This blog has previously discussed fecal transplants (see below).
Now, in response to an article in the New England Journal of Medicine, this topic is discussed in the NY Times:
http://www.nejm.org/doi/full/10.1056/NEJMoa1205037?query=featured_home
(method: duodenal infusion)
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Long-chain polyunsaturated fatty acids (LCPUFA) have been examined due to their potential to affect infant cognition (Long–chain polyunsaturated fatty acids, breastmilk … – gutsandgro). A recent meta-analysis has reviewed 19 studies with regard to LCPUFA supplementation and infant visual acuity (Pediatrics 2013; 131: e262-72 -thanks to Mike Hart for sharing this reference).
Since 75% of U.S. infants are formula fed by 1 year of age and there is widespread dependence on formula for nutritional completeness, these formulas have been designed to mimic breast milk composition. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are the two main LCPUFAs and are integral to the structural membranes of cells in the central nervous system and retina. DHA comprises >50% of the phospholipid content of the retinal membrane bilayer.
These 16 studies (in the abstract it erroneously states 19 studies), identified by a literature search, involved 1949 infants. Overall, a significant benefit of LCPUFA supplementation on infants’ visual acuity was noted at 2, 4, and 12 months of age when assessed by visual evoked potential. A benefit was also seen at 2 months of age by using behavioral methods. Studies were included if they were randomized control trials comparing LCPUFA supplementation to unsupplemented formula. Initially, 286 citations were identified but most did not meet inclusion criteria.
This study findings differ from two recent Cochrane reviews on the effect of LCPUFA on visual acuity. The Cochrane reviews failed to combine trials that measured “visual acuity in logMAR and cycles/degree and assessed preterm and term infants separately.” The authors state that this reduced the Cochrane reviews power to detect potential benefits of LCPUFA supplementation.
While this study demonstrates improvement during the first year of life, there is a scarcity of data beyond this time point. Limitations of this review included heterogeneity in the study results, varying doses of LCPUFA supplementation, variable DHA/AA ratio supplied, and variability in maternal diets.
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Low levels of the long-chain polyunsaturated fatty acids (LCPUFA) docosahexanenoic acid (DHA) and arachidonic acid (ARA) in premature infants are correlated with an increased risk of developmental, respiratory, and infectious morbidities in premature infants. A new report suggests that prolonged exposure to intravenous lipids exacerbates these low levels and could contribute to poor neurodevelopmental outcomes (J Pediatr 2013; 162: 56-61).
This study followed 26 extremely low birth weight premature infants with serial blood draws during the first two months of life using a prospective cohort design. Infants who received more than 28 days of intravenous lipid emulsion had significantly decreased DHA levels compared to infants with shorter duration of parenteral lipid exposure; at 8 weeks, the DHA levels were 2.7 ± 0.6 compared with 4.2 ± 1.9 (all levels reported as g/100 g). DHA levels at birth were 5.5 ± 1.4.
ARA levels decreased in a similar fashion in both groups, though values were mildly lower in the prolonged lipid group. At 8 weeks, the ARA values were 9.4 ± 1.6 and 11.5 ± 2.5 respectively. Thus, with a larger study group, this could be a significant finding as well.
These lower LCPUFA (especially DHA) levels may reflect a suboptimal intravenous lipid emulsion. Alternatively, the underlying reason for the prolonged lipids, like sepsis and NEC , could result in these lower levels. Perhaps attention to LCPUFA in parenteral formulations can improve neurodevelopmental outcomes in this vulnerable population.
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A useful review (Clin Gastroenterol Hepatol 2013; 11: 6-12) provides information on these clinical problems.
Belching or eructation can be divided into gastric belches which are normal and supragastric belching. Supragastric belching which is a behavior (not a reflex), is often provoked by stress. Air does not originate from the stomach or air swallowing (aerophagia). The most common mechanism: a contraction of the diaphragm causes negative pressure in the chest and allows air to be suctioned into the esophagus. It is expelled subsequently as a belch. In some instances, it can occur up to 20 times a minute. Supragastric belching does not occur during sleep and usually does not occur during speaking.
A clinical diagnosis usually is sufficient, though esophageal impedance can document these events as well.
Management:
Hiccups (singultus) are abnormal if lasting more than 48 hours.
Hiccups (at least in adults) have more likelihood of underlying pathology than belching. This review suggests workup including blood tests (CBC, CMP, Amylase/lipase, CRP, Cortisol) and consideration of EKG, CT of chest, Upper endoscopy, MRI of brainstem, and esophageal impedance.
Physical maneuvers have usually been tried and include the following: scaring the patient, rapid drinking, eyeball compression, holding breath, biting a lemon, swallowing sugar, and sniffing vinegar. A good differential diagnosis is given as well in this review -though many cases are idiopathic.
