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Background: NSAIDs are commonly used as first line therapy in chronic nonbacterial osteomyelitis (CNO) but are not effective for all patients. The objective of this study was to identify clinical variables associated with NSAID monotherapy response versus requiring second-line medication in a single-center cohort of patients with CNO. Methods: The charts of children with CNO who attended a CNO clinic at a quaternary care center between 1/1/05 and 7/31/21 were retrospectively reviewed. Patients were divided into 3 groups: NSAID-short (NSAID monotherapy for 3 to < 7 months), NSAID-long (NSAID monotherapy for ≥ 7 months), or second-line treatment. Patients were also categorized by which bodily regions were affected by CNO. Multiple linear and logistic regression models were constructed to predict total NSAID monotherapy days and the odds of needing second-line treatment, respectively. These models were optimized using variable combinations that minimized multicollinearity and maximized predictive power, as indicated by minimized AIC values. Results: One-hundred-sixty-four patients fulfilled inclusion criteria. Thirty-two patients were in the NSAID-short group, 62 in the NSAID-long group, and 70 in the second-line treatment group. Comparing the two NSAID groups showed that patients with unifocal disease at diagnosis required 47% fewer days of NSAIDs than those with multifocal disease. Results from logistic regression indicated that for each additional region affected, the odds of needing second line treatment increased by 1.94 times (p = 0.01) and that patients with symmetric bone lesions were 6.86 times more likely to require second-line treatment (p < 0.001). Conclusions: Patients with unifocal CNO involvement at diagnosis were more likely to require shorter NSAID treatment. Patients with more regions affected and those with symmetric bone lesions were more likely to require second-line treatment. [ABSTRACT FROM AUTHOR]

Aim: to present current data about the frequency and risk factors of upper gastrointestinal complications associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the possibilities of preventing these complications.Key points. The incidence of gastrointestinal complications associated with NSAIDs is 14.7–30.1 %, with the maximum risk noted in the first two weeks of their administration. The use of selective cyclooxygenase-2 inhibitors is associated with a reduced risk of gastrointestinal complications. All patients who are going to receive NSAIDs should be diagnosed with H. pylori and treated with eradication therapy if this infection is detected. Even in patients without risk factors for gastrointestinal complications and with short courses of therapy, coxibs or a combination of NSAIDs and proton pump inhibitors may be considered. Prevention of NSAID-associated lesions of the upper gastrointestinal tract is an indication for the appointment of omeprazole and esomeprazole in accordance with the instructions for medical use. Esomeprazole has a number of pharmacokinetic advantages — a large area under the pharmacokinetic curve, the ability to inhibit CYP4502C19, which determines the high efficiency of therapy in fast and ultrafast metabolizers. Previous clinical studies of esomeprazole for the prevention of NSAID-associated lesions of the upper gastrointestinal tract demonstrate high efficacy. In the randomized OBERON study the risk of gastric and duodenal ulcers after 3 months of low-dose acetylsalicylic acid treatment in the esomeprazole group was 7 times lower.Conclusion. Assessment of risk factors, correction of modifiable risk factors, selection of safer NSAIDs and simultaneous administration of proton pump inhibitors (including esomeprazole) are effective prevention of NSAID-associated upper gastrointestinal lesions.

Background and Objective: Pain is the most common symptom compelling an individual to seek medical attention. The use of Vitamin D3 for nociceptive and inflammatory pain is highly debated. Therefore, this study was undertaken to compare three daily doses (15/30/60 μg/kg) and a single high dose of Vitamin D3 (260 μg/kg) to standard drugs, namely tramadol and diclofenac in two most resorted pain-models in mice. Materials and Methods: Thirty-six Swiss-albino mice were divided into six groups of six mice each. The experiment was conducted using hot plate and writhing test. Same groups of mice were reused after suitable wash-out period. Groups were dosed with 0.25% carboxymethyl-cellulose (negative-control), a positive-control (tramadol for hot-plate and diclofenac for writhing-test). Injection Vitamin D3 was given in three daily doses of 15/30/60 μg/kg. Single dose of 260 μg/kg of Vitamin D3 was also tested. Latency period (LP), percent of maximal-possible-antinociceptive-effect (%MPE), mean number and percentage inhibition of writhes were the parameters evaluated to compare analgesic effect. Data were analyzed using paired t-test, analysis of variance (ANOVA)/Kruskal–Wallis/Friedman’s-ANOVA, and repeated-measures ANOVA with post hoc Dunnett’s tests. Results: In hot-plate method, 60 and 260 μg/kg of Vitamin D3 raised mean LP when compared to baseline and negative control and all groups recorded higher percentage MPE values when compared to negative control. In writhing test, 15-, 30-, and 60 μg/kg/day showed analgesic effect in comparison to negative control. However, 15 and 30 μ/kg/day of Vitamin D3 contradicted its responses when assessed through different parameter. Interpretation and Conclusion: In hot-plate test, 60 and 260 μg/kg of Vitamin D3 showed significant analgesic effect; however, effects were not superior to tramadol. In writhing test, 15-, 30-, and 60 μg/kg/day showed significant analgesic effect which were not superior to diclofenac. Surprisingly, 15 and 30 μ/kg, on instances exhibited irritant effects.

