Is Appendicitis No Longer a Surgical Emergency?

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A recent study indicates that a fairly high number of adults with appendicitis could avoid surgery (JAMA 2015 June 15 [doi:10.1001/jama.2015.6154]).

In this study, patients with CT-confirmed acute uncomplicated appendicitis were randomly assigned to either immediate surgery (n=273) or a 1-day of IV ertapenem followed by 7 days of levofloxacin and metronidazole.

Here’s a summary of the study –from GIHepNews: Antibiotic therapy an option for acute appendicitis  Here’s an excerpt:

The primary endpoint for the antibiotic group – resolution of acute appendicitis with no recurrences for a full year – occurred in 73%. The remaining 27% of patients in this group underwent appendectomy during follow-up, at a median of 102 days after initial presentation. None of these patients developed abscesses or serious infections, “suggesting that the decision to delay appendectomy … can be made with a low likelihood of major complications,” the investigators said 

And commentary from Edward Livingston, M.D., is deputy editor of JAMA. Corrine Vons, M.D., Ph.D., is in the digestive surgery department at Jean-Verdier Hospital, Bondy, France. :

The study findings dispel the notion that appendectomy is always an emergency and suggest instead that, given our current precise diagnostic capabilities and effective wide-spectrum antibiotics, a trial of antibiotic therapy is reasonable. However, it’s important to note that children, adolescents, pregnant women, and patients with complications were excluded from this trial so the findings do not apply to those patient groups.

Dr. Livingston and Dr. Vons made these remarks in an editorial accompanying Dr. Salminen’s report (JAMA 2015;313:2327-8).

My Take: This study indicates, at least in adults with uncomplicated appendicitis, that antibiotic treatment is an option. I think resolving the problem definitively would be my preference.  If you had appendicitis, which therapy would you choose? Take the poll.

Related blog post:

This is Analogous to 'Negative' Studies

This is analogous to ‘negative’ studies

 

What Will They Think of Next? A Vomit Machine for Studying Norovirus!

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A summary of a recent report from NBC news:

Yuck! Vomit Machine Shows Why Norovirus Spreads So Fast

Here’s an excerpt:

They used another virus called MS2 that’s similar to norovirus, that doesn’t make people sick and that’s easy to grow in the lab.,,

“We think that there’s a at least a million particles released in a vomiting event and maybe more.”

Not all of it goes into the air. In fact, very little did in their experiments. But it was enough. They estimate that as many as 13,000 virus particles can be released into the air with a single retch. They made a video that shows how it works.

“There was evidence of aerosolized MS2 after every simulated vomiting episode,” they wrote in their report, published in the Public Library of Science journal PLoS ONE.

People can be infected with as few as 20 to 1,300 microscopic viral particles, so their study shows that vomiting could indeed spread the infection through the air….

“WHEN ONE PERSON VOMITS, THE AEROSOLIZED VIRUS PARTICLES CAN GET INTO ANOTHER PERSON’S MOUTH AND, IF SWALLOWED, CAN LEAD TO INFECTION.”

“There are 21 million cases of human norovirus infection in the U.S. each year, and this virus genus is now recognized as the leading cause of outbreaks of acute gastroenteritis,” the researchers wrote.

It kills up to 800 people a year in the U.S. alone and puts 70,000 into the hospital, so understanding how it spread sand finding ways to stop it could prevent many illnesses, the researchers said.

Related blog posts:

Why a Temporary Nursery Name is a Bad Idea

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An interesting study in Pediatrics has found that avoiding temporary NICU names can result in fewer errors.  Here is the NY Times summary:

More than 80 percent of neonatal intensive-care units, or NICUs, use temporary first names for patients — Babygirl Jackson or Babyboy Goldsmith, for example — a convention that may lead to errors in prescribing medicines. A new study has found that a simple change in this procedure can significantly reduce such errors.

The NICUs at Montefiore Medical Center in the Bronx instituted a new system two years ago. They started naming babies using the mother’s first name — Jennifersgirl Jackson and Karensboy Goldsmith. Researchers compared the number of wrong-patient electronic orders of medicines in the year before the change with the number in the year after. The study, in Pediatrics, included 158,000 orders before the change and 142,000 after.

Over all, the new system reduced errors by 36.3 percent.

My Take: Both with electronic records and with ‘paper’ records, the lack of a specific name leads to errors.  With electronic records, another frustration is when multiple records for the same patient have not been merged into a single entity, allowing key information to be unavailable.

