Anti-TNF therapy and Pregnancy -More Data

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G Broms et al (Clin Gastroenterol Hepatol 2016; 14: 234-41) provide more data on the ‘low risk of birth defects for infants whose mothers are treated with anti-tumor necrosis factor agents during pregnancy.”

From a Danish/Swedish cohort of 1,272,424 live births (2004-2012), the authors found the following (in comparison to healthy infants):

  • Birth defects were increased in chronic inflammatory bowel disease: 4.8% vs. 4.2%
  • 43 (6.3%) of the infants born to women with IBD who received anti-TNF therapy (683) had birth defects.  The OR for any defect was 1.32 (CI 0.93-1.82).  The types of defects were generally similar, including VSD, ASD, hypospadias, and hydronephrosis

Limitations:

  • In infants of mothers with chronic diseases, it is possible that more careful screening identified some less apparent defects.
  • Study did not examine rates of stillborn or abortions

My take: Overall there is a slightly but not significantly increased risk in birth defects based on the use of anti-TNF therapy.  Stopping anti-TNF therapy is likely to be more detrimental.

Briefly noted: P Wils et al. Clin Gastroenterol Hepatol 2016; 14: 242-50.  This retrospective study of 122 patients showed that 65% had a clinical benefit within 3 months of receiving ustekinumab for Crohn’s disease refractory to anti-TNF therapy.  Concomitant immunosuppressant therapy was associated with an increased likelihood of benefit (OR 5.43)

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Which patients with asymptomatic gallstones need a cholecystectomy?

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Update: re: Yesterday’s post on tax inversion.  NPR report: Pfizer calls off Allergan Merger due to anti-inversion rules instituted by Treasury Dept

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“Generally, the clinical course for the majority of gallstones is asymptomatic…Overall, little knowledge exists about the development into symptomatic disease.”  This introduction from a recent study (DM Shabanzadeh et al. Gastroenterol 2016; 150: 156-67-thanks to Ben Gold for sharing his interest in this study) provides the rationale for their study which analyzed 3 randomly selected groups in Denmark (ages 30-70 years) and followed them for a median of 17.4 years.

Out of an initial 6037 participants, 664 had gallstones at baseline (after excluding 189 who had cholecystectomy and 5180 without gallstones). Only 10% were aware that they had gallstones.

Key findings: 

19.6% developed symptomatic disease (8% complicated, 11.6% uncomplicated)

Risks for symptomatic disease: Female sex, Younger age, Stone size >10 mm, Multiple stones

  • Male with small stone: 2/67 (HR 1.0)
  • Male with multiple stones: 4/97 (HR 1.83)
  • Male with large stone: 2/47 (HR 2.79)
  • Male with multiple and large stones: 3/29 (HR 5.12)
  • Female with small stone: 4/102 (HR 2.16)
  • Female with multiples stones (no large stones) 11/120 (HR 3.96)
  • Female with large stone: 12/67 (HR 6.02)
  • Highest risk: female with multiple stones and with largest stone >10 mm: 10/53(HR 11.05)

Interestingly, the 10% who knew that they had gallstones before randomly being selected  into the study had significantly higher rates of all outcomes, especially uncomplicated events.  “This finding may reflect a protopathic bias.” Patients who were aware were more likely to have suffered bilary colic attacks before study entry and thus had a higher risk of events.

My take: First of all, completion of this study over more than 17 years is an astonishing feat, particularly without informing the participants of their gallstone status.  In patients who are truly asymptomatic, my interpretation would be that only those at substantial risk would benefit from cholecystectomy.  This study does not account for other factors that could favor cholecystectomy (in asymptomatic patients) such as hemolytic diseases (e.g. sickle cell), cystic fibrosis, and other conditions in which symptomatic gallbladder disease is more likely to develop.

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Hunter Museum, Chattanooga

Hunter Museum, Chattanooga

Treachery or Sound Business Decision: Health Care Tax Inversions

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An insightful commentary (HJ Warraich, KA Schulman NEJM 2016; 374: 1005-7) provide some insight into “corporate inversion” or “tax inversion” and how they apply specifically to pharmaceutical companies.  This article was prompted by Pfizer’s plans to merge with Ireland-based Allergan which would create the largest pharmaceutical company in the world, worth ~$160 billion.

  • Inversions allow U.S. companies to lower their tax rate from as high as 35% (most never pay the full rate) to as low as Ireland’s corporate rate of 7.7%.  While this seems like a sound idea, there are reasons why U.S. tax payers should be outraged:
  • These firms “generate substantial revenue from purchases made by Medicare, Medicaid, and the Veterans Health Administration.  These programs are supported by revenue from federal taxes — precisely the taxes companies are trying to avoid by inverting.”
  • In fact, Medicare “parts B and D, received 76% and 80%, respectively of their funding from federal tax revenues in 2015.”
  • These companies charge U.S. consumers much more than anywhere else in the world for their products. For Pfizer, for example, in 2013, two of its leading drugs (Enbrel and Celebrex) were twice as expensive in the U.S. as in the U.K.
  • The U.S. government has pursued policies to protect these “domestic” industries in numerous trade agreements to secure intellectual-property rights.
  • The National Institutes of Health has provided funding that supports the development of new pharmaceuticals.

