Prospective evaluation of the emetogenic profile and analgesic efficacy of intravenous ibuprofen and metamizole in the immediate postoperative period of pediatric acute appendicitis. / Evaluación prospectiva del perfil emético y la eficacia analgésica del ibuprofeno y el metamizol intravenosos en el postoperatorio inmediato de la apendicitis aguda pediátrica.

BACKGROUND: Literature comparing different alternatives for pain control in the immediate postoperative period of pediatric acute appendicitis (PAA) is scarce. MATERIALS AND METHODS: We prospectively compared the analgesic and emetogenic profile of intravenous ibuprofen and metamizole in the immediate postoperative period of PAA. For this purpose, we used a sample of patients operated on in 2021 in our center. Participants were recruited on arrival at the Emergency Department and histopathological confirmation of the diagnosis was obtained in all of them. Pain was evaluated every 8 hours after the surgery with validated visual analog scales ranging from 0 to 10 points. Repeated measures ANOVA was used to compare the evolution of pain in the 48 hours after surgery between the two groups. RESULTS: The sample included 95 patients (65% males) with a mean age of 9.7 years (sd: 3.14). 41 patients were treated with Ibuprofen (group 1) and 54 with metamizole (group 2). No significant differences were found in the level of pain either in the comparisons of point measurements or in its evolution in the 48 hours after surgery (p= 0.58). After adjusting for the received fluid therapy, children in the metamizole group had significantly more emetic episodes and needed significantly more doses of ondansetron. CONCLUSIONS: In our cohort, ibuprofen had a similar analgesic efficacy and a better emetogenic profile than metamizole in the immediate postoperative period of PAA. Future prospective, adequately controlled studies with larger sample sizes are needed to validate these findings.

INTRODUCCION: En la literatura existen pocas referencias que comparen las distintas alternativas disponibles para controlar el dolor en el postoperatorio inmediato de la apendicitis aguda pediátrica (AAP). MATERIAL Y METODOS: Comparación prospectiva del perfil analgésico y emético del ibuprofeno y el metamizol intravenosos en el postoperatorio inmediato de la AAP, para lo cual se recurre a una muestra de pacientes operados en 2021 en nuestro centro. Los participantes fueron reclutados a su llegada a Urgencias, obteniéndose confirmación histopatológica del diagnóstico en todos ellos. La evaluación del dolor se llevó a cabo cada 8 horas tras la cirugía mediante escalas analógicas visuales validadas, con valoraciones entre los 0 y los 10 puntos. Se realizó un ANOVA de las medidas repetidas entre los dos grupos para comparar la evolución del dolor en las 48 horas posteriores a la cirugía. RESULTADOS: La muestra estaba compuesta por un total de 95 pacientes (65% de ellos varones) con una edad media de 9,7 años (DT: 3,14). 41 pacientes fueron tratados con ibuprofeno (grupo 1) y 54 con metamizol (grupo 2). No se hallaron diferencias significativas en lo que respecta al dolor, ni en las comparaciones de las mediciones puntuales, ni en su evolución en las 48 horas posteriores a la cirugía (p= 0,58). Una vez realizado el ajuste correspondiente a la terapia de fluidos recibida, los niños del grupo metamizol tuvieron significativamente más episodios eméticos y necesitaron significativamente más dosis de ondansetrón. CONCLUSIONES: En nuestra cohorte, el ibuprofeno tuvo una eficacia analgésica similar y un mejor perfil emético que el metamizol en el postoperatorio inmediato de la AAP. Se hacen necesarios nuevos estudios prospectivos, adecuadamente controlados y con mayor tamaño muestral que validen estos hallazgos.

Non-opioid analgesic combinations following total hip arthroplasty (RECIPE): a randomised, placebo-controlled, blinded, multicentre trial.

