Hepatitis B Vaccine Protects for Up to 30 Years

Posted on March 27, 2016 by gutsandgrowth

From summary at GI & Hepatology News: Hepatitis B vaccine protection lasts 30 years

An excerpt:

Ninety percent of patients in a 1981 hepatitis B vaccine trial still had evidence of immune protection 30 years later, according to a study in the Journal of Infectious Diseases…
243 members of the original cohort who responded to the original primary vaccine series but received no subsequent doses during the 30-year period…
Of the patients tested, 125 (51%) had anti-HBs levels greater than or equal to 10 mIU/mL. Among participants with anti-HBs levels below 10 mIU/mL who were available for follow-up, 75 of 85 (88%) responded to a booster dose with an anti-HBs level greater than or equal to 10 mIU/mL at 30 days.
Read the full study in the Journal of Infectious Diseases (J Infect Dis. 2016 Jan 21. doi: 10.1093/infdis/jiv748).

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LEAP-ON Study: Early Peanuts Prevent Allergies

Posted on March 26, 2016 by gutsandgrowth

A followup study to the LEAP study (The Peanut Story -From NEJM Blog | gutsandgrowth) shows that early peanut exposure produces a durable protection from peanut allergies. NPR summary: Peanut Mush in Infancy Cuts Allergy Risk

Here’s an excerpt:

Researchers followed the kids for one additional year. The kids were between 5 and 6 years old during this follow-up period. It turned out, these high-risk kids’ tolerance to peanuts held up even if they stopped eating peanuts.

“A 12-month period of peanut avoidance was not associated with an increase in the prevalence of peanut allergy,” the authors write in the paper.

This is an important finding, because it wasn’t known whether the kids would need to maintain regular weekly consumption of peanuts in order to stave off developing an allergy…

But that doesn’t mean all parents should just rush in with the peanut mush. The guidance recommends that “infants with eczema or egg allergy in the first 4 to 6 months of life might benefit from evaluation by an allergist” — before they’re introduced to peanut-based foods.

Fajardo, Puerto Rico

Pharmaceutical Prescription Practices Tied to Pharmaceutical Payments to Doctors

Posted on March 25, 2016 by gutsandgrowth

A recent buzz has developed regarding a ProPublica study showing an association between the amount of money physicians receive from pharmaceutical companies and their likelihood of recommending brand (rather than generic) prescription drugs.

Here’s a link to the full story: Now There’s Proof: Docs Who Take Company Cash Tend to Prescribe More Brand-Name Meds

“The more money doctors receive from drug and medical device companies, the more brand-name drugs they tend to prescribe, a new ProPublica analysis shows. Even a meal can make a difference.”

Here’s a link to NPR’s summary: Drug-Company Payments Mirror Doctors’ Brand-Name Prescribing An excerpt:

“A ProPublica analysis has found that doctors who receive payments from the medical industry do indeed prescribe drugs differently on average than their colleagues who don’t. And the more money they receive, the more brand-name medications they tend to prescribe.

We matched records on payments from pharmaceutical and medical device makers in 2014 with corresponding data on doctors’ medication choices in Medicare’s prescription drug program.

Doctors who got money from drug and device makers prescribed a higher percentage of brand-name drugs overall than doctors who didn’t, our analysis showed. Even those who simply got meals from companies prescribed more brand-name drugs, on average.”

My take: Prescription patterns vary widely among physicians and often for good reason. At the same time, it is likely that in many cases variation in prescription patterns is influenced by frequent contact with pharmaceutical companies. As a consequence, this has the potential to make patients question whether their physician always has their best interest in mind and the potential to increase healthcare costs.

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Is Intestinal Function in Children with Autism Different?

Posted on March 24, 2016 by gutsandgrowth

There has been a lot of concern that abnormal GI function contributes to both behavioral and gastrointestinal symptoms in children with autism. To categorize some of these problems, the term ‘leaky gut’ has been used.

An upcoming study (RI Kushak et al. JPGN DOI: 10.1097/MPG.0000000000001174) (thanks to Ben Gold for forwarding this reference) examines this issue. Using a case-control design, pediatric patients with autism spectrum disorder (ASD) (n=61) were compared with 50 children with normal development.

