Longevity Gap Present Even in Wealthy Americans

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S Machado et al. NEJM 2025;392:1310-1319. Association between Wealth and Mortality in the United States and Europe

Methods: This was a longitudinal, retrospective cohort study with 73,838 adults (mean [±SD] age, 65±9.8 years), a total of 13,802 (18.7%) died during a median follow-up of 10 years.

Key findings:

  • The gap in survival between the top and bottom wealth quartiles was wider in the United States than in Europe
  • The poorest Americans appeared to have the lowest survival among all wealth groups in the study sample
  • Survival among the participants in the top wealth quartiles in northern and western Europe and southern Europe appeared to be higher than that among the wealthiest Americans
  • Survival in the wealthiest U.S. quartile appeared to be similar to that in the poorest quartile in northern and western Europe

The countries in the Survey of Health, Ageing, and Retirement in Europe (SHARE) were split into the following three groups: northern and western Europe (Austria, Belgium, Denmark, France, Germany, the Netherlands, Sweden, and Switzerland), southern Europe (Italy, Portugal, and Spain), and eastern Europe (Czech Republic, Estonia, Hungary, Poland, and Slovenia). The shaded area in Panel A indicates the difference between quartile 4 (the wealthiest) and quartile 1 (the poorest) in the Health and Retirement Study (HRS); the same shaded area was added in Panels B, C, and D for the purposes of comparison. The median duration of follow-up was 10 years in both surveys, and the mean (±SD) age at baseline was 65±9.8 years.

In their discussion, the authors note that health care access should not be a factor for wealthy Americans. However, “systematic factors may influence longevity across social strata, such as diet; environment; behavioral, cultural, and social attitudes; and opportunities for social mobility.2,28,32,33 The poorest are most vulnerable to these systemic factors, but these factors are broad and probably affect the entirety of society.”

My take: This study indicates that mortality in the United States is higher than in Europe, even at higher wealth levels.

Commentary on this article from NBC News (4/2/25): Not even wealth is saving Americans from dying at rates seen among some of the poorest Europeans

“Fifty years ago, life expectancy in the U.S. and wealthy European countries was relatively similar. That began to change around 1980. As European life expectancy steadily increased, the U.S. struggled to keep pace — and its life expectancy even began declining in 2014…The wealthiest group in northern and western Europe had mortality rates about 35% lower than the wealthiest group in the U.S.”

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Breaking Down the New mRNA Vaccine for C. difficile

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This NEJM review describes recent developments in vaccines for C difficile.

Background: “Because the pathogenesis of C. difficile infection depends on the production of the potent toxins TcdA (toxin A) and TcdB (toxin B) by vegetative C. difficile cells, there is hope that the development of vaccines targeting these virulence factors…will be successful in limiting the development of C. difficile infection in patients receiving antibiotic treatment.2“

An excerpt:

“A trial of a vaccine composed of formalin-inactivated TcdA and TcdB purified from a highly toxigenic C. difficile strain was stopped at the first planned interim analysis on the basis of clinical futility,3 and the development of this vaccine was terminated. More recently, results were published from the Clostridium difficile Vaccine Efficacy Trial (CLOVER), a phase 3, randomized trial of a genetically detoxified C. difficile vaccine composed of recombinant TcdA and TcdB (containing targeted amino-acid substitutions to limit toxic activity) that were further detoxified by chemical means.4 Although the trial did not show a benefit with respect to the primary end point of preventing a first episode of C. difficile infection, vaccinated patients in whom C. difficile infection developed had a shorter duration of symptoms and were less likely to receive medical attention for their infection than patients who had received placebo.

In this setting, a new type of C. difficile vaccine candidate, described by Alameh, Semon, and colleagues,5 is of interest. These investigators developed a multivalent nucleoside-modified messenger RNA (mRNA) vaccine (see Key Concepts) delivered in lipid nanoparticles (LNPs)…The mRNA–LNP vaccine elicited higher antibody levels to all three vaccine targets than the recombinant vaccine with alum adjuvant. Furthermore, the mRNA–LNP vaccine provided complete protection against challenge with an intraperitoneally administered high dose of purified TcdA or TcdB: all the vaccinated mice survived, whereas all the unvaccinated mice were moribund within 2 days. The recombinant–alum vaccines protected only 20% of the vaccinated animals…

However, protection was not associated with the prevention of colonization: all the vaccinated animals shed high numbers of culturable C. difficile and had histopathological damage to intestinal tissue that was equivalent to that seen in unvaccinated animals according to analyses performed 2 days after infection. This finding suggests that protection was due to blocking of the systemic effects of the C. difficile toxins. However, additional data indicated that inclusion of the PPEP-1 antigen in the multivalent vaccine resulted in more rapid clearance of luminal toxin levels.”

