Chronic fatigue syndrome, Bristol University, and controversial science
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THE 12TH EDITION
Trials on certain treatments of chronic fatigue syndrome, or ME, have pitted patients against researchers, and scientists against scientists – amid furious clashes on the validity of landmark studies into the condition.
Words: Lorna Stephenson
Illustration: florencejacksonillustration.tumblr.com
Can chronic fatigue syndrome (CFS), also known as ME, be treated with exercise and talking therapies? It’s a question that splits the scientific and patient advocacy communities, and has become the basis of an intense international dispute.
Scientists researching the treatments claim they’ve been subjected to harassment and abuse, including death threats. But critics say evidence for these behavioural treatments doesn’t stand up to scientific scrutiny, and that pursuing such lines of inquiry runs counter to mounting evidence that CFS is biological, not psychological.
Bristol University is at the centre of these controversies thanks to ongoing trials into exercise and talking therapies for teenagers with CFS, which is characterised by debilitating long-term fatigue that’s worse after exertion, plus symptoms such as chronic pain. The illness can last months or years and in severe cases leaves people bed-bound and even tube fed. CFS has also baffled scientists as to its causes and the biological markers that characterise it – and there’s no drug treatment for it, only medications that can help manage symptoms.
Bristol University’s current research, a trial known as FITNET-NHS, focuses on the efficacy of delivering cognitive behavioural therapy (CBT – a talking therapy) via the internet. Another trial, MAGENTA, recently looked at the outcomes of graded exercise therapy (GET), an approach via which patients follow a regime of gradually increased activity.
Despite the fact that the Bristol trials have got ethics approval, they’ve thrust the university into the spotlight of a worldwide controversy. Opponents, who include scientists and CFS advocacy groups as well as people with CFS, say GET and CBT treatments are harmful, have been tried before to no meaningful effect, and are only being pursued to protect the reputations of researchers and others in the medical science establishment who continue to study them despite them being debunked by a previous, flawed, trial.
A £5m waste of money?
That trial – the largest on CBT and GET, and which dominates the evidence base for CFS – is known as PACE. It occurred between 2005 and 2010, based at Queen Mary University London and with results published in the Lancet medical journal in 2011. It looked at whether CBT and GET were more effective as treatments for CFS sufferers than ‘pacing’ – exertion management – or standard medical care. More than 600 people took part.
The Lancet reported that CBT and GET yielded significantly more improvement than for patients in other groups. A further paper published in 2013 reported that 22% of the CBT and GET groups had recovered following therapy compared with 7-8% of the other groups. The study was hugely influential, with the NHS, the US’s Center for Disease Control and other institutions subsequently recommending CBT and GET for treatment for CFS.
But not everyone was happy – the trial results caused controversy and disbelief among online networks of people with CFS, who analyse and share news of research developments. Many patients and charities experienced or heard numerous accounts that GET often worsened symptoms, with a 2015 ME Association study finding that many participants in GET courses saw their CFS worsen and that “substantial harm was done to many”. Severe CFS’s defining symptom is that people experience ‘crashes’ following exertion. Of course, researchers such as those at Bristol University say many patients benefit, and the trials are designed to prevent anyone suffering adverse effects.
The methodology of the trial was also ripped apart. Patient activists began Freedom of Information battles to get Queen Mary University to release trial data. One reanalysis of the data, following disclosure in 2015, found recovery rates were “inflated an average of four-fold”.
The new claims were helped out of the online echo chamber by David Tuller, an investigative reporter and public health expert at the University of California Berkeley. His 14,000-word piece, ‘Trial by Error’, detailed various methodological failures and inconsistencies within PACE. These included that investigators had relied solely on subjective outcomes of treatment success and dismissed their objective measures, and switched between methods of assessing fatigue and physical function. But the investigators have always defended their trial and refused to accept the criticisms leveled at them.
Financial and consulting relationships between the main researchers and disability insurance companies have complicated the picture. Conflicts of interest were not disclosed to trial participants, something critics claim violates the Declaration of Helsinki, the ethics governing trials involving humans.
“They have no right to publish any data, it all has to be retracted, so they wasted money from the get-go by not having proper informed consent. It’s a total waste of taxpayer money,” says Tuller. “The NHS has endorsed it, because the MRC [Medical Research Council] approved it – everybody’s at risk in this thing.”