BACKGROUND: Multimodal postoperative analgesia following total hip arthroplasty is recommended, but the optimal combination of drugs remains uncertain. The aim of the RECIPE trial was to investigate the relative benefit and harm of the different combinations of paracetamol, ibuprofen, and the analgesic adjuvant dexamethasone for treatment of postoperative pain following total hip arthroplasty. METHODS: The RECIPE trial was a randomised, blinded, placebo-controlled trial conducted at nine Danish hospitals. Adults scheduled for total hip arthroplasty were randomly assigned (1:1:1:1) using a computer-generated list with stratification by site to receive combinations of oral paracetamol 1000 mg every 6 h, oral ibuprofen 400 mg every 6 h, or a single-dose of intravenous dexamethasone 24 mg in the following groups: paracetamol plus ibuprofen, ibuprofen plus dexamethasone, paracetamol plus dexamethasone, and paracetamol plus ibuprofen plus dexamethasone. The primary outcome was 24 h intravenous morphine consumption, analysed in a modified intention-to-treat population, defined as all randomly assigned participants who underwent total hip arthroplasty. The predefined minimal important difference was 8 mg. Safety outcomes included serious and non-serious adverse events within 90 days and 24 h. The trial was registered with ClinicalTrials.gov, NCT04123873. FINDINGS: Between March 5, 2020, and Nov 15, 2022, we randomly assigned 1060 participants, of whom 1043 (589 [56%] women and 454 [44%] men) were included in the modified intention-to-treat population. 261 were assigned to paracetamol plus ibuprofen, 262 to ibuprofen plus dexamethasone, 262 to paracetamol plus dexamethasone, and 258 to paracetamol plus ibuprofen plus dexamethasone. Median 24 h morphine consumption was 24 mg (IQR 12-38) in the paracetamol plus ibuprofen group, 20 mg (12-32) in the paracetamol plus dexamethasone group, 16 mg (10-30) in the ibuprofen plus dexamethasone group, and 15 mg (8-26) in the paracetamol plus ibuprofen plus dexamethasone group. The paracetamol plus ibuprofen plus dexamethasone group had a significantly reduced 24 h morphine consumption compared with paracetamol plus ibuprofen (Hodges-Lehmann median difference -6 mg [99% CI -10 to -3]; p<0·0001) and paracetamol plus dexamethasone (-4 mg [-8 to -1]; p=0·0013), however, none of the comparisons showed differences reaching the minimal important threshold of 8 mg. 91 (35%) of 258 participants in the paracetamol plus ibuprofen plus dexamethasone group had one or more adverse events, compared with 99 (38%) of 262 in the ibuprofen plus dexamethasone group, 103 (39%) of 262 in the paracetamol plus dexamethasone group, and 165 (63%) of 261 in the paracetamol plus ibuprofen group. INTERPRETATION: In adults undergoing total hip arthroplasty, a combination of paracetamol, ibuprofen, and dexamethasone had the lowest morphine consumption within 24 h following surgery and the most favourable adverse event profile, with a lower incidence of serious and non-serious adverse events (primarily driven by differences in nausea, vomiting, and dizziness) compared with paracetamol plus ibuprofen. FUNDING: The Novo Nordisk Foundation and Næstved-Slagelse-Ringsted Hospitals' Research Fund.

[Effect of preemptive analgesia with ibuprofen on postoperative pain after mandibular third molar extraction: a randomized controlled trial].

Objective: To evaluate the impact of preemptive analgesia with ibuprofen on postoperative pain following the extraction of impacted mandibular third molars in a Chinese population, aiming to provide a clinical reference for its application. Methods: This multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted from April 2022 to October 2023 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), and Beijing Chao-Yang Hospital, Capital Medical University (20 cases). It included 82 patients with impacted mandibular third molars, with 41 in the ibuprofen group and 41 in the control group. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups were instructed to take sustained-release ibuprofen capsules as planned for 3 days post-surgery. Pain intensity was measured using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after surgery, and the use of additional analgesic medication was recorded during days 4 to 6 postoperatively. Results: All 82 patients completed the study according to the protocol. No adverse events such as nausea, vomiting, or allergies were reported in either group during the trial. The ibuprofen group exhibited significantly lower pain scores at 4 h [2.0 (1.0, 4.0) vs. 4.0 (3.0, 5.0)] (Z=-3.73, P<0.001), 6 h [2.0 (1.0, 4.0) vs. 5.0(2.5, 6.0)] (Z=-3.38, P<0.001), and 8 h [2.0 (1.0, 4.0) vs. 5.0 (2.0, 6.0)] (Z=-2.11, P=0.035) postoperatively compared to the control group. There were no statistically significant differences in pain scores between the groups at 30 min, 24 h, 48 h, and 72 h postoperatively (P>0.05). Additionally, 11 out of 41 patients (26.8%) in the ibuprofen group and 23 out of 41 patients (56.1%) in the control group required extra analgesic medication between days 4 and 6 post-surgery, with the ibuprofen group taking significantly fewer additional pills [0.0 (0.0, 1.0) vs. 1.0 (0.0, 3.0)] (Z=-2.81, P=0.005). Conclusions: A pain management regimen involving 300 mg of oral sustained-release ibuprofen capsules administered 15 minutes before surgery and continued for 3 d postoperatively effectively reduces pain levels and the total amount of analgesic medication used after the extraction of impacted mandibular third molars. Considering its efficacy, safety, and cost-effectiveness, ibuprofen is recommended as a first-line drug for perioperative pain management, enhancing patient comfort during diagnosis and treatment in a feasible manner.