Uncle Tom's Point, Yellowstone

Uncle Tom’s Point, Yellowstone

Upside Down Incentives in Pharmaceutical Development –Profit over Patients

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A good read on why cheap effective drugs may not be coming to the market in the U.S. –as well as solutions. (Full text: AR Kellermann, NR Desai. JAMA. Published online August 17, 2015. doi:10.1001/jama.2015.10114)

Here’s an excerpt:

In 2003, Wald and Law proposed to combine 3 half-dose antihypertensive agents, an intermediate-dose statin, low-dose aspirin, and folic acid into a once per day polypill for primary and secondary prevention of cardiovascular disease. Based on epidemiological models, they estimated that daily use by individuals aged 55 years or older could reduce the incidence of MI and stroke by more than 80%.

In the 12 years since this report was published,3 versions of the polypill have been successfully tested in several phase 2 (safety) studies and a few modest-sized phase 3 (efficacy) trials. Collectively, these studies demonstrated that the polypill was well tolerated, achieved good adherence, and based on intermediate end points, such as reduction of blood pressure and low-density lipoprotein cholesterol level, is efficacious…

The 4 drugs in the current version of the polypill have long histories of safe use. Although all 4 are frequently prescribed in the United States, the US Food and Drug Administration (FDA) has not approved combining them in a single pill…

Although the polypill could produce substantial public health benefits, people in the United States are unlikely to find out anytime soon. This is because the pill’s price is so low (≤$1 per tablet) and the cost of the large clinical trials required for FDA approval is so high, it is unattractive to investors. The inventor’s dilemma is that creating a product that improves health is not enough; the product must also be able to generate a healthy return on investment. In the United States, the surest way to generate a healthy return on investment is to increase health care spending, not reduce it.

Related blog posts:

Spice It Up? Curcumin for Ulcerative Colitis

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This past week I’ve been on call and had not finished a few articles.  One article that was on the to do list: A Lang et al. Clinical Gastroenter Hepatol 2015; 13: 1444-9.

I’ve read it now.  However, even before finishing the article, I read a few good summaries of this article, including one from my colleague Stan Cohen/Nutrition4Kids: Curcumin Helps (A Lot) in Ulcerative Colitis

Here’s an excerpt:

The cover of a prestigious medical journal shows a pile of curcumin and over it, the announcement reads: Curcumin Helps Induce Remission in Mild-to-Moderate Ulcerative Colitis.  That’s big news for a lot of reasons: first, this Indian spice (derived from tumeric) is inexpensive and well-tolerated; second, in a well-designed scientific study, curcumin showed that it was more effective than some medicines; and third, it showed, again, that careful trials of long-used herbs can be done with important results being shown.  Again, because an earlier study (H Hanai, Clinical Gastroenterology 2006, pages 1502-6) had previously shown that curcumin can help keep ulcerative colitis (UC) patients from flaring for up to 12 months. 

This new study (A Lang, Clinical Gastroenterology 2015, pages 1444-9) compared curcumin to a placebo in patients who were not doing well on the standard therapy (mesalamine) for mild to moderate UC.  With a single daily dose of 3 grams of curcumin in capsule form, 65% responded (compared to 12% with a placebo) and 54% actually went into remission, having essentially no symptoms.  Perhaps even, more importantly, 38% of those taking the curcumin showed improvement in the intestinal tissue when a colonoscopy was performed.  That’s comparable or better than some of the medications that are being used.

A few other details: The researchers used a product called Cur-Cure from Bara Herbs Inc (Yokneam, Israel).  Also, the associated commentary in the same journal by CN Bernstein (pages 1450-52) suggests that the study may have targeted mild ulcerative colitis (rather than moderate ulcerative colitis). He comments that the increasing rates of ulcerative colitis among Indian immigrants could be related to including less curcumin in their now more westernized diets.  He also notes, as did Dr. Cohen, that there were previous promising studies dating back to 2006.  Why has it taken nine years for this report?

My Take: This is probably an article worth reading.  Although curcumin appears promising, I worry that a lack of financial incentive may hamper research efforts to better define its place as an agent for treatment of ulcerative colitis.

Related blog posts:

Curcumin

This has been a sad week in our office.  Here are links to two poems that come to mind:

What is Wrong with the Glimmer of “Precision Medicine”

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Several thought leaders, including Francis Collins, have heralded the age of “precision medicine.” A recent commentary provides compelling arguments why “enthusiasm is premature.”

The greatest problems we face in improving health care do not require precision medicine.

