Welcome to my blog, a place to explore and learn about the experience of running a psychiatric practice. I post about things that I find useful to know or think about. So, enjoy, and let me know what you think.

Tuesday, February 2, 2016

Laughing Rats

I attended a talk a couple weeks ago at The New York Psychoanalytic Society and Institute (NYPSI), given by Jaak Panksepp, and entitled, Cross Species Affective Neuroscience. It was a really good talk that I'll try to summarize here. Panksepp spoke using a power point that didn't quite work right, through no fault of his own, and gave a talk similar to his TEDx talk about affect in non-human animals, and the way humans can be understood by studying these animals, particularly with respect to depression. His part was followed by the discussant, Jean Roiphe, who presented a corresponding analytic perspective, and highlighted points of overlap and divergence.

First, the speakers. This is from Wikipedia:

And Jean Roiphe's description from the NYPSI site is:

Clinical Associate Professor of Psychiatry, Weill-Cornell Medical College
Associate Attending Psychiatrist, New York-Presbyterian Hospital
Training and Supervising Analyst, New York Psychoanalytic Institute

One of Panksepp's main points is that affect is the foundation for all consciousness, and that most learning takes place through affective shifts. This reminded me of a guy from my medical school class who decided he should memorize everything by singing, because while the Complement pathways eluded him, he could still remember every TV commercial jingle he learned as a kid.

Panksepp briefly addressed the question of why one would choose to study emotional feelings in animals, which is to say, whether animals have minds at all, and pointed out that animal lovers' beliefs that this is the case is an argument from empathy, and that LeDoux is skeptical about whether animals have feelings.

Panksepp, himself, believes that animals have feelings and that all their experiences are labeled "good" or "bad"; that animals can tell us if something is rewarding or punishing. And here, the definition of "good" = leads to survival, while the definition of "bad" = leads to destruction.

He noted, quite emphatically, that in his opinion, all feelings are based in the subcortical system, and pointed out that while Damasio initially believed feelings are generated in the neocortex, he later switched to Panksepp's position, and acknowledged so, which earned him Panksepp's label of, "mensch". Panksepp does not feel similarly about LeDoux.

Panksepp described the seven emotional systems in the brain. This is one of the places where his slides malfunctioned, so I'm taking this from the slide in his TEDx talk:

RAGE---------Pissed Off
CARE--------Tender and Loving
PANIC-------Lonely and Sad

He mentioned that dopamine and the nucleus accumbens are the foundation for all positive emotions, and that this probably represents a general purpose learning system. He also mentioned the association between the Hypothalamus/PAG/Amygdala and the ANGER system.

He returned to his discussion about the subcortical system as the foundation of feelings and consciousness, and pointed out that rats with no neocortex behave "normally", and that raters were not able to differentiate these from rats with neocortices.  In fact, the neocortex-less rats showed more interest in their environment than the normal rats. No inhibition, I suppose.

He focused particularly on the SEEKING, PLAY, and PANIC systems, because these were areas of exploration that have shown promise for the treatment of depression.

SEEKING is associated with the Medial Forebrain Bundle. Bilateral lesions in this region yield profound depression, while bilateral deep brain stimulation in this region yields an antidepressant effect.

One medication that usefully impacts the SEEKING system and acts as an antidepressant is very low dose buprenorphine, which makes juvenile animals play more. He claimed that drug withdrawal shows similarities to the experience of separation distress, which is a model for depression via the PANIC system.

Opioids mediate every good feeling ever studied, and in fact, contact comfort, known to be effective at soothing panic, doesn't work as well if opioid receptors are blocked.

Oxytocin is just as powerful as opioids with respect to depression, in its re-creation of mothering attachment. This has implications for placebo effect, since handing someone a placebo is an act of caring.

Panksepp cited a very small study he did with Yovell using buprenorphine to treat depression and suicidality. The suicidality results are what he included in his slides:

He also spoke about a study using bilateral Deep Brain Stimulation (DBS) to act on the SEEKING system in 7 subjects with treatment resistant depression. 6/7 responded well, with a marked improvement in planning for their futures. It turned out that in the one non-responder, the DBS had missed on one side.

Finally, and to me this was the most important part, he talked about an antidepressant he has been researching, a tetrapeptide called, GLYX-13, that acts on the PLAY system. The results have been promising, with decreases in depression thought to be mediated by promoting positive social feelings, including laughter. Panksepp is big on laughter, and is known for tickling rats to get them to laugh. Unfortunately, he seemed to indicate that GLYX-13 was bought up by a company with a competing antidepressant, so it may not make it to market.

His slides really gave out at this point, so he handed the stage over to Jean Roiphe for her discussion. Spoiler alert: It's quite brilliant, and if you don't think so after reading my summary, it's only because I didn't do it justice.

