Somewhat Funny Flatulent Research

A recent study (CV Almario et al. Clin Gastroenterol Hepatol 2017; 15: 1308-10) was titled: “Old Farts -Fact or Fiction?  Results from a Population-Based Survey of 16,000 Americans Examining the Association Between Age and Flatus.” I was surprised that this was not in an April Fools edition, though I had to read the article because of the intriguing title. The authors premise was to determine if the elderly pass more flatus.

Key findings:

  • Based on self-reporting using a mobile app (MyGiHealth), the authors found that individuals ≥65 years passed flatus less often than the younger age groups. Among those reporting flatulence every 1-2 hours, only 22.6% of those ≥65 years had this frequency; this compared to at least 33% in all other age groups.
  • Most commonly, individuals in all age groups reported passing flatus about every 3-4 hours (36-41%); the next most common frequency was about every 1-2 hours (23-38%) across all age groups. The other frequent category was passing flatus once or twice a day which was reported between 24-29% across all age groups.

The authors indicate that limitations of their study include “social desirability bias” and “information bias.”  In addition, while the entire cohort was >16,000, there were only 296 who were ≥65 years of age.

While I’m not an expert in this field, other limitations could include worsened ability to detect/record flatus with age and/or worsened memory about frequency of passing flatus.

My take: This study shows that almost any study could find a home in some medical journals. In my view, self-reported frequency of passing flatus may not be accurate (the dog did it!).

Pitt Street Bridge, Charleston, SC

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Northern Latitudes -Higher Prevalence of Celiac Disease and Gluten Avoidance

A recent study (A Unalp-Arida et al. Gastroenterol 2017; 152: 1922-32) examines the relationship of latitude and the prevalence of celiac disease and gluten avoidance.

Using the NHANES 2009-2014 survey with 22,277 participants (6 years and older), the authors identified persons with celiac disease (based on serology) along with those who avoided gluten without a diagnosis of celiac disease.

Key findings:

  • 0.7% of participants had celiac disease and 1.1% avoided gluten without celiac disease
  • Celiac disease was more common among individuals who lived at latitudes of above 35 degrees and more common with higher socioeconomic status. Figure 2 map provides latitude lines. In the eastern U.S. the Georgia-Tennessee border corresponds to this latitude line and in the western U.S. the southern tip of Nevada lies on this line.
  • From 35 degrees to 39 degrees the odds ratio was 3.2, whereas the odds ratio was 5.4 for those above 40 degrees.  These odds ratios were independent of race, ethnicity, socioeconomic status and body mass index.
  • Similarly, the prevalence of gluten avoidance without celiac disease was twice as common among persons living north of 40 degrees compared with those residing at latitudes <35 degrees.
  • The findings on latitude were heavily influenced by the increased rate of celiac and gluten avoidance in the Northeast region (more so than in the West)

In their discussion, the authors note that “a North-South gradient in disease occurrence in genetically similar populations has been shown in studies of autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, and rheumatoid arthritis.” Potential environmental factors could include lack of sunshine/vitamin D deficiency, hygiene, and infections.  A study comparing similar populations in Finland and Russia suggested a lower economic status/less hygiene increased the risk of celiac disease despite similar gluten exposure.  The authors note that there was NOT an increased risk in Northern Sweden compared to Southern Sweden.  In fact, this study of children found a higher rate of celiac disease in Southern Sweden (Arch Dis Child 2016; 101: 1114-18).

My take: This is another intriguing study regarding celiac disease epidemiology which strongly points to environmental factors accounting for marked variation in celiac disease prevalence.

More information on this topic from AGA Blog: Do More People Have Celiac Disease in the North vs the South?

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Big Study of Primary Sclerosing Cholangitis

This blog has reviewed multiple publications on primary sclerosing cholangitis (see blog posts below). Now, a study from 37 centers with 7121 patients with PSC has been published: TJ Weismuller et al. Gastroenterol 2017; 152: 1975-84. Given the relative infrequency of PSC, this retrospective report offers more insight into the predictors of the clinical course of PSC.

Key points:

  • Most of the patients in the study had large duct PSC (89.8%); 3.6% had small duct disease and 6.6% had overlapping PSC/autoimmune hepatitis.
  • Mean age of cohort at diagnosis was 38.5 yrs.
  • 70% of PSC patients developed IBD with ulcerative colitis (UC) about 5-times more common than Crohn’s disease.
  • 37% of patients met the primary endpoint of either liver transplantation or death
  • Individuals with small duct PSC had a favorable outcome; only one of 254 (0.4%) developed cholangiocarcinoma (CCA). Risk of primary endpoint was much lower in small duct PSC compared with classical PSC with an adjusted hazard ratio of 0.23.
  • Individuals with PSC/AIH variant also had a reduced risk of primary endpoint compared with classical PSC with an adjusted hazard ratio of 0.73.
  • Overall, CCA occurred in 594 patients (8.3%); the incidence of CCA changed markedly with the age of the patient.  In the youngest group (<20 years), the rate was 1.2 per 100 patient-years, it was 6.0 in 21-30 yr-olds, 9.0 for 31-40 yr-olds, 14.0 fr 41-50 year olds, 15.2 for 51-60 yr-olds, and 21.0 per 100 patient-years in those older than 60 years.
  • The absence of IBD, particularly UC, was associated with a lower risk PSC clinical course. Patients with UC had increased liver disease progression compared with patient’s with Crohn’s disease, with a HR of 1.56.
  • The median transplant-free survival time was 14.5 years; the estimated survival was approximately 21 years in the entire cohort

It is noted that an important limitation is that the cohort is from specialist centers and may not reflect a more typical population-based cohort; that is, this patient population is likely to be severely affected.

My take: Patients with small-duct PSC have a much lower risk of disease progression.

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AGA Blog: What are the complications of PPI Therapy?

AGA Journals Blog: What are the complications of proton pump inhibitor (PPI) Therapy?

The blog post reviews a recent article on PPIs and potential complications.

An excerpt:

review article from Michael F. Vaezi et al discusses potential adverse consequences of proton-pump inhibitor (PPI) therapy in the July issue of Gastroenterology…(2017; 153: 35-48). The authors discuss overzealous conclusions based on weak associations that have caused widespread alarm, leading to inappropriate discontinuation of a medicine that is needed for an established disease process. They present absolute and relative risks for adverse effects associated with long-term use of PPIs…

Vaezi et al review the consistency of proposed associations with PPI use and the time period between the PPI exposure and outcome, and the effects of different doses. They provide guidance for methodologies of future studies.

The review article concludes that PPIs have revolutionized the management of patients with GERD and patients at risk of upper gastrointestinal ulceration and bleeding from aspirin or NSAIDs. However, many patients receive PPIs unnecessarily for conditions or symptoms for which they would not have been expected to provide benefit… Vaezi et al state that, as always, PPIs should be given in the lowest effective dose, for the shortest possible time.

They add that much of the evidence linking PPI use to serious long-term adverse consequences is weak and insubstantial. It should not deter prescribers from using appropriate doses of PPIs for appropriate indications.

Full text of original article: Complications of Proton Pump Inhibitor Therapy

Table 6 lists the strengths of the findings along with other Hill Criteria to assess all of the proposed complications.  The vast majority of potential complications have “weak” proof; the exceptions include bacterieal enteric infections/Clostridium difficile infection which have moderate strength of evidence and and fundic gland polyps which have high strength of evidence.

My take: This study and the associated AGA Journals blog post indicate that most of the reports of complications associated with PPI remain unproven and are based on weak evidence.

 

Long Distance (Medical) Relationships Don’t Always Work

Another study (NZ Borren et al Inflamm Bowel Dis 2017; 23: 1234-9) has shown detrimental outcomes due to distance from the health care team.

In this study with 2136 patients with IBD (1197 Crohn’s disease, 9393 ulcerative colitis) with mean age of 41 years, the distance from the hospital (Massachusetts General) was compared with need for IBD-related surgery and secondary outcomes of needing biological and immunomodulator therapy.

Key findings:

  • In the four quartiles, mean distance was 2.5, 8.8, 22.0, and 50.8 miles.
  • Need for surgery was increased with distance from hospital: closest with odds ratio of 1.0, quartile 2 had OR of 1.68, quartile 3 had OR of 1.94, and quartile 4 had OR of 2.44

According to the authors, with other indications besides IBD, “over three-quarters of the examined studies demonstrated a distance-decay association with worse outcomes in individuals living further away from health care facilities.  Limitation: it is possible that patients who travel a greater distance have more disease severity and that those who have milder diseases are more likely to receive care closer to home.

My take: When highly qualified subspecialists are far away, the associated reduced access likely counters this potential benefit.  Early effective therapy is important in reducing complications.

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PPI and Poor Outcomes

A large observation study provides some bad publicity for proton pump inhibitors (PPI):

BMJ Open Access: Risk of death among users of Proton Pump Inhibitors: a longitudinal
observational cohort study of United States veterans (Y Xie et al BMJ Open
2017;7:e015735. doi:10.1136/bmjopen-2016-01573) Thanks to Ben Enav for this reference.

This study selected ~350,000 patients from a database which identified more than 1.7 million PPI users. These patients were ‘new’ PPI users.

Key finding:  Over a median follow-up of 5.71 years, PPI use was associated with increased risk of death compared with H2 blockers use (HR 1.25, CI 1.23 to 1.28).