Association between postoperative ibuprofen exposure and acute kidney injury after pediatric cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is a common complication after pediatric cardiac surgery and is associated with worse outcomes. Ibuprofen is widely used in the perioperative period and can affect kidney function in children. However, the association between ibuprofen exposure and AKI after pediatric cardiac surgery has not been determined yet. METHODS: In this retrospective cohort study, children undergoing cardiac surgery with cardiopulmonary bypass were studied. Exposure was defined as given ibuprofen in the first 7 days after surgery. Postoperative AKI was diagnosed using the KDIGO criteria. A multivariable Cox regression model was used to assess the association between ibuprofen exposure and postoperative AKI by taking ibuprofen as a time-varying covariate. RESULTS: Among 1,112 included children, 198 of them (17.8%) experienced AKI. In total, 396 children (35.6%) were exposed to ibuprofen. AKI occurred less frequently among children who were administered ibuprofen than among those who were not (46 of 396 [11.6%] vs. 152 of 716 [21.2%], p < 0.001). Using the Cox regression model accounting for time-varying exposures, ibuprofen treatment was not associated with AKI (adjusted HR, 0.99; 95% CI 0.70-1.39, p = 0.932). This insignificant association was consistent across the sensitivity and subgroup analyses. CONCLUSIONS: Postoperative ibuprofen exposure in pediatric patients undergoing cardiac surgery was not associated with an increased risk of AKI.

The impact of the route of administration on the efficacy and safety of the drug therapy for patent ductus arteriosus in premature infants: a systematic review and meta-analysis.

Background: This systematic review and meta-analysis aims to explore the potential impact of the route of administration on the efficacy of therapies and occurrence of adverse events when administering medications to premature infants with patent ductus arteriosus (PDA). Method: The protocol for this review has been registered with PROSPERO (CRD 42022324598). We searched relevant studies in PubMed, Embase, Cochrane, and the Web of Science databases from March 26, 1996, to January 31, 2022. Results: A total of six randomized controlled trials (RCTs) and five observational studies were included for analysis, involving 630 premature neonates in total. Among these infants, 480 were in the ibuprofen group (oral vs. intravenous routes), 78 in the paracetamol group (oral vs. intravenous routes), and 72 in the ibuprofen group (rectal vs. oral routes). Our meta-analysis revealed a significant difference in the rate of PDA closure between the the initial course of oral ibuprofen and intravenous ibuprofen groups (relative risk (RR) = 1.27, 95% confidence interval (CI) [1.13-1.44]; P < 0.0001, I2 = 0%). In contrast, the meta-analysis of paracetamol administration via oral versus intravenous routes showed no significant difference in PDA closure rates (RR = 0.86, 95% CI [0.38-1.91]; P = 0.71, I2 = 76%). However, there was no statistically significant difference in the risk of adverse events or the need for surgical intervention among various drug administration methods after the complete course of drug therapy. Conclusion: This meta-analysis evaluated the safety and effectiveness of different medication routes for treating PDA in premature infants. Our analysis results revealed that compared with intravenous administration, oral ibuprofen may offer certain advantages in closing PDA without increasing the risk of adverse events. Conversely, the use of paracetamol demonstrated no significant difference in PDA closure and the risk of adverse events between oral and intravenous administration.

Effects of the protective and therapeutic effect of yogurt enriched with Citrus sinensis essential oil against ibuprofen-induced gastric ulcer in elderly rats.

The aim of this study was to evaluate the effect of Citrus sinensis essential oil (EO) on the proximate composition of yogurt over a 28-day shelf life and to investigate the therapeutic and prophylactic effects of functional yogurt on ibuprofen-induced gastric ulcers in a rat model. It was observed that the yogurt group containing C. sinensis EO had higher acidity, total solids, and ash values. Histologic evaluation of the stomachs of rats with gastric ulcers revealed that rats fed with functional yogurt had fewer lesions compared to the control group. The treatment group had fewer lesions than the positive control (p > 0.05). Lesions in the glandular mucosa of the prophylactic group were significantly lower than those in the positive control group (p < 0.05). Yogurt with C. sinensis EO may be beneficial in reducing the severity of ulcers and improving overall health.

