Real World Study or Reality Show

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Recently investigators working at the Minneapolis VA Hospital conducted a study examining the efficacy of nonopioids vs opioids in a “pragmatic randomized trial” in knee and low back pain. After considerable angst and restraint, I teamed up once again with Dr. Morty Fein to clarify significant and glaring inconsistencies inherent to this study and how it can only serve to mislead lay press journalists, politicians, and even clinicians that are naïve to sound scientific research and what constitutes validity.

In general, a study like the one above is difficult to conduct, with considerable challenges in enrolling and retaining subjects. The authors are to be commended for taking this study on and for completing it, but that’s about all the kudos they get. Like many studies of its kind, it has many warts and indeed it is tremendously flawed in some ways. That is forgivable. What is not, is the misinterpretation and misstatement of the meaning of the results given how deeply defective this inquiry truly is.

The authors concluded that opioids work no better than nonopioids. They could not show that opioids were more harmful, but they jumped on the anti-opioid fame wagon nonetheless and intimated that opioids are much more harmful and had they had longer they would have demonstrated that too. If they had a modicum of humility, they would have concluded that the opioid algorithm they employed in this study is deeply flawed, and that it needs to be amended. And that when you enshrine and institutionalize non-individualized dosing and keep doses of opioid monotherapy really low, you can enshrine and institutionalize clinical mediocrity. In this way, this study continues a trend, inherent in the CDC guidelines that will ultimately render opioid therapy completely useless by separating out only the responders to the lowest of doses. And testing these doses with an enriched sample of non-opioid responders in one group and an unenriched sample in the opioid group is stacking the deck. Not just against opioids – against patients. Rather than further dignify these approaches, we start calling them “blind-leading-the-blind-lines.” We are creating an opioid strawman that limits the help opioids can afford people with these approaches, and all the while the opioid epidemic has moved on. So in effect, these blind-leading-the-blind-lines that violate every principle of good opioid therapeutics are willing to do so in a misguided effort to end a heroin and illicit fentanyl crisis.

Don’t get us wrong – the old opioid strawman, the “no ceiling, escalate to the stratosphere for every patient done by non-experts with no monitoring” strawman was no better and it caused much harm. We haven’t shown a willingness or ability as a field to really change the standard of care, utilize the tools and practices that have emerged in the interim and individualize care. Instead, we are in a phase of ascientific, watered down opioid therapy that also causes much harm and suffering. One set of bad practices doesn’t justify another, and we grow increasingly pessimistic that this world will ever be able to stop conflating bad opioid practices with bad opioid outcomes and ever have our patients realize what is the true safety and efficacy of opioid therapy when conducted in a more expert fashion.

We don’t know what a pragmatic randomized trial is. Pragmatic supposedly means useful, because this study will prove really useful to the anti-opioid propogandists. We think they meant pragmatic as in real world. But in the real world nobody that knows anything about opioid therapeutics practices like this. So it isn’t real world. The interpretation of this study by the authors, the journal reviewers and by local news talking heads is more like a reality show than real world. Borrowing Trump’s mantra from The Apprentice, study authors, JAMA, and CDC: You’re fired!

And here is the proof of the pudding. Had the results of this study been in favor of opioids there is no way the editors of JAMA would have accepted it and published it given the flaws. As authors and editors of various peer reviewed journals, we are certain of this. If they deny it, they are even more unaware of their anti-opioid bias then they know. Hey JAMA: you’re fired!  Ah, if only we were younger the bar for a JAMA pub was this low.

Here’s some food for thought. This is the same VA that has already begun to minimize the findings coming out that their opioid guidelines and lowering of morphine equivalent daily doses (MEDDs) that has led to an increase in overdoses and suicides with a spike at 50mgs of MEDDs. God bless Dr. Stefan Kertasz for reporting these results in What’s Wrong With Just Counting the Patients on High Dose Opioids and Calling that Bad Care? (3 addiction docs respond to CMS). And why would that happen? Opioid mediocrity leads to people supplementing with illicit opioids and anything they can get and then when the “oxy” or heroin they think they’re buying turns out to be Chinese fentanyl it’s “zaijian”.

The non-opioid group in this study supplemented more with illicit drugs too…we wonder why. With no detail about the nature of the urine drug monitoring used and the frequency of use, we suspect that there was a lot more of this use than they even report out. If we had longer we might be able to prove that.

