Invisible Chronic Illness: Addison’s Disease

This week the Grand Round will be hosted by Invisible Illness Week, a blog dedicated to the National Invisible  Ilness Week, which runs September 14 -20, 2009. The purpose:

National Invisible Chronic Illness Awareness Week  (..) is a worldwide effort to bring together people who live with invisible chronic illness and those who love them. Organizations are encouraged to educate the general public, churches, healthcare professionals and government officials about the impact of living with a chronic illness that is not visually apparent.

The theme of the Grand Round is, not very surprisingly: Invisible chronic Illness.

I won’t write about this professionally -being a librarian-, but I will speak from my own experience.

As many of you know, I’ve the chronic illness Addison’s Disease. Not that I feel ill. It doesn’t affect me, really… Not anymore.. I think.

But many people with Addison’s disease suffer silently from this disease. And like many other diseases this disease is seldomly understood by partners, colleagues, friends ….. and doctors.

Before I explain more about Addison’s disease, first let me say that almost every disease is “invisible” to others. People can never fully understand what an illness means to someone suffering from it.

Cortisol, Image via Wikipedia

Patients with Addison’s disease make no or too small amounts of cortisol, a hormone made by the adrenal cortex. Cortisol has a bad reputation as the stress hormone among many people. It doesn’t deserve this reputation as this hormone is vital to life. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior (Wikipedia)

Too much of this hormone causes Cushing’s disease, too little causes Addison’s disease. If you want to know what Cushing does to your body and mind, then please read the letter of Kate when she was first diagnosed with Cushing’s, at Robin’s “Survive the Journey”.

Here, I will confine myself to Addison’s disease. It is a very good example of an invisible yet serious disease.

There are 3 forms of Addison: primary (defect in the adrenal cortex itself, often also leading to a defect in aldosteron production), secondary Addison (by a defect in the hypophysis or hypothalamus) and iatrogenic Addison (caused by overtreatment with corticosteroids)

Here some reasons why the illness, although “invisible”, can have great impact on your live.

1. Diagnosis.

well-ville.com/images/adrenalQA2.jpg

Diagnosis is often a challenge, especially in patients with primary Addison, most of whom look healthy because of their pigmented skin. Nowadays, the main cause of primary Addison’s disease is immune destruction of the adrenal cortex. This has often a slow onset and in 50% of the patients the diagnosis takes more than 2, sometimes even more than 10 years [1]. 38% of the patients even experience vague complaints, that can later be attributed to Addison, during 11->30 years before diagnosis [1].

Before the diagnosis is made, people with Addison’s Disease often feel extremely tired and miserable. Even when the disease fully manifests itself the symptoms are largely vague and aspecific. The most common symptoms are fatigue, dizziness, muscle weakness, weight loss, difficulty in standing up, vomiting, anxiety, diarrhea, headache, sweating, changes in mood and personality, and joint and muscle pains. Often the symptoms aren’t taken seriously (enough) or the illness is mistaken for anorexia or depression.

My secondary Addison was the consequence of an injury to the pituitary gland as result of heavy blood loss during complicated childbirth (see previous post). The week between the cause and the diagnosis of the disease, was the most terrible week of my life. I felt awful, weak, (well I lost >3 liters of blood to start with), couldn’t give breast milk (no prolactin), and I disgusted food so much, you can’t imagine. I couldn’t get anything down my throat, only the look of it made me vomit. And I felt so bad not being able to care for the baby, but I just couldn’t. I couldn’t even stand for more then a few minutes, couldn’t walk.  And then there was unstoppable diarrhea, dizzyness, and speaking with double tongue. And practically no one took it seriously, not the gynaecologists, not the nurses, not the paediatricians, nor my friends or family.

But this was only one week. How would it have been if it durated 5 or 10 years?

2. Grieve and adaptation.

Once the disease is diagnosed you have to learn to live with a body that has let you down (grieve) and you have to learn to become confident again (adapt). You also have to find a new balance. I’ve lost a few hormones overnight (ACTH, cortisol, thyroid hormone, growth hormone, prolactin, gonadotrope hormones) and believe me, it took me a few years to feel reasonable normal again. It is quite surprising how badly I was informed. Very little information about the risk of an Addisonian crises, the dosing of cortisol under various conditions.
It was also confronting how little people wanted to know about the disease or what I had been through. Visitors after the birth wanted me to be euphoric and didn’t want me to go into any detail of what had happened. They cut me short by saying: “But you have a lovely baby”. Somebody cried that she didn’t want to hear it. So I stopped trying to speak about it.

I took no sick leave, immediately went back to work. My boss – a nephrologist, never asked after my health, not once.

As I said it took a few years before my “come-back”. I didn’t feel myself. It was as if I couldn’t think, as if my head was filled with cottonwool. Afterwards I think the main reason for improval was the reduction of the cortisol from 30 mg to 12.5 per day and the use of DHEAs plus that I regained confidence in myself.

3. Comorbidity

With cortisol I lost some other hormones which are also essential. Patients with primary Addison often miss aldosteron as well, which makes them more liable for an Addisonian crisis. Primary Addisonians may also have other immune diseases, like autoimmune thyroid disease, gonadal failure, type 1 diabetes and vitiligo.

4. Addisonian crisis

An addisonian crisis is an emergency situation, with possible fatal outcome, associated mainly with an acute deficiency of the glucocorticoid cortisol. This occurs in (extremely) stressful situations. Some Addisonpatients are more prone to it than others. You can -and should – take precautions, like wearing alert bracelets or necklaces, so that emergency personnel can identify adrenal insufficiency and provide stress doses of steroids in the event of trauma, surgery, or hospitalization.

Some Addisonians fear these crises so much that they dear not walk or run alone. Many Addison patients don’t go to a country far away, some don’t even pass the border (and you know the Netherlands aren’t that big).

5. Addison’s disease can be treated but not cured.

Addison patients are treated with corticosteroids like hydrocortisone and are substituted with other hormones that they may lack. Without treatment, the disease is lethal, with treatment the disease is not cured. I do feel all right now, but many of my fellow patients don’t. I think that the following excerpt from a Seminar of Wiebke Arlt and Bruno Allolio about adrenal insufficiency [2] makes this very clear.

Despite adequate glucocorticoid and mineralocorticoid replacement, health-related quality of life is greatly impaired in patients with primary and secondary adrenal insufficiency. Predominant complaints are fatigue, lack of energy, depression, and anxiety. In addition, affected women frequently complain about impaired libido. In a survey of 91 individuals, 50% of patients with primary adrenal insufficiency considered themselves unfit to work and 30% needed household help. In another survey of 88 individuals the number of patients who received disablility pensions was two to three times higher than in the general population. The adverse effect of chronic adrenal insufficiency on health-related quality of life is comparable to that of congestive heart failure. However, fine-tuning of glucocorticoid replacement leaves only a narrow margin for improvement, and changes in timing or dose do not result in improved wellbeing.

References

1. Zelissen PM. Addison patients in the Netherlands: medical report of the survey. The Hague: Dutch Addison Society, 1994.
2. Wiebke Arlt, Bruno Allolio. Adrenal Insufficiency, Lancet 2003; 361: 1881–93 , full text on http://www.addisonssupport.com/Documentation/adrenal-insufficiency-2003.pdf

Earlier posts on the subject:

• https://laikaspoetnik.wordpress.com/2008/10/19/changing-care-for-addison-patients/
• https://laikaspoetnik.wordpress.com/2008/10/27/the-importance-of-early-intervention-in-an-addisonian-crisis/

Related articles by Zemanta

• Multimorbidity, and why it’s difficult to care for complex medical patients (kevinmd.com)
• Dear Family and Friends…. (survivethejourney.blogspot.com)
• Please Don’t Ask Me ‘How are You?’ (somebodyhealme.dianalee.net)

Martin Bril: the Author, his Death and his Cancer

Martin Bril is dead.

No “news“, it happened a month ago: April 22.

Martin Bril was a well known Dutch writer, poet and columnist – and the man who invented “skirt day”.

He loved live -and love- in all it’s simplicity. He needed few words to describe the essence of things or as he would say: “The surface is deep enough”. But you know, it is looking at one drop of water and understanding the ocean. …

Other expressions: “Good is better than bad” and “You’ve people that bang the guitar really hard for hours, but I rather hear J.J. Cale. Always finished within 4 minutes, but the music stays with you.”

I liked his stories/columns most of the time, they often made me smile.

It is always sad when somebody dies young (Martin was 49), whether a “celebrity” or not. Especially when he leaves two young children and a wife.

I didn’t expect it and it really hit me. Why? I knew he had had cancer, but I thought it had gone. So did he a few years ago. I found a video-interview with him in 2007, where he said: “soon I will be declared “cured” – but then you will see it will return the other day.” In another interview I read: You never “beat cancer”, that’s Lance Armstrong-language. Cancer goes away or it stays. It often stays.

I always thought he had colon cancer, but it was esophageal cancer. That’s the trouble with Dutch:

• esophagus = slokdarm,
• jejunum, ileum = dunne darm
• colon = dikke darm.

