Gold Medal Winner: Infliximab (anti-TNF competition)

Posted on by

According to a recent retrospective study, (S Singh et al. Clin Gastroenterol Hepatol 2016; 14: 1120-29), infliximab outperformed its rivals.  In the spirit of the recent olympics, we’ll give infliximab a gold medal in the anti-TNF category.

Here’s the play-by-play:

This study used an administrative claims database with more than 100 million US enrollees.  In total, there were 3205 biologic-naive patients with Crohn’s disease (CD) with a mean age of 41 years.  All of the participants had not received a biologic agent for at least 12 months prior to their first study dose (between 2006-2014). In addition, the authors excluded patients who had a concomitant diagnosis which could necessitate a biologic, including rheumatoid arthritis, ankylosing spondylitis, and psoriasis.

Race details:

  • Compared to adalimumab-treated patients, inlfiximab-treated patients had a lower risk of CD-related hospitalization (aHR [adjusted Hazard Ratio] 0.80), abdominal surgery (aHR 0.76), and corticosteroid use (aHR 0.85)
  • Compared to certolizumab pegol-treated patients, infliximab-treated patients had a lower risk of hospitalization (all-cause) (aHR 0.70), and CD-related hospitalization (aHR 0.59).
  • All agents had comparable risk of serious infections

Post-race analysis:

Was this a fair race (ie study)? Definitely.  If anything, this study may have underestimated the benefit of infliximab.  Due to trouble with confounders across retrospective studies, it may be that infliximab was chosen preferentially among sicker patients.

My take: There is limited data on comparative effectiveness of anti-TNF agents.  This retrospective study  indicates that infliximab is likely superior to its competitors.  Definitive proof would necessitate a head-to-head live-action (prospective) competition.

Related blog posts:

Screen Shot 2016-08-14 at 11.46.48 AM

Addressing Medical Issues Before International Travel

Posted on by

Briefly noted: An highly detailed but concise review of “Medical Considerations before International Travel” DO Freedman et al. NEJM 2016; 375: 247-60.

Figure 1:

  • Risk assessment: medical history, prior travel experience, specific itinerary (region, season), type of accommodations, risk tolerance, financial challenges
  • Standard Interventions: Immunizations, Malaria prophylaxis (if risk), Traveler’s diarrhea strategy
  • Focused education: vectorborne diseases, altitude illness, thrombosis risk, STDs/bloodborne infections, transportation risks (eg no car seats), respiratory infections, medical kit, medical insurance

Tables:

  • Table 1: Practices for reducing disease risk (too many to summarize)
  • Table 2: Vaccine Recommendations
  • Table 3: Malaria Prophylaxis
  • Table 4: Recommendations based on location

Short Take Video Link (2 min): Travel Health and Safety

CDC: Traveler’s Health Website

Travel Resource: GeoSentinel Website

My take: This is a handy updated reference for international medical travel

Related blog posts:

beach hut

Screen Shot 2016-07-27 at 5.29.22 PM

Quirky HIDA Study Shows That HIDA Scans Not Too Helpful

Posted on by

As noted in a previous post, Biliary Dyskinesia –“Only in America” | gutsandgrowth, gallbladder dykinesia is a quite dubious diagnosis.  A recent pediatric study (PM Jones et al. JPGN 2016; 63: 71-75) adds to the uncertainty.

This study utilized a large database for a retrospective review of HIDA scans in patients <22 years.  In a group of 2558 patients, 310 patients had a full-text gallbladder pathology report paired with HIDA scan. The majority of these HIDA scans (64.5%) were performed in teenage Caucasian girls.  Key finding:

  • Gallbladder ejection fraction (GBEF) did not correlate with the presence of gallbladder pathology.  The Odd Ratio (OR) for cholecystitis with EF of 16-34 was 0.98.
  • The majority had at least microscopic pathology: 71.6% had microscopic cholecystitis

The authors indicate that other studies have shown that the diagnosis of gallbladder dyskinesia is controversial “because some point to the strong placebo effect of a surgical intervention, as well as the finding that patients who were observed for a year or more had similar symptom improvement  compared with those who had an operation.” [J Pediatric Surg 2006; 41: 1894-8]

Ultimately, the utility of HIDA scans can only be addressed with randomized prospective studies. Perhaps, these studies will show that HIDA scans are not predictive of who needs a cholecystectomy.