Background. Nonsteroidal anti-inflammatory drugs, muscle relaxants, massage, physiotherapy procedures (standard therapy –ST) are widely used in chronic the chest wall pain syndrom (CWPS). Complex therapy (CT) is more effective with CWPS, including additionally personalized kinesiotherapy, psychological treatment methods and the introduction of anesthetics and corticosteroids into the area of identified sources of pain. There are few studies comparing the effectiveness of standard and complex therapy in CWPS, which was the purpose of our study. Aim. To compare the effectiveness of ST and CT for patients with CWPS. Materials and methods. One hundred four patients with CWPS were observed, of which 52 patients (19 men and 33 women, 49±14.6 y.o.) received ST, 52 patients (20 men and 32 women, 47±15.8 y.o.) received CT. Pain intensity was assessed using a digital rating scale, the presence of mental disorders – according the Hospital Anxiety and Depression Scale (HADS), functional status – according to the Oswestry questionnaire, quality of life – according to the SF-12 questionnaire. Results. After 6 months of therapy, the decreases were observed in the intensity of pain from 6.32±0.48 to 3.53±1.9 points in the ST group and from 6.64±0.75 to 2.67±3.2 points in the CT group (p0.001). A decrease in the severity of depression on the HADS scale from 7.78±0.46 to 6.36±2.6 points in the ST group and from 7.69±3.4 to 5.83±3.4 points in the CT group (p0.001). A decrease in the severity of anxiety on the HADS scale from 10.47±0.63 to 7.63±2.5 points in the ST group from 10.53±0.58 to 6.42±4.2 points in the CT group (p0.001). Reduction of functional disorders on the Oswestry scale from 41.14±0.78 to 22.07±14.2% in the ST group and from 40.91±0.56 to 19.1±17.4% in the CT group (p0.001). Improvement of the quality of life according to the SF-12 questionnaire from 35.01±0.84 to 19.3±21.2 points in the ST group and up to 35.12±0.03 to 13.7±9.8 points in the CT group (p0.001). Conclusion. CT in comparison with ST reduces pain more significantly, improves the functional and emotional state of patients, and improves the quality of life. Widespread introduction of CT CWPS into real clinical practice is recommended.

Abstract Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are common drugs in patients with osteoarthritis (OA). NSAIDs are generally used at home by patients, without supervision, requiring proper knowledge and attitudes for correct practice. This study investigated the knowledge, attitude, and practice (KAP) of patients with OA toward NSAIDs. Methods This cross-sectional study enrolled patients with OA at the Qingpu Branch of Zhongshan Hospital of Fudan University between January and March 2024. The KAP scores and demographic information of respondents were collected through a self-designed questionnaire. Results There were 645 participants, with 579 (89.8%) over 45 years old and 394 (61.1%) females. The average scores for knowledge, attitude, and practice were 16.26 ± 3.79 (possible range: 0–24), 18.12 ± 1.99 (possible range: 5–35), and 29.20 ± 5.52 (possible range: 10–50), respectively. The structural equation model (SEM) found that for individuals currently using NSAIDs, the attitude had a direct effect on practice (β = 0.978, P

Percutaneous coronary intervention (PCI) is a very rare cause of acute pericarditis. It usually develops after a latent period but can present early in case of procedural complications. A high degree of suspicion is required for diagnosis as most cases can be easily missed. Here, we highlight a case of 54-year-old admitted as a case of non-ST elevated myocardial infarction who in view of ongoing chest pain underwent urgent coronary angiography, followed by the primary PCI to left anterior descending artery after which the patient became pain-free. However, 12 h after the procedure, the patient developed severe persistent chest pain with positional and respiratory variation. He was suspected to have reinfarction and treated accordingly but had no symptomatic improvement and was planned for check angiography. However, based on dynamic electrocardiogram (ECG) changes, new echocardiographic findings aided laboratory parameters, he was diagnosed with acute pericarditis. He was treated with nonsteroidal anti-inflammatory drugs following which his pain resolved and ECG returned to baseline after 4 days. His follow-up echocardiography showed complete resolution of pericardial effusion. This case highlights the importance of keeping acute pericarditis as a differential diagnosis of chest pain in PCI patients. A high degree of suspicion is required, as most cases are easily missed to diagnose.

