https://www.acsh.org/news/2022/03/01/true-story-morphine-milligram-equivalents-mme-16154

The True Story of Morphine Milligram Equivalents (MME)

By Chuck Dinerstein, MD, MBA — March 1, 2022

They are the foundation of the CDC’s 2016 opioid guidelines, resulting in legislation that limits opioid prescribing in 36 states. Morphine milligram equivalents, or MMEs, are used to set arbitrary prescribing limits for opioids by physicians, since many state legislators fail to understand – and translate into policy and law – the ‘16 guidelines. If we had all known the history of MMEs, perhaps we would not have been so eager to embrace them.

Image courtesy of qimono on Pixabay

What exactly is a Morphine Milligram Equivalent (MME)? The CDC defines it as

“The amount of milligrams of morphine an opioid dose is equal to when prescribed. Calculating MME accounts for differences in opioid drug type and strength.” [emphasis added]

MMEs are used in pain management. Clinically, to help transition patients from an ineffective treatment choice to a more effective dosage, form, or medication. Researchers have also used MMEs in attempting to standardize data on medications and prescribing habits when using varying datasets.

The Source of MMEs – Not at all what you’d think

The origin of MMEs seems to be shrouded in the mists of history. The earliest reference to comparing one opioid to another was in a 1974 JAMA article treating the acute pain of myocardial infarction, “Meperidine hydrochloride in parenterally administered doses of 75 mg provides effective analgesia of the same duration as does 10 mg of morphine sulfate.” Two months later, that view of equivalence was rebutted as

“… counter to that of standard texts and journals of pharmacology and is not consistent with our own experience. While it is accepted that the meperidine dose equivalent to 10 mg of morphine is 75 to 100 mg, duration of analgesia by meperidine may be as little as 50% that of morphine. …in chronic or sustained pain, such as occurs in malignant invasion of bones or in sickle cell crisis, the difference is readily apparent to the alert physician and nurse. It has been suggested that physicians are undertreating patients in pain.” [emphasis added]

All the hallmarks of today’s concerns were there.

• Clinical experience
• Equianalgesic dosage (the amount to provide the same level and duration of pain relief)
• The distinction between acute and chronic pain
• Undertreatment of patients in pain

The next reference I found was published in 1984, coming from a study of 38 patients receiving opioids for chronic, non-malignant pain at Memorial Sloan Kettering’s pain clinic.

“A 25-year-old man developed severe left calf pain associated with swelling and tenderness. He was admitted to hospital in June 1975, taking approximately 28 morphine equivalent mg/24 h for pain.” [emphasis added]

There was no citation. The authors relied on their expertise or some unreferenced work to draw that equivalence.

A paper in the journal Pain from 1996 begins to unravel the underlying scientific studies performed in 1936.

“The morphine dose equivalents for hydromorphone and other opioids derive from single dose studies, all of which involved intramuscular or oral administration and measured pain reduction as the therapeutic endpoint.”

But the authors settle for an even more unsettling definition, based on a 1975 paper in the journal Anaesthesiology. The use of this paper to define MMEs is nothing short of astounding:

“Subjective responses to nurse-observer questions were used to quantitate analgesia for postoperative pain. Hydromorphone is more potent than commonly believed: approximately 0.9 to 1.2 mg is equianalgesic with 10 mg of morphine, with a similar incidence of side effects.”  [emphasis added]

It is scientifically illiterate to use this subjective casual observation to form the basis of policy. Yet, this paper is used as a reference by the CDC in its 2016 Opioid Prescribing Guide.

The CDC’s MMEs – Lost in Translation

The CDC explanation of their MME conversions references this paper, Defacto Long-term Opioid Therapy for Non-Cancer Pain, so let’s take a brief look at this study.

It looked at opioid use of adults in two healthcare plans, between 1997 to 2005, reflective of their regional demographics. There is exactly one sentence in the paper that you need to pay attention to:

“The conversion factors were based on information from multiple sources. After reviewing published conversion factors, consensus was reached among two physicians with clinical experience in pain management and a pharmacist pharmacoepidemiologist.” [emphasis added]

The basis of the CDC recommendations comes down to two physicians and a pharmacoepidemiologist. Not overwhelmingly “established” science. Let’s leave those subjective MME conversions to the side for a moment and consider the researchers’ quest to identify a “threshold” to long-term opioid therapy.

