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Abstract
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<h5 class="section-title" id="d1996448e283">Question</h5>
<p id="d1996448e285">Do pediatric patients with oropharyngeal dysphagia who are treated
with proton pump
inhibitors (PPI) have increased hospitalizations compared with those who are not treated
with PPI?
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<h5 class="section-title" id="d1996448e288">Findings</h5>
<p id="d1996448e290">In this retrospective cohort study of 293 children under 2 years
with aspiration/penetration
on videofluoroscopic swallow study, patients treated with PPI had significantly higher
hospitalization rates and admission nights, with an incident rate ratio of 1.77 compared
with those not treated with PPI, even after adjustment for comorbidities.
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<h5 class="section-title" id="d1996448e293">Meaning</h5>
<p id="d1996448e295">Children with aspiration who are treated with PPI have increased
risk of hospitalization,
supporting growing concern about the risks of PPI use in children.
</p>
</div><p class="first" id="d1996448e298">This retrospective cohort study of 293 children
with oropharyngeal dysphagia examines
hospitalization risk for those treated with proton pump inhibitors compared with those
who were not.
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<h5 class="section-title" id="d1996448e302">Importance</h5>
<p id="d1996448e304">Proton pump inhibitors (PPI) are commonly prescribed to children
with oropharyngeal
dysphagia and resultant aspiration based on the assumption that these patients are
at greater risk for reflux-related lung disease. There is little data to support this
approach and the potential risk for increased infections in children treated with
PPI may outweigh any potential benefit.
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<h5 class="section-title" id="d1996448e307">Objective</h5>
<p id="d1996448e309">The aim of this study was to determine if there is an association
between hospitalization
risk in pediatric patients with oropharyngeal dysphagia and treatment with PPI.
</p>
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<h5 class="section-title" id="d1996448e312">Design, Setting, and Participants</h5>
<p id="d1996448e314">We performed a retrospective cohort study to compare the frequency
and length of hospitalizations
for children who had abnormal results on videofluoroscopic swallow studies that were
performed between January 1, 2015, and December 31, 2015, and who were or were not
treated with PPI, with follow-up through December 31, 2016. Records were reviewed
for children who presented for care at Boston Children’s Hospital, a tertiary referral
center. Participants included 293 children 2 years and younger with evidence of aspiration
or penetration on videofluoroscopic swallow study.
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<h5 class="section-title" id="d1996448e317">Exposures</h5>
<p id="d1996448e319">Groups were compared based on their exposure to PPI treatment.</p>
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<h5 class="section-title" id="d1996448e322">Main Outcomes and Measures</h5>
<p id="d1996448e324">The primary outcomes were hospital admission rate and hospital
admission nights and
these were measured as incident rates. Multivariable analyses were performed to determine
predictors of hospitalization risk after adjusting for comorbidities. Kaplan-Meier
curves were created to determine the association of PPI prescribing with time until
first hospitalization.
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<h5 class="section-title" id="d1996448e327">Results</h5>
<p id="d1996448e329">A total of 293 patients with a mean (SD) age of 8.8 (0.4) months
and a mean (SD) follow-up
time of 18.15 (0.20) months were included in the analysis. Patients treated with PPI
had higher admission rates (Incidence rate ratio [IRR], 1.77; 95% CI, 1.16-2.68) and
admission nights (IRR, 2.51; 95% CI, 1.36-4.62) even after adjustment for comorbidities.
Patients with enteral tubes who were prescribed PPIs were at the highest risk for
admission (hazard ratio [HR], 2.31; 95% CI, 1.24-4.31).
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<h5 class="section-title" id="d1996448e332">Conclusions and Relevance</h5>
<p id="d1996448e334">Children with aspiration who are treated with PPI have increased
risk of hospitalization
compared with untreated patients. These results support growing concern about the
risks of PPI use in children.