Tuller spearheaded a campaign to send open letters to the editors of the Lancet, and the journal Psychological Medicine, which had published further PACE analyses, asking for independent reanalysis of the data.
One signatory was Professor Jonathan Edwards, an emeritus professor of medicine at UCL. “When it comes to CBT and GET, I think we need an open discussion on the fact that the evidence is not there, and people who are going round saying there’s evidence and accusing the patients of being unreasonable – I think that has to stop,” he says. “It’s time the Lancet editor admitted he got it as wrong as he did with [linking] MMR vaccination [to autism].”
The National Institute For Health and Clinical Excellence (NICE) guidelines for treating CFS, which (like worldwide guidelines) are based on the PACE findings, are under review in light of recent developments. Many eminent scientists now argue the £5m trial had ‘major flaws’. But aside from the money and reputations on the line, people with CFS are still waiting for progress into the causes and treatment of the disease.
FITNET and MAGENTA
All this is problematic for Professor Esther Crawley, Bristol University’s clinical lead for paediatrics, who as recently as last November described PACE as a “great, great trial” while discussing her work on BBC Radio Bristol. The FITNET and MAGENTA trials are advertised as extending to teenagers treatments based on ‘good evidence’ in adults – including the PACE trial’s original findings.
The potential impact of GET treatment on participants worries critics such as Jenny Horner, a campaigner in Bristol with pressure group StopGET with her own longstanding CFS diagnosis. “I was shocked they got ethical approval to do this graded exercise therapy research on children, after so many adult patients reported getting worse on graded exercise therapy [and with the controversy over the adult PACE trial methodology being unresolved],” she says.
Horner argues that there is evidence for the harm GET can cause. “Patient surveys consistently show graded exercise therapy to cause more harm than benefit,” she says. “Many of us know people who got severely worse for years after GET. People who were relatively independent become housebound or bedbound or have to start using a wheelchair.”
Psychiatric interventions such as CBT are also touchy subjects for people with CFS, harking back to times when, lacking a biological explanation, psychiatrists claimed the illness was purely in their heads. They were prisoners of their own faulty beliefs, the theory went, and inactivity in turn caused extreme physical ‘deconditioning’ which made activity increasingly difficult.
There’s now a raft of evidence on the physical manifestations of CFS, affecting various systems in the body. If it’s not psychological, why is CBT still recommended and touted as a potential cure? Crawley has argued that the CBT offered during FITNET encourages changes to sleep and activity routines, which benefit patients physiologically.
Nonetheless, some patients remain infuriated at the suggestion that CFS can be tackled with psychological intervention, arguing that it diminishes, in the eyes of others, the severity of the disease. It also strikes many, including Horner, as incompatible with the understanding of CFS as a biological disease.
Extremists
The debate, then, is heated. But if there is truth in the criticisms from patients and CFS advocacy groups and charities, the dominance of the ‘extremist’ opponent narrative – the alleged harassment and abuse of researchers into these treatments – is also troubling. While accepting there may be some intemperate opponents, some critics of PACE and the following trials pursuing similar hypotheses, such as FITNET and MAGENTA at Bristol, say researchers are using the ‘militant’ narrative to deflect legitimate criticisms of bad science.
In 2011 the Observer published an article, ‘Chronic fatigue syndrome researchers face death threats from militants’, in which researchers into GET and CBT outlined the intimidation they said they’d been subjected to from ‘extremist’ patients – from emailed threats, to someone attending a lecture carrying a knife. Crawley featured in the article, saying she received hate mail and checked all packages sent to her office.
Horner is angered by what she sees as a purposeful attempt to discredit the patient community and deflect valid criticism of the research: “I find the nature of these accusations quite distasteful. Over the years ‘psychosocial agenda’ researchers appear to use this as a tactic to silence all patient criticism. It works particularly well in terms of newspaper coverage.”
For now, the Bristol University trials are set to continue amid the online noise of opposition, though other studies into CFS’s biological roots – more promising in the eyes of critics of the CBT and GET paradigm – are also taking place around the world. For people with CFS, for whom all too often life is put on hold, any advances can’t come soon enough.
Bristol University and Professor Crawley declined to comment for this article.
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Thank you for a great article.