In the U.S. the only approved drug treatment is chlorpromazine. Typical starting dose for adults with this condition is 25 mg 3-4/day. Potential side effects include drowsiness and rarely tardive dyskinesia. Potential alternatives include baclofen and gabapentin. Numerous other agents and even surgical options are listed in this review that have been reported in case studies.
Aerophagia indicates excessive swallowing of air (capable of inducing symptoms like bloating or pain). No controlled studies have been completed. Expert opinion suggests using a nasogastric tube and sedatives like lorazepam in severe acute cases. In more typical chronic cases, advice includes restriction of carbonated beverages and possibly speech therapy. Agents like simethicone may be helpful. Laxatives may be helpful in some cases as well.
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Given the increased difficulties of conducting research in the pediatric population, it can take a long time for pediatric patients to benefit from the research advances demonstrated in adults. Fortunately, with hepatitis B virus (HBV) the lag time has not been excessive. A specific example has been a recent study demonstrating the effectiveness of tenofovir in the pediatric population (Hepatology 2012; 56: 2018-26).
In this double-blind, placebo-controlled study, adolescents with chronic HBV were randomized into tenofovir 300 mg (n=52) or placebo (n=54) once daily for 72 weeks. 101 patients completed the 72 weeks of treatment. In this population, 85% had received prior HBV therapy and 91% were HBeAg-positive at baseline. Patients included in the study had to have ALT >2 x ULN or history of this w/in 24 months along with HBV DNA>10 to the 5th copies/mL. The inclusion criteria required a weight of >35 kg.
Findings:
Since suppression of HBV DNA is a limited surrogate endpoint for the development of long-term sequelae much longer followup is needed to determine the impact of this nucleotide analogue. In adults, this agent has been associated with reversal of cirrhosis.
Across the globe, 350 million people live with chronic HBV infection and 600,000 die each year due to HBV infection. About 25% of children with HBV develop cirrhosis or cancer of liver later in life. Given the magnitude of the problem, the most promising approach remains prevention with vaccination. Treatment to prevent complications in those already infected is likely to be offered to a tiny fraction of those who might benefit.
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In Atlanta, patients with Familial Mediterranean Fever (FMF) do not have a specific specialist and may remain in the care of a pediatric gastroenterologist as a consequence. Fortunately, when the diagnosis is established, an effective treatment, colchicine, is available (J Pediatr 2012; 161: 1142-6).
Specific pointers in this reference:
Additional References:
This eponym is derived from E.C. Heyde, a general practitioner from Vancouver, Washington who observed in 1958 that patients with calcific aortic stenosis were prone to massive gastrointestinal bleeding. This clinical observation now has a molecular insight (NEJM 2012; 367: 1954-56).
Submucosal angiodysplasia was identified as the source of GI bleeding. This in turn was discovered to be related to an acquired von Willebrand’s syndrome. What’s happening is that elevated shear stress coverts the globular von Willebrand polymer into an elongated asymmetric protein. This conformational change exposes a site to the protease ADAMTS13 which binds and cleaves the protein, leaving a less competent smaller von Willebrand factor.
Another observation is that the von Willebrand factor is essential for the role that platelets have in maintaining vascular integrity. Degradation of von Willebrand factor as in Heyde’s syndrome allows for the development of the angiodysplasia in these patients and it leads to an intrinsic vascular diathesis in young patients with hereditary von Willebrand’s disease.
It is pretty cool to see how the science explains the clinical picture.
With the ubiquitous availability of smart phones, point-of-care technology becomes increasingly sophisticated. Many are familiar with mobile drug information resources (eg. Lexicomp, Epocrates), but now information is increasingly disease-specific. An example of this and the data supporting this are available in a recent publication with regards to diagnosing Kawasaki disease(KD) (J Pediatr 2013; 162: 183-88).
After simulating a model with a training cohort of 276 patients with KD and 243 febrile control (FC) patients, the authors validated the model with 136 patients with KD and 121 FCs. Inclusion criteria for KD were based on the American Heart Association guidelines.
The scoring system which combined clinical findings and laboratory findings resulted in “a sensitive (>95% PPV) and specific (>95% NPV) diagnosis of ~60% of FCs and ~75% of patients with KD.” In essence, the patients with high or low scores for KD were quite reliable.
To check out the web site:
http://translationalmedicine.stanford.edu/cgi-bin/KD/kd.pl
Potential limitation: The personnel involved in the study were very experienced in KD; thus, the model may be less effective when less skilled personnel obtain the clinical information.
While pediatric gastroenterologists do not frequently see KD patients, the bigger issue is developing point-of care tools. In our electronic health record (EHR), one point-of-care tool I developed was a smart phrase to assess hospitalized patient’s with colitis (see bottom of post in blue). This smart phrase can be pulled up with three key strokes and helps me assess the severity of the patient’s colitis.
