The Curious Case of Hydroxychloroquine

The discipline of medicine has changed. Its traditional cohesion and leadership have fractured into a multitude of disconnected specialty groups, allowing powerful commercial and political forces to increase control over both structure and function of medical practice. The Covid era burst through boundaries long taken for granted.

By examining the manipulation of hydroxychloroquine to attain a political end, this article seeks to illustrate the destructive forces brought to bear on how medicine was practised in Australia, with shameless disregard for the health and survival of patients, or for the integrity of those charged to care for their well-being.

I have practised as a physician in Australia for half a century. I recall when we knew (and revered) the name of the President of the Royal Australasian College of Physicians, while living in fear of their Chief Examiner as we sought qualification! They were great men and women and were the exemplars for ethical practice. They were the leaders and role models, providing evidence-based standards of medical practice. Today they only occasionally question imperfect narratives or challenge the ethics of prevailing medical practice, risking being part of the problem rather than a solution, creating a hiatus.

This essay appears in the current Quadrant.
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I was invited to speak at a symposium, “Medicine at the Crossroads in the Covid Era”. I sought a topic that illustrates contemporary challenges to Western medicine. Few topics could be more relevant than threats to the doctor-patient relationship, and to science-based medicine seen in the Covid pandemic. So I chose “The Curious Tale of Hydroxychloroquine (HCQ)” as a metaphor for the distortion Covid imposed on clinical practice, driven by misinformation aimed at supporting a flawed narrative originating from the highest sources of medical influence.

I am a clinical immunologist. I have a special interest in chronic inflammatory disease and the immunology of the airway. Among the valuable drugs in my clinical practice is HCQ, for which I have written approximately 20,000 prescriptions without any observed major side effect. It is a safe and effective medication that blocks antigen-promoting pathogenic immune responses in patients with autoimmune or hypersensitivity diseases.

Covid made HCQ a household name. No medication attracted more brutal and remorseless assault. It was subjected to unprecedented derision and negativity by medical professionals and the public alike. The mainline press and news media, acting in conformity with instructions from the “trusted news initiative”, ran prominent commentary that included gross misinformation and ridicule of those supporting its use. HCQ presents the dilemma that embodies the extremes of the narrative and science of Covid. In this context and over the last three years, popular narrative and science have gone down quite different paths.

First, a little about hydroxychloroquine. At the molecular level, the drug retains the quinoline ring structure of its parent, quinine, an alkaloid secondary metabolite derived from the bark of the cinchona tree, native to Peru. Known as an allelochemical, meaning that it interacts with other organisms, quinine is a highly evolved antioxidant and free radical scavenger component of the defence network of host plants. Quinine shares with other allelochemicals multiple intracellular targets. Advantages for allelochemicals used as therapeutics in treating disease include modification of the cell response to infection in order to dampen the hijacking of its metabolic machinery to produce pathogen.

Quinine differs from synthetic antivirals that block specific biochemical steps essential for viral replication. Advantages that come with multiple cell targets include resilience to mutant escape, protection against mutated variants resistant to both natural and vaccine-induced immunity, long biological half-lives, and activity over a wider disease cycle, with value in both prevention and therapy. Quinine and its derivatives have a long record of treating infectious disease, most notably malaria, but also have a documented anti-viral effect. Chloroquine was effective in vitro against SARS-CoV-1. So it was no surprise that Chinese scientists included chloroquine in a panel of repurposed drugs testing for anti-Covid activity within weeks of the pandemic being announced. In vitro anti-viral activity in micromolar concentrations was confirmed in several centres.

Numerous small clinical studies appeared through the first half of 2020, supporting drug benefit. Two studies were influential, shaping the immediate future for HCQ, but in unintended ways. First came reports from the infectious disease group in Marseille, led by the controversial Professor Didier Raoult. A successful trial, published in mid-March 2020, which including twenty-four patients, combined the antibiotic azithromycin with HCQ, and gained attention, with Sanofi, a French multinational pharmaceutical and healthcare company, offering large supplies, and President Macron consulting Raoult.

The second was a family doctor in upstate New York, Vlad Zelenko, who noted in an open letter to President Trump in 2020 a dramatic change in outcomes from Covid infection when early disease was treated with HCQ, azithromycin and zinc. His data were later published as a case series of 2200 patients, claiming 95 per cent protection against both admission to hospital and death. Trump’s enthusiasm for Zelenko’s approach led to worldwide publicity and controversy.

