Review of “Oestrogen Matters” Avram Bluming and Carol Tavris, TLS 29th January 2019

In the current TLS I have a brief review of Bluming and Tavris’ book on HRT. The full text is available to subscribers; here is the first paragraph:

Few medical treatments have seen as stark a rise and fall as hormone replacement therapy (HRT). In the early 1940s, methods were developed to extract oestrogen from pregnant mares’ urine, and the resulting medication was named Premarin. Marketed from the 1950s for menopausal symptoms, HRT was catapulted into the public consciousness by the New York gynaecologist Robert Wilson’s bestseller Feminine Forever (1966), and made Ayerst Laboratories, who had developed Premarin and paid Wilson’s expenses for writing the book, extremely rich. HRT was hyped as a wonder drug adding years to life and life to years

Language recognition in the womb – Fetal rhythm-based language discrimination – study from NeuroReport

I have blogged before about on the tendency to grandiosity of neuroscience, or rather (very often) how the science media portray neuroscience. This phobia of neurohype is not the same as a suspicion of neuroscience. The ingenuity of the methodology of studies like this is staggering. I don’t have access via my usual library sources to recent issues of NeuroReport so I’m afraid that I can’t assess the study directly (in so far as as I am at a certain stage of clinical practice, and the consequent distance from what personal study of relevance I have done)

Fetal rhythm-based language discrimination: a biomagnetometry study
Minai, Utakoa; Gustafson, Kathleenb; Fiorentino, Roberta; Jongman, Allarda; Sereno, Joana

Neuroreport: 5 July 2017 – Volume 28 – Issue 10 – p 561–564
Abstract

Using fetal biomagnetometry, this study measured changes in fetal heart rate to assess discrimination of two rhythmically different languages (English and Japanese). Two-minute passages in English and Japanese were read by the same female bilingual speaker. Twenty-four mother–fetus pairs (mean gestational age=35.5 weeks) participated. Fetal magnetocardiography was recorded while the participants were presented first with passage 1, a passage in English, and then, following an 18 min interval, with passage 2, either a different passage in English (English–English condition: N=12) or in Japanese (English–Japanese condition: N=12). The fetal magnetocardiogram was reconstructed following independent components analysis decomposition. The mean interbeat intervals were calculated for a 30 s baseline interval directly preceding each passage and for the first 30 s of each passage. We then subtracted the mean interbeat interval of the 30 s baseline interval from that of the first 30 s interval, yielding an interbeat interval change value for each passage. A significant interaction between condition and passage indicated that the English–Japanese condition elicited a more robust interbeat interval change for passage 2 (novelty phase) than for passage 1 (familiarity phase), reflecting a faster heart rate during passage 2, whereas the English–English condition did not. This effect indicates

that fetuses are sensitive to the change in language from English to Japanese. These findings provide the first evidence for fetal language discrimination as assessed by fetal biomagnetometry and support the hypothesis that rhythm constitutes a prenatally available building block in language acquisition.

The inspirational imperative

“Inspirational” and its derivatives has replaced “passionate” as a CV-staple. “Inspirational” has also become a clickbait-staple. My Twitter feed seems to sag under the burden of just so many “inspirational” and “inspiring” links. “Inspiration”, “inspiring”, “inspirational” – all join “disruptive”, “revolutionary”, “transformational” in the Overused Lexicon.

Recently a video circulated online (OK, “went viral”) of a woman with terminal illness being interviewed by Ryan Tubridy on The Late Late Show. While her own determination to live every moment is entirely admirable, I do wonder if the cult of Inspiration can put pressure on people in this situation (and many others) to Be An Inspiration. Winston Churchill’s battles with the “black dog” of depression are often held up as inspiring – look what he achieved despite his depression! – but this can be demoralising – look what he achieved despite his depression, so why can’t I? Cue guilty spiral…

Currently Sir Bradley Wiggins is facing serious questions about his use of Therapeutic Use Exemptions. Cycling seems a sport that, even more than others, is bound up with a culture of Being Inspirational (perhaps this is because cycling does seem to small-i inspire many adults to take up the bike themselves, in a way watching professional football, for example, doesn’t) . One of the reasons Lance Armstrong got away with his drug cheating was the Inspirational Story he was able to wrap himself in, and a natural reluctance on the part of many to burst an Inspirational bubble.