I’d just like to add, that as an ME/CFS patient harmed by GET, in principle I would welcome compatible psychological interventions while we wait for research into new treatments and a cure.
The problem many of us have with CBT/GET is that its genesis lies in treating patients as if their symptoms are a psychological manifestation of an illness that has since disappeared and that we are simply de-conditioned and stuck in a boom and bust cycle of doing too much, feeling ill, then stopping instead of persevering at a gradually increasing fitness.
The problem with this hypothesis is that it has been proven that:
ME/CFS patients produce 20x more lactic acid in muscles on exertion
ME/CFS patients vs sedentary controls (otherwise healthy people with low physical fitness) have a distinct adverse reaction to exercise.
ME/CFS patients score on V02 max tests (an un-gameable aerobic/anaerobic threshold test) decrease on repetition (so they’re unable to increase fitness, they become more unfit).
Recent studies have found huge irregularities on a cellular level in the energy production cycle (krebs)
In initial studies, patients have been responding to a cancer drug called ‘Rituximab’ which has led to periods of remission for ME/CFS sufferers.
There’s much more as well, but as you can see, the idea that this is some kind of psychological manifestation of a de-conditioning cycle has come and gone. The BPS (biopsychosocial) theory of ME/CFS needs to be binned, they keep attempting to re-purpose it as some kind of complementary therapy, but the fact is, they should divert all funding to promising studies championed by groups like ‘Invest In ME’, the ME Association or ME Research UK. The continued hijacking of our scant resources will see people die with this illness who might have made it to a cure if resources were used appropriately.
Thank you for writing this article, Lorna. You described the situation very well.
Thank you for your excellent article giving a great summation of the whole PACE fiasco with its resulting fallout for ME/CFS patients around the globe. Thank you from an ME/CFS patient in the U.S.
Some criticisms:
It’s unfortunate, to say the least, that you use the misnomer CFS throughout. Even the DWP use CFS/ME.
The claims of harassment and abuse of researchers also didn’t “stand up to scrutiny”, in a court of law.
Chronic fatigue may sometimes last only months but, 17.5 years into this illness, I’ve yet to hear of anyone, even with a diagnosis of CFS, whose illness has lasted less than a year or two at the *very* least. The vast majority are permanently ill.
“Freedom of information battles” – this should be a misnomer and could have been reported as such. QMU’s refusal to release the data and dismissal of such requests as “vexacious” was the big issue, finally dealt with by the courts.
I thank you for this sentence: “If it’s not psychological, why is CBT still recommended and touted as a potential cure?”
As the accusations of harassment were dealt with in a court of law, it’s most unfortunate that you should propagate this idea with the use of Extremists as a paragraph headline.
Criticisms aside, thank you for broaching this subject and for the most balanced article yet to be published for a mainstream audience!
From a slightly braindead PwME.
Thank you for this timely article. People associated with Bristol University need to understand that their institution is supporting researchers who promote harmful treatments for ME patients, including children.
Are they really OK with that?
This is a cogent summary of the debate about CBT and GET therapies for ME/CFS. Thanks for an article that is easy to read and follow.
I would recommend that the author also report on the other side of ME/CFS research—that being the search for the biological cause (and biomarkers) of the illness. It’s a fascinating story on it’s own. Unfortunately, the bio side of research has been underfunded for decades. Even so, dedicated medical researchers are making some novel progress on the underlying biology of ME/CFS.
Would have been nice to mention that in court the ‘threats’ were finally admitted to be one person heckling the researcher at a talk. This admission was iirc a significant factor in the Judges dissension to force the full disclosure of the research material.
Thank you for your journalistic integrity. In this brief article you have managed to do something that has escaped large outfits such as the Guardian, BBC, and Telegraph and that is produce a fair and balanced news report on ME/CFS.
I would like to address one thing. The narrative that patients are opposed to CBT and talking therapy simply because they imply that the disease is psychological is inaccurate. The reality is far more nuanced, and honestly an entire book could be written on the subject.
I am speaking as a person with myalgic encephalomyelitis for 3.5 years and counting. We as patients understand the utility of talking therapy, as will any person who has experienced adversity in their life. We also understand that CBT is used with reported success on patients with diseases such as cancer and multiple sclerosis, and this does not imply that those diseases are psychological, just as using CBT on a patient with CFS or ME does not by default mean CFS or ME are psychological diseases.