Methods for the synthesis of novel heterocyclic compounds bearing an unsaturated γ-lactone ring and an (S)-naproxen moiety were developed. The O-acylation reactions of 3,4-dihalo-5-hydroxy-2(5H)-furanones with (S)-(+)-2-(6-methoxy-2-naphthyl)propionyl chloride in the presence of Et3N afforded optically active furanone derivatives bearing an (S)-naproxen moiety at the 5 position of the lactone ring. Optically active 4-arylsulfanyl derivatives of 2(5H)-furanone were obtained by the reaction of the isolated (R,S) stereoisomers of 3,4-dihalofuranones with aromatic thiols. A series of heterocycles were synthesized based on 5-alkoxy- and 5-haloahkoxy-2(5H)-furanones containing an (S)-naproxen moiety in the side chain of the hydroxyethylthio substituent on the carbon atom C(4) of the five-membered ring. The structures of three new heterocycles were determined by X-ray diffraction. [ABSTRACT FROM AUTHOR]

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have analgesic effects on femoroacetabular impingement (FAI) patients undergoing hip arthroscopy surgery (HAS). However, the influence of medication time on the analgesic effect of NSAIDs is uncertain. This study aimed to compare the analgesic effect, joint function, quality of life (QoL), and patients' satisfaction between preoperative and postoperative NSAIDs in these patients. Methods: In this prospective, observational study, 165 FAI patients undergoing HAS with NSAIDs (celecoxib, meloxicam, and nimesulide) for analgesia were divided into preoperative (PRE-A) and postoperative analgesia (POST-A) groups according to their actual medication. Results: The visual analog scale (VAS) pain scores on the 1st (P < 0.001) and 3rd (D3) (P = 0.015) days after the operation were lower in the PRE-A group versus the POST-A group but not preoperatively (P = 0.262) or on the 7th day after the operation (D7) (P = 0.302). The proportion of patients receiving rescue analgesia decreased in the PRE-A group versus POST-A group (P = 0.041). However, the modified Harris hip score (mHHS), proportion of patients with an mHHS ≥ 70, and EuroQol-5-dimensional score at preoperative, 1st month (M1), and 3rd month (M3) after the operation were similar between the groups (all P > 0.050). The VAS score on D7 was greater in the PRE-A group compared to the POST-A group (P = 0.014), but the scores at M1 and M3 and the satisfaction and very satisfaction rates at D7, M1, and M3 did not differ between the groups (all P > 0.050). Subgroup analysis revealed that the type of NSAID did not affect most outcomes. Conclusion: Preoperative NSAIDs elevate analgesic effect and patients' satisfaction, but not joint function or QoL compared to postoperative NSAIDs in FAI patients undergoing HAS. [ABSTRACT FROM AUTHOR]

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) possess analgesic and anti-inflammatory properties by inhibiting cyclooxygenase (COX) enzymes. Conflicting evidence exists on whether NSAIDs influence signaling related to muscle adaptations and exercise with some research finding a reduction in muscle protein synthesis signaling via the AKT-mTOR pathway, changes in satellite cell signaling, reductions in muscle protein degradation, and reductions in cell proliferation. In this study, we determined if a single maximal dose of flurbiprofen (FLU), celecoxib (CEL), ibuprofen (IBU), or a placebo (PLA) affects the short-term muscle signaling responses to plyometric exercise. Methods: This was a block randomized, double-masked, crossover design, where 12 participants performed four plyometric exercise bouts consisting of 10 sets of 10 plyometric jumps at 40% 1RM. Two hours before exercise, participants consumed a single dose of celecoxib (CEL 200 mg), IBU (800 mg), FLU (100 mg) or PLA with food. Muscle biopsy samples were collected before and 3-h after exercise from the vastus lateralis. Data were analyzed using a repeated measures (RM) ANOVA, ANOVA, or a Friedman test. Significance was considered at p < 0.05. Results: We found no treatment effects on the mRNA expression of PTSG1, PTSG2, MYC, TBP, RPLOP, MYOD1, Pax7, MYOG, Atrogin-1, or MURF1 (all, p > 0.05). We also found no treatment effects on AKT-mTOR signaling or MAPK signaling measured through the phosphorylation status of mTORS2441, mTORS2448, RPS6 235/236, RPS 240/244, 4EBP1, ERK1/2, p38 T180/182 normalized to their respective total abundance (all, p > 0.05). However, we did find a significant difference between MNK1 T197/202 in PLA compared to FLU (p <.05). Conclusion: A single, maximal dose of IBU, CEL, or FLU taken prior to exercise did not affect the signaling of muscle protein synthesis, protein degradation, or ribosome biogenesis three hours after a plyometric training bout. [ABSTRACT FROM AUTHOR]

