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Sunday, November 17, 2013

Drug- Drug War: Clarithro vs CCB

The antibiotic clarithromycin prescribed for patients already taking antihypertensive calcium-channel blockers is associated with increases in hospitalization for acute kidney injury, hypotension, and death, according to new research.


Clarithromycin is an inhibitor of the cytochrome P453A4, the enzyme that metabolizes calcium-channel blockers. The antibiotic can send blood concentrations of calcium-channel blockers soaring by as much as 500% leading to severe hypotension. 

Patients on regular treatment with calcium channel blockers like Amlodipine, Felodipine, Nifedipine, Diltiazem or Verapmil were prescribed Clarithromycin or Azithromycin. These macrolide antibiotics are commonly used for upper respiratory infection, pneumonia, eradication of H. Pylori, and atypical mycobacteria. 

Because azithromycin is only a weak inhibitor of CYP34A, the type of intensification of the calcium-channel blocker that occurs with clarithromycin is not expected.

Also, due to the role of the kidneys in eliminating clarithromycin, guidelines call for reduced dosing of the antibiotic in patients with chronic kidney disease. 

Thus, it is highly advisable, in patients suffering from high blood pressure and on regular medications, to be wary of the antibiotics prescribed or used over the counter. 

Published: November 9 in JAMA 

Sunday, September 08, 2013

Asepsis and Dementia: Can there be a possible interaction?

I have always been taught by my parents the virtues of staying clean and maintaining a good hygiene all through out my life. Being a Muslim, we have to offer prayers 5 times a day. But these cannot be offered without the ablutions. So that means we need to cleanse ourselves at least five times in the day. 
Being a doctor, our professors have always harped on the compulsory aseptic precautions, be it the out patient department, regular routine rounds, or the peri operative wash up.  
The benefits of cleanliness are endless. 
Thus, when my hospital staff showed me this news clipping, I was taken aback. 

Shocking but true. 

An obsession with being too clean and hygienic could lead to a higher risk of dementia, researchers have warned.

Researchers say that people living in wealthier countries may be at higher risk of developing Alzheimer's disease, according to a study published in the journal Evolution, Medicine, and Public Health.
The researchers suggested the ‘hygiene hypothesis’ was behind the difference. This is the theory that an excessively clean lifestyle doesn't allow us to develop immunity levels and thus we are unable to combat many germs.

Results of the analysis revealed that countries with higher levels of sanitation and those with significantly lower rates of infectious disease also had higher rates of Alzheimer's disease.   

Shocking but true.

Thus, I would conclude on this note that   the people suffering from OCDs (Obsessive Compulsive disorders), who repeatedly get the urge to wash and clean themselves, are in for a rude shock. They now have to deal with another neurological issue - Dementia. 

Thursday, August 29, 2013

First time lucky, or unlucky

Whoever would have thought that the first child born (primogeniture) would be a riskier one?

The first one is more intelligent with a higher IQ than the later siblings probably due to the fact that he or she is the 'pearl of the eye' and gets lavish attention from parents that boosts the intellectual development. 

But medical literature antagonizes this. 
Recently, evidence has emerged on the consequences of primogeniture on long-term metabolic and cardiovascular health risks.



There has been a steady decline in the birth rates in the world owing to many factors which include family planning measures, government policies (one child norm) or economic constraints. As a result of this, we have a large percentage of one-child families. Since the first child is prone to health issues, we are now staring at a future population with a high proportion of risk factors. 

Despite similar gestational ages, first borns are 250g lighter than the later siblings at birth. Changes in the placentation are accounted for this difference in birth weights. 
Low birth weight is an indirect indicator of poor intrauterine milieu and adverse health outcomes have been demonstrated in association with decreasing birth weight. Offspring of mothers exposed to nutritional or physiological stress during pregnancy are at increased risk of metabolic and cardiovascular disease in later life. There is extensive evidence linking a reduction in birth weight with increased risk of insulin resistance, Type 2 diabetes mellitus, hypertension, cardiovascular disease, stroke and cancer.

First-born children are taller than the second or third child. Taller stature in childhood is positively associated with overweight status and obesity later in life. 

Various statistics suggest that first-borns were more likely to develop Type 1 diabetes mellitus, hypertension, heart disease, allergic disorders and psychological issues

Primogeniture are the largest identifiable study group (accounting for more than half of the world's population), so that any associated health risks could have enormous public health consequences.