Workup:

Endoscopy (EGD and colonoscopy) with histologic analysis
Disaccharidase analysis
Intestinal permeability studies with lactulose and rhamnose
Fecal biomarkers: calprotectin and lactoferrin

According to the authors, all of the study subjects underwent endoscopy and “all had clinical indications for diagnostic endoscopy.” Most common indications were parental reports of abdominal pain and diarrhea.

Key findings:

Disaccharidase activity levels were not significantly different between the groups. In agreement with prior studies, there was frequent lactase deficiency, with 66% of ASD children in this study with deficient enzyme activity (<15 μmol/min/g). However, lactase activity in the children with ASD was not lower than the non-ASD children.
There were no significant differences in measures of intestinal permeability. Normative values for lactulose and rhamnose ratio are not definitively established. However, when using similar cutoff ratios, there were similar results in both groups.

Calprotectin:

Intestinal inflammatory markers (calprotectin/lactoferrin) were not significantly different, after the authors excluded the five “neurotypical” children who were diagnosed with inflammatory bowel disease.
For calprotectin, the authors considered a level <50 mcg/g to be normal. In the ASD group, 31of 49 (63%) had abnormal calprotectin compared with 19 of 31 (61%) in the non-ASD group.
For calprotectin levels >150 mcg/g, 9 of 49 (18%) reached this level in the ASD group and 8 of 31 (26%) in the non-ASD group.

Histology:

Similar levels of GI tract inflammation were noted in both groups –generally mild.
In the ASD group, 32 (52%) had inflammation somewhere in their GI tract, “but it was generally mild and non-diagnostic.” In the ASD group, five had features consistent with GERD, two had eosinophilic esophagitis (EoE). There were 12 (19%) who had colonic inflammation and 3 (5%) with ileal inflammation. None had celiac disease or H pylori.
In the non-ASD group, four had EoE, four (8%) had ileal inflammation, and nine (18%) had colonic inflammation. The authors noted Crohn’s disease in three and a total of five children with IBD.

My take:

This study suggests that symptomatic children with autism have similar (and probably not worse) GI problems as neurotypical children. The idea that children with autism have a more leaky gut than children without autism is quite dubious based on these results.
The biggest problem for GI physicians is not addressed in this study and involves children with and without autism: appropriate selection for evaluation. While the authors chose children with “clinical indications,” these, in fact, are often subjective and with permissive interpretation could be used to justify endoscopy in 40% of children.
Another huge problem is interpretation of abnormal results. While the authors report large numbers with intestinal inflammation in both groups, most of this was considered to be insignificant clinically. How should trivial inflammation be reported in studies? This problem is not unique to this study and makes it difficult to assess the value of endoscopy more broadly.

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Detrimental Effect of Early Parenteral Nutrition in Critically-ill Children

Posted on March 23, 2016 by gutsandgrowth

Ahead of publication: T Fizez et al. Early versus Late Parenteral Nutrition in Critically Ill Children. DOI: 10.1056/NEJMoa1514762

Link to quick take video summary (<2 minutes) : NEJM Quick Take on Parenteral Nutrition in Children

Abstract:

BACKGROUND

Recent trials have questioned the benefit of early parenteral nutrition in adults. The effect of early parenteral nutrition on clinical outcomes in critically ill children is unclear.

METHODS

We conducted a multicenter, randomized, controlled trial involving 1440 critically ill children to investigate whether withholding parenteral nutrition for 1 week (i.e., providing late parenteral nutrition) in the pediatric intensive care unit (ICU) is clinically superior to providing early parenteral nutrition. Fluid loading was similar in the two groups. The two primary end points were new infection acquired during the ICU stay and the adjusted duration of ICU dependency, as assessed by the number of days in the ICU and as time to discharge alive from ICU. For the 723 patients receiving early parenteral nutrition, parenteral nutrition was initiated within 24 hours after ICU admission, whereas for the 717 patients receiving late parenteral nutrition, parenteral nutrition was not provided until the morning of the 8th day in the ICU. In both groups, enteral nutrition was attempted early and intravenous micronutrients were provided.

