CCFA Conference Notes 2016 (part 4) –Pregnancy and IBD

Posted on April 29, 2016 by gutsandgrowth

Pregnancy and IBD –Dr. Doug Wolf

Dr. Wolf reviewed infertility, pregnancy issues, and PIANO registry. This topic has been covered elsewhere in this blog (IBD and Pregnancy | gutsandgrowth). Vedolizumab is a FDA category B; thus far, it is considered fairly safe. Thiopurines are category D but overall thought to be low risk.

This blog entry has abbreviated/summarized this terrific presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

CCFA Conference Notes 2016 (part 3) -Malignancy and IBD

Posted on April 28, 2016 by gutsandgrowth

This blog entry has abbreviated/summarized this terrific presentation; most of the material has been covered in this blog in prior entries but still this was a useful review. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

3^rd Lecture: Prevention and management of malignancy in IBD –Dr. Thomas Ullman

Malignancy risk (colorectal cancer [CRC]) is present with prolonged ulcerative colitis, though more recent studies have shown lower risk than in the past –not much higher than the general population.

CRC surveillance–colonoscopy monitoring after 8-10 years. Typically colonoscopy every other year for most patients, every year in higher risk patients (eg. PSC).

Unclear if chemoprevention is effective (5-ASA, thiopurines, others).
Chromoendoscopy “has not been consensus on its use in our field (yet).” It is time consuming and expensive and unclear if it will improve outcome.

Does medical therapy for IBD predispose to developing cancer?

Thiopurines increase the risk of malignancy. (Pasternak et al) though the risk returns to near baseline when stopped according to study below.

No overall increased risk with anti-TNF agents with RCTs (may not follow patients long enough) but also not seen in Danish registry either (JAMA study)

No increased risk of malignancy in this study with Anti-TNFs

Lymphoma risks: age, immunodeficiency, EBV
EBV negative are at risk for HLH with thiopurines
HTSCL ~200, >90% men and >90% <35 years. NOT EBV-related. Has not been identified in anti-TNF monotherapy.

Skin cancer –main concern is in non-melanoma skin cancer (possibly melanoma too). Skin cancer increase has not been noted with methotrexate. Prevention: Skin care, and annual dermatology visits.
Cervical cancer—likely increased risk in IBD, probably due to thiopurine exposure and reduced immune surveillance. Prevention: HPV vaccination, Pap testing.
Urinary Tract cancers –especially in those >65 years with thiopurine exposure

CCFA Conference Notes 2016 (part 2) -Pediatric Lecture

Posted on April 27, 2016 by gutsandgrowth

2^nd Lecture: What is Next in Treatments for Pediatric Patients? –Dr. Michael Rosen

I really enjoyed meeting Dr. Rosen. He is super-friendly and knowledgeable.

Combination therapy. Grossi V et al showed improvement in infliximab durability with concomitant therapy.

Now starting COMBINE trial (ImproveCareNow)–randomized to low dose MTX or placebo in combination with anti-TNF agent.

Therapeutic drug monitoring in pediatrics. Is this an alternative to combination therapy? Rationale (see slide): lower antibody formation if trough levels maintained. IFX level >5.5 associated with persistent remission (Singh et al 2014). Children are growing and they may need more adjustments. In Cincy, checking levels at week 14 after initiation and then every 6-12 months.

Acute Severe Ulcerative Colitis. High rates of dose escalation in this population. Some of this is due to more rapid clearance of anti-TNF –leaking in gut and other mechanisms as well. Week 8 level of 40 associated with clinical response. Thus, this population may benefit from 10 mg/kg at start (in those with albumin <3) and may need more frequent dosing, especially early into treatment (?0, 2, 6, 10). ARCH study to look into this further

Vedolizumab. Conrad MA 2015. About 1/3^rd of these refractory patients in this abstract responded.

Ustekinumab . IL-12 & IL-23 blockage. No studies in pediatrics. Case report reviewed of good response in a refractory case.

Enteral therapy. Specific carbohydrate diet experience. These diets have some published data, most retrospective studies. Our group (Cohen SA et al) did perform a small prospective study. Sigall-Boneh R et al showed improvement with partial enteral nutrition.

Very early-onset of IBD. IL-10 receptor deficiency was a key early discovery and can be treated with stem cell transplant. STAT3 mutation case reviewed which was managed with tocilizumab. More targeted therapy expected based on specific mutations.