To have a shred for applicability, the research would need to include a cross-over study putting all of the opioid patients on non-opioids and all of the non-opioid patients on opioids to see if they maintain their same levels of pain.  They also need to go out for more than 1-year to see how many patients on chronic NSAIDS end up with a GI bleed, heart failure, or kidney dysfunction and compare that against incidents of opioid-induced respiratory depression, and then look at drug related deaths from both groups. 

We can drone on to enumerate a list as long as your arm of the methodologic flaws of the study. They may be forgivable. The misrepresentation of what they say are unforgivable. JAMA publishing this garbage is unforgivable. We are now clearly in a world of alternative opioid facts, an altered universe, virtual unreality – not the real world.

Please feel free to comment!

27 thoughts on “Real World Study or Reality Show

  1. In parallel with Jeffrey Fudin and Morty Fein, I also took on some of the glaring weaknesses in the Krebs trials, in an article published this morning on the American Council on Science and Health. That article is available at

    The analogy that I drew was this: “The bottom line is that the study seems to have set up to give a predetermined result: to discredit opioids in favor of NSAIDs and Tylenol. It was a bit like staging a race between some contestants in leg-irons versus others who ran after taking steroids for months.”

  2. I also advise posters here to visit and do this immediately after you read this. There have been some articles there that have been extremely informative about Erin Kreb’s and PROP, Andrew Kolodny and Jane Ballantyne to name a few, and make sure that you go through the stories as soon as possible to get to the perhaps real gems in articles that have been posted there – follow Chriss Rogers and of course the editor Pat Anson, and bookmark pages. FOLLOW the articles mentioned in the articles as soon as you have bookmarked the most interesting articles according to their names. And for heavens sakes, pass this around… show articles to others, friends and loved ones. There will be a contnual treasure trove there I guarantee you.

    Maybe one day OUR families and friends and loved ones will represent us in thisongoing travesty against legirtimate pain patients.

  3. What on earth has happened to using validated methods and tools for proving or disproving a hypothesis? JAMA, once a respected peer-reviewed journal, is obviously more concerned about making profits. A sad day for science when investigators are more interested in proving their opinion rather than following where facts take them. Thank you for your brilliant account and holding the moth to the flame, Dr. Fudin.

  4. This study excluded patients who were previously taking opioids A year of treatment with opioid monotherapy (< 100mg oral morphine/day) did not improve pain-related functioning better than nonopioid multimodal therapy (oral and topical nonopioids; SNRI/gabapentinoids and tramadol). Conclusions should have include caveats that 26% of nonopioid patients received tramadol and twice as many “nonopioid” patients screened positive for illicit drugs and received mental health services more than their opioid counterparts.

  5. Thank you, Dr. Fudin for publishing the article and the commented you received. While I continue to be shocked by the misinformation, “ dis” information and value-laden comments stating that those of us suffering chronic, debilitating pain are abusers and addicts. And that these “conditions” are due to prescription Opioid meds. Clearly none of these so- called healthcare providers or comment writers have ever suffered pain that caused them to retire way before they wanted to, not be able to get out of bed. Or indeed have any quality of life. In my 77 years, starting in 1975 at age 34, I have had breast cancer, 20 spinal surgeries many with instrumentation in both my cervical and lumbar spine, have Ehler- Danlos Syndrome, Fibromyalgia, Chronic Fatigue, total knee replacement………I have, over the years been on every conceivable NSAID, “ approved medications such as Cymbalta(currently the subject of a class action lawsuit against Eli Lily) Celebrex, Lyrica, neurontin, and others. None of these helped. Many of them caused severe side effects that rendered them unusable. Believing that perhaps these so- called experts” were correct, in 2015, I voluntarily entered an inpatient chronic pain program ( was there 40 days)that included detoxing from Fentanyl and withdrawing from Cymbalta in order to establish my true “ pain baseline”. The conclusion was that I responded to opioids, was neither an abuser or an addict. I have not increased my dosage since then, I have no adverse side effects. I have some quality of life back though far from anything beyond being able to take care of myself! I have never been “ high”, do not take them to “ feel good”, and with the help of my physician have learned that I will never be pain free, but have made my peace with that with the level of relief afforded me my the Opioid I take.
    I am beyond distressed at the powers that be who get to impose their biases on people like me. I wish there was a way to have them live in my body just long enough to know what ongoing, daily, debilitating pain is. It would only take a day….2 at the most I am sure for them to recognize our pain is real. Life destroying. Unbearable. It is time, way beyond time, to have their so- called “ studies” tell “ the other side of the so- called opioid epidemic”. How about simply separating out chronic pain sufferers from “ junkies”. The statistics are quite different. Stop blaming the victims. Examine your motives. Confront your prejudices, . Stop good, caring, responsible physicians from leaving their practices due to the malignant, uninformed professionals and agencies who currently have set forth guidelines, rules, etc. that violate the Hippocratic oath of “ first, do no harm”.

