Efficacy and safety of topical NSAIDs combined with physiotherapy for frozen shoulder: a randomized controlled trial.

OBJECTIVE: Frozen shoulder is a prevalent condition among individuals in their middle and later years. Invasive therapy has shown promising results in the treatment of frozen shoulders, but its widespread adoption has been hampered by high costs and the need for advanced medical technology. As a result, patients with frozen shoulders often turn to non-steroidal anti-inflammatory drugs (NSAIDs) for symptomatic relief. However, the oral administration of NSAIDs can lead to troublesome adverse effects on the gastrointestinal, cardiovascular, and urinary systems. In contrast, topical NSAIDs have gained attention for their excellent efficacy and lower adverse effects in various chronic pain conditions. Therefore, our study aimed to investigate the efficacy and safety of topical NSAIDs in improving pain and mobility among patients with frozen shoulders. PATIENTS AND METHODS: A total of 108 patients experiencing moderate to severe pain and mobility impairment due to frozen shoulder were enrolled in this study. The participants were randomly assigned to either the experimental group (n=72) or the control group (n=36). The experimental group received daily treatment with the loxoprofen hydrogel patch (LOX-P) in addition to basic rehabilitation physiotherapy. The control group was treated with flurbiprofen cataplasm (FLU-C) twice a day, along with rehabilitation physiotherapy. The primary endpoint for evaluating the efficacy of the two patches was the Constant-Murley score (CMS). Clinical symptom data, adverse events, and patient satisfaction were also recorded. RESULTS: After 14 days of treatment, the effective rate was 66.67% (n=48) in the experimental group and 41.67% (n=15) in the control group. The overall difference in the effective rates was 25.00% (95% CI=5.20-42.52; p=0.013). The safety profiles of the two topical agents were similar, with only a few adverse events reported. CONCLUSIONS: The loxoprofen hydrogel patch demonstrates a significant ability to alleviate shoulder pain and restore shoulder function in the treatment of frozen shoulder, with minimal adverse reactions. Chictr.org.cn ID: ChiCTR2100052375.

Ultrasound-guided pericapsular nerve group (PENG) block for early analgesia in elderly patients with hip fractures: a single-center prospective randomized controlled study.

BACKGROUND: The aim of this study was to compare the efficacy of ultrasound-guided PENG (pericapsular nerve group) block and drug therapy with intravenous flurbiprofen for early analgesia in elderly patients with hip fractures after hospitalization. METHODS: This is a single-center, observer-blinded, prospective, randomized, controlled trial. A total of 41 elderly patients (aged 60 or older) with hip fractures were enrolled in the current study. Patients were randomly assigned to two groups: Group P (ultrasound-guided PENG block, 20 mL of 0.375% ropivacaine) and Group F (intravenous flurbiprofen 50 mg). The primary outcome measure was the dynamic (passive straight leg raising 15°) NRS (numerical rating scale 0 to 10) pain scores at different time points. The secondary outcomes were the static NRS scores at different time points, the number of rescue analgesia sessions, patient satisfaction, and the incidence of complications. RESULTS: Patients in the two groups had comparable baseline characteristics. The group P had lower dynamic and static NRS scores at 15 min, 30 min, 6 h, and 12 h after intervention (P<0.05) than the group F. The highest NRS pain scores in the group P were still lower than the NRS scores in the group F at 30 min-12 h (Group F: 5.57±1.54 vs. Group P: 3.00±1.12, P<0.001), and there was no significant difference between the two groups at 12-24 h (Group F: 6.35±1.79 vs. Group P: 5.90±1.83, P>0.05). The group P had higher satisfaction scores (Group P: 9 (9,9) vs. Group F: 8 (7,8), P<0.001). There was no statistically significant difference in the number of rescue analgesics at 0-12 h or 12-24 h or the incidence of complications between the groups. CONCLUSIONS: Compared with intravenous flurbiprofen, ultrasound-guided PENG block provides better early analgesic effects in elderly patients with hip fractures, and a PENG block is safe for elderly patients with hip fractures after hospitalization. Trial registration This study was registered in the Chinese Clinical Trial Testing Center (ID: ChiCTR2200062400).

