Results of the SPRINT trial

Not sure what the hullabaloo is all about. Some doctors seem to be jubilant that the SPRINT trial shows lower blood pressure than what is currently recommended is better. But I looked at the data and I'm scratching my head.

A general picture of the trial: Participants were non-diabetic hypertensives aged 50 and older. About half (over 4,600) were randomized to therapy that would reduce their blood pressure to less than 140mm Hg. The other half had more intensive pharmacotherapy to get their bp to less than 120mm Hg. The former group averaged 2.8 medications per day, the latter 1.8 meds. Primary outcome was a composite of cardiovascular events including heart attack, stroke, and CV death.

Results: Here's where the rubber meets the road. And frankly the winner zipped past the finish line just a fraction of second earlier than its competitor. Media reported a 25% drop in cardiovascular events in the intensive therapy group. However, the sober truth behind the lurid reporting is that the absolute risk dropped from 2.19% to 1.65% (after 3 years of treatment). That's a measly one half percent. All-cause mortality dropped even lower--just over a third of a percent.

But given the number of hypertensive patients even in the US alone, such a small reduction could potentially prevent a huge number of CV events--even if the data shows that we'd need to give 185 patients an additional pill daily to save one patient from suffering a heart attack, heart failure, stroke, or some other CV event (after a few years of treatment).

But then the trial also discovered a few worms--big ones which should make doctors wary. The NEJM quick take doesn't provide the numbers, but it does tell us that there were more adverse events in the intensive therapy group, events such as syncope (loss of consciousness from hypotension) and kidney failure.

So you have greater benefits, on the one hand, but then greater risks for adverse events as well. So is it really beneficial for hypertensives to bring their bp down to less than 120? Perhaps it would eventually become a judgement call--a decision that doctor and patient will have to arrive at after taking into account the patient's lifestyle, other medical conditions, goals in life, risk aversion level, etc.

2016 USPSTF breast cancer screening recommendations

The latest recommendations are finally out.

I have a beef with its recommendation for the 50-74 age group: They base their decision on the fact that reviews of studies show a decreased breast cancer mortality in those screened. However, the task force clearly knows that screening does not reduce deaths from all causes. They say so right there in their statement: "None of the trials nor the combined meta-analysis demonstrated a difference in all-cause mortality with screening mammography."

What does this mean? Well, apparently screening programs do reduce the number of breast cancer deaths (within a specified time period, eg. per year) but then increases the deaths from other causes, thus nullifying the reduction in the breast cancer mortality. So some women will not die from from breast cancer while others get the short end of the stick and die from something else instead.

So why recommend screening when it does not affect death rates from all causes? Why not underscore this vital information, make certain women know about it, and then have them decide whether they want to go through a screening regimen to reduce their risk of dying from breast cancer but then increase their risk of dying from other causes?

"Science has taken a turn towards darkness"

The case against science is straightforward: much of the scientific literature, perhaps half, may simply be untrue. Afflicted by studies with small sample sizes, tiny effects, invalid exploratory analyses, and flagrant conflicts of interest, together with an obsession for pursuing fashionable trends of dubious importance, science has taken a turn towards darkness. 

 --Richard Horton, editor-in-chief of the Lancet 

Similar conflicts of interest and biases [as those in psychiatry] exist in virtually every field of medicine, particularly those that rely heavily on drugs or devices. It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor of The New England Journal of Medicine. 

--Marcia Angell, former editor-in-chief of the NEJM

Antidepressants are active placebos

[W]hen the level of blinding was high and it was difficult for the investigators, their staff and depressed patients to guess treatment assignment, the differences between these treatments, controls and placebo became quite small. [Kahn and Brown]

Antidepressants work. But they do so only because they elicit a large placebo effect. As has been shown time and again by randomized clinical trials the placebo control always nearly reaches the therapeutic rate of antidepressants. In other words, antidepressants are largely just expensive placebos.

However, that is not quite on the mark. Antidepressants are not just placebos; they are active placebos. Meaning, they produce a range of side effects. And unfortunately some of these are quite serious such as increased risk of suicide and harm to others (including murder), particularly among children, teens and young adults. Moreover, a number of antidepressants can become addictive in the sense that depression-like symptoms occur if the drug is abruptly stopped after having been taken for months. These are drug withdrawal symptoms not a relapse of depression.

The best advice, particularly for those with mild to moderate depression, is to keep away from antidepressants and go for non-drug therapies instead. Such therapies also trigger the placebo effect but don't have the adverse effects of pharmacological agents.

Oliver Sacks, 1933-2015

He went gentle into that good night
In old age he did not burn and rave at close of day
He did not rage against the dying of the light
He went gentle into that good night

So long, Dr. Sacks

From his article in the New York Times earlier this year:

I have been increasingly conscious, for the last 10 years or so, of deaths among my contemporaries. My generation is on the way out, and each death I have felt as an abruption, a tearing away of part of myself. There will be no one like us when we are gone, but then there is no one like anyone else, ever. When people die, they cannot be replaced. They leave holes that cannot be filled, for it is the fate — the genetic and neural fate — of every human being to be a unique individual, to find his own path, to live his own life, to die his own death. 

I cannot pretend I am without fear. But my predominant feeling is one of gratitude. I have loved and been loved; I have been given much and I have given something in return; I have read and traveled and thought and written. I have had an intercourse with the world, the special intercourse of writers and readers. 

Above all, I have been a sentient being, a thinking animal, on this beautiful planet, and that in itself has been an enormous privilege and adventure.

Keeping blood pressure among the elderly at a high enough level

Alan Cassels talks about the dangers of keeping blood pressure low among the elderly.

People who talk about prescribing in the elderly call it an 'evidence-free zone.' ... [B]lood pressure makes a very poignant example of the kind of care the elderly can often be subject to.... The problem is that trying to get blood pressure that low for someone who is 80 is almost totally irrational. Why? Because the physiology of old people is different and most blood pressure studies have specifically excluded people aged 80 and over. Those few studies that have focused on the elderly find something terribly surprising: the patients in the trials who had lower blood pressure had a higher risk of death.

This gets my goat. Because some doctors treat the elderly like they're middle aged and drown them in antihypertensives to keep their bp within the range appropriate for half century old individuals. Hence adverse effects can kick in. As in dizziness and light headedness in my mom's case. Seemingly unable to think out of the box, these doctors (hopefully in the minority) treat their now septua- and octogenarian patients as if they were still in their 50s. And worse, patients have been indoctrinated into believing there is an unquestionable Goldilocks zone for bp which is true for everyone and for all ages. And so they happily go along with their physicians' recommendations.

False positives, incidentalomas, overdiagnosis

"More testing leads to more false positives and incidental findings (abnormalities that don't pose a risk to your actual health). That leads to a higher probability of treatment. And treatment carries side effects." --Charles Ornstein

And from Dr. Gilbert Welch:

The more tests you do, and this is only the statistical process, the more likely one of them will be falsely abnormal. And the more times you do it, the more chance that something will be falsely abnormal.

The problem is you'll always be catching things out of what we would say is normal. This is anticipatory medicine at its worst, where you're really focused on what could be going wrong in the future and you're trying to pick up [a] signal.

The problem is there's so much noise — because the human body is a living organism. Variation is the very essence of life. People will start reacting to this data. I also think it's really important to label it what it is: data. To me it only becomes information to the extent that it accurately predicts something will happen in the future, and it only becomes useful knowledge — a higher level piece of information — if we can do something about it.

[http://www.npr.org/blogs/health/2015/04/06/397848621/tracking-your-own-health-data-too-closely-can-make-you-sick]