Notice they all have “darm” in them. Mostly colon cancer is called “darmkanker” (or “dikke darmkanker”), and because esophagus is called slokdarm, slokdarmkanker is mistaken for darmkanker, which is quite another disease with other prospects.

Stupid, journalists keep on using the wrong name. Not that it matters a lot now, but still.

More “incorrect” was the fact that I first saw the announcement of his death in a newsletter from dokterdokter.nl (below). It is an online medical information site for patients. I have been getting their newsletter for years now, because -for one thing or another- I’m unsuccessful in unsubscribing to it. Dokterdokter.nl is typically a website that gives very general information, mostly leading to the advise “to check your doctor first”.

What struck me (besides the fact that I was taken by his death) was that his death was presented as Medical News, next to an enormous “oral sex” headline and the headline “what happens if you die?”. As if it was a tabloid. The message (he died the day before):

Martin Bril finally succumbed to esophageal cancer at the age of 49. Esophageal cancer has a bad prognosis. Why?
(if you click: )

“Martin Bril, the well known author …, died of esophageal cancer at the age of 49. He was a real hedonist. Cigarettes and alcohol were part of his life. Many years he had fought cancer, but Wednesday April 22 he lost his fight. Few people really completely recover from this illness.”

(….) Generally, the disease has to do with your lifestyle. In Western Countries, smoking and excessive alcohol consumption are the most important causes of esophageal cancer.

And then it continues summarizing the brochure of the Dutch Cancer Society (KWF- kankerbestrijding)

Whereas most medical sites (including the Dutch Cancer Society, from which all the information was taken) just neutrally say that the cause is unknown, but that alcohol and smoking are known risk factors for esophageal cancer, -and even more so in combination- dokterdokter puts a direct link between Martin’s lifestyle and his death, as if it was his own fault. Maybe it was, but at that moment I didn’t want to know. It didn’t matter. I found it disrespectful, tasteless. I’m quite interested in health and medicine and mechanisms, but the reason of his death -at this moment- was less important than his death itself.

As a matter of fact, Martin stopped using liquor and cocaine in 1997 after given an ultimatum by his wife (“you have two young kids!”) and after attending a trial of a drug baron (Johan V., de Hakkelaar) (to write about). He also wanted to quit smoking. I don’t know whether he succeeded, but he helped STIVORO (“for a smokeless future”) with their campaign (2002) by writing a beautiful column and making a video about (the difficulty of) quitting smoking. “I stopped smoking, because I didn’t like it anymore. Moreover, my kids didn’t want me to die because of smoking……..”

How much better was the reaction of STIVORO to the death of Martin, saying “we have lost a talented author” and thanking him for his input. Just a short notice and ending with the column Martin had written for them: “Did you ever tried to quit smoking?…I did”.

——————

Bij Nederlanders hoef ik Martin Bril nauwelijks te introduceren. Dat ik hier over hem schrijf heeft vooral te maken met het stukje dat ik in de nieuwsbrief van Dokterdokter.nl las. In feite was het dit bericht, waardoor ik wist dat hij gestorven was. Voor mij een schok. Ik lees de Volkskrant niet meer, dus het was mij ontgaan dat het slecht met hem ging. Het is ook een jonge vent, jonger dan ik, met twee dochters, net als ik. Zo kom het altijd nog een beetje dichterbij. En hij kon mooi schrijven. “De oppervlakte was diep genoeg,” zo zei hij, maar het was bij hem net of je in een druppel de hele oceaan kon zien.

Voor het eerst zag ik trouwens dat hij slokdarmkanker had. De meeste journalisten spraken van darmdanker, waar men in de regel toch dikkedarmkanker mee bedoelt. Slokdarmkanker is een heel andere ziekte, met een heel andere prognose. Vreemd dat het meerendeel van de journalisten het toch steeds over darmkanker heeft

Maar dit terzijde. Ik vond het vreemd, dat het bericht als een “nieuwsaankondiging” stond naast de kop “orale sex” en “hoe voelt het als je dood gaat”. Misschien had Martin er wel om kunnen lachen, maar ik vond het bizar. Het verhaal zelf vond ik ook nogal ongepast.

Wat stond er?

De ziekte slokdarmkanker werd schrijver Martin Bril op zijn 49e fataal. Het is een ziekte met slechte vooruitzichten, mede omdat het vaak laat wordt ontdekt.

“Schrijver Martin Bril, bekend van boeken als De kleine keizer en Arbeidsvitaminen en van zijn columns in de Volkskrant, is op 49-jarige leeftijd aan slokdarmkanker overleden. Hij was een echte levensgenieter, sigaretten en alcohol waren een vast onderdeel van zijn leven. Al vele jaren streed hij tegen kanker, maar woensdag 22 april was zijn strijd gestreden. Maar weinig mensen weten volledig te herstellen van deze ziekte.”De ziekte heeft meestal te maken met de leefstijl van mensen. Roken en overmatig alcoholgebruik zijn in Westerse landen de belangrijkste oorzaken voor het ontstaan van slokdarmkanker.

Andere bronnen –ook de KWF-brochure, waar dit stuk aan ontleend is, schrijven steevast dat de oorzaak niet bekend is, maar dat roken en alcohol (vooral in combinatie) de belangrijke risicofactoren zijn. Mogelijk is zijn leefwijze inderdaad de belangrijkste reden geweest dat hij slokdarmkanker heeft gekregen. Nou en? Is het nodig om dit zo op te schrijven? Een dag na zijn dood? Ik vond het nogal oneerbiedig. Misschien dacht men bij dokterdokter.nl dat het schrikeffect mensen zou weerhouden om veel te roken en te drinken, want “kijk, daar krijg je slokdarmkanker van!!” Behalve dat dokterdokter niet bepaald het juiste publiek (de “zelfkanters” en “hedonisten”) zal bereiken, zal zo’n actie sowieso weinig zoden aan de dijk zetten. Dan was Martin’s bijdrage aan de Stivoro campagne “stoppen met roken” (2002/2003) waarschijnlijk veel effectiever. Hij schreef een column voor ze en werkte mee aan een video.

Martin zei: “Ik stopte met roken omdat ik er geen zin meer in had. Bovendien; mijn kinderen vonden dat ik er niet dood aan moest gaan”. Eerder, na een ultimatum van zijn vrouw en het bijwonen van een zitting tegen de drugsbaron de Hakkelaar, was hij al gestopt met alcohol en coke.

Zo anders was ook de reactie van Stivoro. Niets vingertje wijzen: “zie je wel!”, maar dit:

“Samen met de rest van Nederland treurt STIVORO om het heengaan van een bijzonder mens en groot schrijver: Martin Bril

STIVORO heeft Martin leren kennen toen hij zich enthousiast inzette voor onze ‘Stoppen met roken’ campagne van 2002/2003. Hij was toen bereid zijn persoonlijkheid en zijn schrijftalent voor deze campagne in te zetten.

Wij zijn dankbaar dat we met hem hebben mogen samenwerken. We wensen zijn familie en andere dierbaren heel veel sterkte toe.

Hij schreef voor ons de volgende column:

“Bent u wel eens gestopt met roken?
Ik wel……..”

Photo Credit (CC):

• Martin Bril Close Up : http://www.flickr.com/photos/roel1943/309048020/
• Man reading a book of Martin Bril: http://www.flickr.com/photos/wijkerslooth/3492121752/
• Rokjesdag (Skirt Day):http://www.flickr.com/photos/pforret/73554771/

Web 2.0 and Health Care Reform: Two Dutch Examples (1)

The theme for the next Grand Round hosted by Healthcare Technology News is Healthcare Reform.

“We’ll be publishing a wide range of articles, from those that share anecdotes about why we need to improve the health care system, to examples of innovations and care that are working well, through to the policy recommendations that we need.”

Although I easily could give some anecdotal examples from the past about “failures or shortcomings” in Healthcare, I prefer to give some positive examples of how a web 2.0 approach can bring patients and doctors together. There are numerous examples of successful application of web 2.0 tools by patients to find and share information and to improve the management of their disease. There are also many healthcare people who use web 2.0 tools to write down their experiences (blogs, social media), to get their information (RSS) and to put information on the web (wiki’s) for patients or colleagues. There are hospitals that are actively engaged in social media and that facilitate patients to use these tools to gather information, but I’ve seldom seen a real web 2.0 based patient-doctor collaboration…. till recently…. close to home in Nijmegen at the Zorg 2.0 (Health 2.0) event, organized by Lucien Engelen (twitter: zorg20; and on linkedin). In fact, the whole meeting was a success with lots of interesting lectures (i.e. from Bertalan Mesko of Scienceroll and Maarten Lens Fitzgerald of Maarten’s Journey.) and workshops.

All podcasts of the Zorg 2.0 event can be seen here

Two presentations were given by two professors on patient centered care in the so called award winning initiative MijnZorgNet (MyCareNet): Bas Bloem and Jan Kremer.