    1. Thank you ! You are so right. They take away the med’s for chronic pain because the junkies are mixing the deadly drugs together..

  6. With all due respect to all the comments made….

    If this trial is to be criticized (and perhaps some of those criticisms are justified), I would just like someone to tell me where the positive trial data exists in the literature? We’re unfortunately not debating positive data versus negative data. We are debating negative data versus the absence of any data at all. If there is a subset of patients (and I would agree that in all likelihood this group does exist) who can indeed show improvements in pain and function on long term opioid therapy, why has a study never been conducted and published that supports this? Assuming it has NOT already been attempted and failed to show positive results, how would those who are criticizing this JAMA study propose we go about devising a better study?

    After many years of clinical practice in this field and watching first hand patient responses to opioid therapy, I have found it without doubt to be the case that opioid therapy can indeed result in diminished pain control for a not insignificant number of patients. Is this not at least somewhat consistent with theories on hyperalgesia, etc?


      Pain Pract. 2006 Dec;6(4):254-64.
      A study of AVINZA (morphine sulfate extended-release capsules) for chronic moderate-to-severe noncancer pain conducted under real-world treatment conditions–the ACCPT Study.

      “This study showed that once-daily AVINZA significantly reduced pain scores, and resulted in improved sleep and physical functioning in patients with chronic moderate-to-severe pain. These results were achieved with a stable daily morphine dose over the three-month study period.”

    2. Still true:
      “The published literature continues to be very limited, but a growing clinical experience, combined with a critical reevaluation of issues related to efficacy, safety, and addiction or abuse, suggests that there is a subpopulation of patients with chronic pain that can achieve sustained partial analgesia from opioid therapy without the occurrence of intolerable side effects or the development of aberrant drug-related behaviors. Future research must confirm this impression, through controlled clinical trials and clarify those factors that may predict therapeutic success or failure.” – April 1996Volume 11, Issue 4, Pages 203–217
      Opioid therapy for chronic nonmalignant pain: a review of the critical issues
      Russell K. Portenoy, MD