Roiphe described being on safari a decade ago, watching animals spending their days grazing on the veldt, except when they sensed a predator, at which point they would take evasive action. This was pretty much all they did, and it correlates well with the SEEKING and FEAR systems. It made her wonder, now that our survival is so much more assured, at least in some parts of the world, what has happened to our emotional meanings? We now fill our free time with things like art and science and architecture and literature and blogging, but we also fill it with neuroses, anxiety, eating disorders, perversions, and all the many clinical presentations we see in our work.

She noted that while the seven emotional systems are preserved in our brains, it's important to remember that, paraphrasing Kandel, humans now change more by cultural than by biological evolution. At the same time, it's also important to establish a line of communication between those who study the subjective aspects of the mental apparatus, such as psychoanalysts, and those who study its objective aspects, such as neuroscientists. And that the mind is simultaneously and always both a psychological and a biological entity.

She spoke about the value of linking the two approaches, in both directions. For psychoanalysis, the value is having neurological correlates to analytically abstract concepts of the mind, because the former are technologically easier to study, with the proviso that this may not simplify matters all that much, since different neuroscientists can interpret "brain data" differently, as in the above example of Panksepp vs. LeDoux.

And for neuroscience, the value is in learning about the complexity of subjective experience, and recognizing that the human condition is impossible to understand or even study without taking the subjective into account.

In some respects, the emotional systems described by Panksepp correlate with Freud's affect theory, in which affect is a way for a person to tell if his or her drives are being satisfied. Or not. I feel good or I feel bad. This experience is pleasant, that one is unpleasant. However, the seven emotional systems are instinctual, do not need to be learned, and involve behavioral responses, whereas Freud's affect theory involves only a pressured sense that something needs to be fulfilled, and this may or may not lead to a behavioral response, but always leads to mental activity, to thought as trial action. This is a good example of why it's important to avoid the trap of trying to create one to one correspondences between approaches.

Freud's ideas about affect evolved over time, along with his changing theory of anxiety, and his shift from the topographic model (unconscious vs. conscious) to the structural model (id, ego, superego), but ultimately, affect became tied to ego function, as a way for the ego (which acts as a combination of party coordinator and chaperone) to mark the need for some kind of response to something, whether that something is internal or external.

This is similar to the concept of the seven emotional systems as survival mechanisms-X happened, I feel Y in response, and now I need to do Z. The difference lies in the connections between affect, ego function, and object relationships. Human emotions such as guilt, shame, and envy, are generated by the development of the ego in a complicated social context. Uniquely human affects and moods and their corresponding pathologies arise from the interactions of cortical regulatory effects on subcortical systems, and these are mediated by the ego, which becomes itself under the influence of the people around it.

Ego functioning often involves "taming" certain affects, especially through thought and language, but it also involves intensifying some affects, so that people can feel truly alive. A full human life can't be reduced to an all or nothing switch of feeling in response to external events.

We can illustrate the role of the ego in human experience by examining Panksepp's model for depression, which involves the malfunction of the PANIC, SEEKING, and/or PLAY systems. This model corresponds well with anaclitic depression, in which babies separated from their mothers for extended periods became despondent, emotionally withdrawn, and frequently died. Strikingly, Spitz, who studied the syndrome, noted that a way to prevent this deterioration was to find a suitable substitute caregiver, and to allow the babies to move around outside their cribs (see this post). This meshes well with the involvement of both the PANIC/separation distress and SEEKING systems.

Spitz attributed the need for the babies to move around not to an innate SEEKING system, but to a need for discharge of aggression. The absence of aggression is where Panksepp's model for depression diverges from psychoanalytic models, in which aggression is central. Freud's, Mourning and Melancholia, reflects the idea that sadness is not the same as depression, which results when a loss, usually of an ambivalently loved object, precipitates rage, which is then directed towards the self.

There are other types of depression, as well. In an ego depression, the actual self falls short of the wished-for self, as in the loss of a job, or the limitations that come with aging. Depression results when there is an aggressive attack on the self for these losses, "I have failed." In a superego depression, the actual self falls short of the wished for self in moral or ethical values, which results in an aggressive attack on the self: "I'm bad, I should be punished."

Panksepp also considered the evolutionary advantage of depression as a shut down mechanism in PANIC situations. But a psychoanalytic perspective includes not only the concept of depressive pathology, which is a source of immense suffering and need for treatment, but also depressive capacity.

Depressive capacity includes the ability to tame or appropriately redirect aggression, and to tolerate the inevitable disappointments and losses of life. It involves the willingness to accept responsibility for our moral failings by not hiding behind depression-inducing guilt, or other defenses such as blame or projection. And it requires the ability to relinquish ones unattainable dreams, to accept the lack of fulfillment of ones impossible wishes, and to bear the limitations in ones self.