I will discuss their two presentations in separate posts.

This post will summarize the presentation of Bas Bloem, neurologist from the UMC St Radboud Ziekenhuis Nijmegen and initiator of the Parkinson Center.

Bas Bloem began with his “take home message” (with which I couldn’t agree more):

Health 2.0 is not “the world of gadgets”, but a new way of thinking in healthcare:

1. the patient becomes centric, care becomes collaborative: the patient is not passive, he is “equal” to the healthcare provider. It isn’t “he asks, we provide”, but the patient definitively has a voice (and choice) in his own healthcare.
2. coherent and transparent healthcare.
3. expertise (few experts, but with very specialized knowledge).

He set up a program for Parkinson care delivery networks, first in the surroundings of Nijmegen and later throughout the Netherlands. Although his talk is about Parkinson, it can be seen as a model for all kinds of complex diseases.

Bas is an idealist. He believes most healtcare people choose their job to really help people. Doctors choose to care. Only the system doesn’t help them to realize this.

To change this, a paradigm shift is needed. Healthcare needs to be centered round the patient:

1. The patient has the right to see the best specialist -in a structured way; the assessment of the patient is “CENTRAL”, in an intramural setting, i.e. by a neurologist. In the present example, people from the first line can easily contact the specialists or plan an appointment in their agenda. In this way the patient is helped promptly and he notices the good cooperation between the two lines.
2. Daily healthcare is close to home, only performed by a handful of specialists (i.e. physiotherapists) specially trained to treat Parkinson patients. This is called the ParkinsonNet. Patients rather have someone with expertise who is within a 20 minutes distance, than a less experienced person round the corner.
3. There is optimal communication between the “two layers”.
4. The patient plays an active role.

How is this organized?

1. When the patient is referred to the neurologist, he first has to fill in a screening list and has to prioritize 5-10 health problems, which he/she would like to discuss when visiting the Day Center. So one patient may want to see a sexologist, a dietitian and a physiotherapist and an other a rehabilitation physician, gerontologist and a neurologist.
2. Doctors and patients sit round a table, each in the same position (no hierarchy).
3. Consumer reviews are shown (anonymously) on the Internet. This makes healthcare transparent. When scores are bad some action should be taken to improve it.

How is this achieved?

1. Selection of experts who get education (via e learning etc), on basis of geographic distribution. Patients have to travel a bit more, healthcare is canalized,
2. All healthcare workers work according a multidisciplinary guideline. Patients were active co-producers of the guideline.
3. Implementation (see above)
4. Yellowpages (paper and digital version) have been made of healtcare providers, enabling patients to choose.
5. Indicators are developed, patients are invited to give feedback and to grade the healthcare (providers). If someone performs bad, (gets the red card) he/she may ultimately be taken out of the network.

The experiment of patient empowerment in Parkinson’s Disease management has grown from very small (region Nijmegen) to almost national. The blank region (see Figure) is not included to be able to assess the effectiveness of this system compared to the traditional approach.

The next step is the creation of a virtual community. This is certainly important and not out of reach for the elderly. A transmural electronic health record is available (Parkinson dossier) both for the patient and the healthcare worker.

Slides (Dutch): http://www.slideshare.net/lucienengelen/bloem-zorg-20-maart-2009
——————————-

Vodpod videos no longer available.

more about “4. Zorg20 Event Spring 2009 | Keynote…“, posted with vodpod

See http://www.vimeo.com/4271353

* Since the video stuck half way, I may have missed part of the presentation.

Yet Another Negative Trial with Vitamins in Prostate Cancer: Vitamins C and E.

Within a week after the large SELECT (Selenium and Vitamin E Cancer Prevention) Trial was halted due to disappointing results (see previous posts: [1] and [2]), the negative results of yet another large vitamin trial were announced [7].
Again, no benefits were found from either vitamin C or E when it came to preventing prostate ànd other cancers.
Both trials are now prepublished in JAMA. The full text articles and the accompanying editorial are freely available [3, 4, 5].

In The Physicians’ Health Study II Randomized Controlled Trial (PHS II), researchers tested the impact of regular vitamin E and C supplements on cancer rates among 14,641 male physicians over 50: 7641 men from the PHS I study and 7000 new physicians.

The man were randomly assigned to receive vitamin E, vitamin C, or a placebo. Besides vitamin C or E, beta carotene and/or multivitamins were also tested, but beta carotene was terminated on schedule in 2003 and the multivitamin component is continuing at the recommendation of the data and safety monitoring committee.

Similar to the SELECT trial this RCT had a factorial (2×2) design with respect to the vitamins E and C [1]: randomization yielded 4 nearly equal-sized groups receiving:

• 400-IU synthetic {alpha}-tocopherol (vitamin E), every other day and placebo (similar to the SELECT trial)
• 500-mg synthetic ascorbic acid (vitamin C), daily and placebo
• both active agents
• both placebos.

Over 8 years, taking vitamin E had no impact at all on rates of either prostate cancer (the primary outcome for vitamin E), or cancer in general. Vitamin C had no significant effect on total cancer (primary outcome for vitamin C) and prostate cancer. Neither was there an effect of vitamin E and/or C on other site-specific cancers.

How can the negative results be explained in the light of the positive results of earlier trials?

• The conditions may differ from the positive trials:
  • The earlier positive trials had less methodological rigor. These were either observational studies or prostate cancer was not their primary outcome (and may therefore be due to chance). (See previous post The best study design for dummies).
  • Clinical data suggest that the positive effect of vitamin E observed in earlier trials was limited to smokers and/or people with low basal levels of vitamin E, whereas animal models suggest that vitamin E is efficacious against high fat-promoted prostate cancer growth (20), but lacks chemopreventive effects (i.e. see [1,4] and references in [5], a preclinical study we published in 2006).
    Indeed, there were very low levels of smoking in the PHS II study and the effect of the vitamins was mainly assessed on induction not on progression of prostate cancer.
  • Eight times higher vitamin E doses (400IE) have been used than in the ATCB study showing a benefit for vitamin E in decreasing prostate cancer risk! [1,4]
• Other forms of vitamin E and selenium have been proposed to be more effective.
• As Gann noted in the JAMA-editorial, the men in both recent studies were highly motivated and had good access to care. In SELECT, the majority of men were tested for PSA each year. Probably because of this intense surveillance, the mean PSA at diagnosis was low and prostate cancers were detected in an early, curable stage. Strikingly, there was only 1 death from prostate cancer in SELECT, whereas appr. 75-100 deaths were expected. There also were indications of a deficit in advanced prostate cancer in PHS II, although a much smaller one.
  In other words (Gann):
  “how can an agent be shown to prevent serious, clinically significant prostate cancers when PSA testing may be rapidly removing those cancers from the population at risk before they progress?”
• Similarly, in the SELECT trial there was no constraint on the use of other multivitamins and both studies put no restriction on the diet. Indeed the group of physicians who participated in the PHS II trial were healthier overall and ate a more nutritious diet. Therefore Dr Shao wondered
  “Do we really have a placebo group – people with zero exposure? None of these physicians had zero vitamin C and E” [7]. In the Netherlands we were not even able to perform a small phase II trial with certain nutrients for the simple reason that most people already took them.

What can we learn from these negative trials (the SELECT trial and this PHS II-trial)?

• Previous positive results were probably due to chance. In the future a better preselection of compounds and doses in Phase 2 trials should determine which few interventions make it through the pipeline (Gann, Schroder).
• Many other trials disprove the health benefits of high dose vitamins and some single vitamins may even increase risks for specific cancers, heart disease or mortality [9]. In addition vitamin C has recently been shown to interfere with cancer treatment [10].
• The trials make it highly unlikely that vitamins prevent the development of prostate cancer (or other cancers) when given as a single nutrient intervention. Instead, as Dr Sasso puts it “At the end of the day this serves as a reminder that we should get back to basics: keeping your body weight in check, being physically active, not smoking and following a good diet.”
• Single vitamins or high dose vitamins/antioxidants should not be advised to prevent prostate cancer (or any other cancer). Still it is very difficult to convince people not taking supplements.
• Another issue is that all kind of pharmaceutical companies keep on pushing the sales of these “natural products”, selectively referring to positive results only. It is about time to regulate this.

Sources & other reading (click on grey)

1. Huge disappointment: Selenium and Vitamin E fail to Prevent Prostate Cancer.(post on this blog about the SELECT trial)
2. Podcasts: Cochrane Library and MedlinePlus: (post on this blog)
   
3. Vitamins E and C in the Prevention of Prostate and Total Cancer in Men: The Physicians’ Health Study II Randomized Controlled Trial. J. Michael Gaziano et al JAMA. 2008;0(2008):2008862-11.[free full text]
   
4. Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: The Selenium and Vitamin E Cancer Prevention Trial. Scott M. Lippman, Eric A. Klein et al (SELECT)JAMA. 2008;0(2008):2008864-13 [free full text].
   