However, CBT is different from talking therapy. And more importantly, the CBT model used for ME and CFS is not the same CBT model used in cancer or multiple sclerosis. CBT in the latter diseases is used to address the effects of guilt, fear, and uncertainty from having a serious chronic disease, with the goal of improving quality of life.
The CBT model used by Esther Crawley and her contemporaries in ME and CFS research is different and is built on the de facto belief that ME/CFS are psychosomatic diseases. Their model states that ME/CFS are due to a vicious circle; the patient believes they are sick and so they avoid exerting themselves, which leads to physiological deconditoning, which leads to fatigue, which reinforces the patient’s belief that they sick, and so on. The purpose of the CBT model used in ME/CFS is to challenge the presumed “unhelpful cognitions” that the patient has regarding their illness. They are told by the CBT practitioner that they are to ignore their symptoms of pain, fatigue, etc. because the practitioner believes (without adequate evidence) that the patient is not actually sick, and therefore is in no danger by ignoring these important bodily signals. From the beginning, patients are told by the practitioner that this treatment will work, and that it will treat their disease directly. Similarly, graded exercise is used to target the presumed deconditioning aspect of the vicious circle in another attempt to “cure” the disease itself.
To a layperson, this might not seem so unreasonable. However, to biomedical scientists that research the disease, and to patients to have experienced the disease first hand, these models are untenable and at odds with hundreds and hundreds of biomedical research studies. This is why patients and scientists alike are vehemently opposed to the research being done by Crawley and her ilk. Their research is built on a flawed, invalidated model, and is designed in such a way that subjective bias is not avoided and objective measures of improvement are not properly utilized. We are not opposed to research being done on our disease, be it biomedical or biopsychosocial, we are opposed to *bad* research being done on our disease. And Crawley is unquestionably producing bad research.
Those researchers cliaimg to be victims of harrasment have failed to produce any evidence when asked before Tribunal. The Tribunal concluded of the expert witness for the PACE authors that:
“It was clear that his assessment of activist behaviour was, in our view, grossly exaggerated and the only actual evidence was that an individual at a seminar had heckled Professor Chalder”
and
“clearly in our view had some self-interest, exaggerated his evidence and did not seem to us to be entirely impartial. What we got from him was a considerable amount of supposition and speculation, with no actual evidence to support his assertions or counter the respondents arguments.”
I would just like to add that in majority of cases ME/CFS is incurable lifelong condition.
Those researchers claiming to be victims of harrasment have failed to produce any evidence when asked before Tribunal. The Tribunal concluded of the expert witness for the PACE authors that:
“It was clear that his assessment of activist behaviour was, in our view, grossly exaggerated and the only actual evidence was that an individual at a seminar had heckled Professor Chalder”
and
“clearly in our view had some self-interest, exaggerated his evidence and did not seem to us to be entirely impartial. What we got from him was a considerable amount of supposition and speculation, with no actual evidence to support his assertions or counter the respondents arguments.”
I would just like to add that in majority of cases ME/CFS is an incurable lifelong illness.
Great article! This bad science needs to be exposed.
Good article, thank you.
Two points:
1.
The court ordered disclosure of the data that allowed a re-analysis was in 2016, not 2015.
2.
I agree with the comments above about the endless lurid allegations of harassment and threats made by certain researchers against patients. When given the formal opportunity to lay the evidence on the table and prove their very serious and longstanding allegation, all those researchers could offer was a single incident of somebody heckling a researcher at a seminar. Which is just pathetic beyond words.
Questions need to be asked about the real story behind this disgraceful cowardly farce.
as an aside – having had M.E. for around 30 yrs (now 62) – and following the BBC programme Dr Westons casebook, focusing on an acute CFS case, where recovery was helped by a daily dose of antihistamine, (to counter possible excess histamine from the mast cells) – I have been using this now for 6 months with significant improvement allround – (loratadine 10mg). Also, for neuropathy, gabapentin 300 mg twice daily – been on this for more than 6 months and its a big help – but beware of potential mood swings in some patients. As for this CBT study, it amazes me that the government can find £5 million in its coffers to spend on mumbo jumbo, but not to seemingly to research the biological causes or mechanisms of ME/CFS? why is that? – no wonder it results in some patients with an extremist view – they are what’s known as “at the end of their tether” – with no relief in sight.
