Endocrinology

Painless pricks

Problem: Your diabetic patient is not checking blood glucose frequently. She is sick of pain in the prick sites and would rather not check blood sugar

Solution: Make the pricks painless and hope the patient will check blood glucose regularly

Some people might scoff at the solution. How can you make drawing the blood from your patient’s finger painless? It doesn’t make sense? You might perhaps think that making the needle thinner should help. Unfortunately that wouldn’t be enough. Because even thinner needles also have to prick deep enough to draw blood. Besides one might need a thinner needle that goes in just the right amount to draw blood. Often the patient squeezes the finger – which leads to more pain.

One option is to use Lancing pens – they are significantly better than just pricking with any old needle. However they still continue to be painful. This is a problem especially for children with diabetes – there is ample data to show that frequent glucose monitoring and corrective steps are necessary to achieve optimal glycemic control.

It is in this backdrop that a device has been introduced. It’s called Genteel – and it promises pain free blood glucose testing. How does it make a prick  pain free?

  1. It uses vacuum to draw the blood vessels
  2. It plunges only deep enough to hit the blood vessel ( for most people), and avoids the nerve endings*
  3. It has a vibration mechanism that distracts the patient from feeling the minimal pain. The end result is an almost painless prick. The device isn’t available in India at the moment, but it can be ordered online for a price of $ 119(after 10$ discount). (shipping costs extra).

Evidence:
I couldn’t find evidence that this device reduces pain/ improves the frequency of glucose testing /improves glycemic control. There are various testimonials by children who have used it and found it to significantly reduce the pain. Since they probably don’t have any commercial bias, I decided to take their testimonial at face value. However that doesn’t negate the need for some solid scientific evidence.

Realistically we have three choices
1. Wait for the evidence to accrue and avoid experimenting
2. Have a demo pen in the clinic and have the kids try it out. If they like it they can buy it.
3. Do a trial of the device in Indian setting – preferably including the soft end points such as pain and frequency of glucose testing and harder ones like HbA1c.

I favour option 2&3. The reason is simple – it isn’t too costly, there’s a 4 month trial period during which the device can be returned if found useless, and unlike non invasive glucose monitoring systems this one isn’t some black box approach to diabetes.

There are other approaches to relatively painless blood glucose testing. One option is Abbot Freestyle LibrePro. Unlike Abbot Freestyle LibrePro, Genteel is an one time investment. And it can be easily shared among family members*.(the lancets have to be changed)The advantages are obvious. In case you know some type 1 diabetic child who could benefit, please share it with your patient.

Disclosure: I have no conflicts of interest to declare.

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Kudos

The Plain Language Movement & Law

The plain language movement started in both sides of the Atlantic in the 1970s to make law easy to understand. The legal documents were plagued by legalese and were thus inaccessible to the commoner. This problem can be traced back to almost a 1000 years when William, the Duke of Normandy defeated the Anglo-Saxon King Harold in the Battle of Hastings in 1066. As William and his followers spoke a dialect of French, English became the language of the common and lowly folk.
The courts and lawyers soon followed suit. Within a few decades the Legal system had became inscrutable to the common man. With the ascendancy of English came the urge to rid the system of the French and Latin terms and replace them with crisp Anglo Saxon words. The push to make common sense in common language fashionable had a reasonable amount of success.
The legal system and the people benefited a lot from making things simple. Unfortunately, the Plain Language movement only focused on the law, not medicine.

Saving Medicine From Medicalese

Flip(or click) through the pages of any medical journal and you will see how hard our language has become for anyone outside our profession to make sense of. Even among doctors, each discipline has its own jargon and stylistic idiosyncrasies making it harder for others to understand. We live in a time when obfuscation is celebrated as a skill and straight talk is scoffed at.
To give an example, I was reading a top endocrinology journal yesterday and was dismayed to find that the pages have been hijacked by genes, genes and more genes or molecules,molecules and more molecules. It felt like the journal had written in 100 size font in invisible ink – look, this is for the experts. No one else is welcome.
I am not arguing that the top journals should dumb down their content or ask authors to keep click baity titles. However I’m certain that the scientific community will be better served by a Cochrane style plain language summary for every scientific article. In fact developing a written version of the elevator pitch is likely to narrow our focus on what matters. However, most journals don’t have the space/ inclination for such summaries. We need a plain language movement for medicine.

