Probiotics and Recurrent Abdominal Pain

Numerous articles have questioned the effectiveness of probiotics for many of the conditions for which they have been promoted.  A recent systematic review (T Newlover-Delgado, et al. JAMA PediatrPublished online December 28, 2018. doi:10.1001/jamapediatrics.2018.4575) concludes that probiotics “may be effective in the shorter term in improving pain in children with” recurrent abdominal pain (RAP). Thanks to Ben Gold for this reference.

This study extended findings from a 2009 Cochrane review (Huertas-Ceballos AA, et al Cochrane Database Syst Rev 2009; (1):CD003019).  In total, the authors identified 19 eligible studies; of these 15 were not included in the previous review. The most common probiotic studied was Lactobacillus rhamnosus GG in 5 trials.

Key findings:

  • At 0 to 3 months postintervention, ‘based on moderate-quality evidence (odds ratio [OR], 1.63, 95% CI 1.07-2.47; 7 studies, 772 children). The number needed to treat for an additional beneficial outcome was 8.” 
  • There were only 2 studies with results extending 3 to 6 months.  These studies also found reduction in pain in the probiotic-treated children, OR 1.94 (CI 1.10-3.43). 
  • Interestingly, the authors note that fiber-based treatments were not considered more effective than placebo, despite a similar OR of 1.83.  Due to the small number of children in these studies with fiber (n=136), the CI were wide: 0.92-3.65.

The authors discuss some of the limitations such as variations in definitions, choice of probiotic and dosage, and short-term duration.  There is not a discussion of selection bias.  It is quite possible that some negative studies were completed which were not published which could further lower or eliminate the potential benefit.

My take: Probiotics may be helpful for children with recurrent abdominal pain; it is certainly not a panacea.

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Moon over Zabriskie Point, Death Valley -just before sunrise

Almost sunrise at Zabriskie Point, Death Valley

 

Why Stomach Pain Improves in the Summer

A recent small study (published online: KL Pollard et al. JPGN  doi: 10.1097/MPG.0000000000001886) indicates that the well-recognized phenomenon of improvement in functional abdominal pain during the summer months is associated with lower anxiety.  Here is a link to abstract: Seasonal Association of Pediatric Functional Abdominal Pain Disorders and Anxiety

Excerpt:

Results:

In a sample of 34 participants who completed both questionnaires, 22 reported improvements during the summer months. These participants reported a significantly higher seasonal decrease in anxiety than participants whose children’s symptoms did not improve from spring to summer (mean decrease 2.21 vs 0.08, P = 0.017). Both groups reported equal improvements in sleep and decreased stress from spring to summer. Neither group experienced statistically significant seasonal change in physical activity or fruit, vegetables, dairy, or caffeine consumption.

Conclusions:

This study suggests that amelioration of gastrointestinal symptoms in pediatric patients with AP-FGID during summer months is associated with amelioration of anxiety in the same time period. It is not yet clear whether decreased anxiety is the cause or effect of decreased AP-FGID symptom

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#NASPGHAN17 Selected Abstracts

Some of the abstracts that were presented at this year’s meeting –see below.  For a listing of the titles/authors presented, use this link: NASPGHAN Annual Mtg 2017

For complete abstracts: NASPGHAN 2017 Scientific Abstracts

Using a standardized approach along with a protocol for oral cleanouts and saline enemas if needed, the authors showed a marked decline in admissions for fecal impaction:

In this study, the authors found that low risk patients had a 91% likelihood of a negative scope.  However, on closer inspection, this rate OVERESTIMATES the likelihood of finding anything significant.  Most findings in the low risk group had questionable benefit from being identified on endoscopy including “acute colitis,” and H pylori.

The following abstract showed that in patients with EoE and not PPI-REE that topical steroids alone were as effective as PPI with topical steroids.

The following slides indicate the development of A4250, a bile acid transporter, which reduces pruritus. The presenter stated that this drug essentially is a chemical diversion which could replace biliary diversion for pruritic conditions like PFIC and Alagille syndrome.

Best Tweets from Postgraduate Course: #NASPGHAN15

Since I am not at this year’s national meeting, I have followed some of the information on social media.  Here are some of the best tweets:

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UTI in Infancy–New Risk Factor for Chronic Abdominal Pain?

A recent study (Rosen JM, et al. JPGN 2015; 60: 214-16) identifies a history of a urinary tract infection (UTI) in infancy as a risk factor for development of chronic abdominal pain.

The authors identified 57 patients with a history of UTI during the first year of life and compared them to 58 sibling controls.  Mean age of UTI was 4.8 months and mean time since UTI was 9.3 years.

Key finding:

  • Chronic abdominal pain was noted in 10 (17.5%) of patients with prior UTI compared with 2 (3.4%) of controls (P=0.02)

The authors state that this is the first study showing an infection outside the GI tract could increase the risk of chronic abdominal pain.  It is not clear to me if the UTI would truly be a sensitizing factor or whether other factors like the administration of antibiotics could play a role.

Bottomline: While this is a small study and the incidence of chronic abdominal pain was fairly low in both groups, it suggests that a history of a UTI may be a risk factor for recurrent abdominal pain; a bigger study is needed to validate these findings.

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From Twitter

Trending on Twitter -CampWeeKanEatIt Shoutout

Brave New World: Psychotropic Manipulation & Pediatric Functional GI Disorders

A recent review (JPGN 2014; 59: 280-87) provides helpful advice for the use of psychotropic medications in pediatric functional GI disorders.  That being said, a couple key caveats need to be stated first and foremost:

  • “A minority of psychotropic drugs has been studied in children and safety data remain inadequate.  Psychotropic drugs used for gastrointestinal symptoms in pediatric patients will be off-label for the foreseeable future.”
  • “Descriptions of individual drugs in the present review are too brief to provide accurate guidance to someone who is not already familiar with them.”

Given the limited data, the authors, in my opinion, bravely state recommendations regarding these medications.  Despite their common usage, providing explicit recommendations is quite uncommon.  The title of the blog references Aldous Huxley’s book which discusses psychological manipulation.  This book in turn is titled after a line from Shakespeare’s The Tempest, Act V, Scene I (from Wikipedia):

“O wonder!
How many goodly creatures are there here!
How beauteous mankind is! O brave new world,
That has such people in’s.”

Back to the review of psychotropic medications, the authors provide a rationale/pathophysiologic mechanism for the use of these drugs mainly for recurrent abdominal pain and chronic nausea/dyspepsia.  Table 1 lists the authors’ specific suggestions regarding first to fourth choices:

  • For abdominal pain, first choice was amitriptyline, followed by gabapentin, clonidine patch, and SSRI.
  • For nausea/dyspepsia,  first choice was amitriptyline, followed by mirtazapine, buspirone, and clonazepam.
  • For d-IBS,  first choice was amitriptyline, followed by alosetron [not a psychotropic], clonidine patch, and SSRI.
  • For c-IBS (along with polyethylene glycol),  first choice was imipramine, followed by lubiprostone [not a psychotropic], gabapentin, and SSRI.

Table 2 provides dosing suggestions, and common adverse effects.  For example, with amitriptyline, suggested dose is 10-50 mg qhs and “best to begin low dose…titrate up by response.” Other suggestions:

  • SSRIs: “should begin with low dose; titrate up by response.  With SSRIs, benefit is usually apparent after 4 to 6 wk.  Most GI adverse effects disappear in 1 to 2 wk.”
  • Mirtazapine: 7.5 mg dosing for sleep, 15-30 mg qAM for nausea/dyspepsia (higher dose is usually not sedating.  “Few drug interactions; safer than TCAs.” Weight gain is common.
  • Buspirone: 10-60 mg/day, divided twice daily; “may start with half dose in the morning.” Avoid grapefruit juice. Can “used alone or in combination with SSRIs or TCAs.”
  • Gabapentin (100 mg BID to 800 mg TID). “Rare adverse effects include drowsiness and blurred vision…Safe but only effective in about one-third of patients.”
  • Recommends that second-generation antipsychotics (quetiapine, risperidone, and olanzapine) be used only in collaboration with child psychiatry (Figure 2)

Additional pointers:

TCAs:“In RCTs, among children with functional abdominal pain, both amitriptyline and placebo were associated with an excellent therapeutic response.”  It is interesting to note the authors lack of critical comments regarding this statement.  “The usual dose of amitriptyline for chronic functional pain is 1 mg/kg/day up to a maximum of 50 mg/day.”

TCAs and EKGs: “at doses <1 mg/kg/day used to treat chronic pain and nausea, there have been no reports of death or cardiac arrhythmias in >60 years.  An EKG before starting a TCA is unnecessary in otherwise healthy children and adolescents, but may be advisable in those with a personal or family history of corrected QT interval prolongation or heart disease, or in children requiring a dose >50 mg/day.”

TCAs: some tricyclics may be less sedating and constipating including imipramine, doxepin, and nortriptyline.  The later two also come in liquid formulations.

SSRIs: “may be used in combination with TCAs in teens and adolescents…using them simultaneously may increase serum concentrations of both.” “In children there was a single RCT showing citalopram superior to placebo in IBS. Some clinicians obtain an EKG assessing corrected QT interval before initiating citalopram doses >20 mg daily.”

Clonidine has “improved diarrhea-predominant IBS…Common adverse effects include dry mouth, drowsiness, dizziness, and tiredness…checking blood pressure at each clinic visit [is recommended].” It is available as a patch (0.1-0.3 mg/wk).

Melatonin: dosed 3- to 10-mg at bedtime can promote sleep.

Take-home message: This article provides practical advice for the use of these agents.  Discussion with patients and parents regarding the role of these medications in targeting CNS arousal which perpetuates disabling chronic symptoms is crucial as well.  More studies are needed to determine conclusively their effectiveness.

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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.

 

Change the Name: “Functional” is Lousy

A recent commentary explains why “functional” pain is such a lousy term (JAMA Pediatr. Published online June 02, 2014. doi:10.1001/jamapediatrics.2014.530 –thanks to Ben Gold for this reference).  In pediatric GI practice, functional gastrointestinal disorders (FGIDs) constitute a large part of clinical work.

The author, Neil Schechter from the Chronic Pain Program in Boston, makes several important observations:

  • “There is general dissatisfaction with the terminology.”  This stems from the fact that “in common parlance today, functional disorders are typically assumed to be a product of psychological distress.” Yet, parents/patients are “not ready to accept a strictly psychological explanation.”
  • The idea that functional pain is solely a psychological disturbance is inaccurate.  Though, anxiety and depression are common associated problems which often contribute to symptoms.  He states that “hyperexcitability” of the nervous system is “the core biological link and final common pathway for the creation of functional pain disorders.”
  • This category should be labeled dysfunctional pain.  “In effect, calling pain ‘functional’ is like calling disease, ‘ease.'”
  • These disorders frequently respond to centrally acting therapies including antidepressants, anticonvulsants, exercise, cognitive behavioral therapy, and acupuncture.
  • “The search for an appropriate term for these pain problems is far more than semantic…[a patient’s] understanding of their illness is clearly linked to their compliance with medical advice…it may stem their desire for additional costly investigation.”
  • Dr. Schechter proposes the term “primary pain disorder.”  “Unlike Shakespeare’s rose, functional pain would benefit from a new name.”

Take-home message: I wish I had written this commentary.  Explaining “functional” pain and “irritable bowel syndrome” are Sisyphean tasks.  Better nomenclature could ease the burden.  Join me in abandoning the use of the word “functional.”

In the same issue, an editorial on the “Role of Celiac Disease Screening for Children with Functional Gastrointestinal Disorders” (JAMA Pediatr. 2014;168(6):514-515. doi:10.1001/jamapediatrics.2013.5418) comments on a study (JAMA Pediatr. 2014; 168(6):555-60) in the same issue which reports a 4-fold higher prevalence of celiac disease among children who meet clinical criteria for irritable bowel syndrome.  The study reports the results from a cohort of 992 children identified with recurrent abdominal pain in a primary care setting.  In the editorial, the authors note:  “When grouped together, the prevalence rate of celiac disease among all children with FGIDs (IBS included) approaches 2%.  Celiac disease screening in this population would result in a positive tTG-IgA test result in 4%…However, 53% of all positive test results would be falsely elevated.”  As such the editorial advocates in favor of screening for celiac disease in children with IBS but not all FGIDs.

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