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.

Fluconazole-Loaded Ibuprofen In Situ Gel-Based Oral Spray for Oropharyngeal Candidiasis Treatment.

Oral candidiasis is a fungal infection affecting the oral mucous membrane, and this research specifically addresses on a localized treatment through fluconazole-loaded ibuprofen in situ gel-based oral spray. The low solubility of ibuprofen is advantageous for forming a gel when exposed to an aqueous phase. The 1% w/w fluconazole-loaded in situ gel oral sprays were developed utilizing various concentrations of ibuprofen in N-methyl pyrrolidone. The prepared solutions underwent evaluation for viscosity, surface tension, contact angle, water tolerance, gel formation, interface interaction, drug permeation, and antimicrobial studies. The higher amount of ibuprofen reduced the surface tension and retarded solvent exchange. The use of 50% ibuprofen as a gelling agent demonstrated prolonged drug permeation for up to 24 h. The incorporation of Cremophor EL in the formulations resulted in increased drug permeation and exhibited effective inhibition against Candida albicans, Candida krusei, Candida lusitaniae, and Candida tropicalis. While the Cremophor EL-loaded formulation did not exhibit enhanced antifungal effects on agar media, its ability to facilitate the permeation of fluconazole and ibuprofen suggested potential efficacy in countering Candida invasion in the oral mucosa. Moreover, these formulations demonstrated significant thermal inhibition of protein denaturation in egg albumin, indicating anti-inflammatory properties. Consequently, the fluconazole-loaded ibuprofen in situ gel-based oral spray presents itself as a promising dosage form for oropharyngeal candidiasis treatment.

Spatial Arrangement of the Drug Ibuprofen in a Model Membrane in the Presence of Lipid Rafts.

Many pharmaceutical drugs are known to interact with lipid membranes through nonspecific molecular interactions, which affect their therapeutic effect. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) and one of the most commonly prescribed. In the presence of cholesterol, lipid bilayers can separate into nanoscale liquid-disordered and liquid-ordered structures, the latter known as lipid rafts. Here, we study spin-labeled ibuprofen (ibuprofen-SL) in the model membrane consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and cholesterol in the molar ratio of (0.5-0.5xchol)/(0.5-0.5xchol)/xchol. Electron paramagnetic resonance (EPR) spectroscopy is employed, along with its pulsed version of double electron-electron resonance (DEER, also known as PELDOR). The data obtained indicate lateral lipid-mediated clustering of ibuprofen-SL molecules with a local surface density noticeably larger than that expected for random lateral distribution. In the absence of cholesterol, the data can be interpreted as indicating alternating clustering in two opposing leaflets of the bilayer. In the presence of cholesterol, for xchol ≥ 20 mol %, the results show that ibuprofen-SL molecules have a quasi-regular lateral distribution, with a "superlattice" parameter of ∼3.0 nm. This regularity can be explained by the entrapment of ibuprofen-SL molecules by lipid rafts known to exist in this system with the additional assumption that lipid rafts have a nanoscale substructure.

Enhanced Solubility of Ibuprofen by Complexation with ß-Cyclodextrin and Citric Acid.

The ability of ß-CD to form inclusion complexes with ibuprofen (IBU) and at the same time to make a two-phase system with citric acid was explored in the present study for achieving improved solubility and dissolution rate of IBU. Mechanical milling as well as mechanical milling combined with thermal annealing of the powder mixtures were applied as synthetic methods. Solubility and dissolution kinetics of the complexes were studied in compliance with European Pharmacopoeia (ICH Q4B). ß-CD and citric acid (CA) molecules were shown to interact by both ball milling (BM), thermal annealing, as well as BM with subsequent annealing. Complexes were also formed by milling the three compounds (ß-CD, CA and IBU) simultaneously, as well as by a consecutive first including IBU into ß-CD and then binding the formed ß-CD/IBU inclusion complex with CA. As a result, ternary ß-CD/IBU/CA complex formed by initial incorporation of ibuprofen into ß-CD, followed by successive formation of a two-phase mixture with CA, exhibited notably improved dissolution kinetics compared to the pure ibuprofen and slightly better compared to the binary ß-CD/IBU system. Although the addition of CA to ß-CD/IBU does not significantly increase the solubility rate of IBU, it must be considered that the amount of ß-CD is significantly less in the ternary complex compared to the binary ß-CD/IBU.

Mechanistic Modeling of In Vitro Biopharmaceutic Data for a Weak Acid Drug: A Pathway Towards Deriving Fundamental Parameters for Physiologically Based Biopharmaceutic Modeling.

