIC VIRUS 2009, IS THERE A CONSPIRACY HERE?

I was at the dialog with the minister of health this afternoon, representing the private medical practitioners' association. It was a very informative session, both for what we discussed ( the seen) and also for what was not discussed ( what I observed ).
Of course we discussed the current situation. I must say that I occupied quite a lot of microphone time. The minister brief us on how he saw the current situation. He kept saying that the death rates were going up and that there were more and more cases of A H1N1 reported. This was echoed by the deputy Director-General of Health. But when asked, the deputy DG said that he had no statistics of the infection rates. His gut feeling was that infections seemed to have plateaued and slowed down. I informed the minister that my data and observation, tells me that for the last week, the ministry of Health have cease to report the daily infection rates ( something which we advised the minister when we had a private dinner with him on 13th Aug. ). The death rates ( I quoted ) has slowed down from 64 on the 13th Aug meeting with the minister, to 71 till today. In fact the 71st victim died on 20th Aug. and the death was adjudicated by the mortality review committee ( something which we asked the minister to set up on the 13th Aug dinner so that all deaths could be properly "labelled " to make sure that they were all A H1N1 caused ). Basically, about less than one death a day. Well, I argued that if the death rate has slowed and the infection rates have slowed, why are we still in a panic state and calling it a pandemic? In fact, whole wide, the same is occurring. In Australia, UK, China, Hong Kong and USA the infection rates and death rates are plateauing and falling.
What was observed, silently was that in the room ( although this was a session of the private doctors, with the minister and ministry ), there were managers of selected pharmas there. This always makes one wonder whether there are agents out there ( ? selling anti-virals ) hoping to keep the panic on, so that they can sell more drugs. It is true that there are still people who are sick out there, but in my personal opinion, not anywhere near panic proportions. It is important to note that most of the infections now are mild ( assymptomatic carriers, or those with mild flu-like-illness ), 95% of whom will surely recover. Should we keep harping in the press and keep the "panic " on?
I must say that when I saw the generic drug company manager there, it dawn on me that there are agents of profit outthere trying to profit from this "pandemic ". I suppose, in business, in every crisis, there is an opportunity. It does not really matter to some, that some others would suffer, if this "pandemic situation" last too long.
To be complete, we also discussed a whole host of issues, including price of anti-virals, not to bash private doctors in the press, strategies and flow charts to follow in the event of, use of MOH websites for information, data collection, and also a clinical presentation.
All in all, I thought that what was not said came through louder for me than what was discussed. Maybe I am just being too suspicious?

SLEEP AND THE HEART

Sleep is one of the less noted or talked about problems in medicine. In fact when I was in medical school, there were very few sleep disorders taught. Even those taught were usually psychiatric related. Related to Freud and his theories. Acute and chronic depression for example.
Well over the years we are learning that actually sleep forms a very vital part of our health. Inability to rest well at night ( sleep ) gives rise to all kinds of health problems, physical ones I mean. Sleep apnea ( the extreme example ) we now know to be closely related to hypertension and heart disease. More recently, there have been much work done to show that sleep may reflect cardiac health. In the 18th Aug on-line edition of the Public Library of Science medicine, Dr N Punjabi and colleagues from the John Hopkins Medical School, reported their study of a community cohort of 6441 subjects with sleep disorders of various degrees, from an age range of 40-70 years, with followup over 8.2 years. They found that at the end of the followup period, there were. 1047 deaths. Those with sleep disorders were 1.5 times more likely to die from a cardiac event. They divided the sleep disorders into various grades and categories and found that those with the more severe sleep disorders were more like to die, from a cardiac event.
Well, it may be time for all of us to pay sometime to our sleep and make sure that we have 6-8 hours of sleep with adequate periods of deep sleep ( REM sleep ), and that our partners report to us, if we snore excessively, or if we have sleep apnea. We should also pay attention to the fact that we should not be unduely tired the next day. Snoring, with periods of noisy grunting respiration, followed by a cessation ( stop breathing ) in respiration, and feeling very tired the next day ( so tired that we fall asleep while driving the next day ), should make us seek medical attention, in case we have sleep apnea. I had a patient who fall asleep at the traffic light and had all the cars honking.
Sleep apnea is a treatable condition. You would need to consult a neurologist and he will confirm the diagnosis and also prescrobe the treatment.
Remember, a good night's sleep is good for the heart.

A H1N1, A QUICK COMMENT

I am very relieved to hear it announced this morning, that there were no A H1N1 fatality over the weekend, in fact for the third straight day.
In fact, we here that all over the world, reported cases of " influenza-like illness ( ILI ) " have reduced and fatality have reduced.
However, it is timely to remind ourselves that this is no time to celebrate, but to remain vigilante and continue to exercise a good level of personal hygiene. Please know that the natural history is that there will be a phase 2 ( recurrence ) and here the issue of mutation and more or less danger, remains to be seen.
So good so far, but please continue to take care.