In their study, the overwhelming majority of patients took them for less than a month; 80% used opioids for less than a week, 14% took opioids, on average, for only a month. Only 5.5% of the patients receiving opioids took them for longer than a year; they became the focus. In searching for even longer-term use, a possible marker of “addiction,” the researchers found that half of those patients continued therapy into the next year – they were those most likely “to continue frequent use of opioids in future years.” [1] They identified a boundary or signal that an individual’s opioid use might be problematic.

“By setting a clear boundary between acute and episodic use on the one hand, and long-term use on the other, it may be possible for physicians and health plans to establish a check point ….”

There is no mention of MMEs. The variation in the amount of MMEs prescribed or taken among that 6% was too variable [2] to be a threshold; not surprising, given the subjective nature of their calculation. The researcher’s boundary line was the duration of prescribing – a year, the point that would identify that half of the 5.5% they felt to be “at risk.” Most importantly, their boundary was a call to reconsider therapy, not a limit on MME.

Other researchers with similar studies sought their bright line defining those at risk. But quietly, the risk changed from a concern over addiction, as a threshold based on length of treatment would suggest, to a concern over the risk of “overdose.” See the difference in the focus of a 2016 review which concluded

“A clear cut-point in opioid dosage to distinguish between overdose cases and controls was not found. However, lowering the recommended dosage threshold below the 100 MME used in many recent guidelines would affect proportionately few patients not at risk for overdose while potentially benefitting many of those at risk for overdose.”

Somewhere along the way, lost in translation, the concern of addiction morphed to concern over overdose. Despite a lack of “a clear cut-point in opioid dosage,” MMEs replaced fuzziness with pseudo-certainty.

If the ambiguity of what a threshold MME means is insufficient, MME suffers from two additional problems: its calculation and what is being measured. Topics we will address another day.

[1] This does not answer the question of whether their chronic pain had been adequately managed or whether some form of “addiction” or misuse was present.

[2] Among that 6%, there was a greater than 2-fold difference in prescribed amounts and a nearly 4-fold difference in amounts consumed.

Have you ever noticed that “they” always state that non-opiates are “very effective” in treating just about any/all pain, but NO ONE has seemed to use the processes that was originally used to develop the MME’s for all opiates… the basics behind the MME system is – in theory – to compare different “pain meds” ..  but .. apparently no one bothered to include non-opiates when making the MME system comparisons.  Motrin was first marketed in 1975 & Naprosyn was first marketed in 1976 and Aspirin & Tylenol has been around “forever”..

Does anyone, other than me, find it strange that NO ONE has bothered to include these “pain meds ” in the MME system, unless “they” know that the MME ratios would be so pathetic that no medical professional would even consider “prescribing” or recommend a pt taking them for pain.  Not to mention the potential liver and kidney damage that these non-opiates can cause.

Tomorrow is the last day to make a comment on the proposed 2022 CDC opiate dosing guidelines. Should everyone be concerned that the “experts” behind the 2016 & 2022 CDC opiate dosing guidelines were based on and around the MME system that those experts knew or should have known that the MME system was based on NOTHING IN SCIENCE nor any double blind clinical studies.

Here is the link to CDC comment page on the proposed 2022 opiate dosing guidelines https://www.regulations.gov/commenton/CDC-2022-0024-0001  all everyone needs to do is copy the hyperlink to the article  https://www.acsh.org/news/2022/03/01/true-story-morphine-milligram-equivalents-mme-16154 and I suggest that you copy/paste the text of the article as well..  Just request that the CDC rescind/revoke the 2016 guideline and withdrawal the 2022 guidelines…  because both are based on a MME system that has no science and/or double blind clinical studies behind them and in support of them.  You can make comments anonymously !

 

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HHS Secretary Xavier Becerra : Americans are entitled to receive healthcare services

https://www.foxnews.com/politics/biden-hhs-becerra-suggests-support-taxpayer-funded-gender-altering-procedures-children

“Well, Americans are entitled to receive healthcare services. They are entitled to receive any of the case you just mentioned,” Becerra responded.

Later in the exchange, Boebert asked Becerra about a document suggesting removing children from homes is “on the table” if the parents withhold gender-affirming care from their children.

 “Mr. Secretary, do you think that parents who believe in two genders only should have their children removed from them?” Boebert asked?

Becerra responded, “I can respond very quickly. Congresswoman, I believe in supporting and protecting transgender youth. I believe that they, along with their parents and their caregivers, will make the best decisions, and I would really urge that politicians, like you, stay out of their business.”