Much of the discourse online about eHealth can take a similarly  Inspirational Above All turn. Perhaps this is another example of how the can-do, market-focused, startup culture of tech conflicts with the more restrained, evidence-focused, small-c conservative world of healthcare.

 

 

“The Wild West of Health” care: mental health Apps, evidence, and clinical credibility

We read and hear much about the promise of mobile health. Crucial in the acceptance of mobile health by the clinical community is clinical credibility. And now, clinical credibility is synonymous with evidence, and just “evidence” but reliable, solid evidence. I’ve blogged before about studies of the quality of mental health smartphone apps. I missed this piece from Nature which, slightly predictably, is titled “Mental Health: There’s an app for that.” (isn’t “there’s an App for that a little 2011-ish though?) It begins by surveying the immense range of mental health-focused apps out there:

 

Type ‘depression’ into the Apple App Store and a list of at least a hundred programs will pop up on the screen. There are apps that diagnose depression (Depression Test), track moods (Optimism) and help people to “think more positive” (Affirmations!). There’s Depression Cure Hypnosis (“The #1 Depression Cure Hypnosis App in the App Store”), Gratitude Journal (“the easiest and most effective way to rewire your brain in just five minutes a day”), and dozens more. And that’s just for depression. There are apps pitched at people struggling with anxiety, schizophrenia, post-traumatic stress disorder (PTSD), eating disorders and addiction.

The article also has a snazzy  infographic illustrating both the lack of mental health services and the size of the market:

The meat of the article, however, focuses on the lack of evidence and evaluation of these apps. There is a cultural narrative which states that Technology = Good and Efficient, Healthcare = Bad and Broken and which can give the invocation of Tech the status of a godterm, pre-empting critical thought. The Nature piece, however, starkly illustrates the evidence gap:

But the technology is moving a lot faster than the science. Although there is some evidence that empirically based, well-designed mental-health apps can improve outcomes for patients, the vast majority remain unstudied. They may or may not be effective, and some may even be harmful. Scientists and health officials are now beginning to investigate their potential benefits and pitfalls more thoroughly, but there is still a lot left to learn and little guidance for consumers.

“If you type in ‘depression’, its hard to know if the apps that you get back are high quality, if they work, if they’re even safe to use,” says John Torous, a psychiatrist at Harvard Medical School in Boston, Massachusetts, who chairs the American Psychiatric Association’s Smartphone App Evaluation Task Force. “Right now it almost feels like the Wild West of health care.”

There isn’t an absolute lack of evidence, but there are issues with  much of the evidence that is out there:

Much of the research has been limited to pilot studies, and randomized trials tend to be small and unreplicated. Many studies have been conducted by the apps’ own developers, rather than by independent researchers. Placebo-controlled trials are rare, raising the possibility that a ‘digital placebo effect’ may explain some of the positive outcomes that researchers have documented, says Torous. “We know that people have very strong relationships with their smartphones,” and receiving messages and advice through a familiar, personal device may be enough to make some people feel better, he explains.

And even saying that (and, in passing, I would note that in branch of medical practice, a placebo effect is something to be harnessed, not denigrated – but in evaluation and study, rigorously minimising it is crucial) there is a considerable lack of evidence:

But the bare fact is that most apps haven’t been tested at all. A 2013 review⁸ identified more than 1,500 depression-related apps in commercial app stores but just 32 published research papers on the subject. In another study published that year⁹, Australian researchers applied even more stringent criteria, searching the scientific literature for papers that assessed how commercially available apps affected mental-health symptoms or disorders. They found eight papers on five different apps.

The same year, the NHS launched a library of “safe and trusted” health apps that included 14 devoted to treating depression or anxiety. But when two researchers took a close look at these apps last year, they found that only 4 of the 14 provided any evidence to support their claims¹⁰. Simon Leigh, a health economist at Lifecode Solutions in Liverpool, UK, who conducted the analysis, says he wasn’t shocked by the finding because efficacy research is costly and may mean that app developers have less to spend on marketing their products.