My take: It is interesting that pathology did not correlate with HIDA results.  However, the bigger question is whether abnormal gallbladder function, as assessed by HIDA, triggers symptoms that merit cholecystectomy. This is not addressed by this study.

Beach Art

Beach Art

4 Points for C diff in Inflammatory Bowel Disease

Posted on by

A nice review: K Rao, PDR Higgins. Inflamm Bowel Dis 2016; 22: 1744-54.

Many aspects of Clostridium difficile with and without coexisting inflammatory bowel disease has been reviewed on this blog.  This review adds a few additional points:

  1. C difficile testing in patients with IBD, “start with enzyme immunoassay-based tests with a reflex to PCR test for discordant enzyme immunoassay results.”  Rationale: “PCR is quite sensitive for the presence of toxigenic C difficile, it may increase the detection of asymptomatic colonization and shedding.”
  2. Don’t test for C difficile in patients in clinical remission. “Clayton et al evaluated outpatients with IBD who were in clinical remission and had no recent exposure to antimicrobials, corticosteroids, immunomodulatory agents, or hospitalizations.  These patients had toxigenic C difficile carriage rates of 8.2%.”
  3. What to do when IBD patients test positive for C difficile infection (CDI) -treat which one or both? The authors recommend, that “if there is no response to the treatment for CDI after 48 hours, then concurrent immunologic therapy can be started/escalated.”
  4. Safety of FMT with IBD. “There may be additional risk incurred in the IBD population…[in a recent study] 14% of the subgroup of patients with IBD experienced adverse events including IBD flare, requiring hospitalization in some instances.” Overall, there is not enough data to “risk stratify patients in terms of these adverse outcomes.”

In addition to these pointers, advice on treatment based on severity and whether CDI is recurrent is listed on Table 1.

  • For primary CDI (nonsevere): metronidazole, vancomycin or fidaxomicin.
  • For primary CDI (severe): vancomycin or fidaxomicin.
  • For primary CDI (severe & complicated*): vancomycin at highest dose and IV metronidazole and (if ileus present) vancomycin rectally
  • Recurrent CDI: 1st recurrence — same as initial Rx, 2nd recurrence -same as initial Rx, then use either vancomycin pulsed and/or tapered regimen of 6 or more weeks

Related blog posts:

View from Grinnell Glacier Trail, Glacier Nat'l Park

View from Grinnell Glacier Trail, Glacier Nat’l Park

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.

Reappraisal of the Risk of Autoimmune Disease with Celiac, Plus One

Posted on by

Using a matched cohort design with 1215 cases of celiac disease and 6075 controls, C Canova and colleagues (J Pediatric 2016; 174: 146-52) provide data from 1989-2011 regarding the development of hypothyroidism and diabetes.  This retrospective, longitudinal, population-based Italian study relied on data from the integrated National Health Service.

Key findings:

  • Over this >20 year period, the risk of developing hypothyroidism was HR 4.64 and the risk of developing type 1 diabetes mellitus was HR 2.50 (not statistically significant)
  • The risk of hypothyroidism was more prevalent in males with HR 20.00.

The authors note: “The most plausible mechanism explaining the association between CD and T1DM/ATD [autoimmune thyroid disease] is a shared genetic background.”

Also noted: NASPGHAN Clinical Report on the Diagnosis and Treatment of Gluten-related Disorders. ID Hill et al. JPGN 2016; 63L 156-63.  Recommended monitoring for celiac disease, from Table 5:

  • At diagnosis: CD serology, CBC, Iron profile, HFP, Thyroid tests (TSH, free T4), Calcium, Vit D.
  • At 3-6 mo after diagnosis: CD serology (TTG IgA or DGP-IgG)
  • Annually:  CD serology, CBC, Thyroid tests (TSH, free T4), Vit D.

Related blog posts:

Congaree National Park (SC) and the "knees" of the Bald Cypress trees

Congaree National Park (SC) and the “knees” of the Bald Cypress trees

Why Asthma Study is Important: Hygiene Theory

Posted on by

In my view, one of the most important pediatric studies this year was just published (reference below).  For a long time, it has been recognized that growing up on farms can reduce the likelihood of developing conditions like asthma, as well as inflammatory bowel disease (Related post: NYT: Educate Your Immune System | gutsandgrowth).  This study: Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children provides an in depth assessment of 60 children and helps uncover the reason for these epidemiologic results.

Here’s the quick 2 minute summary: Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children

Screen Shot 2016-08-05 at 9.13.14 AM

 

Fecal Calprotectin Monitoring Helpful at Identifying Relapse in IBD

Posted on by

Thanks to Ben Gold for this reference: Y. Zhulina et al. Aliment Pharm Ther 2016; 44: 495-504.

Methods: 

  • Patients aged 18 years or older, with a known diagnosis of IBD in clinical remission, were prospectively studied. Patients provided faecal samples every third month and were prospectively followed until the first clinical relapse or the end of the 2-year follow-up period.  
  • Relapse was defined as increasing symptoms necessitating intensified medical therapy or surgery.

Key finding:

  • Among 104 patients, Crohn’s disease (n = 49) and ulcerative colitis (n = 55), 37 had a relapse. A doubling of faecal calprotectin level between two consecutively collected samples was associated with a 101% increased risk of relapse (HR: 2.01; 95% CI: 1.53–2.65; P < 0.001).

My take: Another study showing that stool calprotectin is quite useful. How long will it be until I will not need to write letters to insurance companies to get this test covered?

Also noted in the same issue: 
“The safety of autologous and metabolically fit bone marrow mesenchymal stromal cells in medically refractory Crohn’s disease – a phase 1 trial with three doses” (pages 471–481) T. Dhere, I. Copland, M. Garcia, K. Y. Chiang, R. Chinnadurai, M. Prasad, J. Galipeau and S. Kugathasan. Aliment Pharm Ther 2016; 44: 471-81. This study examined the use of mesenchymal stromal cells in 12 patients.

In conclusion, a single infusion of fresh autologous bone marrow-derived mesenchymal stromal cells propagated ex vivo using a non xenogeneic human platelet lysate growth supplement at doses ranging 2–10 million cell/kg BW was well tolerated in patients with medically refractory moderate to severe Crohn’s disease in this preliminary study. Our data neither addressed long-term safety nor sustained efficacy. However, this study informs that a future phase 2 study 

A previous study of mesenchymal stromal cells was briefly discussed in a previous blog: Sanjay Gupta is Wrong…about Stem Cell Therapy

Related blog posts:

Hidden Lake at Glacier National Park

Hidden Lake at Glacier National Park

Is Obamacare Causing Skyrocketing Premiums?

Posted on by

Not yet according to a recent commentary: BD Sommers. NEJM 2016; 375: 201-3. The graph below provides some perspective.  In addition, the author cautions those who have voiced early alarm bells regarding upcoming rates.  He notes the same alarms have been raised in the previous 2 years. Though, he notes, “there are reasons to suspect that marketplace premium growth for 2017 will exceed this year’s levels.  Two of the law’s provisions designed to reduce financial risk to insurers in the new markets expire after 2016 — the risk corridor and reinsurance provisions…the country’s continued emergence from the aftermath of the Great Recession may well spur increasing rates of health care inflation for the general population, as well as for the ACA exchanges”

“Premium growth — even when it does reach into the double-digit range that sparks such substantial media attention — is a policy challenge to be examined and addressed and is also part of the general historical pattern that precedes the ACA.”  Those who argue “the law as a whole should be scrapped ignore the devastating effect that repeal would have on the estimated 20 million Americans who have thus far gained insurance under the law.”

My take (from commentary): “Regardless of what ends up happening this year, it seems likely that next spring will bring renewed claims that the sky is falling — when experience should make clear that it isn’t.”

ACA premiums

Image from CGH: Duodenal Diverticulum

Posted on by

Clin Gastroenterol Hepatol 2016; 14: e93

DOI: http://dx.doi.org/10.1016/j.cgh.2015.12.035

Intraluminal duodenal diverticulum is a rare duodenal congenital abnormality caused by an anomalous process of recanalization of the primitive foregut. It has a characteristic radiographic appearance on contrast studies, resembling a “windsock web” or “thumb of a glove”

Screen Shot 2016-07-29 at 10.30.28 PM

An upper gastrointestinal (GI) endoscopy was then performed that revealed a 3-cm pedunculated mass in the second part of the duodenum that was biopsied (Figure A), and the patient was referred for an endoscopic ultrasound. A repeat endoscopy before the endoscopic ultrasound revealed a large intraluminal diverticulum that had the appearance of a mass when inverted. Subsequently (Figure B), an upper GI series was performed that showed a large elongated tubular diverticulum arising from the second portion of the duodenum, 2.5 × 12 cm in size, with rapid filling and peristalsis with oral contrast, which extended to the left aspect of the spine when maximally distended