Arsenic in Rice –New Recommendations

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Over the last two years, there has been increased concern about arsenic in rice.  This has been addressed by consumer reports, the American Academy of Pediatrics (AAP), and is being looked into by the FDA.

Due to the concerns about arsenic in rice, the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) committee on nutrition has published a consensus statement (JPGN 2015; 60: 142-145).  Pediatric gastroenterologists and pediatricians need to familiarize themselves with the report and their recommendations.

Key points:

  • Inorganic arsenic is a carcinogen.
  • “Arsenic content in raw rice varies from 0.1 to 0.4 mg of inorganic arsenic/kg of dry mass.  Rice has a much higher arsenic level than that in other grains.”
  • “Brown rice contains higher concentrations of arsenic.”
  • There is increased inorganic arsenic in products made from rice bran such as rice drinks is much higher due to the concentration of arsenic in the bran layers.
  • “Traditionally in European adults, an average of 9g of rice is consumed daily compared with 300g/day in Asian diets.”
  • “In the US population, mean childhood (1-6 years of age) dietary intake of inorganic arsenic is 3.2 mcg per day”
  • Currently, in the UK, the Food Standards Agency recommends against substitution of breastmilk, formula, or cow’s milk formula by rice drinks up to 4.5 years of age;  in contrast, in Sweden, recommendations advise no rice-based drinks for children <6 years.

Committee Conclusions/Recommendations:

  • “Inorganic arsenic intake during childhood is likely to affect long-term health”
  • “There is a lack of published data on the amount of arsenic in rice protein-based infant formula”
  • Inorganic arsenic in childhood should be as low as possible and the content in dietary products needs to be regulated
  • Rice drinks should not be used in infants and young children
  • Inorganic arsenic exposure can be reduced by including a variety of grains such as oat, barley, wheat, and maize.
  • Rice protein-based infant formulas remain an option in those with cow’s milk protein allergy,,.”the potential risks should be considered”

This is a link to the full length article (available via JPGNonline twitter feed): JGPN “Arsenic in Rice: A Cause for Concern”

This topic has been addressed by Nutrition4Kids website as well. Nutrition4Kids FDA Studying Arsenic

Bottomline: If there is an impact of arsenic in rice on long-term health, it is unclear; the amounts of these exposures are tiny in most cases.  Yet, given the availability of alternatives to rice and rice-based drinks, some changes in practice (ie. adhering to these guidelines) may be worthwhile.

 

 

HCV: When to Spike the Ball

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When a team scores a touchdown in football, often one sees a player spike the ball in celebration.  The equivalent of spiking a ball rarely happens in medicine.  That being said, a recent study (Hepatology 2015; 61: 41-45) indicates that after treatment sofosbuvir regimens, you can celebrate if you have a sustained virological response (SVR) at 12 weeks (SVR12).

The authors conducted a retrospective review of five trials with 863 patients with HCV genotypes 1-6.  “Of the 779 patients with an SVR12, 777 (99.7%) also achieved an SVR24.” Of the patients who relapsed, most (77.6%) did so within 4 weeks of completing therapy.

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Top Physician Skill -Listening

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One physician I’ve worked with recalls a mother of a patient telling him, ‘I really wish my husband would listen the way you do.’  This particular physician replied, ‘Well, just pay him $100 every time you say something.’

While this mother had a good experience with her physician (despite the cost), not all physicians are listening enough.  Here’s a link to a NY Times article that discusses this problem: Doctor, Shut Up and Listen

Here’s an excerpt:

A doctor’s ability to explain, listen and empathize has a profound impact on a patient’s care. Yet, as one survey found, two out of every three patients are discharged from the hospital without even knowing their diagnosis. Another study discovered that in over 60 percent of cases, patients misunderstood directions after a visit to their doctor’s office. And on average, physicians wait just 18 seconds before interrupting patients’ narratives of their symptoms. Evidently, we have a long way to go….

Observation soon revealed that physicians introduced themselves on only about one in four occasions…

Brief, rushed physician encounters were common, with limited opportunity for questions. A lack of empathy was often apparent…

We developed a physician-training program, which involved mock patient interviews and assessment from the actor role-playing the patient. Over 250 physicians were trained using this technique. We also arranged for a “physician coach” to sit in on real patient interviews and provide feedback.

Over the next two years, patient satisfaction with doctors, as measured by a standard questionnaire, moved the hospital’s predicted score up in national rankings by a remarkable 40 percentile points.

My take: I wonder about the accuracy of the information presented in this article.  Despite this, the message is clear that patients want to make sure that physicians are listening to them.