Last week, the Biden administration released a series of documents encouraging gender-reassignment surgery and hormone treatments for minors.

The Department of Health and Human Services’ Office of Population Affairs released a document titled “Gender Affirming Care and Young People.” The same day, the Substance Abuse and Mental Health Services Administration’s National Child Traumatic Stress Network – another subset of the HHS – released a parallel document titled, “Gender-Affirming Care Is Trauma-Informed Care.”

The HHS documents describe what it calls appropriate treatments for transgender adolescents, including: “‘Top’ surgery – to create male-typical chest shape or enhance breasts;” and “‘Bottom’ surgery – surgery on genitals or reproductive organs, facial feminization or other procedures.”

“Medical and psychosocial gender affirming healthcare practices have been demonstrated to yield lower rates of adverse mental health outcomes, build self-esteem, and improve overall quality of life for transgender and gender diverse youth,” the OPA release states.

The White House released a video to coincide with the new policies featuring President Biden speaking on the issue of transgender children.

HHS did not immediately respond to a request for comment from Fox News Digital.

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A Victory for “Off-Label” Prescription Drug Coverage

https://medicareadvocacy.org/a-victory-for-off-label-prescription-drug-coverage/

On February 11, 2022, the U.S. Court of Appeals for the 11^th Circuit reversed a lower-court decision and found that Medicare must provide coverage for a beneficiary’s off-label use of a medication in Dobson v. Secretary of Health & Human Services, No. 20-11996, 2022 WL 424813 (11^th Cir. Feb. 11, 2022). Florida resident Donald Dobson contacted the Center for Medicare Advocacy because his Medicare Part D plan denied coverage for dronabinol. He could not afford the medication without coverage, but he needed it critically. Since he suffered a spinal cord injury and underwent related surgeries, Mr. Dobson has experienced intractable, severe nausea and vomiting that interfere with his ability to function and other aspects of his health. After standard anti-nausea medications failed to alleviate his symptoms, Mr. Dobson’s physicians prescribed dronabinol (brand name Marinol), which worked immediately.

However, when Mr. Dobson became eligible for Medicare based on his disability, his Part D plan denied coverage of dronabinol. The denial was based on the prescription being “off-label,” meaning it was for a non-FDA approved use. Off-label prescribing is a routine, legal practice, frequently used when medications are needed to treat less-common conditions. But Medicare Part D requires more than a doctor’s prescription for off-label coverage. The program allows for coverage only if there is “support” for a particular off-label use in one of the “drug compendia” specified by Medicare law. The drug compendia are essentially reference books that summarize information on prescription medications, including chemical ingredients, potential side effects, clinical studies, and different uses for the drugs. (The compendia are also commercial publications, available only to paid subscribers, so it can be very difficult for Medicare beneficiaries to access the information they need to argue for off-label coverage of needed medications.)

Medicare agreed that dronabinol was medically necessary for Mr. Dobson. There is also a compendium entry indicating dronabinol’s off-label use for intractable nausea and vomiting that is disease-related – his very condition. Yet Medicare denied coverage on the grounds that his use was not “supported by” that compendium entry because Mr. Dobson did not share exactly the same underlying diagnosis as the patient described in the entry’s cited case study.

Conducting a thorough analysis of the Medicare Part D statute, the 11^th Circuit decided that Congress’s intent was clear. For an off-label use to be “supported by” a compendium citation, the citation “must tend to show or help prove the efficacy and safety of the prescribed medication.” Furthermore, “[n]othing about the common meaning of ‘support’ means that a compendium citation must hyperspecifically identify a prescribed off-label use to tend to show or help prove its efficacy and safety.” Using this commonsense meaning of the word “support,” the court concluded that the listing in question requires Medicare to cover Mr. Dobson’s off-label use of dronabinol.

The Center for Medicare Advocacy plans to issue additional material with further details and practice tips for advocates in light of the decision, assuming it stands. The Center is grateful to co-counsel Florida Health Justice Project and Akin Gump Strauss Hauer & Feld.