Monday, July 29, 2013

Obesity: The Pandemic


Obesity is defined as abnormal or excessive fat accumulation that may impair health.

Body mass index (BMI) is a simple index of weight-for-height that is commonly used to classify overweight and obesity in adults. It is defined as a person's weight in kilograms divided by the square of his height in meters (kg/m2).

The WHO definition is:

a BMI greater than or equal to 25 is overweight
a BMI greater than or equal to 30 is obesity.



Obesity is a major public health problem in the world. Two thirds of adults in the  US are overweight, and one third are obese. Being obese increases the risk for other diseases: high blood pressure, heart disease, type 2 diabetes, osteoarthritis, sleep apnea, and even some cancers.


The American Medical Association (AMA) House of Delegates has in June 2013 redefined Obesity from a major public health problem to a Disease. After much debate, the majority ruled that obesity is a disease state with multiple pathophysiologic aspects requiring a range of interventions to advance obesity treatment and prevention. 

This has now given an entirely different perception to this potentially hazardous malady. 

"OBESITY IS A DRIVER OF MUCH SUFFERING, ILL HEALTH, AND EARLIER MORTALITY."

The two sides of the coin

  • Here's the downside of calling obesity a disease. Some worry that this would medicalize obesity and intensify reliance on drugs and surgical treatments rather than relying on diet and exercise to attain a healthy weight. Another concern is that calling obesity a disease could alienate some obese individuals, especially if the emphasis is on achieving ideal weight rather than focusing on healthy eating and increasing physical activity. 
The Body mass index (BMI), that obesity is defined on the basis of, has many limitations. It was originally designed as a research tool: a rough population-level indicator. It's not a great way of measuring body fatness. Some people with a BMI in the so called "normal" range can have too much body fat, as well as metabolic problems. Some with BMIs over 30 kg/m2 -- the so-called obese range -- have plenty of muscle and no excess fat . Some with high BMIs are normal metabolically and also have normal blood pressure and cholesterol levels.

The BMI defines size, not health. 

The National Heart, Lung, and Blood Institute is now working on new guidelines on overweight and obesity in adults. 


  • Here's the pro side. Calling obesity a disease could mean greater investments by the government and the private sector: more research into causes, triggers, and treatments, including more US Food and Drug Administration (FDA)-approved drugs for treatment. Another benefit of making obesity a disease is that it could make it harder for third-party payers to deny coverage.


Obesity paradox: 

A collection of studies suggests that BMIs in the overweight or obese range may have protective effects on mortality risk. 
Experts have suggested that body fat may play a protective role, perhaps in secreting certain beneficial cytokines and hormones. Extra body fat also means extra padding and thus a physical protective barrier from traumatic injuries. In times of illnesses, the additional caloric reserve may give patients more nutritional backup in the healing process. 

However, the ill effects of the excess fat are too pronounced to be ignored. 

The most important advanced technology with which to fight obesity is the bathroom scale, used every day. Don't let that number rise. 

Obesity, after being categorized as a disease, we can now expect that the development of gray hair or the aging process- Senility, to be the next condition considered as a disease.










Sunday, July 21, 2013

Use it or Lose it


What does this phrase imply? 

It means that if you don't continue to practice or use an ability, you might lose the ability. For example, if a person doesn't exercise his or her physical body, he or she will likely lose strength, endurance, and stamina. Similarly, if a person doesn't practice a new skill, such as driving a car or speaking a foreign language, he or she may forget or lose that skill. 

Jean Baptiste Lamarck, a French scientist, proposed that species change because of the use or disuse of features, such as tails or arms. He purported the “use it or lose it” idea. He believed that excessive use of a feature would cause it to grow and lack of use would invite atrophy. 

Let us thus, use this principle to have a positive bearing on the society and impart some quality of life enhancing tips to our elderly population. 

"Erections make erections". Sex is not unlike sports. If you want to be a good tennis player, play lots of tennis; if you want to be a good lover, make lots of love.

The American Journal of Medicine reports that older men who have sex more than once a week are less likely to develop Erectile dysfunction.  

Why does having more sex keep the male organ in trim instead of wearing it out? The likely elixir is oxygen here. 

Coming to a different sort of exercise for the seniors. 