What can we do in the meantime?

kudos-greater-research-impact
Kudos. It is a free online service to explain about your research in plain English. Each paper gets these four pieces of information – Title, What is about, Why is it important and the Perspectives of the author. Kudos also provides shareable links and can automatically post to Facebook, Twitter and LinkedIn. It can even track the response your article is generating! (It’s like having your own Altmetric dashboard)
Here’s a plain language summary of one of our papers – Tumor(s) Induced Osteomalacia- A curious case of double Trouble
If you are an academic, check out Kudos. It’s free and the experience can help you focus on what matters.

The Insulin plant

Yeah..you read that right. There’s actually a plant called insulin plant and it’s supposed to reduce blood glucose levels(no surprise there).You have probably heard of several natural remedies for diabetes and are rolling your eyes now.. The diabetes armamentarium is brimming with antidiabetic agents which are effective and proven. Some like GLP1 analogues and SGLT2 inhibitors have even proven to have cardiovascular benefits.

So why bother about a plant?

For a couple of reasons

  • Research : There are many plants which have potential antidiabetic diabetic activity – infact there are at least 111 plants which are known to reduce blood glucose. (1). However the Indian patent laws do not allow patenting plants and more importantly medicines derived from natural products. I have always had trouble understanding the second clause – even if you do some fancy chemical extraction and make a useful substance that was essentially hidden underground for millennia, you wouldn’t get a patent in India. Consequently the incentive to exploit the “natural remedies” for commercial gain is very limited. Thus,most of these plants/plant based substances may never reach the market as a tablet. Does that mean we can’t study them or learn from them? Not really – one can essentially mimic a natural substance, tweak it, call it bioinspiration and pretend that the molecular structure was an epiphany during a coffee break ! Or at least apply for an AYUSH grant to do some research – I’m a novice here, but I guess there can’t a better time to apply for AYUSH grants than now. Even if we aren’t involved in the business of making drugs, if the natural form is safe enough, we can consume them. Even if the effect is modest.
  • Clinical: Apart from the research aspect, there is a huge public craze for cost effective natural remedies or drugs derived from plants. The runaway success of products like BGR34 is a testimony to this.

Now you might wonder, if this plant stuff is good, it should have a good scientific backing. Indeed there’s a good body of research behind this. But let’s be frank – research is often locked behind paywalls. Even when it is ‘accessible’ it isn’t truly accessible to those outside the profession – most people are turned off by graphs,tables and statistics. The idea of this post is to simply strip the complexity off the published scientific literature and bring the reader upto speed on this quirky plant.

Here’s a brief bio of the insulin plant in Q&A format

What exactly is the insulin plant?

This plant belongs to the Costaceae family – two species are common , the Costus igneus and the Costus pictus. The leaves of this plant are sometimes taken as supplements for reducing blood sugar. Known as the Spiral flag( insulin chedi in Tamil and Malayalam), the plant can grow upto 2 feet and has colorful flowers.

costus-igneus

What does the plant contain?

It contains triterpenoids such as α and β amyrin,lupeol, stigmatsterol.,Diosgenin etc. That’s a lot of active principles- but mostly we are yet to understand how these substances interact with one another and whether isolating them is more useful than the natural mixture in which they are found.

How do I get this plant?

The insulin plant can be obtained from a nursery or someone who is already using it. Care should be taken to avoid mistaking some other plant for this. For the purposes of research, the identity of the plant needs to be confirmed by the Botanical Survey of India,Coimbatore. They give an authentication certificate with a number and date.