“In 2013, the National Research Council (NRC) and the Institute of Medicine (IOM) issued a bleak report on life expectancy and well-being in the United States.  Shorter Lives, Poorer Health documented the extent to which Americans were at a disadvantage at every stage of life compared with their counterparts in peer countries.”  Americans fared worse in all of the following:

  • Birth outcomes
  • Heart disease
  • Motor vehicle accidents
  • Violence
  • Sexually transmitted disease
  • Chronic lung disease

The NRC notes that “health is determined by far more than health care.”

Other points:

  • While the U.S. may have the most advanced healthcare in the world, the “whiz-bang technology just cannot fix what ails us.” (NY T-inequality-is-costing-the-us-on-social issues.html)
  • “Precision medicine itself may ultimately make critical contributions to a narrow set of conditions, but the challenge we face…entails…willingness to address certain persistent social realities”
  • “Our public investments in broad, cross-sectional efforts to minimize…foundational drivers of poor health as poverty…are pitifully few in comparison with those of other countries.”
  • Take-home message from authors: “We worry that an unstinting focus on precision medicine by trusted spokespeople for health is a mistake — and a distraction from the goal of producing a healthier population.”

My view: The challenges posed by the authors do seem monumentally greater than those facing the development of precision medicine.

Related blog posts:

Here's a Book Where the Title May Be Misinterpreted

Here’s a Book Where the Title May Be Misinterpreted

 

Is It a Good Idea for Pregnant Mothers to Take Probiotics?

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A previous study has indicated that maternal probiotic administration was associated with a lower rate of atopic dermatitis.  The overall quality of evidence supporting this association is considered low.

A recent study (CK Dotterud et al. JPGN 2015; 61: 200-7) examined the effect on the intestinal microbiota in both mother and child following maternal perinatal probiotic supplementation. This randomized, double-blind trial examined the effect of probiotic administration (or placebo) from 36 weeks of gestation up to 3 months postnatally while breastfeeding. Stool microbiome was examined in both mother and child.

Key findings:

  • The changes in the infants microbiome were quite limited. “Only the Lactobacillus rhamnosus GG bacteria colonized the children at 10 days and at 3 months of age. There were no significant differences in the abundance of administered probiotic bacteria between the groups at 1 and 2 years of age.”

My take: We know very little about probiotics and their effects on the GI tract. We often do not even the basics: which strains? which dosage?  optimal timing/when to use?  Given the lack of persistent change in the infant’s microbiome, does administration to pregnant mothers really make any sense (outside of research endeavors)?

Disaccharidase Deficiencies in Recurrent Abdominal Pain

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Question for pediatric gastroenterologists (first poll I’ve placed in this blog): Do you think disaccharidases are needed routinely for patients with abdominal pain in the absence of bloating, or diarrhea?

A recent report indicated a high rate of disaccharidase deficiencies among children with recurrent abdominal pain. Here’s the abstract link: Disaccharidase Deficiencies in Children With Chronic Abdominal Pain (K El-Chammas, SE Williams, A Miranda. Published online before print July 9, 2015, doi: 10.1177/0148607115594675JPEN J Parenter Enteral Nutr July 9, 2015 0148607115594675).  Thanks to Kipp Ellsworth for this reference.

Here’s an excerpt:

Data on disaccharidase activity and histology of endoscopic biopsies were collected retrospectively. Only patients with normal histology were included in the study.

Results: A total of 203 pediatric patients with CAP were included. The mean (SD) age was 11.5 (3.1) years, and 32.5% were male. The percentages of abnormally low disaccharidase levels using the standard laboratory cutoffs were lactase, 37%; sucrase, 21%; glucoamylase, 25%; and palatinase, 8%. Thirty-nine percent of the patients with low lactase also had low sucrase, and 67% of the patients with low sucrase had low lactase…Also, no association was found between stool consistency, stool frequency, or location of pain and low disaccharidase activity.

My take: I am highly skeptical regarding these findings–see Twyman’s Law | gutsandgrowth. For sucrase deficiency, for example, this report represents an extraordinarily high rate of deficiency compared with previous reports. In addition, there are numerous errors which can occur in the handling of tissue specimens.  With regard to lactase deficiency, of course, this is common but having lactose intolerance does not prove causality with regard to abdominal pain.  Many physicians encourage families to see if there is a link between milk ingestion and GI symptoms to help determine if lactose intolerance is a likely contributor to stomach pain (before endoscopy). Stomach pain in the absence of milk ingestion is not due to lactose intolerance.