Blowback against HCQ was immediate and without precedent. In France, Raoult was an easy target. By November 2020 he faced a disciplinary hearing for “spreading false information” and eventually lost his job. The mainstream press aimed to quell “disinformation”. It had meshed gears to continue an attack on Raoult which pre-dated Covid and centred on studies in tuberculosis. Opposition became focused on complaints made by a Dr Bik, identifying procedural problems, ethical irregularities and methodology variations (but never fraudulent HCQ claims). Legal proceedings brought by Raoult made him a public talking point. The science of HCQ was lost in the fray.

The ongoing furore ensured the rejection of HCQ as a Covid therapy in France. In the US, Zelenko suffered a similar fate—incomplete patient data combined with the curse of support from President Trump generated widespread condemnation. Comments such as “a jumble of facts, falsehoods, and rumours collides with our fragile information ecosystem” characterised the public and medical response.

Several events in late 2020 combined to stifle any chance of HCQ’s survival as an accepted treatment for Covid. Three large randomised controlled trials (RCT) failed to support HCQ, causing the WHO to distance itself from the drug. In its place the narrative became “Support vaccines at any cost”. Trials of a second repurposed drug with anti-Covid activity (ivermectin) and the imminent launch of the genetic vaccines further shaped the narrative.

The Surgisphere Trial was published in the Lancet in May 2020, the Solidarity Trial, sponsored by the WHO, in the New England Journal of Medicine in October 2020, and the Recovery Trial involving a collaborative UK group, in the New England Journal of Medicine in June 2020. Each study included thousands of hospitalised patients with late and serious disease, with high mortality of 10 to 25 per cent in both study and control arms. The Surgisphere study was withdrawn by the Lancet, with claims of fraud because of data manipulation, while numerous inconsistencies were noted in the other studies. High doses used in sick patients were linked to cardiac arrhythmias. The results of these studies stopped further research. The WHO withdrew support for HCQ, and the Cochrane Review (considered an arbiter of “best practice”) advised against further studies.

The demonstration from Monash University in June 2020 that ivermectin had anti-viral activity in vitro, followed by positive clinical studies, immediately shifted disinformation claims from HCQ to another repurposed drug that threatened the imminent release of the Covid vaccines. Results from phase 3 trials for a series of genetic vaccines appeared in late 2020 amid a fanfare of support, with political, media and medical commitment combining to suppress any treatment option that might hinder vaccine uptake.

Now, in 2024, six discoveries have changed the playing field to give a better understanding of HCQ in management of COVID-19.

The first is identification of a target for HCQ early in viral replication. It was known that HCQ increased pH within lysosomes to reduce lysosomal protein degradation and early autophagy, key events in later aspects of viral replication. However, recent proteomic studies using cloned and tagged viral proteins identified specific protein-protein interaction on cell surfaces that required a Sigma-1R molecule as a chaperone to enable viral entry across the cell membrane. Many drugs were assessed for their capacity to block the action of Sigma-1R. HCQ was the most potent of this group, signalling its potential for effective early treatment.

The second insight came from an analysis of clinical studies concentrating on high-risk subjects with early disease. Despite clear evidence from early 2020 that HCQ had maximum benefit early in disease (as was the case with most anti-viral therapies, as is well known for cold sores and shingles) and in high-risk patients, detractors of HCQ continued to include hospitalised patients with advanced disease in meta-analyses. It was these inappropriate assessments that influenced official advice. This strategy was not accidental.

Professor Harvey Risch, a senior epidemiologist from Yale University, in an evidence brief of June 2021, included a meta-analysis of nine controlled outpatient studies in high-risk subjects. Every study showed protection, with the meta-analyses revealing highly significant protection against hospitalisation at 44 per cent, and death at 75 per cent. Regional studies in India and Brazil found a close temporal relationship between dosing and a reduction in mortality.

The third insight came from a concern over conflict of interest created by grants and payments from pharmaceutical companies to investigators. Where authors had no conflict of interest, success for HCQ treatment was 86 per cent, while in those with a conflict of interest, only 5 per cent had positive outcomes.