Preemptive use of ibuprofen and desensitizer decreases immediate tooth sensitivity after in-office bleaching: A triple-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: The authors evaluated the synergistic analgesic effect of preemptive administration of 400 mg of ibuprofen (IBU) and potassium fluoride 2% (KF2), both in isolation or combination, on the painful perception of tooth sensitivity after tooth bleaching. METHODS: Fifteen patients participated in this triple-blind, randomized, placebo-controlled clinical trial. The study used a crossover design for drug administration and a split-mouth design for desensitizer agent. Four paired groups were formed: IBU plus KF2 (IBU + KF2); IBU (IBU + placebo KF); KF2 (placebo IBU + KF2), and placebo (placebo IBU + placebo KF). The outcome measure was the perception of tooth sensitivity, assessed using a visual analog scale. Data were collected at 4 different times: immediately after tooth bleaching (baseline) and after 6, 30, and 54 hours. Statistical analysis was performed using the Friedman test and relative risk. RESULTS: IBU plus KF2 was found to be more effective in reducing tooth sensitivity immediately after bleaching (baseline) compared with the placebo group (P < .05). The risk of experiencing moderate or severe tooth sensitivity was approximately 4 times higher in the placebo group than in the IBU plus KF2 group (relative risk, 4.00; 95% CI, 1.01 to 15.81; P = .025). CONCLUSIONS: The combined use of 400 mg of IBU and KF2 appears to be beneficial in managing postbleaching tooth sensitivity. It provides a superior analgesic effect compared with placebo. PRACTICAL IMPLICATIONS: The preemptive administration of IBU plus KF2 reduces tooth sensitivity after tooth whitening when compared with placebo. This clinical trial was registered in the Brazilian Clinical Trials Registry Platform. The registration number is U1111-1249-8191.

Trial of Selective Early Treatment of Patent Ductus Arteriosus with Ibuprofen.

BACKGROUND: The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes is not known. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial evaluating early treatment (≤72 hours after birth) with ibuprofen for a large PDA (diameter of ≥1.5 mm with pulsatile flow) in extremely preterm infants (born between 23 weeks 0 days' and 28 weeks 6 days' gestation). The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia evaluated at 36 weeks of postmenstrual age. RESULTS: A total of 326 infants were assigned to receive ibuprofen and 327 to receive placebo; 324 and 322, respectively, had data available for outcome analyses. A primary-outcome event occurred in 220 of 318 infants (69.2%) in the ibuprofen group and 202 of 318 infants (63.5%) in the placebo group (adjusted risk ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died (adjusted risk ratio, 1.32; 95% CI, 0.92 to 1.90). Among the infants who survived to 36 weeks of postmenstrual age, moderate or severe bronchopulmonary dysplasia occurred in 176 of 274 (64.2%) in the ibuprofen group and 169 of 285 (59.3%) in the placebo group (adjusted risk ratio, 1.09; 95% CI, 0.96 to 1.23). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen. CONCLUSIONS: The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age was not significantly lower among infants who received early treatment with ibuprofen than among those who received placebo. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Baby-OSCAR ISRCTN Registry number, ISRCTN84264977.).

A unusual presentation of liver failure caused by Ibuprofen-sustained release capsules: A case report.

