Nonsteroidal Research Articles

Understanding network meta-analysis

Recently, in the World Journal of Clinical Cases , studied the different non-steroidal anti-inflammatory drugs (meloxicam, celecoxib, naproxen, and rofecoxib) for juvenile idiopathic arthritis with network meta-analysis (NMA). This manuscript aims to introduce to clinicians what NMA is. NMA represents a fundamental technique for simultaneously comparing three or more interventions within a single analysis, harnessing both direct and indirect evidence derived from a network of studies. It surpasses pair-wise meta-analysis which are confined to direct comparison of two items in clinical trials. This approach can estimate the relative effects between any pair of interventions within the network, often yielding more precise estimations than those generated from single direct or indirect analyses. NMA necessitates steps akin to those of conventional meta-analysis, involving a thorough literature search, assessment of potential trial biases, statistical analysis of reported pairwise comparisons for all relevant outcomes, and evaluation of overall certainty of evidence on an outcome-specific basis. However, NMA demands substantial resources, given its propensity to address broader inquiries, typically involving a larger number of studies at each phase of the systematic review, from screening to analysis, compared to traditional meta-analyses.

Elbow arthritis

Most patients with primary osteoarthritis of the elbow report a history of heavy lifting work with the affected upper limb. Conservative treatment, including activity modifications, nonsteroidal anti-inflammatory drug (NSAID) intake, and intra-articular injections can provide sufficient pain relief in the early stages when used in combination. If surgery is required, many patients experience significant pain relief from joint-preserving procedures despite existing cartilage damage. Although open debridement procedures are effective, arthroscopic osteocapsular arthroplasty has become established as the preferred surgical procedure. The ulnar nerve should be assessed during surgery and treated if necessary. Total elbow arthroplasty (TEP) is successful in terms of pain relief and function; however, it is recommended for older patients with advanced osteoarthritis or for whom joint-preserving procedures have failed.

Improving dexamethasone drug loading and efficacy in treating rheumatoid arthritis via liposome: Focusing on inflammation and molecular mechanisms.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 0.46% of the global population. Conventional therapeutics for RA, including disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids, frequently result in unintended adverse effects. Dexamethasone (DEX) is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties. Liposomal delivery of DEX, particularly when liposomes are surface-modified with targeting ligands like peptides or sialic acid, can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity. This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA. Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models, reduces joint inflammation and damage, and alleviates cartilage destruction compared to free DEX. The liposomal formulation also shows better hemocompatibility, fewer adverse effects on body weight and immune organ index, and a longer circulation time with higher bioavailability. The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α) and B-cell-activating factor (BAFF), which are key players in the pathogenesis of RA. Additionally, liposomal DEX can induce the expression of anti-inflammatory cytokines like interleukin-10 (IL-10), which has significant anti-inflammatory and immunoregulatory properties. The findings suggest that liposomal DEX represents a promising candidate for effective and safe RA therapy, with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.

Role of Podoplanin (PDPN) in Advancing the Progression and Metastasis of Glioblastoma Multiforme (GBM)

Glioblastoma multiforme (GBM) is a malignant primary brain tumor categorized as a Grade 4 astrocytic glioma by the World Health Organization (WHO). Some of the established risk factors of GBM include inherited genetic syndromes, body mass index, alcohol consumption, use of non-steroidal anti-inflammatory drugs (NSAIDs), and therapeutic ionizing radiation. Vascular anomalies, including local and peripheral thrombosis, are common features of GBM. Podoplanin (PDPN), a ligand of the C-type lectin receptor (CLEC-2), promotes platelet activation, aggregation, venous thromboembolism (VTE), lymphatic vessel formation, and tumor metastasis in GBM patients. It is regulated by Prox1 and is expressed in developing and adult mammalian brains. It was initially identified on lymphatic endothelial cells (LECs) as the E11 antigen and on fibroblastic reticular cells (FRCs) of lymphoid organs and thymic epithelial cells as gp38. In recent research studies, its expression has been linked with prognosis in GBM. PDPN-expressing cancer cells are highly pernicious, with a mutant aptitude to form stem cells. Such cells, on colocalization to the surrounding tissues, transition from epithelial to mesenchymal cells, contributing to the malignant carcinogenesis of GBM. PDPN can be used as an independent prognostic factor in GBM, and this review provides strong preclinical and clinical evidence supporting these claims.

