Relooking at Medications for Constipation-Predominant Irritable Bowel Syndrome

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

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 modreate-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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Cool Genetic Facial Dysmorphism App

I recently downloaded a free Genetics App called Face2Gene.  My colleague Jeffery Lewis told me about this app.  This App helps identify specific genetic syndromes based on facial appearance.  In the first few weeks, a few syndromes that were identified included the following & this was based on very limited usage:

  • Coffin-Lowry
  • Williams Syndrome

Why Hospital$ Are Hiring More Doctor$

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

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

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?

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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