How Common are Clostridium difficile infections?

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In 2011, Clostridium difficile was estimated, by a recent report from the CDC (NEJM 2015; 372: 825-34) to result in 453,000 infections in the U.S. based on surveillance data from 10 geographic regions.

Other key findings:

  • Approximately 29,000 deaths were attributed to Clostridium difficile infections
  • 65.8% of cases were health care associated.
  • 24.2% had onset in the hospital
  • Increased risk was particularly notable among the elderly, with an rate ratio of 8.65 in those 65 years of age or older
  • The aggressive NAP1 strain was evident in 30.7% of health-care associated infections compared with 18.8% of community-associated infections

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Note to blog followers: Yesterday’s blog was retitled to “Radiologic Image for St. Patrick’s Day” rather than “Endoscopic Image for St. Patrick’s Day”

Withdrawing Therapy Leads To Relapse, Even if in Deep Remission

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A recent study, presented as an oral abstract (thanks to Jeff Lewis for forwarding this reference), indicates that even in patients in deep remission, withdrawal of anti-TNF therapy leads to relapse in about 50% even when thiopurines are continued; this is in agreement with previous posts (see below).

Full abstract: OP007 Relapse after Deep Remission in Crohn’s disease. Here are the results and conclusion from the abstract:

Results

Sixty one patients were included and followed-up for a median of 28 months (range 7-47). After withdrawal of anti- TNFa therapy (44 infliximab and 17 adalimumab) 47 (77%) patients continued thiopurines. 32 (52.5%) patients relapsed until the end of follow-up with a median time to relapse of 8 months (range 1-25). The cumulative probability of maintaining remission was 82% at 6 months, 59% at 1 year and 51% at 2 years. Analysis of 28 patients who were in deep remission (endoscopic healing; faecal calprotectin <150mg/kg; CRP <5mg/l) revealed no better survival (82%, 64% and 40% at 6 months, 1 and 2 years, respectively). Four (8%) of relapsing CD patients required surgery 5 to 19 months after anti-TNFa cessation (2 for new stricture development, 1 for medically refractory flare and 1 for high grade dysplasia). In multivariate model only disease localization was risk factor of disease relapse (colonic vs. ileal/ileocolonic: OR 0.16, 95%CI: 0.03-0.72; p=0.02). Type of anti- TNFa preparation, smoking, disease behaviour, corticosteroid or thiopurine therapy, biological markers and anti-TNFa trough levels did not impact disease relapse.

Conclusion

Approximately half of CD patients relapsed within 2 years after anti- TNFa discontinuation despite being in endoscopic remission when anti-TNFa was stopped. The highest relapse rate was observed during the 1st year. Ileal disease increased the risk of disease flare, while no other risk factor was identified.

Related blog posts:

Bryce Canyon

Bryce Canyon

Breath Testing for Bacterial Overgrowth

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A recent review (Clin Gastroenterol Hepatol 2014; 12: 1964-72) provides useful advice on testing for bacterial overgrowth and explains the limitations/obstacles in determining whether bacterial overgrowth is present.

Their recommendations:

  • Preparation: avoid antibiotics for 4 weeks prior to testing, avoid bismuth for 2-4 weeks, avoid probiotics for 2-3 weeks before testing, avoid consumption of non absorbable carbohydrates (eg. pasta, bread, fiber cereal, beans) the night prior
  • Glucose substrate for hydrogen breath testing is likely most suitable.  50 g in 250 mL.  Check baseline and then every 15 minutes over 120 minute testing interval.  Positive study: increase of 12 ppm (or more) over baseline and/or baseline >20 ppm (if proper test conditions)
  • Glucose breath test (GBT): sensitivity 20-93%, specificity 30-86%.  False-positive results can occur with rapid small-bowel transit.  GBT may not detect distal small bowel bacterial overgrowth.  Lactulose breath test (LBT) generally has lower specificity.
  • If breath testing is not available, small-bowel aspiration for quantitative culture is a reasonable consideration (challenging methodology).  Alternatively, a trial of empiric antibiotics may be considered if pretest probability is high.