What should be done?

  • Policies to discourage inversion should be pursued.
  • This could mean that Medicare and Medicaid should be given a free hand to negotiate drug prices with inverted companies or to require additional reviews to qualify their products.
  • The FDA could withhold priority review from companies who have undergone inversion.
  • The IRS could be allowed to levy exit taxes on inverting companies.

My take: Pharmaceutical companies want to extract billions of dollars of benefits from the U.S. taxpayers and charge U.S. consumers higher costs than anywhere else. Avoiding paying U.S. taxes is not business as usual and should be met with consequences.

 

Gibbs Gardens, Ball Ground

Gibbs Gardens, Ball Ground

Goldilocks and Gluten

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A recent study (CA Aronsson et al. Clin Gastroenterol Hepatol 2016; 14: 403-09, editorial 410-12) suggests that how much gluten is given may be another important factor rather than looking at the timing with regard to the development of celiac disease (CD).

In this 1-to-3 nested case-control study with 146 cases of CD and 436 controls, the authors indicate that a larger intake of gluten than controls increased the likelihood of celiac disease.  Specifically, children receiving large amounts of gluten (>5 g/day) during their first 24 months had a 2.6-fold increased risk of CD compared to those who consumed lower quantities.

The associated editorial notes that the total amount of gluten intake was only marginally increased in CD cases versus all control patients (OR 1.05) and that the association was decreased when individuals with first-degree relatives with CD were excluded.  In addition, this high consumption increased the risk after the first 2 years of life, rather than during this period of high consumption.

Does this make sense? Not to me.  These findings need to be replicated in other studies to determine if gluten exposure is like Goldilocks: too little, too much –>just right.

My take: For now, I think sticking with the timing of gluten exposure (recommended at 4-6 months) rather than the quantity is worthwhile.

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Patient Assistance for Lab Testing

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Since 2015, “a partnership of several leading consumer health organizations announced the launch of Patient Assistance for Lab Services (PALS).” (Gastroenterol & Endoscopy News, March 2016, pg 54).  PALS offers access to more than 85 lab tests, most costing only $5 and all of the tests at a fraction of the cost of pricing at competing labs. (See request-a-test for competing costs: requestatest.com)

PALS website: Patient Assistance for Lab Services

Some examples of costs:

$5 tests: (There is a $15 shipping fee as well which covers all testing)

  • Hepatic Function Panel
  • CBC/d
  • Complete Metabolic Panel (CMP)
  • Hemoglobin A1C
  • Cholesterol
  • TSH w reflex to T4

Some tests are more expensive but still heavily discounted:

  • Hepatitis C RNA PCR Quantitative $100

The process of filling out the paperwork & having signed by a physician along with getting the testing complete will likely take a few weeks; so this testing right now is not useful for urgent testing.

My take:  Due to cost constraints, some patients are not receiving lab monitoring as frequently as recommended.  This discounted testing could be a useful for option in this scenario.

Key words:

  • Patient assistance
  • Cheap
  • Inexpensive
  • Lab test
  • Bloodwork
  • No insurance

Related blog post: What physicians can learn from fast-food restaurants and …

Gibbs Gardens

Gibbs Gardens

IBD and Pregnancy

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While managing inflammatory bowel disease during pregnancy is not within the scope of my practice as a pediatric gastroenterologist, it is helpful to have some familiarity with the issues.

Here’s a full-text link to AGA Guidelines: The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy

From the abstract, an excerpt:

Consensus was reached on 29 of the 30 recommendations considered. Preconception counseling and access to specialist care are paramount in optimizing disease management. In general, women on 5-ASA, thiopurine, or anti–tumor necrosis factor (TNF) monotherapy for maintenance should continue therapy throughout pregnancy. Discontinuation of anti-TNF therapy or switching from combination therapy to monotherapy may be considered in very select low-risk patients. Women who have a mild to moderate disease flare while on optimized 5-ASA or thiopurine therapy should be managed with systemic corticosteroid or anti-TNF therapy, and those with a corticosteroid-resistant flare should start anti-TNF therapy. Endoscopy or urgent surgery should not be delayed during pregnancy if indicated. Decisions regarding cesarean delivery should be based on obstetric considerations and not the diagnosis of IBD alone, with the exception of women with active perianal Crohn’s disease. With the exception of methotrexate, the use of medications for IBD should not influence the decision to breast-feed and vice versa. Live vaccinations are not recommended within the first 6 months of life in the offspring of women who were on anti-TNF therapy during pregnancy.