5. Randomized Trials of Antioxidant Supplementation for Cancer Prevention: First Bias, Now Chance-Next, Cause. Peter H. Gann JAMA. 2008;0(2008):2008863-2 [free full text].
   
6. Combined lycopene and vitamin E treatment suppresses the growth of PC-346C human prostate cancer cells in nude mice. Limpens J, Schröder FH, et al. J Nutr. 2006 May;136(5):1287-93 [free full text].
   
   News
   
7. The New York Times (2008/11/19) Study: Vitamins E and C Fail to Prevent Cancer in Men.
8. BBC news: (2008/12/10) Vitamins ‘do not cut cancer risk’.
9. The New York Times (2008/11/20) News keeps getting worse for vitamins.
10. The New York Times (2008/10/01) Vitamin C may interfere with cancer treatment.

Huge disappointment: Selenium and Vitamin E fail to Prevent Prostate Cancer.

October 27th the news was released that ([see here for entire announcement from nih.gov]

“an initial, independent review of study data from the Selenium and Vitamin E Cancer Prevention Trial (SELECT), funded by the National Cancer Institute (NCI) and other institutes that comprise the National Institutes of Health shows that selenium and vitamin E supplements, taken either alone or together, did not prevent prostate cancer. The data also showed two concerning trends: a small but not statistically significant increase in the number of prostate cancer cases among the over 35,000 men age 50 and older in the trial taking only vitamin E and a small, but not statistically significant increase in the number of cases of adult onset diabetes in men taking only selenium. Because this is an early analysis of the data from the study, neither of these findings proves an increased risk from the supplements and both may be due to chance.”

SELECT is the second large-scale study of chemoprevention for prostate cancer. Chemoprevention or chemoprophylaxis refers to the administration of a medication to prevent disease. The SELECT trial aimed to determine whether dietary supplementation with selenium and/or vitamin E could reduce the risk of prostate cancer among healthy men. It is a randomized, prospective, double-blind study with a 2×2 factorial design, which means that the volunteering men received either one of the supplements, both supplements or no supplements (but placebo instead), without knowing which treatment they would receive.
The trial volunteers were randomly assigned to one the following treatments:

1. 200 µg of selenium and 400 IU of vitamin E per day. (both supplements)
2. 200 µg of selenium per day and placebo
3. 400 IU of vitamin E per day and placebo
4. two different placebo’s (neither supplement)
   (µg = micrograms, IU = International Units)

Enrollment for the trial began in 2001 and ended in 2004. Supplements were to be taken for a minimum of 7 years and a maximum of 12 years. Therefore the final results were anticipated in 2013. However, but due to the negative preliminary results, SELECT participants still in the trial are now being told to stop taking the pills. The participants will continue to have their health monitored by study staff for about three more years, continue to respond to the study questionnaires, and will provide a blood sample at their five-year anniversary of joining the trial, to ensure their health and to allow a complete analysis of the study. (see SELECT Q & A).

In an interview with CBS, one of the investigators Dr Katz, said he was highly disappointed and concerned, because he had high hopes for the trial. “I”m disappointed with the study. I’m very concerned about the results of the trial.

Vodpod videos no longer available.

more about “Vitamin E A Flop In Prostate Cancer T…“, (with 15 sec advertisement first) posted with vodpod. This video is derived from CBS news.

Dr. Klein, one of the principal investigators, has published as many as 14 publications on the SELECT trial (see PubMed). He has always been a strong advocate of this huge trial.

The question now is:
Was there enough evidence to support such a large trial? Could this result have been foreseen? Would the trial have had different outcomes if other conditions had been chosen?

The SELECT trial seems to add to the ever growing list of disappointing “preventive” vitamin trials. See for instance this blogpost of sandnsurf on “a systematic review of all the published randomized controlled trials (RCTs) on multivitamins and antioxidant supplements in various diseases, and their effect on overall mortality” concluding:

“Taking the antioxidant vitamins A (and its precursor beta-carotene) and E singly or in multivitamins is dangerous and should be avoided by people eating a healthy diet. On a diet like that recommended here, the intake of these and other important vitamins should be high, with no need for supplementation.”

Quite coincidentally I commented to Sandsnurf blogpost referring to the SELECT trial, 1 week before the bad outcome was announced):

Indeed, in many RCT’s vitamin supplements didn’t have the beneficial effects that they were supposed to have. Already in the early nineties, adverse effects of beta-carotene (higher mortality in smokers) have been shown in several RCT’s. Still, because vitamin E had an expected positive effect on prostate cancer in one such trial, vitamin E is now being tested together with selenium (2X2) in a very large prostate cancer trial. Quite disturbingly, 8 times higher doses vitamin E are being used (400IE) compared to the original study. If the Lawson study is right, the outcome might be harmful. Worrying.

It might be argued that it is easy to criticize a study once the outcome is known. However, this critique is not new.

Already in 2002 a very good critique was written by MA Moyad in Urology entitled: Selenium and vitamin E supplements for prostate cancer: evidence or embellishment?

Here I will summarize the most important arguments against this particular trial (largely based on the Moyad paper)

• SELECT was based on numerous laboratory and observational studies supporting the use of these supplements. As discussed previously such study designs don’t provide the best evidence.
• The incidence, or rate of occurrence, of prostate cancer was not the primary focus or endpoint of the few randomized controlled trials studies on which the SELECT study was based.
• A 2×2 design is inadequate for dose-response evaluations, in other words: before you start the trial, you have to be pretty sure about the optimal dose of each supplement and of the interactive effect of vitamin E and selenium in the particular doses used. The interaction between two agents might be synergistic or additive, also with respect to any negative (i.e. pro-oxidant) effect.
• Eight times higher vitamin E doses (400IE) have been used than in the ATCB study showing a benefit for vitamin E in decreasing prostate cancer risk! This is remarkable, given the fact that high doses of anti-oxidants can be harmful. Indeed, a prospective study has shown, that vitamin E supplements in higher doses (> or =100 IU) are associated with a higher risk of aggressive or fatal prostate cancer in nonsmokers.
• Other forms of vitamin E and selenium have been proposed to be more effective. For instance dietary vitamin E (gamma tocopherol and/or gamma tocotrienols) might be more effective in lowering prostate cancer risk than the chemically-derived vitamin E (dl-alpha tocopherol acetate) used in SELECT. Also the used selenomethionine might be less effective than organically-bound selenium.
  
• Selenium and vitamin E supplements seem to provide a benefit only for those individuals who have lower baseline plasma levels of selenium or vitamin E.
• There may be other compounds that may be more effective, like finasteride, lycopene, statins (or with respect to food: a healthy lifestyle)
  

Katz said. “I would have hoped this would have been the way to prevent cancer in this country.”

Isn’t it a little bit naive to expect such huge effects (25% less prostate cancers) just by taking 2 supplements, given the thoughts summarized above?

In the interview, shown in the CBS-interview LaPook concludes “This is a major disappointment, but it is also progress. Because it’s also important to know what does not prevent cancer.”

Well I wonder whether it is ethical ànd scientifically valid, to do such a costly experiment with 35.000 healthy volunteers, based on such little evidence. Do we have to test each single possibly effective food ingredient as a single intervention?

SOURCES:
Official publications and information
– EA Klein: http://www.ncbi.nlm.nih.gov/pubmed/12756490
– Lippman SM, J Natl Cancer Inst. 2005 Jan 19;97(2):94-102. Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT). (PubMed record)
– The results of the SELECT trial are published in JAMA: Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: The Selenium and Vitamin E Cancer Prevention Trial. Scott M. Lippman, Eric A. Klein et al SELECT)JAMA. 2008;0(2008):2008864-13, published online December 9th 2008.

– SELECT Q&A: www.cancer.gov/newscenter/pressreleases/SELECTQandA
– General information on SELECT http://www.crab.org/select/
– Information on Study design (from Cancer Gov.clinical trialsSWOG s0000) and from clinicaltrials.gov

– More information on study designs and the ATCB trial (on which this study was based) in a previous post: the best study design for dummies

NEWS
– CBS Evening News Exclusive: Vitamin E And Selenium Fail To Prevent The Disease In Large Clinical Trial, NEW YORK, Oct. 27, 2008
– Los Angelos Times; Vitamin E, selenium fail to prevent prostate
– Emaxhealth: NCI stops prostate cancer prevention trial. With many good links to further information

CC (2) Duodecim: Connecting patients (and doctors) to the best-evidence

This is the second post in the series Cochrane Colloquium (CC) 2008.

In the previous post, I mentioned a very interesting opening session.

Here I will summarize one of the presentations in that opening session, i.e. the presentation by Pekka Mustonen, called:

Connecting patients to the best-evidence through technology: An effective solution or “the great seduction”?

Pekka essentially showed us what the Finnish have achieved with their Duodecim database.

Duodecim was started as a health portal for professionals only. It is a database (a decision support system) made by doctors for doctors. It contains Evidence Base (EBM) Guidelines with:

• regularly updated recommendations
• links to evidence, including guidelines and Cochrane Systematic Reviews
• commentaries

Busy Clinicians don’t have the time to perform an extensive search to find the best available evidence each time they have a clinical question. Ideally, they only would have to carry out one search, taking not more than one minute to find the right information.

