An antidote to apathy

Sometimes your moment of epiphany comes in the most unlikely of places. And things are never the same again.

It was November 2012. I had just gotten married and booked tickets to Andamans. On day 2 , we had gone to the Cellular Jail. Little did I know that the night would mark a tectonic shift in my world view. They had arranged a light and sound show to show the tourists about the struggles of countless men incarcerated there during India’s darkest years. The sheer impossibility of escape and the brutal conditions of the jail would break even the strongest men.

I was transfixed and with great respect visited Savarkar’s cell. Veer Savarkar was kept in a cell (strategically) just opposite the gallows – so that he can see the prisoners getting hanged. The man had written  – in Hindi – a poem to the birds,

“I don’t know your language, but If I did, I would teach you the Indian National anthem”

Even now, it’s hard for me to say in any language,including my own, what I felt at that moment. Perhaps a gush or respect , a wave of pride,love for the nation all mixed in intoxicating proportions, that I almost lost balance. It was then that the unthinkable happened.

Several people behind me had been making noises, smoking and making fools of themselves generally. In spite of admonition from the guide, they paid little heed to the sanctity of the ground they were treading. It was a generation that didn’t have to deal with British atrocities. The irony of the situation wasn’t lost on me – that they were able to do that in Cellular jail only because of the sacrifice of thousands of freedom fighters. Sometimes when you get something, without toiling for it, you hardly understand its value. These ungrateful brats had the temerity to go to gallows and make some stupid jokes!

Life had come a full circle. From the time when we were united and used every means to wrest freedom from a cold empire, we had become a nation with no pride or self respect. I,Me and Myself had become the dominant personal ideology. The government had embraced a politics of anything goes and by natural progression, scams rocked the country. The regularity of these scams would put any Swiss watch maker to shame.

I had little idea of Modi or BJP then. Nor was I particularly aware that nationalism was an antidote to the plague I was witnessing. I was one of those happy go lucky guys whose life revolves around a book, a laptop and a cup of coffee. I was decidedly apolitical. Of course, just because we don’t take interest in politics doesn’t mean politics won’t take interest in us.

The questions kept haunting me through out my honeymoon – just like the rhythmic waves that hit the beautiful beaches of Andamans. Why did these people feel no respect or love for the freedom fighters? Why were they not proud of their heritage? Where did we lose the plot? More importantly, what is the solution?

Of course, it was apparent that in a vast and diverse country like India, it is juvenile to expect a knight in shining armor to come and change things. It was also clear that we were at cross roads in history – a decisive moment – when things can only change for the better, if there is a thorough overhaul of the dominant narrative. The political discourse needed some shaking up. We needed to find some way to unite the country – the sleeping giant – and gear up to take a larger role in the world stage.

It was then that Modi happened. The social media powered campaign was a blitzkrieg. Like so many of my country men, I came under his spell. We see only what we want to see, and believe someone who says what we want to hear. He was a master orator and I cursed myself for not knowing enough Hindi to understand his speeches.

Three years on – when I look around – I am happy that things have finally started to change.But sometimes it’s hard to shake off the feeling that we might have gone overboard. The duality has become quite stark – not that is always bad – after all , if you looking at good and bad, you can’t complain of them being totally different. The media has become more polarised – so much so that it’s hard to tell what is true these days. The quality of public discourse is laughably poor – incessant fights on language, religion and caste continue to plague us.

As India has become a global power to reckon with, our vulnerability to external threat has diminished substantially. To put it in our PM’s words, India of 2017 is not the same as India of 1962. The standoff in Doklam and China’s cautious approach is ample testimony to this fact. Our growing clout is undeniable.

Unfortunately we are quite vulnerable to ourselves and our folly. We may have become more divided nation – or so it seems. The very drug of nationalism which was intended to treat the apathy has now reached militant heights. The shrill cry of hypernationalism is threatening to tear the fabric of our cherished diversity. After all, our flag is a tricolor, not some monochrome.

I was and still remain a subclinical sanghi. I do wonder if my political pendulum is beginning to swing towards the centre. On this glorious Independence day, we must realize that our differences don’t matter as much as our shared history and bonds. We need to tell our kids that we take great pride in our Indian identity- the primary identity of all of us.Just like our forefathers who toiled hoping that their children and grandchildren would one day live in a free India, we need to work hard to ensure that we don’t drop the baton. We owe it to those brave souls who shed their blood and sweat in cellular jail.

Happy Independence day!

Jai Hind!

 

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

The God in small things

Name the decisive war that Napoleon lost?

