Use of metamizole and other non-opioid analgesics in Switzerland between 2014 and 2019: an observational study using a large health insurance claims database.

OBJECTIVE: To investigate claims patterns for metamizole and other non-opioid analgesics in Switzerland. To characterise users of these non-opioid analgesics regarding sex, age, comedications and canton of residence. METHODS: We conducted a retrospective descriptive study using administrative claims data of outpatient prescribed non-opioid analgesics of the Swiss health insurance company Helsana between January 2014 and December 2019. First, we evaluated the number of claims and defined daily doses  per year of metamizole, ibuprofen, diclofenac and paracetamol in adults aged 18 years or over. Second, we characterised new users of these non-opioid analgesics in terms of sex, age, claimed comedications and canton of residence. RESULTS: From 2014 to 2019, among the investigated non-opioid analgesics, metamizole showed the highest increase in claims (+9545 claims, +50%) and defined daily doses (+86,869 defined daily doses, +84%) per 100,000 adults. Metamizole users had the highest median age (62 years [IQR: 44-77]) compared to ibuprofen (47 years [IQR: 33-62]), diclofenac (57 years [IQR: 43-71]) and paracetamol (58 years [IQR: 39-75]) users. Metamizole users also more frequently claimed proton pump inhibitors, anticoagulants, platelet aggregation inhibitors and antihypertensive drugs than users of other non-opioid analgesics. While metamizole was most frequently claimed in German-speaking regions of Switzerland, ibuprofen and paracetamol were most frequently claimed in the French-speaking regions and diclofenac in German- and Italian-speaking regions. CONCLUSION: In Switzerland, metamizole was increasingly claimed between 2014 and 2019. Metamizole was most frequently claimed by older adults and patients with comedications suggestive of underlying conditions, which can be worsened or caused by use of nonsteroidal anti-inflammatory drugs. The lack of studies regarding the effectiveness and safety of metamizole in this population warrants further investigation.

[Risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus]. / æœ‰è¡€æµåŠ¨åŠ›å­¦æ„ä¹‰çš„åŠ¨è„‰å¯¼ç®¡æœªé—­æ—©äº§å„¿å¸ƒæ´›èŠ¬æ²»ç–—å¤±è´¥çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA). METHODS: A retrospective collection of clinical data was conducted on preterm infants with a gestational age of <34 weeks who were diagnosed with hsPDA and treated at the Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, from January 2018 to June 2023. The subjects were divided into two groups based on the treatment approach: the ibuprofen group (95 cases) and the ibuprofen plus surgery group (44 cases). The risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA were identified by binary logistic regression analysis. RESULTS: The binary logistic regression analysis revealed that an increased diameter of the ductus arteriosus, a resistance index (RI) value of the middle cerebral artery ≥0.80, and prolonged total invasive mechanical ventilation time were risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). Receiver operating characteristic curve analysis showed that a ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days had significant predictive value for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). The combined predictive value of these three factors was the highest, with an area under the curve of 0.843, a sensitivity of 86.5%, and a specificity of 75.0% (P<0.05). CONCLUSIONS: A ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days are risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA, and they are of significant predictive value for the necessity of surgical treatment following the failure of ibuprofen treatment.

An Evaluation of the Effects of Pineapple-Extract and Bromelain-Based Treatment after Mandibular Third Molar Surgery: A Randomized Three-Arm Clinical Study.

A three-arm, randomized, placebo-controlled clinical study was conducted to assess the impact of lyophilized pineapple extract with titrated bromelain (Brome-Inf®) and purified bromelain on pain, swelling, trismus, and quality of life (QoL) following the surgical extraction of the mandibular third molars. Furthermore, this study examined the need for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) by comparing their effects with a placebo group. This study enrolled 42 individuals requiring the extraction of a single mandibular third molar under local anesthesia. The patients were randomly assigned to receive Brome-Inf®, purified bromelain, or a placebo orally, initiating treatment on the day of surgery and continuing for the next 7 days. The primary outcome measured was the requirement for NSAIDs in the three groups. Pain, swelling, and trismus were secondary outcome variables, evaluated postoperatively at 1, 3, and 7 days. This study also assessed the comparative efficacy of freeze-dried pineapple extract and single-component bromelain. Ultimately, the placebo group showed a statistically higher need for ibuprofen (from days 1 to 7) at the study's conclusion (p < 0.0001). In addition, reductions in pain and swelling were significantly higher in both the bromelain and pineapple groups (p < 0.0001 for almost all patients, at all intervals) than in the placebo group. The active groups also demonstrated a significant difference in QoL compared to the placebo group (p < 0.001). A non-significant reduction in trismus occurred in the treatment groups compared to the placebo group. Therefore, the administration of pineapple extract titrated in bromelain showed significant analgesic and anti-edema effects in addition to improving QoL in the postoperative period for patients who had undergone mandibular third molar surgery. Moreover, both bromelain and Brome-Inf® supplementation reduced the need for ibuprofen to comparable extents, proving that they are good alternatives to NSAIDs in making the postoperative course more comfortable for these patients. A further investigation with larger samples is necessary to assess the pain-relieving and anti-inflammatory impacts of the entire pineapple phytocomplex in surgical procedures aside from mandibular third molar surgery.