Related blog post:

Two Shorts -Minimal Hepatic Encephalopathy and Fish Oil Protection

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Briefly noted: JPGN 2014; 59: 689-94.  In this study, the authors took a consecutive sample of 13  children (ages 4-18 years) with non cirrhotic extrahepatic portal vein portal vein obstruction (EHPVO).  Three tests (fasting ammonia, quantified EEG, a psychometric battery) identified that minimal hepatic encephalopathy (MHE) affects approximately 50% of children with EHPVO.

Also: JPGN 2014; 59: 708-13.  In this study in 7-day old rabbits, those who receive TPN with fish oil-based lipid emulsion had protection against biochemical and liver histologic damage in comparison to rabbits who received TPN with soybean oil. Given the lack of head-to-head randomized studies in infants, this study provides some important evidence of fish oil benefit compared with standardized soybean lipid emulsion.

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In NASH, is ALT Wrongly Used as a Marker of Liver Injury?

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According to a recent report (Hepatology 2015; 61: 153-60), elevation of alanine aminotransferase (ALT) which is frequently used as an indicator to select patients for further investigations (eg. liver biopsy) is NOT a good indicator of liver parenchymal injury in patients with nonalcoholic fatty liver disease (NAFLD).

The researchers enrolled 440 patients and divided them into three groups: no NAFLD (n=60), NALFLD with normal ALT (n=165), and NAFLD with elevated ALT (n=215). The patients were overweight/obese patients prospectively recruited from newspaper ads, general medicine clinics and hepatology clinics at several VA hospitals. Those with history of alcohol abuse were excluded.

Numerous investigations were performed including liver fat by proton magnetic resonance spectroscopy (H-MRS), liver biopsy (n=293), and insulin resistance measurements.

Key findings:

  • NAFLD & NASH patients with elevated ALT had higher liver triglyceride content (P<0.0001), worse adipose tissue insulin resistance (ATIR) (P<0.0001), and lower plasma adiponectin (P<0.05).
  • Steatosis was worse on liver biopsy in those with NASH and elevated ALT (P<0.0001).
  • There were no differences in liver inflammation (P=0.62), ballooning (P=0.13), or fibrosis (P=0.12). Thus, patients with normal versus elevated ALT had similar severity of NASH liver histology.

Take-home message:  In adults, ALT values are “poor surrogate markers of disease activity” in NAFLD.  ALT values, in these patients, are indicative of metabolic disease.  Given the staggering numbers of individuals, adults and children, with fatty liver disease, the lack of simple screen tool is quite problematic.  Equally problematic is a lack of a simple treatment approach.

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Refractory Constipation -Terrific Update

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Recently I attended a terrific talk by my partner, Jose Garza.  This lecture provided a great deal of information on refractory constipation for both pediatricians and pediatric gastroenterologists alike.

Elements of the talk included diagnosis, pathophysiology and differential diagnosis.

Rome III Criteria -Helpful in Diagnosis of Constipation

Rome III Criteria -Helpful in Diagnosis of Constipation

JG1 pathophys

Is it Hirschsprung's Disease?

Is it Hirschsprung’s Disease?

Some of the more useful points.

  1. AXR should not be used to make diagnosis of constipation.
  2. Many refractory constipation patients are stooling fine and actually labeled as constipation instead of a functional abdominal pain disorder.  That is, they are complaining of stomach pain and have been erroneously told they are constipated (see point #1).
  3. Miralax remains a 1st line agent for constipation. In individuals with fecal soiling, if miralax is not working and they have had appropriate cleanout, then senna laxative may be helpful.
  4. Sitz markers are particularly helpful in proving stooling when teenager claims to not be stooling for a month and in proving functional fecal retention rather than nonretentive soiling.
  5. If good treatment is not working, then refer to neurogastroenterology.

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JG3 -Help

 

FMT for Crohn’s Disease -Small Study

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A recent prospective open-label study (Suskind DL, et al. Inflamm Bowel Dis 2015; 21: 556-63) adds a bit more information on fecal microbial transplantation (FMT) for individuals with Crohn’s disease (CD). This study included 9 patients, ages 12-19, and 11 authors.

