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Non-steroidal anti-inflammatory drugs (NSAIDs) have received increasing attention owing to their ubiquitous occurrence in environmental water systems and adverse effects. In order to monitor trace levels of NSAIDs from complex water samples, development of facile and efficient sample pretreatment is of great significance. Herein, a nitrogen-rich covalent organic polymer containing phenyl, triazine and amine groups was fabricated via solvent-free copolymerization. Then, utilizing nitrogen-rich covalent organic polymer as adsorbent for solid phase extraction cartridges, the pretreatment method was combined with high-performance liquid chromatography-diode array detection to quantify five representative NSAIDs (ketoprofen, carprofen, flurbiprofen, diclofenac and mefenamic acid) in environmental water samples. Under the optimal extraction conditions (adsorbent amount: 40 mg; NaCl concentration: 0%; pH 6; extraction time: 20min; eluent solvent: 4 mL of formic acid/acetonitrile (5%, v/v)), the proposed method provided low detection limits (0.06–0.2 μg L-1), wide linear ranges (0.2–100 μg L-1) with correlation coefficients (0.9991–0.9997) and acceptable precision (RSDs, 6.6–8.5% for intra-day, 7.2–9.5% for inter-day). The practical application of the method was confirmed through the successful determination of NSAIDs in tap water, surface water, and sewage. The recoveries in these samples at the four NSAIDs concentration levels ranged from 81.3% to 109.8%, with the RSDs lower than 7.8%.

Reducing the content of micropollutants, including pharmacological ones, in treated wastewater discharged to the receiver, as a result of the introduction of legislative changes, is currently an urgent matter. The commonly used biological wastewater treatment system does not remove it effectively, and expansion with a quaternary wastewater treatment step will be necessary. In the presented research, wastewater treated at a municipal wastewater treatment plant (WWTP) with the removal of biogenic compounds was subjected to further purification processes using hydrogen peroxide, Fenton’s reagent, UV254 irradiation and a combination of these methods, and, for comparison, coagulation with the use of FeSO4. The effectiveness of the methods was determined in terms of removing organic compounds, including non-steroidal anti-inflammatory drugs (fenoprofen, ketoprofen, paracetamol, naproxen, ibuprofen, diclofenac) and antibiotics (trimethoprim, sulfamethoxazole) and reducing the number of psychrophilic and mesophilic bacteria. The best effects of the removal of organic compounds (TOC) were achieved by the Fenton (43.9 %), Fenton+UV254 (51.4 %) and H2O2 (43.5 %), with final carbon concentrations of 7.9–9.1 mg C/L. The process configurations showed different effectiveness in removing pharmaceutical substances. The Fenton process or irradiation combined with H2O2 achieved the removal of all tested pharmaceuticals above 96 %, except for fenoprofen (in the range of 74–83 %) and ibuprofen (90–93 %). The use of UV254 irradiation had the best disinfection effectiveness. For an exposure time of 60 min, with and without H2O2, a higher than 99.99 % reduction in bacteria was achieved.

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed drugs that can reduce pain. This study aimed to measure the concentration of piroxicam and celecoxib in Iranian hospitals, as well as the effect of electron beam irradiation on the degradation of these pollutants in synthetic and real samples. The high-performance liquid chromatography (HPLC) was used to detect the residual analytes in the samples. The Response Surface Methodology (RSM) was used to design the experiment conditions that investigate the effect of electron beam irradiation on degradation of piroxicam and celecoxib from synthetic samples, and then according to the optimum condition, the experiments were carried out for real wastewater samples. The results of wastewater analysis shown that the mean concentration of PIRO and CELE were 6.32 ± 2.5 and 11.5 ± 3.2 μg/L, respectively. Also, the findings show that 98.98 % and 97.62 % of piroxicam and celecoxib was degraded, respectively, when the optimum conditions (pH = 4, electron beam irradiation = 8 kGy, and concentrations of 60 μg/L for piroxicam and 50 μg/L for celecoxib) were applied. Results show that the degradation rates of piroxicam and celecoxib in the real wastewater sample at optimum condition were 89.6 % and 84.25 %, respectively. So, electron beam irradiation is a long-lasting and promising method for removal emerging contaminants from wastewater, like non-steroidal anti-inflammatory drugs, that can't be removed by conventional wastewater treatment methods; so, it can be used in combination with conventional wastewater treatment methods.

A 44-year-old man with chronic idiopathic pseudo-intestinal obstruction and lumbar disc herniation presented with orthostatic dizziness, black vomiting, and stools. He was suspected to have an ulcer caused by nonsteroidal anti-inflammatory drugs and treated conservatively but continued to have transfusion-dependent anemia. Trans-arterial contrast-enhanced computed tomography showed multiple microbleeds in the small intestine. We diffusely embolized 7 small intestine branches of the superior mesenteric artery using imipenem/cilastatin on 2 separate occasions. This stopped the bleeding, and the patient progressed well without ischemic complications and was discharged on the 25th postoperative day.Transcatheter arterial embolization with imipenem/cilastatin may be a viable treatment option for patients with multiple small bowel bleeds in a large area of the small intestine that are unresponsive to conservative treatment or endoscopic methods.

Background: Current aspirin desensitization protocols for aspirin-exacerbated respiratory disease (AERD) require from 1 to 3 days to complete. Objective: Our aim was to assess the implementation of a 1-day versus 2-day aspirin desensitization protocol in patients with aspirin-exacerbated respiratory disease. Methods: We used a preintervention-postintervention quality improvement design to compare the completion rates, reaction rates, and estimated costs of a 2-day versus 1-day aspirin desensitization. The cost for each desensitization was estimated on the basis of 2017-2020 US Medicare standards. We included the predesensitization variables for FEV1 value, urinary leukotriene E4 level, absolute eosinophil count (AEC), and total IgE level for each group. Results: A total of 15 patients underwent a 2-day aspirin desensitization in the 4-year (2017-2020) preintervention period and were compared with 8 patients who underwent a 1-day aspirin desensitization in the 1-year (2021) postintervention period. The desensitization completion rate (93% vs 100% [P = 1]) and the mean number of reactions requiring intervention during the desensitization protocols (0.26 vs 0.8 [P = .14]) were similar between groups. The average time frame between last polypectomy and desensitization was longer in the 2-day group (1946 vs 39.2 days [P = .03]). The mean values for FEV1 level, urinary leukotriene E4 level, absolute eosinophil count, and total IgE level were 76% vs 83% (P = .6), 1084 vs 385 pg/mg (P = .2), 686 vs 306 cells/μL (P = .74), and 735 vs 278 kU/L (P = .5), respectively. The estimated direct cost reduction was $762 per aspirin desensitization for using 1-day vs 2-day aspirin desensitization. Conclusion: Compared with a 2-day protocol, the implementation of a 1-day aspirin desensitization was characterized by similar completion and reaction rates as well as lower costs.

The Gutong Patch (GTP) is common in clinical practice for bone diseases. This study compared the efficacy and safety of GTP and nonsteroidal anti-inflammatory drugs (NSAIDs) for KOA patients from 35 medical centers assigned to GTP, selective COX-2 inhibitor (SCI), GTP + SCI, non-selective COX-2 inhibitor (NSCI), and GTP + NSCI groups. The visual analog scale (VAS) pain score, EuroQol-VAS, EuroQol 5D-3 L, time to articular pain relief / disappearance, and joint motion recovery were the efficacy assessments. Safety assessments included contact dermatitis, gastrointestinal disorders, etc. The p-value

ABSTRACT: The objectives of this descriptive study were to (1) describe the pharmacokinetics of salicylic acid (SA) in the milk and plasma of postpartum dairy cattle following oral administration of acetylsalicylic acid (ASA; aspirin), (2) to estimate a recommended milk withdrawal period for dairy cattle treated with ASA, and (3) to determine the effect of ASA administration on plasma prostaglandin E2 metabolite (PGEM) concentrations. Primiparous (n = 3) and multiparous (n = 7) postpartum Holstein dairy cows received 2 oral treatments with ASA at 200 mg/kg of body weight, 24 h apart. Concentrations of SA in plasma and milk from 0 h through 120 h after ASA administration were analyzed using ultra performance liquid chromatography triple quadrupole mass spectrometry and a milk withdrawal period was estimated using the United States Food and Drug Administration Milk Discard App in R. Two withdrawal periods were estimated: (1) a whole-herd treatment scenario with no dilution factor and (2) an individual animal treatment scenario with a bulk tank factor included in analysis. Plasma PGEM concentrations in samples from 0 h to 24 h after ASA administration were determined using a commercially available competitive ELISA. Milk SA concentrations were undetected in all cows by 48 h after the last ASA treatment. Secondary peaks were observed in plasma at 58 and 82 h after the last treatment and in milk at 87 h after the last treatment. In the absence of a tolerance for SA in milk, the estimated milk withdrawal periods were (1) 156 h for the whole-herd treatment scenario and (2) 120 h for the individual animal treatment scenario. Plasma PGEM concentrations were reduced compared with baseline for up to 12 h after ASA administration, with the greatest reduction observed at 2 h. Results from this study suggest that the current milk withhold recommendation for dairy cattle administered ASA may need revision to 120 h (5 d) and that ASA administration may mitigate postpartum inflammation through reduction in prostaglandin production for up to 12 h after treatment. Pharmacokinetic and milk withdrawal data from this study will inform future recommendations for extra-label use of aspirin in postpartum dairy cows. Further research is required to determine the basis for the secondary SA peaks and to elucidate the long-term effects of ASA administration on dairy cow health.

الملخص: أهداف البحث: الاستعمالات المتكررة والطويلة الأمد للأدوية غيرالستيرويدية المضادة للالتهاب يؤدي الى عدة مخاطر، على الرغم من منافعها السريرية. تسمم الكبد هو أحد تلك المخاطر الذي يتسبب بواسطة الإجهاد التأكسدي ويمكن ان يؤثر على الشاكلة الشحمية. الهدف من الدراسة هو التحقق من إمكانية استعمال فيتامين سي كمضاد تأكسد قوي في عكس التأثيرات الضارة للديكلوفيناك صوديوم والنابروكسين في أكباد الجرذان غير البالغة وتسليط الضوء على علاقة تلك التاثيرات بالشاكلة الشحمية. طرق البحث: استخدمت الدراسة 40 أنثى جرذ غير بالغة. قسمت إلى 3 مجموعات: المجموعة الأولى تم إعطاؤها يوميا عن طريق الفم خمسة ملغرام لكل كيلوغرام من وزن الجسم ديكلوفيناك صوديم (15 جرذ)، والمجموعة الثانية تم إعطاؤها 50 مليغرام لكل كيلوغرام نابروكسين (15 جرذ) لمدة 21 يوم، أما المجموعة الثالثة المكونة من 10 جرذان فاستخدمت للمقارنة كمجموعة شاهدة. بعد نهاية الأسبوع الثالث للتجريع، تم معالجة خمسة جرذان من مجموعة الديكلوفيناك وخمسة جرذان من مجموعة النابروكسين بفيتامين سي (25 مليغرام/ كيلوغرام) يوميا عن طريق الفم. بعد ذلك، قدرت المعايير الكيميائية الحيوية لمصل الدم باستعمال عدد تجارية واستعمل إجراء روتيني للبحث النسيجي المرضي. النتائج: تم تسجيل ارتفاع شديد في مستويات ناقلة أمين الاسبارتات وناقلة أمين الالانين في مجموعتي الديكلوفيناك والنابروكسين بالنسبة إلى مجموعة المقارنة. كذلك، تأثرت البروتينات الشحمية العالية والمنخفضة الكثافة معنويا في المجموعتين الدوائية. أما بالنسبة لأنسجة الكبد فقد لوحظت علامات مرضية عديدة في كل من المجموعتين الدوائية. بعد المعالجة بفيتامين سي، لوحظ تحسن لافت للنظر في تلك التغييرات. الاستنتاجات: استطاعت المعالجة التالية بفيتامين سي أن تحسن كل التغييرات الناجمة عن تسمم الكبد بكل من الديكلوفيناك صوديوم والنابروكسين. Abstract: Objective: Despite the various clinical benefits of nonsteroidal anti-inflammatory drugs, their frequent and prolonged use has led to numerous health risks, including hepatotoxicity. Hepatotoxicity mediated by oxidative stress can affect the lipid profile. The objective was to investigate whether post-treatment with vitamin C can ameliorate the effects of diclofenac and naproxen in the livers of prepubertal rats and to highlight their relationship with lipid profile. Methods: Forty prepubertal female albino rats were distributed among the control group, the diclofenac-administered group (5 mg/kg/day), and the naproxen-administered group (50 mg/kg/day). This study included two phases. In Phase 1, only five rats from each group were dissected after 21 days of oral administration to assess the hepatotoxic effects of nonsteroidal drugs. In Phase 2, five of the remaining animals in each intervention group were post-treated with 25 mg/kg/day of vitamin C for an additional 21 days. After the administration and post-treatment, serum biochemical parameters and histopathological signs were evaluated. Results: Extreme elevation in the levels of aspartate and alanine aminotransferases was observed in the diclofenac and naproxen groups compared with those in the control (p < 0.001). In addition, the levels of high- and low-density lipoproteins were significantly impacted in these drug groups (p < 0.01, p < 0.05 respectively). Several pathological signs in the liver histology were observed in both drug groups. After post-treatment with vitamin C, noticeable amelioration of these alterations was observed. There were slightly elevation in the liver enzymes and insignificant increase and decrease in the high and low-density lipoproteins respectively. Conclusion: Vitamin C post-treatment ameliorated the hepatotoxicity induced by diclofenac sodium and naproxen.

Development of new adsorbents for the efficient removal of organic pollutants from water is one of the most emerging environmental issues. Current studies in this field focus on improving the adsorption capacity of various materials and/or broadening the pH range in which the adsorbents can efficiently remove target pollutants. In this study, we designed bifunctional hyper-cross-linked polymers (HCPs) containing both carbonyl and amine species to investigate the effect of amine functional groups on the efficiency of adsorptive removal of non-steroidal anti-inflammatory drugs (NSAIDs) from water. We revealed that post-synthesis functionalization of carbonyl-rich HCPs with amine species does not have a significant impact on the adsorption capacity of these polymers under strongly acidic conditions (pH < 4; q e  ∼ 544 mg/g), but significantly extends the pH range in which bifunctional polymers can adsorb diclofenac. For example, at native pH (pH ∼ 6), bifunctional HCP-based adsorbents exhibited an adsorption capacity approximately 8 times higher than that of pristine materials (q e  = 191 vs. 24 mg/g, respectively). Furthermore, it was revealed that the adsorbents designed in this study can efficiently remove diclofenac from complex water matrices and exhibit high stability in several adsorption-desorption cycles. Moreover, we demonstrated that selecting a cross-linker with a longer chain results in a polymer with a lower surface area and smaller average pore size, while enabling higher efficiency in amine incorporation via post-synthesis functionalization. This latter feature was crucial for ensuring the high adsorption capacity of HCP-based adsorbents in the removal of NSAID at neutral pH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-2-specific inhibitors provide significant analgesic and opioid-sparing benefits. However, these analgesics are commonly avoided owing to concerns of potential adverse effects. The evidence for NSAID-related adverse effects is conflicting and of poor quality, and these analgesics are safer than what has been implied. Thus, it is imperative that NSAIDs or COX-2-specific inhibitors are administered routinely unless there are well-founded contraindications., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

A new thin film was fabricated using Fe 3 O 4 @SiO 2 -polyoxometalate (POM) as the coating and it was coupled with a HPLC-UV to develop a method for the selective determination of ibuprofen, paracetamol and diclofenac (as the model analytes) from human plasma and urine samples. The prepared magnetic POM was coated on the pores and surface of cotton yarn to prepare the extracting device. The prepared sorbent was characterized by several techniques including: FT-IR, XRD, BET, SEM, and VSM analysis. Using a multivariate optimization strategy (Plackett-Berman design (PBD) and Box-Behnken Design (BBD)), extraction factors were optimized. The optimal condition is: pH=4, extraction time=23 min, desorption time=3 min, desorption volume=400 µL, and Na 2 SO 4 concentration=0.8 %. In the optimal condition, the linearity of the method was in the range of 0.5-200 µg l -1 . LODs, LOQs, and intra-day as well as inter-day RSDs were <0.24 µg L -1 , 0.81 µg L -1 , and 4.1 %, respectively. The enrichment factor (EF) values for the tested substances varied from 16 to 21. The absolute recoveries (ARs%) were also between 64 and 84 %. The sorbent extracted the analytes up to 32 times with little changes in the ER (95 ± 1.5). This method was successfully applied to detect target analytes in biological fluids, achieving high recovery. This novel approach combines efficiency with practicality, making it well-suited for field applications. In addition, the greenness and whiteness of the method (sustainability assessment) were evaluated using the qualitative green assessment tools including AGREE, BAGI and the white analytical chemistry assessment tool (RGB12). The high BAGI (72.5) and RGB 12 (94.7) scores confirmed the method's strong applicability, cost-effectiveness, and sustainability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A new sample preparation and determination method, including HPLC-DAD analysis after Magnetic Solid Phase Extraction (MSPE), was developed to monitor the trace amounts of two types of nonsteroidal anti-inflammatory drugs (NSAIDs), Ibuprofen (IBP) and Ketoprofen (KP). In the proposed method, IBP and KP analytes were extracted from newly synthesized magnetic-based sorbent in a pH 4.0 buffer medium and enriched by desorbing again with ethanol to a smaller volume before chromatographic determinations. The samples were filtered and transferred to HPLC vials before analysis. The experimental variables were optimized step by step such as adsorption time, desorption solvent, pH, etc. After preconcentration of IBP and KP molecules by MSPE, determination of target molecules was carried out by isocratic elution of 30 % Methyl alcohol, 40 % Trifluoro Acetic Acid (TFA) (0.1 %, v:v), 30 % Acetonitrile. By using optimized conditions, the detection limits of target molecules were calculated as 3.43 ng mL -1 and 3.48 ng mL -1 for IBP and KP, respectively. The triplicate measurements made with model solutions containing 100 ng mL -1 of target molecules, RSD %values were found below 3.50 %. The developed method was successfully applied to synthetic urine and pooling urine samples. Finally, the practicality and suitability for green analytical chemistry of the proposed method was evaluated by using Blue Applicability Grade Index (BAGI) and Green Analytical Procedure Index (GAPI)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Traditional blood drug analysis involves large blood consumption and complicated operations and a further reduction in blood consumption is urgently needed. Chip-based monolithic column microextraction is a good strategy for the pretreatment of small-volume samples, and new monolithic materials is the critical factor. Covalent organic frameworks (COFs) are good adsorbents due to large specific surface area and rich conjugated structure. However, the poor dispersion ability of COFs in prepolymer solution severely hinders the preparation of COFs doped monolithic columns. Herein, high internal phase emulsion with viscoelastic properties was adopted to fixed COF particles., Results: The COFs doped monolith exhibited a hierarchical porous structure and improved extraction efficiency for interest nonsteroidal anti-inflammatory drugs (NSAIDs) (68.2-77.3 vs 28.4-57.7 %). A chip-based monolithic column array was fabricated and coupled with high-performance liquid chromatography (HPLC)-ultraviolet detection for online determination of five NSAIDs in microlitre volume of blood. The throughput of the developed method was approximately 3 h -1 , mainly determined by the separation time (22 min) of target NSAIDs in HPLC. Under the optimal conditions (200 μL sample solution, pH = 3 at a sampling folw rate of 5 μL min -1 and 20 μL of acetonitrile/10 mmol L -1 NaOH (9/1, v/v) as desorbent), the detection limit of 4.39-15.5 μg L -1 was obtained for target NSAIDs in blood with RSD of 7.8-15.3 % and R 2 of 0.9943-0.9978. The method was applied to the analysis of human serum (20 μL) and dried blood spot, with recovery of 82.0-118 % for target NSAIDs., Significance: A method was proposed for the preparation of COF doped monolithic columns by emulsion polymerization, avoiding uneven distribution of COFs caused by their easy sedimentation in traditional free radical preparation of monolithic columns. Then a chip-based monolithic column array coupled with on-line HPLC-UV detection was established for the quantification of five NSAIDs in microlitre-blood samples. The developed method merits high automation and good anti-interference ability, with extremely low sample/reagents consumption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract During the past 20 years, we have witnessed the following trends in aspirin usage: (i) a “dropping” trend, characterized by the early discontinuation of low‐dose aspirin from dual antiplatelet therapy or triple antithrombotic therapy (oral anticoagulation plus dual antiplatelet therapy in patients with atrial fibrillation) following an acute coronary syndrome or after percutaneous coronary intervention; (ii) a “combinatorial” trend, featuring the addition of a lower dose of a P2Y12 inhibitor or direct oral anticoagulant drug to low‐dose aspirin for the long‐term treatment of stable patients with atherosclerotic cardiovascular disease; and (iii) a “repurposing” trend, characterized by growing interest in the oncologic community to assess the chemopreventive effect of aspirin against certain types of cancers (particularly of the gastrointestinal tract), both as primary prevention and adjuvant therapy. The aim of this review is to present the mechanistic rationale underlying these trends, discuss the design and findings of trials testing novel treatments or new therapeutic applications of aspirin, and report on the ISTH Congress results on this topic.

The overuse of nonsteroidal anti-inflammatory drugs (NSAIDs) poses many serious environmental and food safety concerns. Development of effective and sensitive sample pretreatment method for monitoring trace NSAIDs from complex samples is of great significance. Depending on the ionic and aromatic structures of NSAIDs, a cationic microporous organic network (MON) named TEPM-BBDC with large specific surface area, good solvent and thermal stabilities, and numerous interaction sites was designed and prepared for efficient solid-phase extraction (SPE) of four typical NSAIDs (flurbiprofen, ketoprofen, naproxen, and diclofenac sodium) from environmental water and milk samples. By anchoring the ionic groups in the conjugated MON frameworks, the prepared TEPM-BBDC offered good extraction for NSAIDs based on the π-π, hydrophobic, ion exchange, and electrostatic interactions. Under the optimal extraction conditions (initial concentration of each NSAID: 200 g L -1 ; sample volume: 50 mL; desorption solvent: 1.5 mL of MeOH + 1 % NH 3 ·H 2 O; sample loading rate: 5 mL min -1 ; NaCl concentration: 0 mmol L -1 ; pH = 5), the proposed TEPM-BBDC-SPE-HPLC-UV method owned wide linear range (0.50-1000 g L -1 ), low limits of detection (0.10-0.40 g L -1 ), large enrichment factors (92.2-99.2), good precisions (intra-day and inter-day, RSD% = 1.3-7.8 %, n = 6) and reproducibility (column-to-column, RSD% = 8.0 %, n = 3). The developed method also exhibited good recoveries (83.6-113.4 %) for the determination of NSAIDs in river water, lake water and milk samples. This work not only revealed the potential of TEPM-BBDC for SPE of ionic NSAIDs in complex samples, but also highlighted the prospect of ionic MONs in sample pretreatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this work, a novel polyaniline-modified magnetic microporous organic network (MMON-PANI) composite was fabricated for effective magnetic solid phase extraction (MSPE) of five typical nonsteroidal anti-inflammatory drugs (NSAIDs) from animal-derived food samples before high performance liquid chromatography (HPLC) detection. The core-shell sea urchin shaped MMON-PANI integrates the merits of Fe 3 O 4 , MON, and PANI, exhibiting large specific surface area, rapid magnetic responsiveness, good stability, and multiple binding sites to NSAIDs. Convenient and effective extraction of trace NSAIDs from chicken, beef and pork samples is realized on MMON-PANI via the synergetic π-π, hydrogen bonding, hydrophobic, and electrostatic interactions. Under optimal conditions, the MMON-PANI-MSPE-HPLC-UV method exhibits wide linear ranges (0.2-1000 μg L -1 ), low limits of detection (0.07-1.7 μg L -1 ), good precisions (intraday and inter-day RSDs < 5.4 %, n = 3), large enrichment factors (98.6-99.9), and less adsorbent consumption (3 mg). The extraction mechanism and selectivity of MMON-PANI are also evaluated in detail. This work proves the incorporation of PANI onto MMON is an efficient way to promote NSAIDs enrichment and provides a new strategy to synthesize multifunctional MON-based composites in sample pretreatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Molecularly imprinted ionic covalent organic framework nanocomposites (MI-IC-COF@SnO 2 ) were prepared as potential adsorbents for the enhanced adsorption of nonsteroidal anti-inflammatory drugs (NSAIDs) from aqueous solution. The resulting material exhibited a pompon mum-like structure, featuring a large surface area, and well-defined mesopores. The presence of uniform positive ions within the three-dimensional skeleton of MI-IC-COF@SnO 2 facilitated a rapid adsorption rate and high adsorption capacity for target analytes. Thermodynamic fitting revealed the adsorption process of NSAIDs to be feasible, endothermic, and spontaneous. Additionally, the adsorbent material exhibited respectable selectivity, as evidenced by imprinting factor values ranging from 2.8 to 6.7. Utilizing MI-IC-COF@SnO 2 as the sorbent, a solid-phase extraction method coupled with high-performance liquid chromatography-ultraviolet detection (SPE-HPLC-UV) was developed and optimized. The proposed method demonstrated good linear range with determination coefficients of 0.998-0.999, and low limit of detection (0.18-1.35 µg L -1 ). Recoveries of NSAIDs in urine and river water samples were 78.1 %-106.1 %, with relative standard deviations lower than 12.5 %. This rapid and sensitive method enables the determination of NSAIDs at trace levels in complex matrices, providing reliable and reproducible results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The total flavonoids of Desmodium styracifolium (TFDS) are flavonoid-rich extracts obtained from Desmodii Styracifolii Herba, which is approved for the treatment of urolithiasis in China. C-glycosylflavones including schaftoside, vicenin-1, vicenin-2, vicenin-3, and isovitexin are the main active constituents. In this study, the plasma protein binding of these compounds was determined for the first time in rat and human plasma by rapid equilibrium dialysis combined with HPLC-MS/MS method. The developed method was validated in terms of specificity, linearity, accuracy, precision, extraction effect, matrix effect, and stability. Schaftoside, vicenin-1, vicenin-2, and vicenin-3 exhibited moderate plasma protein binding, ranging from 56.6% to 61.5% in rat plasma and 55.0%-62.9% in human plasma. In comparison, isovitexin demonstrated a higher plasma protein binding in the range of 92.3-93.1% and 95.1-96.2% in rat and human plasma, respectively. Furthermore, the potential interactions mediated via plasma protein binding between isovitexin and nonsteroidal anti-inflammatory drugs (NSAIDs) were investigated by rapid equilibrium dialysis. No significant changes were observed, indicating a lower likelihood of interaction between TFDS and NSAIDs due to plasma protein binding in the treatment of urinary system disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with various side effects, including cardiovascular and hepatic disorders. Studies suggest that mitochondrial damage and oxidative stress are important mediators of toxicity, yet the underlying mechanisms are poorly understood. In this study, we identified that some NSAIDs, including diclofenac, inhibit autophagic flux in hepatocytes. Further detailed studies demonstrated that diclofenac induced a reactive oxygen species (ROS)-dependent increase in lysosomal pH, attenuated cathepsin activity and blocked autophagosome-lysosome fusion. The reactivation of lysosomal function by treatment with clioquinol or transfection with the transcription factor EB restored lysosomal pH and thus autophagic flux. The production of mitochondrial ROS is critical for this process since scavenging ROS reversed lysosomal dysfunction and activated autophagic flux. The compromised lysosomal activity induced by diclofenac also inhibited the fusion with and degradation of mitochondria by mitophagy. Diclofenac-induced cell death and hepatotoxicity were effectively protected by rapamycin. Thus, we demonstrated that diclofenac induces the intracellular ROS production and lysosomal dysfunction that lead to the suppression of autophagy. Impaired autophagy fails to maintain mitochondrial integrity and aggravates the cellular ROS burden, which leads to diclofenac-induced hepatotoxicity.

Background: Organ failure (OF) of acute pancreatitis (AP) significantly contributes to AP-related mortality. Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced complications of AP., Aims: We aimed to investigate whether NSAIDs ameliorates SIRS and OF in patients with AP., Methods: Eligible patients with AP were retrospectively identified in 4 hospitals between January 2015 and December 2018. Associations between peri-onset NSAIDs use (day -3 to day 3) and OF, persistent OF (POF), and SIRS within the first week were analyzed. Propensity score-matched (PSM) analysis and inverse probability of treatment-weighted (IPTW) analysis were used to estimate risk ratios., Results: Among 1,528 patients with AP (97 [6.3%] with NSAIDs use), 242 (15.8%) developed organ failure, 89 (5.8%) progressed to POF, and 27 (1.8%) died within 3 months. PSM analysis showed no association between peri-onset NSAIDs and OF (risk ratio [RR], 1.00; 95% confidence interval [CI], 0.46 to 2.15) and POF (RR, 0.80; 95% CI, 0.21 to 2.98). IPTW analysis yielded similar results. Patients with and without peri-onset NSAIDs use were comparable with respect to OF, POF, and SIRS across subgroups defined by COX-2 selectivity and dose., Conclusion: Peri-onset NSAIDs use was not significantly associated with reduced OF., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: Ketorolac is one of the most potent nonsteroidal anti-inflammatory drugs commonly used in spine surgery. The purpose of this study is to examine the impact of ketorolac utilization with or without other medications on a patient's postoperative course after lumbar surgery., Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed using PubMed, CINAHL, MEDLINE, and Web of Science in July 2023. Inclusion criteria were RCTs that used ketorolac for lumbar surgery., Results: Thirteen RCTs were included (N = 997; mean age, 54.6 ± 7.8 years; n = 535 in the ketorolac group) in this systematic review. There was no significant difference in the 24-hour and total postoperative morphine utilization (P = 0.185 and P = 0.109, respectively), 24-hour and final postoperative pain scores (0-10 scale) (P = 0.065 and P = 0.582, respectively), and length of stay at the hospital (P = 0.990) between patients in the ketorolac group and patients in the non-ketorolac group who underwent lumbar surgery. Overall, patients had similar rates of major complications (3.7% vs. 5.4%) and minor complications (42.1% vs. 51.7%) between groups after lumbar surgery. However, patients in the ketorolac group had a significantly lower rate of nausea and/or vomiting compared with the non-ketorolac group after lumbar surgery (21.6% vs. 37.1%, respectively; P = 0.018)., Conclusions: There is no significant difference in 24-hour and total postoperative morphine utilization, pain scores, or length of stay, with similar complication rates after lumbar surgery between patients receiving ketorolac and patients not receiving ketorolac via meta-analysis of RCTs., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction and aims: The chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause complications in the gastrointestinal tract. The use of proton pump inhibitors (PPIs) is recommended in high-risk patients to prevent them. Objective: The aim of this article was to evaluate the gastroprotection measures taken in persons with chronic NSAID use. Materials and methods: A descriptive cross-sectional study was conducted. The clinical records were reviewed of patients seen as outpatients at the Rheumatology Department over a 4-month period, choosing those with chronic NSAID use, and intentionally looking for gastroprotection measures according to the recommendations published by the American College of Gastroenterology. Results: A total of 417 patients (347 women; mean age: 48.12 ± 14.2 years) were included. The most frequent diagnosis was rheumatoid arthritis (65%). Nine patients (2.1%) had a history of peptic ulcer, 48 (11.5%) patients were 65 years of age or older, 26 (6.2%) patients took NSAIDs and aspirin, and 130 (31.2%) took NSAIDs with steroids. Tests for Helicobacter pylori infection were done in just 53 cases, and there were positive results in only 9 (16%). Some risk for gastrointestinal toxicity was established in 211 cases and only 65 (30.8%) received gastroprotection. In contrast, 31 (15%) patients received gastroprotection when there was no indication for it. Conclusion: Prophylaxis with PPIs in chronic NSAID users was inadequately employed. It was not prescribed in the majority of patients (69.2%) and it was used with no justification in others (15%).

A novel ferrofluid of Fe 3 O 4 nanoparticles and a deep eutectic solvent (DES) composed of menthol and pentanoic acid was introduced as a green microextraction medium. The ferrofluid was successfully used as an extractant for vortex-assisted liquid-liquid microextraction (VALLME) of nonsteroidal anti-inflammatory drugs (NSAIDs) in environmental waters prior to their determination by HPLC-DAD. Once the ferrofluid was dispersed in the sample by vortex agitation, phase separation could be easily achieved by placing a neodymium magnet next to the tube, which eliminated the centrifugation step and simplified the operational procedure. As a result, the sample pretreatment took only ≈2 min. The experimental parameters, including pH, nanoparticle amount, ferrofluid volume, vortex time, salt amount, and disruptive solvent type and its volume, were optimized stepwise. The method showed linear behavior for all NSAIDs from 5 to 100 μg/L, with limit of detection values and enrichment factors in the ranges of 1.68-2.05 μg/L and 38.9-50.6, respectively. Intra- and Inter-day accuracies obtained from the analysis of spiked river, lake, and tap water samples at low and high-quality control levels (20 and 80 μg/L) ranged from 90.3% to 108.0%, with relative standard deviations less than <12.3%. The results of this study demonstrate that the use of DES-based ferrofluid in VALLME can be considered a simple, environmentally friendly, and reliable alternative for the determination of NSAIDs in environmental waters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The acute treatment of migraine attacks should provide rapid, effective, and long-lasting symptom relief, causing minimal adverse effects. For this purpose, there are several specific and nonspecific acute treatments. In this chapter, we focus on molecules not specifically designed for migraines, including anti-inflammatory not specific analgesics, such as acetaminophen, acetylsalicylic acid, and other non-steroidal anti-inflammatory drugs (or COX-2 inhibitors); antinausea medications like metoclopramide or prochlorperazine, which can alleviate sickness and vomiting associated with migraines, and may also have a direct painkiller effect; combinations of simple analgesics or association of a painkiller with caffeine. This stimulant can help enhance the pain-relieving effects of some headache medications and provide its own analgesic effect; physical approaches: applying cold packs or heating pads on the forehead or neck, can help relieve migraine pain; other classes with limited to no evidence to support their use, such as intravenous corticosteroids or antiepileptic drugs as sodium valproate. Finally, we will briefly mention opioids, barbiturates, or medical cannabis, bearing in mind that their use is not recommended by current guidelines., (Copyright © 2024 Elsevier B.V. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Prostaglandins (PGs) increase in bone in response to mechanical loading and stimulate bone formation. Inhibition of cyclooxygenase (COX), the enzyme responsible for PG synthesis, by non-steroidal anti-inflammatory drugs (NSAIDs) impairs the bone formation response to loading in animals when administered before, but not after, loading. The aim was to determine whether the timing of ibuprofen use (400 mg before versus after exercise sessions) is a significant determinant of the adaptive response of BMD to exercise training in older adults. We hypothesized that taking ibuprofen before exercise would attenuate the improvements in total hip and lumbar spine BMD in response to 36 weeks of training when compared with placebo or with ibuprofen use after exercise. Untrained women and men (N = 189) aged 60 to 75 years were randomly assigned to 1 of 3 treatment arms: placebo before and after exercise (PP); ibuprofen before and placebo after exercise (IP); and placebo before and ibuprofen after exercise (PI). The difference between groups in the change in BMD was not significant when IP was compared with either PP (hip, −0.5% (−1.4, 0.4); spine, 0.1% (−0.9, 1.2)) or PI (hip, 0.3% (−0.6, 1.2); spine, 0.5% (−0.5, 1.5)). Ibuprofen use appeared to have more adverse effects on BMD in women than men. The study demonstrated that ibuprofen use did not significantly alter the BMD adaptations to exercise in older adults, but this finding should be interpreted cautiously. It had been expected that the inhibition of bone formation by ibuprofen would be more robust in men than in women, but this did not appear to be the case and may have limited the power to detect the effects of ibuprofen. Further research is needed to understand whether NSAID use counteracts, in part, the beneficial effects of exercise on bone.

Background: Nonsteroidal anti-inflammatory drugs are the first-line option for treating ankylosing spondylitis (AS) in China. However, no large-scale controlled trials have been conducted in this ethnic population. Objective: To evaluate the efficacy and safety of 6 weeks’ treatment with celecoxib in patients with AS in China. Methods: This Phase 3, double-blind, parallel-group study randomized patients with AS aged ≥18 to 65 years 1:1 to receive celecoxib 200 mg once daily or diclofenac sustained release 75 mg once daily. After 6 weeks, patients could use celecoxib 400 mg once daily or maintain blinded therapy. The primary efficacy end point was mean change from baseline at Week 6 for Patient’s Global Assessment of Pain Intensity score (100-mm visual analog scale). Noninferiority was established if the upper bound of the CI was

Objetivo: Conocer la evolución y la variabilidad en el consumo de los antiinflamarios no esteroideos clásicos (AINE) en las áreas de salud de Costa Rica durante el período 2000-2005. Métodos: Se estudiaron los siguientes medicamentos: ibuprofeno, indometacina, penicilamina, sulindaco, tenoxican y diclofenaco sódico. Se utilizó como medida de consumo la dosis diaria definida por 1.000 habitantes y día (DHD), y en el análisis de variabilidad el coeficiente de variación ponderado por el tamaño de población (CVw), el rango extremo, el rango interpercentil, los gráficos de puntos y los mapas con categorías de consumo. Resultados: En el período 2000-2005 el consumo de los AINE creció un 48% y el coste anual se incrementó un 184%. Los medicamentos de mayor consumo y participación en el gasto fueron sulindaco e indometacina. El consumo de los AINE varió entre 0,1 y 60,39 DHD según las áreas de salud, con un CVw del 66,38%. Los medicamento con mayor variabilidad fueron penicilamina (CVw del 449,89%) y tenoxican (CVw del 315,26%). Conclusiones: Hay un patrón geográfico diferenciado en el consumo de AINE en el país, y tasas muy diferentes dentro de una misma región. Dos posibles factores asociados a esta variabilidad, según los resultados obtenidos, son la oferta de servicios médicos y el porcentaje de población mayor de 65 años adscrita al área de salud.Objective: To determine changing patterns and variability in consumption of classic nonsteroidal anti-inflammatory drugs (NSAIDs) among the health areas in Costa Rica between 2000 and 2005. Methods: The drugs studied were ibuprofen, indomethacin, penicillamine, sulindac, tenoxicam, and diclofenac sodium. To measure consumption, we used the defined daily dose per 1,000 inhabitants per day (DID). To analyze variability, the coefficient of variation weighed by the population size (CVw), extremal ratio, interquartile ratio, dot plot and map graphs were used. Results: From 2000-2005, NSAID consumption increased by 48% and the annual cost rose by 184%. The drugs with greatest consumption and participation in cost were sulindac and indomethacin. NSAID consumption varied between 0.1 and 61.8 DID according to health areas, with a CVw of 66.8%. Variability was greatest with penicillamine (CVw = 449.89%) and tenoxicam (CVw = 315.26%). Conclusions: Clearly differentiated geographical patterns in NSAID consumption were found in Costa Rica, with very different rates within the same region. According to the results obtained, two factors associated with this variability were the supply of health services and the percentage of the population aged 65 years or more within the catchment area.

A workshop, “Chemopreventive properties of nonsteroidal anti-inflammatory drugs (NSAIDs): Role of COXdependent and -independent mechanisms,” sponsored by the Chemical and Physical Carcinogenesis Branch, Division of Cancer Biology of the National Cancer Institute, was held in Rockville, Maryland, on January 8, 2001. The workshop was composed of two parts: oral presentations by a series of speakers, and a group discussion of preselected topics.

Background: Immune checkpoint inhibitors (ICI) are commonly used in the management of patients with advanced non-small cell lung cancer (NSCLC), but response is suboptimal. Preclinical data suggest ICI efficacy may be enhanced with concomitant nonsteroidal anti-inflammatory (NSAID) medications., Patients and Methods: In this retrospective study, the Veterans Health Administration Corporate Data Warehouse was queried for patients diagnosed with NSCLC and treated with ICI from 2010 to 2018. Concomitant NSAID use was defined as NSAID dispensation by a VA pharmacy within 90 days of the any ICI infusion. To mitigate immortal time bias, patients who started NSAIDs 60 or more days after ICI initiation were excluded from analysis. Survival was measured from start of ICI., Results: We identified 3634 patients with NSCLC receiving ICI; 2336 (64.3%) were exposed to concomitant NSAIDs. On multivariable analysis, NSAIDs were associated with better overall survival (HR = 0.90; 95% CI, 0.83-0.98; P = .010). When stratifying by NSAID type, diclofenac was the only NSAID with significant association with overall survival (HR = 0.75; 95% CI, 0.68-0.83; P < .001). Propensity score matching of the original cohort yielded 1251 patients per cohort balanced in characteristics. NSAIDs remained associated with improved overall survival (HR = 0.85; 95% CI, 0.78-0.92; P < .001)., Conclusion: This study of Veterans with NSCLC treated with ICI demonstrated that concomitant NSAIDs are associated with longer OS. This may indicate that NSAIDs can enhance ICI-induced antitumor immunity and should prospectively validated., Competing Interests: Disclosure NTS has no disclosures. WAS has no disclosures. MB has no disclosures. RJ has no disclosures. DAG has no disclosures. ZH has no disclosures. AB has no disclosures. VS has no disclosures. MCL has no disclosures. SSR has received grant funding and/or other support (for consultancy) from Amgen, AstraZeneca, Bristol-Myers Squibb, Merck, Takeda, Tesaro, Advaxis, AbbVie, and Genentech/Roche. VPS is on the SAB of BERG and HiFiBio Therapeutics, and an equity holder in Aggamin Pharmaceuticals and Victa Biotherapeutics. DM has received travel support and speaking honoraria from Varian Medical Systems., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prescribed pharmacologic therapies worldwide due to their therapeutic analgesic efficacy and relative tolerability. In the past several decades, various cardiovascular (CV) adverse events have emerged regarding both traditional NSAIDs (tNSAIDs) and cyclo-oxygenase 2 (COX-2) selective (coxibs). This review will provide an updated report on the CV risk profile of NSAIDs, focusing on several of the larger clinical trials, meta-analyses, and registry studies. We aim to provide rheumatologists with a framework for NSAID use in the context of rheumatologic chronic pain management. Recent findings: In patients with and without CV diseases, the use of NSAIDs, both tNSAIDs and coxibs, is associated with an increased risk of adverse CV events, myocardial infarction, heart failure, and cerebrovascular events. These CV risks have increased within weeks of coxib use and higher doses of tNSAIDs. The risk of adverse CV events is heterogenous across NSAIDs; naproxen and low-dose ibuprofen appear to have lower increased CV risk among NSAIDs. A variation in CV risk is associated with multiple factors, including NSAID class, COX-2 selectivity, treatment dose and duration, and baseline patient risk. Summary: Many important questions remain regarding the safety of NSAIDs and whether the culmination of research performed could inform us whether specific patient subtypes or NSAID class may have a more favorable profile. tNSAIDs such as naproxen and low-dose ibuprofen may have a lower CV risk profile, while coxibs have a more favorable GI risk profile. In general, any NSAID can be optimized if used at the lowest effective dose for the shortest amount of time, especially among individuals with increased CV risk., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Exposure to active pharmaceutical ingredients (APIs) from both human and veterinary sources is an increasing threat to wildlife welfare and conservation. Notwithstanding, tracking the exposure to pharmaceuticals in non-target and sensitive vertebrates, including birds, is seldom performed and relies almost exclusively on analysing internal organs retrieved from carcasses or from experimentally exposed and sacrificed birds. Clearly, this excludes the possibility of performing large-scale monitoring. Analysing feathers collected from healthy birds may permit this, by detecting APIs in wild birds, including protected and declining species of waterbirds, without affecting their welfare. To this end, we set up a non-destructive method for analysing the presence of non-steroidal anti-inflammatory drugs (NSAIDs), selective serotonin reuptake inhibitors (SSRIs) and noradrenaline reuptake inhibitors (SNRIs) in the feathers of fledglings of both the Mediterranean gull (Ichtyaetus melanocephalus) and the Sandwich tern (Thalasseus sandvicensis). The presence of several NSAIDs and SSRIs above the method quantification limits have confirmed that feathers might be a suitable means of evaluating the exposure of birds to APIs. Moreover, the concentrations indicated that waterbirds are exposed to NSAIDs, such as diclofenac, ibuprofen and naproxen, and SSRIs, such as citalopram, desmethylcitalopram, fluvoxamine and sertraline, possibly due to their widespread use and incomplete removal in wastewater treatment plants (WWTPs). The active ingredient diclofenac raises a the primary concern for the ecosystem and the welfare of the waterbirds, due to its high prevalence (100% and 83.3% in Mediterranean gull and Sandwich tern, respectively), its concentrations detected in feathers (11.9 ng g -1 and 6.7 ng g -1 in Mediterranean gull and Sandwich tern, respectively), and its documented toxicity toward certain birds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Treating pain in the context of chronic kidney disease (CKD) is challenging because of altered pharmacokinetics and pharmacodynamics, with an increased risk of toxicity and drug adverse events in this population. The aims of this systematic review and meta-analysis were to assess the prevalence of analgesic use and establish the risk of analgesics-related adverse events, in patients with CKD., Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Medline, Embase, CINAHL, and CENTRAL were searched until January 2021. Random-effects meta-analyses and meta-regression were conducted to pool and summarise prevalence data and measures of association between analgesic use and adverse events., Results: Sixty-two studies relevant to the prevalence of analgesic use and 33 to analgesic-related adverse events were included, combining data on 2.3 and 3 million individuals, respectively. Pooled analyses found that 41% (95% confidence interval [CI], 35-48) of the CKD population regularly use analgesia. The annual period prevalence was estimated at 50% for opioids and 21% for nonsteroidal anti-inflammatory drugs (NSAID). Overall, 20% and 7% of patients with CKD are on chronic opioid or NSAID therapy, respectively. Opioid use was associated with an increased risk of death (1.61; 95% CI, 1.12-2.31; n= 7, I 2 = 91%), hospitalisation (1.38; 95% CI, 1.32-1.45; n=2, I 2 =0%), and fractures (1.51; 95% CI, 1.16-1.96; n=3, I 2 =54%)., Conclusion: High levels of analgesic consumption and related serious adverse outcomes were found in patients with CKD. Consideration needs to be given to how these patients are assessed and managed in order to minimise harms and improve outcomes., Clinical Trial Registration: CRD42019156491 (PROSPERO)., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

A high-performance version of in-line, three-phase direct immersion-single drop microextraction (DI-SDME) coupled with capillary electrophoresis (CE) was demonstrated using a commercial CE instrument, and all the major and minor details were described to provide an easy-to-follow and user-friendly protocol. The excellent sample cleanup and enrichment power of this method was demonstrated with nonsteroidal anti-inflammatory drugs (NSAIDs) in human urine. The only preparation of urine samples was the addition of HCl to acidify the urine sample to pH 2. The acidic NSAIDs in the acidified urine sample were extracted into a basic acceptor drop covered with a thin organic layer attached to the inlet tip of a capillary immersed in the sample. A simple but powerful DI-SDME-CE method could be carried out automatically without any modification of the existing CE instrument. For improved performance, sample agitation and heating were employed by installing a microstirrer and a thermostating jacket in the sample tray. With 10 min of DI-SDME at 35°C with stirring, NSAIDs such as ketoprofen, ibuprofen, and naproxen in urine were enriched 340-970-fold with intraday and interday RSDs of 0.8-2.4% and 1.1-3.6%, respectively. The LODs obtained with in-line coupled CE/UV were 10-50 nM (2-10 µg/L). The performance of DI-SDME-CE/UV was also demonstrated by determining the naproxen level in human urine collected 24 h after taking a single oral dose of the drug. The spike recovery of naproxen from a single-point standard addition to the urine sample was 80%. Our high-performance three-phase DI-SDME-CE method is quite promising for the analysis of ionizable trace analytes in a complex sample matrix., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

A novel microchip electrophoresis method with conductivity detection for the determination of nonsteroidal anti-inflammatory drugs (NSAIDs) in several pharmaceutical formulations was developed. The three frequently used NSAIDs - acetylsalicylic acid, diclofenac and ibuprofen were baseline separated on a poly(methyl methacrylate) microchip with coupled separation channels. Elimination of matrix components such as excipients, was realized through online combination of isotachophoresis (ITP) with zone electrophoresis (ZE). ITP-ZE hyphenation can also facilitate preconcentration of target analytes. ITP was carried out in the first separation channel at pH 6.5, while the second channel of the microchip was used for ZE separation and detection of the analytes at pH 7.0. The developed ITP-ZE method was demonstrated to be applicable for direct and reliable determination of NSAIDs in eleven pharmaceutical formulations. The noticeable advantage of this approach is that only simple sample pretreatment (filtration and dilution) is necessary. The method performance parameters, such as linearity (20-250% of nominal concentration of studied NSAIDs in the test samples), accuracy (98-102%) and precision (less than 2% RSD) were obtained. This universal approach is suitable for the determination of frequently used NSAIDs in a single analysis in less than 15 min. In addition to simple sample pretreatment, low running costs and minimal environmental impact could make this method attractive for the analysis of pharmaceutical preparations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

MIL-101(Cr) and graphene aerogel (GA) were hybridized as a multifunctional adsorbent for the preconcentration of trace analytes. The novel MIL-101(Cr)@GA was prepared and characterized by FTIR, XRD and SEM, where GA is serving as a carrier for MIL-101(Cr). The synthesized composite as a solid phase extraction (SPE) sorbent combined with UPLC-MS/MS was applied for the determination and quantification of five NSAIDs (phenacetin, meloxicam, naproxen, diclofenac sodium and carprofen) in different environmental water samples. The parameters influencing the whole extraction process were systematically optimized. Under the most favorable. conditions, good sensitivity was achieved with a limit of detection between 0.006 and 0.012 ng mL -1 , the linear range of 0.02-2 ng mL -1 for phenacetin, meloxicam and 0.05-5 ng mL -1 for naproxen, diclofenac sodium, carprofen (r 2  ≥ 0.9940). The satisfactory recoveries of the target analytes were in the range from 77.2 to 103.3% with relative standard deviation (RSD) from 0.6% to 8.4%. The established method was proved to be simple, highly sensitive and accurate. The adsorbent could be reusable up to nine cycles without any decrease in performance, which provides economic strategy and little waste generation. Adsorption behaviors were explored by choosing two typical types of NSAIDs as models to measure the adsorption capacity of MIL-101(Cr)@GA. The maximum adsorption capacities for PHE and NAP were 232.5 and 333.3 mg g -1 , respectively., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The in-situ synthesis and application of nanocubic Co 3 O 4 -coated graphene oxide (Co 3 O 4 @ GO) was introduced for the first time to present a cost-effective, stable and convenient operation and a simple device for hollow fiber solid-phase microextraction (HF-SPME) of four selected nonsteroidal anti-inflammatory drugs (NSAIDs) including diclofenac, mefenamic acid, ibuprofen and indomethacin. The extracted analytes were desorbed by an appropriate organic solvent and analyzed via high-performance liquid chromatography-ultraviolet detection (HPLC-UV). The prepared sorbent was approved using different characterization methods such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). The variables effective on the Co 3 O 4 @GO-HF-SPME method including extraction time, desorption time, desorption solvent volume, sample pH, stirring rate and ionic strength were screened via Plackett-Burman design and then optimized by Box-Behnken design. Under optimal condition, the calibration curves were linear within the range of 1.0-200.0 µg L -1 of analyte concentration with detection limits of 0.18-1.1 µg L -1 and the relative standard deviations less than 10.1%. The limits of quantification (LOQs) were in the range of 0.60-3.67 µg L -1 . Matrix effect was not observed with this method; therefore, standard addition is not necessary for quantification of target compounds. The enrichment factors were obtained in the range of 49-68. The relative recoveries of the urine sample analysis were calculated in the range of 93-102%. Finally, the presented method exhibited good sensitivity, excellent repeatability, high reusability and acceptable precision, which will be a promising method to analyze various nonsteroidal anti-inflammatory drugs in urine samples., Competing Interests: Declaration of Competing Interest The author declares to have no conflict of interests., (Copyright © 2021. Published by Elsevier B.V.)

Pain is a global health priority that is challenging to asses. Here we propose a new approach to estimating the burden of pain treatment in a population using wastewater-based epidemiology (WBE). WBE is able to quantify multiple pharmaceutical compounds in order to estimate consumption by a population. Wastewater samples collected from areas representing whole communities can be analysed to estimate the consumption of drugs used to treat pain, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. The collection and analysis of wastewater can be conducted systematically to estimate the total consumption of NSAIDs and/or opioids in the population of a catchment area and to compare changes over time within the catchment or between different catchment populations. Consumption estimates can be combined by standardising the mass consumed to Defined Daily Doses (DDD) or morphine equivalents in order to assess, the population burden of pain treatment from mild to moderate (for NSAIDs) and for strong and severe pain (for opioids). We propose this method could be used to evaluate the total pain treatment burden between locations and over time. While this concept shows promise, future studies should evaluate the applicability as a tool to measure the burden of pain receiving treatment in a community., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The aim of this prospective, randomized, double-blind clinical trial was to evaluate the effect of a preoperative, single, oral dose of diclofenac potassium (DFK) on postoperative pain and rescue analgesic intake in patients with symptomatic irreversible pulpitis in mandibular molars treated in 1 visit., Methods: Seventy emergency patients with moderate to severe preoperative pain randomly received either 50 mg DFK or placebo tablets 1 hour before starting endodontic treatment (n = 35 per group). Patients recorded their pain level 6, 12, 24, and 48 hours after treatment on a 170-mm Heft-Parker visual analog scale. The incidence of rescue analgesic intake was also recorded. Outcome data were statistically analyzed using Mann-Whitney U, Friedman, Wilcoxon signed rank, and chi-square tests. Binary logistic regression assessed the association of predisposing factors with postoperative pain. The significance level (α) was set at 0.05., Results: Of the 70 patients, 68 were analyzed (n = 34 per group). Both groups had similar baseline characteristics (P > .05). DFK showed significantly less pain incidence and intensity than the placebo at 48 hours only (P < .05). A significant decrease occurred from 24 to 48 hours with DFK (P < .05), which was not recorded with the placebo (P > .05). No difference in the incidence of rescue analgesic intake was reported between groups (P > .05). Food intake timing, sex, and rescue analgesic intake were associated with postoperative pain (P < .05)., Conclusions: Premedication by a single, oral dose of 50 mg DFK could be effective in reducing postendodontic pain at 48 hours after 1-visit endodontic treatment in mandibular molars with symptomatic irreversible pulpitis., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

The present study included the procedure of preparing porous titania thin film using a direct nanocrystalline cellulose templating (NCC) as a bio-template. The microextraction applicability of the porous film was investigated by thin film microextraction (TFME) of the nonsteroidal anti-inflammatory drugs (NSAIDs) including ketorolac, meloxicam, diclofenac and mefenamic acid from different types of urine sample. The extracted NSAIDs were analyzed by HPLC-UV. Under optimum conditions, the calibration curves were linear within the range of 1.0-500 µg L -1 (2.0-200 µg L -1 for ketorolac, 2.0-500 µg L -1 for meloxicam, 1.0-200 µg L -1 for diclofenac and 1.0-200 µg L -1 for mefenamic acid). The limit of detection was found to be between 0.2 and 0.5 µg L -1 . The calculated intra- and inter-day relative standard deviations RSDs% (n = 3) at concentration level of 10 µg L -1 were less than 6.3% and 6.0%, respectively. Finally, the method was successfully applied to determine selected NSAIDs in urine samples from different human individuals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To investigate the effectiveness of preemptive analgesia with nonsteroidal anti-inflammatory drugs (NSAIDs) for the relief of inflammatory events (pain, edema, and trismus) after surgical removal of third molars., Materials and Methods: A two-phase PROSPERO-registered systematic review was conducted in accordance with the PRISMA statement. PubMed, Scopus, Web of Science, COCHRANE, LILACS, DOSS, and gray literature were searched using the following terms (MeSH) or their combinations: molar, third; anti-inflammatory agents, non-steroidal; analgesia; preoperative period; pain management., Results: From a total of 2903 articles, 31 (n = 2184 subjects) were selected. All studies presented a low risk of bias but exhibited high heterogeneity in methodology. Ten studies were selected for the meta-analysis. Preemptive analgesia for removal of third molars reduced average pain scores, especially those 1 h and 6 h after surgery (n = 151, p < 0.001, 95% CI = -2.81 to -0.97), reduced the average consumption of medication, and decreased the number of patients requiring medication without affecting the average time for its first consumption., Conclusion: In summary, most NSAIDs showed good results for inflammatory events and reduced average pain scores and consumption of rescue medication. However, more homogeneous and well-delineated clinical studies are necessary to determine a possible association between NSAIDs and the relief of inflammatory events., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier Ltd.)