I am a pediatric gastroenterologist at GI Care for Kids in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information.
A recent commentary, “Mistrust in Science –A Threat to the Patient-Physician Relationship” (RJ Baron, AJ Berinsky.NEJM 2019; 381: 182-5), addresses the deterioration of trust in the patient-physician relationship and potential ways to improve this.
Shortly before reading this, I read a newspaper article titled “Newtown Parents Fight Back” in Sunday’s AJC (related article online: Newton Parents Score a Win…). In this article, some of the parents of the 20 children who were killed in Newton, Connecticut have brought successful lawsuits against ‘hoaxers’ who claimed that the “rampage had been staged, with crisis actors.” Some of the parents have received death threats subsequently.
In this ‘misinformation’ age, it would be naive to expect that medicine and science would be spared. The alluded commentary makes the following points:
“Clinicians enter patient encounters with the reasonable presumption that they will be trusted. After all, they have powerful knowledge and good intentions…But, medicine is changing.”
“The legitimacy of the medical community rests on the the credibility of medical science…Physicians rely on that foundation in every interaction they have with their patients.” And on “the intimate and personal nature of each individual doctor-patient relationship”
“Medical practice is becoming increasingly corporate…In 2016, for the first time, less than half of practicing physicians owned their own practice…Less attention has been paid to how corporatization changes patients’ experience and …trust.”
“Gallup polling has revealed that confidence in almost all institutions in the United States…has deteriorated greatly…confidence in the medical system fell from 80% in 1975 to 37% in 2015.”
“Alternative sources of ‘authority’ have emerged to fill gap” including social media platforms, friends and relatives.
“Given the decline in trust in the institution of medicine, simply asserting medical authority or citing evidence is unlikely to win adherents…Skepticism…is a widespread phenomenon…appealing to a neutral or independent ‘referee’ of the truth…on a given subject–does not actually change minds…attempts by experts to correct misinformation may further entrench erroneous beliefs.”
Pathways to Trust
“Feeling recognized is a precondition for trust.” Having to repeat stories over and over again can be ‘trust-destroying’ as the individual feels as a stranger in the health care system
“Explicitly acknowledging the role…of other members of the health care team may be another way…Speak positively about the staff [and colleagues]…This practice …increased patients’ trust and satisfaction.”
My take: The authors note that in this age, science s devalued and relationships are more influential. Thus, creating trust goes back to Peabody’s 1927 admonition: “The secret of the care of the patient is in caring for the patient.”
In the newspaper article, a book publisher involved in the promoting the Sandy Hook conspiracy had to meet one of the parents as part of a lawsuit. “At the end of the day, Gahary shook Pozner’s hand and apologized. He offered condolences for Noah’s death.” As in medicine, getting to know each other is the surest way to garner trust.
A recent study (C Alessandria et al JPGN 2019; 69: 39-44) enrolled 151 patients to examine for correlation between mucosal disease and autistic children with gastrointestinal symptoms. Patients were prescribed a gluten-casein free diet (GCFD)
134 (89%) had negative celiac disease serology
56 (*37%) showed microscopic inflammation of duodenum
Response to GCFD diet was much higher in those with duodenitis (OR 11.3). It was unrelated to HLA-DQ2/DQ8 positivity (which was present in 48%)
Response to GCFD occureed with both rigourous and partial adherence without statistical difference
My view: The authors suggest that an EGD may help predict who would respond to GCFD. An alternative approach would be to offer a GCFD in those with significant GI symptoms given the unclear clinical relevance of microscopic duodenitis. This view is supported by previous studies which have indicated that the GI findings are similar among children with and without autism.
Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE.
We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0–10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily).
At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P< .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent.
In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029.
A recent study (JR Dayan et al. JPGN 2019; 69: 61-67) provides some helpful insight into the use of ustekinumab.
Background: The authors conducted a retrospective review of 52 patients (73% younger than 18 years, 27% 18-21 years).
Median age at induction was 16.8 years.
10 patients were biologic-naive; 42 had received at least one anti-TNF agent (18 had received two anti-TNFs).
42 of the 52 patients had Crohn’s disease.
Of note, 64% of their patients had a normal baseline CRP and they defined “biomarker remission at 52 weeks” as having a normal CRP. The high rate of normal baseline CRP likely indicates milder disease than many other refractory populations; though nearly half of the patients with Crohn’s disease were receiving steroids when ustekinumab was initiated.
Steroid-free remission was defined by Harvey Bradshaw Index ≤4 or partial Mayo Score <2 and off steroids for >4 weeks.
Dosing: 47 (90%) received induction with ustekinumab IV (260 mg if <55 kg, 390 mg if 55-85 kg, 520 mg if >85 kg) followed by 90 mg subcutaneous injections every 8 weeks
75% of patients continued to receive ustekinumab at 52 weeks.
50% of bio-exposed patients were in steroid-free remission
90% of bio-naive were in steroid-free remission
57% received a dose escalation (increased frequency due to inadequate clinical response); such that at 52 weeks, 12 were receiving q4 weeks, 9 were receiving q6-7 weeks, and 15 continued with q8 weeks.