RATIONALE: Previous studies have shown that acetaminophen has the potential to induce hepatotoxicity in patients, rendering it a prominent drug implicated in the development of acute hepatic failure. However, there is currently no available literature reporting the impact of ibuprofen-sustained release capsules on liver failure. PATIENT CONCERNS: A 65-year-old man was presented with a 4-day history of tea-colored urine with oil avoidance, jaundiced skin, and anorexia, and impaired liver function. One ibuprofen-sustained release capsule was taken on the day before the onset of the disease due to "headache." DIAGNOSES: A diagnosis of this patient was made of liver failure due to taking ibuprofen-sustained release capsules. INTERVENTIONS: Initially, the patient discontinued the use of hepatotoxic drugs in order to prevent further exposure. Subsequently, the patient underwent a standard therapeutic regimen, which encompassed the administration of hepatoprotective agents, nutritional support drugs, correction of acid-base imbalances, and electrolyte abnormalities, as well as other relevant treatments. OUTCOMES: After 9 days of hepatoprotective and nutritional supplement therapy, the patient saw notable improvement in symptoms, reporting an absence of discomfort, subsided skin jaundice, clear urine, and liver function tests returning to a near normal range. The patient was granted permission to be discharged from the hospital while being prescribed drugs. After 2 weeks of follow-up, the patient reported an absence of discomfort and exhibited normal results in the liver function test. CONCLUSIONS: Liver failure caused by ibuprofen-sustained release capsules has not been reported. It is worth noting that conventional treatments such as suspending offending agents, and administration of hepatoprotective agents and nutritional support drugs have proven to be successful. LESSON: There is currently no known peer-reviewed literature indicating that the administration of ibuprofen-sustained release capsules leads to liver failure. When patients taking ibuprofen-sustained release capsules encounter symptoms such as anorexia, skin jaundice, lack of appetite, and nausea, it is recommended that they undertake a cardiac and liver function tests. In the event that ibuprofen-sustained release capsules induce liver injury, it is imperative to administer timely and immediate medical intervention.

Associations between the use of common nonsteroidal anti-inflammatory drugs, genetic susceptibility and dementia in participants with chronic pain: A prospective study based on 194,758 participants from the UK Biobank.

OBJECTIVE: To investigate the potential relationship between common nonsteroidal anti-inflammatory drugs (NSAIDs), genetic susceptibility and all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VD) among individuals experiencing chronic pain. METHODS: This study was based on 194,758 chronic pain participants form UK biobank with a median follow-up of 13.7 years. Participants were categorized into different NSAIDs painkiller regimen groups: No NSAIDs group, Aspirin group, Ibuprofen group, Paracetamol group, and 2-3 NSAIDs group. Cox proportional risk models were used to examine the correlation between regular NSAIDs usage and the risk of ACD, AD, and VD. In addition, we further performed subgroup analyses and sensitivity analyses. RESULTS: 1) Compared to the No NSAIDs group, the aspirin group (HR = 1.12, 95% CI:1.01-1.24, P < 0.05), the paracetamol group (HR = 1.15, 95% CI:1.05-1.27, P < 0.01), and the 2-3 NSAIDs group (HR = 1.2, 95% CI:1.08-1.33, P < 0.05) showed a higher risk of ACD. Furthermore, the 2-3 NSAIDs group was also associated with a higher risk of VD (HR = 1.39, 95% CI: 1.08-1.33, P < 0.05). 2) At high dementia GRS participants with chronic pain, the paracetamol group (HR = 1.2, 95% CI: 1.03-1.43, P < 0.05) and the NSAIDs group (HR = 1.3, 95% CI: 1.07-1.59, P < 0.05) were associated with a higher risk of ACD compared to the no painkiller group. 3) There was no significant association between ibuprofen use and higher risk of dementia. CONCLUSION: In individuals with chronic pain, the use of aspirin and paracetamol was associated with a higher risk of ACD, whereas the use of ibuprofen was not significantly associated with a higher risk of ACD.

The Opioid Analgesic Reduction Study (OARS) Pilot: A Double-Blind Randomized Multicenter Trial.

BACKGROUND: With addiction rates and opioid deaths increasing, health care providers are obligated to help stem the opioid crisis. As limited studies examine the comparative effectiveness of fixed-dose combination nonopioid analgesia to opioid-containing analgesia, a comparative effectiveness study was planned and refined by conducting a pilot study. METHODS: The Opioid Analgesic Reduction Study (OARS) pilot, a stratified, randomized, multisite, double-blind clinical trial, was designed to test technology and procedures to be used in the full OARS trial. Participants engaged in the full protocol, enabling the collection of OARS outcome data. Eligible participants reporting to 1 of 5 sites for partial or full bony impacted mandibular third molar extraction were stratified by biologic sex and randomized to 1 of 2 treatment groups, OPIOID or NONOPIOID. OPIOID participants were provided 20 doses of hydrocodone 5 mg/acetaminophen 300 mg. NONOPIOID participants were provided 20 doses of ibuprofen 400 mg/acetaminophen 500 mg. OARS outcomes data, including pain experience, adverse effects, sleep quality, pain interference, overall satisfaction, and remaining opioid tablets available for diversion, were collected via surveys, electronic medication bottles, eDiary, and activity/sleep monitor. RESULTS: Fifty-three participants were randomized with 50 completing the OARS pilot protocol. Across all outcome pain domains, in all but 1 time period, NONOPIOID was better in managing pain than OPIOID (P < 0.05 level). Other outcomes suggest less pain interference, less adverse events, better sleep quality, better overall satisfaction, and fewer opioid-containing tablets available for diversion. DISCUSSION: Results suggest patients requiring impacted mandibular third molar extraction would benefit from fixed-dose combination nonopioid analgesia. KNOWLEDGE TRANSFER STATEMENT: Study results suggest fixed-dose nonopioid combination ibuprofen 400 mg/acetaminophen 500 mg is superior to opioid-containing analgesic (hydrocodone 5 mg/acetaminophen 500 mg). This knowledge should inform surgeons and patients in the selection of postsurgical analgesia.

