virology blog

Time 2021-04-28 14:08:10

Web Name: virology blog

WebSite: http://www.virology.ws

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*April is crowdfunding month at Berkeley. I conduct this project as a senior fellow in public health and journalism at the university’s Center for Global Public Health. If you would like to support the project with a donation to Berkeley (tax-deductible for US taxpayers), here’s the place:https://crowdfund.berkeley.edu/project/25504I have recently blogged about the multiple mis-citations of a seminal study involving so-called “medically unexplained symptoms” (MUS). The 2010 study, Bermingham et al, found that the amount spent by the National Health Service on working-age people who were assessed as “somatising” accounted for around 10% of what was spent on that population. Since the study was published more than a decade ago, experts in MUS have routinely misrepresented it by asserting that these costs accounted for 10% of total NHS expenditures—in effect more than tripling their apparent financial impact.The costs of addressing MUS have been cited regularly as a reason to increase psychological services for patients identified with the conditions that qualify for such a diagnosis. Under its current framework, the NHS’ Improving Access to Psychological Therapies program considers anyone with ME/CFS, irritable bowel syndrome and other ailments without a clear etiology to be suffering from MUS. That makes them all eligible to be shunted immediately from primary care to IAPT interventions, which are mostly variations on cognitive behavior therapy.On April 17th, I wrote to Professor Anthony David, a neuroscientist at University College London. I was seeking information about why he hasn’t yet corrected this mistake in a paper of which he is the senior author even though another paper he co-authored was corrected for the same mistake 18 months ago. Professor David, an expert in the MUS field, was formerly at King’s College London, home to some of the leaders of the biopsychosocial ideological brigades. KCL luminary Professor Sir Simon Wessely is a co-author on the un-corrected paper. Another KCL scholar, Professor Trudie Chalder, was the senior author of the paper co-authored by Professor David and corrected in October, 2019, after I wrote to her and BMJ Open, the journal that published it.Two days ago, I sent a follow-up note to Professor David after I was alerted by a smart observer to yet another paper of which he is the senior author that includes the same mis-citation. (This one also featured a misspelling “Birmingham” instead of “Bermingham.”)  For Professor David, that’s three separate mis-citations of Bermingham et al or at least that s the number we know of.I have not heard back from Professor David. Whether he responds or not, I do hope he follows through with quick corrections of the two uncorrected papers. And if he made the same mistake elsewhere, I hope he corrects those instances as well so I don t have to bother pointing them out.To be clear: I’m not suggesting that Professor David or anyone mis-cited Bermingham et al deliberately. I assume it happened unintentionally and, over the course of a decade, the false “fact” self-replicated in the literature because no one bothered to double-check it or noticed that it was wrong if they did double-check it. And why would that be? Perhaps because the higher cost meshed nicely with the interests and perceptions of those mis-citing it in the first place. Confirmation bias at play.This rote repetition of untrue information happens routinely in journalism. In this case, the dissemination of the inaccurate data point has the potential to impact public health policy, and perhaps it already has. Given the significance of the error, it seems fair to ask those who have made it to explain how it happened and why other claims they make should be taken at face value. Yet when asked that kind of question and others suggesting problems with their data or argumentation, members of this cohort of investigators have seemed to prefer to utter words like “harassment” than to provide reasonable and credible responses.I have noticed that a 2016 paper on which you were the senior author contains the same misstatement about Bermingham et al as the two more recent papers that I have already highlighted. The 2016 paper, Medically unexplained visual loss in a specialist clinic: a retrospective case–control comparison, was published in the Journal of the Neurological Sciences. I have cc d the corresponding author on this e-mail, and again Vincent Racaniello, Columbia s Higgins Professor of Microbiology andhost of Virology Blog. (Incidentally, in the paper Bermingham is misspelled as Birmingham. )The 2016 paper includes this sentence: In estimation of the associated health costs of medically unexplained symptoms, Birmingham [sic] colleagues propose that healthcare utilisation amounts to £3billion per annum, or 10% of total NHS expenditure. Clearly, this needs to be corrected, since the figure actually represented 10% of NHS expenditures for the