Gastro March2016

Better Discharge Planning Needed

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An interesting commentary in NY Times: Most Dangerous Time at the Hospital? May be When You Leave

An excerpt:

One-fifth of Medicare beneficiaries are readmitted within 30 days of discharge, and one-third are readmitted within 90 days. One studyfound that 20 percent of patients have a complication within three weeks of leaving the hospital — more than half of which could have been prevented or ameliorated. Thankfully most complications are minor, but some can be serious, leading to permanent disability or death. All told, Medicare spends $26 billion annually on readmissions, $17 billion of which is for readmissions that are considered preventable…

there’s often a rush toward the end of hospitalization — when a patient wants to leave or a rehab bed opens up — leading to a haphazard set of final conversations, appointments and prescriptions. And because the exact time of discharge is uncertain, the doctor discharging a patient may not be the one who knows the patient best.

It’s also often not clear exactly when a patient should be discharged….

the remaining diagnostics and treatments are often completed after discharge. But this is where we struggle most. Research suggests direct communication between hospital doctors and primary care doctorsoccurs infrequently and that discharge summaries — detailed records of a patient’s hospital course — are often unavailable at a patient’s first post-hospital visit. Almost 30 percent of patients are discharged with a plan to continue workups after hospitalization, but more than one-third of these are never completed. Similarly, more than 40 percent of patients have lab tests pending at the time of discharge — with 10 percent requiring action—but most physicians remain unaware of them.

My take: This is indeed an area where checklists and attention should be focused.  My top three:

  • Making sure a list of discharged medications is compared to admission medications
  • Identifying outstanding tests and arranging followup workup
  • Direct communication with outpatient physician(s)
Gibbs Gardens

Gibbs Gardens

Plumbism in Flint

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A brief commentary (DC Berlinger NEJM 2016; 1101-3) provides a succinct summary of the medical story from Flint.

Historical:

  • Lead exposure has been known to be a hazard since the 1st century: Dioscorides “observed in his De Materia Medica that ‘lead makes the mind give way.'”
  • In 1723, an industrial hygiene act in the colonies prohibited the use of lead in the apparatus to distill rum due to being “unwholesom.”
  • “Water doesn’t receive as much attention as paint…but,…our word ‘plumbing’ derives from the Latin for lead, and lead poisoning is often called ‘plumbism.'”
  • The past 40 years, the U.S. has had dramatic reductions in blood lead levels.  This is “one of the cardinal public health success stories.”
  • Lead in water poses unique problems because “it rarely originates in the source water.  Rather, the problem usually lies near the point of consumption.”

“There is no safe level of lead, particularly for children”

Flint:

  • In 2014, “the city began taking its water from the Flint river rather than Lake Huron.”  This was expected to save ~$100 per day; now, the cost of repairing infrastructure is estimated to be as high as $1.5 billion.  Yet the Flint river water was “19 times as corrosive,” leading to more lead in the water.
  • The incidence of blood lead concentrations above the reference value of 5 mcg/dL rose from 2.4% to 4.9% from 2013 to 2015.  “The increase was greatest, from 4.0% to 10.6%, among children in neighborhoods with the highest lead concentrations.”
  • Disadvantaged children already are at increased risk due to houses more likely to be in poor repair.  In addition, they are at increased risk from higher levels of lead in solid/dust and lead paint.
  • “In coming years, parents will undoubtedly wonder, with anxiety and even guilt, whether their children’s every developmental stumble stems from this episode.”

My take (borrowed from author): “We have the knowledge required to redress this social crime…what we lack is the political will to do what should be done.”

Related blog post:

Gibbs Gardens

Gibbs Gardens

Eosinophilic Esophagitis: the Limits of “Clinical Remission”

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Among patients with eosinophilic esophagitis (EoE), two issues are particularly vexing for families:

  • The recommendation to use endoscopy to assess response to treatment.
  • Using proton pump inhibitor (PPI) therapy as first line treatment when other therapies have higher response rates

To some extent, these issues are intertwined because PPI therapy works in less than half of patients and to determine this conclusively, an endoscopy is needed.  Clearly, a reliable noninvasive biomarker would be quite helpful.

In the meantime, another study (CE Kuehni et al. Gastroenterol 2016; 150: 581-90, editorial 547-48) has shown that “clinical remission” has modest accuracy in detecting endoscopic and histologic remission in EoE.

This prospective observational study, performed between 2011-14, recruited 269 consecutive adults in Switzerland and U.S.. 67% male median age 39 years.

Key finding:

Of 111 who were in clinical remission (41.3%), only 79 (72%) and 75 (68%) were in endoscopic and histologic (<20 eos/mm2 which corresponds to <5 eos/median hpf) remission respectively.

My take (borrowed): “Physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adult EoE patients.”

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Gibbs Gardens

Gibbs Gardens