Is it safe for human consumption?

Published Toxicity studies in animals show no major toxic effects in the short term (2). Anecdotal human evidence seems to support this. However one should remember that with plants/plant products, there are a lot of variables one must account for – subspecies,soil,part of the plant, extract or whole leaves, growth in shade vs sunlight etc. Since there are no published long term human studies, we are essentially on our own when consuming this. Consequently, those at risk of hypoglycemia (elderly, recurrent hypos, comorbid illness, kidney diseases) and pregnant women should strictly avoid experimenting on themselves.

Is it effective in reducing blood sugar?

Much of the published research on this plant is from animal studies. These animal studies generally show a reduction in blood glucose. You can get a gist of the published research in the form of table by clicking here

Homogeneity is hard to obtain in these studies. Only limited human data is available. The absence of data doesn’t mean absence of useful effect though.

Does it have any other uses?

These days plenty of drugs reduce glucose. It is only natural to expect more !. Plant products tend to have pleiotropic effects and may well have off target effects which we don’t want. There are some of the effects of the insulin plant.

  1. Hypolipidemic effect
  2. Antioxidant effect
  3. Diuretic effect
  4. Anticancer effect
  5. Reduces TSH (3)

What does the current research mean?

Very little is known about the insulin plant – especially the human use of it. However, with the public clamor for natural remedies, there may be a future for this plant/its products. Because of its pleiotropic effects, it might have a role in conditions such as prediabetes,subclinical hypothyroidism apart from diabetes.

To conclude, the insulin plant is a potential plant therapy for diabetes. However at present we don’t know much about its human use and thus must proceed with caution.It opens up several research areas. If found useful in raw form, it may become one of the cheapest ways of treating diabetes.

Further Reading

1. Eddouks M, Bidi A, El Bouhali B, Hajji L, Zeggwagh NA. Antidiabetic plants improving insulin sensitivity. J Pharm Pharmacol. 2014 Sep;66(9):1197–214.

2. Hegde PK, Rao HA, Rao PN. A review on Insulin plant (Costus igneus Nak). Pharmacogn Rev. 2014 Jan;8(15):67–72.

3. Ashwini S, Bobby Z, Sridhar MG, Cleetus CC. Insulin Plant (Costus pictus) Extract Restores Thyroid Hormone Levels in Experimental Hypothyroidism. Pharmacognosy Res. 2017 Mar;9(1):51–9.

Daring to look beyond evidence

Today I attended, along with a lot of others, the much awaited debate about the Paleo diet in Trendo 2017(The Annual Endocine Conference). The hall was jam packed and both the speakers did a fantastic job. This is an issue that I have been ruminating for quite a while now.I had been skeptical about the Paleo diet – the scientific aspect of it. It was a knee jerk reaction. Knee jerk reactions are rarely right – so I decided to do what every doctor has been taught : look at the evidence.
I started the search at a familiar place – PubMed. As expected, there weren’t many studies. . There were studies of short duration, some of which showed great effect and others didn’t. Even the pattern was familiar, just like the place where I started. In fact I couldn’t find a single trial from India. I guess we are content to ask questions and want others to come up with answers.
However, the absence of evidence is not evidence of absence of effect.
Like all searches, I was left with more questions than answers. What exactly is Paleo diet? How far back in human history do we go? Should we just emulate the caveman’s diet or his whole life style? Somehow, drinking butter tea in plush AC rooms alone without working hard like the cave man seemed counter intuitive.
It was at this stage, that I stumbled onto a Facebook group called Arokiyam Nalvazhvu(Healthy Life in Tamil). I can hear the evidence based snobs scoffing . After all , a social network isn’t a traditional place to find answers to one of the fundamental questions of science – how and what should we eat? The group had over 3.5 lakh members, almost all of whom are either taking Paleo diet or planning to. [Talk of big data :-). This would be brilliant data mining project, for those who love to work with unstructure data]. Now this diet isn’t a standardized intervention, these were mostly prescribed by hobbyists who had no background in medicine. I saw some doctors as members of the group too. I decided to become a lurker.
Here’s how the group works:
Members post the pre and post images of themselves and their blood test reports. Several admins are there who approve the post and given them a unique id. The member has to take the requisite blood tests and post in the same thread. Within a couple of days, a paleo diet chart is given. It has its own menu and can be expensive, but if the member requests there are cheaper options as well. After 100 days, the member posts his lab tests/photos or both.The remarkable thing is the dedication of the admins. I have never seen patient empowerment on such a grand scale. Those who follow the diet religiously and lose weight, in turn become evangelists of Paleo and welcome new comers and start mentoring. It is a virtuous cycle. The best part is all of this is done absolutely free of cost.
Interestingly, Paleo has spawned several entrepreneurs as well. The people are home delivering Paleo ingredients. There are even a few Paleo diet hotels around. The members and admins actively go out and raise awareness.
I must say that the photos of people weighing over 150 kgs and becoming 90 kg after paleo are far more impressive than p values <0.05. Of course, this is not to say that statistics is unimportant – quite the contrary. It is to emphasize that just because the data is not available in nice and easy spreadsheets or published in some top tier journal, doesn’t mean there is no data.
In the most unexpected of places, I did learn a few things that aren’t readily understood about Paleo diet. These are not the attributes of the diet itself. They are the extras- the sidekicks. Just like in the best of tales, the sidekicks save the day, even when the hero is down and out.