That was pretty heavy. Now this. I mentioned the problem with Panksepp's power point for a reason. He didn't get to show the video of himself tickling rats. So here it is:

Friday, January 22, 2016

Minding Our P's

I've been reluctant to write this post, even though I've referenced it previously. It's just that I've been trying to gain a better grasp of statistics, and reading 1boringoldman's posts has really helped me, and based on them, I finally managed to explain to myself what p-values actually are, but I just figured that must be completely obvious to everyone but me, so why should I bother writing about it.

What finally convinced me was thinking about how so many studies include p-values as a way of proving one drug is "significantly" better than another or placebo, and don't bother to include effect sizes. This is a great obfuscating tactic, so whoever's conducting these studies must think that people misunderstand p-values. And that makes it worth writing this post.

This is the story of how I clarified p-values to myself.

Let's say we're doing a study comparing two compounds,

Hubba Bubba

and Bubble Yum

to determine which is better at curing the common cold.

We start out with the null hypothesis, which states that we assume there is no difference between the two compounds, or what they can do. If the p-value turns out to be less than 0.05, then we can reject the null hypothesis. I don't like thinking about the null hypothesis because it confuses me. It's like trying to decipher a triple negative. So we're gonna put it aside for now.

We randomize 100 patients to each arm, and follow up the next day, and the day after, with a rating scale, the CQ-7. And this is what we find:

Let's assume we've done all our work honestly and accurately, and we get a p-value less than 0.05. Does this mean that Bubble Yum is significantly better at curing the common cold than Hubba Bubba? It does not. It means we can reject the null hypothesis. But what does THAT mean?

Think of it this way.

Suppose that on the night before the study begins, I sneak into the lab and change the wrappers so that there is no Bubble Yum, only Hubba Bubba. And then suppose we do the study, and we get exactly the same results as above. Can it be? Is it possible that all 100 subjects taking Hubba Bubba wrapped as Bubble Yum got better, and all 100 subjects taking Hubba Bubba wrapped as Hubba Bubba didn't? Yes, it is possible. It's just extremely unlikely. Extremely improbable. How improbable? Well, there's less than a 5% chance that the two compounds could be exactly the same, and yet yield such freakishly different results. That's why the "p" in p-value stands for probability.

In other words, we've rejected the null hypothesis.

Let me repeat. If the p-value is less than 0.05, then there is less than a 5% chance that the null hypothesis is true, i.e. less than a 5% chance that the compounds could be the same and yet yield such disparate results. Which means they're probably not the same. And we choose the significance level to be 0.05, but we could just as easily choose 0.10, or 0.01.

So a very small p-value does not mean that Bubble Yum is significantly better than Hubba Bubba at curing the common cold. It just means that it is extremely unlikely that Bubble Yum could be no better than Hubba Bubba at curing the common cold, with these very different results.

In order to determine how much better Bubble Yum is than Hubba Bubba, you need to look at effect size, and as we have seen any number of times, a small p-value does not imply a large effect size. For example, in the CBT study I recently looked at, p was <0.001, but the effect size was 0.45, only moderate.

This is why many studies leave the effect size out of their publications.

Sunday, January 17, 2016

Long Term Efficacy of CBT?

I get email updates from several places I consider reasonably reputable, like NEJM, that have lists of new and interesting articles. I consider those kinds of updates helpful ways of staying current. I also get other kinds of email updates that feel more like ads, or infomercials, like this one, from Psychiatric News Alert:

Study Finds Long-Term Benefits of CBT for Patients With Treatment-Resistant Depression

Patients with treatment-resistant depression who receive cognitive-behavioral therapy (CBT) in addition to antidepressants over several months may continue to benefit from the therapy years later, according to a study in Lancet Psychiatry...

“Our findings provide robust evidence for the effectiveness of CBT given as an adjunct to usual care that includes medication in reducing depressive symptoms and improving quality of life over the long term,” the study authors wrote. “As most of the CoBalT participants had severe and chronic depression, with physical or psychological comorbidity, or both, these results should offer hope for this population of difficult-to-treat patients.”

You can link to the Lancet Study, Long-term effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: follow-up of the CoBalT randomised controlled trial, by Wiles et al,  here. It's full text.

In brief:

Cognitive behavioural therapy (CBT) is an effective treatment for people whose depression has not responded to antidepressants. However, the long-term outcome is unknown. In a long-term follow-up of the CoBalT trial, we examined the clinical and cost-effectiveness of cognitive behavioural therapy as an adjunct to usual care that included medication over 3–5 years in primary care patients with treatment-resistant depression.