Bilateral Rectus Sheath Block with Continuous Bupivacaine Infusions After Elective Open Gastrectomy: A Randomized Controlled Trial

Background and Objectives: Multimodal analgesia has been shown to be effective in facilitating early postoperative gastrointestinal function and rehabilitation in patients undergoing open gastrectomy. We conducted a clinical trial to investigate the effectiveness of bilateral rectus sheath block (RSB) with continuous bupivacaine infusion in comparison with placebo following elective open gastrectomy. Materials and Methods: Patients indicated for elective open gastrectomy were screened, enrolled, and randomised between October 2021 and September 2023. The patients were randomised to either Group A (intervention—continuous bupivacaine) or Group B (control—NaCl saline). The primary outcome measures were the quantity of an opioid analgesic administered during the initial 72 h post-surgery and the level of postoperative pain as indicated by the visual analogue scale (VAS). Mann–Whitney U test was used for quantitative analysis while Pearson Chi-square was used for categorical variables. Results: A total of 60 patients completed the trial, with 30 patients in each of the two groups. Patients in Group A reported lower median VAS pain scores at all observed time points following surgery (p < 0.001). No patient in Group A required rescue opioid analgesia, although non-steroidal anti-inflammatory drugs were necessary during the initial 12 h postoperatively. Clinically, Group A patients had a significantly shorter time to first gas (p = 0.001), a shorter time to first bowel movement (p < 0.001), a shorter time to first out-of-bed activity (p < 0.001), and a shorter overall hospitalisation duration (p < 0.001) compared to Group B patients. Conclusions: Bilateral RSB with continuous bupivacaine infusion is effective in managing pain and can reduce the use of opioid analgesics in the postoperative period. Furthermore, it promotes early recovery, and a shorter hospital stay.

Prevalence, risk factors, and severity of erectile dysfunction following renal transplantation.

Sexual dysfunction is common among dialysis and transplant patients. Our study evaluated the prevalence, risk factors, and severity of erectile dysfunction (ED) post-transplant in a single center. We conducted a single-centre, observational, non-interventional study of adult male renal graft recipients. Sociodemographic and clinical data were collected, and erectile function was assessed with the International Index of Erectile Function (IIEF) questionnaire. 179 patients transplanted between 1995 and 2021 were enrolled (170 answered the questionnaire). Mild, moderate, and severe ED was noted in 33.5%, 20.6% and 10.6% of cases, respectively. ED prevalence increased with age (42.6% of patients < 40, 47.4% of patients aged 40-60, 78.9% of patients > 60). The total mean IIEF score was 16.32 ± 6.93 (erectile function 19.22 ± 7.9, orgasmic function 6.8 ± 2.9, sexual desire 6.43 ± 2.1, intercourse satisfaction 8.96 ± 3.7, overall satisfaction 6.78 ± 2.6). Age, alcohol consumption, type, time on dialysis pre-transplant, and donor type were significantly associated with erectile dysfunction (p < 0.05). Most patients (93.5%) were treated for comorbidities in addition to immunosuppression. Severe ED was significantly more common among patients taking alpha blockers and non-steroidal anti-inflammatory drugs. Self-reported erectile dysfunction post renal transplantation seems influenced by age, alcohol intake, dialysis history, donor type and certain drugs, but not by comorbidities (hypertension, diabetes, heart disease).