Liposomal preparations play an important role as formulations for transdermal drug delivery; however, the electrical conductivity of these systems is sparingly evaluated. The aim of the study was to outline the range of the values of electrical conductivity values that may be recorded in the future pharmaceutical systems in the context of their viscosity. The electrical conductivity, measured by a conductivity probe of k = 1.0 cm−1, and the dynamic viscosity of liposomal and non-liposomal systems with naproxen sodium, embedded into a methylcellulose hydrophilic gel (0.25%), were compared with data from preparations without naproxen sodium in a range reflecting the naproxen sodium concentrations 0.1·10−2–9.5·10−2 mol/L. The specific conductivity covered a 1.5 μS·cm−1–5616.0 μS·cm−1 range, whereas the viscosity ranged from 0.9 to 9.4 mPa·s. The naproxen sodium highly influenced the electrical conductivity, whereas the dynamic viscosity was a moderate factor. The observed phenomena may be ascribed to the high mobility of sodium ions recruited from naproxen sodium and the relatively low concentrations of applied methylcellulose. The assembly of lecithin in liposomes may have lowered the specific conductivity of the systems with naproxen sodium. These measurements will be further developed for implementation as simple assays of the concentrations of active pharmaceutical ingredient in release experiments of preparations proposed for dermatological applications. [ABSTRACT FROM AUTHOR]

The subject of this article are patients with ankylosing spondylitis and the possibilities of improving the control of morning pain and stiffness characteristic of the disease by applying the principles of chronopharmacology. Chronopharmacology uses knowledge of biological rhythms to develop an optimal pharmacotherapeutic plan. The aim was to study and summarize the modern medical literature on the subject by means of the methods of analysis of the information obtained by keywords in specialized electronic medical databases. In conclusion, it can be said that the results of the study of the available literature show the importance of applying the principles of chronopharmacology to achieve optimal pain control, manage morning stiffness and improve therapeutic results in patients with ankylosing spondylitis. [ABSTRACT FROM AUTHOR]

In this study, in situ electrodeposition of Zn─Al‐layered double hydroxides (Zn─Al‐LDHs) on the surface of pencil graphite substrate were practiced with interlayer modification by ibuprofen. The prepared composite increases the efficiency of the proposed method by increasing the level of interaction between the sorbent and the selected analytes including acetylsalicylic acid and naproxen (NAP) in real sample. Eventually, the extracted target analytes were injected into high‐performance liquid chromatography ultraviolet (HPLC‐UV) for their measurement. The experimental design including PBD and BBD was implemented to obtain the maximize efficiency and optimal condition for extraction of the target analytes. Therefore, in optimal conditions, limits of detection of 0.33–0.64 µg L−1, linear dynamic range (LDR) of 1–100 µg L−1 (with r2 > 0.9934), and limits of quantification (LOQs) of 1.1–2.1 µg L−1 were obtained for target analytes by SPME‐HPLC‐UV. The intra‐day relative standard deviation (RSD%) were found to range in 3.90%–5.30% (4.90%–6.80%) at concentration of 5–50 µg L−1 (2–10 µg L−1). According to obtained result, the relative recovery was calculated between 90% and 109%. Therefore, the obtained results showed that the selected method has a suitable performance for the preconcentration and extraction of acetylsalicylic acid and NAP in biological samples. [ABSTRACT FROM AUTHOR]

Background: Beta-lactam antibiotics are the most common cause of hypersensitivity reactions to medications, followed by nonsteroidal anti-inflammatory drugs (NSAID). Objective: The aim of this study was to classify children with hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAID-H) according to the latest updates. Methods: ENDA recommendations were used to evaluate all patients with suspected NSAID-H. Children were classified as either selective responders (SR) or cross-intolerant based on the results of the drug provocation test (DPT). Results: Sixty-seven patients with suspected NSAID-H were evaluated in this study. NSAID-H was confirmed in 20 patients (29.9%). Among the 20 patients diagnosed with NSAID-H, 15 were classified according to the 2018 EAACI/ENDA Position Paper. Twelve patients (80%) were classified as cross-intolerant and 3 (20%) as SRs. NSAID-H was confirmed in 4 of 37 patients (10.8%) ages <10 years and 16 of 30 patients (53.3%) ages >10 years (p < 0.001). Twelve patients ages >10 years were classified. Cross-intolerance was detected in nine patients (66.6%). In patients >10 years of age, NSAID-induced urticaria/angioedema (NIUA) (16.7%) was the most common type in the group with classifiable cross-intolerant. In addition, NSAID-exacerbated respiratory disease was detected in one patient. Conculsion: Ibuprofen is the most common NSAID-H drug used in children. NIUA is the most common reaction. In pediatric allergy, hypersensitivity to NSAIDs is a challenging diagnostic issue. Hypersensitivity to NSAIDs poses a challenging diagnostic issue in pediatric allergies. The oral challenge test is the main diagnostic tool; however, in clinical practice, performing multiple challenge tests is difficult. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), the most common age‐related neurodegenerative condition, is named after Alois Alzheimer and is marked by a progressive deterioration in memory, cognitive function, and behavior. Research has highlighted the importance of nonsteroidal anti‐inflammatory drugs (NSAIDs) in inhibiting the aggregation of amyloid β‐peptide (Aβ), a key feature of AD pathology. Ibuprofen, an NSAID from the propionic acid class, is widely used to manage osteoarthritis and rheumatoid arthritis, exhibiting strong anti‐inflammatory and antipyretic effects. However, the drug's acidic group limits its selectivity for cyclooxygenase (COX) enzymes and contributes to several adverse effects. This study aimed to modify the acidic moiety of ibuprofen into lactone (IBU‐O 1–4) and lactam (IBU‐I 1–3) derivatives to mitigate these side effects. The structural properties of the synthesized imidazolone (IBU‐I 1–3) and oxazolone (IBU‐O 1–4) derivatives were characterized through Q‐TOF LC‐MS, ¹H‐NMR, ¹3C‐NMR, and IR spectroscopy. Molecular docking studies followed by Ellman's method assessed the inhibitory effects of these compounds on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), while an enzyme immunoassay (EIA) kit was used to evaluate their inhibition of cyclooxygenase‐2 (COX‐2). [ABSTRACT FROM AUTHOR]

