Ibuprofen for acute postoperative pain in children.

BACKGROUND: Children often require pain management following surgery to avoid suffering. Effective pain management has consequences for healing time and quality of life. Ibuprofen, a frequently used non-steroidal anti-inflammatory drug (NSAID) administered to children, is used to treat pain and inflammation in the postoperative period. OBJECTIVES: 1) To assess the efficacy and safety of ibuprofen (any dose) for acute postoperative pain management in children compared with placebo or other active comparators. 2) To compare ibuprofen administered at different doses, routes (e.g. oral, intravenous, etc.), or strategies (e.g. as needed versus as scheduled). SEARCH METHODS: We used standard Cochrane search methods. We searched CENTRAL, MEDLINE, Embase, CINAHL and trials registries in August 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children aged 17 years and younger, treated for acute postoperative or postprocedural pain, that compared ibuprofen to placebo or any active comparator. We included RCTs that compared different administration routes, doses of ibuprofen and schedules. DATA COLLECTION AND ANALYSIS: We adhered to standard Cochrane methods for data collection and analysis. Our primary outcomes were pain relief reported by the child, pain intensity reported by the child, adverse events, and serious adverse events. We present results using risk ratios (RR) and standardised mean differences (SMD), with the associated confidence intervals (CI). We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included 43 RCTs that enroled 4265 children (3935 children included in this review). We rated the overall risk of bias at the study level as high or unclear for 37 studies that had one or several unclear or high risk of bias judgements across the domains. We judged six studies as having a low risk of bias across all domains. Ibuprofen versus placebo (35 RCTs) No studies reported pain relief reported by the child or a third party, or serious adverse events. Ibuprofen probably reduces child-reported pain intensity less than two hours postintervention compared to placebo (SMD -1.12, 95% CI -1.39 to -0.86; 3 studies, 259 children; moderate-certainty evidence). Ibuprofen may reduce child-reported pain intensity, two hours to less than 24 hours postintervention (SMD -1.01, 95% CI -1.24 to -0.78; 5 studies, 345 children; low-certainty evidence). Ibuprofen may result in little to no difference in adverse events compared to placebo (RR 0.79, 95% CI 0.51 to 1.23; 5 studies, 384 children; low-certainty evidence). Ibuprofen versus paracetamol (21 RCTs) No studies reported pain relief reported by the child or a third party, or serious adverse events. Ibuprofen likely reduces child-reported pain intensity less than two hours postintervention compared to paracetamol (SMD -0.42, 95% CI -0.82 to -0.02; 2 studies, 100 children; moderate-certainty evidence). Ibuprofen may slightly reduce child-reported pain intensity two hours to 24 hours postintervention (SMD -0.21, 95% CI -0.40 to -0.02; 6 studies, 422 children; low-certainty evidence). Ibuprofen may result in little to no difference in adverse events (0 events in each group; 1 study, 44 children; low-certainty evidence). Ibuprofen versus morphine (1 RCT) No studies reported pain relief or pain intensity reported by the child or a third party, or serious adverse events. Ibuprofen likely results in a reduction in adverse events compared to morphine (RR 0.58, 95% CI 0.40 to 0.83; risk difference (RD) -0.25, 95% CI -0.40 to -0.09; number needed to treat for an additional beneficial outcome (NNTB) 4; 1 study, 154 children; moderate-certainty evidence). Ibuprofen versus ketorolac (1 RCT) No studies reported pain relief or pain intensity reported by the child, or serious adverse events. Ibuprofen may result in a reduction in adverse events compared to ketorolac (RR 0.51, 95% CI 0.27 to 0.96; RD -0.29, 95% CI -0.53 to -0.04; NNTB 4; 1 study, 59 children; low-certainty evidence). AUTHORS' CONCLUSIONS: Despite identifying 43 RCTs, we remain uncertain about the effect of ibuprofen compared to placebo or active comparators for some critical outcomes and in the comparisons between different doses, schedules and routes for ibuprofen administration. This is largely due to poor reporting on important outcomes such as serious adverse events, and poor study conduct or reporting that reduced our confidence in the results, along with small underpowered studies. Compared to placebo, ibuprofen likely results in pain reduction less than two hours postintervention, however, the efficacy might be lower at two hours to 24 hours. Compared to paracetamol, ibuprofen likely results in pain reduction up to 24 hours postintervention. We could not explore if there was a different effect in different kinds of surgeries or procedures. Ibuprofen likely results in a reduction in adverse events compared to morphine, and in little to no difference in bleeding when compared to paracetamol. We remain mostly uncertain about the safety of ibuprofen compared to other drugs.

Frequency of use and adequacy of Cochrane risk of bias tool 2 in non-Cochrane systematic reviews published in 2020: Meta-research study.

Risk of bias (RoB) assessment is essential to the systematic review methodology. The new version of the Cochrane RoB tool for randomized trials (RoB 2) was published in 2019 to address limitations identified since the first version of the tool was published in 2008 and to increase the reliability of assessments. This study analyzed the frequency of usage of the RoB 2 and the adequacy of reporting the RoB 2 assessments in non-Cochrane reviews published in 2020. This meta-research study included non-Cochrane systematic reviews of interventions published in 2020. For the reviews that used the RoB 2 tool, we analyzed the reporting of the RoB 2 assessment. Among 3880 included reviews, the Cochrane RoB 1 tool was the most frequently used (N = 2228; 57.4%), followed by the Cochrane RoB 2 tool (N = 267; 6.9%). From 267 reviews that reported using the RoB 2 tool, 213 (79.8%) actually used it. In 26 (12.2%) reviews, erroneous statements were used to indicate the RoB 2 assessment. Only 20 (9.4%) reviews presented a complete RoB 2 assessment with a detailed table of answers to all signaling questions. The judgment of risk of bias by the RoB 2 tool was not justified by a comment in 158 (74.2%) reviews. Only in 33 (14.5%) of reviews the judgment in all domains was justified in the accompanying comment. In most reviews (81.7%), the RoB was inadequately assessed at the study level. In conclusion, the majority of non-Cochrane reviews published in 2020 still used the Cochrane RoB 1 tool. Many reviews used the RoB 2 tool inadequately. Further studies about the uptake and the use of the RoB 2 tool are needed.

Association between human chorionic gonadotropin (hCG) levels and adverse pregnancy outcomes: A systematic review and meta-analysis.

Human chorionic gonadotropin (hCG), a glycoprotein produced in the placenta, is crucial for a healthy pregnancy. We investigated the relationship between hCG levels and adverse pregnancy outcomes. We conducted a systematic review including studies measuring hCG blood levels in the first or second trimester, reporting on any of the 12 predefined adverse pregnancy outcomes with logistic regression-adjusted association estimates. The primary outcomes were placenta-associated complications, such as miscarriage, preeclampsia, intrauterine growth restriction, and preterm delivery. We searched PubMed, Embase and CINAHL Complete. The hCG levels were analysed as multiple of the median (MoM). Odds ratio (OR) and 95% confidence interval (CI) were used. Risk of bias and the certainty of evidence were assessed using ROBINS-I and GRADE, respectively. Meta-analysis also showed that hCG levels, reported as MoM ≥2/2.31/2.5, might be associated with an increased risk of preeclampsia (OR 2.08, 95% CI 1.26 to 3.44) and preterm delivery (OR 1.29, 95% CI 1.12 to 1.47), but the evidence is very uncertain. High second trimester hCG levels may be associated with preeclampsia and preterm delivery but confidence in evidence is low.