A H1N1 PREVENTION : MEASURES

After the letter to the STAR editor came out yesterday, this morning, many of my senior patients are asking about the measures that they must take. As you all know, I am a practising cardiologist and all my patients are considered in the " High Risk " group. So, despite the fact that early this morning, I have posted on " Ghost writing ", I thought that I will write a post on A H1N1 prevention.

Basic understanding:
The A H1N1 is a virus that causes this present round of " flu ". " Flu" is a common layman term for influenza. Influenza is an upper respiratory infection due to the flu virus, in this case A H1N1. Upper respiratory tract is that part of our body which includes the nose ( nostrils ), throat, and wind pipe. Should the infection get worse, it may involve also the lower respiratory tract, namely lower bronchus and the lungs ( left, or right or both ). The flu virus is highly contagious and is spread by droplet spread. That means that it is carried in the air, transmitted by persons carrying the virus, upon coughing, sneezing, spitting, ot even breathing. The airdroplets can be so fine that we do not feel it, and yet the virus is there. Anyone within touching distance of the infected host, is at risk of inhaling the droplets with the virus, into our upper respiratory tract, where the virus will fester and multiply. It will reside in the cells of the upper respiratory tract causing the symptoms of fever, sorethroat, cough, running nose, sneezing, etc. Of course, if the host is weak, the virus can overwhelm the host defence mechanisms thereby causing pneumonia and possible death if not treated. The incubation period is about 3-4 days, and once you have recovered, it may take a few days ( a week ) to get rid of all the virus.
It is important to note the presentation of flu can be very varied, depending on the virulence ( strength to cause harm) of the virus and the resistance of the host ( your body's ability to fight infection ). A low viral virulence and a strong host will mean almost no symptoms, or minimal symptoms and a strong virulence and low host body resistance will mean severe flu, which may result in pneumonia and death. The pneumonia ( infection of the lungs ) from flu, in a compromised host, may be viral ( viral pneumonitis ) or secondary bacterial ( means another bacterial has infected the weakened lung, causing the pneumonia ).

How to prevent?:
That's is why, in our strategy, it is important to identify those at risk, or what the minister likes to call the hish risk group. That allows us to try and target our main effort to select out those who need the most attention and management. Of course, every case is imporatnt, but some cases, we must treat early, because they are already weaked by their other condition.
The high risk group will include, anyone with any other chronic condition on drug treatment : example, diabetics, patient with heart disease, patient with strokes, patients with renal failure, patient with chronic lung disease, patients with cancers especially those on chemotherapy, chronic rheumatoid arthritis, etc. The list is probably too long to list down. It would need a textbook. But it is safe to assume that if you have a condition with requires and regular drug therapy, you should consider your self at increase risk.
People in the high risk category, if they have any fever for 48 hrs or more should see a doctor, better their own GP, for assessment. This are the people who may need close monitoring, oseltamivir early or antibiotics early, or they may need to be refered for admission. No harm going early to see your GP. The price to pay for going late is too severe. So go early for consultation. Of course, if you have no fever, don't go simply. At this point in time medical clinics and healthcare facilities, are also sources to pick up A H1N1.

For the general public who are NOT in the high risk category, please observe the following. If you cannot remember all the steps, basically, just keep good personal hygiene. Ok, lets go
1. Know that A H1N1 spread by droplet spread. Close contact of any sort ( within arms length ) with anyone is a danger because, we do not know who is a carrier of the virus. So avoid crowded places, unless you really have to, no choice. This would include all forms of public transport, buses, trains, airplanes, lifts, crowded shops, pasar malams, clinics and hospitals, large scale gatherings and events.
2. Wearing a mask helps but does not guaranteer against picking up the virus. It may reduce the infecting dose and give you a milder infection, but it does not avoid it all together. People wearing mask can still get the infection. It helps a little. There is minimal difference between the various brands of mask, which cost various amounts of cash. It may be wiser to change any mask that is wet, or well used.
3. Change your clothes whenever you come in from public places.
4. Clean your hands and areas of your body in contact which public objects during your visit outside and also upon your return home.
5. Drink plenty of fluids.
6. If you have flu or flu-like symptoms, stay at home, drink plenty of fluids, and rest. If the fever does not improve in 48hours, see a doctor.
7. If your fever also causes you to cough severely, resulting in breathlessness, please see a doctors urgently.
8. All flu at this point in time, should be treated as if it is A H1N1. Swab or no swab, makes little difference. Getting you well is the most important.
9. Do not cough or sneeze in public places, if you can help it. If you cant, cover your mouth and nostrils with a piece of paper or tissue and throw the paper / tissue away, once you are done. Handkies are not so hygienic. Of course, do not spit.
10. Do not panic, if you have fever. 99.98% of patients recover. The fatality rate is 0.01% at the moment.
11. Take care of your body at all times. Do not abuse your body.
12. When in doubt seek medical advice.

Please keep good personal hygiene. Keep yourself healthy so that your body resistance is strong. God help us, and see us through this crisis.

GHOST WRITING. ITS IMPLICATION FOR MALAYSIA

I thought that today, I should write about "Healthcare fraud " or " physician fraud ". We doctors depend on clinical trials ( the corner stone for gathering scientific data ), to establish practice patterns. Sometimes these same clinical trials are also used to form practice guidelines. Locally, our specialist tend to copy wholesale USA or European guidelines, as our own ( almost a "cut" and "paste" approach. Since the early nineties, we have suspected that some clinical papers in USA were written by professional ghost writers, sometimes employed by pharmas. So we have the pharma write a report, proportedly on an important clinical trial of one of their blockbuster drugs, pass it to a ghost-writing firm to touch up. Then they will pay some biggun in the medical circle to add their name as the first author, and send it to the esteemed journal for publication. Sometimes the pharma also time the date of release, just a day or two after it was "leaked" to the Wall Street Journal, for maximum impact. Afterall, it is a business and some physicians are co-operative to commit fraud. This seem to be the case with Vioxx, the important paper was by a Dr Kostam, in Circulation in 2001, reporting that Vioxx is safe. Unfortunately, this article was picked up by Senator Grassley, who began looking into the issue of "ghost-writing " and found that it was fairly common and not an isolated incident. There are even ghost writing companies out there, do this fulltime. He named one, DesignWrite, and the case quoted was a paper on OG products. In fact, Sen Grassley, together with Sen Kohl, is passing an act through senae called the " Physician Payment Sunshine Act " to ask pharmas the name of the doctors who had received USD 100 or more from the pharma for the year.
In cardiac circles, at all big meetings, the speakers all declare if they have any conflict of interest with the products used in their presentation, and of course everyone is clean as a wheasel.
In Malaysia the problem is a little different. Vety few of us do original research to get into US or European guidelines. Although I do hope that this will change, I don't see this happening in my lifetime. However, they are many " big boys and girls " who travel and holiday with and by pharmas and device companies, in exchange for their co-operation to get their products endorsed and pass through the DCA or government tenders. Business class travels, shopping holidays while on " conference ", some even bringing relatives along. When I am told these, I always say, "to each his/her own". It just tells me, what kind of values and person you are. I do not thing that I am in any position to stop it. I just wanted to highlight it and let the public know that sometimes the products and practice guidelines endorsed, are severely biased and not wholely in the interest of the patient. Doctors are not so clean afterall. Medicine is becoming more and more like a business.
Yes, when I was pioneering the stent work, I have many companies hosting me. I took a policy or rotation, and always go with the most evidence based product. I had an advantage. Since we are pioneering the work, we had alot of inside information on products, which is safe, which is good and which lacks evidence. That allowed us to use the best one for our patients and as it turns out, we chose the right one from 1991 till now ( for the stents at least ). Anyway, we are buying ( consigning ) such small amounts that it is virually no point " bribing" us, I suppose except for the marketing publicity.
Maybe Malaysia should also have a " Physician conflict of interest Act " to ty and safe guard the public and patients. But then, we are third world in many ways.

LATEST ON A H1N1 CRISIS : LETTER TO THE EDITOR-STAR

Letter to editor – The STAR

“AH1N1 – NEED TO RESTRATEGISE”

Dear Sir,

I am writing in support of the statement given by Dr C.Lee that appeared in the STAR 19^th Aug 2009. “Expert: case fatality rate not that high “. What Dr Lee said is true.

However, there is a problem.

A H1N1 is a very infectious disease. It spreads by droplet spread and so it is easily transmitted. The DG of Health calls it a high attack rate. For a country of 27 million, struggling with this crisis since April 2009, and with national and international transportation being so widely used, for such an infectious disease, 4,200 reported cases so far is a severe under-reporting. There are probably 20x that number of cases out there that are not reported. Because of this issue of under-reporting, many countries have stopped trying to report the number of new cases.

Unfortunately, 67 have died. This is regrettable. But if you were to be objective, 67 deaths, out of possible 70-80,000 cases, give a death rate of 0.08%. Still a bit higher than the usual seasonal flu death rate of 0.04%, but surely not any where near panic proportions. A closer look at the deaths revealed that 80% were A H1N1 associated, or were incidentally found to have contacted the virus, the virus by no means causing the death. We can call this A H1N1 associated death or death with incidental A H1N1 infection. So, if the certification of death is proper, it may be that only 15 deaths were actually due to A H1N1, giving a fatality rate of 0.02%.

The flu itself is usually a mild disease in the majority of cases. From all available clinical epidemiological evidence, the bulk of patients dying in flu pandemics are from secondary bacterial pneumonias. This has been shown to be the case in all flu epidemics and pandemics.

To consolidate measures that are already in place, it would be wise for the MOH to restrategise and put into effect mechanisms for the prevention of secondary bacterial pneumonia. This should include a national level SOP whereby all affected patients with secondary bacterial pneumonias would be immediately triage for intensive tertiary level care.

There is no cause for panic. We should all be vigilant, because there is a very infectious disease in our midst. We should exercise good personal hygiene, now and at all times, even after this crisis. If you are not well, as always, seek medical advice. There is certainly no need to panic and there is no national emergency here.

There is already too much misinformation and misperception of the situation out in the lay media without having to distract the public with the hype about national emergency.

.

Dr Ng Swee Choon

Committee member

Medical Affairs Committee,

Federation of Private Medical Practitioners’ Associations Malaysia.

FRACTURES AND " GLITAZONES " .

" Glitazones " are a group of drugs that we use to treat Type 2 Diabetes. They belong to a family of drugs called " ppar gamma " agonist. There are two drugs comercially available in the market namely rosiglitazones ( Avandia-GSK ) and pioglitazone ( Actos-Takeda ). They were both FDA approved. If you remember, about 5 years ago, there was this hooha about the glitazones being associated with an increase risk of CV events? This was highly controversial and many of us still use it with caution. But eversince the release of the results of ADOPT and RECORD, there was a high index of suspicion that " Glitazones " may increase the incidence of fractures. In fact, FDA required the companies to put in a labelling warning of the risk of fractures. At that time, some did not agree and felt that the fracture risk was minimal and may not be due to the drug.
In the 10th August issue of the Archives of Internal Medicine, workers in University of British Columbia, Vancouver, led by Dr Colin Dormuth, published an observational study of follow ups in 84,000 patients on the glitazones for at least 3 years duration and found that there was a 28% increase incidence of peripheral fractures in the long bones of their patients, there was minimal difference in the fracture incidence between pioglitazone ( slightly more ) and rosiglitazone. There was also no difference in the incidence between the sexes, although it was earlier believed that females were more prone. When they work out the statistics, for every 84 patients treated with the glitazones for 3 years, 1 may result in a fracture. Although it is not alot, it is worrying as these patients have diabetes and are usually in the older age group. adding another co-morbidity certainly does not help.
It is interesting to spectculate on the reason for this, although no one actually know. The ppar agonist ligand is involved in cell metabolism and protein formation. I really do not know the connection between the glitazones and bone matrix and calcium metabolism.
I have quite a few patients on rosiglitazone and so I must warn them that the evidence is stronger now that rosiglitazones may increase their risk of fractures.

THE AH1N1 HEALTH CRISIS IN MALAYSIA

I am going to deviate off my cardiac posting today, to talk about the AH1N1 crisis. Is there a crisis? What is happening now is getting crazier.

How does a senior clinician, albeit a cardiologist, see it?.

The whole situation began in Feb when news came out the the had been a " flu " outbreak in Mexico. The Mexican, did us all a severe injustice ( how to blame them, their healthcare system is probably worse than ours ), by not containing the infection in Mexico. Before you know it, the virus is all over the world. That is probably mistake number 1. The horse has bolted and left the stable. How to catch the wind?

Then WHO, who was monitoring the situation declared a pandemic sometime in June, when the infection seemed to have spread to 3 continents. This was a very liberal definition of a pandemic, without assessing the severity and also the virus strain. There are many of us who suspect that WHO was heavily pushed by drug makers. This is mistake number 2. Looks like the WHO is not beyond reproach. Now you have the whole world in some sort of a panic

Back home in Malaysia, we reacted and follow the flawed WHO advisory ( we did not think for ourselves ) by instituting measures that make people not want to come forward for treatment. We threaten to throat swab everyone, and quarantine them for seven days. This just drove everyone underground. This is mistake number 3. As a result, we now do not know the real incidence and pattern of disease and spread. Not getting the private GPs involved, and in fact blaming them for this that and the other, did not help. Now we have a situation whereby, our basic data collection is severely flawed.