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are common drugs in patients with osteoarthritis (OA). NSAIDs are generally used at home by patients, without supervision, requiring proper knowledge and attitudes for correct practice. This study investigated the knowledge, attitude, and practice (KAP) of patients with OA toward NSAIDs. Methods This cross-sectional study enrolled patients with OA at the Qingpu Branch of Zhongshan Hospital of Fudan University between January and March 2024. The KAP scores and demographic information of respondents were collected through a self-designed questionnaire. Results There were 645 participants, with 579 (89.8%) over 45 years old and 394 (61.1%) females. The average scores for knowledge, attitude, and practice were 16.26 ± 3.79 (possible range: 0–24), 18.12 ± 1.99 (possible range: 5–35), and 29.20 ± 5.52 (possible range: 10–50), respectively. The structural equation model (SEM) found that for individuals currently using NSAIDs, the attitude had a direct effect on practice (β = 0.978, P < 0.001). For individuals not using NSAIDs, the attitude had a direct effect on practice (β = 0.936, P < 0.001). Conclusion This study suggested that adequate NSAID knowledge is the prerequisite for correct NSAID-related medical decisions, while attitude has a crucial intermediary effect. Healthcare professionals and society should strengthen education regarding the relevant knowledge of NSAIDs and guide the cultivation of positive attitudes toward NSAIDs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background Managing medication use in older orthopedic patients is imperative to extend their healthy life expectancy in an aging society. However, the actual situation regarding polypharmacy, the intake of potentially inappropriate medications (PIMs), and fall risk-increasing drugs (FRIDs) among older orthopedic patients is not well characterized. This study aimed to investigate the medication-based profiles of older orthopedic patients to highlight the critical points of concern. Methods We retrospectively reviewed the clinical data of consecutive patients aged ≥ 65 years who underwent orthopedic surgery at two acute care hospitals between April 2020 and March 2021. The cutoff number of prescribed drugs for polypharmacy was set at 6. According to the specified guidelines, 19 categories of drugs were identified as PIMs, and 10 categories were classified as FRIDs. Results A total of 995 older patients with orthopedic surgery were assessed, of which 57.4% were diagnosed with polypharmacy, 66.0% were receiving PIMs, and 41.7% were receiving FRIDs. The prevalence of FRID intake did not significantly differ among patients with degenerative spinal disease (n = 316), degenerative disease of extremities (n = 331), and fractures (n = 272). Compared with patients with degenerative disease of the extremities, the multivariable-adjusted prevalence ratios (PRs) of polypharmacy and PIM intake were significantly higher in patients with degenerative spinal disease (1.26 [confidence intervals (CI): 1.11–1.44] and 1.12 [CI: 1.00–1.25]), respectively. Use of antiemetic drugs (adjusted PR, 13.36; 95% CI: 3.14–56.81) and nonsteroidal anti-inflammatory drugs (adjusted PR, 1.37; 95% CI: 1.05–1.78) was significantly higher in patients with degenerative spinal disease. Among patients with degenerative spinal disease, the prevalence of antiemetic drug intake was 8.7% in lumbar spinal patients and 0% in cervical spinal patients. Conclusions More than half of the orthopedic patients in this study were affected by polypharmacy, and approximately two-thirds were prescribed some form of PIMs. Patients with degenerative spinal disease showed a significantly higher prevalence of polypharmacy and PIM use compared with other orthopedic diseases. Particular attention should be paid to the high frequency of antiemetic drugs and nonsteroidal anti-inflammatory drugs intake among patients with degenerative lumbar spine conditions.

Objective To investigate the effects of new and traditional non-steroidal anti-inflammatory drugs (NSAIDs) on the proliferation, morphology, adhesion, activity and expression of osteoblast related genes of MG-63 osteoblasts by establishing a osteogenic model of implants. Methods MG-63 cells were implanted on sand-blasted, largegrit, acid-etched titanium plates surface (SLA) to establish a model of osseointegration between implant surface and osteoblasts. The experiments included NO-flurbiprofen group, flurbiprofen group and the control group. Cell proliferation was detected by CCK-8 assay, cell morphology was observed by scanning electron microscopy (SEM), cell adhesion was detected by MTT assay, alkaline phosphatase (ALP) activity was detected by chemical method, calcified nodules was observed after Alizarin red staining, and the expression of bone formation related genes ALP, OCN, Runx-2 was detected by RT-qPCR. Results CCK-8 assay showed that statistical difference was observed in cell proliferation among the groups treated with different drug concentrations (P < 0.01). Cell proliferation was higher in the NO-flurbiprofen group and the flurbiprofen group than the control group, and in the NO-flurbiprofen group than the flurbiprofen group (P < 0.01). SEM displayed that the cells from the NO-flurbiprofen group grew to multiple lays first. Cell adhesion results showed that the number of cell adhesion was lower in the NO-flurbiprofen group than the flurbiprofen group and the control group (P < 0.01). ALP activity of drug groups was lower than the control group (P < 0.01). No typical red deeply stained calcified nodules were observed in neither NO-flurbiprofen group nor flurbiprofen group during the observation period. RT-qPCR indicated that the mRNA expression of OCN in the NO-flurbiprofen group and Runx-2 in the flurbiprofen group was higher than those of the control group, while the mRNA level of ALP was lower than that of the control group (P < 0.01). Conclusion Both NO-flurbiprofen and flurbiprofen effectively promote the proliferation of osteoblasts on the surface of titanium plates and the expression of some osteogenic related genes. The promotion effect of NO-flurbiprofen is more significant.

Increasing evidence supports that depression including major depressive disorder (MDD) is associated with an increased risk of falls. However, some studies suggest no association between MDD and falls. Therefore, the specific causal relationship whereby MDD affects the risk of falls remains elusive, and the potential mediators are unclear. Summary-level data for MDD and falls were collected from the Genome-wide association studies (GWAS) in this study. Mendelian randomization (MR) and multivariable MR (MVMR) analyses were performed to evaluate the causal associations between MDD and falls. A Two-step MR analysis was employed to analyze the mediating effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the causal association between MDD and the risk of falls. Using the inverse-variance weighted (IVW) method, genetically predicted MDD was associated with an increased risk of falls (β = 0.15, SE = 0.034; P = 1.61E-5). MVMR and two-step MR analyses demonstrated that MDD was a causal determinant of increased falls independent of body mass index (BMI), smoking initiation, and alcohol consumption and that this causal relationship was mediated by NSAID medication. Extracted GWAS summary statistics are from European ancestry. Stratified analyses by sex and age were not included in our study. Therefore, it is unclear whether the results are the same for other ethnic groups, genders, and ages. Our results demonstrate that MDD is independently associated with an increased risk of falls, in which NSAIDs mediate the association. This study suggests that avoiding the use of NSAIDs may reduce the risk of falls in patients diagnosed with MDD. • Genetically predicted MDD has a causal effect on an increased risk of falls. • Genetically predicted MDD affects the fall risk independently of BMI, smoking initiation, and alcohol consumption. • The causal effect of genetically predicted MDD on falls is mediated by NSAIDs. • Avoiding taking NSAIDs may reduce the risk of falls in patients diagnosed with MDD. [ABSTRACT FROM AUTHOR]

Rising melanoma rates have spurred interest in preventive strategies. Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, show potential in reducing cancer risks. NSAIDs act on cyclooxygenase (COX) enzymes, impacting COX-2 associated with inflammation and cancer progression. This paper explores aspirin's role in cutaneous melanoma prevention, elucidating its mechanisms and acknowledging varying literature outcomes. Rather than providing conclusive recommendations, the review emphasizes the influence of individual factors, contributing to the ongoing dialogue on aspirin's complexities in melanoma prevention. A PubMed search using "Aspirin" AND "Cutaneous melanoma" yielded relevant English-language, peer-reviewed studies. Selection criteria focused exclusively on skin cancers, specifically cutaneous melanoma. Exclusions included studies covering various cancers, some non-dermatologic, and those not evaluating aspirin use independently but in conjunction with NSAIDs. The potential chemopreventive effects of aspirin and NSAIDs against melanoma have gained attention due to their association with a reduced risk of various cancers including gastric, colorectal, and breast. By inhibiting COX enzymes and the NF-κB pathway, these agents theoretically slow malignant cell activities, presenting a prospect for cancer prevention. Aspirin exhibits noteworthy effects, depleting growth-stimulating hormones, generating reactive oxygen species harmful to cancerous cells, and inhibiting COX-2 linked to cancer progression. Limited literature suggests survival benefits with aspirin use in stage II and III melanoma, possibly due to slowing disease progression, evident in smaller Breslow depths. Gender-specific responses to aspirin are notable, with some studies reporting a stronger chemopreventive correlation in females. It's crucial to note that geographic disparities, demographic cohorts, and individual-specific factors are confounding variables that may contribute to conflicting findings regarding aspirin's impact on melanoma. The association between aspirin use and melanoma risk is complex, with conflicting findings across diverse populations. Although it appears that more studies suggest a protective role for aspirin rather than not, evidence lacks consistency. Factors such as gender, geography, race, sun exposure, and health conditions play a role in shaping these varied outcomes, necessitating large-scale, prospective studies research and standardized parameters for more conclusive insights that may help guide tailored clinical strategies for melanoma prevention. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine the effects of prolonged administration of the oral NSAIDs phenylbutazone and firocoxib on concentrations of cytokines and growth factors in platelet-rich plasma (PRP) and autologous protein solution (APS). ANIMALS 6 adult University owned horses. METHODS Horses were randomized to receive phenylbutazone (1 g, orally, q 12 h) or firocoxib (57 mg, orally, q 24 h) for 6 days. Blood was obtained and processed for APS (Pro-Stride) and PRP (Restigen) before the administration of NSAIDs and at 7 days (1 day following cessation of NSAIDs). Horses underwent a two-week washout period, during which blood was obtained at 14 days and 21 days. The protocol was repeated with a crossover design. PRP and APS were analyzed for concentrations of platelets, leukocytes, and several cytokines (IL-1β, IL-10, IL-6, IL-8, and tumor necrosis factor-α) and growth factors (PDGF, FGF-2, and TGF-β1) using immunoassays. Plasma was evaluated for drug concentrations. RESULTS No significant differences existed in concentrations of growth factors and cytokines before or after prolonged administration of NSAIDs. There were significant differences in concentrations of leukocytes and platelets in PRP compared to APS, with higher concentrations of leukocytes at the day 7 time point (T) in APS (phenylbutazone) and in concentrations of platelets in APS at T0 (firocoxib) and in APS at T7 (phenylbutazone). CLINICAL RELEVANCE Veterinarians can recommend the administration of these oral NSAIDs prior to obtaining blood for PRP and APS provided a single-day washout period is instituted [ABSTRACT FROM AUTHOR]

