Raynaud’s Phenomenon

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IN 1862, Maurice Raynaud described a 26-year-old female patient: “Under the influence of a very moderate cold…she sees her fingers become ex-sanguine, completely insensible, and of a whitish-yellow color.  This phenomenon …lasts a variable time, and terminates by a period of very painful reaction, during which the circulation is re-established…and recurs to the normal state.”

An updated review on Raynaud’s: FM Wigley, NA Flavahan. NEJM 2016; 375: 556-65.

This review highlights treatments and the differential diagnosis of primary Raynaud’s phenomenon form secondary causes (eg scleroderma, SLE, dermatomyositis, Sjogren’s and others).

A) Pallor phase B) Cyanotic phase C) Normal nailfold capillaries (primary phenomenon) D) Abnormal nailfold capillaries typical of microvascular disease

A) Pallor phase B) Cyanotic phase C) Normal nailfold capillaries (primary phenomenon) D) Abnormal nailfold capillaries typical of microvascular disease

Lower Fiber Intake May Increase Risk of Crohn’s Flare

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According to a recent study, lower fiber intake was associated with an increased risk of a flare of Crohn’s disease over a 6-month period (CS Brotherton et al. Clin Gastroenterol Hepatol 2016; 1130-36).

This study examined dietary surveys from 1619 participants (Crohn’s disease in 1130, Ulcerative colitis in 489).  All participants were considered to be in remission at baseline. The key endpoint was disease flare at 6 months which was defined as a disease activity index score exceeding remission cutoff values.

Key finding: “Compared with those in the lowest quartile of fiber consumption, participants with Crohn’s disease in the highest quartile were less likely to have a flare” (adjusted odds ratio 0.58). There was no significant association with ulcerative colitis.

The associated editorial (1137-39) notes that “among 12 RCTs that enrolled patients with Crohn’s disease, fiber did not influence disease activity in studies of induction (flare to remission) or maintenance (remission to flare)…most RCTs had small sample size.”

My take (borrowed from editorial): “A high fiber diet is likely safe in patients with IBD [in the absence of a known stricture/obstructive symptoms] and may impart a weak benefit.”  Overall, dietary approaches are gaining traction and careful evaluation of competing claims will likely be of great benefit.

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This is where I was completely soaked. Grinnell Trail

This is where (moments later) I was completely soaked. Grinnell Trail

More on Ustekinumab, plus Allopurinol Study

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More data emerging that indicates that subcutaneous ustekinumab will be useful for refractory Crohn’s disease: S Khorrami et al. Inflamm Bowel Dis 2016; 22: 1662-69.

  • This open-label cohort of 116 patients identified a clinical response (Harvey-Bradshaw Index) in 97 (84%) after loading dose, and clinical benefit in 58% at 12 months of followup.
  • Perianal disease improved in 11 of 18 (61%).
  • This cohort had refractory disease with almost 90% had failed or were intolerant to 2 or more anti-TNFs.

Another strategy for managing inflammatory bowel disease is using allopurinol which can help low-dose azathioprine achieve therapeutic levels.  In the largest cohort to date, Pavlidis et al (Inflamm Bowel Dis 2016; 22: 1639-46) showed that at the end of followup (median 19 months after treatment initiation) 113/164 (69%) of patients with Crohn’s disease and 83/136 (61%) with ulcerative/unclassified colitis had a clinical response; 52% and 54% respectively were in remission. The azathioprine dose was 25% of weight-based monotherapy dose adjusted based on TPMT status; thus, for normal/high TPMT activity, azathioprine was dosed at 0.5 mg/kg whereas for heterozygous/intermediate activity, azathioprine was dosed at 0.25 mg/kg.

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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.

Vickery Creek, Sandy Springs

Vickery Creek, Sandy Springs

FMT in the “Real World”

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At DDW 2016, OpenBiome presented data (abstract Su1737) from 2,050 patients who received fecal microbiata transplants (FMT) in “the real world.”

Key findings:

  • Overall, 84% clinical cure rate with a single treatment
  • 85% of patients were treated with FMT via colonoscopy (250 mL) and 15% via nasal tube (50 mL). Nasal tube administration had a lower clinical cure rate of 77.9%, compared with 85.1% who had FMT via colonoscopy.

More information on this study: “Closet Thing to Miracle Cure”: Study Confirms Benefit of FMT in C difficile  Gastroenterology & Endoscopy News July 2016  This link also presents data on use of FMT in ulcerative colitis and the use of capsule FMT.

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Lymphonodular Hyperplasia2

Psychological Therapies for Irritable Bowel Syndrome

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A recent meta-analysis (KT Laird et al. Clin Gastroenterol Hepatol 2016; 14: 937-47) of 41 randomized, controlled trials shows that psychological therapies improved symptoms of irritable bowel in adults.

Key finding:

  • “On average, individuals who received psychotherapy had a greater reduction in GI symptoms after treatment than 75% of individuals assigned to a control condition…This effect remained significant” for at least 6-12 months.

A summary of this study from GIHepNews.com:  Psychological Therapies for Irritable Bowel Syndrome

Excerpt of commentary by Dr. Christopher Almario:

While these findings are impressive and continue to support the use of psychotherapy in IBS, important issues remain. First, these results are based on data gathered in the highly controlled environment of randomized controlled trials (RCTs), and it is unclear whether they will translate to the “real world.” RCT participants may be more willing to complete psychotherapy because they know they are being observed by research staff (referred to as the Hawthorne, or observer, effect). However, in real clinical practice, patients with IBS not subject to the Hawthorne effect may be less compliant with such therapies.

Other issues relate to the current limited adoption of psychotherapy in clinical practice. Factors contributing to the low uptake include variable third-party reimbursement and poor patient and provider acceptance (JAMA. 2015 Mar;313:949-58). Another factor is limited access to qualified psychotherapists.

My take: I often refer patients to a “pain psychologist” who works in our office.  With the right psychologist, this can be very helpful.  In addition, I feel that families are more willing to see a psychologist than in the past.

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JulyClinGastroCover

 

Gold Medal Winner: Infliximab (anti-TNF competition)

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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.

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Addressing Medical Issues Before International Travel

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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

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Screen Shot 2016-07-27 at 5.29.22 PM

Quirky HIDA Study Shows That HIDA Scans Not Too Helpful

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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

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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

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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.