Now we hear of more and more deaths, as if this infection is very deadly, when it is not. Just for statistical purpose, we are suppose to have about 2,000 reported, positive cases of AH1N1. Any epidermiologist ( specialist in the study of disease patterns ) will tell you that for every case reported, there are probably 20x the number unreported, especially in a disease as infective as AH1N1. If you apply that rule of the thumb, there should be about 40,000 people ( including boys and girls out there ) who have AH1N1. It is true that when the MOH surveillance system sampled the cases with throat swabs, they were all H1N1 ( so far ). There were no mutant strains at this point in time. Death is something that no one can hide. In our language, death is a hard endpoint. There were to date, 51 deaths, giving us a mortality of 0.1% ( if you agree that we have about 40,000 cases as predicted ) , still too high for a seasonal " flu" mortality, but not a deadly disease " panic provoking " situation. Mistake number 4 would be to make it sound like a deadly virus is going around the country. Which is not true. In fact, many of the deaths were not well documented, so one wonders whether it was like a post 9/11 situation, where all catastrophe was blamed on "al-qeeda ". All deaths now, with a throat swab positive done post-mortem, is labelled as a AH1N1 death. We have urged the Minister to set up a task force to examine all deaths and try and give us some real numbers.

There is a prevailing consencus ( following the WHO line ), of pushing the use of " oseltamivir " ( the generic name of the branded Tamiflu ), as if it is the magic cure. That is simply not true. If fact, in Feb, 2009 the CDC of USA released a document saying that about 100% of the H1N1 in their population was " oseltamivir resistant ". What is even worse is that Roche, the maker of Tamiflu, is holding out on their supply of Tamiflu. The conspiracy theory people feel that they are keeping it for the US winter that is ahead of us. This has forced our government to buy hurriedly prepared generic " oseltamivir ", who's quality and BE studies are not even available. We could be getting nothing better then " flour pills " . This is mistake number 5. Oseltamivir is not a magic bullet to cure AH1N1. At best, it may reduce the disease period and reduce suffering. At worse, it may not work and give patient a false sense of security. Some of the anti-virals have known side effects.

Many guidelines have been dished out to health professionals and to the public as to what to do. Many are not well thought of. Patients are told to keep good personal hygeine. That is correct and probably the best advice. To get all patients with fever 38oC for 2 days admitted is crazy. There will not be enough beds to house them, be it in public or private hospitals. Most of the patients with AH1N1 survive. Some ( especially in the high risk group ) surcumb to secondary bacterial pneumonia. Giving patients in the high risk group antibiotics early may be a worth while strategy. To get all patients with " flu " symptoms tested with the rapid test, is useless. In an epidermic, treat all as if they have AH1N1, and detect complications early and treat it as necessary. To be, announcing that we have oseltamivir when we do not have enough stock, is a joke. Now you have built up expectation, and cannot deliver. And when you deliver, it is generic drugs, which have not undergone stringent safety and efficacy testing.

What then can be done?
Well the authorities have to calm down and begin to play down this crisis. Encourage good hygeine and allow patients to care for themselves at home. GPs should be advised to treat all with " Flu " symptoms as AH1N1, and start antibiotics early. Those who suffer compliactions ( high fever, with cough and breathlessness ) should go to hospital immediately for hospitalisation. That allow the hospitals to function more efficiently. It is important to note that the death rates of AH1N1 at the big public hospitals like the Sungei Buloh Hospital is low ( one to be exact ) although they deal with complicated ones. Most of the deaths have occurred in peripherals hospitals where the care may not have been so good. In fact, many of us see this AH1N1 crisis as a stress test for the acute healthcare delivery system of Malaysia, and so far, the system seem to have failed. With a system like this, it may be wiser to ride out the crisis and treat the complicated ones, and not to hype the issues and blame this and the other. Let us gather data and learn more about this " flu " so that in future we will be smarter. For the moment, this crisis is still on, but let us not panic. Let us all prepared for a surge in number of cases with the Hari Raya holidays infront of us. With people movement and travelling, there will be an increase. Let us be prepared, take precaution and keep good hygeine.

For sure, this AH1N1 crisis will pass ( and we hope soon ), but the authorities must learn their lesson. And the best people to end the crisis are the people, by taking care of themselves and avoid infection ( if possible ) Besides avoiding infection, it is also important to keep our body healthy to increase their body resistance. This is what should have been emphasize at the beginning. Maybe some deaths could have been avoided.