Study details:

  • Pretreated with rifaximin 200 mg TID x 3 days and Miralax 17 gm TID x 2 days prior, and omeprazole day before and morning of procedure
  • Patients continued on prior treatment: 4 on methotrexate, 2 on thiopurine, and 3 on mesalamine (1 mesalamine patient was receiving methotrexate also)
  • Stool donor was a screened parent
  • Stool administered via NG
  • Stool DNA studied –>metagenomic sequencing

Key findings:

  • FMT engraftment was demonstrated in 7 of 9 patients
  • Mean PCDAI improved –baseline 19.7 –>6.4 at 2 weeks–>8.6 at 6 weeks
  • 5 of 9 patients who did not receive additional medical therapy were in remission at 6 and 12 weeks.

One particular advance with this study was the correlation between microbial species before and after FMT.  One speculation from the authors was that “the more divergent a Crohn’s patient is from his donor the more the potential benefit of transplantation.”  Thus, this same study with unrelated donor stool (eg. OpenBiome) would be of interest as well.

My Take: While this study offers encouragement for bigger studies, we will not know if FMT is effective (& how to administer optimally) until we have studies with more patients than authors.

Related blog posts:

 

 

Can Apple Make Research Cool?

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For anyone who has looked at Apple’s March presentation, there is big news with regard to research (thanks to Seth for this information).  Here’s a link to the March announcement –around minute 16 there is the research presentation: Apple March Event

Screenshot: Rationale for Apple iPhone for Research -Large Research Pool

Screenshot: Rationale for Apple iPhone for Research -Large Research Pool

The presentation makes it clear that Apple wants to dramatically increase the participation in research studies by leveraging 700 million iPhone users.  Using an app called, “ResearchKit”, Apple has partnered with leading academic centers to help study Parkinson’s, Diabetes, Asthma, Cardiovascular disease, and Breast Cancer.  For the GI community, I hope that someone will work collaboratively to add inflammatory bowel disease to the list.

Besides increased participation, iPhone-based research has the ability to lower research costs, collect data at frequent intervals, and allow a wider demographic representation.

A shorter ~4 minute video on a separate area of the website explains ResearchKit: ResearchKit video

Screenshot: Research Kit


Screenshot: ResearchKit

NBC News provides a condensed summary along with the caveat that there will be concerns about accuracy of data collected with ResearchKit.  That being said, most critics have not always appreciated the impact of previous Apple innovations.

Has someone from our national organization (NASPGHAN) or from ImproveCareNow started working with Apple? If not, this looks like a great opportunity.

Transoral Fundoplication for Refractory Gastroesophageal Reflux

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A new endoscopic technique’s efficacy has recently been reported (Gastroenterol 2015; 148: 324-33).  Since this technique is not likely to be broadly applicable to the pediatric population for some time, I will not delve into all of the details.

In essence, a carefully selected group (n=129 from a screened group of 696) of adult patients with persistent regurgitation underwent transoral fundoplication; this eliminated troublesome regurgitation in 67% compared to 45% who were randomized to sham/PPI.  Severe complications were rare.

Here is a picture of the technique:

Transoral Fundoplication

Transoral Fundoplication

Link: Description and a video animation of the procedure

Bottomline: This endoscopic procedure along with the Stretta procedure and the LINX device (using magnets) offer alternatives to surgical fundoplication in carefully-selected patients with refractory gastroesophageal reflux symptoms.

New drugs approved by FDA:

Ceftolozane (Zerbaxa) -combines a cephalosporin with a beta-lactamase inhibitor (tazobactam).  Indications: complicated intra-abdominal infections (in combination with metronidazole), and complicated urinary tract infections. From FDA: FDA approves new antibacterial drug Zerbaxa

Viekira Pak -combination of 3 new drugs: ombitasvir, paritaprevir, and dasabuvir along with  older drug: ritonavir.  Indications: Hepatitis C genotype 1. From FDA: FDA approves Viekira Pak to treat hepatitis C

Related blog posts to fundoplication: