One of those weeks which leave me battered and bruised.
My ego's taken a severe beating this fortnight: a series of failed experiments in lab, failed because of my carelessness, a so-so presentation by me about my work at lab meeting, halfway through which I realize the lack of multiple important controls in the experiment and have to come up with mediocre explanations for the same, someone at home admitting that he didn't feel comfortable there because it was too disorganized and untidy for him, and so on and so forth.
Ouch.
I have become expert at shoving unpleasant thoughts to the back of my mind and forcing them there till I can forget about them. Until they come crowding in all at once and catch me unawares.
It's 20F outside and I need to leave soon to pick up Ani from the day care and carry him back home. Haven't given the poor kid a bath in two days (though, hey, he did get his teeth brushed everyday. That's gotta count for something).
Okay, let's focus on the positives:
a) Ani's smile at he waved goodbye to me in the morning at daycare
b) I taught someone how to think through the preparation for a PhD Comprehensive Exam and I think she was pretty inspired and impressed.
c) My friendship with my labmates- in this lab and in my previous one. So see? SOMEbody likes me, I'm not all terrible.
d) Hmm... positive stuff in the sphere of scientific research that I have done... aaaarrgghh nothing that I have done recently, but my journal club presentation was pretty good.
e) Something positive in the home front... let's forget about tidiness and laundry and clutter now... Oh, hey, you know what? I have been cooking great, healthy, reasonably tasty food at home every single day (and many times, more than once a day) for 4 straight months now. I have made sure that everybody who is at home gets something decent to eat. There. Okay, so that's my answer to whoever sticks their nose up about the state of the house. Which actually, by the way, is pretty damn good. If you're going to be hyper-sensitive, and want everything to be spic and span, don't come home.
So...I think I do a darn fine job of holding everything together...for now... somehow...
Thursday, January 19, 2012
Friday, January 13, 2012
The ACCORD study
Am attempting to increase my knowledge about the field of diabetes research by scanning the top journals for all their articles on beta cells and diabetes. Came across the ACCORD study (Action to Control Cardiovascular Risk in Diabetes), which concluded prematurely in 2008 because the treatment arm of the clinical trial ended up with greater numbers of deaths than the control arm.
The writeup in Science is found here: http://www.sciencemag.org/content/319/5865/884.full.pdf?sid=2b4ab30f-345c-4a91-8c91-537ac10f410b
This is the gist of it:
People with diabetes are at an increased risk of cardiovascular diseases and can die of heart attacks.
The hypothesis was: if you control diabetes, you should be able to reduce the number of fatalities due to heart attacks or other cardiovascular diseases (CVD for short).
Therefore, aggressive lowering of blood glucose levels should protect against CVD.
So to test this hypothesis out, they got about 5000 people in the treatment arm (so these guys were diabetics who were considered high risk for dying of CVD and who had their blood glucose lowered by aggressive treatment with a variety of drugs) and another 5000 people in the control arm (also diabetic, but no treatment, other than their usual regimen)
Then they found that there were greater numbers of people dying of heart attacks in the treatment group, compared to the control.
Uh oh.
Questions to be asked:
a) What was the blood glucose lowered to? How was this being measured? - They measured something called hemoglobin Ac, or HbAc, as a surrogate marker for glucose in the red blood cells
b) Is the HbAc measure a suitable surrogate to monitor blood glucose?
-Apparently so. Lots of people use it in clinics and hospitals.
c) Is there a relationship between HbAc levels and risk of cardiovascular disease?
- Very important point. And tellingly, NO! Nobody has shown that HbAc levels correlate with risk of CVD. Also, one may not have diabetes, but have an HbAc value of greater than 6.
So, it seems to me that firstly (and frankly, this is probably the most minor point) the wrong surrogate marker was used.
Secondly, what about the drugs used to lower the HbAc? Assuming that phamacologists went through the drug list and found that these drugs did not interact adversely with each other, might they not have side-effects that would increase CVD risk?
Thirdly, and this is a great point made by one of the researchers who was arguing against this hypothesis from the beginning: the population under trial have had diabetes for a long time, and are considered high risk for CVD. This means they probably already have plaques in their blood vessels. Lowering the blood glucose may loosen these plaques: apparently, plaques contain sugar and it is the sugar that thickens and strengthens the plaques. If you were to lower blood sugar drastically, these plaques may not stick around on the walls of the blood vessels anymore, but begin to float around and eventually get stuck in the heart, causing a massive heart attack.
Very interesting, no?
There is a possibility that things become worse before they come better. That is to say, that perhaps if they had continued the study for a few more years, and continued monitoring the people who got the aggressive treatment (and survived it), they would have seen better prognostic markers, (and indeed this has been shown in smaller studies), but who knows? For the safety of the people involved, the trial was stopped 18 months before it should have.