PATIENT EXPOSURE TO RADIATION IN INTERVENTIONAL PROCEDURES

With the advent of interventional cardiology, and now also interventional radiology, more and more patients are exposure to radiation, both adults and also children. Paediatric Interventional Cardiology has grown by leaps and bounds, and many forms of congenital heart disease can be fixed by percutaneous interventional procedures. In many studies done, it is well documented that cardiologist and staff are usually well protected from excessive radiation exposure, but inadequate protection is often taken to protect the patient. I suppose, part of the reason would be that whereas staff are repeatedly exposed ( they work in the angiogram suite ), the patient may be there on a one off procedure. But it is common now for patients to have repeat procedure throughout their life, for example, PCI with in-stent restenosis. There are also those " normal checkup 64-MSCT angios " done annually for " heart checks ".
My interest in this subject was partly prompted by the widespread use of 64-MSCT and also when I saw that some intervetional radiological procedures, could take the whole day with 9 hours procedural time and 300-400mins of flouroscopy time. Some of my colleagues in Japan, when they do CTOs can sometimes take 5-6 hours to complete a complex PCI/CTO, giving the patient 200mins of flouroscopy radiation.
I think the subject of radiation disease should again be highlighted.
In the August issue of the Amnerican Journal of Roentgenology, Tsapaki V and colleagues published the paper " Radiation exposure to patients during interventional procedures in 20 countries: initial IAEA project results." The authors reviewed the radiation risk in 20 countries, mainly developing ones and found there in many countries, radiation doses to patients undergoing procedures were way in excess of acceptable limits, prompting their call that more attention and safe-guards for patients.
I suppose that it is true that most of us interventionist, never factored in the patient radiation risk, and we spend little time explaining to patient about them. Some of us have our own startegy that all pprocedures should not exceed 2 hours, because we will be too tired to think straight. A tired mind tend to make mistakes and also we are afraid of excessive radiation. However, some interventionist almost never gives up and go on and on, oblivious to the effect that they are harming themselves, their staff and their patient. This is made worse when they are intervening in disease subsects where the medical data is what we call a class 2 b indication ( the procedure done may have little benefit for the patient and only supported by clinical opinion of some experts ). It will be terrible practice, to take an assymptomatic CAD, discovered to have 3 vessel disease on 64-MSCT, into the angio suite, to try and do the 3V-CAD, spending 2-3 hours repairing complications and trying to cross a stable CTO. One wonders whether that procedure is good for the patient, the doctor or the staff, especially in the light of the " COURAGE trial" and many studies like that.
I only wish that the patients will always ask their doctor: 1. Is thia procedure necessary ( will it benefit me/patient )? and 2, what are the risk?, and in intevetional cardiology, what are the radiation risk. Not to forget that one 64-MSCT angio, is equivalent to a radiation exposure of one coronary angiogram, which is equivalent to the radiation exposure of 500 CXRays ( and that is only a fluoroscopy time of about 5-10mins. What then is the radation dose when you have a flouro time of 200mins??

GENERICS Vs BRANDED DRUGS : With a paragraph on generic Drug-Eluting Stents.

This piece is written for the mass media, following the workshop on " The Malaysian National Medicines Policy-mid term review 2009 ". It is reproduced here for infromation to all of you.

With rising cost in healthcare, many countries find that one of the easiest way to reduce healthcare cost is to switch to the use of generic drugs. Of course, the healthcare providers make the assumption that generic drugs is the same as the branded drugs, albeit without the bigger price tag. Is this true? Are generic drugs the same, especially in terms of efficacy ( after all drugs are used in the treatment of disease conditions ).

Let me begin with a few definitions. ( Medical science always like to define things so that you are sure what we are talking about ).

Medical drugs are chemical compounds prescribed by qualified medical practitioners, in the treatment of disease conditions. They are usually prescribed for a given duration, or in chronic disease states, may be given long term. Their use are subjected to approval by the relevant national authorities.

Branded drugs are drugs produced by a company ( usually multi-national companies-MNC ) with a patent on them. These drugs are usually well researched for safety and efficacy, and are proven by large scale clinical trials to be of benefit in curing or controlling disease states.
On the other hand, generic drugs are drugs produced by any company, once the patency has expired, as a copycat of the branded drug.
The use of both branded drugs and generic drugs are subjected to approval by the relevant national authorities.
Generic drugs are of course cheaper, as the generic drug companies save clinical research, marketing and promotion. And of course, competition also drives down cost.

Because of severe competition in both the branded drugs and the generic drug markets, most MNC have their own generic division so that they can also produce their own generics to compete in the generic drug market.

What then is the difference between generic drugs and branded drugs?