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains the most frequent and severe complication following ERCP, elevating both patient suffering and healthcare costs, and posing challenges to the advancement of ERCP techniques. Empirical evidence supports the prophylactic use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the prevention of PEP, especially in high-risk populations, as endorsed by both the American Society for Gastrointestinal Endoscopy (ASGE) and the European Society for Gastrointestinal Endoscopy (ESGE). However, the prophylactic efficacy of NSAIDs in average-risk individuals, alongside the ideal drug selection, dosing, and timing of NSAID administration, remains to be elucidated. Furthermore, the synergistic preventive potential of NSAIDs when integrated with other interventions, such as hydration, pancreatic stenting, somatostatin administration, sublingual nitrate application, and epinephrine, warrants further clarification. In this paper, we conduct an exhaustive review of the prophylactic effect and clinical administration of NSAIDs for PEP. We comprehensively synthesize findings from clinical trials investigating NSAIDs, both in monotherapy and combination regimens, for PEP prevention. Additionally, we scrutinize the current landscape of NSAID usage in clinical practice and evaluate their cost-effectiveness. Future research should concentrate on refining NSAID prophylaxis strategies for PEP in patients at different risk levels, while also enhancing adherence to clinical guidelines and alleviating the issue of NSAID cost inflation. [ABSTRACT FROM AUTHOR]

Background and Objective: Pain is the most common symptom compelling an individual to seek medical attention. The use of Vitamin D3 for nociceptive and inflammatory pain is highly debated. Therefore, this study was undertaken to compare three daily doses (15/30/60 μg/kg) and a single high dose of Vitamin D3 (260 μg/kg) to standard drugs, namely tramadol and diclofenac in two most resorted pain-models in mice. Materials and Methods: Thirty-six Swiss-albino mice were divided into six groups of six mice each. The experiment was conducted using hot plate and writhing test. Same groups of mice were reused after suitable wash-out period. Groups were dosed with 0.25% carboxymethyl-cellulose (negative-control), a positive-control (tramadol for hot-plate and diclofenac for writhing-test). Injection Vitamin D3 was given in three daily doses of 15/30/60 μg/kg. Single dose of 260 μg/kg of Vitamin D3 was also tested. Latency period (LP), percent of maximal-possible-antinociceptive-effect (%MPE), mean number and percentage inhibition of writhes were the parameters evaluated to compare analgesic effect. Data were analyzed using paired t -test, analysis of variance (ANOVA)/Kruskal–Wallis/Friedman's-ANOVA, and repeated-measures ANOVA with post hoc Dunnett's tests. Results: In hot-plate method, 60 and 260 μg/kg of Vitamin D3 raised mean LP when compared to baseline and negative control and all groups recorded higher percentage MPE values when compared to negative control. In writhing test, 15-, 30-, and 60 μg/kg/day showed analgesic effect in comparison to negative control. However, 15 and 30 μ/kg/day of Vitamin D3 contradicted its responses when assessed through different parameter. Interpretation and Conclusion: In hot-plate test, 60 and 260 μg/kg of Vitamin D3 showed significant analgesic effect; however, effects were not superior to tramadol. In writhing test, 15-, 30-, and 60 μg/kg/day showed significant analgesic effect which were not superior to diclofenac. Surprisingly, 15 and 30 μ/kg, on instances exhibited irritant effects. [ABSTRACT FROM AUTHOR]