Another NY Times article worth a glance: The Drugs That Companies Promote to Doctors Are Rarely Breakthroughs  One quote: If a drug is either the first to treat a disease or is much better than existing drugs, said Dr. Sidney Wolfe, the founder and now senior adviser to Public Citizen’s Health Research Group, “they ‘sell themselves’ on the merits of their unique benefits.”

Heavy Heart due to Obesity

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A recent study (J Pediatr 2014; 165: 1184-9) documents a “cardiometabolic phenotype” which indicates that obesity and metabolic disease exert effects at a young age.

Design: A cohort of 281 white children from Italy were carefully studied with antropometrics, lipids profiles, blood pressure, glucose, and echocardiography. Of these children, 105 were obese (mean age 11 years) and 105 were morbidly obese (mean age 12 years); 31 had normal weight and 40 were overweight.

Key findings:

  • Heart disease: 53 had eccentric left ventricular hypertrophy (LVH), 36 had concentric LV remodeling, 44 had concentric LVH, 148 had normal echocardiograms.
  • Children with concentric LVH exhibited the most severe metabolic disturbances (graphically demonstrated in Figure 1)

Bottomline: The authors conclude that “we have identified a “cardiometabolic phenotype” occurring early in life, characterized by concentric LVH, visceral obesity, high BP, high Tg/HDL-C, and high-normal FPG [fasting plasma glucose].  This result may be clinically relevant because, in adulthood, a concentric LV geometric pattern is associated with a greater risk of CV events.”

Yosemite

Yosemite

IBD Update January 2015 (Part 2)

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1. A retrospective study (Inflamm Bowel Dis 2014; 20: 2292-98) of 217 patients with inflammatory bowel disease(108 infliximab-treated, 109 adalimumab-treated) provides data which indicates that combination therapy (mainly with thiopurines) resulted in higher trough levels and lower antibodies to infliximab (ATI) than monotherapy in patients treated with infliximab (IFX).  This was not evident in the adalimumab (ADA)-treated patients. Overall, approximately 90% of study population had Crohn’s disease.

Key points from this study:

  • The majority of trough level/antidrug antibody levels were drawn due to loss of response.  This is a major limitation of this study.
  • Among IFX-treated patients, those with combination therapy had trough level of 7.5 mcg/mL compared with 4.6 mcg/mL.  In combination therapy patients, the incidence of ATIs was 5.7% compared with 29.8% in monotherapy patients.
  • According to this study, the dose of the immunomodulator (IM) did not significantly influence the infliximab trough level or antibody formation; that is, more than half of patients were receiving “suboptimal dosed IM” and their infliximab levels/ATIs were similar to those who were optimally-dosed.
  • Among those who were receiving combination therapy, the incidence of antibody formation was lower in IFX-treated patients who started IM concurrently with IFX compared with those in which IM was added subsequently.
  • There were many other limitations in this study, including the finding that 94% of monotherapy patients had received previous immunomodulator therapy.

Bottomline: This study suggests that combination therapy is beneficial for patients receiving infliximab (in agreement with the previous SONIC study) and may not be beneficial for patients receiving adalimumab; however, only a well-designed prospective study

2. Inflamm Bowel Dis 2014; 20: 2266-70.  This study with 749 patients from Sweden showed that a large number of inflammatory bowel disease patients did not receive with iron supplementation: “Only 46% of patients with anemia were treated with iron supplementation or blood transfusion.”  This study showed frequent persistence of anemia one year after diagnosis, especially in children. At time of diagnosis, 55% of children and 27% of adults had anemia and 28% and 16% at one year followup, respectively.

My take: Treatment of the underlying IBD, often helps anemia.  However, in some patients treating the anemia with iron may help improve symptoms as much or more than other aspects of treatment.

3. Inflamm Bowel Dis 2014; 20: 2433-49.  Reviews pain management approaches for patients with IBD. The article emphasizes how pain can be multifactoral and that opiod-induced hyperalgesia may worsen pain.

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Bryce Canyon

Bryce Canyon

 

IBD Update January 2015 (Part 1)

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1. From the recent Advances in IBD Conference, Healio Gastroenterology reports on Dr. Baldassano’s update on PLEASE study which examined enteral nutrition in comparison to anti-TNF therapy.  Here’s the link: Enteral Nutrition Outcomes (Thanks to Kipp Ellsworth for this reference)

Here’s an excerpt:

Citing the findings from the Pediatric Longitudinal Study of Semi-Elemental Diet and Stool Microbiome (PLEASE), Baldassano demonstrated that greater mucosal healing was achieved in CD patients on exclusive enteral nutrition compared with partial enteral nutrition therapy. In this prospective cohort study, 38 children received enteral therapy with defined formula diet and 52 controls received anti-TNF-alpha therapy. The enteral nutrition group was further stratified to evaluate mucosal healing on a more restrictive diet; one subgroup received 80% to 90% of total caloric needs from enteral therapy, of which 14% achieved induction of remission at 8 weeks, the other subgroup received 90% to 100% of total caloric needs from enteral therapy, of which 45% achieved remission, and 62% of controls achieved remission.