I always tell my patients, whenever they ask, that the difference between generic drugs and branded drugs is in the quality control. Here, one must not think that, in the manufacture of a drug, one only has to consider the active ingredient, important as that may be. The drug that you take does not consist of only the active ingredient. As an illustration, a drug consist of the active compound ( that which helps to make the patient well ), another compound added to make the active compound stable, another compound added to make the compound soluble so that it can be absorbed in whatever form it is to be taken. Some even add some colouring to the drug, so that it does not have the same colour as the original branded drug. Of course with so many chemical compounds added, the quality of the chemicals sourced becomes important, especially the expiry dates. To cut down the cost of production ( generic drugs must be cheap and yet have good profit margin ) what is there to stop the profit oriented companies to use good quality chemicals in the batches scheduled to be tested for approvals and once approval is granted, all subsequent batches have chemicals with short expiry dates ( cheap stocks ). After all, non of us would knowingly take expired food stuff. Therefore, if quality control is lax ( both by the manufacturers and also the enforcement authorities ), the generic drugs would have highly variable efficacy and safety. In fact, some generic drugs are no better then sugar pills or flour pills.
Of course there are standards to test these things. Each drug, to be registered, is required to undergo “ bio-availability “ studies, and “ bio-equivalence “ studies. What do these mean?
Bio-availability means how much of the drug, once absorbed, into the blood stream, is available in the blood serum, for it to act at the target sites in the body. This can be tested in the laboratory.
Bio-equivalence means that the generic drug is tested in the laboratory ( animal testing ) or given to normal humans, to observe their pharmacological action, to see if they have an equivalent action, as the branded drug. For both of these, the standards are that the generic drug have to be +/-20% of the branded.
Overall, we can sum up all that I have written so far, in that generic drug manufacturers, like branded drug manufacturers, must observe and adhere to “ Good Manufacturing Practice “ standards. This good manufacturing practice includes details of manufacture and sourcing of the chemicals and their expiry dates, details on the control of all stages in the manufacture of the drug, instructions and procedures are written clearly in unambiguous language, details are meticulously recorded and kept for inspection, operators are well trained to carry out and document procedures, deviations from the procedure are investigated and recorded, records of manufacture and distribution are kept so that anyone batch can be trace, in the event of a recall, a system of recall is detailed in the event that this is necessary.
Good Manufacturing Practice ( GMP ), is not a prescription on how to manufacture drugs. It is a set of principles for the company to adhere to to guide them to manufacture drugs of a sufficient standard. In fact, each country have their own GMPs. The WHO have their own GMP, the European Union have theirs, The US have their FDA version. The UK have the “ orange book “ or the Medicines Act ( 1968 ). Good manufacturing practice must also come with good enforcement. Besides checking that companies producing generic drugs adhere to GMP, enforcement agencies must also undertake post-marketing surveillance, to see how the drug is performing in the market place. There should also be a system of adverse events reporting, so that if that batch is bad, it can be recall, as it happens every now and then with some branded drugs. I think that it is fair to say that post-marketing surveillance and adverse events reporting in Malaysia, still have much room for improvement.
Because each country and each company, have their own standards of GMP and also enforcement, it is reasonable to assume that not all generic drugs are the same. The generic drugs that are produced in countries with GMP and good enforcement agencies, thend to be of a higher quality, and the generic drugs manufactured in countries with poor GMP standards and also with poor enforcement agencies, tend to be of poor quality.

We therefore differentiate even between generics. Many MNC drug companies with branded drugs, have began to set up generic divisions to manufacture generic drugs. Because of their branding and corporate culture ( transparency, accountability, social responsibility and the light ), we are confident that their generic drugs will be of almost equal quality, when compared to their own branded drugs. There are some first world countries who manufacture generic drugs of good quality, like generic drugs from Canada, Israel ( not used here ), Sweden, France, Germany, Australia, USA etc. Then there are generic drugs manufactured in Brazil, India, Taiwan, Indonesia etc, and there are generic drugs manufactured locally. Not all generic drugs are the same. That may also be why not all generic drugs have the same price. Do you wish to take a chance with generic drugs, having read all that have been written, for your health and maybe your life.

Although this article is written primarily to discuss generic drugs, it is equally applicable to generic devices like drug-eluting stents. Drug-eluting stents are slotted metal-tubes that we insert, via a process called angioplasty, into coronary arteries, to treat blockages in coronary arteries. As it is commonly known, angioplasty’s Achilles heel is restenosis ( the process of re-blockage of the stent after successful implantation. Re-stenosis is due to a process of excessive scar healing following the stent placement. To address this issue, the innovative cardiologist have invented the drug-eluting stent. This drug-eluting stent or DES for short, has a metal platform ( like the old stents ), on which is coated a polymer coating, in which drugs to combat scar tissue formation is impregnated. DES have proven very successful in the fight against CAD and in-particular against re-stenosis following coronary stenting. Of course DES do not come cheap. Because of the cost of DES, we now see the emergence of generic DES. Of course generic DES manufacture must also adhere to the “ Good Manufacture Practice “. ( To the best of my knowledge, there are no generic DES manufactured in Malaysia ). Therefore like generic drugs, there are also different generic DES of different quality, safety and efficacy. This generic DES issue is somewhat more serious, ( and I am not saying that the generic drug issue is not a serious issue ), because these generic DES are permanent implants in the coronary arteries, so they can create long-term harm. It is important to note that unlike drugs ( at the present all drugs must be registered with the Ministry of Health Malaysia ), presently registration of medical devices and their use is not yet compulsory in Malaysia. It is very much voluntary.