I, too, have found that antihistamines substantially reduce itching, migraines, and gut symptoms. Aspirin improves my orthostatic intolerance (difficulty staying upright). This suggests mast cells behaving badly. But since I don’t experience hives, doctors refuse to investigate.
Unfortunately most doctors are as ignorant about mast cells as they are about ME, Irritable Bowel Syndrome, Postural Orthostatic Tachycardia Syndrome, Neurally Mediated Hypotension, and all the other problems we have.
They must be good for something besides lecturing patients to exercise more and to eat, drink alcohol, and smoke less, but I’m not sure what exactly.
Thank you for this article. If I may suggest one correction.
“The National Institute For Health and Clinical Excellence (NICE) guidelines for treating CFS, which (like worldwide guidelines) are based on the PACE findings, are under review in light of recent developments.”
Worldwide guidelines are changing. As of May 2017, the Centers for Disease Control in the U.S. has completely removed any mention of GET/CBT. They have also changed from listing the disease as CFS, to ME-CFS, and made considerable updates throughout their site. The CDC seems to have turned to the strong biological research coming out of the University of Bergen in Norway, Griffith University in Australia, Stanford & Columbia Universities in the US, etc. Concurrently, the NIH in the US has doubled ME-CFS funding and launched a large-scale study to pin down biomarkers. The CDC and especially the NIH are behemoth institutions which struggle with government funding, more so now under a science/health-hostile administration. And yet they have made changes following current research and evidence, for which they are sticklers.
https://www.cdc.gov/me-cfs/treatment/index.html
Brilliant and balanced article. Thank you for saying what others are too scared to say.
Thanks for the reasonably balanced article, a rarity in ME/CFS coverage that usually takes the “militant” claims at face value.
From memory even that ‘knife at a conference’ claim is dodgy, I recall it was a small paring knife to peel the apple the person was eating! Though I suppose in a post 9/11 or 7/7 world carrying a knife in public is potentially dangerous even with innocent intent.
As a person who has suffered with CFS/ME I have found that the best definition of the condition is ‘mitochondrial dysfunction due to low output heart failure’. I first heard this in 2008 and it certainly matches my experience of the condition. CBT is always a helpful intervention but it can be patronising/matronising to ignore the very real physical ramifications of this condition. With more and more research into genes, and understanding our own genetic inheritance, it is becoming easier to understand this condition. Dr Myhill here in the UK, in my opinion, gets the reality of this condition more than any one else in the world…and her work was influenced by a well-known heart specialist in America – a Dr Sinatra. Her website is very informative and she wrote several papers published in medical journals on the topic. All conditions have a physical, mental, emotional and spiritual component….sadly, I see that when people do not understand something there is a tendency to blame ‘the attitude’ of the person alone. CFS/ME is a complex condition with many different ‘aspects’. If one searches for mitochondrial dysfunction due to low output heart failure – a whole new world of information appears. I am well now. This definition helped me support myself, with the help from doctors and medical professionals, to get well.
From another perspective of a long term sufferer with M.E. I find the article heavily weighted, if not deliberately biased, as no picture is presented of the reality of M.E. as experienced by many thousands of sufferer who are not helped by the treatments under trial.
“The World Health Organization International Classification of Diseases (ICD-10) classifies chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) under neurological disorders at Reference 93.3 and uses the terms post-viral fatigue syndrome (PVS) and benign myalgic encephalomyelitis. The Department (of Health) accepts this classification and recognises CFS/ME as a neurological condition of unknown origin.” http://www.meassociation.org.uk/2013/02/parliamentary-question-who-classification-of-cfs-11-february-2013/
Neurological, not a psychiatric condition. While it is undoubtedly true that many M.E. patients may have psychological problems, like any other sector of the populace, this begs the question: is M.E. a symptom of psychological disturbance or is psychological disturbance a symptom of M.E.?
Whilst being tired all the time may be a symptom of depression, depression in otherwise motivated individuals who are crippled by M.E. can be a direct result of the frustration and inability to lead a “normal” life as well as high-handed, contemptuous treatment at the hands of the “caring” profession whose job it is to diagnose and help.
Additionally, M.E. is NOT simply feeling tired, it is NOT the simple healthy fatigue resulting from a hard days work and relieved by a good nights rest.