  •  Paleo diet is like a religion. It’s more a way a life than a diet. Just like religion acts as a vehicle to take good ideas and principles to the masses, the Paleo brand helps in bringing common sense and not so common sense dietary principles to the masses. Just like religion, there are high priests,evangelists and followers. Just like religion, there is a strong sense of belonging – for which people give their love and labor for free. Just like religion, it has spawned a parallel economy, where members enrich themselves and others through innovative business models.
  • Just like religion, Paleo has its own issues. Since there’s no universal agreement on even what constitutes Paleo diet ( you can be pretty sure that the cave man didn’t take butter tea!), there are often conflicting views on some topics. These conflicts are resolved not through research, but personal experience of the admins and volunteers. However unlike religions, the group and the shared culture, ultimately puts the power in the hands of the people. 
  • Paleo diet groups are like corporations – they work with a clear hierarchy. They use data to continuously refine the advice and through rapid iteration understand what works and what doesn’t.Unlike corporations, they don’t operate for profit and don’t chase the bottom line. 
  • Paleo diet groups are like cooperative societies. Through the sheer strength of numbers, they are able to bargain with the labs and vendors and reduce the prices.
  • Paleo diet groups are like schools – where the pupils are educated on a radically new diet and the pitfalls to watch out for. The advice may not always be in sync with what the medical community believes, but there can be no denying that it has worked in the short term for many people. The long term health effects of ketosis are largely unknown.

In short, the Paleo diet clearly goes beyond the boundaries of a diet – it’s more of a subaltern lifestyle. Some would even call it a social revolution – for it is of the people,by the people and for the people. There in lies its strength. It’s not an edifice built on multicenter clinical trials – but a belief system that has surprisingly worked for many people and continues to do so. Evidence is accumulating that it is effective in many lifestyle diseases. Even as the neo converts to the EBM decry the lack of evidence, we cannot forget that evidence often takes time. Seeing is believing ,but the reverse is true too – you need to believe in something strongly enough to see the results. For instance, if Gandhiji had asked for evidence that ahimsa can wrest political power from a powerful empire before embarking on the struggle, he would have come up with a nought – after all, there was no historical precedent- and we might have remained under imperial rule!

