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发表于 2011-4-24 09:39:48
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re:Pre-existing problem...
Pre-existing problems
Both child 4 and child 8 were among the eight whose parents were reported to have blamed the vaccine. But although the paper specified that all 12 children were “previously normal,”61 both had developmental delays, and also facial dysmorphisms, noted before MMR vaccination.
In the case of child 4, who received the vaccine at age 4 years, Wakefield played down problems, suggesting that early issues had resolved. “Child four was kept under review for the first year of life because of wide bridging of the nose,” he reported in the paper. “He was discharged from follow-up as developmentally normal at age 1 year.”
But medical records, presented by the GMC, give a different picture for this child. Reports from his pre-MMR years were peppered with “concerns over his head and appearance,”62 “recurrent” diarrhoea,63 “developmental delay,”64 “general delay,” and restricted vocabulary.65 And although before his referral to Wakefield his mother had inquired about vaccine damage compensation,66 his files include a report of a “very small deletion within the fragile X gene,”67 and a note of the mother’s view that her concerns about his development had begun when he was 18 months old.68
“In general, his mother thinks he developed normally initially and subsequently his problems worsened, and he lost some of his milestones, but he subsequently improved on a restrictive exclusion diet,” wrote his general practitioner, William Tapsfield, referring the boy, then aged 9, after a phone conversation with Wakefield. “The professionals who have known [child 4] since birth don’t entirely agree with this, however, and there is a suggestion that some of his problems may have started before vaccination.”69
Similarly with child 8, who was also described in the Lancet as having overcome problems recorded before vaccination. “The only girl . . . was noted to be a slow developer compared with her older sister,” the paper said. “She was subsequently found to have coarctation of the aorta. After surgical repair of the aorta at the age of 14 months, she progressed rapidly, and learnt to talk. Speech was lost later.”
But Wakefield was not a paediatrician. He was a former trainee gastrointestinal surgeon with a non-clinical medical school contract.70 And his interpretation differed from that of local consultants (including a developmental paediatrician and a geneticist) who had actually looked after the girl. Her doctors put the coarctation side by side with the delay and dysmorphism,71 and noted of her vocabulary that, before MMR at 18 months, she vocalised only 72 “two or three words.” 73
“[Child 8’s] mother has been to see me and said you need a referral letter from me in order to accept [child 8] into your investigation programme,” the general practitioner, Diana Jelley, wrote to Wakefield at referral, when the girl was aged 3 and a half years. “I would simply re-iterate . . . that both the hospital and members of the primary care team involved with [child 8] had significant concerns about her development some months before she had her MMR.”74
The girl’s general practice notes also provide insight into the background to the 12 children’s referrals. After person(s) unknown told Mrs 8 that her daughter may have inflammatory bowel disease, Jelley wrote: “Mum taking her to Dr Wakefield, Royal Free Hospital for CT scans/gut biopsies ?Crohn’s—will need ref letter—Dr W to phone me. Funded through legal aid.”75
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The child was “pale”
The remaining five children served Wakefield’s claims no better. There was still no convincing MMR syndrome. Child 1, aged 3 years when he was referred to London, lived 100 miles from the Royal Free, and had an older brother who was diagnosed as autistic.76 Child 1’s recorded story began when he was aged 9 months, with a “new patient” note by general practitioner Andrea Barrow.77 One of the mother’s concerns was that he could not hear properly—which might sound like a hallmark presentation of classical autism, the emergence of which is often insidious. Indeed, a Royal Free history, by neurologist and coauthor Peter Harvey, noted “normal milestones” until “18 months or so.”78
Child 1 was vaccinated at 12 months of age, however. 79 Thus neither 9 nor 18 months helped Wakefield’s case. But in the Lancet, the “first behavioural symptom” was reported “1 week” after the injection, holding the evidence for the lawsuit on track.
Step 1 to achieve this: two and a half years after the child was vaccinated, Walker-Smith took an outpatient history. Although the mother apparently had no worries following her son’s vaccination,80 the professor elicited that the boy was “pale” 7-10 days after the shot. He also elicited that the child “possibly” had a fever, and “may” have been delirious, as well as pale.81
“It’s difficult to associate a clear historical link with the MMR and the answer to autism,” Walker-Smith wrote to the general practitioner,82 with a similar letter to Wakefield, “although [Mrs 1] does believe that [child 1] had an illness 7-10 days after MMR when he was pale, ?fever, ?delirious, but wasn’t actually seen by a doctor.”
Step 2: for the Lancet, Wakefield dropped the question marks, turning Walker-Smith’s queries into assertions. And, although Royal Free admission83 and discharge84 records refer to “classical” autism, step 3, the former surgeon reported “delirium” as the first “behavioural symptom” of regressive autism, with, step 4, a “time to onset” of 7 days.
So here—behind the paper—is how Wakefield evidenced his “syndrome” for the lawsuit, and built his platform to launch the vaccine scare.
“It is significant that this syndrome only appeared with the introduction of the polyvalent MMR vaccine in 1988 rather than with the monovalent measles vaccine introduced in 1968,” he claimed in one of a string of patents he filed for businesses to be spun from the research.85 “This indicates that MMR is responsible for this condition rather than just the measles virus.”
Three of the four remaining children were seen in outpatients on the same day—in November 1996. None of their families were reported in the paper as blaming the vaccine. Child 5, from Berkshire, aged 7 at admission, had received MMR at 16 months.86 The paper reported concerns at 18 months, but the medical records noted fits87 and parental worries88 at 11 months. Child 9, aged 6, from Jersey, also had MMR at 16 months.89 His mother dated problems from 18-20 months.90 Child 10, aged 4, from south Wales, contracted a viral infection, which was suspected by parents and doctors to have caused his disorder, four months after his vaccination.91
“Behavioural changes included repetitive behaviour, disinterest in play or head banging,” said a question and answer statement issued by the medical school, concerning the Lancet 12, on the day of the paper’s publication.
Another discrepancy to emerge during the GMC hearing concerned the number of families who blamed MMR. The paper said that eight (1, 2, 3, 4, 6, 7, 8, and 11) linked developmental issues with the vaccine. But the total in the records was actually 11. The parents of child 5,92 9,93 and 1294 were also noted at the hospital as blaming the vaccine, but their stated beliefs were omitted from the journal.
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Case selection
The frequency of these beliefs should not have surprised Wakefield, retained as he was to support a lawsuit. In the month that Barr engaged him—two years before the paper was published—the lawyer touted the doctor in a confidential newsletter to his MMR clients and contacts. “He has deeply depressing views about the effect of vaccines on the nation’s children,” Barr said.95 “He is also anxious to arrange for tests to be carried out on any children . . . who are showing symptoms of possible Crohn’s disease. The following are signs to look for. If your child has suffered from all or any of these symptoms could you please contact us, and it may be appropriate to put you in touch with Dr Wakefield.”
The listed symptoms included pain, weight loss, fever, and mouth ulcers. Clients and contacts were quickly referred.96 Thus, an association between autism, digestive issues, and worries about MMR—the evidence that launched the vaccine scare—was bound to be found by the Royal Free’s clinicians because this was how the children were selected.97
Moreover, through the omission from the paper of some parents’ beliefs that the vaccine was to blame, the time link for the lawsuit sharpened. With concerns logged from 11 of 12 families, the maximum time given to the onset of alleged symptoms was a (forensically unhelpful) four months. But, in a version of the paper circulated at the Royal Free six months before publication, reported concerns fell to nine of 12 families but with a still unhelpful maximum of 56 days.98 Finally, Wakefield settled on 8 of 12 families, with a maximum interval to alleged symptoms of 14 days.
Between the latter two versions, revisions also slashed the mean time to alleged symptoms—from 14 to 6.3 days. “In these children the mean interval from exposure to the MMR vaccine to the development of the first behavioural symptom was six days, indicating a strong temporal association,” he emphasised in a patent for, among other things, his own prophylactic measles vaccine,99 eight months before the Lancet paper.
This leaves child 3. He was 6½ and lived on Merseyside: 200 miles from the hospital. He received MMR at 14 months,100 with the first concerns recorded in the general practitioner’s notes 15 months after that.101 His mother—who 4 years later contacted Wakefield on the advice of JABS102—told me that her son had become aggressive towards a brother, and records say that his vocabulary had not developed.103
“We both felt that the MMR needle had made [child 3] go the way he is today,” the parents wrote to a local paediatric neurologist, Lewis Rosenbloom, 18 months before their son’s referral to London.104 They told him they wanted “justice” from the vaccine’s manufacturer, and that they had been turned down for legal aid.105 “Although it is said that the MMR has never been proven to make children to be autistic, we believe that the injection has made [child 3] to be mentally delayed, which in turn may have triggered off the autism.”
I visited this family twice. Their affected son was now a teenager and a challenge both to himself and to others. His mother said his diagnosis was originally “severe learning difficulties with autistic tendencies” but that she had fought to get it changed to autism.106
As for a connection with MMR, there was only suspicion. I do not think his family was sure, one way or the other.107 When I asked why they took him to the Royal Free, his father replied: “We were just vulnerable, we were looking for answers.”
What was unquestionably true was that child 3 had serious bowel trouble: intractable, lifelong, constipation.108 This was the most consistent feature among the 12 children’s symptoms and signs109 but, being the opposite of an expected finding in inflammatory bowel disease,110 111 it was nowhere mentioned in the paper. This young man’s was so severe that he was dosed at his special school, his mother said, with up to five packets of laxative a day.
“You always knew when his stomach was hard,” she told me, in terms echoed over the years by many parents involved with Wakefield. “He would start headbutting, kicking, breaking anything in the house. Then he would go to the toilet and release it.”
For the Royal Free team, however, when reporting on these patients, such motility issues 112 were sidelined in the hunt for Wakefield’s syndrome. In almost all the children, they noted commonly swollen glands in the terminal ileum, and what was reported as “non-specific colitis.”113 114 In fact, as I revealed in the BMJ last April,115 the hospital’s pathology service found the children’s colons to be largely normal, but a medical school “review” changed the results.
In this evolution of the gut pathology noted in the records to what was published in the paper, child 3’s case is a prime example. After ileocolonoscopy (which, GMC prosecution and defence experts agreed, was not clinically indicated116), the hospital’s pathologists found all colonic samples to be “within normal histological limits”.117 But three months after the boy was discharged, Walker-Smith recalled the records and changed the diagnosis to “indeterminate ileocolitis”.118
“I think, sadly, this was the first child who was referred, and the long term help we were able to give in terms of dealing with constipation was not there,” he told the GMC panel. “However, we had excluded Crohn’s disease and we had done our best to try and help this child, but in the end we did not.”
So that is the Lancet 12: the foundation of the vaccine scare. No case was free of misreporting or alteration. Taken together, NHS records cannot be reconciled with what was published, to such devastating effect, in the journal (table⇓).
View this table:In this windowIn a new windowComparison of three features of the 12 children in the Lancet paper with features apparent in the NHS records, including those from the Royal Free hospital
Wakefield, however, denies wrongdoing, in any respect whatsoever.119 He says he never claimed that the children had regressive autism, nor that he said they were previously normal. He never misreported or changed any findings in the study, and never patented a measles vaccine. None of the children were Barr’s clients before referral to the hospital, and he never received huge payments from the lawyer. There were no conflicts of interest. He is the victim of a conspiracy.120 121 He never linked autism with MMR.
“Mr Deer’s implications of fraud against me are claims that a trained physician and researcher of good standing had suddenly decided he was going to fake data for his own enrichment,” he said in a now abandoned complaint against me to the UK Press Complaints Commission. “The other authors generated and ‘prepared’ all the data that was reported in the Lancet. I merely put their completed data in tables and narrative form for the purpose of submission for publication.”
But, despite signing up to claim credit for a paper in the Lancet, his co-authors Walker-Smith and Murch did not even know which case was which. Walker-Smith said he had “trusted” Wakefield.122 “When I signed that paper, I signed with good intent,” he told the GMC panel. Denying any wrongdoing, he argued that the published report was not even about MMR, but merely described a new “clinico-pathological entity”. He said that the admissions to the Royal Free were “entirely related to gastroenterological illness” and how the children were sourced was “irrelevant” and “immaterial.” His lawyers said that he was appealing against the panel’s decision and on these grounds they had advised him not to respond to my questions.
The journal, meanwhile, took 12 years to retract the paper, by which time its mischief had been exported. As parents’ confidence slowly returned in Britain, the scare took off around the world, unleashing fear, guilt, and infectious diseases—and fuelling suspicion of vaccines in general. In addition to measles outbreaks, other infections are resurgent, with Mr 11’s home state of California last summer seeing 10 babies dead from whooping cough, in the worst outbreak since 1958.123
Wakefield, nevertheless, now apparently self-employed and professionally ruined, remains championed by a sad rump of disciples. “Dr Wakefield is a hero,” is how one mother caught their mood in a recent Dateline NBC TV investigation, featuring the story of the doctor and me.124 “I don’t know where we would be without him.”
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