Efficacy and safety of flurbiprofen cataplasms versus loxoprofen sodium cataplasms in knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA. METHODS: This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0-10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events. RESULTS: Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147-0.681); P <0.001 for non-inferiority; P = 0.001 for superiority). Similar results were observed of the VAS scores for the current pain and pain during exercise. WOMAC scores were also lower in the FPC group at week 4 (12.50 [8.00-22.50] vs . 16.00 [11.00-27.00], P = 0.010), mainly driven by the dimension of daily activity difficulty. In addition, the FPC group experienced a significantly lower incidence of adverse events (5.6% [7/124] vs . 33.6% [42/125], P <0.001), including irritation, rash and pain of the skin, and sticky hair uncovering pain. CONCLUSIONS: This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief, joint function improvement, and safety profile.

Anti-inflammatory mechanisms of eucalyptol rich Eucalyptus globulus essential oil alone and in combination with flurbiprofen.

Inflammation is the core contributor in the pathogenesis of various acute and chronic illness including appendicitis, bronchitis, arthritis, cancer and neurological diseases. NSAIDs, commonly used medications for inflammatory diseases, on prolonged use cause GI bleeding, ulcers and many more issues. Plant-based therapeutic agents including essential oils in combination with low-dose synthetic drugs have been shown to produce synergistic effects and reduce complications of synthetic drugs. This study was designed to evaluate the anti-inflammatory, analgesic and anti-pyretic properties of Eucalyptus globulus essential oil alone and in combination with flurbiprofen. GC-MS analysis was performed to screen chemical composition of oil. In vitro anti-inflammatory assay (membrane stabilization assay) and in vivo inflammatory acute (carrageenan and histamine-induced paw oedema) and chronic (cotton pellet-induced granuloma and Complete Freund's adjuvant-induced arthritis) models were performed to check anti-inflammatory properties. Acetic acid-induced algesia and yeast-induced pyrexia models were performed to check analgesic and anti-pyretic properties. qRT-PCR was performed to study the effect of treatments on the expression of inflammatory biomarkers. GC-MS analysis of E. globulus essential oil showed the presence of eucalyptol along with other active biomolecules. 500 + 10 mg/kg of oil-drug combination showed significantly (p < 0.05) better in vitro membrane stabilization effects as compared with groups treated with 500 mg/kg of E. globulus oil and 10 mg/kg of Flurbiprofen alone. 500 + 10 mg/kg of oil-drug combination showed significantly (p < 0.05) better anti-inflammatory, analgesic and antipyretic effects as compared to 500 mg/kg of E. globulus oil alone in all in vivo models. When comparison was done between 500 + 10 mg/kg of oil-drug combination-treated and 10 mg/kg Flurbiprofen-treated group, the former group showed significantly (p < 0.05) better anti-inflammatory and anti-pyretic effects, but there were non-significant differences in the analgesic model. Animal group treated with 10 mg/kg of Flurbiprofen showed significantly (p < 0.05) better anti-inflammatory and analgesic effects than group treated with 500 mg/kg of oil alone while, there were non-significant differences in anti-pyretic effects. qRT-PCR analysis showed significant (p < 0.05) down-regulation in the expression of IL-4 and TNF-α in serum samples of animals treated with 500 + 10 mg/kg of oil-drug combination as compared to the diseased control (arthritic) group. Overall, the current research demonstrates that Eucalyptus globulus essential oil in combination with flurbiprofen showed better anti-inflammatory, analgesic and anti-pyretic effects than oil and flurbiprofen alone which is attributed to the down-regulation of pro-inflammatory biomarkers (IL-4 and TNF-α). Further studies are required to formulate a stable dosage form and to check the anti-inflammatory efficacy in different inflammatory disorders.

Evidence of the Efficacy of Flurbiprofen 8.75 mg Lozenges for Patients Receiving Antibiotics for Laboratory-Confirmed Streptococcal Pharyngitis.

OBJECTIVES: To determine the efficacy of flurbiprofen 8.75 mg lozenges for patients with laboratory-confirmed streptococcal pharyngitis both before and concomitant with antibiotics. METHODS: This post hoc analysis comprised adult participants from 2 earlier randomized, double-blind, placebo-controlled studies evaluating the analgesic efficacy of flurbiprofen 8.75 mg lozenges in acute pharyngitis. Throat swabs were obtained to diagnose streptococcal infection. Prior to and 2 hours after each dose of study medication (flurbiprofen or placebo lozenges), patients rated 3 symptoms of acute pharyngitis (sore throat pain, difficulty swallowing, and swollen throat) using visual analogue scales. Appropriate antibiotic treatment was initiated when culture results were reported. Mean changes in each pharyngeal symptom were compared over the immediate 24 hours before and during the initial 24 hours of antibiotic treatment. RESULTS: Twenty-four patients provided both preantibiotic and concomitant antibiotic efficacy outcomes. Relief of throat pain was 93% greater in the flurbiprofen group than in the placebo group before antibiotic coadministration and 84% greater than placebo during antibiotic administration (both P < .05). Relief of difficulty swallowing was 71% greater in the flurbiprofen group than in the placebo before antibiotic administration (P = .16) and 107% greater during concomitant antibiotic administration (P = .04). Relief of the sensation of throat swelling was 295% greater with flurbiprofen than placebo before antibiotic administration (P = .008) and 70% greater during concomitant antibiotic administration (P = .06). For placebo-treated patients, relief from throat pain and difficulty swallowing were similar before and during antibiotic treatment (P > .05), indicating no benefit with antibiotic administration for these symptoms. No treatment-related discontinuations or serious adverse events were reported. CONCLUSIONS: Irrespective of antibiotic use, flurbiprofen 8.75 mg lozenges provide well-tolerated, effective relief of pharyngeal symptoms in patients with streptococcal infection. In the 24 hours after administration, antibiotics provide no relief of throat pain or difficulty swallowing beyond the topical demulcent effects of placebo lozenges.

The cost-effectiveness analysis of analgesic treatment options for postoperative pain following laparotomy surgeries.

BACKGROUND: Postoperative pain control remains unsatisfactory. Patients who underwent laparotomy may have moderate to severe acute postoperative pain. Comparative cost-effectiveness of the following postoperative pain treatment options remains to be investigated: patient-controlled intravenous analgesia (PCIA) with flurbiprofen therapy, flurbiprofen monotherapy, parecoxib monotherapy, or dezocine monotherapy. AIM: To provide a cost-effectiveness analysis (CEA) of four analgesic regimens for patients with postoperative pain following laparotomy surgeries. METHOD: Patients with postoperative pain following laparotomy were retrospectively reviewed from a postoperative pain management database created by pharmacists, and divided into four groups according to analgesic regimens. The clinical outcomes were visual analogue scale (VAS) scores and the incidence of adverse drug events. The CEA was conducted by developing a decision tree model based on retrospective data. The maximum incremental cost-effectiveness ratio (ICER) of the four regimens was used as the willingness-to-pay (WTP) value. Meanwhile, the uncertainty of the base-case results was examined by one-way and probabilistic sensitivity analyses. RESULTS: A total of 677 patients were included in the retrospective study. PCIA with flurbiprofen therapy had the lowest VAS scores at 6, 24, 48 h postoperatively. Based on the base-case results, PCIA plus flurbiprofen was the optimal regimen with the highest effectiveness, while flurbiprofen monotherapy had the lowest cost. PCIA plus flurbiprofen was the optimal regimen even with a WTP value of 0 dollars. CONCLUSION: PCIA plus flurbiprofen therapy was the optimal regimen. Parecoxib monotherapy was more cost-effective than flurbiprofen monotherapy. The findings may guide the selection of postoperative pain management.

Efficacy and safety of flurbiprofen cataplasms versus loxoprofen sodium cataplasms in knee osteoarthritis: a randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA.@*METHODS@#This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0-10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events.@*RESULTS@#Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147-0.681); P <0.001 for non-inferiority; P = 0.001 for superiority). Similar results were observed of the VAS scores for the current pain and pain during exercise. WOMAC scores were also lower in the FPC group at week 4 (12.50 [8.00-22.50] vs . 16.00 [11.00-27.00], P = 0.010), mainly driven by the dimension of daily activity difficulty. In addition, the FPC group experienced a significantly lower incidence of adverse events (5.6% [7/124] vs . 33.6% [42/125], P <0.001), including irritation, rash and pain of the skin, and sticky hair uncovering pain.@*CONCLUSIONS@#This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief, joint function improvement, and safety profile.

Analgesic outcomes of tramadol alone and in combination with Butorphanol or Flurbiprofen Axetil after cesarean section: a retrospective study with propensity score matching analysis.

BACKGROUND: The Society for Obstetric Anesthesia and Perinatology recommends a multimodal analgesia regimen for cesarean delivery analgesia. This study aimed to compare the analgesic effects of tramadol alone and combined with butorphanol or flurbiprofen axetil after a cesarean section. METHODS: We performed a retrospective analysis based on the electronic medical records of a teaching hospital in China from January 2018 to January 2020. We collected data on demographic characteristics, anesthesia, analgesia strategy, and pain intensity postoperatively during the first 48 hours. Inadequate postoperative analgesia during this period was defined as an NRS score ≥ 4. We also collected data regarding off-bed activity and intestinal function recovery. Participants were classified into three groups according to analgesia regimens. Groups T, TF, and TB received tramadol, a mixture of tramadol and flurbiprofen axetil, and a combination of tramadol and butorphanol, respectively. Analgesic outcomes were compared using propensity score matching analysis. RESULTS: Data from 2323 cases of caesarean section were included in the analysis, and 521 pairs were matched in each group according to their propensity score. Compared with group T, The inadequate analgesia on pain at rest and pain at movement was lower in group TF (RR: 0.42, 95% CI: 0.36-0.49, P = 0.001 and RR: 0.58, 95% CI: 0.48-0.69, P < 0.001, respectively),and the incidence of inadequate control of pain at movement was higher in group TB (RR: 1.38, 95% CI: 1.22-1.55, P < 0.001). Additionally, the percentage of off-bed activity at 2 days postoperatively was higher in group TB than in groups TF and T (78.7% vs. 68.5 and 78.7% vs. 64.9%, respectively, P < 0.001). The incidence of intestinal function recovery 2 days after cesarean delivery in group TB was higher than that in group TF (73.3% vs. 66.2%, P = 0.013). CONCLUSIONS: Combining tramadol and flurbiprofen axetil could enhance the analgesic effect and be safely used for analgesia after a cesarean section. However, combining tramadol and butorphanol may produce an antagonistic effect.

Effects of Knee Debridement with Flurbiprofen on Knee Function, Inflammatory Levels, and Bone Metabolism Activity in Patients with Knee Osteoarthritis.

Objective: The objective of this study is to explore the effects of knee debridement with flurbiprofen on the knee function, inflammatory levels, and bone metabolism activity in patients with knee osteoarthritis. Methods: 110 patients with knee osteoarthritis who underwent arthroscopic debridement in our hospital from 2020.01 to 2022.01 were selected for retrospective analysis. Based on whether or not flurbiprofen was used in combination during the perioperative phase, the patients were divided into the control group (only arthroscopic debridement of the knee) and the research group (flurbiprofen with arthroscopic debridement of the knee), with 55 cases in each group. The indexes such as knee function, inflammatory levels, and bone metabolism activity of the two groups were analyzed. Results: According to hospital for special surgery (HSS) evaluation for knee function, most patients in the control group were assessed as "moderate," while patients in the research group were mainly focused on "excellent" and "good," and their excellent and good rates were remarkably higher than those in the control group (P < 0.05). There were no significant variations in bone metabolism indices such as osteoprotegerin levels (OPG), insulin-like growth factor-1 (IGF-1), ß-isomerized C-terminal telopeptide (ß-CTX), and receptor activator of nuclear factor-κB ligand (RANKL) before treatment between both groups (P > 0.05), with higher OPG, IGF-1 levels, and remarkably lower ß-CTX, RANKL levels in the research group than those in the control group after treatment (P < 0.05). There were no remarkable differences in pain between both groups before treatment (P > 0.05), while at 24 h and 48 h after surgery, the VAS scores in the research group were remarkably lower than those in the control group (P < 0.05). In terms of inflammatory factors, the levels of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) in the research group were remarkably lower than those in the control group after treatment (P < 0.05). Conclusion: Arthroscopy coupled with flurbiprofen provides a good analgesic effect in the therapeutic treatment of patients with knee osteoarthritis, which contributes to the recovery of knee function with definite results. Its mechanism may be associated with the control of inflammatory response and the regulation of bone metabolism disorder.

Effects of multimodal analgesia of flurbiprofen axetil, nalbuphine and patient controlled intravenous analgesia on inflammatory factor levels and stress response in patients after laparoscopic radical gynecological malignancy surgery.

To evaluate the efficacy of multimodal analgesia of flurbiprofen axetil, nalbuphine hydrochloride and patient controlled intravenous analgesia (PCIA) on inflammatory factor levels and stress response in patients after laparoscopic radical gynecological malignancy surgery. The data of 100 patients admitted to our hospital from May 2019 to May 2020 for laparoscopic radical gynecological malignancy surgery were retrospectively analyzed and they were assigned (1:1) to either an experimental group or a control group according to the alphabetical order of their initials. The experimental group was given preemptive analgesia with flurbiprofen axetil, postoperative analgesia with nalbuphine hydrochloride, and PCIA and the control group was given conventional analgesic measures. The pain scores at 1h, 6h, 12h, 24h and 48h postoperatively in the experimental group were remarkably lower than those in the control group (P<0.001). The experimental group showed significantly lower inflammatory factor levels, pain mediator levels and stress response indexes in the morning before surgery, 1d, and 2d after surgery than the control group (P<0.001). The multimodal analgesia of flurbiprofen axetil, nalbuphine hydrochloride and PCIA can effectively alleviate the stress response and inflammatory response in patients after radical gynecologic malignancy surgery and the patients' pain perception is reduced with a high safety profile.

Efficacy and safety of S-flurbiprofen plaster in knee osteoarthritis patients: A 2-week randomized controlled Phase III clinical trial compared to diclofenac gel.

AIM: S-flurbiprofen plaster (SFPP) is a novel topical nonsteroidal anti-inflammatory drug (NSAID) patch. This study aimed to assess the efficacy and safety of SFPP in knee osteoarthritis (OA) patients compared to diclofenac gel. METHODS: This study was a multicenter, randomized, active-controlled, open-label, non-inferiority phase III trial. There were 311 enrolled patients treated by SFPP or diclofenac gel for 2 weeks. The primary efficacy outcome was the knee pain when rising from the specially arranged chair assessed by visual analog scale (rVAS). The other efficacy outcomes were clinical symptoms, pain on walking, global assessment by both investigator and patient, and use/non-use of the rescue drugs during the treatment period. Adverse events (AEs) were evaluated as the safety outcome. RESULTS: The least-squares mean (95% CI) of ΔrVAS at the end of the study was 41.52 (39.16-43.88) mm in the SFPP group and 36.01 (33.69-38.33) mm in the diclofenac gel group, with a between-group difference of 5.51 (2.20-8.82), indicating non-inferiority. There were statistically significant differences between the groups in rVAS, clinical symptoms, pain on walking, and the global assessment by both investigator and patient. The incidence rate of AEs in the SFPP group was 5.8%, and there was no statistically significant difference from that in the diclofenac gel group (5.2%). Most of the AEs were mild, and no AE led to discontinuation. CONCLUSION: Non-inferiority of SFPP to diclofenac gel was demonstrated in the efficacy for pain on rising from a chair. SFPP was also well-tolerated in knee OA patients.

Continuous Serratus Anterior Plane Block Improved Early Pulmonary Function After Lung Cancer Surgical Procedure.