There is nothing “Benign” about it, like the “benign” prostatic tumour that killed my father: the excessive growth, while not technically malignant blocked his waterworks and his kidneys failed very suddenly and irreversibly.
ME can and does kill.
It is continual and it is painful and has a very wide spectrum of symptoms: heart palpitations, muscle spasms and cramps, hypersensitivity to light, sound and touch which makes crowded noisy places whether supermarkets or festivals an unbearable nightmare, emotional lability thanks to erratic adrenalin regulation.
To name a but few symptoms from a long list.
Imagine the worst hang-over you ever had, or remember the time you had a bout of flu and were bed-ridden in pain for a week.
Imagine feeling like that 24/7/365.
I have formerly used the metaphor of being thoroughly and professionally beaten with rubber truncheons by the secret police on the way home from the greatest party and waking up next day with painful but invisible bruising all over and a massive head-ache included.
You are forced to take frequent bed-rest, yet wake up not refreshed and fit for the fray, but feeling worse.
Waking from daily afternoon forced bed-rest I used to feel paralysed, as if buried alive by the said secret police and only a supreme effort of will would move my limbs, coupled with the knowledge that with some movement, some slight ease would come. Until the next period of bed-rest became inevitable and unavoidable.
There is a huge amount of confusion and controversy around the subject, not helped by the fact that different countries and research departments have different policies and criteria for diagnosis.
Additionally, different patients have different combinations of the myriad symptoms and differ in their ability to cope with and overcome their individual challenge. Every individual has their own individual set of symptoms and circumstances.
I suffered various indignities and abuses, subtle and not so subtle, in my 20 year search for a diagnosis, kicked about like a football and thoroughly abused, being told there “is nothing wrong that we can find” with the sub-text of “Go away, you’re a nuisance, get a proper job”.
Without a diagnosis, I did not know that normal exercise just makes things worse: training in a normal sort of way, lane swimming, cycling, taking 26 flights of stairs two at a time if not actually running; pushing the boundaries does NOT work and can result in further deterioration.
Since I had the diagnosis I have been able to manage my condition better, most days I can have some activity although the all-over body pain remains along with the constant headache and other symptoms. The only real improvement has been the ability to manage my energy levels sustainably without constantly hitting the wall, crash and burn out cycle.
I also object strenuously to the illustration, implying as it does that M.E. is a Narcissistic Personality Disorder. Perhaps that is not what was intended, but that certainly is the message that the illustration presents, and plays right into the hands of the Psychiatric Establishment who want to corner the condition for themselves and manage it with a pill.
The establishment psychiatrists want us to believe that M.E. is a psychological condition, contrary to the WHO statement that it is “Neurological”.
It may be that the UoB is getting some results, but there is no “one size fits all” treatment or cure ever going to be available since ME/CFS is not a single identifiable disease: it is a combination of multiple symptoms with innumerable permutations among every personality type; it is a “syndrome” with multiple causes and nobody is immune.
To my mind, I can use the “Canary in the Coal mine” analogy: Sufferers with M.E. are, not the weakest, but the most sensitive people, whether genetically or psychologically, and highly receptive to the harmful man made pollution that is all pervading.
Pesticides, Herbicides, Fertilizers; allopathic medicines and artificial hormones in the drinking water and the air we breathe thick with chemicals of all kinds.
ICE exhaust fumes and particulates, powerful radio waves of so many frequencies which would literally fry the body if the source were approached.
Malnourishment in the midst of Plenty: Junk foods industrially processed with complex additives devoid of substance and fuelling an epidemic of clinical obesity.
Never before experienced by humankind.
How many people getting brain tumours from excessive and inappropriate use of mobile phones?
Like so much of present day malaise, the causes are obvious to those with eyes to see and ears to hear. Why do we spend so much time and money to find cures instead of eliminating the causes?
For the same reason the NHS concentrates on quick fixes of what can be fixed and ignores the rest….Kudos, Ego, Money and Power and the interests of Big Pharma.
As a regular frequenter of NHS services since 1988, having been harried from pillar to post, I am only too well aware that there is a sickness at the heart of the NHS which will never be cured by throwing money at it; that is merely feeding the beast.
The golden calf of the NHS is the great false god and idol that demands our obeisance and complete subjection…but that is another subject.
This is an excellent article thankyou☺