PREEMPTIVE INTRAVENOUS IBUPROFEN AND LOCAL KETAMINE IMPROVE POSTOPERATIVE ANALGESIA FOLLOWING THIRD MOLAR SURGERY: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED CLINICAL STUDY.

OBJECTIVE: To compare the efficacy of preemptive ibuprofen, local ketamine, and their combination in managing postoperative pain and trismus following third molar surgery. MATERIALS AND METHODS: One hundred patients were randomly divided into 4 groups. The Intrafen Group had their impacted third molars surgically removed under local anesthesia after receiving intravenous (IV) ibuprofen for preemptive effect. The Ketamine Group received an IV placebo before the surgery, and the extraction process was completed with a local anesthetic-ketamine combination. The Combined Group received preemptive IV ibuprofen before the procedure, and the surgery was performed with a local anesthetic-ketamine combination. The Control Group received an IV placebo before the procedure and then had their impacted third molars removed under local anesthesia. The Visual Analogue Scale (VAS) values, corresponding to the patients' pain levels at the 2nd and 12th postoperative hours and the total amount of analgesic dose used in the first 24 hours, were recorded, and evaluated. The maximum mouth opening of the patients was measured immediately before the procedure, and on the second and seventh postoperative days. The level of patient satisfaction in all groups was assessed during the procedure. RESULTS: The mean VAS value corresponding to the second-hour pain level of the combined group was statistically significantly lower than the other groups (P = .003). A statistically significant difference was found in the mean VAS values corresponding to the pain levels of the groups, favoring the combined group compared to the other groups (P ≤ .001). A significant difference was observed between the VAS difference values corresponding to the pain levels of the Intrafen group and the Ketamine group, favoring the Intrafen group (P = .038). The Ketamine group consumed the most analgesic on average over the first 24 hours, whereas the Combined group consumed the least. No statistically significant difference was found between the mean trismus levels of the groups on days 0-2 (P = .528) and days 0-7 (P = .129). The intraoperative patient satisfaction level of the combined group was significantly higher than that of the other groups (P = .030). CONCLUSION: Preemptive Intrafen is an effective regimen for postoperative pain management and is superior to the local anesthetic-ketamine regimen. The most effective method to reduce postoperative pain following third molar surgery is to use a combination of these 2 regimens. However, none of the treatment methods used in the study had a positive effect on postoperative trismus.

Investigating the Effect of an Anti-Inflammatory Drug in Determining NURR1 Expression and Thus Exploring the Progression of Parkinson's Disease.

Nonsteroidal anti-inflammatory drugs are the most widely used drugs for Parkinson's disease (PD), of which ibuprofen shows positive effects in suppressing symptoms; however, the associated risk needs to be addressed in different pathological stages. Initially, we developed an initial and advanced stage of the Parkinson disease mouse model by intraperitoneal injection of MPTP (20 mg/kg; 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine) for 10 and 20 days, respectively. Subsequently, ibuprofen treatment was administered for 2 months, and a pole test, rotarod test, histology, immunohistochemistry, and western blotting were performed to determine neuronal motor function. Histological analysis for 10 days after mice were injected with MPTP showed the onset of neurodegeneration and cell aggregation, indicating the initial stages of Parkinson's disease. Advanced Parkinson's disease was marked by Lewy body formation after another 10 days of MPTP injection. Neurodegeneration reverted after ibuprofen therapy in initial Parkinson's disease but not in advanced Parkinson's disease. The pole and rotarod tests confirmed that motor activity in the initial Parkinson disease with ibuprofen treatment recovered (p<0.01). However, no improvement was observed in the ibuprofen-treated mice with advanced disease mice. Interestingly, ibuprofen treatment resulted in a significant improvement (p<0.01) in NURR1 (Nuclear receptor-related 1) expression in mice with early PD, but no substantial improvement was observed in its expression in mice with advanced PD. Our findings indicate that NURR1 exerts anti-inflammatory and neuroprotective effects. Overall, NURR1 contributed to the effects of ibuprofen on PD at different pathological stages.