CoBalT was a randomised controlled trial done across 73 general practices in three UK centres. CoBalT recruited patients aged 18–75 years who had adhered to antidepressants for at least 6 weeks and had substantial depressive symptoms (Beck Depression Inventory [BDI-II] score ≥14 and met ICD-10 depression criteria). Participants were randomly assigned using a computer generated code, to receive either usual care or CBT in addition to usual care. Patients eligible for the long-term follow-up were those who had not withdrawn by the 12 month follow-up and had given their consent to being re-contacted. Those willing to participate were asked to return the postal questionnaire to the research team. One postal reminder was sent and non-responders were contacted by telephone to complete a brief questionnaire. Data were also collected from general practitioner notes. Follow-up took place at a variable interval after randomisation (3–5 years). The primary outcome was self-report of depressive symptoms assessed by BDI-II score (range 0–63), analysed by intention to treat. Cost-utility analysis compared health and social care costs with quality-adjusted life-years (QALYs)...

They took an old study, with subjects who had taken antidepressants for at least 6 weeks and had substantial depression symptoms characterized by a BDI-II score of at least 14, and followed up with a questionnaire and GP notes. Primary outcome was self-report of depressive symptoms assessed by BDI-II score. They also did a cost analysis.

Between Nov 4, 2008, and Sept 30, 2010, 469 eligible participants were randomised into the CoBalT study. Of these, 248 individuals completed a long-term follow-up questionnaire and provided data for the primary outcome (136 in the intervention group vs 112 in the usual care group). At follow-up (median 45·5 months [IQR 42·5–51·1]), the intervention group had a mean BDI-II score of 19·2 (SD 13·8) compared with a mean BDI-II score of 23·4 (SD 13·2) for the usual care group (repeated measures analysis over the 46 months: difference in means −4·7 [95% CI −6·4 to −3·0, p<0·001]). Follow-up was, on average, 40 months after therapy ended. The average annual cost of trial CBT per participant was £343 (SD 129). The incremental cost-effectiveness ratio was £5374 per QALY gain. This represented a 92% probability of being cost effective at the National Institute for Health and Care Excellence QALY threshold of £20 000.

Follow-up was a median of 45.5 months, at which point, the CBT group had a mean BDI-II of 19.2, and the control group a mean BDI-II of 23.4

CBT as an adjunct to usual care that includes antidepressants is clinically effective and cost effective over the long-term for individuals whose depression has not responded to pharmacotherapy. In view of this robust evidence of long-term effectiveness and the fact that the intervention represented good value-for-money, clinicians should discuss referral for CBT with all those for whom antidepressants are not effective.

Note that "individuals whose depression has not responded to pharmacotherapy," were taking antidepressants for 6 weeks. The study states later that, "This definition of treatment-resistant depression was inclusive and directly relevant to primary care."

Let's look at the details. I'll start by stating that I'm not going to consider the cost effectiveness, because I don't know how. And it may be that even if the clinical effects turn out to not be impressive (spoiler!), the treatment may be worthwhile from a financial standpoint.

At the start of the current study, all patients were taking antidepressants, and were randomized to 12-18 sessions of CBT, or usual care from their GPs. I find this confusing. It seems like medication ought to be a confounder, since depression is cyclic to begin with and people respond to medications at variable rates. Also, if you consider these patients to be treatment resistant, why continue them on antidepressants?

I also find what they did with the outcome measures confusing:

The primary outcome was self-report of depressive symptoms assessed by BDI-II score (range 0–63). Secondary outcomes were response (≥50% reduction in depressive symptoms relative to baseline); remission (BDI-II score <10); quality of life (Short-Form health survey 12 [SF-12]); and measures of depression (PHQ-9) and anxiety (Generalised Anxiety Disorder assessment 7 [GAD-7])...

The primary outcome for the main trial was a binary response variable; for this follow-up, the primary outcome was specified as a continuous outcome (BDI-II score) to maximise power. The change in the specification of the primary outcome for the long-term follow-up was made at the time the request for additional funding was submitted to the funder (Nov 6, 2012).

Does this mean they changed the primary outcome? In the original CoBalT trial, "The primary outcome was response, defined as at least 50% reduction in depressive symptoms (BDI score) at 6 months compared with baseline." Did the present study start out using response, and then switch to change in BDI-II score after the fact, which we all know is a no-no? They're claiming they changed it when they requested funding for the current study, but is that before or after they had established their primary outcome measure?

Or did the current study start with change in BDI-II score as the primary outcome measure, and is that okay? In other words, if you're basing your current study on a previous study, is it valid to establish your protocol with a different outcome measure than the original study? I don't know.

Moving on. The study makes a lot of claims about secondary outcomes, and whether or not subjects were still taking antidepressants, but I'm restricting myself to thinking about the primary outcome, and the BDI-II measures are as follows:

The effect size, according to this chart, is 0.45, which is on the low side of moderate. I don't know how they did their computation, but when I used 1BoringOldman's spreadsheet (see this post), I got a Cohen's d effect size of 0.31, which is low.

I'm not sure how this constitutes "Robust evidence." I'm also not sure what's robust about a mean BDI-II of 19.2, when by their definition, a BDI-II score of more than 14 is considered "Substantial depressive symptoms."