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Pushed to Their Limits, 1 in 5 Physicians Intends to Leave Practice

https://jamanetwork.com/journals/jama/fullarticle/2790791

On the same day in March 2020 that President Donald Trump declared the COVID-19 pandemic a national emergency, researchers at the Larry A. Green Center in Virginia launched an ongoing survey of COVID-19’s effects on primary care practices. Over the past 2 years, more than 36 000 survey responses from clinicians across the country have painted an alarming picture of a workforce that’s increasingly burned out, traumatized, anxious, and depressed. As Green Center codirector Rebecca S. Etz, PhD, summed up her survey’s findings in a recent interview with JAMA, “It’s been bad for primary care over the pandemic and it’s getting worse.”

iStock.com/Armand Burger

Another national health care worker survey, the Coping With COVID study, found that burnout approached 50% in 2020 among 9266 physicians across medical disciplines. Last year’s survey results, which haven’t been published yet, are more dire still, according to study coauthor Mark Linzer, MD, a professor of medicine at the University of Minnesota whose research focuses on burnout. His takeaway: burnout has increased considerably as the pandemic has dragged on.

“It has been a very, very trying 2 years for the clinician workforce, and the health care workforce in general,” Linzer said in an interview. “Particularly over the last 6 months, I think people have really just needed to process what they’ve been through and have time to recuperate. But there really has not been time, given all the pent-up demand for care and the continuing pandemic and the Omicron surge.”

Meanwhile, Lotte Dyrbye, MD, MHPE, chief well-being officer for the University of Colorado School of Medicine, said that some physicians have had the opposite experience during the pandemic—too little work. “An important thing to realize is that how the pandemic has affected physicians is incredibly heterogeneous,” she said in an interview.

Many medical specialties saw the workload decrease in the pandemic’s first year and even during subsequent surges, when demand for non–COVID-19–related visits and elective procedures evaporated. Some practices watched their business and finances dry up.

Experts warn that the COVID-19 pandemic, now entering its third year, has pushed an already fragile workforce to the brink. For many clinicians the workplace challenges—ranging from high stress and burnout to understaffing and reduced income, often in combination—have become insurmountable.

Worsening staffing issues are now the biggest stressor for clinicians. Health care worker shortages, especially in rural and otherwise underserved areas of the country, have reached critical and unsustainable levels, according to the National Institute for Occupational Safety and Health (NIOSH).

“The evidence shows that health workers have been leaving the workforce at an alarming rate over the past 2 years,” Thomas R. Cunningham, PhD, a senior behavioral scientist at NIOSH, wrote in a statement emailed to JAMA.

In the absence of national data, Etz says the Green Center data point to a meaningful reduction in the primary care workforce during the pandemic. In the February 2022 survey, 62% of 847 clinicians had personal knowledge of other primary care clinicians who retired early or quit during the pandemic and 29% knew of practices that had closed up shop. That’s on top of a preexisting shortage of general and family medicine physicians. “I think we have a platform that is collapsed, and we haven’t recognized it yet,” Etz said.

In fact, surveys indicate that a “great clinician resignation” lies ahead. A quarter of clinicians said they planned to leave primary care within 3 years in Etz’s February survey. The Coping With COVID study predicts a more widespread clinician exodus: in the pandemic’s first year, 23.8% of the more than 9000 physicians from various disciplines in the study and 40% of 2301 nurses planned to exit their practice in the next 2 years. (The Coping With COVID study was funded by the American Medical Association, the publisher of JAMA.)

A lesson that’s been underscored during the pandemic is that physician wellness has a lot to do with other health workers’ satisfaction. “The ‘great resignation’ is affecting a lot of our staff, who don’t feel necessarily cared for by their organizations,” Linzer said. “The staff are leaving, which leaves the physicians to do more nonphysician work. So really, in order to solve this, we need to pay attention to all of our health care workers.”

Nurses who said they intended to leave their positions within 6 months cited 3 main drivers in an American Nurses Foundation survey: work negatively affecting their health and well-being, insufficient staffing, and a lack of employer support during the pandemic.

“Health care is a team sport,” L. Casey Chosewood, MD, MPH, director of the NIOSH Office for Total Worker Health, wrote in the agency’s emailed statement. “When nurses and other support personnel are under tremendous strain or not able to perform at optimal levels, or when staffing is inadequate, the impact flows both upstream to physicians who then face a heavier workload and loss of efficiency, and downstream impacting patient care and treatment outcomes.”

The pandemic began to take its toll on primary care clinicians early on, says Etz, who is a professor in the department of family medicine and population health at Virginia Commonwealth University. Although primary care offices typically handle the vast majority of respiratory infections in the community, they weren’t prioritized for personal protective equipment (PPE) and other crucial supplies when COVID-19 struck. “Our survey showed, going as far as 6 months into the pandemic, half the [clinicians] still didn’t have PPE,” Etz said. “People were wearing coffee filters and garbage bags to take care of their patients.”

The Green Center survey showed that primary care clinicians’ stress levels improved last summer as vaccines became widely available in the US, but the Delta variant surge reversed this. Since then, physician mental and physical exhaustion has returned to prevaccine levels.

As of this February, only about a fifth of Green Center survey respondents were fully staffed, and 44% had open clinician positions they could not fill. Still, 40% of respondents said they had taken on an influx of new patients whose previous practices closed. The pandemic also required primary care practices to provide new or expanded services—telehealth, home monitoring of patients with COVID-19, and more mental health care, to name a few.

They’ve done all this with limited resources. Throughout the public health crisis, primary care physician practices have struggled with low reimbursement for telehealth and long-overdue payments from insurers, Etz says. Applying for aid, such as Paycheck Protection Program (PPP) or Small Business Association (SBA) loans, was onerous and itself often costly. “The primary care practices that I know that were able to get money from PPP and the SBA loans that were available had to hire accountants to help them figure out how to do it,” Etz said. Unpublished data from various states and task forces suggest that less than 5% of health care sector financial assistance may have gone to primary care, she noted.Trying to do more for patients while dealing with shrinking staff and resources—all during an unprecedented infectious disease crisis—has left some clinicians traumatized. “In our qualitative comments,” Etz said of the Green Survey, “we still get people sharing suicidal ideation. Talking about panic attacks in their sleep and pulling over on their way to work to puke because they’re under so much stress.” Recent survey responses reflect the ongoing distress:

“I cannot continue to work at this pace and retire at 65. I am 50. I am chronically exhausted. There is no relief in sight.”

“I’m burned out. The patients have so much anxiety and it has affected me. I see 21 patients daily for relatively low pay. I’m on my way out of this position—I can’t remain healthy and stay here.”

“I am emotionally traumatized and experiencing severe burnout. I would quit if I was able.”

“I had planned to work for at least 10 more years, now I’m thinking about ways to retire as soon as possible.”

“I have been in practice for over 30 years and have never felt so emotionally and physically drained as I have this year. I have given up trying to correct COVID misinformation and this is so very discouraging.”

“I’ve exited practice. Pray I don’t ever need to go back. It’s miserable with no positive indicators for improvement.”

Etz, who trained as a cultural anthropologist, sees a troubling pattern in the responses: lack of hope. Hopelessness was also apparent in a mid-2021 survey by the nonprofit Physicians Foundation. About 20% of 2504 physicians said they knew a physician who had either considered, attempted, or died by suicide during the COVID-19 pandemic.

Today, frontline clinicians are experiencing high rates of depression, anxiety, sleep disturbance, and posttraumatic stress disorder, according to Dyrbye, who is a member of the National Academies of Medicine’s Clinician Well-being Collaborative. “Many of them are running on the very last steam,” she said. She noted that compassion fatigue, a result of high levels of work stress, has also set in for some: “They’re getting tired of taking care of patients who are incredibly sick and aren’t vaccinated.”

“There’s clearly still widespread burnout, fatigue, and frustration not only related to the earlier phases of the pandemic, but also the aftermath related to shortage of staffing,” Lou Baptista, MD, MPH, executive vice chair of the department of psychiatry at Columbia University Medical Center (CUMC), said in an interview.

As a result, some physicians are cutting their clinical hours for the first time or jumping ship to different institutions where they feel they’ll be better cared for. Baptista says that many mental health professionals at CUMC are leaving for private practice, where they can work fewer days, make more money, and practice telemedicine from the comfort of their own home.

An important mitigator of health care burnout and intention to leave, it turns out, is feeling valued by one’s organization, which Linzer says requires more from employers than simply expressing the sentiment. Dyrbye says health care organizations must undertake systemic steps to improve the work environment. That means finding ways to reduce workload, improve work efficiency, maximize teamwork, and promote a culture of wellness.

Linzer, who directs the Hennepin Healthcare Institute for Professional Worklife, offered a workload solution: if resources allow, float physicians can be hired for periodic coverage, or locum tenens clinicians could be brought in to cover shifts during critical times. “I’m hoping that our health system has learned that as we go through these crises, not unlike in the military, one needs to plan how many times you deploy someone, how long you deploy them for, when you give them a rest to put somebody else in place,” he said.

