Category Archives: Pediatric Gastroenterology Intestinal Disorder

CDC Guideline for Prescribing Opioids for Chronic Pain

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Full Text: CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016

D Dowell et al. JAMA. Published online March 15, 2016. doi:10.1001/jama.2016.1464 .

Excerpts:

  • No evidence shows a long-term benefit of opioids in pain and function vs no opioids for chronic pain with outcomes examined at least 1 year later (with most placebo-controlled randomized clinical trials ≤6 weeks in duration).

  • Extensive evidence shows the possible harms of opioids (including opioid use disorder, overdose, and motor vehicle injury).

  • Extensive evidence suggests some benefits of nonpharmacologic and nonopioid pharmacologic therapy, with less harm.

CDC: “We know of no other medication routinely used for a nonfatal condition that kills patients so frequently,”

1st Six Recommendations (12 total)

1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient. If opioids are used, they should be combined with nonpharmacologic therapy and nonopioid pharmacologic therapy, as appropriate. (Recommendation category: A; evidence type: 3)

2. Before starting opioid therapy for chronic pain, clinicians should establish treatment goals with all patients, including realistic goals for pain and function, and consider how opioid therapy will be discontinued if benefits do not outweigh risks. Clinicians should continue opioid therapy only if there is clinically meaningful improvement in pain and function that outweighs risks to patient safety. (Recommendation category: A; evidence type: 4)

3. Before starting and periodically during opioid therapy, clinicians should discuss with patients known risks and realistic benefits of opioid therapy and patient and clinician responsibilities for managing therapy. (Recommendation category: A; evidence type: 3)

4. When starting opioid therapy for chronic pain, clinicians should prescribe immediate-release opioids instead of extended-release/long-acting (ER/LA) opioids. (Recommendation category: A; evidence type: 4)

5. When opioids are started, clinicians should prescribe the lowest effective dosage.  (Recommendation category: A; evidence type: 3)

6. Long-term opioid use often begins with treatment of acute pain. When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediate-release opioids and should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids. Three days or less will often be sufficient; more than 7 days will rarely be needed. (Recommendation category: A; evidence type: 4)

Other points:

  • Avoid concurrent benzodiazepines
  • Review state prescription drug monitoring program to look for dangerous combination therapies and prior opiod dosing
  • Consider risk mitigation strategies (eg. naloxone)
  • Suggests urine screening at start to screen for illicit substance abuse which increases risk

USAToday’s review of these guidelines: CDC issues new guideline on opiods

Bottomline: This report is very important for those who prescribe opiods for chronic pain.

Law Library, Univ of Michigan

Law Library, Univ of Michigan

More on Hidradenitis Suppurativa and Inflammatory Bowel Disease

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In a population-based inception cohort study (S Yada et al. Clin Gastroenterol Hepatol 2016; 14: 65-70) of 679 patients with inflammatory bowel disease (IBD) followed for a median of more than 19.8 years, it was determined that patients with IBD were ~9 times more likely to develop hidradenitis suppurativa (HS) compared with general population. 8 of 679 patients developed HS; only one had HS prior to IBD.

Other findings:

  • Most Crohn’s disease patients with HS had perianal disease.  Most ulcerative colitis patients developed HS after colectomy.
  • Female sex and obesity were risk factors for HS.

In a second retrospective study (N Kamal et al. Clin Gastroenterol Hepatol 2016; 14: 71-9), the authors identified 15 patients with CD and HS.  10 patients had perianal disease.  In this population, “both diseases were characterized by their severity, requirement of systemic medical therapies including anti-TNF and high operative rate.” this article contained some very helpful pictures.

Unrelated article: F Wang, JL Kaplan, BD Gold et al. Cell Reports; 2016: 14: 945-55.  This highly technical study used two independent cohorts of patients with Crohn’s disease and non-IBD controls.  One cohort, RISK, had over 700 patients and ~30,000 mean number of reads per sample; the other cohort, PIBD-CC, and 87 patients and ~3000 mean number of reads per sample.  Overall, the study showed associations between Crohn’s disease and bacteria in the lumen and the study helps provide an information-based method to depict dysbiosis.

Related blog post: Add it to the list

San Juan

San Juan

“Cat in the Hat” Effect with Transjugular Intrahepatic Portosystemic Shunt (TIPS)

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IL Holster et al (Hepatology 2016; 63: 581-89) provide useful data on the use of transjugular portosystemic shunt (TIPS) compared with endoscopic therapy/Beta-blocker for prevention of variceal rebleeding.

In this multicenter randomized trial, TIPS was compared with either endoscopic variceal ligation or glue injection along with beta-blocker treatment in 72 patients with either a first or 2nd episode of variceal bleeding.  The median followup was 23 months.

Key findings:

  • 0 of 37 (0%) of TIPS patients had rebleeding compared with 10 of 35 (29%) in the endoscopic group.
  • TIPS mortality 32% compared with endoscopic group mortality of 26% (P=0.418)
  • Hepatic encephalopathy was 35% (TIPS) vs 14% (endoscopic group) (P=0.035)

This study shows that rebleeding is common in the endoscopic therapy group but that TIPS, while fixing bleeding, often resulted in other problems.  In “The Cat in the Hat” analogy, this would equate to moving the bathtub stain to the dress or curtains but not really improving the situation.

My take: It is helpful to see how these treatment strategies compare.  The data from this study does not clearly point to one strategy over another for dealing with this serious consequence of cirrhosis.

Related blog posts:

Statue at Ferry Dock, Culebra

Statue at Ferry Dock, Culebra

“Simple Remedies for Constipation”

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“Common sense is not so common” –Voltaire

A useful review of constipation management in the NY Times: Simple Remedies for Constipation

This review explains the role of diet and exercise in treatment of constipation.  The author notes that coffee helps many and that laxatives are safe. In addition, the idea of “autointoxication” due to infrequent bowel movements is debunked.

Here’s an excerpt:

Dr. Wald and others say that properly designed studies of these [stimulatory] laxatives have shown no harm to the colon when they are taken in recommended amounts.

Yet many doctors still warn – inappropriately, Dr. Wald says — against taking stimulatory laxatives for more than a few days. Indeed, the website FamilyDoctor.org states, “When these laxatives are taken for a long time, the bowel can lose its muscle tone and ‘forget’ how to push the stool out on its own.” Best to forget this outdated idea as long as you stick to the recommended dose if you must take these products.

Related blog posts:

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High Risk of Relapse in Younger Patients after anti-TNF Therapy Withdrawal

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From KT Park’s Twitter Feed:

Article first published online: 19 FEB 2016

NA Kennedy et al.  Aliment Pharm Ther; 2016. DOI: 10.1111/apt.13547

Abstract:

Background

Infliximab and adalimumab have established roles in inflammatory bowel disease (IBD) therapy. UK regulators mandate reassessment after 12 months’ anti-TNF therapy for IBD, with consideration of treatment withdrawal. There is a need for more data to establish the relapse rates following treatment cessation.

Aim

To establish outcomes following anti-TNF withdrawal for sustained remission using new data from a large UK cohort, and assimilation of all available literature for systematic review and meta-analysis.

Methods

A retrospective observational study was performed on 166 patients with IBD (146 with Crohn’s disease (CD) and 20 with ulcerative colitis [UC) and IBD unclassified (IBDU)] withdrawn from anti-TNF for sustained remission. Meta-analysis was undertaken of all published studies incorporating 11 further cohorts totalling 746 patients (624 CD, 122 UC).

Results

Relapse rates in the UK cohort were 36% by 1 year and 56% by 2 years for CD, and 42% by 1 year and 47% by 2 years for UC/IBDU. Increased relapse risk in CD was associated with age at diagnosis [hazard ratio (HR) 2.78 for age <22 years], white cell count (HR 3.22 for >5.25 × 109/L) and faecal calprotectin (HR 2.95 for >50 μg/g) at drug withdrawal. Neither continued immunomodulators nor endoscopic remission were predictors. In the meta-analysis, estimated 1-year relapse rates were 39% and 35% for CD and UC/IBDU respectively. Retreatment with anti-TNF was successful in 88% for CD and 76% UC/IBDU.

Conclusions

Assimilation of all available data reveals remarkable homogeneity. Approximately one-third of patients with IBD flare within 12 months of withdrawal of anti-TNF therapy for sustained remission.

Related blog posts:

El Junque, Puerto Rico

El Junque, Puerto Rico

Epidemiology of Eosinophilic Disorders

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Jensen et al. JPGN 2016; 62: 36-42.  The researchers used a large database (>75 million individuals) representative of US commercially-insured population to provide estimates of the prevalence of several eosinophilic disorders:

  • Eosinophilic gastritis 6.3 per 100,000
  • Eosinophilic gastroenteritis 8.4 per 100,000
  • Eosinophilic colitis 3.3 per 100,000

In the associated commentary by Furuta et al (pg 1), clinicians are encouraged to urge patients with EGID to register on the Consortium for Eosinophilic Gastrointestinal Disease Research registry: https://www.rarediseasesnetwork.org/cms/CEGIR

Related blog posts:

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Celiac Studies

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Three reports on celiac disease:

  • KM Simmons et al. J Pediatr 2016; 169: 44-8.
  • NR Reilly et al. J Pediatr 2016; 169: 40-54
  • MMS Wessels et al. J Pediatr 2016; 169: 55-60.

