Introduction

The safety profile of proton pump inhibitors (PPIs) is considered excellent; however, concerns regarding the potential side effects linked to prolonged usage are emerging.

Aims & Methods

This work focused on assessing the risk of Clostridioides difficile infection (CDI) in patients undergoing treatment with PPIs compared to non-users, in the context of randomized controlled trials (RCTs). The study protocol was prospectively registered on PROSPERO (CRD42023403322). The systematic search was conducted on March 2nd, 2023 across three medical databases (PubMed, Embase, and CENTRAL). We included all RCTs that reported the rates of CDI in adults receiving treatment with PPIs compared to non-users (placebo, other medications). Risk ratio (RR) with its corresponding 95% confidence interval (CI) was used as an effect size measure using a random effects model. Heterogeneity was described using Higgins and Thompson’s I2 statistics. The risk of bias was estimated using the Revised Cochrane Risk-of-bias Tool for Randomized Trials (RoB 2).

Results

We identified and analysed seven RCTs investigating the rates of CDI in individuals receiving treatment with PPIs compared to placebo, which included 25.118 patients. No significant difference was observed regarding the risk of acquiring CDI between the two study groups (32/12.561 vs. 33/12.557; RR: 0.94, 95% CI: 0.55; 1.59, I²=0%). Four RCTs compared subjects receiving PPIs to H2-receptor blockers, totalling 27.254 patients. Similarly, the pooled analysis found no significant difference regarding the risk of developing CDI between the two study groups (43/13.658 vs. 59/13.598; RR: 0.72, 95% CI: 0.49; 1.07, I2=0%). We would like to highlight the fact that the overall number of events in the included studies were low. Additional subgroup analyses were intended based on patient population, treatment duration, and follow-up time; however, there was insufficient data available for conducting meta-analytical calculations.

Conclusion

Previous works that reported associations between PPI use and adverse effects have been derived from observational data only. It is known that these types of studies cannot definitely establish causality and are highly susceptible to bias, such as confounding by indication and protopathic bias. Based on data derived from RCTs only, treatment with PPIs does not seem to increase the risk of acquiring CDI, both when compared to placebo and to other acid-suppressive medications.

Introduction

The Montreal consensus recognizes chronic cough as an extra-oesophageal manifestation of gastroesophageal reflux disease, for which acid-suppressive medications have been proposed as a treatment option.

Aims & Methods

We performed a meta-analysis to assess the therapeutic effects of proton pump inhibitors (PPIs) on cough severity and quality of life (QoL) in adults with non-specific chronic cough.
The protocol was prospectively registered on PROSPERO (CRD42022368769). Placebo-controlled randomized trials (RCTs) which assessed the impact of acid-suppressive medications on cough severity or QoL in adults with non-specific chronic cough were eligible for inclusion. The systematic search was performed on the 1st of November 2022 in three databases (PubMed, Embase, and CENTRAL), with additional citation searching. A random-effects model was used for the calculation of the results. The effect size was the standardized mean difference (SMD) with a corresponding 95% confidence interval (CI), for which Hedges’ g was used. Heterogeneity was assessed using Higgins and Thompson I² statistics. The risk of bias was evaluated using the Revised Cochrane Risk-of-bias Tool for Randomized Trials (RoB 2).

Results

Eleven RCTs with more than 600 patients were eligible for inclusion. Compared to placebo, PPIs slightly decreased the cough severity (SMD 0.33; CI: 0.05, 0.61). This effect seemed greater in patients with abnormal reflux studies (SMD 0.49; CI: -0.41, 1.39). Time dependency analysis found that prolonged treatment durations do not result in greater symptomatic improvement (SMD 0.33 (CI: -0.22, 0.88), 0.31 (CI: -1.74, 2.35), 0.32 (CI: -0.29, 0.93), 0.34 (CI: -0.16, 0.85) following 4, 6, 8 and 12 weeks of treatment, respectively). PPIs seemed to moderately improve the QoL compared to placebo (SMD 0.39; CI: -0.51, 1.29); however, when an outlying trial was omitted, the resulting effect was relatively small (SMD 0.11; CI: -0.39; 0.62).

Conclusion

PPIs slightly decrease the severity of cough, irrespective of treatment duration. Symptomatic improvement seems to be greater in patients with abnormal results on reflux studies.

Introduction

Despite lack of evidence, patients are kept nil by mouth for 48 to 96 hours after upper gastrointestinal bleeding (UGIB) due to fear of rebleeding. However, many trials have demonstrated the benefits of early nutrition after UGIB. We conducted a meta-analysis of randomized controlled trials to evaluate the safety and outcomes of early nutrition compared to delayed nutrition after UGIB.

Aims & Methods

The protocol was registered on PROSPERO in advance (CRD42022372306). Five databases (PubMed, Embase, CENTRAL, Scopus, and Web of Science) were searched on the 10th of November 2022 to identify randomized controlled trials that met our eligibility criteria. In-hospital and 30-day outcomes were pooled separately. Mortality rate, rebleeding rate, and length of hospital stay were the primary outcomes. The pooled risk ratio (RR), mean difference (MD), and the corresponding 95% confidence interval (CI) were calculated using a random effects model.

