PERSUADE Study: I Guarantee That It Will …

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Peppermint oil (PO) products have been promoted for irritable bowel syndrome (IBS) for quite a long time.  When I have recommended PO as a possible treatment, I frequently say that “I guarantee that it will….give you fresh breath.  It might help your stomach symptoms.”

A recent randomized, double-blind “PERSUADE” study (Zsa Zsa R. M. Weerts et al Gastroenterol 2020; 158: 123-36) shows that PO likely has some efficacy for stomach symptoms in IBS. This trial enrolled 189 patients & 178 completed study (mean age, 34 years, 78% female) from the Netherlands.  Subjects were divided in three groups -instructed to take the study capsule 3/day for 8 weeks:

  • 182 mg small-intestinal release PO-SI
  • 182 mg ileocolonic release PO-IC
  • Placebo

The primary endpoint was at least a 30% decrease in the weekly average of worst daily abdominal pain

Key findings:

  • The primary endpoint did NOT differ significantly between the three groups: PO-SI with 46.8%, PO-IC with 41.3%, and Placebo with 34.4% response.
  • The PO-SI but not PO-IC was associated in secondary improvements compared to placebo in abdominal pain (P=.06), discomfort (P=.02), and IBS severity (P=.02).
  • Adverse events were mild with PO, but more common than placebo. Adverse events included heartburn, belching, and headache.
  • The authors calculate that the number needed to treat with PO-SI would be 8 which is higher than recent ACG monograph which suggested an NNT of 4 (Am J Gastroenterol 2018; 113: 1-18).  Even an NNT of 8 compares favorably with other treatments: linaclotide 6, plecanatide 10, and eluxadoline 12.5.

Limitations:

  • the studied population was mainly young adult, predominantly white and female; thus the findings may not be generalized to other groups
  • the peppermint smell could have undermined blinding despite presentation in capsule form
  • relatively short duration study

The associated editorial by BD Cash (pgs 36-37) notes that PO medicinal use began in 1753 by Carl Linnaeus.  PO is thought to work via smooth muscle calcium channel antagonism.  The findings of working in the small intestine and not ileocolonic release could “spur additional therapeutic development.”

My take (borrowed in part from editorial): “These results reaffirm that PO can improve viscerosensory symptoms of IBS …and is well-tolerated… [It is] clearly not a gangbuster as a monotherapy.”  While the findings show modest effect, the findings are supported by a “robust” study as this is the first randomized, double-blind placebo-controlled clinical trial of PO.

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Also, fidaxomicin has received FDA approval for pediatric use for C diff infections:

Electronic Health Record: 16 minutes Per Patient

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How Allergy Testing Can Lead to More Allergies

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Dr. Dave Stutkus shared some slides (on twitter) recently based on a lecture at Nationwide Children’s.  Since I see children everyday who are undergoing poorly-conceived allergy testing, I wanted to share some of them.

  • Excluding foods from diet based on allergy testing without concurrent symptoms can lead to allergies rather than tolerance:

  • Newer antihistamines are safer

  • Most individuals with penicillin allergy are not truly penicillin allergic.  Also, there is a low rate of cross-reactivity with most cephalosporins.

  • Proper allergy testing relies on the basic understanding that sensitization is not equivalent to being allergic.  In addition, allergy testing has a high rate of false positives; therefore, testing needs to be limited (avoid broad panels).

Also, link to AAP guidelines on breastfeeding & eczema and introduction of foods to minimize development of allergies: The Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants and Children: The Role of Maternal Dietary
Restriction, Breastfeeding, Hydrolyzed Formulas, and Timing of Introduction of Allergenic Complementary Foods

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

USDA Changing School Rules –Policy Should Get an “F”

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From NPR: More Pizza And Fries? USDA Proposes To ‘Simplify’ Obama-Era School Lunch Rules

An excerpt:

The U.S. Department of Agriculture has proposed new rules for school meals aimed at giving administrators more flexibility in what they serve in school cafeterias around the country each day.