In the first study, the authors examined bone mineral density (BMD), glycemic control with hemoglobin A1c, and celiac autoimmunity in children with type 1 diabetes (T1D).  This was a cross-sectional study of 252 children with T1D; 123 had positive serology were anti-tissue transglutaminase (tTG) antibody.  In addition, another cohort (n=141) of children without T1D were examined who carried HLD-DR, DQ genotypes with (n=71) and without (n=70) tTG.  Key findings:

  • Children with T1D: those positive for tTG had significantly worse BMD L1-L4 (-0.45 ± 1.22 vs 0.09 ± 1.10, P= .0003).  Higher tTG and higher HgbA1c were independent predictors of lower BMI.
  • In children without T1D: no differences in BMD were found based on tTG status.
  • The authors concluded that celiac autoimmunity and hyperglycemia had synergistic effects on low BMD.

In the second study, the researchers used a population-based cohort study and compared 958 individuals with both T1D and celiac disease (CD) to 4598 similar individuals with T1D alone. Key finding: Over a 13 year period, 12 patients with both T1D and CD had a fracture (1 osteoporotic fracture). CD did not influence the risk of any fracture (aHR 0.77) in patients with T1D.  The researches concluded: “CD does not seem to influence fracture risk in young patients with T1D.”

My take: Looking at these studies in juxtaposition shows how important it is to consider multiple studies and how frequent discrepant results occur.  While the second study does not show a significant fracture risk, the preponderance of evidence does show an association between celiac disease and low BMD particularly in adults. In addition, a gluten free diet has been shown to reverse low BMD in those with CD.

Relevant studies:

  1. Gastroenterology 2010; 139: 763.
  2. Aliment Pharmacol Ther 2000; 14: 35-43.
  3. JPGN 2003; 37: 434-6.
  4. Gut 1996; 38: 322-7.

In the third study, the investigators looked at “complementary” investigation in children with CD.  These included tests like hemoglobin, ferritin, folate, vitamin B12, calcium, vitamin D, and thyroid assays.  Between 2009-2014, 182 children were evaluated included 119 with new diagnosis. Key findings:

  • At time of diagnosis: Iron deficiency (28%), iron deficiency anemia (9%), folate deficiency (14%), vitamin B12 (1%), and vitamin D deficiency (27%) were identified. No hypocalcemia or thyroid dysfunction was found.
  • At followup: iron deficiency (8%), iron deficiency anemia (2%), folate (3%), vitamin D (25%) were identified and no other abnormalities were evident.
  • The investigators concluded that these complementary tests “are relevant at the time of diagnosis of CD but have little diagnostic yield during followup-visits” after institution of gluten-free diet.

My take: Particularly at followup, identification of nutrient deficiencies is typically similar to the general population.

Related posts:

Castillo San Felipe del Morro, San Juan

Castillo San Felipe del Morro, San Juan

Piling on PPIs -Now Concerns about Dementia

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A recent study (see abstract below -from Mike Hart) indicates the possibility that proton pump inhibitors (PPIs) could increase the risk of dementia to a small degree.  Despite the big numbers, this study cannot adequately control for numerous factors that could influence these results.  As is often said, association does not prove causation.  Nevertheless, this study is another reminder to use PPIs when indicated and to use them for the appropriate length of therapy.

Here’s NBC News Narrative: Popular Heartburn Drugs Linked to Dementia

ONLINE FIRST

Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis

Willy Gomm, PhD1; Klaus von Holt, MD, PhD1; Friederike Thomé, MSc1; Karl Broich, MD2; Wolfgang Maier, MD1,3; Anne Fink, MSc1,4; Gabriele Doblhammer, PhD1,4,5,6; Britta Haenisch, PhD1

JAMA Neurol. Published online February 15, 2016. doi:10.1001/jamaneurol.2015.4791
 
ABSTRACT

Importance  Medications that influence the risk of dementia in the elderly can be relevant for dementia prevention. Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases but have also been shown to be potentially involved in cognitive decline.

Objective  To examine the association between the use of PPIs and the risk of incident dementia in the elderly.

