Linking Reflux and Tooth Erosion

Posted on May 4, 2016 by gutsandgrowth

Every now and then a dentist sends a kid to our GI practice due to eroded teeth because of concerns about reflux damaging the enamel. While it is recognized that reflux may damage teeth, the exact frequency is unclear. Other questions:

Which asymptomatic kids with poor dentition require GI evaluation?
What is the best way to evaluate these children?
If reflux is identified, how long should they remain on treatment? Forever?
How effective is reflux treatment in reducing tooth damage?

While none of these questions have been definitely answered, Rosen et al (JPGN 2016; 62: 309-13) show that acid reflux rather than nonacid reflux is predictive of tooth erosion. In this study, the authors used a prospective cohort of 27 children (age ≥3 years)–ALL of them were ON acid suppression (for >1 year) at the time of pH-MII testing. Key findings:

Prevalence of tooth erosion was 10 or 27 (37%)
There was correlation with acid reflux episodes (& time in reflux) and tooth erosion, r=0.44, P=0.02
There was correlation with reflux index as well, r=0.54, P=0.004, In the tooth erosion group, the mean reflux index was 7.3% compared with 1.6% in no dental erosion group.
There was no correlation with nonacid reflux with tooth erosion

The authors’ discussion highlights many prior relevant studies and indicates that a pH-metry study alone (rather than pH-MII) “may be adequate.” They note some of the limitations of this study which included a small number of patients and potential referral bias, as these children had suspected GERD. In the methods section, the authors state that their standard practice, at the time of the study, was to maintain patients on prior acid suppression medication. It would be useful to acknowledge that many experts, at this time, recommend doing pH-MII studies as well as standard pH studies off all acid suppression due to improved sensitivity/accuracy.

My take: This study shows that in the 10 children with tooth erosion who had suspected GERD, there was correlation with acid reflux but not with nonacid reflux.

Related blog post: Notes from PPI Webinar GutsandGrowth

Unrelated but interesting: Are medical errors really the 3rd leading cause of death in U.S.? Here’s NPR’s summary of a recent BMJ article which makes that claim: Only Heart Disease and Cancer Exceed Medical Errors As Cause of U.S. Death

Gibbs Gardens

Here’s What I Really Want to Know about an MRE Study –What is the Correlation with PGA?

Posted on May 3, 2016 by gutsandgrowth

A nice pediatric study (CG Sauer et al. JPGN 2016; 62: 378-83) provides data on 101 children from a single center who underwent MRE to evaluate their Crohn’s disease. This study was a retrospective chart review using a prospectively maintained MRE database. All of the children in this study underwent MRE greater than 180 days after diagnosis. MRE was ordered at the discretion of the treating gastroenterologist. Median followup was 2.8 years after MRE.

Key findings:

MRE correlated with meaningful clinical outcomes. Of the 65 with active inflammation on MRE, only 44.6% achieved clinical remission (another 30% progressed to mild disease activity). Of the 36 without active inflammation, 88.9% achieved clinical remission.
Children with active inflammation on MRE were more likely to undergo surgery (18.5% vs. 2.8%) and more likely to have medication changes (44.6% vs. 8.3%).

While this population may have had more disease than those who did not undergo MRE (since it was done at the discretion of gastroenterologist), what would interest me would be the correlation with the physician global assessment. A rough calculation would suggest that only 40% of these patients achieved a clinical remission which is well below ImproveCareNow reported benchmarks, but not much different from previous studies using objective markers. Furthermore, it would be of interest to look at whether individual clinicians incorporated their abnormal MREs into their assessment of PGA. If the patient was doing well clinically but their MRE was markedly abnormal or even mildly abnormal, were these patients classified as in remission or otherwise.

My take: MRE is an excellent & expensive tool to assess for mucosal healing. As our treatments continue to improve, MRE will be useful to monitor our progress. How we incorporate our objective markers with our clinical markers needs further work.

Related blog posts:

ERAS -Enhanced Recovery After Surgery

Posted on May 2, 2016 by gutsandgrowth

Fortunately, only a small number of children need colorectal surgery. For those who do need this surgery, there are advancements which are helping to reduce length of stay and shorten recovery. Some of the concepts with “Enhanced Recovery After Surgery” or ERAs have been around for more than 10 years. One of our surgical colleagues, Dr. Kurt Heiss, described his experience in applying these techniques in the pediatric population and was kind enough to share his slides. Slide 10 (see below) outlines the key points.