Fourth was a retrospective analysis of the experience of the Marseille group, previously directed by Professor Raoult. Data on 30,400 subjects treated to the end of 2021 were included. Sensitivity to earlier criticism about accuracy and objectivity led to the study including an external judicial officer in the study. Amongst this treated group, subjects treated with HCQ had a mortality of 0.1 per cent. When those treated with HCQ were compared with those not treated with HCQ, the HCQ-treated subjects had a significant advantage with respect to mortality (70 per cent protection in outpatients, and 45 per cent in inpatients), providing strong support for the inclusion of HCQ in early therapeutic regimens.

Fifth was the registration of the specific antiviral drugs molnupiravir and paxlovid based on scanty and controversial data. Molnupiravir is a powerful mutagen with untested toxicity in humans and little evidence of clinical value. A UK study of 20,000 infected subjects failed to show any benefit in preventing serious disease for molnupiravir, yet it is the common drug of choice in Australia for most patients with COVID-19. Paxlovid reduces both admission to hospital and mortality, but to a lesser extent than does HCQ. It has age restrictions, drug incompatibilities and a high relapse rate.

Accusation of undue influence over regulatory assessment of both drugs despite these concerns, and costs in excess of $1000 per course, may have contributed to both HCQ and ivermectin being quietly released by the Australian Therapeutic Goods Administration for off-label use. Just twelve months ago, a doctor in Queensland could be jailed for prescribing HCQ, while others across Australia faced being deregistered. The data have not changed. But the damage had been done.

A sixth reason was concern that the vaccine narrative, which drove the suppression of repurposed drugs, had become tarnished with repeated boosters failing to protect—even promoting infection—amidst growing alarm over severe adverse events.

The curious tale of HCQ is a story of tension between a narrative to protect pharmaceutical interests, and science. It should never have happened because long-established clinical practice involves informed consent and decisions based on what may work within the doctor-patient relationship. This includes judicious use of off-label drugs of known safety and mechanism of action.

As a clinical immunologist whose patients often have rare diseases, and are all different, I need to individualise the therapy I prescribe. In the Covid era, HCQ came to symbolise a change in the order of medical business—of denying patients best-practice medicine that may have saved many lives, and ridiculing individuals and institutions who promoted it. 

A major driver of opinion about Covid has been the World Health Organisation (WHO). Its Health Emergencies Program in its proposed form, designed to strengthen disease-specific systems and capacities, including for vaccines, pharmaceuticals and other public health interventions, may be a serious threat to independent local health systems. Given it is an unelected body responsive to powerful lobbies, and with a performance short of wide approval in its overarching role in the recent pandemic, there is reason to tread carefully.

The WHO has moved a long way from its founding principles in 1948 to keep the world safe by connecting nations, partners and people to promote health. Covid laid bare an agenda to manipulate world-best practice and centralise its control. Suppressing HCQ was a rehearsal. By controlling major clinical trials and using their influence on regulatory bodies, with supportive propaganda, the WHO and its partners shifted decision-making from grass-roots medicine to international forces driven by power and financial reward.

The WHO is a complex organisation, subject to many political and economic influences. It is vulnerable to manipulation because of chronic underfunding and the crossfire of conflicting national agendas. Its support for expensive, potentially dangerous, and variably effective patented antiviral drugs (remdesivir, molnupiravir and paxlovid), alongside its negativity with respect to safe, cheap and effective repurposed drugs such as HCQ and ivermectin, may reflect the influence of massive pharmaceutical companies and their host nations on its fragile agenda.

Things started to go wrong in mid-2020 with the Solidarity Study mentioned above recruiting more than 3550 hospitalised patients with advanced COVID-19 in thirty-five countries and 400 hospitals. They were unlikely to respond to any therapy. Unless initiated within twenty-four to forty-eight hours, anti-viral treatment is rarely beneficial. On the basis of results from this study, WHO posted on December 31, 2020, a release recommending against HCQ as a dangerous and ineffective drug likely to cause ventricular arrhythmias. That posting remains, supported by “30 trials with more than 10,000 patients”. Again, all were in late-stage infection and, as usual, evidence that HCQ works well in early disease was pointedly ignored.