This demand seems to be reasonably met by Duodecim.

Notably, Duodecim is not only very popular as a source for clinicians ànd nurses, the guidelines are also read and followed by them. Those familiar with healthcare know that this is the main obstacle: getting doctors and nurses to actually use the guidelines.

According to Pekka, patients are even more important than doctors to implement guidelines: Half of the patients don’t seem to follow their doctor’s advice. If the advice is to keep on inhaled steroids for long-term management for asthma, many patients won’t follow that advice, for instance. “When you reach patients, small changes can have large benefits”, he said.

However, although many patients rely on internet to find health information, formal health information sites face fierce competition on Internet. It is difficult for consumers to separate chaff from wheat:

Still, Duodecim has managed to make a website for the general public that is now as popular as the original physicians database is for doctors, the only difference being that doctors use the database continuously, whereas the general public just consults the database when they are confronted with a health problem.
The database contains 1000 EBM key articles, where the content is integrated with personal health records. The site looks rather straightforward, not glitzy nor flashy. Intentionally, in order to look like a serious and trustworthy professional health care site.

A survey revealed that Duodecim performed a lot better than Google in answering health care questions, and does lead to more people either deciding NOT to consult a physician (because they are reassured), or deciding to consult one (because the symptoms might be more serious than thought). Thus it can make a difference!

The results are communicated differently to patients compared to doctors. For instance, whether it is useful to wear stockings during long-haul flights to prevent deep venous thrombosis in patients that have either a low or a high risk for thrombosis is explained to the physician in terms of RR, ARR, RRR and NNT.
Patients see a table with red (high risk patients) and green columns (low risk patients). Conclusions will be translated as follows:

If 1000 patients with a low risk for DVT wear stockings on long-haul flights

• 9 will avoid it
• 1 will get it
  
• 1 out of 1000 (will get it)
• 990 use stocking in vain

If 1000 patients at high risk for DVT wear stockings on long-haul flights:

• 27 will avoid it
• 3 will get it
  
• 1 out of 333 (will get it)
• 970 use stocking in vain

This database will be integrated with permanent health records and virtual health checks. It is also linked to a tv program with the aim of changing the way of living. Online you can do a life expectancy test to see what age you would reach if you continue your life style as you do (compare “je echte leeftijd”, “your real age”[dutch]).

“What young people don’t realize”, Pekka said, is that most older people find that the best of life starts at the age of 60(?!) Thus, it doesn’t end at 30, as most youngsters think. But young people will only notice, when they reach old age in good health. To do this, they must change their habits already when young.

The Finnish database is for free for Finnish people.

Quite coincidentally (asking for a free usb-stick at the Wiley stand 😉 ) I found out that Wiley’s database EBM Guidelines links to the Duodecim platform (see below). Quite interesting to take a trial, I think.

(Although this presumably is only the professional part of Duodecim, thus not the patient oriented database.)

The (un)usefulness of regular breast exam

Regular breast exam, either by women theirselves (BSE, breast self exam) or a doctor or nurse, has been promoted for many years, because this would help to detect breast cancer earlier, and “when breast cancer is found earlier, it’s easier to treat and cure” . At least that is what most people believe and what has been advocated by organizations and Internet companies (i.e. selling special gloves) (see figure).

The idea that regular breast exam is truly beneficial, however, has recently been challenged by a Cochrane Systematic Review, conducted by Kösters and Gøtzsche.[1] This review has stirred up quite a debate among doctors, guideline-makers, patients and women. Many major organizations and advocacy groups have stopped recommending routine BSE. Reactions of patients vary from ‘reluctant’ to ‘confused that it is no longer needed’ or even a bit angry (‘it is my body and I decide whether I check it or not’). See for instance these reactions: 1, 2, 3. Coverage in the media is sometimes misleading, but reactions of (some) doctors or “experts in the field” also do not always help to convey a clear message to the public either. Some seize the opportunity to rant against EBM (Evidence Based Medicine) in general, which makes things even less transparent, see for instance this post by Dr Rich (although he has some good points as well), this story in the Herald and this one in Medcape.

In a question-answer like way I try to cover the story.

1. What is the conclusion from the study?
The authors conclude that regular breast examination (BE) does more harm than good and is therefore not recommended.

2. Which harm, which good?
Breast examination didn’t lower mortality (not beneficial), whereas it led to more unnecessary biopsies (harm).

3. Why did they look at mortality only?
They didn’t, they also scored the number and stage of cancers identified. However mortality (or really survival) is an outcome that matters most for patients. Suppose the screening finds more breast cancers, but early intervention does not lead to any cure, than the early recognition of the cancer is of no real value to the patient.

4. Why are more unnecessary biopsies considered as harm?
Biopsies are an invasive procedure and lead to unnecessary anxiety, that can have a long-lasting effect on psychological well-being. Extra tests to rule out that it is not cancer also cost a lot of money. Whether it is ‘worth it’ depends on whether -and to which extent- people’s lives are saved (or quality of life improved).

5. What kind of study is it?
It is a systematic review (of controlled clinical trials) made by the Cochrane Collaboration (see glossary). Generally these systematic reviews are of high methodological quality, because of the systematic and explicit methods used to identify, select and critically appraise relevant research. After extensively searching for all trials, only controlled clinical trials (studies of the highest evidence) with predefined characteristics are included. Thus authors are really looking for all the high level evidence there is, instead of grabbing some papers from the drawer or looking at the core English language journals only.

6. Is this new information?
No, not really. In fact this systematic review is an update of a previous version, published in 2003. The studies included and the conclusions remain the same. As shown from the scheme below (taken from a figure in a very interesting opinion paper entitled “Challenges to cancer control by screening” (see abstract here), the attitude towards breast self examination already changed soon after the original trials were published.

M.N. Pollak and W.D. Foulkes: Nature Reviews Cancer 3, 297 (2003)

7. Omg? ….
All Cochrane Systematic have to be regularly updated to see if there isn’t any new evidence that could alter the conclusions. In this case, after updating the search, no new studies of good quality were found. However, there are still some trials ongoing.

8. Can we rely on these conclusions? Is the Cochrane Review of good enough quality?
The Cochrane Review itself is of high quality, but the two randomized studies included, one from Russia (1999: ~122,500 participants) and one from Shanghai (2002: ~266,000 participants) have some serious flaws. For instance, both studies did not have an adequate allocation concealment (keeping clinicians and participants unaware of the assignments). An inadequate concealment undermines the validity of a trial (see for instance this 2002 Lancet paper). Also, description of statistical methods was lacking. Furthermore, data from the Moscow-branch of the Russian study were incomplete (these are excluded), mammography might have been used additionally and in the Shanghai trial there was a large difference in all-cause mortality in favor of the control group, suggesting that the two groups were imbalanced from the start.

9. Can the results of these rather old trials from countries as China and Russia be directly translated to the situation in Western Countries with a high standard of care?
Intuitively I would say ‘probably not’. However, we still don’t know whether the current western quality of care would actually lead to a better outcome after early detection, because it has never be tested in a well performed controlled trial.

10. Is this outcome applicable to anyone?
No, the studies are applicable to healthy, middle-aged woman without any particular risk. Screening methods might be more useful or even required for woman at high risk (i.e. familiar predisposition, previous ovarian or breast cancer).

11. Still, in recent interviews experts in the field say they do know that BSE is beneficial. One doctor for instance referred (in this Medscape paper) to a recent trial, that concluded that breast self-examination should be promoted for early detection of breast cancer (see here).
Either these doctors/experts give their personal opinion, refer to unpublished data or to studies with a lower evidence level. For instance the study referred to by Dr. Goldstein above was a retrospective study looking at how accurately woman could detect a breast tumor. Retrospective studies are more biased (see previous post on levels of evidence for dummies). Furthermore this study didn’t evaluate a hard outcome (survival, better prognosis) and there are just as many retrospective studies that claim the opposite, i.e. this article of Newcomb et al in J Natl Cancer Inst. 1991(abstract).

12. Should woman refrain from breast self examination then?
I found a short article (half A4) in the Dutch woman’s magazine (!) Viva very clear and concise.
Four woman gave their opinion.
A patient who had had a previous breast tumor kept on checking it (high risk group).

http://breastselfexam.ca/section1slide2.html

The director of a patient association said: “there is no evidence that BSE is beneficial: don’t feel quilty if you don’t check your breasts. But it might have a reassuring effect if you do”.
The spokeswoman of the Dutch association “struggle against cancer” (KWF) said that they didn’t promote structural breast exam any longer, but they advised to “know your body” and know the alarm signals (retracting nipple etc), much the same way as you check for alterations in nevi. Most woman find small alterations anyway, said another, for instance when taking a shower. Indeed, exemplified by my own experience: 18 years ago my mother detected breast cancer when feeling a lump in her breast under the shower (malignant, but curable).