Design, Setting, and Participants  We conducted a prospective cohort study using observational data from 2004 to 2011, derived from the largest German statutory health insurer, Allgemeine Ortskrankenkassen (AOK). Data on inpatient and outpatient diagnoses (coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision) and drug prescriptions (categorized according to the Anatomical Therapeutic Chemical Classification System) were available on a quarterly basis. Data analysis was performed from August to November 2015.

Exposures  Prescription of omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole.

Main Outcomes and Measures  The main outcome was a diagnosis of incident dementia coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. The association between PPI use and dementia was analyzed using time-dependent Cox regression. The model was adjusted for potential confounding factors, including age, sex, comorbidities, and polypharmacy.

Results  A total of 73 679 participants 75 years of age or older and free of dementia at baseline were analyzed. The patients receiving regular PPI medication (n = 2950; mean [SD] age, 83.8 [5.4] years; 77.9% female) had a significantly increased risk of incident dementia compared with the patients not receiving PPI medication (n = 70 729; mean [SD] age, 83.0 [5.6] years; 73.6% female) (hazard ratio, 1.44 [95% CI, 1.36-1.52]; P < .001).

Conclusions and Relevance  The avoidance of PPI medication may prevent the development of dementia. This finding is supported by recent pharmacoepidemiological analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of β-amyloid in the brains of mice. Randomized, prospective clinical trials are needed to examine this connection in more detail.

Related blog post: Proton Pump Inhibitors Webinar

Unrelated article (from Ben Gold): J Molina-Infante et al. Am J Gastroenterol 2015; 110: 1567-1575.  This study examined 75 patients (mean age 38 years) with proton-pump inhibitor responsive esophageal eosinophilia (PPI-REE).  55 (73%) had long-term sustained histologic remission with low-dose PPI therapy (20 mg once or twice daily). In addition, the article noted that 9 of 10 relapsers with distal eosinophilia were noted to have a CYP2C19 rapid metabolizer genotype and regained histologic remission with dose intensification.

Briefly noted: AI Sharara et al. Clin Gastroenterol Hepatol 2016; 14: 317-21.  Among 414 who met inclusion criteria (at least 6 months of PPI usage and at least 1 serum magnesium level), 57 (13.8%) had at least 1 low serum magnesium –44 of these patients had recognizable causes (eg. diuretics, chronic diarrhea).  Of the remainder who continued with PPI therapy, the level was normal at final measurement and only mildly low levels were noted previously.  Thus, in patients without other reasons for low magnesium, the authors found that use of a PPI does not appear to be associated with hypomagnesemia.

 

Guts and Valentines?

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I learned this week that the Crohn’s & Colitis Foundation of America (CCFA) was founded in part  based on a love story:

From CCFA: Irwin M. Rosenthal, one of the visionary co–founders of CCFA, and Suzanne were due to be married in a few months time when suddenly Suzanne became very ill. Motivated by her struggle with Crohn’s disease, Irwin, along with William and Shelby Modell, and Dr. Henry D. Janowitz, established the Foundation for Research in Ileitis, now known as the Crohn’s & Colitis Foundation of America.

To send an CCFA eValentine: CCFA Valentine E-card

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What We Should Not Worry About

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A few useful studies provide reassurances regarding exposures in the prenatal period and perinatal period that we should NOT worry about.

CN Bernstein et al. Clin Gastroenterol Hepatol 2016; 14: 50-7.

In this study with 1671 individuals with inflammatory bowel disease and 10,488 controls, “people with IBD were not more likely to have been born by cesarean section than controls or siblings without IBD.  These findings indicate that events of the immediate postpartum period that shape the developing intestinal microbiome do not affect risk for IBD.”

J Julvez et al. Am. J. Epidemiol. (2016) Full Text Link: doi: 10.1093/aje/kwv195. First published online: January 5, 2016 (thanks to Mike Hart for this reference)

For parents of autistic kids who avoid fish, this article provides information indicating that this is counter-productive.  ” Seafood consumption during pregnancy is thought to be beneficial for child neuropsychological development, but to our knowledge no large cohort studies with high fatty fish consumption have analyzed the association by seafood subtype.” The authors “evaluated 1,892 and 1,589 mother-child pairs at the ages of 14 months and 5 years, respectively, in a population-based Spanish birth cohort established during 2004–2008…” Key finding: “Consumption of large fatty fish during pregnancy presents moderate child neuropsychological benefits, including improvements in cognitive functioning and some protection from autism-spectrum traits.”

My take: We often worry about the wrong things.  These articles provide reassurance that mode of birth and consumption of seafood during pregnancy are things we should not worry about.

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