BACKGROUND: Serratus anterior plane block (SAPB) has been proven to be an efficient way to control postoperative pain. This study explored whether the use of continuous SAPB in combination with flurbiprofen could improve early pulmonary function in lung cancer patients undergoing video-assisted thoracoscopic surgery (VATS). METHODS: From July 2019 to April 2020, patients who scheduled for elective lung resection undergoing VATS were randomly allocated to receive patient-controlled SAPB in combination with intravenous flurbiprofen or patient-controlled intravenous analgesia. Postoperative pulmonary function variables, including forced expiratory volume in 1 second, and forced vital capacity were collected before and 24, 48, and 72 hours after Surgical Procedure. Pain intensity was measured at rest and on coughing. Comfort scores during breathing exercises, postoperative pulmonary complications, and adverse events were recorded. RESULTS: A substantial reduction in lung function was exhibited in both groups after Surgical Procedure (P < .001), but lung function variables in the continuous SAPB group were significantly higher (P < .001) throughout the postoperative period up to 72 hours, regardless of the surgical procedure type. Meanwhile, there were significant differences of pain intensity at rest and on coughing between the groups (P < .001). The incidence of pneumonia, pulmonary atelectasis, hypoxemia, vomiting, and the comfort score in the continuous SAPB group was significantly lower (P < .05). CONCLUSIONS: Postoperative acute pain treatment with continuous SAPB in combination with flurbiprofen enhanced pulmonary function and reduced postoperative pulmonary complications in lung cancer patients undergoing VATS.

γ-Cyclodextrin-based polypseudorotaxane hydrogels for ophthalmic delivery of flurbiprofen to treat anterior uveitis.

Anterior uveitis is a sight-threatening inflammation inside the eyes. Conventional eye drops for anti-inflammatory therapy need to be administered frequently owing to the rapid elimination and corneal barrier. To address these issues, polypseudorotaxane hydrogels were developed by mixing Soluplus micelles (99.4 nm) and cyclodextrins solution. The optimized hydrogels exhibited shear-thinning and sustained release properties. The hydrogels exhibited higher transcorneal permeability coefficient (Papp, 1.84 folds) than that of drug solutions. Moreover, animal study indicated that the hydrogels significantly increased the precorneal retention (AUC, 21.2 folds) and intraocular bioavailability of flurbiprofen (AUCAqueous humor, 17.8 folds) in comparison with drug solutions. Importantly, the hydrogels obviously boosted anti-inflammatory efficacy in rabbit model of endotoxin-induced uveitis at a reduced administration frequency. Additionally, the safety of hydrogels was confirmed by cytotoxicity and ocular irritation studies. In all, the present study demonstrates a friendly non-invasive strategy based on γ-CD-based polypseudorotaxane hydrogels for ocular drug delivery.

[Evaluation of the application of dexmedetomidine combined with flurbiprofen axetil in extraction of multiple complex teeth under local anesthesia].

PURPOSE: To evaluate the safety and efficacy of sedation and analgesia using dexmedetomidine combined with flurbiprofen axetil in multiple complex teeth extraction under local anesthesia. METHODS: According to the inclusion and exclusion criteria of the study, 40 patients scheduled for multiple complex teeth (4-6) extraction were randomly divided into 2 groups: experimental group (sedation and analgesia using dexmedetomidine combined with flurbiprofen axetil in addition to local anesthesia, n=20) and control group (local anesthesia, n=20). The mean arterial pressure(MAP), heart rate(HR), Ramsay sedation score, VAS pain score of each patient at T0(basis value), T1 (during local anesthesia), T2(during extraction), T3(10 minutes after extraction) and the follow-up results were recorded. SAS 8.0 software was used for statistical analysis. RESULTS: Compared to T0 and control group at the same time, the experimental group revealed more stable mood and hemodynamic manifestation and better analgesic effect (P<0.05), from T1 to T3, patients in the control group showed increased blood pressure, heart rate, emotional fluctuation, bodily and facial pain(P<0.05). The follow-up results showed 5 and 0 patients taking painkillers in the control and experimental group, respectively(P<0.05). CONCLUSIONS: Sedation and analgesia using dexmedetomidine combined with flurbiprofen axetil in addition to local anesthesia is a safe and effective approach in multiple complex teeth extraction.

Effect of perioperative flurbiprofen axetil on long-term survival of patients with esophageal carcinoma who underwent thoracoscopic esophagectomy: A retrospective study.

BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) have an anti-inflammatory response, but it remains unclear whether the perioperative use of flurbiprofen axetil can influence postoperative tumor recurrence and survival in esophageal carcinoma. We aimed to explore the effect of perioperative intravenous flurbiprofen axetil on recurrence-free survival (RFS) and overall survival (OS) in patients with esophageal carcinoma who underwent thoracoscopic esophagectomy. METHODS: This retrospective study included patients who underwent surgery for esophageal carcinoma between December 2009 and May 2015 at the Department of Thoracic Surgery, Anhui Provincial Hospital. Patients were categorized into a non-NSAIDs group (did not receive flurbiprofen axetil), single-dose NSAIDs group (received a single dose of flurbiprofen axetil intravenously), and multiple-dose NSAIDs group (received multiple doses of flurbiprofen). RESULTS: A total of 847 eligible patients were enrolled. Univariable and multivariable analyses revealed that the intraoperative use of flurbiprofen was associated with long-term RFS (hazard ratio [HR]: 0.56, 95% confidence interval [CI]: 0.42-0.76, p = .001) and prolonged OS (HR: 0.49, 95% CI: 0.38-0.63, p = .001). CONCLUSIONS: Perioperative flurbiprofen axetil therapy may be associated with prolonged RFS and OS in patients with esophageal carcinoma undergoing thoracoscopic esophagectomy.

Effects of Oxycodone Combined With Flurbiprofen Axetil on Postoperative Analgesia and Immune Function in Patients Undergoing Radical Resection of Colorectal Cancer.

The influence of surgery and anesthesia on immune function during the perioperative period should not be neglected. In this study, we evaluated the effects of oxycodone combined with flurbiprofen axetil on postoperative analgesia and immune function in patients undergoing radical resection of colorectal cancer (CRC). One hundred and thirty-three were randomized into the oxycodone combined with flurbiprofen axetil (OF) group or the sufentanil combined with flurbiprofen axetil (SF) group. Patients in the OF group were prescribed oxycodone hydrochloride 0.1 mg/kg combined with flurbiprofen axetil 3 mg/kg for postoperative analgesia, whereas the SF group received sufentanil 0.1 µg/kg combined with flurbiprofen axetil 3 mg/kg. The primary outcome was visual analog scale (VAS) score. Secondary outcomes included the quantities of CD4+ , CD8+ , and natural killer (NK) T cells, tumor necrosis factor (TNF)-α level, and interleukin (IL)-6 in peripheral blood, the consumption of analgesics, and the incidence of adverse reactions, and so forth. The VAS scores at rest were similar in both group. However, the VAS scores at cough in the OF group at 8, 12, and 24 hours postsurgery were lower than those in the SF group. Compared with the SF group, the count of CD4+ T cells and ratio of CD4+ /CD8+ were higher in the OF group at 12, 24, 48, and 72 hours postsurgery, although the count of CD8+ and NK T cells was higher than that in the SF group at 48 and 72 hours postsurgery. In addition, the serum level of TNF-α and IL-6 at 12, 24, 48, and 72 hours postsurgery in the OF group was lower than that in the SF group. In addition, the incidence of postoperative nausea, postoperative vomiting, and pruritus was lower, the time to first flatus and bowel movement was earlier in the OF group. Oxycodone combined with flurbiprofen axetil applied for patient-controlled intravenous analgesia could effectively reduce pain intensity, particularly for visceral pain, and help to reverse the status of immunosuppression during radical resection of CRC.

Multicentre randomised phase II study of the perioperative administration of flurbiprofen axetil in patients with non-small cell lung cancer: study protocol of the FLAX Study.