A review of all studies provides perspective. The website “HCQ for COVID-19” ( maintains an updated and annotated compendium of meta-analyses, including every study on every drug tested against Covid. Current data on early treatment with HCQ gives 62 per cent protection in thirty-six studies with 56,000 patients. Mortality following early treatment was 72 per cent lower in the treated group, according to a meta-analysis including fifteen studies and 52,000 patients. This data source includes a review of thirty-nine published physician case series of early treatment in 237,000 subjects. The mean protection against hospitalisation and mortality was 94 per cent. While these real-life data sets are subject to bias, include different drug combinations, and they lack patient details, they are consistent with more formal studies. 

This article has followed the science, arguing that HCQ has a pivotal role in early treatment of high-risk individuals with COVID-19 infection. The argument has had to battle alternative stories—espoused by much of the mainline press and promoted by an aggressive pharmaceutical industry with widespread grants—that vaccines and expensive antiviral drugs are the exclusive key to controlling Covid.

The handling of HCQ in Covid has three major elements. First, given that HCQ was an approved pharmaceutical whose safety profile and mechanism of action were well known, it could be argued that the physician operating with informed consent within the doctor-patient relationship should be free to determine whether the off-label use of HCQ would benefit that patient.

Second, the fate of HCQ is a story about switching decision-making in medicine from a core of experienced clinicians familiar with local needs, to powerful global political and commercial interests. 

Third, the Covid pandemic has shifted towards an endemic disease, but remains a frequent infection which in the aged and those with risk factors carries significant mortality. Hydroxychloroquine (and ivermectin) as cheap, safe and available drugs, are drugs of choice for early treatment today, as they always have been.

The curious tale of HCQ in the Covid era raises questions about how best to make clinical decisions for our patients. Traditional Australian confidence in the doctor-patient relationship, and in science, have served us well. We should be careful to defend and strengthen them. The WHO has an important role in monitoring disease, providing advice and co-ordinating programs that otherwise are beyond local resources. However, these essential activities must not conflict with sovereign authorities in domains equipped with quality health services based on local knowledge, strong science infrastructure and a tradition of medical practice based on personal responsibility.

Robert Clancy is Emeritus Professor of Pathology at the University of Newcastle Medical School. He is a member of the Australian Academy of Science’s Covid-19 Expert Database. He also wrote on aspects of the Covid pandemic in Quadrant’s July-August and October 2022 issues. He thanks Professor Stephen Leeder AO for his editorial help in preparing this article.


19 thoughts on “The Curious Case of Hydroxychloroquine

  • Stephen Due says:

    The TGA banned the use of Ivermectin for Covid, in part because of the risk that its use would lead to ‘vaccine hesitancy’. The Australian government reportedly destroyed the stockpile of millions of doses of hydroxychloroquine imported by Clive Palmer, presumably for the same reason. In the mainstream medical literature, fraudulent studies appeared, debunking the use of hydroxychloroquine in hospitalised patients (when it was given too late in the course of the disease to be effective, and in toxic doses). Once again, the motive appears to have been to discourage the use of an effective drug that would detract from the planned global vaccination program.
    What are we to make of the sustained campaign by the Australian authorities to prevent GPs using these proven remedies? Was this done purely through following a ‘narrative’ put out on mainstream media? Was it done at the behest of pharma? Evidently no attempt was made to consult either experts such as Professor Clancy, or the medical literature, which clearly showed the effectiveness of hydroxychloroquine in SARS (e.g. Vincent MJ Nichol ST Chloroquine is a potent inhibitor of SARS coronavirus infection and spread, Virology Journal 22 August 2005).
    It seems that the story put out by vaccine promoter and profiteer Bill Gates – that the only solution to the pandemic was ‘a needle in every arm’ – won the day over informed scientific opinion. What saddens me, as a ‘consumer’ of healthcare, is that the Australian government prevented my doctor from advising me as he saw fit, both on the vaccines and on treating the illness. When I consult my doctor, I want his opinion, not that of a government official.
    Australians must resist the tendency by government to interfere in the doctor-patient relationship. It is quite possible that misguided bureaucratic zeal cost the lives of some Australians during Covid, and very likely that it contributed to unnecessary disease severity and duration in others. It also diminished the trust of the public in government health advice, and in the treatment (if any) offered by GPs for a worrying and sometimes serious illness. Proven early treatment in the community, which normally is the first line of defence in viral respiratory diseases, was left out of the picture. In its place the people were offered (and in some instances coerced into taking) inadequately tested genetic vaccines which proved to be relatively ineffective and were suspected of causing multiple adverse effects.