RESULTS

Although mortality was similar in the two groups, the percentage of patients with a new infection was 10.7% in the group receiving late parenteral nutrition, as compared with 18.5% in the group receiving early parenteral nutrition (adjusted odds ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66). The mean (±SE) duration of ICU stay was 6.5±0.4 days in the group receiving late parenteral nutrition, as compared with 9.2±0.8 days in the group receiving early parenteral nutrition; there was also a higher likelihood of an earlier live discharge from the ICU at any time in the late-parenteral-nutrition group (adjusted hazard ratio, 1.23; 95% CI, 1.11 to 1.37). Late parenteral nutrition was associated with a shorter duration of mechanical ventilatory support than was early parenteral nutrition (P=0.001), as well as a smaller proportion of patients receiving renal-replacement therapy (P=0.04) and a shorter duration of hospital stay (P=0.001). Late parenteral nutrition was also associated with lower plasma levels of γ-glutamyltransferase and alkaline phosphatase than was early parenteral nutrition (P=0.001 and P=0.04, respectively), as well as higher levels of bilirubin (P=0.004) and C-reactive protein (P=0.006).

CONCLUSIONS

In critically ill children, withholding parenteral nutrition for 1 week in the ICU was clinically superior to providing early parenteral nutrition. (Funded by the Flemish Agency for Innovation through Science and Technology and others; ClinicalTrials.gov number, NCT01536275.)

More details:

Methods:

“In both study groups, enteral nutrition was initiated early and was increased in accordance with local guidelines. Both study groups also received intravenous micronutrients (trace elements, minerals, and vitamins) starting from day 2 and continuing until the enteral nutrition provided reached 80% of the caloric targets. Starting from the morning of day 8 in the pediatric ICU, supplementary parenteral nutrition was provided for patients in both groups who were not yet receiving 80% of the caloric target enterally.”
45% of patients were less than 1 year of age

Discussion:

“Late parenteral nutrition resulted in fewer new infections, a shorter duration of dependency on intensive care, and a shorter hospital stay. The clinical superiority of late parenteral nutrition was shown irrespective of diagnosis, severity of illness, risk of malnutrition, or age of the child.”

My take: The concept of providing early aggressive nutrition is NOT supported by this study; this study shows that early parenteral nutrition may be detrimental in critically-ill children. This study echoes the results of a similar study in adults: Early versus late parenteral nutrition in critically ill adults

Springtime in my neighborhood

Torsion of Accessory Spleen

Posted on March 22, 2016 by gutsandgrowth

A case report (PM Guglietta et al. NEJM 2016; 374; 373-82) presents a 9 year-old girl who had repeated episodes of abdominal pain with associated nonbilious vomiting. These pains started 5 years prior and were often sudden episodes of sharp pain on the left side or epigastric region and were associated with tachycardia.

AXR in Case Report

Ultimately the diagnosis was established with a CT scan. “Most persons with accessory spleens are asymptomatic, but abdominal pain can occur with torsion.”

While the case report is interesting, one aspect I did not like was the discussants justification of the delay of the diagnosis based on the presumption of constipation. The radiologist even commented: “a moderate-to-abundant amount of stool distributed in the colon, particularly the ascending colon; these findings are consistent with the clinical history of constipation.” This and other comments in the case study go against previous expert recommendations to avoid routine radiographs in the diagnosis of constipation and the finding of reviews which have not found a correlation between clinical symptoms and so-called fecal loading on abdominal radiographs.

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What happens with 98,500 IU/day of Vitamin A

Posted on March 21, 2016 by gutsandgrowth

An interesting case report (LA Beste et al. NEJM 2016; 374: 73-8) reviews the presentation of a previously healthy 54 year old with ascites. He initially indicated that he was taking 100 IU per day of vitamin A (his current dose), but later on directed questioning admitted that he had averaged 98,500 IU/day for prior 6 months.

The clinical-problem solving case reviews useful pointers about portal hypertension and in particularly noncirrhotic portal hypertension. Vitamin A is a rare cause of noncirrhotic portal hypertension.

Other causes of noncirrhotic portal hypertension:

Prehepatic level: portal vein or splenic vein thrombosis, splanchnic arteriovenous malformation
Intrahepatic level: hepatic vasculitis, HIV infection, infiltrative disease, and medications
Posthepatic: Budd-Chiari syndrome, IVC obstruction, restrictive cardiac disease.
Worldwide, schistosomiasis is the most common reason.
When other causes have been excluded, idiopathic noncirrhotic portal hypertension may be diagnosed, “especially in patients with chronic infection, thrombophilia, and immunologic conditions such as SLE.” In one series of 69 patients, the diagnosis of idiopathic noncirrhotic portal hypertension was delayed for more than a year in 25% of cases and 7% received an erroneous diagnosis of cryptogenic cirrhosis.