Another useful smartphrase in blue (that was shared with me from Mike Hart), also retrieved with three key strokes, is the following:
Here is a weblink on youtube for a video on changing Mic-Key buttons:
http://www.youtube.com/watch?v=Mn4ePSBiCTk
I often share this link with parents at the end of my “after visit summary” note.
These types of tools can improve recognition and treatment in a wide range of areas and are only limited by our imagination.
Pediatric UC Activity Index:
1. Abd pain
No pain —0 points, Pain can be ignored —5 points, Pain cannot be ignored—10 points
2. Rectal bleeding
None —0 points, Small amount & in <50% of stools — 10 points, small with most stools —20 Large amount —30 points
3. Stool consistency
Formed — 0 points, partially formed — 5 points, completely unformed —10 points.
4. #Stools/24hrs
0-2 —0 points, 3-5 —5 points, 6-8 — 10 points, > 8 15 points
5. Nocturnal Stools
No —0 points, Yes —10 points
6. Activity Level
No limitation —0 points, Occasional limitation —5 points, Severe limitations —10 points
Total Score: *** @TD@
Interpretation:
Remission <10, Mild dz 10-30, Mod dz 31-64, Severe dz >65
References:
1. Gastroenterology 2010; 138: 2282-2291. PUCAI helps predict IV steroid failure in hospitalized pediatric colitis pts. n=128. 37 failed IV steroids (29%)
Score >45 (on day 3) indicates pts likely to fail IV steroids: Pos PPV 43%, Neg PPV 94%
Score >70 (on day 5) indicates need for alternate rx (+PPV100%)
25/33 steroid failures responded to IFX. Colectomy rate 9% initial, & 19% at 1 year.
2. Gastroeterology 2007; 133: 423-32. Turner et al.
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A recent randomized, double-blind, placebo-controlled crossover functional dyspepsia (FD) trial showed that 4 weeks of treatment with buspirone (10 mg TID) improved overall symptom severity, including early satiety and bloating (Clin Gastroenterol Hepatol 2012; 10: 1239-45).
This study enrolled 17 patients (13 women) with a mean age of 38.5 years. There were two 2-week treatment periods and a 2-week washout in between. Patients filled out a dyspepsia symptom score before treatment and at the conclusion. In addition, patients underwent gastric emptying by using breath tests and barostat measurement.
Overall symptom score was improved with buspirone compared to placebo: 7.5 ± 1.3 vs. 11.5 ± 1.2. Symptoms of postprandial fullness, early satiety, and abdominal bloating all improved significantly.
Buspirone treatment increased gastric accommodation compared with placebo: 229 ± 28 vs. 141 ± 32 mL respectively. Overall, gastric emptying was not affected by buspirone treatment; however, delayed emptying of liquids was evident (half-life = 64 vs. 119 minutes respectively).
The effect of buspirone on FD appears to be primarily related to improvement in gastric accommodation. Impaired accommodation has been identified in about 40% of FD patients. Buspirone which is a 5-HT1A receptor agonist acts on cholinergic nerve endings and leads to relaxation of the proximal stomach.
Buspirone also is used for the treatment of anxiety. In the present study, baseline anxiety scores were not correlated to symptom improvement but these scores were not followed at the end of treatment.
In this small study, buspirone was well tolerated and had similar adverse events as placebo. In previous studies, it has been associated with light-headedness, dizziness, and nausea.
Given the small scale of the study, it would be premature to consider buspirone a proven treatment for FD; however, this study provides the framework for larger studies to determine more conclusively the role of buspirone for FD.
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This blog has been a fan of calprotectin levels (see related posts below) as both a screening test for inflammatory bowel disease and as a marker of disease activity. Now more data is available indicating that calprotectin levels, much like endoscopic mucosal healing, after induction therapy correlates with long-term response (Inflamm Bowel Dis 2012; 18: 2011-17).
This retrospective study (2005-2010) examined 60 patients with IBD with elevated baseline calprotectin levels. 34 patients had Crohn’s disease (CD) and 26 had ulcerative colitis (UC). 42 patients received infliximab therapy and 18 patients received adalimumab. After induction therapy, therapy was discontinued in primary non responders or continued as scheduled maintenance therapy for at least one year if not relapsing.
The average age at induction for CD patients was 30 and the corresponding age at diagnosis was 21. For UC patients, the average age at induction was 29 and the corresponding age at diagnosis was 26.
Median calprotectin level at baseline was 810 μg/g (n=60). After induction, the median value dropped to 97 μg/g (n=60) and at 1 year the value dropped to 27 μg/g (n=25). The calprotectin level normalized in 31 patients after induction. At 12 months, the sustained remission was present in 84% (26/31). In contrast, only 38% (11/29) who had elevated levels after induction were in remission at 12 months.
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gutsandgrowth 