Oral analgesic for musculoskeletal injuries in children: A systematic review and network meta-analysis.

OBJECTIVE: Pain in pediatric musculoskeletal (MSK) injuries can lead to increased anxiety, fear, and avoidance of medical care, making analgesic management critical. Therefore, we evaluated analgesic efficacy and adverse effects to select the optimal analgesic agent in pediatric patients with MSK injuries. METHODS: Four databases were searched from inception to March 2023 for peer-reviewed, open randomized controlled trials (RCTs). Inclusion criteria were: (1) trials with RCT design, (2) children aged 1 month-18 years with MSK injury, (3) outpatient setting, (4) interventions and control, (5) primary outcome of pain score at 60 and 120 min and secondary outcome of adverse effects, and (6) full-text and peer-reviewed articles. Two reviewers screened, extracted data, and assessed the risk of bias. A frequentist random-effects network meta-analysis (NMA) was performed. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation working group approach. RESULTS: We included eight trials comprising 1645 children. Ibuprofen was significantly associated with pain reduction at 120 min, compared with acetaminophen (SMD 0.31 [95% CI 0.11-0.51]; moderate certainty) and opioids (SMD 0.34 [95% CI 0.20-0.48]; moderate certainty). Compared with opioids alone, ibuprofen-opioid combination was significantly associated with pain reduction at 120 min (SMD 0.19 [95% CI 0.03-0.35]). No significant differences were found in pain interventions at 60 min. Ibuprofen had statistically fewer adverse events than opioids (RR, 0.54 [95% CI 0.33-0.90]; moderate certainty) and ibuprofen with opioids (RR 0.47 [95% CI 0.25-0.89]; moderate certainty). In terms of limitations, the eight RCTs included had relatively small sample sizes; only two were high-quality RCTs. CONCLUSIONS: Our NMA found ibuprofen to be the most effective and least adverse analgesic in pediatric patients with MSK injuries.

Drug-induced immune hemolytic anemia: detection of new signals and risk assessment in a nationwide cohort study.

ABSTRACT: More than 130 drugs have been suspected to induce immune hemolytic anemia. Comparative studies measuring the risk of drug-induced immune hemolytic anemia (DIIHA) are lacking. We aimed (1) to detect new signals of DIIHA, excluding vaccines, and (2) to assess the association between all suspected drugs and the occurrence of immune hemolytic anemia in a nationwide comparative study. The new signals were identified using a disproportionality study (case/noncase design) in the World Pharmacovigilance Database, Vigibase, among the cases of adverse drug reactions reported up to February 2020 (>20 million). We then conducted a comparative study in the French National health database that links sociodemographic, out-of-hospital, and hospital data for the entire population (67 million individuals). Associations between exposure to drugs (those already reported as DIIHA, plus new signals identified in Vigibase) and incident cases of immune hemolytic anemia (D59.0 and D59.1 diagnosis codes of the International Classification of Diseases, version 10) from 2012 to 2018 were assessed with case-control and case-crossover designs. In Vigibase, 3371 cases of DIIHA were recorded. Fifty-nine new signals were identified resulting in a final list of 112 drugs marketed in France and measurable in the nationwide cohort (n = 4746 patients with incident immune hemolytic anemia included in the case-control analysis matched with 22 447 controls from the general population). We identified an association between immune hemolytic anemia occurrence and some antibiotics, antifungal drugs, ibuprofen, acetaminophen, furosemide, azathioprine, and iomeprol.

Paracetamol versus ibuprofen in treating episodic tension-type headache: a systematic review and network meta-analysis.