Look. I'm not a big fan of CBT, but I'm willing to consider it as a useful treatment if you show me good data. Just don't go hyping your at-best-mediocre data like it's amazing. But of course, Psychiatric News is a product of the APA.

Thursday, January 14, 2016

DIY Study Evaluation

If you have any interest at all in being able to evaluate the results of clinical trials on your own, say because you don't trust what the pharmaceutical companies are telling you, then I HIGHLY recommend you head on over to 1 Boring Old Man and read through his posts from the last few weeks. Basically, he's writing a statistics manual for clinicians, complete with downloadable spreadsheets of his own devising.

His explanations are clear, but I wanted to make sure I could do this on my own, so I tried it out. Here's how it worked.

I would categorize myself as a fairly conservative prescriber, by which I mean that I'm not eager to jump on the new drug bandwagon, and I like to wait a year or two, until we know a little about the effects and side effects of a new drug, before I write for it. I also wait a few weeks before upgrading my iOS for the same reason, so there ya go. But I recently had occasion to prescribe the antidepressant, Brintellix, or vortioxetine. I can't get into the clinical details, but suffice it to say there were reasons. So with Brintellix on my mind, I decided to try out the 1 Boring Old Man spreadsheet on one of their studies that I found on clinicaltrials.gov, specifically, Efficacy Study of Vortioxetine (LuAA 21004) in Adults with Major Depressive Disorder, the results of which were submitted to clinicaltrials.gov in October 2013.

From the get-go, it's looks like a poor study. There were 50 study sites scattered all over Asia, Europe, Australia, and Africa, and it looks like they did something to the outcome measures midstream. But I'm just trying out the spreadsheet, so I'm ignoring all that for now.

The primary outcome measure was change in HAM-D score, which means that I needed to use the spreadsheet for continuous variables, because mean change could have been any number. If the measure was, "Achieved remission," however they define, "remission," then the results would be tabulated in Yes/No form, and I would have had to use a different spreadsheet designed for categorical variables.

But let me pause here and ask a question: Just what am I looking for? Well, I'm looking for effect size, which generally isn't given in results. Usually, we just get to see p-values, but I'll get to why that's not sufficient in a later post.

As a reminder, effect size is the difference between treatment groups, expressed in standard deviations. Roughly speaking, a large effect size is 0.8, medium is 0.5, and small is 0.2. So, for example, if the effect size of A v. B is 0.8, then A did 0.8 of a standard deviation better than B, and this is considered a large effect. So if I know the effect size, then I can tell how much better one group did than another. I can quantify the difference between groups. Cohen's d is often used as a measure of effect size.

It turns out that you only need three pieces of information to determine effect size, all generally available in typical papers. For each arm of the study, you need the number of subjects in that arm, the mean, and the standard error of measure (SEM) or standard deviation, which are interchangeable via the formula (sorry, I don't have Greek letters in my font):

That's it: n, mean, SEM.

Here is that information from the study report.  Note that there were four arms: Placebo; Vortioxetine 1mg, 5mg, and 10mg.

Let's plug 'em all in to the 1BOM spreadsheet, while noting that I'm not including the ANOVA, which you really need to do first, to make sure the four groups aren't all the same in comparison to each other, because if they are, then any result you get when you compare 1 group directly with 1 other group is invalid. Just so you know, I computed the ANOVA using this calculator, also recommended by 1BOM, which requires exactly the same information as you need to compute effect sizes, and it turns out that the groups are NOT all the same (this is another thing related to p value, which I plan to discuss in a later post).

The top three rows show the effect sizes for the three active arms, compared with placebo. Note that the effect sizes are in the moderate range, 0.423 to 0.591.

In the next three rows, I also checked to see how the active arms compared with each other in a pairwise fashion, and the 10mg really doesn't do much better than the 5mg or even the 1mg, with 0.170 the largest effect size.

Just considering effect sizes in this one study, Brintellix looks okay.

So you can see that there are powerful things you can do in the privacy of your home, to understand what a study is really telling you, using only minimal information. That feels pretty good. At the same time, you have to take into account other elements, like the fact that they seem to have changed outcome measures after the protocol was already established. That should invalidate the whole kit and kaboodle, but sometimes you need to try out a new drug, and the studies aren't great, but it's the best you can do.

Tuesday, January 12, 2016

Shrinks, Once More, Again

Yes, I thought I was done with Jeffery Liebermans's, Shrinks: The Untold Story of Psychiatry, but it was not to be.

Clinical Psychiatry News asked me to write a shorter review than the one on my blog, from the angle of whether it would be a good book for a psychiatrist to recommend to patients.

So how could I resist? This one is much shorter, and less of a rant.

So please surf over there and check it out. It feels good to have my opinion expressed beyond these confines. I think the site is free but you may have to register. Also, the print version will be out in a few weeks.

Enjoy, and come back here to comment, if you like.

Thursday, December 31, 2015

Mourning and Falconry-A Book Review

I recently finished reading, H is for Hawk, by Helen Macdonald. I stumbled across it in a bookstore in Berkeley called, Books Inc. A real bookstore. The small kind that has a mini-review or commentary by the staff every few books on the shelf. It was refreshing to be there.  I didn't realize it was a NY Times Bestseller. It just drew my eye and looked interesting.

According to her page at The Marsh Agency, Ms. Macdonald is a, "writer, poet, illustrator, historian, and naturalist, and an affiliated research scholar at the Department of History and Philosophy of Science at the University of Cambridge. Over the years she's also worked as a Research Fellow at Jesus College, Cambridge, as a professional falconer, assisted with the management of raptor research and conservation projects across Eurasia, and bred hunting falcons for Arab royalty. She's also sold paintings, worked as an antiquarian bookseller, organised academic conferences, shepherded a flock of fifty ewes and once attended an arms fair by mistake."

H is for Hawk is moving and fascinating, but I'm also very happy to report that even if the subject didn't interest me, I would have enjoyed the book because the woman can write. Sometimes I'll read a book, particularly fiction, and while I may be enjoying the story, I find myself editing the writing- this passage was awkwardly phrased, that sentence would have been better at the end of the paragraph, etc. Not so for Macdonald's writing. It's both beautiful and accessible.

Here's a sample (p. 181):

But then the pheasant is flushed, a pale and burring chunk of muscle and feathers, and the hawk crashes from the hedge towards it. And all the lines that connect heart and head and future possibilities, those lines that also connect me with the hawk and the pheasant and with life and death, suddenly become safe, become tied together in a small muddle of feathers and gripping talons that stand in mud in the middle of a small field in the middle of a small county in a small country on the edge of winter.

Shortly after her father's sudden death,  Macdonald decided to train a goshawk. She'd been fascinated by hawks all her life, and had extensive experience training them. But this was her first attempt at training the notoriously challenging goshawk.

There are a number of reasons she made this decision. One early-Spring morning, she felt restless, got up at dawn, and for no discernible reason, drove to the Brecklands to see goshawks, which are rarely visible in the open except at that time of year. The experience reminded her of watching for sparrowhawks with her father, when she was a child. She brought home a piece of reindeer moss she'd been gripping while watching the goshawks that day, and three weeks later, she was staring at the moss when her mother called to tell her her father had died.

That's the first connection. One of the brilliant things about the book, and there are many, is that Macdonald clearly recognizes the complex interactions between her thoughts and feelings, and her behavior. But she does not dwell on them, as one would in a typical psychoanalytic case report. She simply describes them, and leaves the reader to draw conclusions, although she does, occasionally, mention Melanie Klein, Freud, and other analytic thinkers.

The next connection is closer to the heart of her mourning. She describes a summer experience she set up for herself when she was 12, and went to spend several weeks with some gentlemen who flew goshawks:

I was terrified. Not of the hawks: of the falconers. I'd never met men like these. They wore tweed and offered me snuff. They were clubbable men with battered Range Rovers and vowels that bespoke Eton and Oxford, and I was having the first uncomfortable inklings that while I wanted to be a falconer more than anything, it was possible I might not be entirely like these men...

On the first day of that trip, she watched a goshawk kill a pheasant, her first sight of death. She also watched as later that same day, the goshawks seemed to lose interest in their handlers and flew off into the trees. Some took hours before returning:

The disposition of their hawks was peculiar. But it wasn't unsociable. It was something much stranger. It seemed that the hawks couldn't see us at all, that they'd slipped out of our world entirely and moved into another, wilder world from which humans had been utterly erased.

After that summer, she chose to stay away from goshawks:

I never forgot those silent, wayward goshawks. But when I became a falconer I never wanted to fly one. They unnerved me. The were things of death and difficulty: spooky, pale-eyed psychopaths that lived and killed in woodland thickets. Falcons were the raptors I loved...

Yet another connection has to do with T. H. White, best known as the author of, The Once and Future King. He also wrote a book entitled, The Goshawk, his firsthand account of training his own goshawk, who he named, Gos. It was a disaster. It's like an instruction manual for how NOT to train a goshawk, or any other animal, for that matter. As a child, Macdonald reviled White for his inconsistent, and ultimately cruel treatment of Gos. But in H is for Hawk, she comes to view, The Goshawk, differently, as White's account of his conflicts surrounding sadism and love, and his struggle to become himself through his identification with Gos.

Macdonald is a much better trainer than White, although she doubts herself constantly. Is she feeding Mabel (her goshawk) too much, or too little, or the wrong kind of food? The feeding of a goshawk is not a trivial, Jewish mother issue. Goshawks weigh around two pounds, and a couple ounces either way can throw off their flying completely. But the level of Macdonald's worry is indicative of her mourning, which, by her own acknowledgement, is mixed with depression to a degree that would bewilder the most hardcore DSM-5 enthusiast.