2. NEJM 2014; 371: 2418-27. This is a case report of a 9-year-old with Crohn’s Disease and pulmonary nodules.  This report serves as a useful review.

3. Standardized use of fecal calprotectin (here’s the link -from KT Park’s Twitter feed):

Fecal calprotectin -use for identifying IBD and for identifying relapse risk

4. Inflamm Bowel Dis 2014; 20: 2247-59. Study examined factors associated with infliximab clearance.  Higher clearance noted with low albumin, high body weight, and the presence of antibodies to infliximab (ATI).  The authors note that higher concentrations with dose escalation are more likely when the dose interval was shortened than by increasing the administered dose.

5. Inflamm Bowel Dis 2014; 20: 2260-65. “Natural History of Perianal Crohn’s Disease After Fecal Diversion.”  Despite greater use of biologics, only 15 of 49 patients reestablished intestinal continuity between 2000-2011.  In this group of 15, only 5 remained reconnected and 3 of these 5 patients had procedures to control sepsis.  The likelihood of sustained intestinal continuity remains low in patients who have required a diverting procedure.

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Sandy Springs, Georgia

Sandy Springs, Georgia

Miralax -More Scrutiny, Research Study

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A recent NY Times article is probably ‘required reading’ for all pediatric gastroenterologists, pediatricians, and family practitioners:

Here’s the link: Mirlax -Scrutiny for a Childhood Remedy

Here are some excerpts:

The [FDA] agency has asked a team of scientists in Philadelphia to look more closely at the active ingredient in Miralax and similar generic products, called polyethylene glycol 3350, or PEG 3350. While outlining the scope of the research, the agency also disclosed that its scientists had discovered trace amounts of two potential toxins in batches of Miralax tested six years ago.

The news is likely to surprise parents and some doctors.

“Every pediatric GI physician, I would guarantee you, has told a family this is a safe product,” said Dr. Kent C. Williams, a gastroenterologist at Nationwide Children’s Hospital in Columbus, Ohio. Now, he worries, “it may not be true.”

Doctors have long recommended these laxatives for their convenience and on the grounds that very little PEG 3350 is absorbed in the intestines. But the F.D.A. says there is little data on its absorption in children, especially the very young and chronically constipated. The agency never approved long-term daily use of the laxatives, even in adults….

Moreover, for years the F.D.A. has received occasional reports of tremors, tics and obsessive-compulsive behavior in children given laxatives containing PEG 3350. It is not known whether the laxatives are the cause….

The F.D.A. said that it had tested eight batches of Miralax and found tiny amounts of ethylene glycol (EG) and diethylene glycol (DEG), ingredients in antifreeze, in all of them. The agency said the toxins were impurities resulting from the manufacturing process.

Those tests were conducted in 2008..The agency again tested PEG 3350 laxatives from five makers in 2013, Mr. Ventura said. None had detectable amounts of EG or DEG. “The amounts were so low,” he added, and “complied with internationally recognized safety standards.”

Bottomline: The previous pediatric studies of Miralax that have been published have shown favorable benefits and not disclosed adverse effects.  It is difficult to exclude the possibility that there is a small subset of children in which Miralax results in adverse effects.  As with many medications, more pediatric data is needed.

Question: Will this or should this change how Miralax is discussed with families?

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IBD Incidence Increasing: 30 Years of Data from Manitoba

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A recent study (JPGN 2014; 59: 763-66) shows a steady trend of increased incidence of IBD in Manitoba. This figure is available online:

 

Increasing IBD Incidence in Children

Increasing IBD Incidence in Children from JPGNonline

Abstract:

Objectives: The aim of this study was to describe the incidence and prevalence of inflammatory bowel disease (IBD) in children <17 years of age in 30 years from 1978 to 2007.

Methods: From January 1, 1978, to December 31, 2007, the sex- and age-adjusted annual incidence and prevalence of pediatric IBD per 100,000 population were calculated based on the pediatric IBD database of the only pediatric tertiary center in the province. The annual health statistics records for the Province of Manitoba were used to calculate population estimates for the participants. To ensure validity of data, the University of Manitoba IBD Epidemiology Database was analyzed for patients <17 years of age from 1989 to 2000.

