Study done by the NIH on antibiotic therapy for Lyme disease.

Discussion in 'Fibromyalgia Main Forum' started by matthewson, Aug 15, 2005.

  1. matthewson

    matthewson New Member


    A clinical study on the efficacy of antibiotic therapy for treating chronic Lyme disease was completed in late 2000. It was funded through a contract awarded to the New England Medical Center (NEMC) in Boston and involved randomized, double-blind, placebo-controlled multicenter studies to examine the safety and efficacy of ceftriaxone and doxycycline for treating patients with either seropositive or seronegative chronic Lyme disease. The clinical protocols for these studies, which have been posted on the NIAID Web site, were developed with extensive review and input from Lyme disease research experts as well as an NIAID Lyme Disease Advisory Panel.

    The panel is composed of patients with Lyme disease, members of patient advocate groups, practicing physicians who treat patients with Lyme disease, and basic research scientists with expertise in either infectious diseases or Lyme disease. The panel provided input on implementing the protocols selected for use in this as well as in intramural clinical studies. Since all of these clinical studies include an extensive research component, they represent the most comprehensive and thorough characterization of Lyme disease extant. They already have provided—and will continue to generate—a wealth of new information that can be used to devise more effective therapeutic approaches.

    On November 14, 2000, the Data and Safety Monitoring Board (DSMB) for NEMC clinical trials on the efficacy of antibiotic therapy for the treatment of chronic Lyme disease reviewed a planned interim analysis of the data obtained. These trials involved testing the safety and efficacy of intensive antibiotic treatment in people with Lyme disease who had developed chronic symptoms, despite earlier treatments with antibiotics. The trials compared treatment with 30 days of intravenous ceftriaxone followed by 60 days of oral doxycycline to treatment with intravenous placebo followed by oral placebo for the same duration, using patients who were either seropositive or seronegative at the time of enrollment. Both trials enrolled patients with a well-documented history of prior Lyme disease and used the same regimen.

    After its review, the DSMB unanimously recommended that NIAID terminate the treatment component of these studies. Their preliminary analysis showed that after 90 days of continuous antibiotic therapy there were no significant differences in the percentage of patients who felt that their symptoms had improved, gotten worse, or stayed the same between the antibiotic treatment and placebo groups in either trial.

    DSMB’s review suggested there was only a slight chance that a difference between the placebo- and antibiotic-treated groups would be found even with continued accrual of another 131 patients, the number needed to reach full enrollment. Therefore, the Board recommended that the treatment component of the studies stop enrolling new patients and that those currently receiving treatment discontinue that therapy. It further recommended that the investigators continue to follow the study patients to monitor their longer-term safety and to obtain additional information that might have value in determining the underlying basis of chronic Lyme disease and in suggesting more effective therapeutic approaches. These rather extensive follow-up studies are still in progress. No new therapeutic studies are contemplated until they have been completed and the results analyzed. The results of the NEMC clinical trials were published in The New England Journal of Medicine (NEJM 345:85-93, 2001).

    In another placebo-controlled study conducted at the State University of New York (SUNY) at Stony Brook, 55 patients with post-treatment chronic Lyme disease (PTCLD) were given either ceftriaxone or placebo (intravenous) for 28 days. They were then evaluated to determine whether there was significant improvement with respect to fatigue, cognitive function, and the clearance of OspA antigen that was present in the spinal fluid of only 16 percent of all enrolled patients. Ceftriaxone therapy was associated with improvement in fatigue but not with other primary outcome markers considered (Neurology 60:1923, 2003).

    It is noteworthy that in both the NEMC and SUNY clinical trials cited above, 40 percent of patients given placebo alone reported improvement in their symptoms (placebo effect). Also, aside from their ability to eliminate persisting infection, several antibiotics have beneficial effects that can alleviate some of the musculoskeletal and neurological symptoms generally associated with chronic Lyme disease. For example, the anti-inflammatory properties of doxycycline and tetracyclines are well-known, and several beta lactam and cephalosporin antibiotics—including ceftriaxone which is commonly used to treat chronic Lyme disease—have neuroprotective properties that can positively influence various neurological disorders (Nature 433: 73-77, 2005). In view of these considerations, valid conclusions on the efficacy of any proposed therapy for treating chronic Lyme disease can be achieved only by conducting carefully designed, placebo-controlled clinical trials in which sufficient numbers of patients are enrolled to permit rigorous statistical analysis.

    Because fatigue, which is a non-specific symptom, was the only primary outcome measure affected and because the treatment examined was associated with adverse events, the results of this study do not support the use of additional antibiotic therapy with parenteral ceftriaxone in post-treatment, persistently fatigued PLS patients. We do not know whether the benefit observed for fatigue is due to antibacterial effects or some other mechanism. Additional follow-up studies on patients enrolled in both the NIAID-supported NEMC and SUNY studies revealed that 28 to 90 days of antibiotic therapy had no beneficial effect with respect to several measures of cognitive function (Neurology 60:1916, 2003).

    Both the intramural and extramural studies mentioned above involve data collection as well as the maintenance of specimen repositories. Such specimens have been made available to other investigators working on Lyme disease and thus have contributed significantly to the development of improved and/or novel diagnostic procedures.

    Appropriate animal models also have provided considerable information on the transmission and pathogenesis of Lyme borreliosis, as well as on the mechanisms involved in the development of protective immunity. NIAID, in collaboration with NINDS, has broadened these efforts to include comprehensive studies on non-human primate animal models for experimental research on the neuropathology associated with chronic Lyme borreliosis. A major goal of these studies is to optimize the Rhesus model of Lyme borreliosis as well as to determine the pathogenesis of the disease with a focus on the neurological manifestations. We anticipate these studies, which were undertaken at the urging of several Lyme disease patient advocates, will expand our knowledge of those factors that contribute to the pathology associated with persistent infection of the central nervous system by B. burgdorferi and ultimately will enable us to devise more effective clinical approaches for treating chronic Lyme borreliosis in humans. They also will supplement and enhance the results of current clinical studies on the efficacy of antibiotic therapies for treating chronic Lyme disease and provide precedents for use in designing future clinical studies.

    Other studies have shown that B. burgdorferi can be detected in mice for at least 3 months after treatment with therapeutic doses of various antibiotics (ceftriaxone, doxycycline, or azithromycin). These surviving spirochetes could not be transmitted to healthy mice and some lacked plasmid genes associated with infectivity. By 6 months, antibiotic-treated mice no longer tested positive for the presence of B. burgdorferi, and even cortisone immunosuppression failed to alter this result; that is, it failed to activate infection. Nine months after antibiotic treatment, low levels of Borrelia DNA still could be detected in some—but not all—of the mice. These findings indicate that noninfectious B. burgdorferi can persist in mice for a limited period of time after antibiotic therapy. The implications of these findings to persistent infection and the nature of chronic Lyme disease in humans remain to be assessed.

    Since various published reports suggested the possibility that B. burgdorferi may play a role in the etiology of Alzheimer’s disease, NIAID intramural scientists examined this issue in greater detail. The results of a recent study, using a very sensitive PCR assay capable of amplifying a Borrelia-specific DNA target sequence from all strains of B. burgdorferi sensu lato species known to cause disease in humans, provided no evidence to indicate the presence of Borrelia in the brains of deceased patients with Alzheimer’s disease. Although the Lyme Urinary Antigen Test (LUAT) is one of several diagnostic tests used routinely in NIAID’s clinical studies on chronic Lyme disease, the results of independent quality control assessments of tests conducted by extramural and intramural scientists showed the LUAT to be unreliable because it yields an unacceptably high percentage of false positive reactions. By contrast, the similar assessments confirmed a high degree of reproducibility and concordance (virtually 100 percent) for the results obtained using ELISA and Western blot assays.

    NIAID expects to sustain a high level of activity in research on Lyme disease in the coming years. It will continue to encourage research on alternative modes of therapy as well as the development of animal models that mimic human infection to enhance or supplement ongoing clinical studies. NIAID investigators conducting controlled clinical studies on therapeutic approaches for treating chronic Lyme disease participated in an NINDS-sponsored conference on neuroborreliosis to facilitate the exchange and application of new knowledge as well as to foster collaborative interactions. Since the complete genome of B. burgdorferi has been sequenced by scientists at The Institute for Genomic Research (TIGR), the widespread application of this information will play a significant role in increasing our understanding of the pathogenesis of Lyme disease at the molecular and cellular levels, as well as to accelerate the development of improved diagnostic tests. Researchers already are applying microarray technology to this end.