With a median f/u of 18 months, the authors reported few serious adverse events: two patients had an anaphylactoid reaction with IV induction (Rx with steroids and epinephrine). One of these two went on to experience arthralgias, fatigue and headaches with maintenance injection and treatment was discontinued. One patient experienced “self-limited paresthesia of bilateral lower extremities at 16 months on therapy” (CHOP experience with 22 patients reported one case of transverse myelitis: #NASPGHAN17 More Abstracts)
The authors note low immunogeiecity of ustekinumab and “suggest that ustekinumab monotherapy is possible and preferable in children”
Limitations: Lack of better objective markers for response to treatment
My take: This data indicates that ustekinumab therapy was associated with clinical remission in 50% of patients who had received anti-TNF therapy and had higher response in a small sample of biologically-naive patients. More experience is needed to confirm drug safety with long-term usage
New Test Expedites the Diagnosis of Biliary Atresia
A groundbreaking test developed at Cincinnati Children’s can expedite a diagnosis of biliary atresia (BA), helping physicians decide quickly whether to perform a liver biopsy followed by an operative cholangiogram, the definitive test for BA. The test quantifies the concentration of MMP-7 (matrix metalloproteinase-7), a serum protein that researchers at Cincinnati Children’s discovered in 2017 is a biomarker of BA.
Physicians can order the MMP-7 assay by submitting a requisition form. Test results are available within 48 hours, and a pediatric hepatologist is always available for consultation regarding the interpretation of test results.
On April 3, 2019, Representatives Tim Ryan (D-OH) and Tom Cole (R-OK) introduced H.R. 2074, the Gluten in Medicine Disclosure Act of 2019. The bill intends to make it easier to identify gluten in prescription medications by requiring drug manufacturers to label medications with the list of ingredients, their source, and whether gluten is present.
The Celiac Disease Foundation has been working with Representative Ryan’s staff since 2012 on the need for labeling of gluten in medication and is proud to endorse this bill. The Gluten in Medicine Disclosure Act of 2019 was introduced in the House of Representatives and referred to the House Committee on Energy and Commerce. If passed by the House, the bill will move forward for review by the Senate.
Read the full text of the Gluten in Medicine Disclosure Act of 2019 here.
The Centers for Disease Control and Prevention published a report last week about the increased number of outbreaks caused by the fecal parasite Cryptosporidium, more commonly known as “Crypto.”…
The warning came from the CDC’s recent Morbidity and Mortality Weekly Report, which highlighted an average 13 percent increase in cryptosporidiosis outbreaks each year from 2009 to 2017.
The CDC said that over the past decade, there have been more than 400 reported outbreaks in the United States, leading to nearly 7,500 people becoming sick. Of those, more than 200 people were hospitalized, and one person died as a result of the disease, according to the report…
In about 35 percent of the outbreaks, sicknesses were linked to swimming pools and playgrounds, according to the report.
Re: Duijvestein M, et al. Abstract 144. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.
Background: “Researchers conducted a placebo-controlled trial comprising 143 patients with CD to assess the potential anti-inflammatory effects of vitamin D. Patients were randomly assigned to receive either 25,000 International Units of vitamin D3 (n = 72) or placebo (n = 71) weekly for 6 months after their first or second ileocolonic resection.”
Key Finding: “While serum vitamin D levels increased in the vitamin D group and remained unchanged in the placebo group, investigators found no difference in the incidence or severity of endoscopic recurrence at week 26 between the two groups. Cumulative clinical recurrence rates at week 26 were also comparable.”
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
A Dige et al. Gastroenterol 2019; 156: 2208-16. This study evaluated the efficacy of freshly collected autologous adipose tissue injection for healing of perianal fistulas in Crohn’s disease. The overall healing rate was 57% and the treatment had a good safety profile.
HK Somineni et al. Gastroenterol 2019; 156: 2254-65. The researchers found that DNA methylation patterns (from ~850,000 sites) in blood samples from pediatric patients with Crohn’s disease (n=164) were associated with inflammation and resolved with treatment of inflammation; thus, the changes in DNA methylation are less likely to be a causative agent in disease development or progression and more likely a biomarker of inflammation.
OB Kelly et al. Inflamm Bowel Dis 2019; 25: 1066-71. Among 316 patients who underwent A/P CT scan for any reason, 49 (16%) had evidence of sacroilitis, indicating this is underdiagnosed in patients with IBD.
BG Feagan et al.Inflamm Bowel Dis 2019; 25: 1028-35. In a post hoc analysis of GEMINI 1 trial (n=769 patients: 149 placebo, 620 vedolizumab), a randomized placebo-controlled trial of vedolizumab for ulcerative coliis, compared to placebo ~40% more patients receiving a full induction of vedolizumab had a sustained clinical remission after 52 weeks of therapy. Of patients in clinical remission at week 14, 66.5% achieved a sustained clinical remission at week 52 compared with 267% of placebo-treated patients based on partial Mayo score.. Sustained clinical remission was based on partial Mayo score and rectal bleeding subscore..
When someone gets bitten by a shark, it often makes the news. Yet, the frequency of shark attacks is rare and it is probably much more dangerous driving to the beach than getting into the water.
For proton pump inhibitors, it seems that they get similar press coverage as shark bites. Many times potential adverse effects are covered heavily by the media even though many of these effects are unproven or very infrequent.
A recent study (“Safety of Proton Pump Inhibitors Based on a Large, Multi-year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin” Moayyedi, Paul et al. Gastroenterology DOI: https://doi.org/10.1053/j.gastro.2019.05.056) shows that 3 years of pantoprazole had an excellent safety profile.
Here is the abstract:
Background & Aims
Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial.
We performed a 3×2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n=8791) or placebo (n=8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient years of follow up.
There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% CI, 1.01–1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant.