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.

Related blog posts:

Shem Creek, SC

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.

Related blog posts:

The Battery, Charleston, SC

 

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.

Related blog posts:

Chattahoochee River

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.

Irritable Bowel Syndrome 2017 (part 1)

A terrific 12 page review of irritable bowel syndrome (IBS): AC Ford, BE Lacy, NJ Talley. NEJM 2017; 376: 2566-78.

Diagnosis of Irritable Bowel:

Testing: National guidelines recommend that for a patient who meets Rome IV criteria, “the physician should make a positive diagnosis of IBS without resorting to a battery of tests.” Nevertheless, many physicians obtain some workup.  If a workup is undertaken, the authors state “consider limited testing (CBC, CRP level, celiac serological test, fecal calprotectin level)”

Rome IV criteria of IBS are reviewed in Table 1 and includes warning signs.  Summary of Rome IV critieria from emedicine website on Irritable Bowel Syndrome: The Rome IV criteria for the diagnosis of irritable bowel syndrome require that patients have had recurrent abdominal pain on average at least 1 day per week during the previous 3 months that is associated with 2 or more of the following [2]:

  • Related to defecation (may be increased or unchanged by defecation)
  • Associated with a change in stool frequency
  • Associated with a change in stool form or appearance

The Rome IV criteria (May 2016) only require abdominal pain in defining this condition; “discomfort” is no longer a requirement owing to its nonspecificity, and the recurrent abdominal pain. 

Supporting symptoms include the following:

  • Altered stool frequency
  • Altered stool form
  • Altered stool passage (straining and/or urgency)
  • Mucorrhea
  • Abdominal bloating or subjective distention

Four bowel patterns may be seen with irritable bowel syndrome, and these remain in the Rome IV classification. These patterns include the following:

  • IBS-D (diarrhea predominant)
  • IBS-C (constipation predominant)
  • IBS-M (mixed diarrhea and constipation)
  • IBS-U (unclassified; the symptoms cannot be categorized into one of the above three subtypes)

Symptoms not consistent with irritable bowel syndrome should alert the clinician to the possibility of an organic pathology. Inconsistent symptoms include the following:

  • Onset in middle age or older
  • Acute symptoms (irritable bowel syndrome is defined by chronicity)
  • Progressive symptoms
  • Nocturnal symptoms
  • Anorexia or weight loss
  • Fever
  • Rectal bleeding
  • Painless diarrhea
  • Steatorrhea
  • Gluten intolerance

The authors provide a diagnostic algorithm which is straight-forward.  The caption includes “tenderness is not increased by tensing abdominal wall muscles.”  The inclusion of Carnett’s sign is a useful reminder to consider/exclude muscle wall etiologies.

Another important point is that bile-acid diarrhea occurs in a significant fraction of adults with the diarrhea subtype of IBS, more than 25% of cases in a meta-analysis; thus, a therapeutic trial of a bile acid sequestrant may be useful.

Pathophysiology:

There are likely multiple pathways leading to IBS. In fact, Figure 2 lays out a Brain-Gut pathway as well as a Gut-Brain pathway. In the former, genetic predisposition and environmental factors/CNS alterations, could make one more susceptible to IBS after localized GI inflammation.  In the later, changes in the GI tract induced by infection, inflammation, food antigens, and medications which could alter intestinal permeability and/or microbiome could result in changes in CNS function (eg. new-onset anxiety, depression or somatization).  It is well-recognized that after gastrointestinal infections (bacterial, protozoal, viral), “IBS-type symptoms persist in 10 to 20% of infected patients.”

Image from NEJM twitter feed. It is noted that not all pathophysiological processes shown occur in all patients with IBS or in all IBS subtypes.

 

 

Diet, Meat, and Colorectal Cancer

A recent study (RS Mehta et al. Gastroenterol 2017; 152: 1944 & summarized in editorial, 1821-23) examined the effects of a “Western” diet and a “prudent” diet on the risk of colorectal cancer (CRC). Data was derived from two large prospective cohorts involving more than 137,000 participants for up to 32 years; this equated to 3.6 million person-years of follow-up.