Most of us would answer Waterloo. In fact , Waterloo is almost a synonym for final comeuppance. The reality though is a little different. Napoleon actually won Waterloo. Yet, he managed to snatch defeat from the jaws of victory.

When Napoleon escaped from Elba in 1815 and the Hundred Day Campaign begun, the capitals of Europe instantly sprang to activity. The political uncertainty was profound , as everyone was well aware of Napoleon’s military genius. To put it mildly, the future of Europe and thus of the world was at stake. As fate would have it, it fell upon Colonel Cornelius Frazier,battalion commander of Wellington to face Napoleon. The British had cleverly planned to fight from high ground at Mont Saint-Jean. Napoleon was least bothered -he had the best of men, horses and lances -commanded by the mighty Napoleon himself. He decided to mount a deadly cavalry attack and separate the enemy forces from their cannons. Facing Napoleon’s marauding army, the British forces tried their best to avert disaster. There was only so much they could do and before long they started abandoning their cannons and ran for life. Napoleon beamed -he had defeated Wellington at Waterloo. He thought he would dine in Brussels that night.

I might have been writing this post in French, instead of English, had Napoleon’s men not forgotten a tiny detail. Those days, the cannons were muzzle loaded and were ‘triggered’ by placing flame in the touchhole. It was customary to destroy enemy cannons after capture by hammering a headless nail into the touchhole, making the cannon useless. Napoleon’s men had forgotten to bring that pack of nails!

As the battle raged on, the British realized the French blunder. This energized the British forces who thought they were staring at death. Eventually the British recaptured the cannons and the tide turned. Napoleon watched in horror as he lost the battle he had just won, all for want of a few nails. He had the best men and weapons, but that didn’t matter. A small detail, overlooked, changed the history of the world.

As doctors, we will see patients and we will make mistakes.Sometimes a mistake will cost the life of a patient. It may not change the history of the world, but it may snuff out the future of someone, who means the world to his loved ones. No one is immune to mistakes, but we take each mistake seriously and learn from them.

For instance,a mortality meeting is one such probe for mistakes. The kind of things we want to avoid. Learning from someone else’s mistakes is easier and less painful than learning from our own. I have made my lion’s share of mistakes. Thinking back, some were as disastrous as Napoleon’s nails and others much less so. But each one taught me that small things matter. As they say God is in the details, but so is the devil.

Our experience is the sum total of our successes and failures. We will only ever truly fail, if we fail to learn from our mistakes. In life or in medicine.

Getting started with case reports

A case report is the perfect starting point for a resident new to scholarly publishing. It is easy to write, requires little creativity (after all it is just a documentation of a patient that came to meet the doctor) and though has limited impact, has good educational value. More than anything else, it lowers the barrier to scientific writing.


There is a catch though – case reports are the low hanging fruits. Accordingly there is quite a bit of competition there – lot of people want to write, very few publishers want to publish. This has created a vacuum which has been fulfilled by speciality case report journals. These journals publish only case reports and therefore have a much higher acceptance rate – somewhere in the range of 30 to 70 %. The increased demand also causes a situation where publishers may resort to questionable practices. In fact, almost half the journals are found to be dubious.



How to identify the genuine journals?


The trick is to find those case report journals which are PubMed Indexed. Only one PubMed Indexed journal(published by Baishideng group) is known to indulge in questionable practices[Refer to the Excel file linked at the end of the article]. So a case report journal that is PubMed Indexed is highly likely to be genuine. For example, my first publication was a case report in BMJ case reports.  BMJ case reports has a decent acceptance rate, but in order to submit one of the authors or the institution must have subscription. Individual subscription costs around 185 GBP (around Rs.15000), but just one subscription in a department is more than enough. Be sure to check if your institution has subscription – in which case, you can contact the librarian to get the submission access code. BMJ case reports doesn’t have an impact factor as such (many case report only journals don’t.). However you can use the scimagojr 2 year citations per article as a reasonable proxy.


Of course, case reports are also published by journals that publish other stuff like reviews and original articles. However the acceptance rate is likely to be lower in these journals. If you are confident of your material, it is best to try in a general journal first before trying a case reports only journal. When in doubt, ask an expert.



A master list of case reports only journals can be accessed in Excel format here. Sadly I couldn’t get a master list of submission fees – if you have details on that, do let me know. If you found this post useful, please share with your friends.


Further reading


New journals for publishing medical case reports

Hope for the “helmet” times

I have shared this one before in social media. Luckily Journal of Social Health and Diabetes was willing to publish it. If you haven’t read about the heroic work of my friends in managing a patient with unusual features of Type 1 Diabetes, you can read it in the link below.

Hope for the “helmet” times