Probiotics and Recurrent Abdominal Pain

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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 Pediatr. Published 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

 

What to Do with Adolescents with Common Bile Duct Stones

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Many times throughout the year we will receive a request to accept a 15-17 year old weighing more than 200 pounds with gallstones who needs to be transferred so that he/she can be cared for in a pediatric facility. The really crazy part is that some of these ‘kids’ need to transferred back to an adult facility to have an ERCP to remove the gallstones if they are lodged in the common bile duct (CBD). Very few pediatric gastroenterologists are adequately trained in ERCP.

A recent retrospective study (PC Bonasso et al JPGN 2019; 68: 64-7) shows some of the consequences of this problem –longer hospitalizations and delays in treatment. The authors compared 79 (48%) pediatric patients who required transfer compared to 85 (52%) who were managed at the tertiary care pediatric hospital.  The median age was 15 years with 42% obese and 23% overweight.

Key findings:

  • Transfer group patients had longer length of stay, median 7 days vs 5 days for non-transfer group (P< 0.0001) and more days between ERCP and surgery.
  • Transfer patients were more likely to have an MRCP (34% vs 8% for non-transfer).
  • Transfer patients were more likely to have a stent placement, 9% vs 5% (which would require a subsequent anesthetic to remove).
  • Transfer patients were more likely to have a non-therapeutic ERCP;  stone/sludge removal was 70% in transfer group vs 86% in non-transfer group. This could be related to the delay (eg. more time for stone to pass) or due to the evaluation by team not responsible for ERCP.

The authors note that there are fewer than 20 pediatric gastroenterologists trained in ERCP; this is not likely to change much in the near term due to the large number of ERCPs needed to become proficient and few options for pediatric training. Their study notes that 46% had adult gastroenterologist management for non-transfer group.

My take: This is clearly an area in need of collaboration.  More pediatric hospitals need to have adult gastroenterologists available and adult hospitals need to consider keeping some of these young adults to improve both the care and costs for these individuals.

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This article was referenced previously on this blog

 

How Safe is Marijuana?

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A recent link to Malcolm Gladwell’s article in the New Yorker: Is Marijuana as Safe as We Think? One of my sons informed me of this article.

Excerpt from Malcolm Gladwell’s analysis:

A few years ago, the National Academy of Medicine convened a panel of sixteen leading medical experts to analyze the scientific literature on cannabis. The report they prepared, which came out in January of 2017, runs to four hundred and sixty-eight pages. It contains no bombshells or surprises, which perhaps explains why it went largely unnoticed. It simply stated, over and over again, that a drug North Americans have become enthusiastic about remains a mystery.

For example, smoking pot is widely supposed to diminish the nausea associated with chemotherapy. But, the panel pointed out, “there are no good-quality randomized trials investigating this option.” We have evidence for marijuana as a treatment for pain, but “very little is known about the efficacy, dose, routes of administration, or side effects of commonly used and commercially available cannabis products in the United States.” The caveats continue. Is it good for epilepsy? “Insufficient evidence.” Tourette’s syndrome? Limited evidence. A.L.S., Huntington’s, and Parkinson’s? Insufficient evidence. Irritable-bowel syndrome? Insufficient evidence. Dementia and glaucoma? Probably not. Anxiety? Maybe. Depression? Probably not.

Then come Chapters 5 through 13, the heart of the report, which concern marijuana’s potential risks. The haze of uncertainty continues. Does the use of cannabis increase the likelihood of fatal car accidents? Yes. By how much? Unclear. Does it affect motivation and cognition? Hard to say, but probably. Does it affect employment prospects? Probably. Will it impair academic achievement? Limited evidence. This goes on for pages…

Several points discussed in article:

  • Marijuana may increase the risk of psychiatric illnesses. “Many people with serious psychiatric illness smoke lots of pot. The marijuana lobby typically responds to this fact by saying that pot-smoking is a response to mental illness, not the cause of it—that people with psychiatric issues use marijuana to self-medicate. That is only partly true. In some cases, heavy cannabis use does seem to cause mental illness”…
  • Marijuana may increase aggression,  In the state of Washington was the first U.S. jurisdiction to legalize recreational marijuana. “Between 2013 and 2017, the state’s murder and aggravated-assault rates rose forty per cent—twice the national homicide increase and four times the national aggravated-assault increase”
  • Does cannabis serve as a gateway drug?  Like e-cigarettes, cannabis is being formulated into products attractive to youth: gummy bears, bites, and brownies.

My take (borrowed in part from author): “Permitting pot is one thing; promoting its use is another.” We really don’t know that much about marijuana.

CDC Link: Marijuana and Public Health

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Relooking at Medications for Constipation-Predominant Irritable Bowel Syndrome

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A recent study (CJ Black et al. Gastroenterol 2018; 155: 1753-63) examined the effectiveness of secretagogues for constipation-predominant irritable bowel syndrome (IBS-C).  The authors conducted a systematic review and network meta-analysis with 15 eligible randomized controlled trials (8462 patients).

Key findings:

  • Linaclotide (290 mcg per day) was ranked first in efficacy using the end point recommended by the FDA for IBS-C trials
  • Tenapanor (50 mg twice a day) was ranked first for bloating
  • Plecanatide (6 mg per day) ranked first for safety
  • Diarrhea was significantly more common with all of the secretagogues except for lubiprostone; nausea was significantly more common with lubiprostone

The authors acknowledge the limitations in comparing medicines without direct head-to-head trials (which may never occur).  They state that linaclotide being superior to other treatments had a probability of 88%.

My take: This study indicates that linaclotide may be more likely to be effective than other IBS-C medications; all of these secretagogues have been shown to be superior to placebo.

In this same issue, pgs 1666-9 (J Ruddy), a patient describes her long journey with abdominal pain/GI symptoms.  She describes her initial experiences with physicians who were dismissive and not attentive. Ultimately, a physician listened to her and  helped her improve after explaining that she had a postinfectious IBS and provided treatment.

Related study: S Ishague et al. BMC Gastroenterol 2018; 18:71.  This randomized controlled trial which compared a multistrain probiotic (Bio-Kult, n=181) to placebo (n=179).  The probiotic group had a 69% decrease in abdominal pain compared to a 47% decrease in placebo group.

Sunrise, Death Valley

Five Ways to Lower the Risk of Colon Cancer

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A recent study (PR Carr, et al. Gastroenterol 2018; 155: 1805-15) used an ongoing population-based case-control DACHS study (in Germany since 2003) to determine the effects of lifestyle factors on the risk of colorectal cancer (CRC).

Among 4092 patients with CRC and 3032 control patients without CRC, the investigators examined five factors:

  • Smoking – For smoking, one point was given for being a nonsmoker or a former smoker with <30 pack years.
  • Alcohol consumption –  For alcohol, a point was garnered if consumption was moderate according to AICR recommendations.
  • Diet –  Diet quality was assessed based on WCRF/AICR recommendations (supplement table 1 [https://doi.org/10.1053/j.gastro.2018.08.044]). 1 point was given with highest diet scores.
  • Physical activity – A point was given with favorable physical activity which was based on moderate-intensity aerobic exercise for at least 150 minutes per week or 75 minutes of vigorous activity.
  • Body fatness – Those with a BMI between 18.5 and 25 which was considered a healthy weight were awarded a point.

 Key findings:

Compared to patients with 0 or 1 healthy lifestyle factor:

  • Participants with 2 points had odds ratio of 0.85
  • Participants with 3 points had odds ratio of 0.62
  • Participants with 4 points had odds ratio of 0.53
  • Participants with 5 points had odds ratio of 0.33

My take (borrowed from authors): Overall, 45% of CRC cases could be attributed to these lifestyle factors.  This occurred despite the patient’s genetic profile

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Why Hospital$ Are Hiring More Doctor$

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A recent article in the Wall Street Journal details the consequence of hospitals hiring more doctors, especially primary care.:

The Hidden System That Explains How Your Doctor Makes Referrals

Key points:

  • “Hospitals are getting more aggressive in directing how physicians refer for things such as surgeries, specialty care and magnetic resonance imaging scans, or MRIs.” This often results in more out-of-pocket expenses for patients.
  • “Insurers have been working to steer patients toward doctors’ offices and other non-hospital locations for many types of care, because they are generally less expensive. The same service often costs twice as much or more when delivered in a hospital setting, compared with a doctor’s office.”

Thanks to Bryan Vartabedian’s 33mail for this reference. He notes: “The doctors in the private space relished the article as evidence of the dangers of the physician employee. But we have to remember that when doctors own their own businesses, the pressure to do things for money is huge.”

Near Zabriskie Point at Sunrise, Death Valley

NPR: How to Help Kid Overcome Fear of Doctors and Shots

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From NPR: How to Quell A Kid’s Fear of Doctors and Shots

An excerpt:

Sasha Albani, a child and adolescent psychotherapist… suggests parents calm themselves and find age-appropriate ways to help children face their medical fears instead of fleeing them.

For very young kids, who have a hard time putting words to thoughts and emotions, imaginary play with mom or dad before the appointment can help, Albani says.

“Use a toy doctor kit to explain what will happen at the appointment and to discuss your child’s specific worries,” she advises…

Children under age 6 may benefit from the book, “Daniel Visits the Doctor” by Becky Friedman.

Kids with needle phobias may be helped by reading, “Lions Aren’t Scared of Shots: A Story for Children About Visiting the Doctor,” by Howard S. Bennett. And the book “Imagine a Rainbow: A Child’s Guide for Soothing Pain,” by Brenda S. Miles, may be useful for older kids between the ages of 8 and 10.

Playing The Coping Skills Board Game can bolster the confidence of preteens… And smartphone apps like “Stop, Breathe & Think Kids” can be a fun way to learn mindful breathing techniques and other relaxation tips that help turn down the alarm of worrisome feelings.

Ledipasvir-Sofosbuvir for Children 6-11 years

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Almost two years ago, the FDA approved Ledipasvir-Sofosbuvir (aka Harvoni) for pediatric patients 12-17 years of age with hepatitis C virus (HCV) infection.  Now, a recent study (KF Murray, WF Balistreri, S Bansal et al. Hepatology 2018; 68: 2158-66) is likely to expedite approval for children ages 6-11 years of age.

In this open-label study with 92 patients, 88 had genotype 1, 89 received treatment with ledipasvir-sofosbuvir without ribavirin for 12 weeks, 97% were perinatally-infected, and 78% were treatment naive.  The median age was 9 years. The dose (determined by intense pharmacokinetics) was 45 mg-200 mg (half the adult dosage). Two patients with genotype 3 HCV received ledipasvir-sofosbuvir for 24 weeks along with ribavirin.

Key findings:

  • SVR12 was 99% (91/91).  The single patient without SVR12 had relapsed 4 weeks after completing a 12 week treatment course.
  • Ledipasvir-sofosbuvir was well-tolerated; the common adverse events reported were headache and pyrexia.

The authors note that while most children are considered to have mild symptoms or are asymptomatic, some progress to have significant fibrosis or cirrhosis, a small minority develop hepatocellular carcinoma, and HCV infection can impact both cognitive development and overall health.

My take: This study confirms that effectiveness of DAA therapy with ledipasvir/sofosbuvir in children as young as 6 years of age.

Related study: F Tucci et al. Hepatology 2018; 68: 2434-37. The authors report the successful treatment with ledipasvir/sofosbuvir of an infant with both SCID and HCV infection.

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Mesquite Flat Sand Dunes, Death Valley

Vedolizumab -Could it Work for Eosinophilic Gastroenteritis?

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A recent study with only five patients (HP Kim et al. Clin Gastroenterol Hepatol 2018; 16: 1992-4) examined the use of vedolizumab for eosinophilic gastroenteritis.. The rationale was that α4β7 integrin may play an important role in eosinophilic localization in IBD and that blocking α4β7 may inhibit eosinophil recruitment to intestinal mucosa.  In addition, there are few proven therapies for EGE beyond steroids and dietary treatments.  The five patients in this study had been tried on numerous prior treatments and had a disease course of 6-17 years prior to vedolizumab.

Key findings:

  • Two of the five patients were able to wean/discontinue steroids, reported symptom improvement and had normal gastric and small bowel biopsies.  The median time to histologic followup was 2.2 months.
  • A third patient reported symptom improvement but declined a followup biopsy.

My take: A larger study of vedolizumab is needed for EGE.

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Calgary