[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.

Percutaneous closure of patent ductus arteriosus versus surgical treatment in low-birth-weight preterms: a systematic review and meta-analysis.

INTRODUCTION: The optimal management of a patent ductus arteriosus in a population of preterm infants is controversial. Traditionally, when the patent ductus arteriosus does not close either with conservative treatment or in response to pharmacological therapy, the only option is surgical closure. However, transcatheter occlusion might provide a therapeutic alternative. METHODS: We searched PubMed, Embase, and Cochrane databases for non-randomised and randomised controlled trials that compared transcatheter percutaneous closure of patent ductus arteriosus with surgical ligation in low-birth-weight preterm infants (<2,500 g). A random-effects model was used for outcomes with high heterogeneity. RESULTS: We included twelve studies comprising 4,668 low-birth-weight preterm infants, of whom 966 (20.7%) were in the transcatheter percutaneous closure group, and 3,702 (79.3%) patients were included in the surgical group. All-cause mortality (OR 0.28; 95% confidence interval 0.18-0.423; p < 0.00001; I2 = 0%) and haemodynamic instability (OR 0.10; 95% confidence interval 0.05-0.21; p < 0.001; I2 = 14%) were significantly lower in the transcatheter percutaneous closure group. There was no significant difference between transcatheter and surgical patent ductus arteriosus closure for the outcomes of bronchopulmonary dysplasia (0.93; 95% confidence interval 0.46-1.87; p = 0.83; I2 = 0%) and major complications (OR 0.76; 95% confidence interval 0.34-1.69; p = 0.51; I2 = 43%). CONCLUSION: These findings suggest that transcatheter patent ductus arteriosus closure in preterm infants under 2,500 g is a safe and effective alternative to surgical treatment. There was a substantial reduction in all-cause mortality and haemodynamic instability with transcatheter intervention compared to surgical closure.

Effect of topical application of ibuprofen/arginine on the in-office bleaching-induced tooth sensitivity: A randomized, triple-blind controlled trial.

OBJECTIVE: The application of anti-inflammatories as topical desensitizers before dental bleaching is an approach to reduce bleaching-induced tooth sensitivity (TS). This randomized controlled trial compared the risk and intensity of TS and the color change resulting from in-office dental bleaching after using an experimental desensitizing gel containing ibuprofen and arginine. METHODS: Sixty-two participants with upper canine shades A2 or darker were randomly assigned to either the ibuprofen-arginine desensitizing group or the placebo group. The desensitizing gel was applied for 15 min before in-office bleaching with 35 % hydrogen peroxide gel for 50 min (2 sessions). To assess the absolute risk and intensity of TS, visual (0-10) and numeric rating (0-5) scales were used, and group comparisons were made using the McNemar test, Wilcoxon test, and paired Student t-test (α = 0.05). Color change was evaluated using Vita Classical, Vita Bleachedguide (ΔSGU), and Vita EasyShade (ΔEab, ΔE00, and ΔWID) before and one month after the bleaching procedure. Group comparisons for color change were done using a paired t-test (α = 0.05). RESULTS: The odds ratio for TS was 0.14 [95 % CI 0.02 to 0.6], meaning lower odds of TS for the desensitizing gel. A lower intensity of TS was also observed for the experimental group (p < 0.005) up to 48 h after bleaching. All color evaluation tools demonstrated effective and similar whitening for both groups (p > 0.05). CONCLUSIONS: Using the experimental desensitizing gel containing ibuprofen and arginine effectively reduced the risk and intensity of TS without compromising the bleaching efficacy. CLINICAL RELEVANCE: The topical application of ibuprofen/arginine on the in-office bleaching reduced risk and intensity of bleaching-induced tooth sensitivity.

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.).

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.

The effectiveness of interventions in reducing pain related to orthodontic separation: a systematic review and meta-analysis.