Early in the pandemic, when time off wasn’t a reality for New York City’s frontline health workers, Baptista helped organize a group of CUMC psychologists and psychiatrists who began volunteering their services to other clinicians in the health system. The program, called CopeColumbia, offered 30-minute peer-to-peer telehealth support sessions, small group sessions customized for different clinical departments, and larger webinars and town halls devoted to topics like stress, trauma, and grief.

“Our thinking was, can we create these brief spaces of just half an hour to give them support,” said Baptista, who last year was named chief well-being officer at ColumbiaDoctors. About a third of the early peer-to-peer sessions led to referrals for clinical care. Over the past 24 months, CopeColumbia has expanded to become the main platform that provides well-being resources and peer support to all medical center employees, not just clinicians.

Last year, NIOSH launched a campaign to address health worker stress, burnout, depression, anxiety, substance use disorders, and suicidal behavior—long-standing problems exacerbated by the pandemic. A goal of the Health Worker Mental Health Initiative is system-wide, organizational-level improvements. The program’s research, funded by the American Rescue Plan Act, could help inform fundamental changes to health care worker shifts, workloads, benefits, time off, and more.

NIOSH’s Chosewood acknowledged the challenge ahead: “The design of work in healthcare needs an overhaul,” he wrote. “Ideally, health worker jobs are so well-designed that doctors, nurses and technicians go home at the end of a fulfilling work day even healthier than when they arrived. I don’t think that’s a pipe dream.”

Linzer agrees that changes are overdue to reduce burnout. “I think there’s a lot of ways that things could be done differently—a lot of work that could be done by others, that would give a chance for physicians to grieve, debrief, heal, and then continue again,” he said. “But the idea of just rushing to start again is, I think, not going to work.”

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Sugar substitutes may interfere with liver’s ability to detoxify, researchers say

https://www.foxnews.com/health/sugar-substitutes-interfere-liver-ability-detoxify

‘With an estimated 40% of Americans regularly consuming non-nutritive sweeteners, it’s important to understand how they affect the body’

Two sugar substitutes, also known as non-nutritive sweeteners, may disrupt the function of a protein that plays an important role in detoxifying the liver and the metabolizing certain drugs, including blood pressure medications and antidepressants, a new study suggested. 

These sweeteners are commonly used in foods and even some medications to give a sweet taste while providing an alternative to table sugar with few or no calories, according to nutrition experts. 

“With an estimated 40% of Americans regularly consuming non-nutritive sweeteners, it’s important to understand how they affect the body,” Laura Danner, a doctoral student at the Medical College of Wisconsin said in the release.

Danner, who presented the new research at the American Society for Biochemistry and Molecular Biology annual meeting this week in Philadelphia, also said in the release, “In fact, many people don’t realize that these sweeteners are found in light or zero-sugar versions of yogurts and snack foods and even in non-food products like liquid medicines and certain cosmetics.” 

Non-nutritive sweeteners, acesulfame potassium and sucralose, were analyzed while using liver cells and cell-free assays, which allow the study of cellular processes such as transport, the authors explained in the release. 

The investigators found that acesulfame potassium and sucralose inhibited the activity of a protein in the body called P-glycoprotein (PGP). PGP pumps many foreign substances out of cells, according to health experts, and is part of a group of transporters that help cleanse the body of drugs, toxins, and drug metabolites. 

“We observed that sweeteners impacted PGP activity in liver cells at concentrations expected through consumption of common foods and beverages, far below the recommended FDA maximum limits,” Stephanie Olivier Van Stichelen, PhD, who lead the research team, said in the release. “To our knowledge, we are the first group to decipher the molecular mechanism by which non-nutritive sweeteners impact detoxification in the liver.” 

According to the team’s work, the study also showed that the sweeteners stimulate transport activity and likely bind to PGP. This causes a competition with and inhibits the transport of other substrates such as xenobiotics, drugs and their metabolites, short-chain lipids and bile acids, the release stated. According to a presentation by Danner, this potentially leaves other PGP substrates such as certain medications left trapped in cells, possibly leading to liver toxicity.

In a case where an individual takes blood pressure medications, antidepressants and antibiotics, which are medications that rely on PGP as a primary detoxification transporter, this could be problematic, the researchers said in the release. 

The researchers did recommend that the findings be further confirmed through preclinical and clinical studies, since their study is preliminary. 