Brief sessions of exercise for the aging brain like crossword puzzles and reading can have long-lasting benefits for elderly people, helping them stay mentally fit for at least five years. 

Retirement may not be good for your brain, according to a new study from France, which links older age at retirement to a reduced risk of developing dementia.

Mounting evidence suggests that engaging in intellectually stimulating activity throughout life may protect against the development of Alzheimer's disease and other dementias. 


"So if you are old and you are not contributing...maybe there is some penalty attached to that..., encourage older people, not just to be a negative burden on the State but to actually be a positive part of the Society."



Sunday, June 23, 2013

Vitamin Alcohol: Is it a cardio tonic ?

Alcohol or liquor.  दारू or शराब in local lingo. The word is a deterrent in social circles especially the Muslim community. The topic itself is taboo and any discussion related to that would be considered a heinous crime. 
But, doctors as we are. Our medical history isn't complete without the mandatory questions related to alcohol or tobacco intake. 
Just the other day, I was put in a terrible professional dilemma. A middle aged, educated Muslim gentleman who had visited my chambers for a consultation, didn't deny that he was a social drinker. Since it was a routine health check up, I safely sidestepped the sensitive issue of alcoholism and gave the other relevant medical advice. But, Mr.X then posed the most difficult question to me. Doctor, he said, "Can I safely still continue my social drinking if all my parameters are normal?"
Being a Muslim myself, it was tough for me to allow him that liberty. But being a medico, I tried to sound politically correct and said, "better to avoid". And it was then that he asked the inevitable. The question that I dreaded to answer since long. "On the contrary, medical science says that moderate drinking is healthy for the heart and and helpful in various other conditions", he argued. I was left speechless. 


Heavy or binge alcohol consumption unquestionably leads to increased morbidity and mortality. Nevertheless, moderate alcohol consumption, especially alcoholic beverages rich in polyphenols, such as wine and beer, seem to confer cardiovascular protective effects in patients with documented CVD and even in healthy subjects.


Alcohol is absolutely contraindicated for pregnant women, children, patients with liver disease and in combination with certain medications. 

The basis of this theory dates back a long way to the times of the French Paradox

French Paradox:

It was the paradoxical observation that the French have a low incidence of coronary heart disease (CHD) despite subsisting on a diet rich in saturated fats.      

The two possible explanations are: First, the theory linking saturated fats to CHD is totally invalid. 
Second, the link between saturated fats and CHD is correct, but some intermediate factor in the diet or lifestyle of the French mitigates this risk. This factor was then identified as Red wine

This French paradox then triggered many a study where the effects of red wine and its components - polyphenols and resveratrol were evaluated. It also opened a debate as to which alcoholic beverage was more cardio protective. 


Moderate alcohol consumption is cardio protective. But how much is moderate?
The common man defines it thus: Moderate drinking may be defined as drinking that does not generally cause problems, either for the drinker or for the society. 

But US National Institute on Alcohol Abuse and Alcoholism (NIAAA) has defined moderate levels categorically as:-

Men: Maximum of 2 drinks per day or 14 drinks per week or 
4 drinks in a single day
Women: Maximum of 1 drink per day or 7 drinks per week or
3 drinks in a single day

Examples of one drink include:

Beer: 12 fluid ounces (355 milliliters)
Wine: 5 fluid ounces (148 milliliters)
Distilled spirits (80 proof): 1.5 fluid ounces (44 milliliters).


This difference in the gender is because the female sex is unable to metabolize alcohol as efficiently as its male counterpart due to reduced levels of the enzymes alcohol and aldehyde dehydrogenase. These enzymes help in the breakdown of alcohol and since females have a relative deficiency of these enzymes, they show higher levels of intoxication for the same amount of alcohol ingestion. 

To conclude,

The latest dietary guidelines thus make it clear that no one should begin drinking or drink more frequently on the basis of potential health benefits. So don't feel pressured to drink alcohol. But if you do drink alcohol and you're healthy, there's probably no need to stop as long as you drink responsibly and in moderation.








Tuesday, June 18, 2013

Fish Oils: Food for thought

Omega-3 fatty acids refers to a group of three fats called ALA - α-linolenic acid (found in plant oils like flaxseed) , EPA-eicosapentaenoic acid and DHA- docosahexaenoic acid (both commonly found in fish oils). 