BACKGROUND: Pain is an unpleasant experience and annoying sensation. To control this pain during orthodontic separation, different pharmacological and non-pharmacological methods have been used. OBJECTIVE: This systematic review and meta-analysis aimed to critically assess the evidence of the effectiveness of pharmacological and non-pharmacological methods in reducing pain induced by orthodontic separation. SEARCH STRATEGY: An electronic search was conducted using the following databases: PubMed® (Medline), Scopus®, EMBASE®, Web of ScienceTM, Google ScholarTM, ProQuest, and Cochrane Central Register of controlled trials (CENTRAL) searching for the studies published between January 2012 and April 2023. SELECTION CRITERIA: Only randomized controlled trials (RCTs) were included, each experimental group included patients who received elastomeric separators and one kind of pharmacological or non-pharmacological interventions for pain reduction during the separation stage. DATA COLLECTION AND ANALYSIS: Cochrane's risk of bias tool (RoB2 tool) was applied. The Grading of Recommendations Assessment, Development, and Evaluation [GRADE] approach was used to evaluate the strength of the evidence. RESULTS: Thirty-one studies (RCTs) were included in this systematic review. Nineteen of them were appropriate for quantitative synthesis and used VAS for pain assessment. Meta-analysis showed that low-level laser therapy (LLLT) was an effective approach for pain relief after separators placement with standard mean difference of 13.79 mm (95% confidence interval (CI): -15.64, -11.94) at 6 h and 23.34 mm at 24 h (95% CI: -25.91, -20.77). LLLT was also effective when applied in split-mouth and the standard mean difference was 8.9 mm at 6 h (95% CI: -12.86, -3.33) and 17.15 mm at 24 h (95% CI: -30.12, -4.17). Ibuprofen had a pain control effect at 6 h and at 24 h compared with the placebo group. The standard mean difference was 14.37 mm (95% CI: -20.54, -8.19) and 20.46 mm (95% CI: -27.79, -13.13), respectively. There was no difference in pain control between ibuprofen and acetaminophen. Naproxen had lower visual analog scale scores in pain perception at 6 h and the standard mean difference was 7.03 mm (95% CI: -12.67, -1.40). CONCLUSIONS: The application of LLLT decreased the pain induced by the separation during the first day of teeth separation; the pain reduction showed an increase from 6 h to the end of the 24 h. However, the evidence is weak to moderate. The analgesics reduced the pain compared to placebo; this pain reduction had shown an increase from 6 h to the end of the 24 h. The strength of the evidence is moderate. Naproxen gel effectively reduced the pain compared to placebo; the evidence in this regard is moderate. Naproxen gel effectively reduced the pain compared to placebo, but it was less effective than the oral intake of non-steroidal anti-inflammatory drugs. However, the evidence in this regard is moderate. REGISTRATION: This systematic review was registered with PROSPERO (CRD42022335553) during the first stages of its conduction.

Synthesis and biological evaluation of new nicotinic acid derivatives as potential anti-inflammatory agents with enhanced gastric safety profile.

Two innovative series derived from nicotinic acid scaffold were synthesized and evaluated for their anti-inflammatory activity. Ibuprofen, celecoxib and indomethacin were used as standard drugs. All the newly synthesized compounds were in vitro screened for their anti-inflammatory activity adopting 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide dye (MTT), as well as Griess assays. The results showed that all compounds exhibited significant anti-inflammatory activity without affecting the viability of the macrophages compared to ibuprofen. In addition, compounds 4d, 4f, 4g, 4h and 5b exhibited the most potent nitrite inhibition activity and consequently superior anti-inflammatory activity with MTT results ranging between values 86.109 ± 0.51 to 119.084 ± 0.09. The most active compounds were subjected to evaluation of TNF-α, IL-6, iNOS and COX-2 levels in LPS/INF γ-stimulated RAW 264.7 macrophage cells in comparison to ibuprofen as a reference compound. The five compounds showed comparable inhibition potency of these inflammatory cytokines compared to ibuprofen. Same compounds were further in vivo evaluated for their anti-inflammatory activity via carrageenan induced arthritis in rats. Regarding the ulcerogenic profile, compound 4h showed mild infiltration of gastric mucosa superb to compound 5b displayed severe gastritis. Molecular docking of 4h and 5b in the COX-2 active site was performed to evaluate their preferential COX-2 inhibitory potency. The docking results were in accordance with the biological findings.

Comparison of intravenous ibuprofen and paracetamol for peri-operative analgesia in paediatric day care tonsillectomy.