Key findings:

  • Those in the highest quartile of a Western dietary pattern had a 31% increased CRC risk (RR=1.31) compared to those in the lowest quartile. In this context, a Western diet was characterized by consumption of red and processed meats, high-fat dairy products (such as whole milk), refined grains, and desserts.
  • The prudent diet cohort, had a 14% reduced risk for those in the highest quartile compared to the lowest quartile. The ‘prudent’ diet included high intakes of vegetables, fruits, whole grains, and fish.

Based on this study and others, the editorial notes the following:

  • Limit red and processed meat consumption to 0.5 servings or 42 g/day of lean red meat
  • A more ‘prudent’ diet has health benefits beyond reduction of CRC, including lower cardiovascular disease mortality

Related blog post: Colon Cancer at Younger Ages

Piedmont Park, Atlanta

Recent Study Did NOT Find Dementia Risk with PPIs

When performing retrospective studies, many times a potential association can be found with medications or diet and specific problems.  When these risks/associations are low (i.e. relative risks <2), often, these findings do not hold up, particularly with prospective studies which are much more able to control for confounding variables.

For proton pump inhibitors (PPIs), many potential complications have been suggested at  low relative risk findings in poorly-controlled studies.  A recent study has contradicted previous findings suggesting that PPIs increase the risk of dementia.

Goldstein FC, et al. J Am Geriatr Soc. 2017;doi:10.1111/jgs.14956. (Thanks to Ben Gold for this reference)

A link and an excerpt from a summary of this study from Healio Gastroenterology:

Link: Study finds no link between PPIs, dementia, Alzheimer’s risk

Excerpt:

They evaluated 10,486 volunteers within the NIH-supported Alzheimer’s Disease Centers who were aged 50 years and older and had either normal cognition or mild cognitive impairment at baseline. Participants underwent neuropsychological evaluations and self-reported PPI use at two to six annual visits between 2005 and 2015.

Overall, 884 reported they were taking PPIs at every visit, 1,925 reported they took PPIs intermittently, and 7,677 never reported taking PPIs.

Those who reported continuous PPI use showed a lower risk for cognitive function decline compared with those who never reported using PPIs (HR = 0.78; 95% CI, 0.66-0.93) as well as a lower risk for developing mild cognitive impairment or Alzheimer’s disease (HR = 0.82; 95% CI, 0.69-0.98).

Those who reported using PPIs intermittently also showed a lower risk for cognitive function decline (HR = 0.84; 95% CI, 0.76–0.93) and for developing mild cognitive impairment or Alzheimer’s disease (HR = 0.82; 95% CI, 0.74–0.91).

My take: This study provides reassurance that PPIs are unlikely to result in cognitive decline. Particularly when a study suggests a low risk of an association, further studies are needed to clarify the true risks.

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Lennon Wall, Prague

Mandated Malpractice in IBD Care?

A recent study (A Yada et al. Inflamm Bowel Dis 2017; 23: 853-7) finds that insurance policies are not in compliance with expert guidelines.  The authors reviewed 79 policies from the top insurance companies to examine their policies regarding anti-TNF agents, vedolizumab, and ustekinumab.  These policies were compared with the American Gastroenterological Association (AGA) clinical pathway recommendations for ulcerative colitis (UC) and Crohn’s disease (CD).

Key findings:

  • “90% of the policies required step-wise failure prior to starting anti-TNF for non-fistulizing CD.”
  • “When choosing anti-TNF therapy, 26% of policies required the use of adalimumab as the first anti-TNF agent.”
  • 98% of policies are inconsistent with AGA IBD guidelines

Discussion from authors:

  • “The plans do not allow for treatment based on disease severity but rather dictate treatment based on the required failure of different drug classes.”
  • “Only 2% of UC policies and 10% of CD policies allowed for early initiation of biologic therapy to reduce the risk of complications.”
  • “The goal of medical management is to minimize the use of corticosteroids…However, the majority of the current policies…preclude this standard-of-care management.”

My take (from authors): “Most insurance companies do not comply with the current standard of care for treating IBD.” My expectation is that these problems will continue and/or worsen as the options for IBD treatment become more complex.

Normandy American Cementary