If I have not been clear from the beginning, the purpose of this article is to inform the public about the issue of generic drugs versus branded drugs. It is my sincere hope that when your doctor prescribe the drugs for the treatment of your condition, you should be better empowered to ask the relevant questions about generic drugs and their safety and efficacy, and then make an informed choice. You are the patient, and you have a say in whatever treatment given to you.

Remember, the saying is true, “ cheap things no good, good things no cheap “ . Basically, you get what you pay for.

TAKING LEAVE OF CARDIOLOGY. TO ISSUES OF CURRENT PUBLIC INTEREST

I would like to ask leave of my readers, to deal with two issues of public interest that I am very concerned about.

1. The H1N1 issue : When this global infection first started to affect the world and our country in early 2009, almost 6-7 months ago, I must say that I thought that it was just another " flu " but with the potential of mutating ( H1N1 from humans, infecting animals including birds / swines, and then returning to infect humans ) thereby causing a deadly form. One of the problems in this present " Pandermic " is the politicising of the health issue. One sometimes find it difficult to separate the real health issues with statements by politicians and also pharma companies, who have an obvious conflict of interest. Say what you like, this infection is spreading, but not " rapid ". With globalisation and a global transport, a rapidly spreading infection would have involved millions by now. It has not. In a country of 27 millions in Malaysia, after 6 months, we have 1,400 cases. Yes, it is still spreading, but no, it is not spreading rapidly.
But what I am very concerned about are the two latest deaths, last week and yesterday, which involved two kids, who have no previous illness. Of course, we need more details, but the sudden rapid onset of the infection resulting rapidly in death in someone not predisposed, does not sound like " flu" anymore. It makes me wonder whether the H1N1 has mutated already into the more virulent forms like " swine " flu or " bird " flu. Of course, the other possibility is that the anti-virals, used indiscriminately, may have caused side-effects and further damaged the host immunity. After-all, anti-virals are anti-RNA like-products, and do have known side-effects. In fact many experts have advised that in patients with H1N1, complicated by pneumonia, antibiotics to treat the super-imposed infection, maybe better than using expensive anti-virals. Heavy doses of anti-virals, and vaccines, are of very limited value ( although pharmas are cashing in, giving rise to many conspiracy theories.
I would have thought that the best thing wthat we can all do is to maintain a healthy body ( a body with strong immunity to infections ) and also to observe good hygiene. The Ministry of Health must help us to trace all cases, especially fatalities , study the pattern of spread and devise stategies to contain and control. Blaming doctors every now and then, is not a good strategy. It is time to work together, to fight this infection. And even more important, to tell us what kind of virus, we are dealing with, H1N1, or H5N1, or others, if possible, without causing panic.

2. Generic Drugs : Last week, I was also involved in a three day Ministry of Health ( MOH )meeting on the Malaysian National Medicine Policy ( MNMP ). Apparently, in 2006, the MOH had written a drug policy, and we are now task with doing a workshop to see how to update the Policy. Our comments at the meeting, was that, although doctors are one of three important stake-holders of the MNMP, there were only two doctor organisations invited to participate, and only three non-government doctors present. This would not be a good forum to formulate a MNMP. There were of course, multitudes of pharmacist, and ministry officials.
A quick look at the agenda, will reveal that the MOH is very keen to push generic ( copycat of drugs whose patency has expired ) drugs. What is even more important to note, is that the MOH seem to be pushing for " generic drug substitution ", meaning that the pharmacist can substitute a drug that the doctor has prescribe, with a copycat copy, whose stock, he/she is holding. Now this is very dangerous and against the pharmacy code of ethics. For awhile, from expediency ( read profit ), this ethical code is forgotten. Well after some "hooha" the ethical code book is refered to and now, pharmacist will have to seek the permission of the prescriber, before substituting. There is also an obvious trend in the discussion and agenda, to separate prescibing from dispensing. We also managed to suggest to MOH that there should be a list of drugs ( drawn up by the doctors ) that cannot and must not be substituted.
It does look like pharmacist is pushing very hard to take over the doctors role to dispense. There are pros and cons in this debate. I feel that, whatever policy we make, the patient must have a choice. In the free market society that we profess to be, the consumer must have a choice. We should not legislate a system, where the consumer have no choice.

There are many other pressing health issues, but I should not take up cardiac space, too much.