Microbiome Predicts Constipation plus two

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In brief:

G Parthasarathy et al. Gastroenterol 2016; 150: 367-79.  Mucosal and fecal microbiota samples were collected from 25 healthy women and 25 women with chronic constipation.  Key finding: The mucosal, but not fecal, microbiota profile were 94% predictive of constipation. The associated editorial (pg 300) provides a framework for understanding these findings and show the complexity of trying understand the interations between diet, motility and microbes.

S Fukudo et al. Gastroenterol 2016; 150: 358-66.  This prospective study of Ramosetron for 576 women with IBS-D.  Key finding: 50.7% of treatment patients reported global improvement compared with 32.0% of control patients.  Patients had less abdominal pain, less discomfort, and better stool consistency.  Ramosetron, a 5-HT3 antagonist, has not been reported to cause ischemic colitis (in contrast to alosetron).

In followup to a post earlier in the week, another worrisome study on the Zika virus in pregnancy from NEJM. Here’s an excerpt:

Fetal abnormalities were detected by Doppler ultrasonography in 12 of the 42 ZIKV-positive women (29%) and in none of the 16 ZIKV-negative women. Adverse findings included fetal deaths at 36 and 38 weeks of gestation (2 fetuses), in utero growth restriction with or without microcephaly (5 fetuses), ventricular calcifications or other central nervous system (CNS) lesions (7 fetuses), and abnormal amniotic fluid volume or cerebral or umbilical artery flow (7 fetuses).

Farjado, Puerto Rico

Farjado, Puerto Rico

“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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Worried About the Zika Virus

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While Zika virus infections may not be seen frequently by pediatric gastroenterologists, this infection will be a common concern for the families we treat and we may end up taking care of children with feeding problems/neurologic impairment due to congenital infection.

I attended a recent Georgia American Academy of Pediatrics board meeting.  One of the topics discussed was the Zika virus.  An update was given by Dr. Harry Keyserling, chair of the infectious disease committee (who has given permission for me to share some of his slides).  Some of the important points from his talk:

  • The Zika virus shares some similarities with the Dengue virus. The Zika virus is a single-stranded RNA flavivirus. Incubation period is 3 days to a few weeks.  It can be acquired from mosquito bites, spread sexually, transplacentally or intrapartum.  It may be transmissible via blood, organ donation or possibly breastmilk.

 

History of Zika Virus

History of Zika Virus

Most are asymptomatic. The clinical spectrum in those with symptoms are noted above.

Most are asymptomatic. The clinical spectrum in those with symptoms are noted above.

  • 80% of infected individuals are asymptomatic.
Approximate distribution of mosquito vector

Approximate distribution of mosquito vector

  • Due to the geographic distribution of the vector, it is likely that there will be many more cases in Georgia.

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US DATA 1

US DATA 2

  • The most alarming association has been with microcephaly.  In some locations, there have been recommendations to avoid pregnancy until 2018.  After natural infection has spread, it is likely to lead to immunity and then should be safe to become pregnant.

Prevention

  • Zika can be acquired through sexual-transmission which indicates that pregnant women in endemic areas could need to avoid sex.

More resources:

My take: Because the Zika virus is going to continue to spread and the methods for prevention are not entirely effective, the next few years are going to present a lot of challenges.  This will continue until some population immunity develops (following infection or perhaps after development of an effective vaccine).

Is Gabapentin a Good Idea for Neonates with Irritability?

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A recent case report (CM Cotten, et al. J Pediatr 2016; 169: 310-2) retrospectively reviewed 11 neonates (8 preterm) who received gabapentin mainly for “visceral hyperalgesia/agitation.”  The starting doses generally ranged from a low of 5 mg/kg/dose every 24 hrs to 5 mg/kg/dose every 8 hrs.  Generally, there were improved symptoms and lower need for opioids and benzodiazepines; the most frequent adverse reaction noted was bradycardia.  The authors caution against abrupt withdrawal of gabapentin.

My take: Like most medications, gabapentin has not been adequately evaluated in neonates, but it would not surprise me if it were useful for irritability.

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

Old San Juan

Old San Juan

More on Hepatitis B Treatment in Children

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A recent post (New Hepatitis B Treatment Guidelines -AASLD) described the updated treatment recommendations.  When these guidelines were published, a separate review devoted specifically to pediatrics was published (Hepatology 2016; 63: 307-18).