Certainly, Mabel is a comfort to Macdonald. She turns out to be not that difficult to train, and is even playful-there's a lovely description of a game involving some rolled up paper, with Macdonald commenting that she hadn't realized goshawks DID play. She attributes at least some of their affinity to their shared gender, and notes that all the falconers and austringers (solitary goshawk trainers) who have described the bird as difficult and sulky have been men.

Incidentally, I attempted to contact Macdonald through her agent to get permission to use a photo of Mabel that I found online, in this post, but I never heard back from either of them-I suspect my message didn't get through-so I'm not comfortable using the picture here. But if you google "Mabel the goshawk" you will see that she was very beautiful.

Macdonald traces her bonding with Mabel, as well as her use of Mabel to isolate herself while she's mourning. We sense the appeal of the hawk's ability to "slip out of this world". By identifying with Mabel, she can distance herself from her pain, or access her father, who has "moved into another, wilder world from which humans had been utterly erased."

And we see the painful, drawn out process of letting go that Freud wrote about in Mourning and Melancholia (Freud, S. (1917). Mourning and Melancholia. The Standard Edition of the Complete Psychological Works of Sigmund Freud, Volume XIV, Pp. 244-5):

In what, now, does the work which mourning performs consist? I do not think there is anything far-fetched in presenting it in the following way. Reality-testing has shown that the loved object no longer exists, and it proceeds to demand that all libido shall be withdrawn from its attachments to that object. This demand arouses understandable opposition—it is a matter of general observation that people never willingly abandon a libidinal position, not even, indeed, when a substitute is already beckoning to them. This opposition can be so intense that a turning away from reality takes place and a clinging to the object through the medium of a hallucinatory wishful psychosis. Normally, respect for reality gains the day. Nevertheless its orders cannot be obeyed at once. They are carried out bit by bit, at great expense of time and cathectic energy, and in the meantime the existence of the lost object is psychically prolonged. Each single one of the memories and expectations in which the libido is bound to the object is brought up and hyper-cathected, and detachment of the libido is accomplished in respect of it.

At some point, Macdonald has to literally let go of Mabel's jesses and allow her to fly free, to have faith that she'll return.

I learned a lot of fun terminology from the book, too. Jesses are the leather straps that fit through the anklets on a hawk's legs. Bating is a, "Headlong dive of rage and terror, by which a leashed hawk leaps from the fist in a wild bid for freedom." That was me quoting Macdonald quoting White.

She describes making jesses as a child. Then she comments, " I have a suspicion that all those hours making jesses and leashes weren't just preparation games...It reminds me of a paper by the psychoanalyst D. W. Winnicott, the one about the child obsessed with string; a boy who tied together chairs and tables, tied cushions to the fireplace, even...Winnicott saw this behaviour as a way of dealing with fears of abandonment by the boy's mother, who'd suffered bouts of depression. For the boy, the string was a kind of wordless communication, a symbolic means of joining. It was a denial of separation. Holding tight. Perhaps those jesses might have been unspoken attempts to hold on to something that had already flown away."

Macdonald had a twin brother who died shortly after birth. She wasn't told about him until years later, but she wasn't that surprised by the news. She wonders if a detailed drawing of a kestrel's jesses, that she drew when she was six, was, "...a way of holding tight to something I didn't know I'd lost, but knew had gone..." And she imagines that the jesses she makes for Mabel are a way of similarly holding on to her father. But I wondered if her father's death hit her as hard as it did, in part, because of the unremembered but somehow perceived loss of her twin, now being re-experienced. And I wondered further what it means to her that she survived, and her brother didn't.

Because we also see the connection between death and aggression. Mabel is beautiful and playful, but she is a powerful killer. That's what she does. That's why Macdonald got her in the first place. So they could hunt together.

Mabel, as she kills her prey, becomes the actualization of Macdonald's rage against her father's death, and against her father, for dying. When she and the bird are one, she becomes the master of death, able to decide who lives and who dies. A powerful wish fulfilled, only too late for her father.

Ultimately, with Mabel's assistance, but also of her own accord, Macdonald gets through her mourning period and is able to resume her life with some joy. To begin again.

Happy New Year!


I really don't get twitter. I couldn't figure out how to send a private message to Helen Macdonald to ask permission to use a photo of Mabel, which is why I contacted her agent. But when I tweeted this post, I added her twitter handle, and she read the tweet, and apparently the post, and gave me permission to use a photo. So, this is Mabel. Wasn't she beautiful? (Disclosure: I grew up with parakeets, and I have a soft spot for birds):

Thursday, December 17, 2015

Thank You, Mickey! Part II

Picking up where I left off in Thank You, Mickey! Part I, I was about to describe how the article I'm examining, Effectiveness of influenza vaccine for preventing laboratory-confirmed influenza hospitalizations in adults, 2011-2012 influenza season, figured out that there is a 71% reduction in flu-related hospitalizations in patients who have been vaccinated against flu, vs. those who haven't.