Mechanistic modeling of in vitro experiments using metabolic enzyme systems enables the extrapolation of metabolic clearance for in vitro-in vivo predictions. This is particularly important for successful clearance predictions using physiologically based pharmacokinetic (PBPK) modeling. The concept of mechanistic modeling can also be extended to biopharmaceutics, where in vitro data is used to predict the in vivo pharmacokinetic profile of the drug. This approach further allows for the identification of parameters that are critical for oral drug absorption in vivo. However, the routine use of this analysis approach has been hindered by the lack of an integrated analysis workflow. The objective of this tutorial is to (1) review processes and parameters contributing to oral drug absorption in increasing levels of complexity, (2) outline a general physiologically based biopharmaceutic modeling workflow for weak acids, and (3) illustrate the outlined concepts via an ibuprofen (i.e., a weak, poorly soluble acid) case example in order to provide practical guidance on how to integrate biopharmaceutic and physiological data to better understand oral drug absorption. In the future, we plan to explore the usefulness of this tutorial/roadmap to inform the development of PBPK models for BCS 2 weak bases, by expanding the stepwise modeling approach to accommodate more intricate scenarios, including the presence of diprotic basic compounds and acidifying agents within the formulation.

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.

Polyethyleneimine-functionalized magnetic sugarcane bagasse cellulose film for the efficient adsorption of ibuprofen.

Polyethyleneimine-modified magnetic sugarcane bagasse cellulose film (P-SBC/Fe3O4 film) was simply fabricated for the removal of ibuprofen (IBP), a typical emerging organic contaminant. The P-SBC/Fe3O4 film exhibited an equilibrium adsorption amount of 370.52 mg/g for IBP and a corresponding removal efficiency of 92.63 % under following adsorption conditions: 318 K, pH 4, and 0.25 mg/mL dosage. Thermodynamic studies indicated that adsorption of IBP on the P-SBC/Fe3O4 film was spontaneous (∆G < 0) and endothermic (∆H > 0). The adsorption data conformed to the Freundlich isotherm model and multilayer adsorption model (two layers), and an average of 3-4 active sites on the P-SBC/Fe3O4 film share an IBP molecule. Both the EDR-IDR and AOAS models vividly described the dynamic characteristics of adsorption process. Model fitting results, theoretical calculations, and comprehensive characterization revealed that adsorption is driven by electrostatic interactions between the primary amine of P-SBC/Fe3O4 film and the carboxyl group of IBP molecule, while other weak interactions are also non-ignorable. Furthermore, quantitative calculations based on density functional theory (DFT) underscored the importance of PEI functionalization. In conclusion, P-SBC/Fe3O4 film is an environmentally friendly and cost-effective adsorbent with significant potential for effectively removing IBP, while maintaining its efficacy over multiple cycles.

Characterization of microcrystalline cellulose prepared from long and short fibers and its application in ibuprofen tablets.

As a bio-based material, microcrystalline cellulose (MCC) has been applied in many fields including pharmaceuticals, foods, and cosmetics in recent years. However, traditional preparation methods of MCC are facing many challenges due to economic and eco-environmental issues. In this study, softwood dissolved pulp was sieved to long fiber (LF) and short fiber (SF), and subsequently to prepare LF-MCC and SF-MCC by hydrochloric acid hydrolysis at different acid dosages (3-7 wt%), reaction times (30-90 min), and temperatures (75-95 °C). The as-obtained MCC products were compared in terms of morphology, size, crystallinity, and chemical structure. The results indicated that the crystallinity and yield of LF-MCC were high, with maximum values of 78.41 % and 98.68 %, respectively. The particle size distribution of SF-MCC was more uniform in the range of 20-80 µm, with a maximum of 59.44 % at 20-80 µm occupancy proportion. Moreover, SF-MCC had a typical rod-like shape and larger surface area as well as better thermal behavior than LF-MCC. When LF-MCC and SF-MCC were used as fillers in the production of ibuprofen tablets, the tablets added with LF-MCC exhibited higher hardness, friability, dissolution rate, and shorter disintegration time. Therefore, this work is very beneficial for the preparation and application of MCC.

Studies on the Application of PGM Nanocatalysts from Spent Automotive Converters for Degradation of Ibuprofen in Aqueous Solutions.

There is an increasing concern about the presence of various types of pharmaceuticals in drinking water, as long-term exposure of people to even low concentrations of drugs can lead to many problems, such as endocrine disorders or drug resistance. As the removal in sewage treatment plants is not effective enough, as indicated, among others, by the EC and OECD reports, it is justified to search for new materials that will allow for an effective and rapid reduction of these pollutants in water. Therefore, in our work, catalytically active nanomaterials containing platinum group metals (PGMs) were synthesized from model and real multicomponent solutions and examined in reactions of organic compounds. The nanoparticles (NPs) were obtained from real solutions from the hydrometallurgical processing of spent automotive converters (SACs), and to the best of our knowledge, the novelty of the proposed paper is the application of solutions from SAC processing as precursors for PGM-NPs. The synthesized PGM-NPs were deposited on a support (TiO2), characterized and, finally, examined as nanocatalysts in a degradation reaction of ibuprofen (IB) from model aqueous solutions. The degree of IB degradation reached more than 90%. The main products of IB degradation were p-isobutylphenol and CO2.

Prednisone and ibuprofen conjugate Janus dendrimers and their anticancer activity.