Our diet is very dear to us – which explain why we have a strong bias towards the status quo. When I see a morbidly obese man becoming fit in the short, without going under the surgeon’s scalpel, I know that’s special. It’s life changing. The biggest impact this search had on me was that now I find it impossibly hard to recommend bariatric surgery to anyone before a paleo trial – I cannot unsee the photos after all !
Of course, the jury is still out on the science of Paleo diet. However I am convinced that even good principles and ideas,like religion, require good packaging and branding. The social component of the Paleo groups is incredibly hard to replicate. We just can’t peddle good advice to people and expect it to catch on like wildfire. In that sense, Paleo might have already transcended the outer limits of conventional medicine.
I still remain a lurker in the group. I eat normal diet. I love statistics. However, when people quote meta analyses and p values, merely to buttress their belief system and show no effort to search for the truth, I chuckle inside. It takes a bit of humility and guts to say we don’t know. May be deep down, we don’t want to know.
May be we don’t want to look beyond evidence. When we do dare to look, the view is breathtaking.

Has my glucometer gone bonkers?

A common problem faced by many diabetic patients is the ‘perceived’ or real inaccuracy of their glucometer. This happens when the glucose reading on the meter is widely different from what is expected – say a very high value after a usual walk that is known to reduce blood glucose or a very low value in a patient who’s not experiencing any symptoms.

When such aberrations occur the common tendency is to blame the glucometer. Some people claim that their glucometer has gone bonkers!However that may not be a good idea.

There are several standards that a blood glucose meter should satisfy before coming to the market. You can access these ISO standards here. Specifically 99% of readings must fall within zones A and B of the Consensus Error Grid for type 1 diabetes. Let me explain further.

What is an error grid ?

When a glucometer is validated for clinical or regulatory purposes, the values measured by the glucometer is compared with a reference method (method comparison study). A scatter plot is drawn and a grid is superimposed on the scatter graph.

For example, a pair (300 mg/dl, 550 mg/dl) represents a large numerical discrepancy, but is unlikely to result in an adverse clinical outcome since in either case the patient will probably receive insulin. On the other hand, a discrepancy of 70 vs. 110 could have serious clinical consequences since hypoglycemic therapy may be administered in the former case, possibly erroneously.

An error grid basically gives clinical context to the discrepancy in measurement between the two methods. Two major systems are in use : Clarke’s error grid and Parke’s(consensus) error grid.Both systems place paired reference/test values into one of five zones – “A”, “B”, “C”, “D” or “E” based on the expected clinical impact of the discrepency.

This is how Clarke’s and Parke’s Error grids look like 

ega

ega2

 

For regulatory clearance , 99 % of the values must fall within zone A or B. So glucometers from standard companies have a high bar to clear before they reach our hands.

In spite of all this, occasionally we get patients complaining of discrepant values. Let’s see what can be done if we get discrepant values. By going through a check list of questions, we can identify whether the reading is inaccurate and the source of inaccuracy. 

The inaccuracy can result from three sources – patient, glucose strip and glucometer

  1. Wrong technique of pricking – usually minor
    • Did you clean your fingers before pricking? This is common in children with type 1 diabetes/ the active type 2 diabetics who play/engage in outdoor activities. A finger that is covered with grime is unlikely to be accurate.Hence accurate cleaning is essential.
    • Did you squeeze your finger hard? Squeezing fingers is not recommended because it leads to estimation of blood glucose in the interstitial fluid, not the capillary blood(the one we want). Choose a lancet , or prick with the appropriate size needle to ensure you get enough blood.
  1. Problem with glucose strip – uncommon
    • Did you store the glucose strip properly? There is a reason glucostrips are packaged in black plastic containers. Exposure to excessive heat/moisture can lead to inaccuracy in glucose readings. Make sure that the glucose strip is stored correctly.
    • Have you used the correct code ? Most modern gluco meters don’t require you to set the code manually.In case you are using a older version of glucometer, it is important to input the correct code. Otherwise wrong readings are possible.
    • Has your strip expired? Glucose strips, like medicines, have expiry dates. It is important to make sure that the strip you are using is not an ancient one.
  2. Problem with glucometer
    • Did you drop the glucometer recently? Glucometers are sensitive devices which should be handled with care. Dropping the glucometer from a height , (like any other electronic device) can result in glucometer malfunction.
    • Water/heat or any other physical damage to the glucometer? Physical damage to the glucometer is easy to detect. You will have to replace the glucometer in this case.