Other points:

When ascites is due to cirrhosis, other signs of liver disease are typically present, including jaundice and laboratory findings (low albumin, coagulopathy, hyperbilirubinemia) as well as absence of cirrhosis on biopsy.
Serum retinol levels poorly reflect total body stores of vitamin A (& was normal in this patient)
Vitamin A supplementation in appropriate doses can prevent blindness in areas where food stores are not secure. But, consuming excessive doses can lead to being a case report.

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Expert advice on portal hypertension | gutsandgrowth

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Excess Childhood Salt Intake Associated with Obesity

Posted on March 20, 2016 by gutsandgrowth

A recent study (C Grimes et al. 24-h urinary sodium excretion is associated with obesity in a cross-sectional sample of Australian schoolchildren British Journal of Nutrition Volume 115 / Issue 06 / March 2016, pp 1071 – 1079) was summarized at AJP.com.au: Childhood salt intake linked to obesity.

An excerpt:

The study also found that in both four-to-seven-year olds and eight-to-12-year-olds, the prevalence of abdominal obesity was also higher in children with a higher intake of salt.

The recent findings published in the British Journal of Nutrition came from the SONIC (Salt and Other Nutrient Intakes in Children) study that measured salt intake in 666 primary schoolchildren aged four to 12 years….

“We found that 70% of Australian children are eating over the maximum amount of salt recommended for good health.

“In this study children were eating on average six grams of salt a day, which is over a teaspoon, and they should be aiming to eat about 4-5 grams a day.

”For every additional gram of salt children ate this was associated with a 23% greater likelihood of being overweight or obese. Such high intakes of salt are setting children up for a lifetime risk of future chronic disease such as high blood pressure and heart disease”

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21 Year Data for Cancer Survivors

Posted on March 19, 2016 by gutsandgrowth

Most pediatric gastroenterologists see many children with pediatric cancers, so it is gratifying to see data showing improving long-term outcomes (GT Armstrong et al. NEJM 2016; 374: 833-42). In addition, pediatric oncology serves as a model for improving therapy by enrolling virtually all of its patients in research protocols.

The authors evaluated late mortality among 34,033 patients in the Childhood Cancer Survivor Study. All of these patients had survived at least 5 years after childhood cancer. During the study which had a median followup of 21 years, there were 3958 deaths and 1618 (41%) of these were attributable to health-related causes, including subsequent neoplasms (n=746), cardiac (n=241), and pulmonary (n=137).

The improvement in treatment regimens have included reductions in radiotherapy and anthracycline exposure. The graph below shows survival rates 20 years after being cancer-free (15 years after being cancer-free for 5 years).

My take: This study confirms that these improved regimens have long-lasting effects on mortality. Through cooperative research, we can do better in oncology and in all of pediatrics.

Incidence of death from any cause from patients treated between 1970-1999.

Bad News Bili

Posted on March 18, 2016 by gutsandgrowth

A study (BL Schneider et al. J Pediatr 2016; 170: 211-7) from ChiLDReN (Childhood Liver Disease Research Network) shows that infants with biliary atresia whose total bilirubin (TB) does not drop below 2 mg/dL (34.2 microM) at anytime during the first 3 months after hepatoportoenterostomy (HPE) (Kasai) are at high risk for disease progression.

Key findings:

68/137 (50%) had TB <2.0 at some point following HPE.
In the cohort with TB ≥ 2.0, the odds ratio for liver transplantation or death was 16.8. Higher TB was associated with diminished weight gain, coagulopathy, and hypoalbuminemia
In the cohort with TB ≥ 2.0, transplant-free survival at 2 year occurred in only 20% compared with 86% in the TB <2.0 group
Interestingly, only 6.6% had variceal bleeding among the entire cohort by age 2 years.

The TB was associated with multiple other parameters of worsening liver function, indicating that TB is not the only measure to affect the decision of liver transplantation.

My take: About half of all patients following a Kasai were at high risk for early progressive liver disease. TB ≥ 2.0 is a useful indicator of high risk.

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