Omega-3 fatty acids or PUFA are considered essential fatty acids because these are not made in the body or are inefficiently converted from ALA to EPA and DHA. Thus, we need to get them from our diet .

Omega-3 fatty acids reduce the risk of arrhythmias, decrease the triglyceride levels, slow the growth of the atherosclerosis and marginally reduce the blood pressure -by reducing the inflammation and lowering the clotting risk. They also play a beneficial role in dementia, depression, arthritis and certain cancers. 

American Heart Association has recommended eating fish like salmon, mackerel, tuna, herring and sardines which are rich in omega-3 at least twice a week. Some types of fish like the shark, swordfish contain high levels of mercury
and environmental contaminants and need to be avoided especially in pregnant ladies. 

Experts usually recommend 1 gram of DHA and EPA combined from fish oil daily for those with heart disease. People with high levels of triglycerides may take doses of up to 4 grams a day under the supervision of a physician. There is an increased tendency of bleeding in people taking high doses and especially those who are on anti platelet drugs and anti coagulants. 

However, the recent randomized trials
in high-risk populations (those with either multiple risk factors or a history of cardiovascular disease) have suggested very little benefit from omega-3 fatty acids.

Patients with multiple cardiovascular risk factors were given 1 gram of fish oil per day vs placebo, and it showed no benefit. Also, other meta-analyses have been published in the past year that looked at all of the randomized trials in aggregate. These are secondary-prevention, randomized trials with high-risk populations. In general, these meta-analyses have shown disappointing results.

It is very important to keep in mind that these high-risk populations -- include many individuals who are already taking multiple heart medications such as statins, aspirin, and ACE inhibitors, which may obscure the effect of omega-3 fatty acids. There may be very little incremental benefit from omega-3 fatty acids in that setting. 

Conclusion:

First, these randomized trials of fish oil do not advise against the recommendation to have at least 2 servings of dietary fish per week. That is a recommendation from the American Heart Association and many other professional societies, and many studies suggest benefit. Some of the benefit may be because dietary fish is replacing other foods that could increase risk, such as red meat or foods high in saturated fat.

Second, in patients who are candidates for prescription omega-3 fatty acids, especially those who have very high triglyceride levels, these findings do not cast a doubt on that indication for use. That would still be an appropriate use. In patients who are taking fish oil and are doing very well on it and feel strongly that the fish oil is helping their symptoms or are a benefit to them, there is no strong basis from these studies for encouraging them to stop, because there were no major risks associated with fish oil found in the studies.

To sum it all up. Omega-3 fatty acids are not needed nor recommended for primary or secondary prevention of cardiovascular-related mortality and morbidity. However if the patient is using it and is tolerating it, it can be continued. 
But, in those people whose triglycerides are very high, these may still be a good recommendation. 




Saturday, May 25, 2013

Wielding the Vitamin C weapon against the Mycobacteria

An experiment that was being conducted to check for Isoniazid resistance to Mycobacterium tuberculosis in fact turned turtle and an accidental discovery of Vitamin C killing the bacteria was made.

A reducing agent cysteine along with isoniazid was added to a culture medium growing mycobacteria expecting the bacteria to develop drug resistance. Instead the culture was killed. The cysteine was then replaced with another reducing agent, Vitamin C. Lo and behold!! The result was the same. 
More drama was to unfold. Isoniazid was left out and Vitamin C was left alone. When the result was same yet again, it was concluded that Vitamin C kills mycobacteria. 
Drug resistant strains also tested with this vitamin yielded the same outcome. 

There has been a long-standing observation that vitamin C is toxic to M tuberculosis, a Gram-positive bacterium. Experiments in the 1930s showed that only 6% of guinea pigs exposed to the bacteria and given tomato juice became infected compared with 70% of guinea pigs not given the vitamin C–rich juice. 
In vitro experiments conducted in 1950 confirmed the effect of the vitamin on bacterial cultures, and a study in 2011 correlated vitamin C content of various medicinal plants with antibacterial effects.

TB was declared a global health emergency by the World Health Organisation (WHO) 20 years ago, but remains a leading cause of death by an infectious disease despite a 41% drop in the death rate from 1990 to 2011.

Further research into the potential uses of Vitamin C in TB treatment is definitely the need of the hour since it is "inexpensive, widely available and very safe to use."