Tension-type headache (TTH) is the most common type of headache worldwide. It is defined and classified according to the International Classification of Headache Disorders. TTH is treated with over-the-counter medications, mostly paracetamol or ibuprofen. The purpose was to assess the effectiveness of paracetamol versus ibuprofen in treating episodic tension-type headache (ETTH) through direct and indirect comparisons of randomized controlled trials (RCTs). We included RCTs comparing paracetamol with a placebo, ibuprofen with a placebo, or paracetamol with ibuprofen for acute ETTH treatment that were published between 1988 and 2022. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and the Web of Science. The Cochrane Collaboration risk of bias tool was used to assess the risk of bias. We identified 14 studies including 6521 people with ETTH. None of the studies had a low risk of bias for all domains; this was most likely due to inadequate reporting and a small sample size. Ibuprofen (odds ratio (OR): 1.73, 95% confidence interval (CI): 1.17-2.56) showed better efficacy than paracetamol (OR: 1.62, 95% CI 1.24-2.13) for pain-free status at 2 h, while paracetamol (OR: 1.42, 95% CI 0.87-2.30) showed better efficacy than ibuprofen (OR: 1.20, 95% CI 0.58-2.48) for pain-free status at 1 h. Paracetamol was associated with the lowest likelihood of rescue medication use (OR: 0.49, 95% CI 0.37-0.65). Ibuprofen was associated with a lower likelihood of the occurrence of any events and gastrointestinal adverse events compared with placebo and paracetamol (OR: 0.95, 95% CI 0.64-1.41 and OR: 0.81, 95% CI 0.44-1.50, respectively). Paracetamol and ibuprofen showed better efficacy than placebo in treating ETTH; there was no statistically significant difference in efficacy between the two drugs. For individuals at a higher risk (like renal insufficiency or risk of GI bleeding), paracetamol may be considered as a preferred option instead of Ibuprofen. Further meta-analyses of head-to-head trials are needed for direct comparisons in the future.PROSPERO registration number: CRD42022340936.

Association of regular use of ibuprofen and paracetamol, genetic susceptibility, and new-onset dementia in the older population.

OBJECTIVE: Although the possible efficacy and adverse effects of paracetamol and ibuprofen on dementia are of global clinical and public health importance, to date, the relationship of the use of paracetamol and ibuprofen with incident dementia remains uncertain. We aimed to assess the prospective association of regular use of ibuprofen and paracetamol with new-onset dementia in an older population. METHODS: This study included 212,968 participants from the UK Biobank, aged ≥60 years, with available data of ibuprofen, paracetamol use and without dementia at baseline. The primary outcome was new-onset all-cause dementia. The secondary outcomes included new-onset Alzheimer's disease and new-onset vascular dementia. RESULTS: During a median follow-up of 12.3 years, 6407 (3.0%) participants developed new-onset all-cause dementia. Participants who regularly used paracetamol had a significantly higher risk of new-onset all-cause dementia (adjusted HR, 1.18; 95%CI: 1.10-1.26), compared with non-users. However, there was no significant association between regular use of ibuprofen and new-onset all-cause dementia (users vs. non-users; adjusted HR, 1.06; 95%CI: 0.97-1.16). Furthermore, APOE ε4 dosage and genetic risk scores (GRS) of Alzheimer's disease calculated by 25 single nucleotide polymorphisms did not significantly modify the relationship of regular use of paracetamol and ibuprofen with new-onset all-cause dementia (Both P-interactions >0.05). Similar results were found in the propensity score analysis. Similar findings were also observed for new-onset Alzheimer's disease and new-onset vascular dementia. CONCLUSIONS: Regular use of paracetamol, but not ibuprofen, was associated with a significantly higher risk of new-onset dementia in the old population, regardless of genetic risks of dementia.

Different Patterns of Response in Hypersensitivity Reactions to Arylpropionic Acid Derivatives.