INTRODUCTION: In patients with non-small cell lung cancer, surgical treatment with postoperative adjuvant chemotherapy is performed. However, the improvement of overall survival achieved by postoperative adjuvant chemotherapy may be insufficient in consideration of the deterioration of quality of life (QOL). Considering the relationships among surgical treatments, inflammation and carcinogenesis, non-steroidal anti-inflammatory drugs (NSAIDs) are a candidate postoperative treatment for preventing recurrence and maintaining QOL. In this study, we investigate the effects of the perioperative administration of flurbiprofen axetil on postoperative recurrence in patients with non-small cell lung cancer. METHODS AND ANALYSIS: This study is a multicentre, parallel group, open label, randomised controlled trial. Patients clinically suspected of non-small cell lung cancer are randomly assigned to the flurbiprofen axetil group or the no-NSAIDs group. A total of 420 patients (210 per group) will be registered. The primary analysis will evaluate the treatment effect of flurbiprofen axetil on postoperative recurrence. ETHICS AND DISSEMINATION: The study protocol was approved by the Clinical Research Review Board of Saitama Medical University in September 2019 (No. 192002) and will be approved by each institutional review board of all participating institutions before patient enrolment. This study complies with the latest version of the Declaration of Helsinki, Clinical Trial Act and related notifications. Results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Japan Registry of Clinical Trials (jRCTs031190167; Pre-results) (https://jrct.niph.go.jp/).

Bis-conjugation of Bioactive Molecules to Cisplatin-like Complexes through (2,2'-Bipyridine)-4,4'-Dicarboxylic Acid with Optimal Cytotoxicity Profile Provided by the Combination Ethacrynic Acid/Flurbiprofen.

A facile route to PtII complexes doubly functionalized with bioactive molecules through a bipyridine-type ligand is described. Initially, ligands LEE (containing two ethacrynic acid units), LEF (ethacrynic acid+flurbiprofen) and LEB (ethacrynic acid+biotin) were obtained in moderate to good yields from 2,2'-bipyridine-4,4'-dicarboxylic acid. Subsequent reaction of the ligands with [PtCl2 (DMSO)2 ] afforded complexes [PtCl2 (LEE )] (2), [PtCl2 (LEF )] (3) and [PtCl2 (LEB )] (4) in high yields. All compounds were fully characterized by analytical and spectroscopic methods. Complexes 2-4 are highly stable in water/DMSO solution at 37 °C after 72 h, whereas progressive release of the bioactive fragments was detected in a cell culture medium. The compounds were assessed for their in vitro antiproliferative activity towards tumorigenic A2780, A2780cisR and Y79 cells and non-tumourigenic HEK293 cells. In particular, the combination of ethacrynic acid and flurbiprofen in 3 overcomes cisplatin-based resistance and provides strong cancer cell selectivity. Enzyme inhibition assays on human GST P1 and human COX-2 and cross-experiments with complex 1, analogous to 2-4 but lacking bio-groups, revealed a clear synergy between the PtII frame and the bioactive organic components.

Anti-Aß agents for mild to moderate Alzheimer's disease: systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of Aß-targeting agents for mild to moderate Alzheimer's disease. METHODS: The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform search portal were searched from their inception to April 2020. We generated pooled estimates using random effects meta-analyses. RESULTS: Nineteen randomised controlled trials, of which 17 had a low risk of bias, included 12 903 participants. The meta-analysis showed no difference in the cognitive subscale of Alzheimer's Disease Assessment Scale (ADAS-Cog) between anti-Aß drugs and placebo (mean difference (MD): 0.20, 95% CI -0.40 to 0.81; I 2=99.8%; minimal important difference 3.1-3.8 points, moderate-certainty evidence). For ADAS-Cog, results suggested that one drug that increases Aß clearance may differ in effect (MD: -0.96, 95% CI -0.99 to -0.92) from drugs that reduce Aß production (MD: 0.78, 95% CI 0.25 to 1.32) (interaction p<0.000001); this difference also existed in the outcome of MMSE and CDR-SOB. Compared with placebo, anti-Aß drug-related adverse events were as follows: anxiety, depression, diarrhoea, fatigue, rash, syncope and vomit. DISCUSSION: From current evidence, anti-Aß interventions are unlikely to have an important impact on slowing cognitive or functional decline. Although the subgroup analysis suggested possible benefits from Aß clearance drugs, the analysis has limited credibility, and a benefit from drugs that increase clearance, if real, is very small. TRIAL REGISTRATION NUMBER: PROSPERO registration number CRD42019126272.