An Evolutionary Medicine Perspective on Treatment of Pediatric Functional Abdominal Pain.

In a recent issue, Kovacic et al. analyze data from a randomized sham-controlled trial and show that pretreatment vagal efficiency, an index related to respiratory sinus arrhythmia, is a predictor of pain improvement in adolescents with functional abdominal pain when treated with auricular percutaneous electrical nerve field stimulation. The underlying premise is the polyvagal hypothesis, an explanatory framework for the evolution of the mammalian autonomic nervous system, which proposes that functional gastrointestinal disorders can result from a chronic maladaptive state of autonomic neural control mechanisms after traumatic stress. This is an opportunity for us to stimulate physicians' interest in evolutionary medicine.

Clinical Practice Guidelines for the Use of Video Capsule Endoscopy.

BACKGROUND & AIMS: Video capsule endoscopy (CE) provides a noninvasive option to assess the small intestine, but its use with respect to endoscopic procedures and cross-sectional imaging varies widely. The aim of this consensus was to provide guidance on the appropriate use of CE in clinical practice. METHODS: A systematic literature search identified studies on the use of CE in patients with Crohn's disease, celiac disease, gastrointestinal bleeding, and anemia. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. RESULTS: The consensus includes 21 statements focused on the use of small-bowel CE and colon capsule endoscopy. CE was recommended for patients with suspected, known, or relapsed Crohn's disease when ileocolonoscopy and imaging studies were negative if it was imperative to know whether active Crohn's disease was present in the small bowel. It was not recommended in patients with chronic abdominal pain or diarrhea, in whom there was no evidence of abnormal biomarkers typically associated with Crohn's disease. CE was recommended to assess patients with celiac disease who have unexplained symptoms despite appropriate treatment, but not to make the diagnosis. In patients with overt gastrointestinal bleeding, and negative findings on esophagogastroduodenoscopy and colonoscopy, CE should be performed as soon as possible. CE was recommended only in selected patients with unexplained, mild, chronic iron-deficiency anemia. CE was suggested for surveillance in patients with polyposis syndromes or other small-bowel cancers, who required small-bowel studies. Colon capsule endoscopy should not be substituted routinely for colonoscopy. Patients should be made aware of the potential risks of CE including a failed procedure, capsule retention, or a missed lesion. Finally, standardized criteria for training and reporting in CE should be defined. CONCLUSIONS: CE generally should be considered a complementary test in patients with gastrointestinal bleeding, Crohn's disease, or celiac disease, who have had negative or inconclusive endoscopic or imaging studies.

Recent safety concerns with proton pump inhibitors.

There have been recent concerns about the safety of proton pump inhibitors (PPIs). We focus here on 3 specific concerns-the possible interaction between PPIs and clopidogrel, the postulated link between PPI use and fractures, and the possibility that long-term PPI use might lead to hypomagnesemia. There is evidence for an in vitro interaction between clopidogrel and at least some PPIs. The Food and Drug Administration (FDA) has warned against the use of certain PPIs by patients on clopidogrel. However, a randomized controlled trial that compared clopidogrel alone with the combination of clopidogrel and omeprazole found no increase in adverse cardiovascular outcomes and a reduction in the rate of adverse gastrointestinal outcomes attributable to omeprazole. PPI use may be a weak risk factor for certain fractures, but the quality of evidence is relatively poor and there is a strong possibility of confounding. The mechanism whereby PPI use might increase fracture risk is unknown. Currently, no additional measures concerning calcium supplementation or bone mineral density monitoring are recommended for patients on a PPI. The FDA has suggested monitoring serum magnesium levels in patients on PPI therapy. The mechanism and frequency of PPI-induced hypomagnesemia are unclear. PPI treatment should not be withheld from patients who genuinely require it, but the PPI should be taken in the lowest effective dose and only for as long as clinically indicated. The same is, of course, true for all medicines. The benefits of PPI therapy greatly outweigh the risks.

Proton pump inhibitors and risk of fracture: a systematic review and meta-analysis of observational studies.

OBJECTIVES: Proton pump inhibitors (PPIs) are widely used in several acid-related gastrointestinal disorders. In vivo studies have suggested that gastric suppression by PPIs could result in decreased intestinal calcium absorption. Subsequently, there have been concerns that the chronic use of a PPI is associated with an increased risk of bone fracture. However, the results of clinical studies are conflicting. METHODS: We performed a systematic review and meta-analysis of controlled observational studies to evaluate the risks of PPI use on fracture outcome. All controlled observational studies that compared fracture outcome in patients with PPI therapy with a control group were included. We calculated pooled odds ratios (ORs) using a random-effects model. RESULTS: Of 1,668 identified studies, 10 (4 cohort and 6 case-control) with 223,210 fracture cases were included in our analysis. In PPI users, compared with non/past users, the OR for hip fracture (n=9) was 1.25 (95% confidence interval (CI)=1.14-1.37). The OR for vertebral fracture (n=4) was 1.50 (95% CI=1.32-1.72) and for wrist/forearm fracture (n=3) was 1.09 (95% CI=0.95-1.24). In subgroup analysis of hip fracture, this association was observed in both high-dose and low-dose PPI exposure. When stratified by duration of exposure, the short duration of PPI use was associated with increased risk of developing hip fracture (OR=1.24; 95% CI=1.19-1.28), whereas there was no significant increase in risk of hip fracture in long-term PPI users (OR=1.30; 95% CI=0.98-1.70). There was significant statistical and clinical heterogeneity among studies for the main analysis and most of the subgroup analyses. CONCLUSIONS: Our results should be interpreted with caution. We found a modest association between PPI use and increased risk of hip and vertebral fractures, but no evidence of duration effect in subgroup analysis. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding. Thus, randomized controlled studies are required to confirm or refute these results.