BACKGROUND: Ibuprofen and other arylpropionic acid derivatives (APs) are among the most consumed nonsteroidal anti-inflammatory drugs worldwide at all age ranges; however, little is known about drug hypersensitivity reactions (DHRs) they induce. OBJECTIVE: To characterize in detail patients reporting DHRs to APs. METHODS: We prospectively evaluated patients with symptoms suggestive of AP-DHRs and analyzed their clinical characteristics, reported reactions, and diagnostic approaches. RESULTS: Six hundred sixty-two patients confirmed as hypersensitive to APs were included: 489 with cross-reactive reactions (CRs) (73.86%) and 173 with selective reactions (SRs) (26.13%). The percentage of subjects reporting reactions to ibuprofen and dexketoprofen was higher in CRs (P = .005 and P = .01, respectively), whereas naproxen and ketoprofen were more frequently involved in SRs (P = .0002 and P = .00001, respectively). The most frequent symptoms induced by ibuprofen, dexketoprofen, and naproxen were isolated angioedema and urticaria, combined or not with angioedema in both CRs and SRs. The result of nasal provocation test with lysine acetylsalicylate was positive in 156 cases (77.14% in patients showing exclusively respiratory symptoms, and in 68.18% of those with both cutaneous and respiratory involvement). To confirm diagnosis, drug provocation test with acetylsalicylic acid was required in 246 CR patients (50.3%), whereas in 28 SR patients (16.18%) drug provocation test with the culprit AP was required. CONCLUSIONS: Skin is the organ most commonly involved in AP-DHRs, with ibuprofen and dexketoprofen inducing most frequently CRs, and naproxen and ketoprofen SRs. More studies are necessary to clarify the underlying mechanism in DHRs induced by APs.

Ibuprofen, other NSAIDs and COVID-19: a narrative review.

At the start of the coronavirus disease 2019 (COVID-19) pandemic (March 2020), there was speculation that non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, used to manage some of the symptoms of COVID-19, could increase the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and negatively impact clinical outcomes. In the absence of any robust mechanistic and clinical evidence, this speculation led to confusion about the safety of ibuprofen, contributing to the so-called 'infodemic' surrounding COVID-19. A wealth of evidence has been generated in subsequent years, and this narrative review aims to consider the body of in vitro and in vivo research, observational studies, systematic reviews and meta-analyses on the use of NSAIDs, including ibuprofen, in COVID-19. Overall, the direction of evidence supports that NSAIDs do not increase susceptibility to infection, nor worsen disease outcomes in patients with COVID-19. Neither do they impact the immune response to COVID-19 vaccines. There is no basis to limit the use of NSAIDs, and doing so may deprive patients of effective self-care measures to control symptoms.

Treatment of fever and associated symptoms in the emergency department: which drug to choose?

OBJECTIVE: Fever is a frequent cause of admission to the Emergency Department (ED) worldwide. Although it can be caused by a wide range of conditions, the most effective treatment based on its etiology is still undetermined. PATIENTS AND METHODS: This prospective, single-center, observational study enrolled adult patients who accessed the ED for fever. Physicians were free to administer paracetamol 1,000 mg (P), the combination paracetamol 500 mg/ibuprofen 150 mg (PI) or Ibuprofen 600 mg (I). The primary endpoint was both 1-degree and 1-point reduction in body temperature for all associated symptoms on the Numerical Rating Scale (NRS) after 1 hour (T1). The secondary endpoint was the reduction of at least 2 points on the NRS after two hours (T2). Adverse events, the need for rescue therapy, and the response based on the underlying etiology (bacterial, viral, or immune/neoplastic) were also evaluated. RESULTS: 324 patients (170 males, mean age 71±6 years) were enrolled: 187 had bacterial, 80 viral, and 57 neoplastic/inflammatory fever. Fever was treated with Paracetamol 1,000 mg (P) in 189 patients and with Paracetamol/Ibuprofen 500/150 mg (PI) in 135 subjects, while none of the patients were primarily treated with I. Based on the fever etiology P was administered to 113 patients with bacterial fever (59.8%), 48 patients with viral fever (25.4%), and 28 subjects with neoplastic/inflammatory fever (14.8%). PI was administered to 74 patients with bacterial fever (54.8%), 32 patients with viral fever (23.7%), and 29 subjects with neoplastic/inflammatory fever (21.5%). The primary endpoint was achieved by 126 patients, 70 of them (37.0%) were treated with P and 56 (41.5%) with PI (p=0.418). The secondary endpoint was achieved by 295 patients, 171 (90.5%) of them treated with P and 124 (91.9%) treated with PI (p=0.669). No significant differences were found between groups treated with P and PI concerning rescue therapy (15 vs. 6 patients; p=0.893). Interestingly, PI was more effective than P in patients with bacterial fever at T1 (P 33.6% vs. PI 48.6%; p=0.040), while efficacy of P and PI was similar at T2 for all kind of fever. CONCLUSIONS: Paracetamol 1,000 mg represents the first choice for the treatment of fever in the ED, followed by Paracetamol/Ibuprofen 500/150 mg. Interestingly, Paracetamol/Ibuprofen combination resulted in being more effective in patients with bacterial fever one hour after its administration.