The authors note the limitations of this observational study; however, they suggest that the findings cannot be fully explained by residual confounders.  They recommend limiting PPI use to “instances and durations where it is medically indicated.”

My take: As noted in a recent post (see below), some risks attributed to PPIs in observational studies do not pan out.  Yet, PPI therapies need to be better-targeted to those who will truly benefit from them.

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Irritable Bowel Syndrome (part 2)

A terrific 12 page review of irritable bowel syndrome (IBS): AC Ford, BE Lacy, NJ Talley. NEJM 2017; 376: 2566-78. While yesterday’s post reviewed some of the updated diagnostic and pathophysiology information, today’s will focus on treatment.

The article’s Table 2 outlines the most frequent treatments, their efficacy, side effects, costs, and quality of evidence. I’ve tried to highlight the key points from table and discussion:

  1. Soluble fiber (eg. psyllium). Efficacy: effective -start at low doses. Quality of evidence: Moderate, Cost: $15-30 per month.
  2. Low-FODMAP diet. Efficacy: “May be effective, nutritionist guidance helpful.” While there have been studies showing this diet can be effective, two studies have shown that this diet is not significantly superior to conventional IBS diets (eg. “eating small, regular meals and avoiding insoluble fiber, fatty foods, and caffeine”).Quality of evidence: Very low.
  3. Gluten-free diet.  Efficacy: May be effective.  “No additive effect over that of a low-FODMAP diet in another small RCT.” Quality of evidence: Very low.
  4. Antispasmodic drugs (eg. dicyclomine).Efficacy: May be effective. Quality of evidence: Low, “No high-quality trials.” Cost: $50 per month.
  5. Peppermint oil. Efficacy: Effective, though few RCTs and no FDA-approved end points. Quality of evidence: Moderate. “No high-quality trials.”  Cost: $9-19 per month
  6. Lubiprostone. Efficacy: Effective, though “only a modest benefit over placebo, particularly for abdominal pain.” Quality of evidence: Moderate. Cost: ~$350 per month.
  7. Linaclotide.  Efficacy: Effective.. ” Quality of evidence: High. “No high-quality trials.”  Cost: ~$350 per month.
  8. Alosetron/5-HT3 receptor antagonists.  Efficacy: Effective. ” Quality of evidence: High. “No high-quality trials.”  Cost: ~$350-1100 per month. Alosetron may trigger ischemic colitis.
  9. Eluxadoline.  Efficacy: Effective, though “only a modest benefit over placebo for global symptoms and no benefit over placebo for abdominal pain.”  Quality of evidence: High. “No high-quality trials.”  Cost: ~$1100 per month. May trigger pancreatitis.
  10. Rifaximin. Efficacy: Effective. Quality of evidence: Moderate. “Modest benefit over placebo.”  “Relapse among patients who have a response is usual.” Cost: ~$1500 per month.
  11. Probiotics. Efficacy: May be effective.  Quality of evidence: Low. “Few high-quality trials and no FDA-approved end points.”  Cost: ~$20 per month.
  12. Tricyclic antidepressants. Efficacy: Effective. Quality of evidence: Moderate.  “Few high-quality trials and no FDA-approved end points.”   “A meta-analysis showed that tricyclic antidepressants were more effective than placebo in 11 randomized trials involving a total of 744 patients.” Cost: ~$5-10 per month.
  13. Psychological treatments. Efficacy: Effective. Quality of evidence: Low.  “Few high-quality trials and no FDA-approved end points.” “Their efficacy may be overestimated because of the lack of blinding.” There is also difficulty for many patients in finding an appropriate provider.  Cost: ??
  14. Placebo. In treatment trials, a placebo response is noted in 30-40%.
  15. Complementary/Alternative Therapies.  “Herbal therapies remain unclear.  STW5 (Iberogast) has been tested and “showed superiority over placebo.” Melatonin “has been reported to reduce abdominal pain in patients with IBS.”

The authors recommend judicious testing  “Any reassurance derived from colonoscopy to rule out organic disease in patients with IBS is short-lived.”

The authors outline their typical approach.  “Reassurance, explanation, and a positive diagnosis are essential steps in management. We recommend starting with dietary modification (slowly increasing soluble fiber if the patient has IBS with constipation or instituting a low-FODMAP diet temporarily  if the patient has IBS with diarrhea or the mixed subtype of IBS). We also recommend increased exercise and stress reduction.  A probiotic may be added, especially if bloating is prominent.  Pain may be ameliorated with an antispasmodic agent or a tricyclic antidepressant, diarrhea with loperamide or a bile acid sequestrant (eg. colestipol) and constipation with polyethylene glycol.” The other therapies may be used in those with persistent IBS symptoms.

My take: When a disease has this many treatments, usually this means that none of the treatments are all that great.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  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.