    If you have done all the steps correctly, and still have abnormal values, you need to don the Sherlock Holmes hat and see why it is happening.

    Here are the steps to be followed

    1. Recheck again – this is the first step. If the second value is very similar to the first one, then perhaps error is not random. This of course, doesn’t mean that the value is correct. There could still be a systematic error (an example is a weighing machine that always shows you are 5 kg heavier:-)) . Systematic errors rarely happen in glucometers, but they are possible.
    2. If the repeat value is significantly different, (in spite of keeping all other conditions constant), then the technique is not the culprit. So the issue is with either the glucose strip or the glucometer.
    3. You have two optionscheck blood glucose with the nearby reliable lab or use a control solution. Control solutions contain a known amount of glucose and if the glucometer is working properly, it should be able to give the expected value. It is sort of like measuring a known 1 kg stone in an electronic weighing machine.If the machine shows abnormal reading, then something is wrong with the machine. However control solutions are not commonly used. Most pharmacies don’t event stock them and the glucometer doesn’t come with the control solution. The solution has to be purchased separately (can be got online) and once opened can be used for 3 months only. However they can be conveniently used at home.

    Conclusions

    • Standard glucometers go through stringent quality checks
    • Whenever a discrepant glucose measurement is seen, think of the different levels where things can go wrong – patient, strip or glucometer
    • When in doubt measure in a standard lab or use a control solution.
    • As usual, proper patient education can avoid unnecessary confusion 

    Further reading

    1. Parkes, J. L., S. L. Slatin, S. Pardo, and B.H. Ginsberg. “A New Consensus Error Grid to Evaluate the Clinical Significance of Inaccuracies in the Measurement of Blood Glucose.” Diabetes Care 23, no. 8 (August 2000): 1143-48
    2. Pfutzner, Andreas, David C. Klonoff, Scott Pardo, and Joan L. Parkes. “Technical Aspects of the Parkes Error Grid.” Journal of Diabetes Science and Technology 7, no. 5 (September 2013): 1275-81

 

Progesterone perils

A lot of women are prescribed progesterone for the treatment of threatened abortion and staining during early pregnancy – with the ostensible purpose of saving the pregnancy. Unfortunately some doctors use progesterone as a kind of insurance against miscarriage and this practice is becoming increasingly common. The progesterone levels in the body are naturally higher during early pregnancy. So several doctors think that adding a bit of exogenous progesterone for support will have little or no adverse effects. However not all adverse events are immediately apparent.
A recent paper by Reinisch et al, in Archives of sexual behaviour had a provocative argument. The intake of synthetic progestin by the mother, called lutocyclin was associated with a higher risk of bisexuality in the child. As sexual behaviour and preference can only be discerned after puberty, this intriguing signal is very interesting. Several animal studies show that exposure to progesterone in the prenatal period can cause weird sexual behaviour in the offspring.However animals are largely free of the societal pressures that humans have to face – so the data cannot be directly extrapolated to humans.
The determinants of human sexuality are fiendishly complex. Many are unknown. It is conceivable that exposure of the developing fetal brain to exogenous hormones can have effects that are very hard to predict. To make matters worse, the long latent period between prenatal exposure and the first sexual behaviour makes it very hard to pin any adverse event on a particular drug / event. People with bad experience tend to remember the details that they feel might be related to the issue – the recall bias. Furtheremore it is impractical and unethical to round up a group of mothers, randomly split them into two groups and given one group progesterone and see what happens to their kids later on.So how can we investigate the possible link , between prenatal progesterone exposure and sexual preference in the child?
One way is to have a natural birth cohort. To identify the women who were given progesterone and track the children from birth and compare them with the children of women who were not given progesterone. As long as the children are of the same social background and have good follow up, we might be able to compare them. That’s what the authors did in the study.
They had tracked 34 individuals and found that the tendency for bisexuality (being attracted to both sexes) is higher in the children of mothers treated with progesterone. There was also a dose response effect – crucial in determining casuality. The Bradford hill criteria are commonly used to assess causality