The Cochrane authors are also very clear in their review about the necessity of women noticing changes to their breast.

“Some women will continue with breast self-examination or will wish to be taught the technique. We suggest that the lack of supporting evidence from the two major studies should be discussed with these women to enable them to make an informed decision.
It would be wrong, however, to conclude that women need not be aware of any breast changes. It is possible that increased breast awareness may have contributed to the decrease in mortality from breast cancer that has been noted in some countries. Women should, therefore, be encouraged to seek medical advice if they detect any change in their breasts that may be breast cancer.”

Listen to this Podcast featuring the Cochrane authors to learn more about their findings

[audio: http://cochrane.org/podcasts/review_summaries/mp3/issue3_2008_breast.mp3%5D

Link to this Cochrane Podcast:
http://cochrane.org/podcasts/review_summaries/2008issue3/issue3_2008_breast.html
Sources; further reading
[1] Kösters JP, Gøtzsche PC. Regular self-examination or clinical examination for early detection of breast cancer. Cochrane Database of Systematic Reviews 2003, Issue 2. Art. No.: CD003373. DOI: 10.1002/14651858.CD003373. (HubMed – record)
[2] Good (but older) review about pitfalls of cancer screening: Michael N. et al; Nature Reviews Cancer 3, 297-303 (2003) Opinion: Challenges to cancer control by screening (abstract)

[3] Media coverage:
CBSnews (2008/07/16): health, webmd
Medscape (577842, 2008/07/22): Breast Examination May Not Improve Breast Cancer Survival (CME/CE)
Medscape (579590, 2008/08/26): Media Coverage About Breast Self-Exam Misleading, Say Experts (with conflicting opinions)

————————————

Periodieke borstcontrole, uitgevoerd door vrouwen zelf of door artsen/verplegers, is jarenlang gepromoot, omdat je hierdoor eerder borstkanker zou ontdekken, waardoor het beter te genezen is. Deze gedachte wordt actief uitgedragen door verschillende organisaties en Internetbedrijven (die bijvoorbeeld speciale handschoenen verkopen, zie figuur).

Dat regelmatige borstcontrole zinvol zou zijn, wordt echter tegengesproken door een recent Cochrane Systematisch Review, uitgevoerd door Kösters and Gøtzsche.[1] Dit review heeft heel wat losgemaakt bij dokters, makers van richtlijnen, patienten en vrouwen in het algemeen. Veel belangrijke organisaties bevelen niet langer het maandelijks controleren van de borsten aan. De reacties van (engelstalige) patienten varieert van ‘opgelucht’ tot ‘in verwarring gebracht’ of lichtelijk boos (‘ik maak verdorie zelf nog wel even uit wat ik doe’). Zie bijv. enige reacties hier: 1, 2, 3. De berichtgeving door sommige media is soms misleidend. Dat is vaker zo, maar vervelender is het dat reacties van sommige artsen of ‘experts’ heel gekleurd zijn, waardoor de boodschap niet goed overkomt bij het publiek. Sommigen grijpen de gelegenheid aan om even goed op EBM (Evidence Based Medicine) af te geven, zie bijv. deze post van Dr Rich (die overigens ook zinnige dingen opmerkt), dit bericht in de Herald and dit in Medcape (zie onder).

Ik zal proberen om dit onderwerp in een vraag-en antwoord-vorm te bespreken.

1. Wat zijn de conclusies uit de studie?
Dat structureel borstonderzoek door vrouwen zelf of door artsen/verplegers meer kwaad dan goed doet, en dus niet langer aanbevolen kan worden.

2. Welk kwaad, welk goed?
Maandelijkse controle van de borsten leidt niet tot minder sterfte (niet ‘beter’), maar wel tot 2x zoveel biopsies (kwaad, ‘harm’).

3. Waarom kijken ze alleen naar sterfte?
Ze keken ook naar het aantal ontdekte kankers en hun stadia, maar sterfte (of eigenlijk overleving) is veel belangrijker voor de patient. Stel dàt je eerder borstkanker vindt door screening, maar dit leidt niet tot genezing en/of een betere kwaliteit van leven, dan schiet de patient daar niets mee op, integendeel (zij weet het langer).

4. Waarom worden biopsies als ‘schadelijk’ gezien?
Een biopsie is een medische ingreep, die -zeker in het geval van vermoede kanker-, een langdurig negatief kan effect hebben op iemand’s psychische gesteldheid. Biopsies en andere testen, die nodig zijn om kanker uit te sluiten kosten veel geld. Of dit het ‘waard’ is hangt af van hoe nuttig die testen werkelijk zijn, dus of ze de kans op overleving of een betere kwaliteit van leven verhogen.

5. Wat voor een studie is het?
Het is een systematisch review (van “gecontrolleerde” klinische studies), gemaakt door auteurs van de Cochrane Collaboration (zie Glossary). Over het algemeen zijn deze reviews van uitstekende methodologische kwaliteit, omdat studies volgens een vast stramien gezocht, geselecteerd, beoordeeld en samengevat worden. Van te voren worden alle criteria vastgelegd. Dus de auteurs proberen echt alle evidence (positief of negatief, zonder taalbeperking) boven water te krijgen in plaats van wat artikelen uit de kast te trekken of alleen maar de top-tijdschriften te selecteren.

6. Is deze informatie nieuw?
Nee, niet echt. Dit systematische review is in feite een update van een vorige versie uit 2003. De geincludeerde studies en de conclusies zijn hetzelfde. Zoals te zien in het schema hieronder (Nature Reviews Cancer 2003, samenvatting hier), is de houding ten opzichte van borstzelfcontrole al sinds de publicaties van de oorspronkelijke studies (die in het Cochrane Review opgenomen zijn) veranderd. De Amerikaanse Cancer Society beveelt bijvoorbeeld al sindsdien maandelijks zelfonderzoek niet meer aan.

M.N. Pollak et al: Nature Reviews Cancer 3, 297 (2003)

7. Huh? ….
Alle Cochrane Systematische Reviews behoren regelmatig ge-update te worden om te kijken of er geen nieuwe evidence is die tot een andere conclusie leidt. In dit geval werden er geen nieuwe studies van goede kwaliteit gevonden. Wel lopen er nog enkele studies.

8. Kunnen we van deze conclusies op aan? Zijn Cochrane Reviews van een voldoende kwaliteit?
Het Cochrane Review zelf is van een goede kwaliteit, maar op de 2 studies die opgenomen zijn in het review (een uit Rusland uit 1999 met ca. 122.500 deelnemers en een uit Shanghai uit 2002 met ca. 266.000 deelnemers) is wel het een en het ander aan te merken. In beide studies was de blindering van de patienten en de behandelaars voor de toewijzing van de behandeling (concealment of allocation) onvoldoende. Daarmee wordt zo’n studie minder valide (zie bijv. dit artikel uit de Lancet van 2002). Verder was de beschrijving van de statistische methoden onvolledig, waren gegevens van de Moskouse tak van de studie Russische studie niet compleet (zijn wel uitgesloten) , en was er in de Shanghai studie een groot verschil in algehele sterfte (dus niet alleen borstkanker), wat een duidelijke aanwijzing is dat de 2 groepen al vanaf het begin niet gelijkwaardig waren.

9. Zijn de resultaten uit deze oudere studies uit landen als China en Rusland zondermeer op Westerse landen van toepassing?
Intuitief zou ik zeggen van niet. De zorg in Westerse landen en de hedendaagse behandelingen zijn mogelijk beter. Alleen weten we niet of screening door zelfonderzoek hier wel tot een betere uitkomst zou leiden, omdat dat nooit in goede gecontroleerde studies is bestudeerd.

10. Gelden de conclusies voor alle vrouwen?
Nee, de studies zijn allen gedaan -en daarom alleen van toepassing op gezonde vrouwen van zo’n 35 tot 65 jaar. Screeningsmethoden, waaronder borstzelfonderzoek, zijn wel aan te bevelen voor vrouwen, die tot de risicogroep behoren (vrouwen die erfelijk belast zijn of die eerder al borst- of eierstokkanker hebben gehad).

11. Toch stellen bepaalde deskundigen dat zelfonderzoek wel gunstig is. Een dokter (Dr. Goldstein) verwees daarbij in een interview in Medscape (zie hier) naar een heel recente studie (zie hier).
Deze artsen/deskundigen geven hun persoonlijke mening, verwijzen naar niet-gepubliceerde studies of naar studies met een lagere bewijskracht. De studie waar Dr. Goldstein naar verwijst is bijvoorbeeld een retrospectieve studie, die alleen onderzoekt hoe goed vrouwen borstkanker kunnen vaststellen. Retrospectieve studies hebben altijd meer vertekening (zie een vorig bericht over het beste studietype… voor dummies). Verder keek deze studie niet naar harde uitkomsten (overleving, betere prognose). Daarnaast zijn er evengoed retrospectieve studies die het tegenovergestelde beweren, zie bijvoorbeeld dit artikel van Newcomb PA et al in J Natl Cancer Inst. 1991(abstract).