working-age population and only about 3% of total NHS expenditures.For what it s worth, the title of Bermingham et al itself specifies the age parameters of the study population, so the repetition of this false information across a decade continues to mystify me. Any explanation you might offer to help me understand this phenomenon would be much appreciated.Thanks for your quick attention to this matter. I look forward to seeing the corrections in both this paper and the more recent one inPsychological Medicine.What does it mean that the top investigators in a field of research have collectively and consistently misrepresented a seminal figure in their purported domain of expertise? I’m talking about all those who present themselves as authorities on the topic of so-called “medically unexplained symptoms” (MUS) but have found it difficult to accurately cite a study that examined the purported costs of these conditions to the National Health Service. (This phenomenon was initially pointed out to me by an observant sleuth; I first wrote about it here.)The study in question, Bermingham et al, is called The cost of somatisation among the working-age population in England for the year 2008-2009. It was published in 2010 in the journal Mental Health in Family Medicine. As one of its core findings, it estimated something very specific: NHS costs for patients of working age identified as “somatising” to even a minor extent accounted for around 10% of the total costs for that demographic category. In paper after paper, “experts” in MUS have translated that straightforward data point this way: Patients with MUS accounted for 10% of total NHS costs. The effect of that error is to more than triple the apparent impact of MUS on the NHS budget.(Special Note for MUS experts reading this post: References to Bermingham et al s age parameters are in mentioned in the title of the paper itself.)It is unclear why these thought leaders have been so statistically challenged across so many years. I assume the mistake has been unintentional. Nonetheless, it has served to support the argument for desired policy outcomes, which could explain why it went unnoticed by the authors as well as any like-minded colleagues who peer reviewed the papers in question. If health officials wrongly believe that costs related to MUS account for 10% of their budgets, they would presumably be more amenable to ramping up psychological services along the lines of the ones proposed by those disseminating the false information.I have recently been engaged in an exchange with Professor Robin Murry, one of the two top editors at the venerable journal Psychological Medicine. At issue is a paper that once again includes the false statement about NHS costs. I have also written separately to the senior author, Professor Anthony David, since a previous paper he co-authored was corrected for the exact same mistake 18 months ago.I have not heard back about a correction from either Professor Murray or Professor David. I sent Professor Murray a follow-up message this morning. I have shared it below.Two workweeks have passed since I contacted you about the significant error in Characteristics of patients with motor functional neurological disorder in a large UK mental health service: a case-control study. (The authors are O Connell, Nicholson, Wessely, David.) You indicated you would check with the authors.In reality, it should take the authors no more than a few minutes to review the mis-cited study, Bermingham et al, as well as the other papers in which the exact same mistake has already been corrected. That is even more the case since Professor David, the senior author, was also a co-author on one of the previously corrected papers. Moreover, I cc’d the corresponding author of Bermingham et al in my e-mail communications, in case of any lingering confusion about the meaning of the study findings.I am therefore surprised that I haven’t heard back from you yet about the correction. Perhaps this seems like an insignificant matter or a minor irritation to you and the authors. However, as I have noted, investigators who study so-called “medically unexplained symptoms” have spent a decade disseminating a false account of the findings of this seminal research in their own field of purported expertise. Coincidentally or not, this mistake aligns with these experts’ professional interests in promoting more services for people who would meet their diagnostic criteria for MUS.When the peer review process fails repeatedly to catch the same substantive error in publication after publication, journal editors should be alarmed. Perhaps the lesson is this: If a school of researchers appears to be engaging in what might be called groupthink by, for example, collectively misrepresenting a key data point in the medical literature, it would be wise to extend peer review invitations to a wider circle of readers and to ensure that references are cross-checked against claims being made.I look forward to a prompt update on the forthcoming correction to O’Connell et al. As I have suggested, I hope the