CCFA Conference Notes (Part 1): Preemptive Therapeutic Drug Monitoring Not That Helpful

Posted on April 26, 2016 by gutsandgrowth

Optimizing Therapeutic Drug Monitoring –Dr. Hans Herfarth

Trough levels have been recognized to correlate with remission rates. Good data from SONIC (2010) for infliximab. Ultra2 trial (2013) showed similar data for adalimumab.

Low albumin predicts higher rates of failure, possibly due to loss of infliximab in stool.

Reviewed algorithm for loss of response to infliximab based on trough levels. If low infliximab and no antibodies, increase dosing of infliximab has high likelihood of clinical response.
If high infliximab and not responding, evaluate for other reasons including irritable bowel, and strictures.

Scenarios that create confusion with therapeutic drug monitoring:

If clinically-well patient has antibodies and adequate drug level, could observe or possibly add immunosuppressive agent. ~3% of patients have simultaneous ATI and IFX detection.
If clinically-well with low infliximab level, could increase dose or observe.

In TAXIT study, however, lowering dose (panel B above) to get in target range was associated with a lower rate of response. No clear difference between clinically-based changes compared with proactive monitoring. Proactive adaption of trough levels may help prevent relapse in ~10% but not shown to alter long-term outcomes

TAILORIX study looked at tailoring dose at week 14. ‘Week 14 adaption did not make a significant difference at 1 year.’ Limitation: 122 patients.

Hard to see Group C (clinically-based group) in this slide

Drug monitoring has become popular but its importance as a preemptive measure is unclear. Dr. Herfarth’s practice is to monitor when loss of response but not to monitor if doing well. His view: if someone is doing well, therapeutic drug monitoring can be confusing. It is not proven that optimizing drug levels will improve long-term outcomes. (In children, especially due to growth, drug monitoring may be more important.)

One other recommendation from Dr. Herfarth: he recommends combination therapy in his patients are started on a 2^nd anti-TNFs.

Don’t Touch That Cute Turtle

Posted on April 25, 2016 by gutsandgrowth

The risk of Salmonella from turtles is well-known. A recent report (Walters MS et al. Pediatrics 2016; 137: 1-9) with data from 2011-2013 highlights the ongoing risk with reports of 8 multi-state outbreaks of Salmonella and pet turtles were the key risk factor.

Children <5 years and Hispanics were disproportionately affected.
88% of the turtles were considered small (< 4 inches)

Here’s an excerpt from the abstract:

RESULTS: We identified 8 outbreaks totaling 473 cases from 41 states, Washington DC, and Puerto Rico with illness onsets during May 2011–September 2013. The median patient age was 4 years (range: 1 month–94 years); 45% percent were Hispanic; and 28% were hospitalized. In the week preceding illness, 68% (187 of 273) of case-patients reported turtle exposure; among these, 88% (124 of 141) described small turtles. Outbreak strains were isolated from turtle habitats linked to human illnesses in seven outbreaks. Traceback investigations identified 2 Louisiana turtle farms as the source of small turtles linked to 1 outbreak; 1 outbreak strain was isolated from turtle pond water from 1 turtle farm.

My take: Turtles make lousy pets. Salmonella infection can be fatal in some and in others leave lasting problems.

Related posts:

Eric Carle artwork at High Museum

“What Do I Need to Learn Today?”

Posted on April 24, 2016 by gutsandgrowth

A recent commentary (GT McMahon. NEJM 2016; 374: 1403-5) provides some perspective on adult learning. In this era of ubiquitous information, developing the right strategy for learning is crucial, not just in medicine but globally. Key points:

“Physicians seeking professional development can recognize when they’re actively learning and tend to embrace activities that allow them to do so.”
“Many clinicians appreciate learning alongside their peers but may struggle with the feeling that times spent in group educational settings is not efficient or productive enough to be worthwhile.”
“CME is most effective in changing physician performance and patient health outcomes if it is interactive.”
“Adults prefer education that’s self-directed, based on needs they have identified, goal-oriented, relevant, and practical.”
Learning facilitated by working in small groups to solve problems and with interaction (eg. smartphone polls). Other strategies include simulation programs and social media.
Working at getting CME to count towards other regulatory burdens (eg. maintenance of board certification), can “reduce the burden on physicians and promote lifelong learning.”

My take (with help from author): Incorporating educational innovation is important to improve physician performance and patient care. “All of that change begins with each of us having the humility and presence of mind to ask ourselves, ‘What do I need to learn today?’”

Vik Muniz Art. George Stinney Jr, the youngest person executed in U.S. at age 14 years. This artwork is composed of hundreds of pictures.