12. Moeten vrouwen dan helemaal geen borstcontrole meer doen?
Ik kwam toevallig ergens op een terrasje een klein stukje in de Viva (1-7 aug 2008) tegen dat ik heel duidelijk vond.
4 Vrouwen gaven hun mening.
Een vrouw die eerder borstkanker had gehad bleef maandelijks controleren (risicogroep). De directeur van de Borstkankervereniging zei: “Wetenschappelijk is aangetoond dat borstcontrole niet zorgt voor minder sterfte door borstkanker. Voel je niet schuldig als je het niet doet. Doe je het wel om zo je borsten goed te leren kennen, dan heeft dat vooral een psychologisch effect”. De woordvoerdster van de KWF Kankerbestrijding zei dat ze periodieke zelfcontrole niet langer promoten, maar dat ze ook niet zeggen dat het zinloos is. Het is net als bij moedervlekken, die controleer je ook niet gestructureerd, maar als je een verandering ziet ga je wel naar de huisarts. Daarmee in overeenstemming zei de directeur van Pink Ribbon dat 90% van de vrouwen borstkanker zelf opmerkt: als er iets zit merk je het toch wel, bijvoorbeeld tijdens het douchen. Inderdaad kan ik dat uit eigen ervaring bevestigen. Mijn moeder voelde jaren geleden een knobbeltje terwijl ze zich aan het douchen was (kwaardaardig, maar genezen).

De Cochrane auteurs zeggen in hun review ook heel expliciet dat het absoluut noodzakelijk is om naar de dokter te gaan als vrouwen veranderingen aan hun borst opmerken.

“Some women will continue with breast self-examination or will wish to be taught the technique. We suggest that the lack of supporting evidence from the two major studies should be discussed with these women to enable them to make an informed decision.
It would be wrong, however, to conclude that women need not be aware of any breast changes. It is possible that increased breast awareness may have contributed to the decrease in mortality from breast cancer that has been noted in some countries. Women should, therefore, be encouraged to seek medical advice if they detect any change in their breasts that may be breast cancer.”

Hier is de Podcast waarin de Cochrane auteurs over hun studie vertellen.

[audio: http://cochrane.org/podcasts/review_summaries/mp3/issue3_2008_breast.mp3%5D

Link naar deze Cochrane Podcast:
http://cochrane.org/podcasts/review_summaries/2008issue3/issue3_2008_breast.html
Bronnen:

zie Engels gedeelte hierboven

Farmaceutische industrie & wetenschap: je zou er depressief van worden.

Ook in de Psychiatrie een nauwe verstrengeling tussen farmaceutische industrie en wetenschap.

Beluister hier het interview met Trudy Dehue in het radioprogramma Argos (de Ochtenden) van de VPRO/VARA (vrijdag 6 juni 2008), over haar boek De Depressie Epidemie
[ISBN: 9789045700953] .

In dit interview komt vooral de invloed van de industrie op het (te vaak) voorschrijven van depressiva (prozac e.d.) en het verdoezelen van bijwerkingen aan de orde.

In deze audio-opname wordt er ook op gewezen dat editors van vooraanstaande engelstalige tijdschriften (Lancet, BMJ) regelmatig de verstrengeling van geneesmiddelenindustie en wetenschappelijk onderzoek stevig aan de kaak stellen.

Klik hier voor zo’n editorial van Fiona Godlee BMJ 2008;336: “Editor’s Choice – Doctors and the drug industry” en hier voor een editorial van RE Ferner – BMJ 2005; 330: 855-856: “The influence of big pharma”.

Toevallig speelt nu ook de kwestie van het ADHD-medicijn Strattera, dat volgens het Nederlands Comité voor de Rechten van de Mens (NCRM) het risico op suïcidaal gedrag, hartaandoeningen en leverbeschadigingen zou verhogen. De NCRM beschikt over een gedeelte van het evaluatierapport over dit medicijn ‘Strattera Risk Benefit Assessment’ (2006). In de 67 beschikbare pagina’s zijn o.a. de volgende gegevens te vinden:

• 130 meldingen van suicidaal gedrag in één maand
• 766 spontane meldingen van hartaandoeningen
• 172 meldingen van leverbeschadigingen
• 20 geslaagde zelfmoorden

Morgen [9 juni 2008] is er een zitting van de Bestuursrechtbank in Amsterdam aangaande de openbaarmaking van het hele rapport in het kader van de Wet Openbaarheid Bestuur. Het Nederlands College ter Beoordeling van Geneesmiddelen (CBG) wilde het rapport namelijk niet vrijgeven.

Bronnen:

• Spits vrijdag 6 juni (papieren versie) , 5 juni e-versie: klik hier
• http://ncrm.nl/nieuws.htm
  

Appropriate bedside manners

Do you prefer a doctor that is crying at the bedside or rather one that stays calm and keeps at a professional distance???

My previous post on Etiquette Based Medicine also dealt with ‘correct’ attitudes of doctors towards their patients. Here I quoted Dr. Khan who believes that “patients may care less about whether their doctors are reflective and empathic than whether they are respectful and attentive”. His opinion is shared by many, but certainly not by all. I allready cited a British Journal of General Practice issue on doctor-patient communication, where different viewes were presented. Well, the debate is still ongoing. In the NY Times of 22^nd April was a interesting piece about physicians crying at the bedside: At Bedside, Stay Stoic or Display Emotions? [*requires registration].

Some excerpts:

“A young doctor sat down with a terminal lung cancer patient and her husband to discuss the woman’s gloomy prognosis. The patient began to cry. Then the doctor did, too.

At a recent meeting of the Society of General Internal Medicine, Dr. Anthony D. Sung of Harvard Medical School and colleagues reported that 69 percent of medical students and 74 percent of interns said they had cried at least once.

In the 1988 PBS documentary “Can We Make a Better Doctor?” a Harvard medical student, Jane Liebschutz, sees her patient unexpectedly die during a cardiac bypass operation. She suddenly bursts into tears and wanders away from her colleagues until the chief surgeon, who has witnessed what happened, assures her that her response was natural.

Dr. Benita Burke, skipped lunch to spend extra time with her cancer patients. They dubbed this time “mental health rounds,” during which they could address issues that were not strictly medical. Many times, Dr. Burke would wind up in tears or giving an embrace.

The comments in the NY Times and at two blogs (DB’s Medical Rants and Clinical Cases and Images) are also worth reading. These responses illustrate that there is not one truth. Whether strong emotions like crying are appropriate depends on the doctor, the patient, the situation and where and how emotions are expressed. Most patients do not seem to appreciate outright crying at their bedside as it makes them insecure. A crying doctor might also feel like a final verdict: no hope is left. But nobody would blame an intern for crying with his or her mates. And a doctor who cries in front of the patient’s family when sharing information about a serious medical error might help to accept what happened.

So, what kind of doctor would you prefer?

I agree with Dr Hiram Cody, cited in the NY Times, who cautions against excess emotions. Although Dr. Cody emphasizes the need for doctors “to understand, to sympathize, to empathize and to reassure,” he says his job “is not to be emotional and/or cry with his patients for two reasons: It is not therapeutic for the patient, and it will cause “emotional burnout”. (although I’m not sure about the latter)

Personally I prefer a doctor with great knowledge, but openminded to other ideas, attentive and empathic, but without loosing a certain distance, a good listener, explaining disease and treatment options, ….. but no crying, please, never! Never when I’m around. Not when I’m the patient.

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Toevallig kwam ik in mijn Feed-Reader een bericht tegen uit de New York Times van 22 april, dat perfect aansluit op mijn vorige post over Etiquette Based Medicine: At Bedside, Stay Stoic or Display Emotions? [*registratie vereist].

Dit stuk bespreekt de voor en tegens van een dokter die zich “laat gaan”.

Enkele citaten:

“A young doctor sat down with a terminal lung cancer patient and her husband to discuss the woman’s gloomy prognosis. The patient began to cry. Then the doctor did, too.

At a recent meeting of the Society of General Internal Medicine, Dr. Anthony D. Sung of Harvard Medical School and colleagues reported that 69 percent of medical students and 74 percent of interns said they had cried at least once.

In the 1988 PBS documentary “Can We Make a Better Doctor?” a Harvard medical student, Jane Liebschutz, sees her patient unexpectedly die during a cardiac bypass operation. She suddenly bursts into tears and wanders away from her colleagues until the chief surgeon, who has witnessed what happened, assures her that her response was natural.

Dr. Benita Burke, skipped lunch to spend extra time with her cancer patients. They dubbed this time “mental health rounds,” during which they could address issues that were not strictly medical. Many times, Dr. Burke would wind up in tears or giving an embrace.