correction also includes an explanation for the 18-month delay since the previous paper co-authored by the senior author was corrected for the exact same mistake.Early in the COVID-19 pandemic, SARS-CoV-2 genome variation appeared to be low, with an average of 10 base differences in the 30,000 base genome between any two isolates. Late in 2020, as many more people were infected, variants were isolated that had more changes than previously seen. A study of variation at the genome level indicates that diversity in a single host has been underestimated.SARS-CoV-2 variants certainly arise in each infected individual, and these may be subjected to selection pressures such as those imposed by antibodies binding to spike protein. Commonly used sequencing technologies do not permit detection of virus variants within single samples. To address this limitation, a high-throughput sequencing method was developed for sequencing individual virus RNA genomes in patient samples. The results demonstrate that SARS-CoV-2 variants emerge in each host and are subject to immune selection pressure.When this method was used to analyze a patient isolate of SARS-CoV-2 after four passages in Vero cells, in the regions encoding spike, ORF3, envelope, and M protein, 18 unique combinations of mutations were detected. Over half of the single genome sequences differed from the reference sequence. Many of the changes led to amino acid substitutions, suggesting selection pressure occurring during cell culture adaptation. In-host diversity was then examined for 7 patients sampled between days 8 and 17 of illness onset. Only a few sequence haplotypes were detected, with no clear consensus among the amino acid changes. These relatively homogeneous sequences might have been a consequence of sampling early in infection when limited antibody pressure was present. Examination of the antibody response in longitudinal samples revealed an increasing and broadening antibody response to the spike.A study of antibody responses and presence of mutations in individual genomes revealed a correlation between the emergence of antibodies to the N-terminal domain of spike protein, the emergence of amino acid changes in regions that bind these antibodies, and a delay in clearance of virus. These results are consistent with antibody pressure during infection leading to selection of SARS-CoV-2 spike variants (pictured).SARS-CoV-2 variation in a single host had not been previously described, probably due to the inability of previous sequencing methods to distinguish variation from technical errors. It is also likely that high-quality data were acquired early in infection when viral titers are high yet antibody pressure is not yet present. There are several take-home messages from these findings. They illustrate how diversity in a single host might give rise to antibody-resistant variants that could spread in a population if they have the appropriate fitness. In-host escape might be avoided by containing viral reproduction early in infection, either by prior immunity or by antiviral therapy, before selection by antibody takes place. This method should be applied to studying more COVID-19 patient samples to understand the extent of potential in-host SARS-CoV-2 variation.Trial By Error: More on the Lightning Process and the Science Media Centre s Collusion With UK Journalists22 April 2021 by David Tuller 3 Comments By David Tuller, DrPH*April is crowdfunding month at Berkeley. I conduct this project as a senior fellow in public health and journalism at the university’s Center for Global Public Health. If you would like to support the project with a donation to Berkeley (tax-deductible for US taxpayers), here’s the place:https://crowdfund.berkeley.edu/project/25504My story on the Lightning Process this week, published by Coda Story, was pretty long. Even so, it didn’t cover everything I would have liked to include. Here a bit more about the issue.As we now know, the pediatric Lightning Process study conducted by Professor Esther Crawley, Bristol University’s methodologically and ethically challenged pediatrician, violated core concepts of scientific inquiry but was published anyway. BMJ whitewashed what appeared to be research misconduct by posting a 3,000-word correction/clarification rather than retracting the paper. Coda Story is an excellent news organization focused on international stories related to the misuse of science and technology, among other topics. Today, it published a piece of mine about the training program called the Lightning Process. Sites devoted to the Lightning Process are full of tales of recovery from prolonged illness. I included one such account in my Coda article along with accounts from others who reported suffering severe relapses after the training. The article also points out that the scientific claims cannot withstand scrutiny.A recent Wall Street Journal opinion piece accused an apparently powerful queer feminist wellness collective of causing an international wave of mental illness, which is being expressed as reports of persistent disabling symptoms after an acute bout of COVID-19. The article was written by a psychiatry resident at Canada s McMaster University in Canada. Given the arguments advanced by the resident, my friend and colleague decided to check in with the university s psychiatry department. Can McMaster University Medical School Psychiatrists Be Trusted to Treat ME/CFS Patients?*April is crowdfunding month at Berkeley. I conduct this project as a senior fellow in public health and journalism at the university’s Center for Global Public Health. If you would like to support the project with a donation to Berkeley (tax-deductible for US taxpayers), here’s the place:https://crowdfund.berkeley.edu/project/25504Earlier this week, I wrote to the journal Psychological Medicine about a significant mistake in a paper on functional neurological disorders. The mistake involved a misquotation of Bermingham et al, a key 2010 analysis of the National Health Service costs associated with care for working-age people found to be “somatising.” One of Psychological Medicine s two editors-in-chief, Professor Robin Murray of King’s College London, responded promptly and indicated that he was checking with the authors about the matter.I subsequently followed up with Professor Murray to point out that the senior author of the paper was also co-author of another paper that had been corrected for the same mistake in October, 2019. He again responded promptly and indicated that he would check on it.When I first investigated the PACE trail in 2015, one of the features most shocking to me was the investigators blatant violation of a core human rights document that they had promised in their protocol to adhere to. That violation of the Declaration of Helsinki involved their failure to tell study participants about their close ties with the insurance industry. For years, the lead investigators had advised disability insurers that the interventions being tested in PACE for efficacy were in fact effective and could get claimants back to work.When the B.1.1.7 variant of SARS-CoV-2 was first detected in the UK in December 2020 it was accompanied by unsubstantiated claims of increased transmissibility and virulence. The results of a hospital-based study in London reveals no association of the variant with severe disease in this cohort.In a note published by NERVTAG on 21 January 2021, the panel concluded that ‘there is a realistic possibility that infection with VOC B.1.1.7 is associated with an increased risk of death compared to infection with non-VOC viruses. The death risk ratio for VOC infected individuals compared with non-VOC infected individuals was 1.65. This conclusion was based on analysis of COVID-19 related deaths at several hospitals in the UK. The authors noted in this report that The data set used in the LSHTM, Imperial, Exeter and PHE analyses is based on a limited subset of the total deaths. This includes approximately 8% of the total deaths occurring during the study period’.In the present study, SARS-CoV-2 PCR-positive samples from hospitalized patients were analyzed that had been collected between 9 November and 20 December 2020 in London. Of these, 341 (58%) were infected with B.1.1.7 and 143 (42%) were infected with an ancestral virus. Results of statistical models showed no association between severe disease and death and the B.1.1.7 lineage. I hope that these results can begin to reverse the disturbing narrative advanced by some that B.1.1.7 is 50% more virulent than its ancestor. This conclusion was never firmly grounded, yet it has been echoed by mainstream media as if it were dogma. Unfortunately the authors of this paper continue to promote the idea that B.1.1.7 viruses are more transmissible. Their conclusion is based on increased levels of viral RNA in patient samples as determined by RT-PCR (cycle threshold 28.8 in VOC infected patients versus 32.0 in non-VOC infected patients) and genomic reads by sequencing (1280 vs 831). Increased viral load determined by these methods might be an indication of increased viral fitness, but it does not prove increased transmission. It is not known if VOC-infected patients shed more infectious virus, which might be consistent with increased transmission. Until such experiments are done, it can only be speculated that B.1.1.7 and other VOC have increased transmissibility.Next Page Primary Sidebarby Vincent RacanielloEarth's virology ProfessorQuestions? virology@virology.wsWith David Tullerand Gertrud U. ReyFollowFacebook, Twitter, YouTube,InstagramGet updates by RSS orEmailContentsTable of ContentsME/CFSInside a BSL-4The Wall of PolioMicrobe ArtInterviews With VirologistsEarth s Virology Course Columbia UVirologia en EspañolVirology 101Influenza 101Podcasts This Week in VirologyThis Week in MicrobiologyThis Week in ParasitismUrban AgricultureThis Week in EvolutionVirus WatchAll at MicrobeTVUseful ResourcesLecturio Online CoursesHealthMapmSpherePolio eradicationPromed-MailSmall Things ConsideredViralZoneVirus Particle ExplorerThe Living RiverParasites Without Borders

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