OBJECTIVE: To determine the effectiveness of intravenous ibuprofen and acetaminophen as perioperative analgesics in paediatric patients undergoing day- care tonsillectomy with general anaesthesia. METHODS: The quasi-experimental stud y was conduc ted at the Ana esthe sia D epartment of Pa k Emirates M ilitary Hospital, Rawalpindi , Pak ist an, from July 20 21 to June 2022, and comp rised paediatric pa t ients aged 5-12 yea r s undergoing day- care tonsil lec tomy with gen era l anaesthesia. The sub jec ts were divid ed into two equa l groups. Patients in Group I received intravenous ibuprofen 7mg/kg and patients in Group P received intravenous paracetamol 10mg/kg im media t ely after induction of anaesthesi a. All patients recei ved standard general anaesthesia with endotracheal intubation. The primary outcome measured was revised faces pain score immediately after recovery and at the time of discharge 6 hours later. Adverse events were also noted. Data was analysed using SPSS 26. RESULTS: Of the 100 patients, there were 50(50%) in Group I; 21(42%) boys and 29(58%) girls with mean age 7.82±1.903 years. The remaining 50(50%) subjects were in Group P; 25(50%) boys and 25(50%) girls with mean age 7.68±1.812 years. At baseline, 44(88%) patients in Group I and 42(84%) in Group P reported no pain, while 6(12%) and 8(16%) patients in the two groups, respectively, reported pain (p=0.56). At discharge, 35(70%) patients in Group I and 18(36%) in Group P reported no pain (p<0.001). Adverse events were not significantly different between the groups (p>0.05). CONCLUSIONS: I ntravenous ibuprofen was found to b e a superior pain-killer than intravenous paracetamol for perioperative care of paediatric patients in day- care tonsillectomy.

Facts and trends in dental antibiotic and analgesic prescriptions in Germany, 2012-2021.

OBJECTIVES: The study aims to overview German dentists' development of antibiotic and analgesic prescriptions from 2012 to 2021. MATERIALS AND METHODS: A longitudinal database analysis was performed based on the annual reports of the "Research Institute for Local Health Care Systems" (WIdO, Berlin). RESULTS: From 2012 until 2021, dental antibiotic prescriptions fell by 17.9%. In contrast, the dental proportion of antibiotic prescriptions compared to all antibiotic prescriptions in Germany increased from 9.1 to 13.6%. Aminopenicillins enhanced their share from 35.6 to 49.4%, while clindamycin prescriptions declined from 37.8 to 23.4%. The proportion of ibuprofen prescriptions significantly increased from 60.4% in 2012 to 79.0% in 2021. CONCLUSIONS: Since 2013, the most frequently prescribed antibiotic by German dentists has been amoxicillin reaching nearly half of all dental antibiotic prescriptions in 2021. Simultaneously, the proportion of clindamycin has steadily decreased, but the level is still high compared to international data. During the past decade, ibuprofen as a first-line analgesic in German dentistry was continuously gaining in importance. CLINICAL RELEVANCE: Aminopenicillins have the best risk-benefit balance in dentistry, but the use of antibiotics generally must be limited only to cases of severe infections or compromised patients. Pre-existing diseases or permanent medications should always be considered when choosing an analgesic.

The Predictive Value of Cold Pack Test for Pain After Third Molar Surgery.