causality

The children of mothers who were treated with higher doses for longer duration were more likely to have bisexuality. The sexual preferences were self reported. Interestingly heterosexual attraction was not diminished in those who reported bisexuality – it ‘s as if they had developed additional attraction to the same sex as well. This is different from a shift to homosexuality – thus showing that a bidimensional model where in both homo and heterosexuality exists in the same individual, with each one having high and low poles.

What do we make of this research?

As we all know , it takes a lot more than a single study to come to conclusions. However a single study which shows consistent findings, with a dose response effect, should raise some alarm. There are some doubts, whether the trade name lutocyclin ( made in late 1950’s, the time the birth cohort was established) was actually progesterone. However the author seems certain. The magnitude of effect and the numbers are small, but the effect itself appears concerning.
In the mean time, it is vitally important that we acknowledge the uncertainty surrounding the effects of prenatal hormone exposure. Studying the effects of such hormone use is very hard.
Hormones are to be used with care – a lot of things like metabolism, receptor affinity,distribution and post receptor mechanisms can result in varying effects in different individuals.

The most important question to ask before taking a hormone is – do I really need it?

Further reading

  1. Prenatal Exposure to Progesterone Affects Sexual Orientation in Humans

Marriage and the nocebo effect

 

Today morning, I opened The Lancet, to see an interesting Statin trial that looked at SAMS (Statin associated muscle symptoms). You can read the trial here


Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase

 

Statins are cholesterol lowering drugs that are sometimes associated with muscle pains. Unlike myopathy or myonecrosis, muscle pains have no objective  biochemical or histological component. The authors had analyzed the statin related adverse effects during the blinded(patient doesn’t know he’s taking statin) and the unblinded(patient knows he’s taking statin) phase of ASCOT trial. When the patients knew they were taking statins, they complained of muscle pains. When they didn’t know what they were taking, they had no symptoms !


In other words, their expectation of what statin might cause (after learning about it from net/other sources) influenced their symptoms. This fascinating phenomenon is called the nocebo effect.It’s the negative cousin of the well known placebo effect. It reflects changes in human psychobiology involving the brain, body, and behaviour rather than drug toxicity.Muscle related adverse effects are often low in randomized trials  compared with observational studies. The strength of this study is that these were the same patients, no run-in period existed to exclude patients intolerant to therapy, and few patients had previously taken any statins.


This reminded me of some of the unfortunate posts on marriage I ve been seeing in Facebook and Quora of late. The liberal rants have an unmistakable pattern – they claim that marriage is the worst thing that can happen to a person. There are some sites (such as this one) whose only job appears to “educate” people on the evils of marriage and praise any and every form of decadence. You can see this in present day movies as well – the premise is that if you get married you are screwed. All these sources happen to think the plural of anecdote is data – it’s not.


It’s possible this can have a “nocebo effect” on our youth – for example,some of the fine boys I know appear to have become unusually nervous at the thought of getting married. Such negativity  may even become a self fulfilling doomsday prophecy. At the expense of committing the same sin as the liberals(the plural of anecdotes!), I must say there is nothing to be afraid of about marriage. Sure,occasional mishaps happen – but they are ,thankfully, still not the norm. Of course, our world view is colored by our own atomized experinces. I am also aware that just because,my experience is overwhelmingly positive doesn’t mean everyone’s will be the same. In any case, it’s important to keep an open mind. Negative thoughts are clearly useless.


PS: Here’s a pro tip: Stay away from the leftist/liberal websites that spew constant trash, if you can. You won’t regret it.