Results: The sex- and age-adjusted incidence of pediatric Crohn disease has increased from 1.2/100,000 in 1978 to 4.68/100,000 in 2007 (P < 0.001). For ulcerative colitis, the incidence has increased from 0.47/100,000 in 1978 to 1.64/100,000 in 2007 (P < 0.001). During the same time period, the prevalence of Crohn disease has increased from 3.1 to 18.9/100,000 (P < 0.001) and from 0.7 to 12.7/100,000 for ulcerative colitis (P < 0.001). During the last 5 years of the study the average annual incidence of IBD in urban patients was 8.69/100,000 as compared with 4.75/100,000 for rural patients (P < 0.001).

Conclusions: The incidence and prevalence of pediatric IBD are increasing. The majority of patients were residents of urban Manitoba, confirming the important role of environmental factors in the etiopathogenesis of IBD.

Unrelated: As a bonus for those who made it to the bottom of this post : there’s a new Bristol Stool App for iPhones.  Here’s the link: http://www.bristol-stool-scale.com (from John Pohl’s twitter feed)

 

Prenatal Testing, Statistics, and Life-Altering Decisions

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Much of my day is spent interpreting lab work.  Sometimes it is very easy but not always. Many families and health care professionals do not understand the concepts of sensitivity, specificity, positive predictive value and negative predictive value.  These values are affected greatly by the prevalence of the condition (or disease) that is being tested for in a specific population.

For many conditions, doctors prefer a highly sensitive test.  Tests that are highly sensitive will detect almost all of the individuals with the condition (or disease) being tested for and miss very few people (false-negative) with the condition. However, tests that are very sensitive often detect individuals who do not have the condition (false-positives). Therefore, when using tests with high sensitivity, more precise followup tests can determine conclusively if the condition (or disease) is present with much greater specificity.

A report from NBC news highlights how tests that are billed as “99 percent” accurate can be quite difficult to interpret and could lead to abortions of healthy fetuses.  Here’s the link: Sensitivity, Positive Predictive Value, and Prenatal Testing

Here’s an excerpt:

Positive results can be wrong 50 percent or more of the time…Noninvasive prenatal tests, or the “cell free DNA test,” are merely screening tests of placental DNA found in the mother’s blood…

The true likelihood that a positive test is positive depends on another calculation — the positive predictive value or PPV, which factors in other variables, such as a woman’s age and the prevalence of the disease in that population…

A woman over 35 where genetic disorders are more common — the likelihood of Trisomy 18 given a positive screening result is about 64 percent. For a younger woman, the PPV would be under 50 percent, according to the investigation.

Another example of understanding tests and statistics involves mammograms.  The relatively low reduction in averted cancer deaths related to mammograms has been discussed previously on this blog (see links below).  A good infographic and description is also available at NPR.  Here’s the link: What happens after your mammogram

 

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Blue-footed Booby

Blue-footed Booby

Enthusiasm for Vedolizumab

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A recent GI & Hepatology News article quoted several leading IBD researchers stating that they consider Vedolizumab a first-line biologic therapy for ulcerative colitis.  Here’s the link:

Vedolizumab for UC

Here’s an excerpt:

Dr. Feagan presented outcome results after 80 and 104 weeks of vedolizumab treatment of 278 patients with ulcerative colitis who had completed a full year of treatment during the GEMINI 1 trial [Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab in Patients with Moderate to Severe Ulcerative Colitis] (N. Engl. J. Med. 2013;369:699-710). He reported that the percentage of patients in clinical remission grew from 66% after 52 weeks on treatment (the time of entry into the long-term phase of the study), to 77% after 80 weeks, which then dropped to 73% after 104 weeks. Patients with a clinical response increased from 78% after 52 weeks to 88% after 80 weeks, and then dropped to 83% after 104 weeks.

During weeks 53-104 on treatment the rates of adverse events, serious adverse events, serious infections, adverse events resulting in treatment discontinuation, enteric infections, and malignancies were all low and similar to the event rates seen among the patients randomized to placebo in the GEMINI 1 study.

The results suggest that with vedolizumab treatment of inflammatory bowel disease “once you achieve an effect it is long-lasting,” Dr. Rutgeerts said in an interview. But he cautioned that the long-lasting efficacy was achieved with treatment every 4 weeks. While this approach was safe, it would also be expensive in routine practice, he noted. “The safety looks good, but the cost would be very high.”

“A key concept of vedolizumab is that it builds efficacy over time,” commented Dr. Silvio Danese during a talk at the meeting. “Vedolizumab is not the fastest runner, but [treating inflammatory bowel disease] is a marathon, and the important thing is getting to the finish”

Bottomline: Head-to-head trials would be helpful to determine which biologic agent should be considered first-line.

Related blog posts:

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