BACKGROUND: Early identification of patients who are prone to postoperative pain may provide individualization of postoperative analgesia strategies. PURPOSE: The aim of the study was to investigate whether the cold pack test is associated with postoperative pain levels after mandibular third molar surgery. STUDY DESIGN, SETTING, SAMPLE: This prospective cohort study included healthy male patients admitted to Department of Oral and Maxillofacial Surgery of a tertiary health-care center between June 2022 and December 2022 and scheduled for lower third molar extraction. Those who had used any analgesic within the past 10 days or had a history of intolerance/allergy to analgesics were excluded. PREDICTOR VARIABLE: The primary predictor variable was pain tolerance, measured using the endurance test score. Subjects were grouped into two categories, low tolerance test score (withdrew the hand from the cold pack in <240 seconds) and high tolerance test score (maintained the hand on the cold pack for 240 seconds). MAIN OUTCOME VARIABLES: The primary outcome variable was pain measured by the patients from 0 to 10 with the visual analog scale, and the secondary outcome variables were the amount of ibuprofen and paracetamol consumed in the postoperative period. Pain measurements and ibuprofen consumption were recorded at 0-2, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, and 96 hours (0-2 interval of the first 2 hours immediately after surgery). COVARIATES: Age, classification and position of mandibular third molar were utilized as covariates. ANALYSES: The relationship between pain tolerance and postoperative pain was analyzed using the Mann-Whitney U test and the Fisher exact test. Statistical analysis was performed using the SPSS version 28.0 software. RESULTS: A total of 30 male patients with a mean age of 22.5 ± 4.8 years were included in our study. In the group with low pain tolerance, the pain scores at the first 2 hours, 32, and 48 hours after the operation (4.55 ± 3.59, 2.91 ± 2.59, 2.91 ± 2.43, respectively) were found to be significantly higher than the group with high pain tolerance (2.00 ± 2.67, 0.95 ± 1.68, 0.95 ± 1.39, respectively) (P < .05). In the first 2 hours after the operation, the amount of ibuprofen consumed was also significantly higher in the group with low pain tolerance compared to the other group, and 81.8% of this group felt the need to consume ibuprofen (P < .05). CONCLUSIONS AND RELEVANCE: The cold pack test, a more practical version of quantitative sensory testing, is useful in identifying male patients at risk of developing greater pain after third molar surgery. It can be helpful to provide effective analgesia in male patients with different pain tolerance thresholds.

Ibuprofen inhibits anaplastic thyroid cells in vivo and in vitro by triggering NLRP3-ASC-GSDMD-dependent pyroptosis.

Pyroptosis is a novel type of proinflammatory programmed cell death that is associated with inflammation, immunity, and cancer. Anaplastic thyroid carcinoma (ATC) has a high fatality rate, and there is no effective or standard treatment. The disease progresses rapidly and these tumors can invade the trachea and esophagus, leading to breathing and swallowing difficulties. Hence, new treatment methods are greatly needed. Ibuprofen is a common drug that can exert antitumor effects in some cancers. In this study, we demonstrated in vitro and in vivo that ibuprofen can induce ATC pyroptosis. Hence, we treated C643 and OCUT-2C ATC cells with ibuprofen and found that several dying cells presented the characteristic morphological features of pyroptosis, such as bubble-like swelling and membrane rupture, accompanied by activation of ASC and NLRP3 and cleavage of GSDMD. Along with the increased release of LDH, ibuprofen treatment promoted apoptosis and inhibited viability, invasion, and migration. However, overexpression of GSDMD significantly inhibited ibuprofen-induced pyroptosis. In vivo, research has demonstrated that thyroid tumor growth in nude mice can be suppressed by ibuprofen-induced pyroptosis in a dose-dependent manner. In this research, we explored a new mechanism by which ibuprofen inhibits ATC growth and progression and highlighted its promise as a therapeutic agent for ATC.

Pharmacokinetic and Pharmacodynamic Analysis of Acetaminophen and Ibuprofen Dual Therapy for Patent Ductus Arteriosus Closure in Preterm Neonates at Less Than 29 Weeks of Gestation.

Patent ductus arteriosus (PDA) is a blood vessel that critically supports fetal circulation. The ductus naturally closes within a few days after birth. However, it can stay open in premature neonates for an extended period of time, which is associated with increased mortality and various co-morbidities. Ibuprofen and indomethacin are currently the only 2 drugs approved for inducing PDA closure, but both have been associated with adverse renal and bleeding events. Clinical evidence suggests that combining acetaminophen (APAP) and ibuprofen treatments can decrease the need for surgical ligation. The objective of this study was to establish a disease-drug-trial model to characterize and predict PDA closure following single and combination drug therapy with ibuprofen and/or APAP in children at less than 29 weeks of gestation. The model was informed by a comprehensive literature review. The results of our analysis suggest that ibuprofen and APAP achieve therapeutic synergy. They further suggest that the younger the preterm neonates, the higher the treatment benefit. A 5-day oral dosing regimen consisting of ibuprofen (20 mg/kg Q24h on day 1, followed by 10 mg/kg Q24h on days 2-5) plus APAP (15 mg/kg Q6h) was deemed appropriate to achieve at least 90% PDA in all preterm neonates evaluated within 1 month of life. The model can now be used to design prospective pediatric trials to evaluate optimal drug combinations for PDA closure in preterm neonates and to refine optimal dosing regimens in cohorts of differing gestational age.