Thursday, May 23, 2013

Chelation for your heart: Is it really that absurd?

Chelation therapy: An incredibly implausible therapy based on a hugely simplistic concept that because calcium accumulates in atherosclerotic lesions, then using chelation therapy, we could remove the calcium and reduce the lesions. Chelation therapy is a favorite treatment option recommended by naturopaths, and the claims made for it border on the absurd. It’s frequently referred to as “a “safe and effective” alternative to angioplasty or coronary artery bypass surgery.

Since it is being practiced by many  physicians and is a hotly debated topic in circles, a trial funded by The National Institutes of Health's National Heart, Lung, and Blood Institute (NHLBI) and National Center for Complementary and Alternative Medicine (NCCAM), was undertaken to provide some scientific evidence warranting the rise in the use of this therapy. 

Trial To Assess Chelation Therapy (TACT):

The purpose of this study was to determine the safety and effectiveness of ethylene diamine tetra-acetic (EDTA) chelation therapy in individuals with coronary artery disease.


For the TACT study, the protocol specified 40 infusions. For the active chelation arm, a 10-component chelation solution was selected to match most closely the standard solution used by chelation practitioners. The solution contained disodium EDTA, ascorbic acid, magnesium chloride, procaine hydrochloride, unfractionated heparin, potassium chloride, sodium bicarbonate, pantothenic acid, thiamine, pyridoxine, procaine, and sterile water to make up 500 mL of solution. The placebo solution consisted of 500 mL of normal saline and 1.2 percent dextrose.

Over the four-year follow-up, the difference in the primary endpoint, (a composite of all-cause mortality, MI, stroke, revascularisation, and hospitalization for angina), between the two groups just reached statistical significance. 
In a subgroup analysis, the 31 percent of the study population with diabetes showed greater benefit for the primary endpoint compared with nondiabetic patients. 

Thus, this trial did show some promise but needed further evidence to back it. 

But TACT was panned by the critics who started questioning and rejecting the results because they were having trouble dealing with the results of a trial that seems to support a therapy that they find absurd. 

They echoed this sentiment. "Given the numerous concerns with this expensive, federally funded clinical trial, including missing data, potential investigator or patient unmasking, use of subjective end points, and intentional unblinding of the sponsor, the results cannot be accepted as reliable and do not demonstrate a benefit of chelation therapy. The findings of TACT should not be used as a justification for increased use of this controversial therapy."

An explanation was offered for the positive results. Heparin, it was said, was the reason for the benefits of chelation and not EDTA.

To add fuel to the fire, this trial very recently got its publication in JAMA which has further triggered a fascinating debate in the blogosphere.

The critics came alive yet again. "So messed up was this trial that it’s hard to fathom the decision of JAMA’s editors to publish it.  If published at all, TACT should have been published in some crappy, bottom-feeding journal, because that’s all that it deserves."

If we have little faith in chelation therapy, then it is hard to turn 180 degrees with a positive result and suddenly completely believe in it and recommend its use. Any trial can give an anomalous result and we need to be careful about jumping to a new position with each new piece of evidence. However, we cannot on one hand promote evidence-based medicine and on the other hand ignore what we do not like. 



Wednesday, April 24, 2013

Calcium Controversy 3 - The role of the traffic cop

As discussed in my previous blogpost, calcium supplements have a tendency to get deposited in the blood vessel walls and thereby predispose to cardiovascular disease.
Now comes a saviour molecule to negate those effects. Not a new discovery. Just an old one with a new role. Would you believe it!! A VITAMIN.
Vitamin K2.

Vit K has always been known to have blood clotting properties. What wasn't well known was that it has 3 subtypes:


  • Vitamin K1, or phylloquinone, is found naturally in plants, especially green vegetables; K1 goes directly to the liver and helps maintain healthy blood clotting.
  • Vitamin K2, also called menaquinone, is made by the bacteria that line the gastrointestinal tract; it is found in poultry and dairy products as well as animal based foods. K2 goes straight to blood vessel walls, bones, and tissues other than the liver.
  • Vitamin K3, or menadione, is a synthetic form.

Vitamin K1 exclusively participates in blood clotting. K2 on the other hand comes from a whole different set of food sources, and its biological role is to help move calcium into the proper areas in the body, such as bones and teeth. It also plays a role in removing calcium from areas where it shouldn't be, such as in arteries and soft tissues.

"K2 is really critical for keeping our bones strong and our arteries clear"

How does K2 do the job?

Vitamin K2 helps to activate vitamin K-dependent proteins responsible for healthy tissues. In bone, it activates osteocalcin, a protein required to bind calcium to the mineral matrix, thus strengthening the skeleton. In circulation, Vitamin K2 participates in carboxylation of Matrix Gla Protein (MGP), the most potent inhibitor of arterial calcification known, lowering the risk of vascular damage.

Evolution:

For treatment of osteoporosis, calcium supplements used to be prescribed. To enhance the absorption of these calciums, Vitamin D was supplemented. It is now a proven fact that calcium supplements can increase the incidence of cardiac events.
When we take vitamin D, our body creates more of these vitamin K2-dependent proteins, thereby increasing the demand for K2. If K2 is not supplemented, there is a definite possibility of Vit D toxicity and calcification of the arterial walls. Thus, if we opt for oral vitamin D, we need to also consume in our food or take supplemental vitamin K2.

Summarizing things. The Vitamin D acts as a gatekeeper, facilitating the entry of the traffic - read Calcium. Vitamin K2 is the traffic cop directing the traffic in the right direction.
Lots of traffic -- but no traffic cop -- means clogging, crowding and chaos everywhere!

In other words, without the help of vitamin K2, the calcium that our vitamin D so effectively lets in might be working AGAINST us-- by building up our coronary arteries rather than our bones.





Wednesday, April 17, 2013

Statins: The Diabetes dilemma

Continuing our trend of discussing the latest controversies of medical sciences, this one has the potential of overshadowing all the others.

Statins - Atorvastatin, Simvastatin, Rosuvastatin, to name a few, is a group of drugs which were primarily used to reduce the lipid levels. Over the course of time, many beneficial effects of this class of drugs were unearthed which has led to widespread and over the counter use of these tablets.

These beneficial/pleiotropic effects of statins include plaque stabilization, reduction of inflammation, reversal of endothelial dysfunction, and decreased thrombogenicity.

Numerous trials have shown a benefit for statin therapy both as primary patients who have never had heart disease and are taking statins to lower their risk (so-called primary prevention) and secondary prevention of cardiovascular disease (CVD) and mortality. Trials like the Collaborative Atorvastatin Diabetes Study (CARDS), proved beyond doubt that patients with type 2 diabetes and other risk factors for CVD should be treated with a statin, apparently disregarding their initial LDL cholesterol level.
Also, according to the New Canadian guidelines, all patients with Diabetes should start taking statins when they turn 40.

Diabetes Dilemma:

A number of large, clinical trials have now shown that use of statins can increase the risk of developing type-2 diabetes by about 9 percent.
Risk factors for Diabetes
This is fairly serious, especially if you are in the large group of patients who have not yet had a cardiovascular event, but just take statin drugs to lower your risks of heart disease.

Statins reduce the levels of Coenzyme Q10 which is needed for energy and other cellular functions. Also, they reduce the levels of a protein GLUT4 which leads to insulin resistance and onset of type 2 Diabetes mellitus. Supplementation of CoQ10 may possibly negate this effect.

Complications of Diabetes

In one study, diabetes mellitus was diagnosed in 27% more patients receiving a statin (rosuvastatin) compared with patients receiving placebo (an identical appearing pill that does not contain medication), but patients receiving the statin had a significant 54% lower risk of heart attack, 48% lower risk of stroke, and 20% lower risk of death.

Symptoms of Diabetes
There is a wealth of clinical data showing that patients with diabetes mellitus benefit greatly from statin therapy to prevent cardiac events. The current data do not support discontinuing statins if you have diabetes mellitus or if you are newly diagnosed with diabetes mellitus.


Conclusion:

What should people who are taking statins do? If these are prescribed for someone who has already had heart disease or a stroke, the benefit is overriding — no changes are suggested. However, physicians need to monitor the sugars of these patients. But in the vast majority of people who take statins — those who have never had any heart disease — there should be a careful review of whether the statin is necessary, in light of the risk of diabetes and the relatively small benefit that can be derived. Maybe a dose reduction or use of a less potent statin should be considered on an individual basis.