Before accepting these high rates, improved methodology (eg. control group and duplicating results) would be helpful.

Related blog post: Congenital Sucrase Isomaltase Deficiency

 

Lipid Testing: Why Screen and Fail to Act?

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There has been controversy regarding the American Academy of Pediatric recommendations on lipid screening and treatment, mainly because the guidelines propose earlier screening and more aggressive treatment than other guidelines, including guidelines from the American College of Cardiology and the American Heart Association.  However, according to a recent article (N Joyce et al. J Pediatr 2015; 167: 113-9), it does not appear that many children (8-20 years) are actually being treated.

The authors used commercial health plan data between 2004-2010 and collected data from more than 13 million children.  Only 665 were initiated on lipid lowering therapy which equates to an incidence rate of 2.6/100,000 person-years.

Rates of lipid lowering therapy were higher in those ≥15 years with odds ratio of 2.9 and much higher in those with a familial hypercholesterolemia (OR 165.2).

Take home message from authors: “our findings suggest lipid lowering therapy is underutilized in this population.”   It is likely that many who have undergone testing and who have abnormal lipids are not being treated.  If so, why bother testing?

Related posts:

Helpful Review on Biliary Atresia

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Biliary atresia (BA) remains the leading cause of pediatric liver transplantation and a frequent cause of cholestasis in newborns.  A recent review (AG Feldman, CL Mack. JPGN 2015; 61: 167-75) provides a helpful update. The article begins with a review on pathogenesis, though this remains unknown and continues to be an area of speculation.

The section on evaluation includes a suggested diagnostic algorithm for neonatal cholestasis.  In short, for a 2 week old with jaundice , the authors recommend (STEP 1) fractionating the bilirubin.  The infant is considered cholestasis if the direct bilirubin is ≥1 mg/dL (if total bilirubin is <5 mg/dL) or if direct bilirubin ≥20% of total bilirubin (if total bilirubin is >5 mg/dL).

Among cholestatic infants, the authors recommend (STEP 2) next checking ultrasound and alpha-one antitrypsin (A1AT) (level & phenotype).  The text implies that the authors would check a GGTP.  While this is not in their algorithm, many would suggest checking urine reducing substances, coags, serum glucose, and consideration of sepsis evaluation; these tests can identify issues that are more urgent than identifying biliary atresia.

STEP 3: If U/S and A1AT, are not diagnostic, consider urine culture, urine reducing substances, urine succinylacetone, and additional infectious studies.

STEP 4: Proceed with liver biopsy. If findings of biliary atresia (eg. bile plugs, bile duct proliferation, portal fibrosis), proceed with intraoperative cholangiogram.

Other points:

  • “It is rare for an infant with BA to have a GGTP level <200 U/L.” If low GGTP, consider PFIC, inborn error of bile acid metabolism, and panhypopituitarism.
  • Extensive differential diagnosis table given ((Table 1)
  • “Late diagnosis of BA remains a problem in the United States. The average age of HPE [hepatoportoenterostomy] is 61 days and 44% of patients still undergo HPE after 60 days of life.”  The authors indicate a goal for HPE of taking place  at <45 days of life.
  • Successful HPE can occur even with late diagnosis. 10% to 20% of children who undergo HPE after 100 to 120 days of life still have success in restoring bile flow.”
  • Early/successful HPE is helpful in increasing 10-year transplant-free rate.  Early on, 3 months after HPE, those with a total bilirubin <2 mg/dL compared with those with a total bilirubin of >6 mg/dL have a much lower likelihood of liver transplantation by 2 years of age: 84% vs. 16%.
  • Recommends checking a pulse oximetry at routine followup visits following HPE to look for the possibility of hepatopulmonary syndrome.
  • The article reviews complications including ascites, portal hypertension/GI bleeding, cholangitis, malignancy, and hepatopulmonary syndrome/portopulmonary hypertension.
  • Outcomes: With HPE, “up to two-thirds of patients with BA have short-term clearance of jaundice.” Yet, “80% of patients with biliary atresia will require liver transplantation during childhood.”

Also noted:

“Biliary Atresia is Associated with Hypertension” JPGN 2015; 61: 182-86.

“Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes” A Asai, A Miethke, JA Bezerra. Nat Rev Gastroenterol Hepatol 2015; 12: 343-52.  This review provides in-depth review examines more precise phenotyping, influencing factors (eg. cytomegalovirus), and potential mechanisms.

Related blog posts:

From Mt Washburn, Yellowstone

From Mt Washburn, Yellowstone