Like any healthcare intervention, an App can have adverse effects:

When a team of Australian researchers reviewed 82 commercially available smartphone apps for people with bipolar disorder¹², they found that some presented information that was “critically wrong”. One, called iBipolar, advised people in the middle of a manic episode to drink hard liquor to help them to sleep, and another, called What is Biopolar Disorder, suggested that bipolar disorder could be contagious. Neither app seems to be available any more.

And even more fundamentally, in some situations the App concept itself and the close relationship with gamification can backfire:

Even well-intentioned apps can produce unpredictable outcomes. Take Promillekoll, a smartphone app created by Sweden’s government-owned liquor retailer, designed to help curb risky drinking. While out at a pub or a party, users enter each drink they consume and the app spits out an approximate blood-alcohol concentration.

When Swedish researchers tested the app on college students, they found that men who were randomly assigned to use the app ended up drinking more frequently than before, although their total alcohol consumption did not increase. “We can only speculate that app users may have felt more confident that they could rely on the app to reduce negative effects of drinking and therefore felt able to drink more often,” the researchers wrote in their 2014 paper¹³.

It’s also possible, the scientists say, that the app spurred male students to turn drinking into a game. “I think that these apps are kind of playthings,” says Anne Berman, a clinical psychologist at the Karolinska Institute in Stockholm and one of the study’s authors. There are other risks too. In early trials of ClinTouch, researchers found that the symptom-monitoring app actually exacerbated symptoms for a small number of patients with psychotic disorders, says John Ainsworth at the University of Manchester, who helped to develop the app. “We need to very carefully manage the initial phases of somebody using this kind of technology and make sure they’re well monitored,” he says.

I am very glad to read that one of the mHealth apps which is a model of evidence based practice is one that I have both used and recommended myself – Sleepio:

One digital health company that has earned praise from experts is Big Health, co-founded by Colin Espie, a sleep scientist at the University of Oxford, UK, and entrepreneur Peter Hames. The London-based company’s first product is Sleepio, a digital treatment for insomnia that can be accessed online or as a smartphone app. The app teaches users a variety of evidence-based strategies for tackling insomnia, including techniques for managing anxious and intrusive thoughts, boosting relaxation, and establishing a sleep-friendly environment and routine.

Before putting Sleepio to the test, Espie insisted on creating a placebo version of the app, which had the same look and feel as the real app, but led users through a set of sham visualization exercises with no known clinical benefits. In a randomized trial, published in 2012, Espie and his colleagues found that insomniacs using Sleepio reported greater gains in sleep efficiency — the percentage of time someone is asleep, out of the total time he or she spends in bed — and slightly larger improvements in daytime functioning than those using the placebo app¹⁵. In a follow-up 2014 paper¹⁶, they reported that Sleepio also reduced the racing, intrusive thoughts that can often interfere with sleep.

The Sleepio team is currently recruiting participants for a large, international trial and has provided vouchers for the app to several groups of independent researchers so that patients who enrol in their studies can access Sleepio for free.

This is extremely heartening – and as stated above, clinical credibility is key in the success of any eHealth / mHealth approach. And what does clinical credibility really mean? That something works, and works well.

 

 

Evidence based medicine and evidence based policy

There was a fair bit of media coverage of the finding that teenage-pregnancy-prevention programmes using simulated babies are associated with an increased rather than decreased teenage pregnancy rate. Some of the media discussion focused on the role of evidence in public policy.

Via Twitter, I came across this article on evidence-based policy by Howard White in The Independent

Evidence-based medicine has transformed medical practice. TheCochrane Library has published more than 6,000 studies summarising high quality evidence for health interventions. Notable cases include breast screening, which used to be recommended for women from the age of 40 until the evidence showed that the number of false positives recorded was in fact doing more harm than good. The risks from unnecessary surgery were greater than the often small benefits from early treatment forbreast cancer.