    The results of recent studies conducted by NIAID and NINDS intramural scientists indicate that T cells from patients with chronic Lyme disease are reactive not only against B. burgdorferi -specific antigens but also against various host (self) antigens. Such antigenic mimicry has the potential to generate autoimmune inflammatory reactions that could be responsible for arthritic as well as some neurological symptoms associated with chronic Lyme disease. Intramural and extramural scientists are exploring the implications of this finding.

    In other clinical studies conducted by NIAID-supported extramural scientists, case subject patients with symptoms persisting after treatment for acute Lyme disease (patients with PTCLD) and control subjects without such symptoms after the same treatment were compared for the presence of several human leukocyte antigen (HLA) class II (DRB1 and DQB1) genetic markers, some of which are known to be associated with the expression of autoimmune reactivity. The results obtained did not support the involvement of an autoimmune mechanism in PTCLD. However, it is noteworthy that because not all autoimmune diseases are associated with specific HLA haplotypes, these findings do not necessarily exclude that possibility. Definitive proof clearly would involve demonstrating the presence of significant levels of relevant autoimmune antibodies and/or autoreactive T cells in patients with PTCLD but not in treated control subjects without such symptoms.

    Interesting to note the anti-inflammatory properties of doxycycline and tetracycline. Could explain why patients feel better when they are on these antibiotics long term.
    The jury seems to be out though on whether long term antibiotic therapy for chronic lyme disease is effective and no studies that I could find on the effects on the body of long-term treatment with doxycycline.

    And the autoimmune inflammatory reactions that could be responsible for the arthritic and neurological symptoms associated with chronic lyme disease are an interesting sideline.

    I will try to dig up more current research, but I recommend a visit to the NIH site.
  2. tansy

    tansy New Member

    William Harvey has written about this controversy in various papers including



    (Human-transmitted, or late “Lyme” disease)


    In this article Bill Harvey makes an attempt to describes the two different patients groups which help to explain the unnecessary confusion and controversy regarding what is often referred to as chronic or late stage lyme disease. This is his opinion of course but at least it is an attempt to explain what an increasing number of doctors are now finding. Dr Harvey suggests ***One group carries the label “Lyme disease”. The other group, still commonly called “chronic Lyme disease”, is labeled by us as “Epidemic Human Borreliosis”.***

    Extract from the above article

    ***“Lyme disease”

    is well researched and in most ways is exactly as the CDC and texts conceive it. The illness comes from infected animals (called a zoonosis), and is transferred incidentally by an intermediate carrier, primarily a tick. The standard tests for diagnosis, agreed upon by scientists in 1994, are for antibodies, and presume recent infection. Qualifying patients are expected to come primarily from regions where many animals and ticks are infected. Treatment appears successful with oral antibiotics in as short a time as two weeks.

    Unfortunately, chronic patients having many symptoms are considered to be suffering from the effects of the initial infection left by the assumed long-departed spirochete.

    “Epidemic Human Borreliosis”

    is a conceptualization created by us and published in May 2003 in the journal Medical Hypotheses (A copy can be found at this website: It is identical to “chronic Lyme disease”. In the paper, we propose a much larger group of Borrelia infected humans primarily infected by inter-human transfer (mostly mother-to-fetus, but many by sexual contact). Unless treated, patients appear to be infected for life. Symptoms, however, may be absent, progress, cycle, disappear intermittently, or activate unexpectedly. They typically differ from early “Lyme disease” symptoms in the extent of body involvement and lack of swollen, hot joints. Identification of infected patients became possible only after tests were developed assuming low or no antibody presence. Prolonged antibiotic treatment is required to eliminate symptoms successfully.

    “Epidemic Human Borreliosis”

    is a conceptualization created by us and published in May 2003 in the journal Medical Hypotheses (A copy can be found at this website: It is identical to “chronic Lyme disease”. In the paper, we propose a much larger group of Borrelia infected humans primarily infected by inter-human transfer (mostly mother-to-fetus, but many by sexual contact). Unless treated, patients appear to be infected for life. Symptoms, however, may be absent, progress, cycle, disappear intermittently, or activate unexpectedly. They typically differ from early “Lyme disease” symptoms in the extent of body involvement and lack of swollen, hot joints. Identification of infected patients became possible only after tests were developed assuming low or no antibody presence. Prolonged antibiotic treatment is required to eliminate symptoms successfully.

    The present controversy

    stems from the assumptions now built into the “Lyme disease” definition. These arguable assumptions are: (1) The illness comes only from tick vectors, (2) The infection eventually disappears, often within a year, (3) Chronic symptoms come from leftover tissue damage, (4) Antibodies would persist in the patient for years if the spirochete were present, (5) Most Borrelia-infected patients come from, or have visited, tick-borne regions (endemic areas), (6) Chronic patients testing positively for Borrelia who come from outside these endemic areas have false results. (7) Within the U.S., only patients who come from endemic areas and have evidence of recent tick bite are used in most studies of the illness to date. These imposed criteria have literally forced the definition of all Borrelia-infected patients to conform to the strict definition of zoonotic “Lyme disease”. In so doing, chronically ill patients not fitting these criteria have not been studied, leaving undone the research needed to identify, characterize and treat them correctly.

    In summary, virtually all our patients fall outside the rigid definition of “Lyme disease”. Although that term is indeed valid as defined and is precisely as texts and the CDC say it is, we avoid use of it in our patients who do not fit this label.

    We recommend that, if found infected with Borrelia, you avoid use of the term “Lyme disease” completely, and substitute a term such as “Human Borreliosis” until the confusion and misunderstanding of this infection is resolved, either by broadening the definition of “Lyme disease” or adopting an alternative name for the inter-human form.***

    This is why my LLMD uses the terms chronic borreliosis and lyme disease as appropiate; he recommends his patients read Bill Harvey’s papers to understand why the different terms may be important.


    [This Message was Edited on 08/15/2005]
  3. Mikie

    Mikie Moderator

    When dealing with cell-wall-deficient bacteria, it takes at least six months of ABX treatment to effect improvement. It can take years on ABX to destroy mycoplasma bacteria. That the Lyme bacteria can mutate and reactivate would seem to make it even more difficult to treat.

    Do we have members here who have improved after long-term treatment with ABX for Lyme? I would like to hear from them. I know it's not scientific, but anecdotal info is helpful. I know we disagree on this point, but I do hope some of our members with Lyme wade in on this.

    As for long-term treatment with ABX, I think it depends on which type of ABX is used. Many have been on the Doxy for years with no apparent harm. I was on it for 2 1/2 years. As you know, the Doxy doesn't outright kill the bacteria and that may make it safer than those which do.

    Mycoplasma infection also carries the risk of developing an autoimmune illness. The bacteria use the body's own DNA to fool the immune system. Should the immune system stop being fooled and recognize not only the bacteria as foreign but also mistakenly identify any of the body's attached DNA as foreign, it sets the stage for autoimmunity.

    This is why Dr. Nicolson is adamant about taking the ABX long enough to get rid of the mycoplasmas. It can be difficult to decide when one has taken them long enough without followup PCR DNA tests.

    Thanks for posting this. Not everyone will agree with you, as you know. I removed the insulting response and your response to her.

    Love, Mikie
  4. victoria

    victoria New Member

    I agree with you; the abx that are being given to my son are different than what is used in above study and are changed regularly, which makes sense to me as they do different things. I hope the bills get passed in Congress giving $$ to research Lyme further; but at the same time, there needs to be more of a disconnect between gov't funding and big pharma in my opinion.

    is there as much controversy over the treatment of mycoplasma as there is over Lyme?


    ANNXYZ New Member

    of Houston ( immunologist who treats patients from allll
    over the earth ) has recently written a paper on lyme based on her experience treating lyme patients . She reports most patients do not BEGIN to start noticing benefits of ABX therapy until 3-6 months .

    Other members here have posted they began feeling better after their eighth or ninth month of abx treatment .

    The fact that no one in the study was cured of chronic lyme in THREE months does NOT indicate that the patients
    did not really have lyme infections .Who is to say that all
    true lyme infections ( esp chronic lyme) are eradicated in three months of therapy ?

    Anyone who has been treated for lyme OR mycoplasma will tell you that the first three months on antibiotics generally cause one to feel noticeably worse from the
    herxhimer reaction.

  6. Mikie

    Mikie Moderator

    I think it is the Lyme's ability to mutate into other forms which makes it difficult to treat. The mycoplasmas have been developed to have some properties of a virus which makes them more virulent, but they respond to ABX like bacteria.

    The controversy over the mycoplasma infections has centered on Dr. Nicolson's work linking them to GWI. Most mycoplasma bacteria are harmless, so it took a lot of work just to convince the powers that be that mycoplasmas can go chronic and stealth in the body.

    More and more, docs are getting over their reluctance to use ABX in long-term treatment of mycoplasma infections. I think once a doc realizes how dangerous it is to carry these pathogens around inside our cells, including the danger of an autoimmune response, taking the ABX long term makes sense. It's certainly better than leaving a horrible infection to take over a person's body and brain.

    Initially, when a person takes an ABX, the bacteria will become more active in an effort to survivie. That, in addition to the Herxing, can make a person feel much worse. ABX can be more effective at lower doses when combined with Heparin. The Heparin will also cause one to feel worse as the pathogens no longer have the fibrin to hide out in.

    I think one study is not enough to draw absolute conclusions. There are so many variables in these studies. A study such as this would need to be of a longer duration to draw any conclusions about the efficacy of ABX in treating Lyme or any other infection which is chronic.

    If a person has a theory and designs a study, it is likely that the bias will be built into the study and it will turn out to "prove" that theory correct. Many studies are done this way. This is why studies should be viewed with skepticism.

    Just because patients didn't improve in the time limit in the study doesn't mean that this treatment should not be used. They should have been curious enough to extend the study to see whether longer use of the ABX would reduce the symptoms.

    To take this to the rediculous--suppose that strep throat were something new to us. We could theorize that treating it for two days with ABX doesn't work and therefore strep throat shouldn't be treated with ABX. A study which gave the ABX to strep patients for two days would likely reveal the same result as this study did.

    Not only should researchers be very careful in designing their studies, they have to be very careful in the conclusions they draw from those studies.

    Love, Mikie
  7. karatelady52

    karatelady52 New Member

    I am taking Biaxin which is an antibiotic. BUT, they also are giving me Heparin (shots twice a day) to thin the blood and a product called Lumbrokinase which breaks up the fibrin so that the Lyme can't hide.

    I have had some days with more energy and other days where I know I'm herxing big time.


  8. cbs1234

    cbs1234 New Member

    Frankly, I believe Lyme is a fad diagnosis. Some may have it, but it seems to be all the rage with alt docs these days without a lot of good science backing up the diagnosis. I believe you are taking a lot of unnecessary risks by ingesting abx on a long term basis. Many of the side effects of the abx are much worse than the side effects of lyme. You are taking a huge risk by taking abx over the long haul. Especially any of the fluoroquinolones.

    ANNXYZ New Member

    How can you say there is a lack of good science validating the existence of lyme ? Do you think the Bradford microscope is made by Fisher Price ?

    You clearly imply that the side effects of lyme are
    not too troublesome . Do you have lyme ? You seem to discount the thousands of testimonies of people who
    have suffered every kind of imaginable loss , along with pain and damage to organs .

    You obviously do not speak out of personal experience .
  10. Krista47

    Krista47 New Member

    Just putting this info out there.

    The Oregon Health and Science University FMS clinic informed me that their research has found that ABX does not treat Lyme Disease. They did not have an answer for what does.

    I have used ABX to treat it and felt awful during the treatment but once it was over I had the longest remissions I've experienced.

    I appreciate the info on this thread as it has a lot of info that I was pondering. I was wondering if the ABX was really treating the mycoplasmic infection that the Lyme might have mutated to or a coinfection I have.

    From what I've been told by OHSU and have read, what I'm now dealing with is the die-off and left over effects of the initial infection over 16 years ago.

    If that is the case, Dr. Jernigan has a point, and what I need to be doing is detoxing from the die-off that has lodged into my organs and is floating around in my system.

    I hope they continue their work on this. Thanks to all for the helpful info.

    Best regards,
  11. tansy

    tansy New Member

    enabled one specialist/researcher to video the spirochetes emerging from his patients’ blood cells, it’s difficult to dismiss a finding like that.

    By the time my borreliosis was confirmed I pretty much knew this was part of my problems, the inevitable niggling doubts where quickly swept aside by the initial die off on my protocol. But like many here I have additional chronic infections and other health issues, I understand many of them better now and that’s why the last few months have been very much better for me. I cannot say how long this will last, or how things will go in the future, but local PWME/Cs have said "whatever you are taking, we want some too".