The immediate challenge in improving the quality of surgical care is not discovering new knowledge, but rather how to integrate what we already know into practice –Urbach DR, Baxter NN, BMJ 2005

Preoperative:

Counseling family
Avoid bowel prep –>can lead to bowel edema
Avoid prolonged fast prior to surgery. Fluid/carbohydrate loading
Use of Neurontin preoperative
Antibiotic prophylaxis
Thromboprophylaxis

Intraoperative:

Short-acting anesthetics
Use of TAP and/or short-term epidural. Avoid narcotics
Avoid excessive fluid administration
No drains
Maintenance of normothermia

Postoperative:

Early feeding (same night)
No NG
Avoid/minimize narcotics
Early mobilization

ERAS: leads to shorter length of stay, reduced nonsurgical complications and no increase in readmission rates.

Resources:

Full slides (courtesy of Dr. Heiss): ERAS 2016
Link: ERAS Society website

My take: ERAS concept/team approach is leading to better outcomes. GI surgery is likely to benefit more than other areas due to the often-slow recovery of the GI tract after operations.

Colorectal Adenomas

Posted on May 1, 2016 by gutsandgrowth

A good review on colorectal adenomas: WB Strum. NEJM 2016; 374: 1065.

A couple of points from review:

There has been a wealth of new data in last 10 years.
In 2016, ~134,000 persons in U.S. will be found to have colorectal cancer & 49.000 will die from it.
Adenomas are present in 20-53% of the U.S. population older than 50 years of age.
Adults in the U.S. have a lifetime risk of ~5% of adenocarcinoma.
Two major pathways from adenomas to adenocarcinoma: chromosomal instability and micro satellite instability via predominantly ~25 genes.
Screening interval recommendations (Table 1): 10 years for no polyps or juvenile polyps in rectum/sigmoid.
Aspirin therapy may be beneficial but apply to persons who have no increased risk of bleeding and are willing to take low-dose aspirin (81 mg) daily. The greatest benefit is expected in persons 50 to 59 years and a potential benefit in 60 to 69 years of age.
Diets that are low in fat, regular physical exercise, maintenance of an appropriate body-mass index, and avoidance of smoking are recommended to lower risk.

“The USPSTF recommends initiating low-dose aspirin use for the primary prevention of CVD and CRC in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years. (B recommendation)The decision to initiate low-dose aspirin use for the primary prevention of CVD and CRC in adults aged 60 to 69 years who have a 10% or greater 10-year CVD risk should be an individual one.”

Related blog posts:

CCFA Conference Notes 2016 (part 5) -Emerging Therapies

Posted on April 30, 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 (can use search function to find additional relevant material) 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.

Emerging Therapies in IBD –Dr. Gary Lichtenstein

Background: This lecture started with a review of current therapies. We have learned how to use our current therapies better. There still remain a large number of patients that face surgery with IBD; though there has been improvement (?50% reduction).

Issues with thiopurines were reviewed. May take 2-6 months to take effect, though monotherapy with thiopurines are fairly ineffective for Crohn’s disease as initial therapy.

Leukocyte Trafficking Agents:

Natalizumab
Vedolizumab
AJM300 –oral agent. Initial safety data were fine.
AMG 181
Etrolizumab (Vermeire S Lancet 2014) –low rates of endoscopic healing, but better than placebo

PF-00547,659

S1P Modulators:

Fingolimod

Ozanimod (RPC1063) (oral agent, fairly rapid onset) causes S1P-r on lymphocytes to be internalized –more selective than Fingolimod. Good safety has been noted thus far. No notable cardiac problems. Infrequent elevations of transaminases; this issue will need to be followed.

Tofacitinib oral Janus Kinus (JAK) Inhibitor (Sanborn WJ et al. NEJM 2012; 367: 616-24). Dr. Lichtenstein thinks 10 mg will be recommended dose. Follow lipids. For UC

Mongerson related post: Mongerson -Phase II Data Available in NEJM | gutsandgrowth

Ustekinumab

Related article from GI & Hep News: Ustekinumab for complex Crohn’s from ECCO conference/UNITI-1 Study (n=741)

FMT. Further studies are needed

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.

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Eric Carle artwork at High Museum