    • Citizen Kane says:

      Pfizer, Gates , Fauci et al. were all desperate to usher in the brave new world of mRNA technology, which was seen as the next great leap forward in therapeutics. This was no ordinary ‘vaccine’ but essentially gene therapy allowing for the endogenous synthesis and production of a foreign protein (in this instance the covid spike protein). It cannot be understated that the impetus to introduce (ram through in the absence of proper clinical trial assessment) mRNA technology for the first time into the compendium of commercial therapeutic agents was the primary driver behind what unfolded. He great irony being, that the therapy is an abject failure!

    • SB says:

      I suspect that TDS was a major factor in all of this, particularly where the media were concerned.

  • Jack Brown says:

    The way the sickness industry deliberately loaded their HCQ studies with hospitalised patients even though its proponents had not claimed effectiveness in such situations (but only in the very early stages after diagnosis) surely was no accident. When one of the medical establishment’s bureaucratic enablers featured in the ads by the Australian Dept of Health a year ago promoting a commercial antiviral for COVID he emphasised that it had to be taken early in the episode he had no sense of shame in the hyoocrisy involved:

    The other aspect of the deliberate sabotage of HCQ, and later IVM, was that the studies commissioned seemed to be focussed on the drug used in isolation. This may be relevant in the case of new drugs and especially so when testing for safety but the proponents of HCQ, and later IVM, were speaking about treatments involving known drugs in combination. Just because there might not be a significant marginal effect due to any one component used in isolation this does not mean in combination there is no combined effect. The interaction effect is well recognised in terms of potential harmful interactions (eg when the other drug is alcohol) which doctors watch for but other combinations can have beneficial effect, and this was the case with the HCQ+Zinc+Azithromycin protocol.

  • nfw says:

    “The TGA banned the use of Ivermectin for Covid, in part because of the risk that its use would lead to ‘vaccine hesitancy’. The Australian government reportedly destroyed the stockpile of millions of doses of hydroxychloroquine imported by Clive Palmer, presumably for the same reason.”

    The real reason would be the corruption of public servants and politicians by Big Pharma and the huge profits to be made and shared in experimental untested death drugs. I particularly disliked the misinformation campaign about Ivermectin being a “horse medicine”. The Nobel Prize winning inventors gave the patent to the world to save live which it has done, not become rich. The Wuhan Flu experimental drug cheer squad needs to keep being reminded Pfizer is a herbicide company and the proper name for the “disease” is the Wuhan Flu.

    • Ceres says:

      Prof Clancy’s articles were required reading during the dark years of covid hysteria.
      Many of us, after much critical research and the inability to get ivermectin prescribed for off label use, turned to the ivermectin derogatorily called “horse paste” which seemed to serve us well. No covid. Taken in correct dosage and with vitamin d and zinc. Will never forgive the insanity of the so called chief medical officers denying us drugs which at the very least were not going to do us any harm.

  • vickisanderson says:

    Thank you, Professor Clancy, once more for your integrity in using your lifetime of professional experience and knowledge in vouchsafing the treatment that you know to be effective. I think everyone who reads Quadrant understands the opposition and resentment that will have been focussed on you as a result of your courageous validation of the repurposed drugs such as Hydroxychloroquine and Ivermectin in the treatment of Covid.

    Many of us are deeply grateful to yourself, Dr. Phillip Altman and a few others who have steadfastly maintained your arguments. It has been a bitter disappointment to those who refused to accept novel and suspect mRNA vaccines that they were unable to access safe, repurposed drugs when they contracted Covid 19. It is doubly frustrating that the campaign to control the off label prescriptions was so effective that GPs are still loathe to prescribe them, and the general public still is sceptical of their value.

    • Stephen Due says:

      It could be argued that a government-imposed inability to access safe repurposed drugs in this context was also a form of coercion directed at forcing people to take the injections. The longstanding statement on the TGA website that the use of Ivermectin for Covid would encourage ‘vaccine hesitancy’ clearly indicates the policy of preventing its use was intended for this purpose only (the other reasons offered were obviously bogus).

  • ianl says:

    Thanks again to Robert Clancy for his insightful persistence.