For instance, instead of being required to offer higher quantities of nutrient-dense red and orange vegetables such as carrots, peppers and buttternut squash, schools would have more discretion over the varieties of vegetables they offer each day. In addition, students will be allowed to purchase more entree items as a la carte selections…

Critics say the proposed changes from the Trump administration amount to further rollbacks of the nutrition standards put in place during the Obama administration following the passage of the Healthy, Hunger-Free Kids Act of 2010…

“In practice, if finalized, this would create a huge loophole in school nutrition guidelines, paving the way for children to choose pizza, burgers, French fries, and other foods high in calories, saturated fat or sodium in place of balanced school meals every day,” The proposal follows a spate of rule changes announced by Perdue in 2018 that weakened the whole grain requirements and gave school administrators more leeway to serve up white breads and biscuits. 

My take: School lunch standards do not need to be rolled back.  While improving nutrition at schools will not solve the epidemic of obesity, it needs to be at least one piece of a much bigger puzzle.

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Legislative Agenda for Drug Pricing

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There have been some recent terrific advances in pharmacology –a few that come to mind:

The one common feature is that these are all very expensive; there are many other expensive medications with less benefit.  Given the rise in costs of these medications, there is a need to do a better job in getting good value in our drug costs.  A potential path forward is outlined in a recent commentaries (SB Dusetzina, J Oberlander. NEJM 2019; 381: 2081-4; PB Bach. NEJM 2019; 381: 2084-6).

In the first commentary, the authors review the Elijah E Cummings Lower Drug Costs Now Act of 2019 (HR 3).

  • In essence, this act establishes a drug-price negotiation process and limits price increases on existing products.  “Companies whose products are selected for ‘negotiation’ will in reality face price regulation and a severe penalty for noncompliance.”
  • The act would examine U.S. prices compared to prices paid in other countries.  “There would also be a legislatively set maximum price that could not exceed 120% of the average net price paid for the same drug in designated countries.”
  • The bill also would cap Medicare Part D out-of-pocket spending at $2000 per year.

In the second commentary, Dr. Bach notes that drugs that have too little evidence to support full approval and those that are ‘too late in their life cycle’ both should have their pricing negotiated by the government.  This would side step some of the arguments about undermining the incentive for new drug development.

“Too little”

  • The FDA grants approval of some drugs on the market conditionally on the basis of data indicating that they improve a surrogate marker of patient benefit. “Despite the conditional nature of the approval, …the pharmaceutical firms currently charge the same high prices that fully approved drugs capture.”
  • Required studies frequently show that these conditionally-approved medications are ineffective.  Of the 198 indications granted accelerated approval since 1992, only 115 have garnered full approval.  Also, conditional approval may result in less incentive to complete the needed trials in a timely fashion.

“Too late”

  • In this category, the author notes that some medications have found many ways to extend their monopolies, which are intended as a time-limited reward for the effort of developing a new medication.  These include overlapping patents, refusing to provide samples to competitors, and paying other companies to delay bringing generic or biosimilar products to market
  • Most of the potential for savings are in this category rather than the ‘too little’ category
  • Negotiating prices of the top 10 too little and 10 too late medications with reference to 120% of UK pricing would have provided about nearly 27 billion in savings in 2019

My take: While current partisanship makes reaching agreement difficult, targeting soaring pharmaceutical costs is one area in which I predict common ground can be found.  While many are going to benefit from the therapeutic advances listed above, there are other medications which are overpriced and should be negotiated like in other high-income countries.

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Bathroom mural for bicycle enthusiasts (at a stop on the Petit Train du Nord Linear Park)

The Best Information We Have To Date on the Emerging Coronavirus

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The NEJM has made the information it has on the emerging coronavirus open access.  Here are the links:

An excerpt from the editorial:

For the third time in as many decades, a zoonotic coronavirus has crossed species to infect human populations. This virus, provisionally called 2019-nCoV, was first identified in Wuhan, China, in persons exposed to a seafood or wet market. The rapid response of the Chinese public health, clinical, and scientific communities facilitated recognition of the clinical disease and initial understanding of the epidemiology of the infection. First reports indicated that human-to-human transmission was limited or nonexistent, but we now know that such transmission occurs, although to what extent remains unknown. Like outbreaks caused by two other pathogenic human respiratory coronaviruses (severe acute respiratory syndrome coronavirus [SARS-CoV] and Middle East respiratory syndrome coronavirus [MERS-CoV]), 2019-nCoV causes respiratory disease that is often severe.1 As of January 24, 2020, there were more than 800 reported cases, with a mortality rate of 3%…

Both SARS-CoV and MERS-CoV infect intrapulmonary epithelial cells more than cells of the upper airways.4,6 Consequently, transmission occurs primarily from patients with recognized illness and not from patients with mild, nonspecific signs. It appears that 2019-nCoV uses the same cellular receptor as SARS-CoV (human angiotensin-converting enzyme 2 [hACE2]),3 so transmission is expected only after signs of lower respiratory tract disease develop…

It is likely that 2019-nCoV will behave more like SARS-CoV and further adapt to the human host, with enhanced binding to hACE2.