“If future studies confirm that non-nutritive sweeteners impair the body’s detoxification process, it would be essential to study the potential interactions and determine safe levels of consumption for at-risk groups,” Danner said in the release and added, “It might also be important to include specific amounts non-nutritive sweeteners included on food labels so that people can better track their intake.” The researchers noted in the release that PGP also plays a role with maintaining the blood-brain barrier and therefore it is important to explore how inhibition of this protein may interfere with the function of cells in other organs besides the liver. 

The researchers plan on conducting further research on the two sweeteners using more complex models of drug transport and also plan on studying mixes of these sweeteners, since that is typically how they are found in food products.

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Dear Pain Warriors , our feature documentary film on the epidemic of Chronic Pain is going strong on Amazon Prime and Tubi, for FREE . We have 8 stars on IMDB , the international data base of movies.

Our goal is to get it seen by doctors ,nurses , healthcare providers and decision makers . Please SHARE and help us spread the word.

We were just awarded 3 prizes at film festivals around the world for our efforts. People are getting the message that Chronic Pain is a serious issue that MUST be recognized by society. Please help our stories be told. Thanks 

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Perhaps you can help with this relatively new practice of pharmacists in FL.  It just started occurring over the last month or so, where a patient who has been going to the same pharmacy for years, suddenly out of nowhere and without reason, the pharmacist is stating, “l am not comfortable filling this prescription”. Another arbitrary statement is ,”…it’s my clinical opinion you are on too much medication” ( or something to that effect).

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Evidence for Pharmacogenetic Testing in Patients With Treatment-Resistant Depression

https://www.uspharmacist.com/article/evidence-for-pharmacogenetic-testing-in-patients-with-treatmentresistant-depression

Toronto—Pharmacogenetic testing is increasingly a game-changer when it comes to selecting medications for a range of conditions.

In fact, a new Canadian study suggests that it was associated with an 89% increase in remission rates compared with treatment-as-usual (TAU) in patients with treatment-resistant depression (TRD).

The 52-week double-blind study, comparing pharmacogenetic testing-guided treatment to TAU, from the Centre for Addiction and Mental Health (CAMH) in Toronto was published recently in the journal Translational Psychiatry. It is touted as the first-of-its-kind in Canada.

The participants were 276 patients who had been previously diagnosed with TRD; this meant they did not improve after trying at least two antidepressant medications.

“Remission, or full recovery from symptoms, is one of the most challenging endpoints to achieve when treating major depressive disorder,” stated senior author James Kennedy, MD, PhD, head of the Tanenbaum Centre for Pharmacogenetics at the Campbell Family Mental Health Research Institute at CAMH. “The findings from this study contribute the first randomized, controlled data in Canada to the growing body of evidence of the clinical value of combined multi-gene pharmacogenetic testing.”

Pharmacogenetics uses customized genetic testing, usually with a cheek swab, to help clinicians select appropriate drugs and dosages based on their unique genetic makeup.

Background information in the study pointed out that the pharmacological treatment of depression “consists of stages of trial and error, with less than 40% of patients achieving remission during first medication trial.”

The authors noted, however, that in a large, randomized-controlled trial (RCT) in the U.S. called Genomics Used to Improve Depression Decisions (GUIDED), significant improvements in response and remission rates were observed in patients who received treatment guided by combinatorial pharmacogenomic testing.

The Canadian “GAPP-MDD” RCT was a year-long, three-arm, multicenter, participant- and rater–blinded trial that evaluated clinical outcomes among patients with depression whose treatment was guided by combinatorial pharmacogenomic testing compared with TAU. Defined as the outcome was symptom improvement (change in 17-item Hamilton Depression Rating Scale [HAM-D17]) at Week 8. Secondary outcomes included response (>50% decrease in HAM-D17) and remission (HAM-D17 <7) during the same time period.

The researchers found that patients in the guided-care arm had greater symptom improvement (27.6% vs. 22.7%), response (30.3% vs. 22.7%), and remission rates (15.7% vs. 8.3%) compared with TAU, although the differences were not statistically significant. Still, the authors observed that relative improvements in response and remission rates were consistent between the GAPP-MDD (33.0% response, 89.0% remission) and GUIDED (31.0% response, 51.0% remission) trials.

“Together with GUIDED, the results from the GAPP-MDD trial indicate that combinatorial pharmacogenomic testing can be an effective tool to help guide depression treatment in the context of the Canadian healthcare setting,” they wrote.

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