My take: An effective vaccine would be a welcome advance and perhaps limit the shitty treatments we have had to date.

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White Temple, Chiang Rai, Thailand


Jose Garza: Belching, Bloating and Best Advice

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Recently Dr. Garza gave our group an excellent lecture. It is always great learning more about how the GI tract really works and what is going wrong when patients are having symptoms. I have taken some notes and shared some slides. There may be inadvertent omissions and mistakes in my notes.

Physiology:

  • Air in the GI tract needs to either be expelled from mouth, be absorbed or be expelled rectally. Nitrogen gas is not well-absorbed. Bacteria in GI tract can contribute to gas production and can also absorb gas.
  • Only about 23% of GI tract air is expelled rectally as gas. Most gas is absorbed and can be expelled from the lungs subsequently.
  • GI tract makes adjustments after swallowing air to help with comfort. This includes raising of the diaphragm. Toddlers frequently have aerophagia but infrequently have symptoms due to distention. Symptoms may worsen in teens/older individuals due to not allowing gas passage

Bloating:

  • Bloating is a sensation that can occur with and without distention.
  • Up to 85% of patients with DGBIs c/o bloating
  • Reasonable to check for celiac disease and possibly other tests if alarm symptoms like bilious vomiting, weight loss and poor growth
  • Increased air in the small bowel is rare and often indicative of dysmotility
  • Elegant studies with CT scan have shown that the typical increase in excess gas during bloating symptoms is only 22 mL. With pseudoobstruction, excess volume of gas is around 3000 mL.
  • pH-impedance is good at detecting aerophagia which often contributes to bloating. Aerophagia prevalence was 3.66% in one study
  • The amount of air from bacterial overgrowth (SIBO) is usually NOT enough to cause most of the reported symptoms of bloating (though may be a contributing factor).
  • A lot of bloating symptoms are due to increased sensitivity and ‘weird gas handling.’ The latter could include compression of diaphragm rather than elevation.
  • Diets (eg lower fructan) can decrease gas but likely also work in other ways. Diets also have side effects and this needs to be carefully considered due to potential issues with eating disorders/ARFID
  • Treat constipation IF PRESENT
  • Diaphragmatic breathing, CBT, neuromodulators and peppermint oil are potential treatment options
  • Increased activity helps with bloating and gas passage

Belching:

  • Descriptions of belching date back more than a hundred years
  • Most belching is normal. Most belching is due to gastric belching and is physiologic
  • Supragastric belching is abnormal. Hallmarks are frequent symptoms and can be associated with worsening reflux and rumination
  • Differences between gastric and supragastric belching can usually be distinguished with clinical presentation (see below). Manometry findings are distinctive between the two. With supragastric belching, With supragastric belching, the air that is expelled is from the esophagus. With gastric belching, air that has reached the stomach is expelled.  
  • Main treatments for supragastric belching are diaphragmatic breathing, and CBT

Inability to Belch:

  • In patients unable to burp, many have retrograde cricopharyngeus dysfunction. This is due to dysfunction of upper esophageal sphincter which had increased pressure and not allowing air in the esophagus to escape. This, in turn, causes discomfort and gurgling noises. While this disorder was reported in 1987, more widespread recognition has occurred since 2019
  • Manometry should be done prior to botox therapy which results in improvement in most patients

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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.

Impact of Testing (or No Testing) for Rumination Syndrome Outcomes

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JS Khoo et al. J Pediatr Gastroenterol Nutr. 2025;80:611–616. Impact of diagnostic testing on outcomes of children with rumination syndrome

Background: “A prior study from our institution showed that many patients undergo extensive diagnostic testing, which is associated with high financial cost with low clinical yield and delay in diagnosis.”

Methods: This was a retrospective study with 152 children (60% female, median age of diagnosis 13 years) with rumination syndrome (RS). 22 patients (14%) had diagnostic testing that confirmed RS.

Key findings:

  • The confirmatory testing group was more likely to need supplemental nutrition (p ≤ 0.001) and to receive intensive treatment (68% vs 24%) (p < 0.001)
  • After treatment, the proportion of patients without vomiting increased in both groups without a statistically significant difference between the two groups or needing supplemental nutrition.