One of the articles Mickey sent me was from the World Health Organization (WHO), Field Evaluation of Vaccine Efficacy, written in 1985 by Orenstein, et al, and published in the Bulletin of the WHO. This article was, in fact, listed in the bibliography, but I didn't notice it. Thanks again, Mickey.

In general, Vaccine Efficacy (VE) is the difference between the incidence or attack rate of disease among the unvaccinated (ARU) and vaccinated (ARV), divided by the ARU, and multiplied by 100.

VE=(ARU-ARV)/ARU x 100.

So, for a perfect vaccine, the ARV would be zero, and then

VE= (ARU-0)/ARU x 100
     = ARU/ARU x 100
     = 100%

For a vaccine that didn't work at all, the ARU would equal the ARV, and then

VE=(ARU-ARU)/ARU x 100
     = 0/ARU x 100
     = 0%

In the study, we have the following data:

The ARU is the number of those who were unvaccinated and flu positive divided by the total number of unvaccinated.

ARU= 11/65 = 0.169


ARV= 6/104 = 0.058

Therefore, the VE= (0.169-0.058)/0.169 x 100 = 0.111/0.169 x 100 = 66%

It's close, but it's not 71%, and the reason for this is that this is the general formula for VE. The study had a case-control design with unmatched pair analysis, in which case,

VE= (1-RR) x 100,

where RR = relative risk, which is roughly equal to the Odds Ratio (OR) in this case.

OR = (Flu+, Vaccinated)(Flu-, Unvaccinated)/(Flu-, Vaccinated)(Flu+, Unvaccinated)
      = 6x54/98x11
      = 324/1078
      = 0.301

So VE= (1-0.301) x 100
           = 0.700 x 100
           = 70%

The study got 71%, but I'm assuming they had a better calculation of the OR, so 70% is close enough.

Okay, now we know how they determined that the flu vaccine effectiveness was 71%. So I'm going to act like an analyst and ask, "What does this really MEAN?"

The article claims it means that there was a 71% reduction in flu-related hospitalizations in patients who have been vaccinated against flu, vs. those who haven't.

But I don't think that's correct, and it was one of the things I went back and forth about with Mickey.

They looked at patients' vaccination statuses, and at which patients tested positive for flu. The appropriate conclusion to draw from this data is that vaccination resulted in a 71% reduction in flu INFECTION, in this population.

They did NOT look at patients' vaccination status, which patients tested positive for flu, AND which patients ended up hospitalized. They couldn't possibly look at that, because the entire population was hospitalized. So they can't logically draw any conclusions about whether vaccination reduced hospitalization or not.

For example, let's say they looked at 3000 people in the community, 1000 of whom were vaccinated against flu, and 2000 of whom were unvaccinated. And let's say they checked to see who was hospitalized with an illness that looked like flu, and it turned out that 104 vaccinated patients and 65 unvaccinated patients were hospitalized. These are the same numbers as in the study.

Now let's say they checked to see which of the hospitalized patients were flu+, and it turned out that 6 of the vaccinated, and 11 of the unvaccinated patients were flu+.  Again, same numbers.

Then 6/1000 = 0.60% of the vaccinated patients were flu+ and hospitalized,

And 11/2000 = 0.55% of the unvaccinated patients were flu+ and hospitalized.

So how would the vaccination have reduced flu-related hospitalizations by 71%, when the rate of flu-related hospitalization is lower for the unvaccinated patients?

Obviously, I just made up the 1000 and 2000 figures, but my point is you can't know whether vaccination reduced flu-related hospitalizations without knowing how many were NOT hospitalized.

The thing is, I really know very little about statistics. So I suspect I'm missing something here. But I can't figure out what. And in case I'm not missing something, it's a pretty big deal that the CDC is using this result to support their recommendation for universal flu vaccination.

The truth is, a vaccine efficacy of 71% is not so great. By comparison, the inactivated polio vaccine has an efficacy of 90% after 2 doses, and 99% after 3 doses (link). This doesn't mean there isn't good reason to recommend universal flu vaccination. For one thing, older people, who stand to benefit greatly from not getting flu, don't have a good serologic response to the flu vaccine, simply by virtue of age. The best way to protect them, then, is herd immunity, which you can get from having younger adults vaccinated.

I would really appreciate comments on this post. In particular, comments from people who know some statistics and have taken a look at the article. I'd like to know what I'm not seeing correctly, or if perhaps I am seeing things correctly.

Thanks for your help, especially Mickey.