Perhaps a gradual decrease of blood glucose, instead of a drastic one, might have less numbers of fatalities?
More relevantly, how sustainable is this approach? I mean, assume that this trial really had showed that aggressive treatment lowers risk of CVD. So what? Wouldn't this person have to take those medicines for the rest of his life anyway? And who is to say that those drugs in turn do not cause some other kind of damage- liver failure or renal issues? What then?
From the little I know about this issue, it seems to be that the long term risks outweigh the benefits.
So I would have to say that it's a good thing that trial showed what it did and forced everybody to think a lot harder about what that glucose in the blood is really doing.
The writeup in Science is found here: http://www.sciencemag.org/content/319/5865/884.full.pdf?sid=2b4ab30f-345c-4a91-8c91-537ac10f410b
This is the gist of it:
People with diabetes are at an increased risk of cardiovascular diseases and can die of heart attacks.
The hypothesis was: if you control diabetes, you should be able to reduce the number of fatalities due to heart attacks or other cardiovascular diseases (CVD for short).
Therefore, aggressive lowering of blood glucose levels should protect against CVD.
So to test this hypothesis out, they got about 5000 people in the treatment arm (so these guys were diabetics who were considered high risk for dying of CVD and who had their blood glucose lowered by aggressive treatment with a variety of drugs) and another 5000 people in the control arm (also diabetic, but no treatment, other than their usual regimen)
Then they found that there were greater numbers of people dying of heart attacks in the treatment group, compared to the control.
Uh oh.
Questions to be asked:
a) What was the blood glucose lowered to? How was this being measured? - They measured something called hemoglobin Ac, or HbAc, as a surrogate marker for glucose in the red blood cells
b) Is the HbAc measure a suitable surrogate to monitor blood glucose?
-Apparently so. Lots of people use it in clinics and hospitals.
c) Is there a relationship between HbAc levels and risk of cardiovascular disease?
- Very important point. And tellingly, NO! Nobody has shown that HbAc levels correlate with risk of CVD. Also, one may not have diabetes, but have an HbAc value of greater than 6.
So, it seems to me that firstly (and frankly, this is probably the most minor point) the wrong surrogate marker was used.
Secondly, what about the drugs used to lower the HbAc? Assuming that phamacologists went through the drug list and found that these drugs did not interact adversely with each other, might they not have side-effects that would increase CVD risk?
Thirdly, and this is a great point made by one of the researchers who was arguing against this hypothesis from the beginning: the population under trial have had diabetes for a long time, and are considered high risk for CVD. This means they probably already have plaques in their blood vessels. Lowering the blood glucose may loosen these plaques: apparently, plaques contain sugar and it is the sugar that thickens and strengthens the plaques. If you were to lower blood sugar drastically, these plaques may not stick around on the walls of the blood vessels anymore, but begin to float around and eventually get stuck in the heart, causing a massive heart attack.
Very interesting, no?
There is a possibility that things become worse before they come better. That is to say, that perhaps if they had continued the study for a few more years, and continued monitoring the people who got the aggressive treatment (and survived it), they would have seen better prognostic markers, (and indeed this has been shown in smaller studies), but who knows? For the safety of the people involved, the trial was stopped 18 months before it should have.
Perhaps a gradual decrease of blood glucose, instead of a drastic one, might have less numbers of fatalities?
More relevantly, how sustainable is this approach? I mean, assume that this trial really had showed that aggressive treatment lowers risk of CVD. So what? Wouldn't this person have to take those medicines for the rest of his life anyway? And who is to say that those drugs in turn do not cause some other kind of damage- liver failure or renal issues? What then?
From the little I know about this issue, it seems to be that the long term risks outweigh the benefits.
So I would have to say that it's a good thing that trial showed what it did and forced everybody to think a lot harder about what that glucose in the blood is really doing.
Sunday, January 8, 2012
My book
I am going to write a book. I am fairly sure it is NOT going to get published in Mills and Boon, which is where I will first send it to because they have some kind of audition going on to find India's next great Mills and Boon writer (did you even know India had a Mills and Boon-India edition? I didn't. Checked out the books that have been published under its aegis- exactly the same story lines as the British/Aussie ones, except with Indian names... and maybe with brown skin. I say maybe, because that really is not a sure deal with these things- for all you know, the heroine will be described as being "tall, fair with green eyes", with a name like Ashtanga, so that non-Indian readers will be familiar with it).