Drug release from hyperbranched Janus dendrimer-drug conjugates and their subsequent activity are influenced by the different drugs in each dendron and the linker. To understand these effects, we synthetized new Janus-type dendrimers of first and second generation. One dendron with 2,2-Bis(hydroxymethyl)propionic acid functionalized with ibuprofen and the second dendron was obtained with 3-aminopropanol-amidoamine and prednisone. The dendrimers were obtained by copper(I)-catalyzed Click azide-alkyne cycloaddition for the formation of a triazole as a dendrimeric nucleus of Janus dendrimer conjugates are reported. The influence of ibuprofen, prednisone, and spacer on cancer activity of Janus dendrimers conjugates is reported. The IC50 values of the anticancer activity on cancer cell lines the Janus dendrimer of second generation was higher in comparison to the first generation dendrimer. Similarly, the anticancer activity was higher compared to the dendron conjugates. Also, no cytotoxic effects of dendrons and dendrimers on non-cancerous kidney COS-7 cell line was observed. The interesting anticancer activity of the prepared prednisone-ibuprofen Janus dendrimer conjugates suggest that the dendrimers could be of potential use as new anticancer drug.

Evaluation of organo-vermiculites as sorbent phases for solid-phase extraction of ibuprofen from water.

The study of ibuprofen (IBU) preconcentration was carried out making use of a homemade column for solid-phase extraction (SPE), using vermiculite (VT) or organo-vermiculites (OVTs) as sorbent phases. Aqueous samples (50.0 mL) percolated the column and IBU was sorbed onto the VT or OVT and then desorbed using acetonitrile. Employing this SPE system and OVT, calibration curves were generated for IBU, by spectrophotometric quantification using the α-naphthylamine method. R2 values higher than 0.9950 and LOD between 12 and 18 µg L-1 were observed, for real enrichment factors of 21 and 31, by using OVTs. The analytical protocol was applied to three water samples, which were spiked with IBU solutions to evaluate the precision and accuracy of the method. Recoveries between 77 and 110% at three different IBU concentrations and RSD lower than 18% were observed, even by using the spectrophotometric method. The protocol developed in this study demonstrated that the OVT was appropriate to work as a preconcentration phase for IBU determination in water samples.

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.

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.

Shoulder pain management strategies and early functional outcome after arthroscopic rotator cuff tear repair. A randomized controlled study.

BACKGROUND: The management of acute postoperative pain after rotator cuff surgery can be challenging. To our knowledge, there are no data available in the literature correlating satisfactory pain control with improvement in terms of function. The purposes of the present study were to evaluate: 1) pain pattern after arthroscopic rotator cuff repair in patients operated with two different techniques (transosseous vs transosseous equivalent); 2) safety/efficacy of three different pharmacological pain control strategies; 3) possible relationship between a correct shoulder pain management protocol in the early post-operative period and patients' functional improvement. METHODS: 114 patients underwent rotator cuff tear repair, either with a Transosseus or a Transosseus equivalent technique. 62 (54%) were male and 52 (46%) were female. The average age was 59 ± 9 years. They were randomly assigned into three different pain management protocols: Paracetamol as needed (max 3 tablets/day) for 1 week (Protocol A), Paracetamol + Codein 1 tablet three times per day for 7 days (Protocol B), or Paracetamol + Ibuprofen 1 tablet two times per day for 7 days (Protocol C). Immediate passive mobilization of the operated shoulder was allowed. VAS and Passive Flexion values were recorded at 7 (T1), 15 (T2) and 30 (T3) days post-surgery. DASH values were recorded at 90 days post-surgery. All patients were asked to register any kind of signs/symptoms that may appear during drug assumption according to each pain management protocols. RESULTS: All the pain management protocols administered were well tolerated by all the study population, and no adverse signs/symptoms were highlighted during drug assumption. Pain pattern: in both surgical techniques, patients within Protocol A were associated with worst results in terms of mean VAS at each time point examined when compared to Protocol B and C (p < 0,05). In patients within Protocol A, no statistically significant differences were found at each point time examined comparing the two surgical techniques, with the exception of T2, where the TO was associated with an higher VAS value than TOE (p < 0.05). No differences were highlighted in Protocol B and C when comparing the values between two surgical techniques. ROM: in both surgical techniques, patients within Protocol A were associated with worst results in terms of mean PROM at each time point examined when compared to Protocol B and C (p < 0,05). In the TO group, patients within Protocol B had better PROM values at T1 (p < 0,05) and T2 (p < 0,05) compared to Protocol C, but no differences were highlighted at T3. In the TOE group, no statistically significant differences were found between patients within Protocol B and C at each time point examined. DASH: In the TO group, no statistically significant differences were found regarding the DASH values comparing Protocol B vs Protocol C, but they were highlighted comparing the values between Protocol A and Protocol B (p < 0,05), and between Protocol A and Protocol C (p < 0,05). Similar results were recorded in the TOE group. CONCLUSION: Post-operative pain is influenced by the surgical technique used being transosseous more painful in the first 15 days after surgery. Oral anti-inflammatory drugs are a feasible strategy to appropriately control post-operative pain. An association between Paracetamol and either Codein or Ibuprofen can lead to better outcomes in terms of VAS reduction and early recovery of passive ROM.

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.