Results

A total of 10 trials with 1,051 patients were included in the analysis. Comparing the two groups, 7-day mortality showed no significant difference (RR=1.23, CI: 0.72 - 2.10), while there was a clear tendency for a decrease in 30-day mortality in the early nutrition group (RR=0.57, CI: 0.31 – 1.04). As for 7-day and 30-day rebleeding, there was no statistically significant difference between the two groups (RR=1.05, CI: 0.63 – 1.74 and RR=1.16, CI: 0.59 – 2.26, respectively). In addition, our analysis showed that the early nutrition group needed a reduced length of hospital stay compared to the delayed nutrition group (MD= - 1.22, CI: -2.43 to -0.01).

Conclusion

Compared with delayed nutrition, early nutrition appears to be a safe intervention and could reduce the length of hospital stay without increasing the risk of complications regarding rebleeding or mortality after upper gastrointestinal bleeding.

Disclosure

The authors declare no potential conflict of interest.

Introduction

Despite a lack of evidence, patients are often not fed for 48 to 96 hours after upper gastrointestinal bleeding (UGIB); however, many trials have demonstrated the benefits of early nutrition (EN). We conducted a meta-analysis of randomized controlled trials (RTCs) to evaluate the outcomes of EN compared to delayed nutrition (DN) after UGIB.

Aims & Methods

The protocol was registered on PROSPERO (CRD42022372306). PubMed, Embase, CENTRAL, Scopus, and Web of Science were searched on the 27^th of August 2023 to identify eligible RCTs. The primary outcomes were early (within 7 days) and late (within 30-42 days) mortality and rebleeding. Pooled risk ratios (RR), mean differences (MD), and corresponding 95% confidence intervals (CI) were calculated using a random-effects model.

Results

A total of 10 trials with 1,051 patients were included in the analysis. Early mortality was not significantly different between the two groups (RR: 1.20, CI: 0.85 – 1.71, I² = 0%), whereas late mortality was reduced to a clinically relevant extent in the EN group (RR: 0.61, CI: 0.35 – 1.06, I² = 0%). When comparing the two groups, we found no significant difference in terms of early and late rebleeding (RR: 1.04, CI: 0.66 – 1.63, I² = 0% and RR: 1.16, CI: 0.63 – 2.13, I² = 0%, respectively). Our analysis also showed that the length of hospital stay was reduced in the EN group compared to the DN group (MD: - 1.22 days, CI: - 2.43 to - 0.01, I² = 94%).

Conclusion

Compared with DN, EN (within 24 hours) appears to be a safe intervention and could reduce the length of hospital stay without increasing the risk of complications after UGIB.

Disclosure

None to declare.

Introduction

Critically ill patients are at high risk for upper gastrointestinal (GI) bleeding.¹ Proton pump inhibitors (PPIs) are commonly used for prophylaxis, but their safety and efficacy compared to histamine-2 receptor antagonists (H2 blockers) and placebo remain unclear.^1–4

Aims & Methods

Our systematic review and meta-analysis aims to assess the safety and efficacy of PPIs for preventing upper GI bleeding in critically ill adults. We conducted a comprehensive search of Scopus, Web of Science, PubMed, and Cochrane Central for relevant randomized controlled trials (RCTs) from inception until March 2024. Data were extracted from eligible studies and pooled as mean difference (MD) for continuous outcomes and Odds ratio (OR) for dichotomous data in a random-effect model meta-analysis, using R software.

Results

Nineteen RCTs were included in this meta-analysis with a total of 62221 patients. Our study showed that PPI was superior to control in terms of GI bleeding [RR 0.55, (95% CI, 0.42 to 0.72); P = <0.01]. However, the overall effect did not favor either of the two groups in terms of ICU, mortality rate, and nosocomial infection [MD -1.45, (95% CI, -5.31 to 2.42); P = 0.4], [RR 1.04, (95% CI, 1.00 to 1.09); P = 0.07], and [RR 1.27, (95% CI, 0.98 to 1.65); P = 0.07], respectively.

Conclusion

In conclusion, our findings demonstrated a significant reduction in GI bleeding risk associated with PPI use. At the same time, we did not find a statistically significant difference between PPI and control groups regarding ICU mortality rate, overall mortality rate, or nosocomial infection rates. These findings suggest that PPIs may be effective in reducing upper GI bleeding in critically ill patients. However, further research might be necessary to definitively determine the impact of PPIs on mortality and infection risks in this population.

References

.1. Wang Y, Ye Z, Ge L, et al. Efficacy and safety of gastrointestinal bleeding prophylaxis in critically ill patients: Systematic review and network meta-analysis. The BMJ. 2020;368. doi:10.1136/bmj.l6744
2. Kondo Y, Ohbe H, Matsui H, Fushimi K, Tanaka H, Yasunaga H. Proton pump inhibitors versus histamine-2 receptor antagonists for stress ulcer prophylaxis during extracorporeal membrane oxygenation: a propensity score-matched analysis. BMJ Open. 2020;10(9):e037534. doi:10.1136/bmjopen-2020-037534
3. Alshamsi F, Belley-Cote E, Cook D, et al. Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: A systematic review and meta-analysis of randomized trials. Crit Care. 2016;20(1). doi:10.1186/S13054-016-1305-6
4. Jung YS, Park JH, Park CH. Impact of proton pump inhibitors on the risk of small bowel or colorectal bleeding: A systematic review and meta-analysis. United European Gastroenterol J. 2023;11(9):861-873. doi:10.1002/ueg2.12448