    Jernigan’s theories and protocols have had their successes. To get where I am now I have had to consider other factors beyond those directly related to the borrelia.

    Do keep us up to date on how you get on. Info posted here, and on similar boards, proved invaluable for me just as it has for many others.

    Love, Tansy
  12. matthewson

    matthewson New Member

    Could you post a link to that picture. I would like to see it. I have never heard of a Bradford microscope, but I have heard of a Robert Bradford who was associated with laetrile in the 1970's and now heads the Bradford Research Institute.

  13. HppeandMe

    HppeandMe New Member


    How can you possibly state that Lyme doesn't exist? Do you work for the CDC? We don't have the proof needed that CFS and FM are truly a disease but we know they are real! How could you possibly be a person with CFS or FM and say such a thing?? Maybe you are in denial or maybe you just are on the board for fun.

    Many of us are severely ill including myself and I may have Lyme, CFS or both. I have been diagnosed with both and never in my life would ever doubt anyone again about anything they are feeling. Unless you have some concrete evidence and are sure Lyme doesn't exist than please don't insult our intelligence.

    Thank You.
  14. victoria

    victoria New Member

    Very interesting about mycoplasmas; as scary as lyme. What's next?

    I agree about responses to abx. My son is a good example for lyme; had his 3rd lyme app't today... After reviewing what his responses have been to the different combinations of abx, it is obvious what is working the best for him. As they explained, there are different strains of the Bb and they respond differently to the different abx.

    So, when he felt the worse (during first month), that combination of abx was doing the most, altho he didn't feel much better than he had prior to taking any abx during his week off from abx;

    he felt slightly less worse during 2nd month's combination but felt better during the week off between courses;

    and after going off the last month's combination of abx for this last week, he didn't feel ANY better, unlike the times before.

    So that would mean this last month's abx weren't really doing anything. He is starting back on the combination he took the second month, then after a month will take the combination he took the first time.

    Hmmm, this may cause some controversy here...

    but, seems like everything I'm ever involved with is always controversial... probably true for most of us with these DDs!


    [This Message was Edited on 08/16/2005]
  15. dontlikeliver

    dontlikeliver New Member

    I know I am only one person on here, and my long-term time on abx is not even that long, 14 months, I have improved a lot.

    Most others I know of, who are way ahead of me and doing well (working full-time, having a life, even having babies) are not posting on these (Lyme) forums anymore. I don't blame them either.

    In addition to the abx taking a long time to make any difference, once has to be on the right antibiotic, the right antibiotic combinations, and know when to switch, as well as be on the right dosage.
  16. ANNXYZ

    ANNXYZ New Member

    It is encouraging to hear you are improving and that ABX
    are helping . It is also great to hear that you are acquainted with others who are regaining their health and lives . I am on them also and hoping for a good outcome
    eventually , though I realize there is no garauntee.
  17. tansy

    tansy New Member

    I wrote about were carried out at conferences, making them all the more convincing since no editing was involved; patients have also been able to see what has been identified for themselves using this technique.

    There are links to images at

    love, Tansy
  18. dontlikeliver

    dontlikeliver New Member


    I am glad to hear of your improvement, and although there appears to be some negativity about Lyme on this board (and, OK, it is as FM/CFS board after all), it makes it worthwhile (to come back here and get a bit bashed from time to time) for me to hear that another patient who was dx'd with CFS/FM (or whatever) is getting well finally, with a right diagnosis and right treatment.

  19. karatelady52

    karatelady52 New Member

    Your post was very encouraging to me. I've only been on antibiotics (Biaxin also) for a week so I have a long way to go and I keep wondering if I need to be on this to get better. The Biaxin made me feel so sick the first couple of days but its better now. The metallic taste is awful. Did you continue to taste it?

    I'm doing other treatments alongside the antibiotic to help with coagulation and breaking up the fibrin in the blood.

    I had 5 positive bands on the IgM and one on the IgG Western blot.

    So thanks for posting. We need to hear encouraging stories because of the length of treatment.

  20. dontlikeliver

    dontlikeliver New Member

    I took Biaxin (with Atovaquone) for 9 months. The odd taste never went away, but I did get used to it, FYI.


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