Hormone replacement therapy (HRT) is another example. It was routinely used to reduce heart disease, but then became far less common when evidence showed adverse effects. There is now a more nuanced understanding of which women will benefit from HRT and which will not.

Prior to Cochrane, doctors based their advice on out-of-date knowledge, personal experience and the influence of drug reps. Today, doctors have access to evidence-based guidelines. Decisions on what the NHS can and should fund are informed by the advice of the National Institute for Health Clinical Excellence after a review of the evidence.

So why can’t we do the same for social and economic policy?

For those who are interested, I engaged (or am engaging) in a twitter exchange on this with Howard White, whose replies have been very gracious. As in so many of these exchanges I suspect that we agree on more than we disagree on (and possibly agree on everything with a difference in emphasis)

Of course policy should be based on evidence, where available. This not only seems extremely reasonable and  rational – it is eminently reasonable and rational. I also write as an admirer of the Cochrane Collaboration.

However, I always feel a sense of caution when clinical concepts are introduced into political discourse. The best definitions of EBM always include the word “judicious”, as here

“Evidence-based medicine is the conscientious explicit and judicious use of current best evidence in making decisions about the care of individual patients.”

Judicious is key – judgment and reflection are required. Does this body of evidence apply to my patient, this individual person in front of me, or does it not? As I wrote on another point:

it is one thing to have an evidence base for a specific therapy in medical practice, quite another for a specific intervention in society itself.

My review of Helen Pearson’s The Life Project is still to be published, when it does I will perhaps write a little more on “evidence-based policy”, a concept which began to enjoy great vogue in the 1990s.What Pearson’s book shows, however, is that the devil can cite evidence for his own purpose; “evidence” can be wielded with agendas.

Obviously the Campbell Collaboration aims to address this, by being transparent about the evidence used and the methodology used to synthesise it.

A further point is that evidence-based policy tends to presuppose consensus on the ends of policy  – and emphasise technocratic means of getting there. Thereby the focus on specific interventions, rather than any wider sense of not merely social goals but of social meaning. Of course, this very much in keeping with a time in which we are all supposed to be beyond “grand narratives” – which is of course itself a “grand narrative.” I would suggest that many recent events in politics around the world are best understood as testing this notion to destruction.

Bringing it all back to a question I asked a while ago about the best kind of evidence for health informatics innovations, perhaps what this illustrates is that the way we do evidence now tends to be to focus on specific interventions and, as far as possible, measure their effects as specific interventions and without reference to an overall system. Indeed, this is obviously necessary for assessing therapies and treatments. But is it necessarily missing something when it comes to a system?

Engaging clinicians and the evidence for informatics innovations

A few weeks ago Richard Gibson from Gartner spoke to members of the CCIO group. It was a fascinating, wide-ranging talk – managing the time effectively was a challenge. Dr Gibson talked about the implications for acute care and long term care of technological innovations – as might be obvious from my previous post here, I have a concern that much of the focus on empowerment via wearables and consumer technology misses the point that the vast bulk of healthcare is acute care and long term care. As Dr Gibson pointed out, at the rate things are going healthcare will be the only economic, social, indeed human activity in years to go

One long term concern I have about connected health approaches is engaging the wide group of clinicians. Groups like the CCIO do a good job (in my experience!) of engaging the already interested, more than likely unabashedly enthusiastic. At the other extreme, there always going to be some resistance to innovation almost on principle. In between, there is a larger group interested but perhaps sceptical.

One occasional response from peers to what I will call “informatics innovations” (to emphasise that this not about ICT but also about care planning and various other approaches that do not depend on “tech” for implementation) is to ask “where is the evidence?” And often this is not a call for empirical studies as such, but for an impossible standard – RCTs!

Now, I advocate for empirical studies of any innovation, and a willingness to admit when things are going wrong based on actual experience rather than theoretical evidence. In education, I strongly support the concept of Best Evidence Medical Education and indeed in following public debates and media coverage about education I personally find it frustrating that there is a sense that educational practice is purely opinion-based.

With innovation, the demand for the kind of RCT based evidence is something of a category error. There is also a wider issue of how “evidence-based” has migrated from healthcare to politics. In Helen Pearson’s Life Project we read how birth cohorts went from ignored, chronically underfunded studies ran by a few eccentrics to celebrated, slightly less underfunded, flagship projects of British epidemiology and sociology. Since the 1990s, they have enjoyed a policy vogue in tandem with a political emphasis on “evidence-based policy.” My own thought on this is that it is one thing to have an evidence base for a specific therapy in medical practice, quite another for a specific intervention in society itself.

I am also reminded of a passage in the closing chapters of Donald Berwick’s Escape Fire (I don’t have a copy of the book to hand so bear with me) which essentially consists of a dialogue between a younger, reforming doctor and an older, traditionally focused doctor. Somewhat in the manner of the Socratic dialogues in which (despite the meaning ascribed now to “Socratic”) Socrates turns out to be correct and his interlocutors wrong, the younger doctor has ready counters for the grumpy arguments of the older one. That is until towards the very end, when in a heartfelt speech the older doctor reveals his concerns not only about the changes of practice but what they mean for their own patients. It is easy to get into a false dichotomy between doctors open to change and those closed to change; often what can be perceived by eager reformers as resistance to change is based on legitimate concern about patient care. There are also concerns about an impersonal approach to medicine. Perhaps ensuring that colleagues know, to as robust a level as innovation allows, that patient care will be improved, is one way through this impasse.

 

I have finished Evidence Based Medicine (for a while)

This evening, I logged on to do some Embase screening:

Saturday Night at the @embase , don’t care which trials I screen. pic.twitter.com/zn35bHdTYX

— Seamus MacSuibhne (@JamesMcQueen78) December 19, 2015

Noting that there were a mere 100 records to screen, I worked away for a while, until:

.@embase “There is one record waiting to be screened.” What will happen next? #victoryscreen pic.twitter.com/8oYwH4gyoT

— Seamus MacSuibhne (@JamesMcQueen78) December 19, 2015

 

With bated breath I screen the one remaining record (naturally enough, a Reject verdict), and after a bit of deliberation clicked on “Save and Exit”, to discover that :

.@embase At last someone can truthfully say, “no further research is needed.” ALL YOUR RCTS ARE BELONG TO US. #VEday pic.twitter.com/GBP8W5il6S

— Seamus MacSuibhne (@JamesMcQueen78) December 19, 2015

 

Of course, I know that a gigantic batch of records will no doubt be delivered to Embase for screening, if it hasn’t already (and I am probably misunderstanding something even more basic) but, for the moment, there is a pleasing sensation of having reached the ultimate extreme of human knowledge (only mild hyperbole here!)

Great moments in personality research: Study of the personality of patients with spontaneous pneumothorax

If it wasn’t for EMBASE screening, I would never have come across this gem:

 

Study of the personality of patients with spontaneous pneumothorax

Martín Martín M1, Cuesta Serrahima L, Rami Porta R, Soler Insa P, Mateu Navarro M.

INTRODUCTION:
Medical psychology has contributed to a greater understanding of many diseases that are predominantly medical and has also helped to improve prognosis. This study explores a surgical entity, namely spontaneous pneumothorax.
OBJECTIVES:
The aim was to compare the personality, depression, anxiety and type-A behavior pattern in a group of 34 patients with spontaneous pneumothorax to a group of 33 control patients admitted for a variety of minor surgical procedures.
MATERIAL AND METHODS:
The following objective assessment instruments were used: Trait Anxiety Inventory, Beck Depression Inventory, Jenkins Activity Inventory, Eysenck Personality Questionnaire. The questionnaires were administered before the intervention of the surgeon and after an informative interview.
RESULTS:
The rate of type-A behavior was statistically different in the two groups. No differences were seen for personality, depression or anxiety.
CONCLUSION:
We conclude that type-A behavior patterns should be reduced in patients who suffer spontaneous pneumothorax in order to improve outcome.

I love that sweeping conclusion “type-A behaviour patterns should be reduced” – just like that! – but also admire the researchers choice of an apparently unpromising area to research. I will try, if I have time, to read the original paper.