Behalve dit stuk zijn ook de commentaren in de NY-times zelf en op 2 blogs (DB’s Medical Rants en Clinical Cases and Images) de moeite van het lezen waard. Diverse meningen passeren de revue, zowel die van dokters als patiënten of familie. Hieruit blijkt dat er niet één waarheid is. Of het uiten van heel sterke emoties kàn, hangt erg af van de dokter, de patient, hun relatie en de situatie. De meeste patienten vinden het uiten van emoties wél belangrijk (“een dokter moet geen robot zijn”), maar velen vinden te sterke emoties zoals het in huilen uitbarsten waar de patient bijstaat niet prettig, omdat ze juist willen dat ze op hun arts kunnen steunen. Gaat het om een heel slechte boodschap (kanker bijvoorbeeld) dan kan de patient het ook ervaren dat hij opgegeven is: de arts neemt alle hoop dan in een keer weg. Maar als een co-assistent bij het overlijden van zijn/haar “eerste” patient bij haar vrienden uithuilt kan iedereen dat begrijpen. Als een dokter huilt wanneer hij slecht nieuws brengt over een dierbare ten gevolge van een medische fout, dan kan dat bij de verwerking helpen.

Maar welke dokter zou jij verkiezen?

Ik ben het in grote lijnen met Dr Hiram Cody eens. In de NY Times waarschuwt hij tegen overmatige emoties. Hij benadrukt weliswaar dat artsen begripvol moeten zijn, moeten meeleven, empathisch moeten zijn en gerust moeten stellen, maar echt emotioneel zijn en huilen raadt hij af omdat het noch de patient noch de arts goed doet.

Persoonlijk verkies ik een arts met een goede kennis van zaken, maar die wel openstaat voor andere opvattingen, die meeleeft en empathisch is wanneer nodig. Hij moet goed kunnen luisteren, mij serieus nemen, goed kunnen uitleggen waarom ik iets heb en welke behandelingsmogelijkheden er zijn (met hun voor-en nadelen). Hij moet eerlijk zijn en als ik het nodig zou hebben is een beetje emotie en een beetje warmte prettig. Maar huilen, nee. Geen huilen waar ik bij ben. Niet wanneer ik de patient ben.

Etiquette-Based Medicine

Every now and than my collegue Heleen provides me with an interesting paper (a nice web 1.0 way of sharing things). Last Friday I found this paper on my desk: “Etiquette-Based medicine” from Michael W Kahn. The paper in this week’s New England Journal of Medicine is not about the substition of “evidence based medicine” or “eminence-based medicine” by “etiquette-based medicine”. It is about the importance of a good attitude of doctors towards their patients.

When psychiatrist Dr. Khan hears patients complain about doctors, their criticism often has nothing to do with not feeling understood or empathized with. Instead, they object that “he just stared at his computer screen,” “she never smiles,” or “I had no idea who I was talking to”, he writes.
On the contrary, during his own hospitalization he noticed the professional attitude of his European-born surgeon having Old World manners (dress, body language, eye contact etc.).

“The impression this surgeon made was remarkably calming, and it helped to confirm my suspicion that patients may care less about whether their doctors are reflective and empathic than whether they are respectful and attentive”, wrote Dr. Kahn.

Therefore, Khan suggests that medical education and postgraduate training should place more emphasis on “etiquette-based medicine” as it forms the basis of the patient-doctor relationship. One approach would be to introduce a checklist to enforce an etiquette-based approach. A checklist for the first meeting with a patient would for instance cover items like ‘asking permission to enter the room and wait for an answer’, ‘introducing yourselve, showing your ID badge’ and ‘explaining you role on the team’.

This approach bears resemblance to the program introduced at several Academical Medical Centres in the Netherlands. For instance Maas Jan Heineman, nowadays Professor Gynaecology in the Amsterdam Medical Centre (AMC), Amsterdam, helped to introduce such a “etiquette program” in Groningen and in Amsterdam. The competences of the doctors and the integration of knowledge, skills and attitude are now central to the new curricula. As Heineman says it: “What good are doctors who have great knowledge but behave badly. Or vice versa”?! )

These thoughts are (of course) not specifically Dutch (nor European). The entire 2005 January issue of the British Journal of General practice focuses on this subject.

The journal issue ends with a bookreview of a ‘UK-US guide‘ to communicating with patients, consisting of a book ‘Skills for Communicating with Patients’ and a companion volume, ‘Teaching and Learning Communication Skills in Medicine‘, which translates the first book into a framework that can be used in designing and delivering curricula for communications skills teaching in both the academic and clinical setting.

The reviewer, Iain Lawrie, is very positive about the content:

“The layout and language are clear and unambiguous throughout. Important points are emphasised where necessary, and at no time does reading become laborious. Far more importantly, however, the authors have employed an evidence-based approach that moves these titles from the realm of personal opinion and musings to an authoritative work. The frequent use of examples further serves to promote this series as a ‘useable’ guide. (….)
The book gives examples Skills for Communicating with Patients, the authors use a logical approach to analyse the various aspects of communication relevant throughout the consultation process, which are then explored in greater depth over six chapters. They move from the initiation of a consultation (!), through information gathering, structuring, and relationship building, to the often neglected areas of explaining and planning and, finally, closing the encounter.”

Thus it seems that the awareness within the medical community about the necessity of good communication skills is growing. The tools are there, some curricula have already embraced “etiquette based medicine” (although not called by that name) and it seems just a matter of time before “etiquette” becomes an integral part of medical education.

Lets conclude with a quote from the abovementioned book, that also applies to professions other than medical:

‘If you can’t communicate, it doesn’t matter what you know’

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Van mijn collega Heleen krijg ik af en toe een artikel of een krantenknipsel toegeschoven. Nog geheel op de ouderwetse web 1.0 manier, maar eigenlijk wel zo leuk. Van de week lag er een artikel in mijn postvak getiteld “Etiquette-Based medicine”, geschreven door Michael W Kahn. Ik dacht eerst “weer een zogenaamd alternatief voor “evidence based-“ of “eminence-based medicine”, maar het artikel in het laatste nummer van de New England Journal of Medicine ziet “Etiquette-Based medicine” meer als een aanvulling. Het gaat over het belang van een juiste attitude van de arts tegenover zijn patient.

De klachten die Dr. Khan als psychiater van patiënten over artsen hoort gaan meestal niet over gebrek aan empathie maar veel meer over zaken als: “hij staarde maar naar zijn computerscherm”, “er kan geen lachje af”, “ik had geen idee met wie ik nou te maken had”.

Toen Khan zelf in het ziekenhuis lag had hij precies de tegenovergestelde ervaring. De behandelend chirurg van europese herkomst kwam door zijn zogenaamde ‘Oude-Wereld’ houding (kleding, lichaamstaal, oogcontact) bijzonder professioneel en geruststellend over.

Dit sterkte Khan in zijn idee dat patiënten het veel belangrijker vinden dat hun arts hen met respect en met aandacht bejegent dan dat hij heel erg meelevend is.

Hij stelt daarom dat er in het medisch onderwijs meer aandacht moet komen voor wat hij “etiquette-based medicine” noemt, daar dit de grondslag van een goede patient-doctor relatie vormt. Een checklist zou daarbij kunnen helpen. Als een arts de patient voor het eerst ziet zou hij bijvoorbeeld eerst moeten vragen of hij welkom is en pas als de patiënt akkoord is zou hij naar binnen moeten gaan, een hand moeten geven en zich voor moeten stellen.

Iets dergelijks gebeurt reeds in diverse Nederlandse universitair medische centra. Professor Maas Jan Heineman heeft zo’n “etiquette programma” eerst in het UMCG in Groningen en nu in het AMC te Amsterdam geïnitieerd. In het nieuwe curriculum staan de competenties van de arts centraal en een integratie van kennis, vaardigheden en gedrag. Je hebt tenslotte niets aan een dokter die weliswaar veel weet, maar zich vreselijk gedraagt, of andersom”, aldus Heineman. )

Zo’n benadering is niet specifiek Nederlands, noch Europees. Een heel nummer van het British Journal of General practice (jan 2005) gaat enkel over dit onderwerp.

Het laatste artikel is een boekbespreking van een ‘UK-US gids’ over communicatievaardigheden: ‘Skills for Communicating with Patients” en een begeleidend boekje, “Teaching and Learning Communication Skills in Medicine“. ]

De recensent Iain Lawrie is erg positief over het boek. Het is helder geschreven en legt de juiste nadrukken. Verder stijgt het werk door de evidence-based benadering boven een opeensomming van feitjes en meningen uit. Het begeleidende boek geeft voorbeelden van hoe te handelen in bepaalde situaties, bijvoorbeeld tijdens het eerste consult. Het boek omvat dus precies wat Khan suggereerde.

Het lijkt er dus op dat men zich binnen de medische wereld steeds meer bewust wordt van de noodzaak van goede communicatievaardigheden. Er zijn al ‘leermethoden’ beschikbaar en in enkele curriculums is etiquette based medicine reeds verweven (zij het onder een andere naam). Het is slechts een kwestie van tijd voordat etiquette een vanzelfsprekend onderdeel van de medische vorming is.

Tot slot een citaat uit het eerder aangehaalde boek (dat eigenlijk op veel meer beroepen van toepassing is):

‘If you can’t communicate, it doesn’t matter what you know.’