My mother-in-law and I had a conversation about this some time back when she was here in the US. We share a deep love of romance novels. I had mentioned to her that I wished there were at least one book with an Indian hero. The only romance stories with Indian heroes in them are the truly ghastly ones in Women's Era and frankly, I get completely sidetracked with the spelling and grammatical mistakes and can't pay attention to the story, which is probably pedantic and pedestrian anyway. That's one thing my story will not have: spelling and grammatical mistakes. I might throw in a few split-infinitives here and there (because I don't know what they are, but believe that they are not in vogue), but I make a solemn promise here and now: my book won't make any self-respecting person who likes words and grammar cringe or wince. Of course, it may make its readers cringe or wince for other reasons, but that's something I do not promise not to do. See? I keep achievable goals for myself.
So where was I? Oh right, I was whinging about the lack of truly great Indian romantic heroes and my mother in law said, "Well. What do you expect? Your hero will probably want curd rice and pickle for dinner, and he'll keep shedding hair all over the place and burp and fart and expect his wife to do pretty much everything around the house" (she didn't say those exact words, but you get the picture). Hmm... she had a good point. But then again, novels are fiction, not fact. And in my novel, I can pretty much make my guy into whatever I want. He will be the epitome of a romantic hero- courteous, considerate, courageous, compassionate, funny and handsome... hey, kind of like my husband, without the burps and the farts and the shed hair!
Actually, our great classical books and stories have some pretty damn good heroes, except they are not in the modern mold. I just have to pick up a convenient one and tweak him here and there. Let's see: I don't think I would pick Arjuna or Bhima, for obvious reasons. Maybe Yudhistira, but he's a gambler and those guys are always a bad bet. Maybe Nakula or Sahadeva, about whom I know nothing except they were good with animals (... not bad... maybe I'll make my guy a veterinarian). Or how about Harishchandra- the king who valued truth above everything else... maybe after his stint as a grave digger? Or maybe Chandra Gupta, with his daring and cunning and political machinations... or am I thinking of Chandragupta Maurya? Who was the king who was made king with the help of Chanakya? Can't remember whether he was a Gupta or a Maurya. Or... a truly radical thought... I could just go right up to the heavens and pick Krishna... all the elements of the great romantic hero are in Krishna: he's handsome, affectionate, funny, wily, enigmatic, loves everybody and everybody loves him. Too much of a playboy, perhaps? There's good potential there.
Anyway, lots of decisions to be made and lots of writing to be done. I love being busy with such projects!
My mother-in-law and I had a conversation about this some time back when she was here in the US. We share a deep love of romance novels. I had mentioned to her that I wished there were at least one book with an Indian hero. The only romance stories with Indian heroes in them are the truly ghastly ones in Women's Era and frankly, I get completely sidetracked with the spelling and grammatical mistakes and can't pay attention to the story, which is probably pedantic and pedestrian anyway. That's one thing my story will not have: spelling and grammatical mistakes. I might throw in a few split-infinitives here and there (because I don't know what they are, but believe that they are not in vogue), but I make a solemn promise here and now: my book won't make any self-respecting person who likes words and grammar cringe or wince. Of course, it may make its readers cringe or wince for other reasons, but that's something I do not promise not to do. See? I keep achievable goals for myself.
So where was I? Oh right, I was whinging about the lack of truly great Indian romantic heroes and my mother in law said, "Well. What do you expect? Your hero will probably want curd rice and pickle for dinner, and he'll keep shedding hair all over the place and burp and fart and expect his wife to do pretty much everything around the house" (she didn't say those exact words, but you get the picture). Hmm... she had a good point. But then again, novels are fiction, not fact. And in my novel, I can pretty much make my guy into whatever I want. He will be the epitome of a romantic hero- courteous, considerate, courageous, compassionate, funny and handsome... hey, kind of like my husband, without the burps and the farts and the shed hair!
Actually, our great classical books and stories have some pretty damn good heroes, except they are not in the modern mold. I just have to pick up a convenient one and tweak him here and there. Let's see: I don't think I would pick Arjuna or Bhima, for obvious reasons. Maybe Yudhistira, but he's a gambler and those guys are always a bad bet. Maybe Nakula or Sahadeva, about whom I know nothing except they were good with animals (... not bad... maybe I'll make my guy a veterinarian). Or how about Harishchandra- the king who valued truth above everything else... maybe after his stint as a grave digger? Or maybe Chandra Gupta, with his daring and cunning and political machinations... or am I thinking of Chandragupta Maurya? Who was the king who was made king with the help of Chanakya? Can't remember whether he was a Gupta or a Maurya. Or... a truly radical thought... I could just go right up to the heavens and pick Krishna... all the elements of the great romantic hero are in Krishna: he's handsome, affectionate, funny, wily, enigmatic, loves everybody and everybody loves him. Too much of a playboy, perhaps? There's good potential there.
Anyway, lots of decisions to be made and lots of writing to be done. I love being busy with such projects!
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