</p>
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The propensity score is a balancing score: conditional on the propensity score, treated and untreated subjects have the same distribution of observed baseline characteristics. Four methods of using the propensity score have been described in the literature: stratification on the propensity score, propensity score matching, inverse probability of treatment weighting using the propensity score, and covariate adjustment using the propensity score. However, the relative ability of these methods to reduce systematic differences between treated and untreated subjects has not been examined. The authors used an empirical case study and Monte Carlo simulations to examine the relative ability of the 4 methods to balance baseline covariates between treated and untreated subjects. They used standardized differences in the propensity score matched sample and in the weighted sample. For stratification on the propensity score, within-quintile standardized differences were computed comparing the distribution of baseline covariates between treated and untreated subjects within the same quintile of the propensity score. These quintile-specific standardized differences were then averaged across the quintiles. For covariate adjustment, the authors used the weighted conditional standardized absolute difference to compare balance between treated and untreated subjects. In both the empirical case study and in the Monte Carlo simulations, they found that matching on the propensity score and weighting using the inverse probability of treatment eliminated a greater degree of the systematic differences between treated and untreated subjects compared with the other 2 methods. In the Monte Carlo simulations, propensity score matching tended to have either comparable or marginally superior performance compared with propensity-score weighting.
Objective Proton pump inhibitors (PPIs) are widely used, and their use is associated with increased risk of adverse events. However, whether PPI use is associated with excess risk of death is unknown. We aimed to examine the association between PPI use and risk of all-cause mortality. Design Longitudinal observational cohort study. Setting US Department of Veterans Affairs. Participants Primary cohort of new users of PPI or histamine H2 receptor antagonists (H2 blockers) (n=349 312); additional cohorts included PPI versus no PPI (n=3 288 092) and PPI versus no PPI and no H2 blockers (n=2 887 030). Main outcome measures Risk of death. Results Over a median follow-up of 5.71 years (IQR 5.11–6.37), PPI use was associated with increased risk of death compared with H2 blockers use (HR 1.25, CI 1.23 to 1.28). Risk of death associated with PPI use was higher in analyses adjusted for high-dimensional propensity score (HR 1.16, CI 1.13 to 1.18), in two-stage residual inclusion estimation (HR 1.21, CI 1.16 to 1.26) and in 1:1 time-dependent propensity score-matched cohort (HR 1.34, CI 1.29 to 1.39). The risk of death was increased when considering PPI use versus no PPI (HR 1.15, CI 1.14 to 1.15), and PPI use versus no PPI and no H2 blockers (HR 1.23, CI 1.22 to 1.24). Risk of death associated with PPI use was increased among participants without gastrointestinal conditions: PPI versus H2 blockers (HR 1.24, CI 1.21 to 1.27), PPI use versus no PPI (HR 1.19, CI 1.18 to 1.20) and PPI use versus no PPI and no H2 blockers (HR 1.22, CI 1.21 to 1.23). Among new PPI users, there was a graded association between the duration of exposure and the risk of death. Conclusions The results suggest excess risk of death among PPI users; risk is also increased among those without gastrointestinal conditions and with prolonged duration of use. Limiting PPI use and duration to instances where it is medically indicated may be warranted.
Proton pump inhibitors (PPIs), used to treat gastro-esophageal reflux and prevent gastric ulcers, are among the most widely used drugs in the world. The use of PPIs is associated with an increased risk of enteric infections. Since the gut microbiota can, depending on composition, increase or decrease the risk of enteric infections, we investigated the effect of PPI-use on the gut microbiota. We discovered profound differences in the gut microbiota of PPI users: 20% of their bacterial taxa were statistically significantly altered compared with those of non-users. Moreover, we found that it is not only PPIs, but also antibiotics, antidepressants, statins and other commonly used medication were associated with distinct gut microbiota signatures. As a consequence, commonly used medications could affect how the gut microbiota resist enteric infections, promote or ameliorate gut inflammation, or change the host's metabolism. More studies are clearly needed to understand the role of commonly used medication in altering the gut microbiota as well as the subsequent health consequences.
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