 

Neurologic Toll of Celiac Disease

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A recent prospective cohort study (M Hadjivassiliou et al. Clin Gastroenterol Hepatol 2019; 17: 2678-86) shows an alarmingly-high level of neurologic deficits in 100 consecutive adults (mean age 43 years) with a new diagnosis of celiac disease.

Key findings:

  • Gait instability in 24%
  • Persistent sensory symptoms in 12%; peripheral neuropathy was identified in 2%
  • Frequent headaches in 42%
  • Abnormal results from Brain MRI in 60%; 25% had brain white matter lesions beyond expectation for age group and 46% had abnormal MR spectroscopy of the cerebellum
  • Anti-TG6 antibodies were detected in 40% of patients and this subgroup had significant atrophy of subcortical brain regions compared to patients who were Anti-TG6 antibody-negative

Some neurologic findings improve on a gluten-free diet (GFD).  In previous studies of patients with CD and headaches, 75-80% improved or subsided after a year of strict adherence to a GFD.

My take: This study indicates that early diagnosis of celiac disease along with strict adherence to a gluten-free diet is likely to prevent permanent neurologic disability.

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“Original Sin” and U.S. Health Care

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Several recent articles regarding reforming our current healthcare system have been published in Annals of Internal Medicine (Jan 2020) and are open access.  Highlighted text in images below by Eric Topol, MD.

Link: Envisioning a Better U.S. Health Care System for All: Health Care Delivery and Payment System Reforms

In this position paper, the American College of Physicians (ACP) proposes strategies to address social determinants of health and reduce barriers to care in order to achieve ACP’s vision for a better U.S. health care system for all. The ACP’s vision, outlined in an accompanying call to action (1), includes 10 vision statements, 4 of which are particularly relevant to the policies discussed in this paper (Figure). The companion position papers address improving payment and delivery systems (2) and coverage and cost of care (3). Together, these papers provide a policy framework to achieve ACP’s vision for a better U.S. health care system.

Link: Envisioning a Better U.S. Health Care System for All: Coverage and Cost of Care

Link: The American College of Physician’s Endorsement of Single-Payor Reform

An excerpt:

Public choice’s second purported advantage may also be illusory. Although surveys indicate that voters value choice, it’s choice of doctor and hospital—not insurer—that they care about.
Although no reform achieves perfection, evidence indicates that a well-structured single-payer reform might resolve our nation’s coverage and affordability problems, preserve the choices patients value, and allow doctors to focus on what matters most: caring for our patients.

Link: “Original Sin” and U.S. Health Care

An excerpt:

This series of articles describes a vision and makes important recommendations to improve coverage and control costs; reform health care delivery and payment to promote person-centered; high-value primary care; and address social and environmental determinants of health…

Seen through the lens of the American College of Physicians’ recommendations, how might addressing an original sin of failure to directly finance universal coverage in the United States facilitate progress on other recommendations?…

Implementation of the American College of Physicians’ recommendations, with an emphasis on promoting transparent, direct financing of universal access, holds great promise for replacing the current system of opaque and distorting subsidies with one that better serves all Americans.

Link: A New Vision for Quality and Equity

 

Link: Health is More Than Health Care

Link: Envisioning a Better U.S. Health Care System for All: A Call to Action by the American College of Physicians

Link:  The U.S. Health Care System Is Ill and Needs a Bold New Prescription

Alcohol -More Deadly Than Opioids

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NPR: U.S. Alcohol-Related Deaths Have Doubled, Study Says

An excerpt:

Death certificates spanning 2017 indicate nearly 73,000 people died in the U.S because of liver disease and other alcohol-related illnesses. That is up from just under 36,000 deaths in 1999…

Overall, researchers found men died at a higher rate than women. But when analyzing annual increases in deaths, the largest increase was among white women…

Only cigarettes are deadlier than alcohol: More than 480,000 people die each year in the U.S. because of smoking-related illnesses.

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