Discussion Points:

“Our findings reveal that despite advancements in testing methodologies, undergoing diagnostic testing and receiving a positive result for RS is not associated with improved outcomes, specifically in cessation of vomiting, after treatment. In situations where patients and caregivers have difficulty accepting the clinical diagnosis, selective testing may be justified as acceptance of the diagnosis is a crucial aspect of the therapeutic plan for all gut-brain interaction disorders.”

Limitations included selection bias. While there were not overt differences in outcomes, the confirmatory testing group required more intensive treatment. As such, the testing may have some benefit in this group (though this was not identified in this retrospective study).

My take (borrowed in part from the authors): “We recommend that clinicians avoid diagnostic testing in children who clearly meet symptom-based criteria for RS and accept the diagnosis.”

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Train bridge near Chickamauga dam (Tennessee River).
There is a blue heron about to take flight due to the oncoming train

Advancements in Pediatric Cholestatic Liver Disease Management

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KR Mysore et al. J Pediatr Gastroenterol Nutr. 2025;80:549–558. Recent advances in the management of pediatric cholestatic liver diseases

This is a useful review summarizing advances in the management of cholestatic diseases.

Treatment with IBAT inhibitors:

“Improvement in both pruritus and serum BAs/bilirubin levels has been associated with improved event‐free survival and 6‐year transplant‐free survival in ALGS patients treated with maralixibat. Additionally, this class of medication improved overall growth of the patient by improving mean height and weight Z scores that may be related to reduced impact of high serum bile acid levels on the growth axis although further studies are needed to better define the mechanism responsible for this out-come. This finding suggests these parameters could be used as surrogate end‐points for disease severity in diseases like ALGS or PFIC, where the time course to develop the need for LT commonly occurs over many years.”

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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.

Pharmaceutical Company Sponsoring Telehealth Visits –Is This a Good Idea?

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ECF Brown et al NEJM 2025; 392: 1148-51. Partnerships between Pharmaceutical and Telehealth Companies — Increasing Access or Driving Inappropriate Prescribing?

This recent commentary discusses the upsides and pitfall of online platforms launched by pharmaceutical companies that direct users to websites run by telehealth companies.

An excerpt:

Proponents highlight the potential for pharmaceutical–telehealth partnerships to facilitate access to prescriptions for some patients, such as those in rural areas…. Virtual consultations can be cheaper and less time-consuming for patients than in-person appointments. For stigmatized conditions such as obesity, patients may be more likely to seek care …

But partnerships between drug and telehealth companies have prompted concerns as well…about the risks these arrangements pose in terms of inappropriate prescribing, inadequate follow-up care, and unnecessary spending on brand-name medications.1 There is also concern that telehealth advertisements, including those on social media, may be misleading, since they sometimes lack disclosures of a product’s risks and contraindications.

The key law governing these relationships in the United States is the federal Anti-Kickback Statute (AKS). The AKS is intended to prevent and penalize the use of financial incentives for patient referrals or other arrangements that encourage clinicians to provide inappropriate or unnecessary health care, thereby increasing government expenditures…

Under the AKS, a pharmaceutical company cannot compensate a telehealth company or its affiliated clinicians on the basis of the number or monetary value of prescribed products. Nor may a telehealth company pay a pharmaceutical company for making patient referrals…

The OIG also noted several characteristics of telehealth arrangements that heighten the risk of an AKS violation. These characteristics include patient recruitment using targeted advertising (including on social media), insufficient patient evaluation or follow-up, and steering of patients toward specific treatments without adequate consideration of clinical appropriateness or alternatives…

More information about the nature of financial arrangements between pharmaceutical and telehealth companies should be reported. Such reporting could be mandated as part of an expansion of the Physician Payments Sunshine Act.

My take: There needs to be closer scrutiny of the relationship between pharmaceutical companies and affiliated telehealth companies. While the online telehealth partnershps improve access, the current set up is likely to promote inappropriate care.

Mai Khao Beach, Phuket

U.S. Measles Outbreak Is Not Slowing

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These charts show measles data through April 7th. Some additional data through Apirl 11th is listed below.

For those interested in a deeper dive into the measles numbers, you can follow Caitlin Rivers substack. From her notes on April 11:

  • “Since my last update on Tuesday, Arkansas and Hawaii reported cases for the first time this year. At least five states have reported ten or more cases, which is very unusual. Texas continues to register the most cases, with 541 to date.”
  • “According to the CDC, 712 cases have been reported so far this year. 1 in 3 (32%) are under the age of 5, and 1 in 10 (11%) have been hospitalized.”

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Understanding the Economic Burden of Inflammatory Bowel Disease

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J Burisch et al. Clin Gastroenterol Hepatol 2025; 23: 386-395. Open Access! The Cost of Inflammatory Bowel Disease Care: How to Make it Sustainable

This article is a terrific review of care cost drivers in inflammatory bowel disease (IBD) but it does not actually have useful information on how to make the costs of care sustainable.

Key points:

  • The most recent data from the United States (U.S.) estimated that the prevalence of IBD
    was 0.7% of the population, representing 2.39 million individuals living with IBD…the annual cost of IBD in the U.S. approximates $50 billion
  • All studies demonstrated a shift over time from costs associated with hospitalizations to costs of medications
  • The costs of prescription drugs for IBD vary significantly worldwide… A particular outlier among high-income countries is the U.S., where manufacturers set prices freely. The lack of
    nationwide price regulation, coupled with the fragmentation of the U.S. health care system and prolonged market exclusivity periods, result in U.S. drug prices that exceed, on average, international prices by several-fold…Even when insurers are successful at negotiating discounts, patients seldom benefit, as costsharing paid at the point-of-sale is based on the full, non-discounted price
  • Using a “top-down” clinical paradigm, guidelines suggest starting biologic medications early to induce remission of moderate-to-severe IBD, thereby reducing risk of complications, surgeries, and hospitalizations and improving quality of life.55,58 A randomized controlled
    trial demonstrated a clear benefit in steroid-free and surgery-free remission among patients randomized to top-down vs step-up care (79% vs 15%; P < .0001) [PROFILE study]

In terms of improving cost sustainability, here is what the authors propose “Strategies for cost reduction in the clinical treatment of IBD”:

My take: This article highlights the cost drivers in IBD but does not identify a path that appears to help address affordability.

This article is one of 11 articles in special issue discussing the future of IBD care.

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Clinical Response to Risankizumab Dose Intensification for Crohn’s Disease

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RS Dalal et al. Clin Gastroenterol Hepatol 2025; 23: 662-664. Outcomes After Dose Intensification of Risankizumab for Crohn’s Disease

This retrospective study reviewed adults with Crohn’s disease (CD) who underwent dose intensification of maintenance from 360 mg every 8 weeks to every 6 weeks (n=11) or every 4 weeks (n=11).

Key findings:

  • Median time to first intensified dose was 228 days
  • Harvey Bradshaw Index (HBI) improved from a mean of 7.1 to 4.3 after 8 to 16 weeks
  • There was also improvement (not statistically significant) in mean CRP (1.64–>0.42 mg/dL) and mean calprotectin (774 –>650 mcg/g)
  • At 8 to 16 weeks, 64% (14 of 22) had a clinical response, 45% (10 of 22) achieved steroid free clinical remission

My take: This small study suggests that the majority of patients with a loss of response to standard dosing can be recaptured with dose intensification.

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Old Town in Conyers, GA

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.

Treatment Disparities in Adult vs. Pediatric IBD Care Related to Provider Specialization

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JD Lewis et al. Clinical Gastroenterology and Hepatology. 2024; Volume 22, Issue 12, 2475 – 2486.e14. Open Access ! Provider Specialization in Inflammatory Bowel Diseases: Quality of Care and Outcomes

Methods:  This was a retrospective cohort of newly diagnosed patients with IBD using data from Optum’s deidentified Clinformatics Data Mart Database (2000–2020). The study included 772 children treated by 493 providers and 2864 adults treated by 2076 providers.

Key findings:

  • In adults, care from an IBD-focused provider was associated with more use of biologics, combination therapy, and imaging and endoscopy, and less mesalamine use for Crohn’s disease (P < .05 for all comparisons)
  • In children, none of the associations between provider focus and process or outcome measures were significant. Although not statistically significant among children, the OR for mesalamine use was 0.64, suggesting a similar association as that seen among adults
Time to first dispensing of a biologic therapy in (A) children and (B) adults

My take: This study indicates significant treatment disparities between IBD-focused care providers and providers without an IBD focus in the care for adults, but not in the care of children. This could be related to improved collaboration among pediatric care providers, better training, and parental involvement.

In addition, this study focused on patients with newly-diagnosed disease. Treatment is more complicated in patients who have not responded to initial treatments; as such, IBD-focused providers may be more important in this population.

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