Some of the key points:

  • This pediatric review included 14 studies with 1425 children.  The authors note that 7 of these trials had a high risk of bias.  Also, the studies are limited by relying on surrogate markers of long-term outcomes as clinical outcomes like cirrhosis, HCC, and death are rare in childhood.
  • Among oral agents, entecavir and lamivudine are approved for use in children ≥ 2 years, whereas adefovir and tenofovir are approved for use in children ≥ 12 years.  Both lamivudine and adefovir are associated with frequent development of viral resistance
  • For children with elevated ALT (>1.5 times upper limit of normal [ULN]), treatment is recommended:

9A. The AASLD suggests antiviral therapy in HBeAg-positive children (ages 2 to <18 years) with both elevated ALT and measurable HBV DNA levels, with the goal of achieving sustained HBeAg seroconversion.

Why not treat everyone?

  • Children with immune-tolerant HBV infection (normal or near-normal ALT [< 1.5-2 times ULN] along with high HBV DNA [>10 million IU/mL]), “are not typically candidates for treatment because treatment with any of the currently available drugs has not been demonstrated to improve HBeAg seroconversion compared with no treatment.”
  • Children with ALT >10 time ULN may be in the process of spontaneous seroconversion “and should be observed for several months before treatment” is initiated.
  • “Prolonged treatment with nucleoside or nucleotide analogs in children who are in immune-tolerant phase has not been associated with substantial benefit and carries a risk of developing antiviral drug resistance…An exception may be those…undergoing immunosuppressive therapy.”
Mina Falls, El Yunque Rainforest

Mina Falls, El Yunque Rainforest

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

Surgery Resident Sleep & Flexibility in Training

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A recent study (KY Bilimoria et al. NEJM 2016; DOI: 10.1056/NEJMoa1515724) indicates that some flexibility in training hours did not result in increased adverse outcomes and improved continuity of care. This study examined the care of nearly 140,000 patients.

For a 2 minute quick take -video available at this link along with full-text and abstract: National Cluster-Randomized Trial of Duty-Hour Flexibility in Surgical Training

Related blog posts:

Guidelines: Microscopic Colitis & Vascular Diseases of the Liver

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In brief:

AGA Microscopic Colitis Guideline: GC Nguyen et al. Gastroenterol 2016; 150: 242-6. Technical review DS Pardi et al. Gastroenterol 2016; 150: 247-74. Patient guide: pg 275.

EASL Clinical Practice Guidelines: Vascular diseases of the liver. J Hepatology 2016; 64: 179-202.  Topics covered include Budd-Chiari, Portal vein obstruction, Heriditary hemorrhagic telangiectasia, veno-occlusive disease of the liver, management of anticoagulation in liver disease

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

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Breath Test Reliability for Bacterial Overgrowth

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While breath test reliability for bacterial overgrowth has been a concern for a long time, another study (EC Lin, BT Massey. Clin Gastroenterol Hepatol 2016; 14: 203-08) takes a new approach to show that the glucose breath tests are subject to a high false-positive rate.  This is often related to rapid transit time.

Here’s what they did:

In a retrospective study, they examined data from 139 patients with suspected small bowel bacterial overgrowth (SBBO) (2003-2013).  Abnormal glucose breath tests were indicated by either hydrogen or methane >15 parts per million within 90 minutes after glucose ingestion.  In addition, they used concurrent scintigraphy (by labeling glucose with a Tc99m compound) to determine whether this increase occurred before or after glucose bolus arrived in the cecum.

Findings:

  • 46 (33%) had abnormal breath tests.  Of these 22 (48%) had false-positive results due to colonic fermentation.
  • False-positives were higher (65%) in the subset of patients with prior upper gastrointestinal surgery.  The nonsurgical group had a 13% false-positive rate.
  • This study shows that with rapid transit, significant glucose malabsorption is possible.

Because direct culture of small bowel contents is expensive, invasive and subject to contamination, physicians have relied on breath tests for diagnosis of SBBO or have empirically treated for SBBO.  The discussion and related editorial (pg 209) explain that lactulose breath testing is not more reliable than glucose breath testing.

My take: For patients with prior GI surgery (who are at the highest risk for SBBO), breath testing may not be more reliable than flipping a coin.  True positive results are more likely if hydrogen peak occurs within 60 minutes of glucose administration.

Related blog post: 

Flamenco Beach, Culebra

Flamenco Beach, Culebra