Pediatric Nutritionist: Blenderized & Pureed Gtube Diets

Posted on April 23, 2016 by gutsandgrowth

A recent Children’s Healthcare of Atlanta Nutrition Support Colloquium provided a terrific update on the use of blenderized and pureed diets via gastrostomy tube.

Here’s the link to the talk (including slides) and a summary on the Pediatric Nutritionist blog site: The Blenderized and Pureed by Gtube Diets

I’ve found these diets to be particularly useful in children with retching. In addition, these diets can lower costs, reduce other symptoms like constipation, and appeal to parents who desire more typical foods in their child’s diet.

Related blog post: Nutrition University -Part 1 | gutsandgrowth

Gibbs Gardens

Guidelines for Traveler’s Diarrhea in Adults

Posted on April 22, 2016 by gutsandgrowth

Full text: Guidelines on Traveler’s diarrhea in Adults from ACG

Some of the recommendations:

-use of oral rehydration if severe diarrhea (especially elderly). “Most individuals with acute diarrhea…can keep up with fluids and salt by consumption of water, juices, sports drinks, soups, and saltine crackers
-against use of probiotics for acute diarrhea except in cases of post antibiotic-associated diarrhea
-for use of bismuth subsalicylates to slow stool passage
-for use of adjunctive loperamide in patients receiving antibiotics for traveler’s diarrhea (to increase chance for cure)
-for antibiotics in traveler’s diarrhea “where the likelihood of bacterial pathogens is high enough to justify the potential side effects of antibiotics”
-against antibiotics for community-acquired diarrhea

Table 4 outlines antibiotic selection.

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.

Don’t Let the Chief of Staff Review This Constipation Study

Posted on April 21, 2016 by gutsandgrowth

A useful study from Cincinnati (D Klaus et al. J Pediatr 2016; 171: 183-8) provides data on the high prevalence of constipation in Duchenne Muscular Dystrophy. (DMD) Though, the authors acknowledge that rectal examination was “deferred unless clinically indicated.” I’m fairly certain that the former chief of staff, if asked for input, would have stated that the only two reasons for not doing this part of the exam was “either no rectum or no finger.”

In this prospective cross-sectional study, the authors relied on the Questionnaire on Pediatric Gastrointestinal Symptoms based on Rome-III criteria (QPGS-RIII) to identify constipation. Based on this questionnaire, 46.7% (56 of 120) of patients with DMD were diagnosed with functional constipation.

Traditional features of constipation like bowel movement infrequency of <3/week and hard stools were present in only 16% and 17% respectively.
Other features that identified constipation included straining with defecation in 35.1%, painful defecation (27.8%), and clogging toilet (22.6%)
The Bristol Stool scale had a low sensitivity for detecting constipation (only 18%) but had a high specificity of 95% if type 1 or 2.
Constipation did not increase with age or functional status which makes the concern that this is primarily related to an ineffective bear-down (Valsalva) less likely

My take: Constipation in children with DMD is underreported and often overlooked. It needs to be considered more carefully at routine visits.

Related posts:

Vik Muniz Art at High Museum

When you look closely at the horse’s nose, you can see that this art was completed with toy soldiers

CDC: Increase in Acute Hep B in Appalachia

Posted on April 20, 2016 by gutsandgrowth

MMWR 2016; 65: 47-50. Increases in Acute Hepatitis B Virus Infections — Kentucky, Tennessee, and West Virginia, 2006–2013

An excerpt:

During 2006–2013, a total of 3,305 cases of acute HBV infection were reported to CDC from Kentucky, Tennessee, and West Virginia. During 2009–2013, incidence of acute HBV infection increased 114% in these three states, but remained stable in the United States overall
Among cases in which at least one risk factor was reported, the proportion of persons reporting injection drug use as a risk factor was significantly greater in 2010–2013, compared with 2006–2009 (75% versus 53%; p<0.001)…the increase was statistically significant only among cases occurring in non-urban counties
The findings in this report are subject to …limitations. First, NNDSS is a passive surveillance system, and therefore, unreported cases might have been missed. Second, the current case definition for acute HBV infection captures only symptomatic persons and excludes persons with asymptomatic HBV … Third, … certain populations at high risk (e.g., persons who are incarcerated, homeless, and uninsured) with limited access to care could potentially be underrepresented

My take: Increased drug use appears to be driving an increase in acute HBV in Appalachia. “Evidence-based prevention strategies, including increasing hepatitis B vaccination coverage, testing and linkage to care activities, and education campaigns targeting persons who inject drugs are urgently needed.”

Gibbs Gardens, Ball Ground