    3. Keith Warshany, I suffer from Traumatic Brain Injury due to being electrocuted in 1991 at the age of 29. I was one of those horrible pharmaceutical sales representatives at the time of the accident. There’s not enough space to tell my story, but I will say a few things: I’ve torn ligaments and cartilage in my knee, I’ve broken the same wrist bone 4-5 times, and I’ve ruptured spinal discs L-4 & L-5. The pain experienced when each of those injuries initially occurred is nothing – absolutely nothing – compared to the head pain that I’ve lived with on a nearly daily basis for 27 years now. I’ve tried every treatment, non-traditional and traditional, you can think of as a physician: acupuncture until the practitioner told me to stop; hypnosis on a dozen occasions; 2 separate weeks spent at two highly rated pain clinics where I mastered biofeedback, relaxation and even meditation (I choose prayer over meditation by a long-shot); deep tissue massage; strict diet; and even aromatherapy. I’ve been prescribed blood pressure med; anti-seizure meds; antidepressants; every migraine medicine from the 50′ until the next one comes out; and more that I can’t recall. (Probably due to the brain damage to the right frontal lobe or the increasing abnormal white matter or possibly the nerves destroyed by the 15 minutes of being electrocuted before I was found.) As for “narcotics” as they used to be called, I’ve was started on a 5mg/acetaminophen pill, 2 per day. Then, after a year or so, I was given the next strength level of pills, maybe 3 per day. At two separate points, I went a calendar year without any narcotic pain meds to determine whether my pain was due to “bounce back” headaches. (I never use “ache” because this is severe “pain”.) All of this happened with different doctors because when one couldn’t “help” me, I was passed on to another doctor. Eventually, I had a doctor who was writing me so many pain pills that I couldn’t take them all – and they didn’t work. Every time I told this particular doctor I wasn’t getting relief, she wrote more. I can’t recall how many I ended up returning to my one pharmacy for disposal. Oh, and during all these years, I was having to go to the ER for shots at least once a month, minimum. All the while, I’d get treated as a drug seeker, even though I didn’t suffer from withdrawals or buy/use any illegal drugs (it’s deja vu all over again, now). In 2002, when I was ready to leave this pain behind, I found a neuropsychiatrist who is a Pain Management Specialist. Finally, without my asking because I didn’t know it existed, he put me on fentanyl patches and fentanyl lozenges for breakthrough pain. After about a year and a half of adjustments, I/we found the right combination. Guess what happened? I’ve NEVER been back to an ER. I still suffer from severe flares that require time spent in the “pain room” my wife and I have had in all three homes we’ve lived in. It may last for 3 days or 13 days, but this medicine helps it get below a 10, which is a suicide level of pain. I have had only one adjustment to these meds in 16 YEARS. And all this time, I’ve been living with osteoarthritis in my right knee which should have been replaced two years ago according to the doctor who performed my fourth surgery 6 years ago. My second ruptured spinal disc happened in 2010, mainly because I’ve spent 75% of my life in bed since 1991. So, I live with the same pain as these test subjects, but I never want to take any more medicine. Because now, I have a somewhat semi-normal life now. I go to church occasionally and can see friends sometimes, unlike 1991 – 2002 when I rarely left the house. I don’t abuse my meds because they can’t be abused, no matter what the druggie abusers say. Chewing on a patch is stupid and risky. I certainly have a physical dependence on these meds, but I am not an addict. I’ve passed every urine drug test at every appointment. So now the CMS, CDC, and DOJ/DEA are going to bust every doctor prescribing “too much opioids” or the insurance company will deny my script because it’s “too much opioids”?! Live my life for ONE MONTH. I dare you or any other anti-opioid miscreant. You couldn’t do it, not without opioids. No freakin’ way.

    4. In the trials & studies I’ve seen in the past few years almost half the patients getting nonopioids did not take long to realize which group they were in and dropped out rather than participate for a year. Some of those studies dont bother to tell you that.
      I agree that instead of punishing millions of chronic, noncancer patients weed out the addicts and get back to practicing good pain management.

    5. Long term studies in the USA are problematically few for numerous reasons but 1 of the main ones is the fact that the FDA requirement in this area is only 3 months duration. That being said, “the absence of evidence is not the evidence of absence”
      There is a wealth of anecdotal information supporting the long term effectiveness of opioid pain medications. Whatever happened to the concept in medicine of “ask the patient how they are doing” Quality of life is by far the most important factor. If opioids are prescribed responsibly and patients carefully monitored they can literally be a life saver for people suffering chronic and/or intractable pain.

      There’s a great article by Josh Bloom that touches on the anti opioid zealots never ending screeching about long term opioid use. You can find it here:

      Also Dr. Forest Tennant published findings of a study he did over a 10 year period. To say Dr. Tennant is one of the most highly respected medical professionals in the pain field. You can read it for yourself here:


  7. Serving in the trenches of primary care medicine I have felt opioids are worse then other modalities of pain control for chronic non cancer pain. I am glad organized medicine is finally realizing this. Life might entail pain, and modern medicine really has no cure. Sorry I agree with this study even if flawed. I do not agree that chronic daily exposure to opioids is needed in any chronic non cancer pain.

    1. Good for you – I hope that a family member or you never end up with a constellation of complex medical problem(s) topped off with arachnoiditis after enduring a motor vehicle accident, losing a limb, and topped off rheumatoid arthritis. A person like this would rather die from cancer than endure the pain. Your comments are quite heartless for a physician, especially when admitting that the study is flawed.

    2. You may not feel that way if you suffered severe, chronic 24/7 pain, Jeff. I have been on opioids for over seven years and my quality of life has greatly improved. I’ve gone from housebound to a happy, productive person.

    3. Jeff, in the trenches” Might I ask, how your health is, your age and if you or your spouse was suffering from an incurable genetic diease or life altering illness or injury. Perhaps you would care to share your hypothetical treatment plan? Long term NSAID’s what if there is an allergy or a history of GI problems, Pancreatic reactions etc.? How about corticosteroids, maybe prednisone! Oh but the aromatase inhibitor required due to cancer battle conflicts and can result in hypoxia and certainly isn’t advised given the HER2 positive Dx ? I hear all of the “bad” attributed to opioids. However, I have yet to hear the truth about the lack of other longterm successful treatments +/-. Quite frankly if you have never suffered from…we’ll say cancer or amputation, autoimmune, neurological or an orthopedic disorder from birth or any of the far too many to list illness’s, You are, in my POV not unlike the person in the grocery line, exclaiming oh I’m so sorry to hear of your illness. You look good with no hair .My grandmother had cancer, it was awful. So hard to watch…. it was a blessing that she finally DIED! Keep on with the rhetoric. Fact is if you haven’t been impacted personally, look at the numbers. It isn’t a matter of if only a matter of when! I would really like your take on what you think works for severe intractable pain, in a difficult case. A case your personally invested in. Also, why is there data and testing available which can indicate how a person metabolizes medications along with actual real data regarding inflammation, c reactive, Sed rates etc. Risk vs Benefit…is it better for anyone to be less active to not active due to chronic pain, how about the effects of extended HBP on every system, depression due to inability to work or interact with family, friends, hobbies etc vs the evil opioid medications? Also why is it necessary to NOT explain the differences between illicit and legal and the actual numbers ( heroin vs Morphine or illegal street Fentanyl /carfentanyl vs legal Duragesic patch and please what are the method or mode of onboarding and the difference that can make as well… i.e. IV heroin use, time released transdermal patch? It seems odd to me I have yet to see any legitimate abuser upset or outcry that they can’t get their Rx for an overpriced monthly medication, only after jumping thru hoops such as monitoring, UA’s (paid for by patient), unscheduled time from work for surprise counts ( again patient is charged) etc. oh and don’t forget the monthly cost of insurance and the co pay or if no insurance straight cash pay, regardless, going every 1 to 3 months to the physician. They’re not, why is that? Perhaps because it ‘s cheaper and easier to simply go to illicit means. With all due respect, I would love to hear your thoughts…. thank you.

  8. Here are my comments on a paper in the current JAMA called “Effect of opioid vs nonopijoid medications on pain-related function in patients with chronic backpain or hip or knee osteoarthritis pain: The SPACE randomized clinical trial.” The conclusions, were: “Treatment with opioids was not superior to treatment with nonopioid medications for improving pain-related function over 12 months. Results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain.”

    The conclusions of this study were front-page news in yesterday’s Arizona Daily Star. I’m sure they were front-page news because they support the public perception that the cause of the opioid crisis is doctor prescribing.

    I found the paper very confusing. The authors recruited VA “patients with OA-related back, knee, or hip pain and randomized patients with at least moderate severity despite analgesic use” to either opioid treatment or nonopioid therapy (acetaminophen, NSAIDs). They were followed for 1 year. I found multiple problems with the report:

    I. The Study population

    1. There is no mention of WHAT analgesics and what doses the patients were taking at the start of the study.
    2. “Patients on long-term opioid therapy were excluded.”
    3. The Figure (p. 874) says that patients who were using opioids or benzos were excluded from the study.
    4. The last sentence in the Limitations section says “Patients with physiological opioid dependence due to ongoing opioid use were excluded, so results do not apply to this population.”

    What does this information tell us about the patient population on which this study is based? We don’t know how long the patients were having the OA-related pain. We don’t know what other modalities were being used before the study. What we know is that patients whose pain was enough to have resulted in being prescribed opioids and/or bentos were EXCLUDED from the study; had they been included, it makes sense to think that they would have done better if treated with opioids than only with acetaminophen or NSAIDs. Thus, this entire study is only about patients with relatively moderate pain, not (as the title implies) a random group of OA-related pain patients.