Non‐steroidal anti‐inflammatory drugs (NSAIDs) are extensively prescribed pharmaceutical agents worldwide. Due to their analgesic, antipyretic, and anti‐inflammatory properties, they are used in clinical practice for the treatment of numerous inflammatory diseases. The mechanism of action primarily involves the inhibition of prostaglandin synthesis mediated by cyclooxygenases (COX), key enzymes of the inflammatory cascade. Indomethacin, a non‐selective derivative of indole‐3‐acetic acid exhibits diverse mechanisms to exert its anti‐tumor effects, including angiogenesis suppression, induction of apoptosis, and reduction of tumorigenesis through immune modulation. Numerous studies suggest that derivatives of indomethacin may inhibit cell proliferation and reduce levels of anti‐apoptotic proteins through COX‐independent mechanisms. Given the diverse potential mechanisms through which indomethacin impacts cancer progression, this review provides an overview of structural analogs that possess antitumor activity and outlines future directions in developing new candidates that may have substantial efficacy in cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Managing medication use in older orthopedic patients is imperative to extend their healthy life expectancy in an aging society. However, the actual situation regarding polypharmacy, the intake of potentially inappropriate medications (PIMs), and fall risk-increasing drugs (FRIDs) among older orthopedic patients is not well characterized. This study aimed to investigate the medication-based profiles of older orthopedic patients to highlight the critical points of concern. Methods: We retrospectively reviewed the clinical data of consecutive patients aged ≥ 65 years who underwent orthopedic surgery at two acute care hospitals between April 2020 and March 2021. The cutoff number of prescribed drugs for polypharmacy was set at 6. According to the specified guidelines, 19 categories of drugs were identified as PIMs, and 10 categories were classified as FRIDs. Results: A total of 995 older patients with orthopedic surgery were assessed, of which 57.4% were diagnosed with polypharmacy, 66.0% were receiving PIMs, and 41.7% were receiving FRIDs. The prevalence of FRID intake did not significantly differ among patients with degenerative spinal disease (n = 316), degenerative disease of extremities (n = 331), and fractures (n = 272). Compared with patients with degenerative disease of the extremities, the multivariable-adjusted prevalence ratios (PRs) of polypharmacy and PIM intake were significantly higher in patients with degenerative spinal disease (1.26 [confidence intervals (CI): 1.11–1.44] and 1.12 [CI: 1.00–1.25]), respectively. Use of antiemetic drugs (adjusted PR, 13.36; 95% CI: 3.14–56.81) and nonsteroidal anti-inflammatory drugs (adjusted PR, 1.37; 95% CI: 1.05–1.78) was significantly higher in patients with degenerative spinal disease. Among patients with degenerative spinal disease, the prevalence of antiemetic drug intake was 8.7% in lumbar spinal patients and 0% in cervical spinal patients. Conclusions: More than half of the orthopedic patients in this study were affected by polypharmacy, and approximately two-thirds were prescribed some form of PIMs. Patients with degenerative spinal disease showed a significantly higher prevalence of polypharmacy and PIM use compared with other orthopedic diseases. Particular attention should be paid to the high frequency of antiemetic drugs and nonsteroidal anti-inflammatory drugs intake among patients with degenerative lumbar spine conditions. [ABSTRACT FROM AUTHOR]

Objective: Guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin for 2-4 weeks with colchicine for 3 months for the treatment of acute pericarditis. In patients with HFrEF and/or CAD, the adverse effect profile of NSAIDs pose concern. While previous studies evaluated colchicine as adjunctive therapy, colchicine monotherapy has never been assessed. This study aims to compare the efficacy of colchicine monotherapy to NSAID monotherapy or combination therapy for the prevention of recurrent pericarditis in patients with HFrEF and/or CAD. Methods: This was a single health-system, retrospective, observational cohort study. Patients were 18 years or older, had a diagnosis of acute pericarditis and HFrEF and/or CAD, and were discharged on colchicine and/or NSAID therapy. Patients were excluded if they had an episode of pericarditis within the previous 12 months. The primary outcome was the incidence of pericarditis recurrence or documentation of incessant symptoms within 12 months of the index hospitalization. Results: Of the 77 patients included, 43 (55.8%) were treated with colchicine monotherapy, 7 (9.1%) were treated with NSAID monotherapy, and 27 (35.1%) were treated with combination therapy. Pericarditis recurrence or documentation of incessant symptoms occurred in 16.3% of patients treated with colchicine monotherapy, 28.6% of those treated with NSAID monotherapy, and 18.5% of those treated with combination therapy (P =.740). Conclusion: In this study, no difference in the primary outcome was observed between groups. However, a prospective, randomized trial is needed to further elucidate the efficacy of colchicine monotherapy for the treatment of acute pericarditis in patients with HFrEF and/or CAD. [ABSTRACT FROM AUTHOR]