    That he is correct is constantly confirmed by the sneaky reluctance of our “betters” to engage with him and their persistence in mis-labelling hard questioning as disinformation. Legislation currently before the Senate will strengthen their position in that if passed in its’ current form it will prevent even the publication of articles such as this.

  • David King says:

    Robert – so many similarities here withe the scientific distortions around the climate change debate. For WHO read IPCC.
    David King

  • pbw says:

    As befits his expressed subject, Professor Clancy discusses in detail the various findings with respect to HCQ, undergirding his conclusions. Towards the end of his article, he says, “Hydroxychloroquine (and ivermectin) as cheap, safe and available drugs, are drugs of choice for early treatment today, as they always have been.” I note the inclusion of Ivermectin.
    There is still a great deal of criticism of “Vitamin-I”, some of it quite recent. I would love to see a similar discussion from Professor Clancy of the validity of academic and research attacks on the usefulness of ivermectin in the treatment of Covid-19.
    Incidentally, I recall reading quite early in the panic a paper by a group of Indian doctors on the public health approach in India. Early news reports from that country read like a disaster movie script; then, suddenly, silence. Various States in India distributed medicine kits containing vitamins (C and D, for example), zinc tablets (often), an antibiotic and either HCQ or Ivermectin. At the time the paper was written, the supply of HCQ was much more common than Ivermectin. Since then, both drugs have been removed from the treatment protocols, and the water has been very much muddied. Any detached analysis of the situation in India would be welcome.

  • Peter OBrien says:

    Thank you again Dr Clancy for a very illuminating article. Heads should roll, but of course they won’t.


    A real medical crisis predicates that any reasonable treatment or procedure that is available should be used. Mandating and enforcing only one exclusive treatment when cheaper, more effective treatments of historically proven efficacy are available for a multi-factetd approach is an indictment of malfeasance and malpractice. It has been known for some time that the real, and main reason, for enforcing the bans of Ivermectin and Hydroxychloroquine was to ensure Emergancy Use Authorization (EUA) for mRNA technology misappropriated as vaccines.These were rushed, without the usual lengthy trials and testing, into full scale production followed by rapid world wide human inoculation.
    It is no coincidence, of course, that the EUA also facillitated hideous profits for certain drug companies who functioned as government protected cartels during the Covid fiasco.

  • NDee53 says:

    I have been in agreement with, indeed in awe of, Professor Clancy from day 1 and I am much impressed by today’s article. There are many enquiries ongoing around the world into Covid-19, and the treatment of it, all of which ought to be so excoriating of the establishment and its disgraceful conduct in almost all aspects thereof that there can never be a repetition. The difficulty however is with the bureaucracy which never admits error (on anything), won’t change its ways, and always finds a means to simply double down and do it all again.

  • bomber49 says:

    The Ruling Elite always knows best.

  • Petrea says:

    And yes, we having been convinced of the cost benefit outcomes being positive for repurposed drugs mentioned plus Zinc, Vit D etc.,

    must not forget that the mandated Rx with experimental mRNA vaccines brought questionable benefit, and was accompanied by multitudinous side effects of a very serious nature on into the future, at great financial, health and personal cost.

  • Stephen Due says:

    When all is said and done, one is left to wonder whether the entire pandemic response might have been vastly better if the government had done absolutely nothing. The GPs would have treated Covid, just as they have always treated respiratory viral infections. Because it was a new virus, there might have been some adjusting to do, but, as Professor Clancy points out, the principles and methods of early treatment were already well known. In addition, many doctors around the world, who were providing early treatment, such as Dr. Chetty in South Africa and Drs. Fareed and Tyson in California, were reporting zero deaths and were sharing their protocols.
    Assuming early treatment of cases was adequate to control the pandemic, most government actions would have been rendered superfluous, including mass testing, contact tracing, quarantining, mask mandates, school closures, social distancing, lockdowns – and the vaccine program. The financial cost of these measures, which were largely useless, was astronomical. But the cost to the general public in terms of an unnecessary burden of disease, financial hardship, loss of employment, business losses, lost school time, the stress of social isolation, separation from sick and dying family members…. that loss, all a result of the government’s determination to thwart early treatment in favour inadequately tested vaccines, was perhaps the greatest disaster Australia has suffered since WW2. And it was all for nothing.

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