    II. The Treatment
    1.There is no mention of what non-opioid meds or other modalities were also used in any of the patients. Physical therapy? Home exercise? Psychological?
    2. Tables 4 states that tramadol was not considered an opioid in the study — meaning that 1 or more patients in the control group may have been given tramadol, which is certainly an opioid.
    3. “Opioids were titrated to a maximum daily dosage of 100 mg morphine equivalents”, Also it says (p. 879 last paragraph), “In each 90-day follow-up period, fewer than 15% of the patients in the opioid group had a mean dispensed dosage of ≥50 ME/day or more.”

    What does this tell us? That the great majority of the patients in the opioid group were given only 50 ME/day or less. Remember that a typical starting dose for any type of pain is Percocet 5 mg, 1-2 qid prn, which is 40 mg oxycodone/day, which is 60 mg ME/day. A rather low dose, yet more than most of the opioid group were given. Which would of course diminish the number of patients who might benefit “from opioids” when the dose is that low.

    In other words, from what I can tell, this study is based on a patient population that at the start of the study did not have a lot of pain, and in which the opioid treatment group received only a rather low dose of opioids. I do not think that one can generalize from this study to the benefit, or lack thereof, of opioid treatment for OA-related back, knee or hip pain. Opioids may still be very helpful for many people with OA. To say that opioid treatment is not useful for OA, which is what the newspaper article (and others. . .) said, cannot be legitimately concluded from this study.
    Jennifer Schneider, M.D., Ph.D. Internal Medicine, Pain Management & Addiction specialist

    1. I also find it interesting that this trial stopped at 12 months given the heavy criticism the CDC guidelines placed on trials that did not go beyond a year.

      1. Agreed! A wellxwritten and helpful exposition of the facts. How sad, though, that is will convince everyone – since we are just a headline society, and so few will understand these crucial issues.. But we will persevere and educate as we can!

  9. My husband is a disabled Veteran. He suffers from mixed connective tissue disorder, has 3 non-operable disc herniations in his neck, post shoulder surgery and bilateral carpal tunnel release. He has service-connected anterior and posterior fusion from L3-4 to L5-S1. He has 3 disc herniation with significant stenosis and impingement above the fusion that they won’t touch, and we understand that. He has very significant neuropathy down his legs and into his feet. Last winter, while in Indiana (we’re FL residents and that’s where his V.A. doctors are) my husband saw his prior PCP for problems he was having with low testosterone levels that was causing him to experience signs of anxiety and aggressive behavior that was completely out of character for him. The doctor gave him hormone therapy and .025 mg Xanax for anxiety. Last summer, after my own back surgery and evacuation from Irma, we had lots to do and I decided to call in refills for the meds we were low on. He, of course takes lots of non-narcotic drugs such as synthyroid. Placquinal for the mixed connective tissue disorder, blood pressure Med, etc. His pain medicine from the V.A. was Tramadol and Gabapentin. Pretty heavy stuff, right? By accident, this summer, I refilled that 30 day refill for .025 mg Xanax. No big deal, I thought. When he called the V.A. to refill his Tramadol, he received a letter through the mail starting they wouldn’t refill the Tramadol because he had received Xanax (the lowest dose possible) from an outside source. When we got online, we found they also d/c’d his Gabapentin. So with all he’s got going on, he’s gone months now without any pain medication. He’s lost some functioning and is in significant pain 24/7. So if the V.A. think NSAIDS works better than even a low-tiered Opioid such as Tramadol, I’ll respectfully submit that they are out of their freaking minds. My husband got no appointment to discuss it or even a stinking phone call. The gutless wonders sent him a letter to say what diminished quality of life you were able to achieve using Tramadol to control your pain is done. Over. You messed up, dude, it’s over. I guess I got off point. In summary, there is no comparison – NSAIDS are not effective for pain, especially neuropathy, and they’re out of their stinking minds if they think even Tramadol isn’t more effective. I tried to tell this as professionally as I could. You wouldn’t want to hear what I’d really like to say about my hysband’s Suffering for months now. Thank you for your service, but we found a reason to say SCREW YOU! Up go out stats. Yay! Another Veteran off opioids. Yippie-Kit-YO-KI-Yay!!! Screw you VA! Thankfully we still have our BCBS. We’re moving out of the Sunshine State to be where our real doctors are. So our dreams of retiring in Florida didn’t work out. You do what ya gotta do.

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