Reactive arthritis

Reactive arthritis (ReA) is adisease caused by an extra-articular infection that manifests as asterile joint inflammation. In contrast to bacterial septic arthritis no pathogens can be cultured from the joint in ReA but pathogen components, such as antigens or DNA are more frequently detectable in the joint, suggesting an intra-articular culture-negative persistent infection or at least an intra-articular interaction between the host and pathogen components. The primary extra-articular infection in classical ReA is of bacterial origin and usually affects either the urogenital, gastrointestinal or, less frequently, the respiratory tract. Chlamydia (C.trachomatis and less frequently C.pneumoniae) and enterobacteria are among the most common pathogens causing ReA. The prevalence of ReA is estimated at 40/100,000 and the incidence at 5/100,000. Typical clinical manifestations are mostly self-limiting peripheral arthritis (monoarticular or oligoarticular), dactylitis and, more rarely, axial involvement and in half of the cases, there is an association with HLA-B27. Due to these similarities, classical ReA is categorized as aform of spondyloarthritis (SpA). The diagnosis is made on the basis of atypical clinical picture, evidence of aprevious or persistent infection and the exclusion of other causes of arthritis. Treatment includes physical measures, the use of anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs (NSAID) or glucocorticoids, in the case of persistent arthritis, immunomodulating substances such as sulphasalazine, methotrexate and in individual cases biologics and Janus kinase inhibitors (JAKi) are used. In general, antibiotic treatment of ReA does not shorten the duration of the disease.

Investigating pain-related medication use and contribution to polypharmacy in adults with intellectual disabilities: a systematic review

BackgroundAdults with intellectual disability experience more pain than adults without and, despite a higher number of medications being prescribed, may be less likely to receive medication for pain. We conducted a systematic review of existing literature on medication for pain and painful conditions in adults with intellectual disability to explore if there is any association with polypharmacy, multimorbidity or demographic characteristics.MethodsThis systematic review followed PRISMA guidelines. Medline, Embase, PubMed, PsycINFO, Web of Science, CINAHL, Cochrane Library and Scopus were searched from January 2000 to 21st October 2024. We included original, peer-reviewed observational, qualitative or mixed-method studies published in English with data on medication for pain or painful conditions in adults with intellectual disability. Two independent reviewers performed study selection, data extraction, and quality assessment; disagreements were resolved by a third reviewer. Adapted Newcastle–Ottawa Scale or the Critical Appraisal Skills Programme for qualitative studies was used for quality assessment of included studies and findings were reported via narrative synthesis. PROSPERO registration: CRD42023415051.ResultsTwenty-seven of 26,170 articles met the eligibility criteria. Adults with intellectual disability were more likely to have simple analgesic medication than non-steroidal anti-inflammatory drugs, opioids or adjuvant pain medications than the general population. Psychotropic medications were more commonly prescribed in adults with intellectual disability than medication for pain or painful conditions. Adults with intellectual disability and caregivers reported under-recognition and most likely under-treatment of pain.ConclusionsAdults with intellectual disability may receive less pharmacological management of pain with analgesics and medication for painful conditions despite the high prevalence of polypharmacy, suggesting pain is under-treated. Better assessment and pharmacological treatment of pain and painful conditions is a key future research priority to address this health inequality and improve quality of life for this vulnerable group of people.

Adsorption of Ibuprofen from Water Using Banana Peel Biochar: Experimental Investigation and Machine Learning Algorithms

Ibuprofen is a significant nonsteroidal anti-inflammatory drug that poses environmental and health risks when present in wastewater because of its persistence and probable toxicity. This study investigates the use of banana peel biochar (BPB) made at 600 °C to 900 °C to eliminate ibuprofen from aqueous solutions. The uniqueness of this work lies in the high-temperature pyrolysis process, which has not been previously explored for the ibuprofen removal efficiency using BPB. The batch experiment was conducted considering initial concentrations, pH, and contact time. The data were compared with different algorithms, with Linear Regression (LR), Support Vector Machines (SVM), Decision Trees (DT), Random Forest (RF), and k-Nearest Neighbor (k-NN) to forecast the performance. The results revealed that banana peel biochar at 900 °C exhibited the highest ibuprofen removal efficiency (69.28 ± 0.83%) at 125 mg/L concentration with the sequence of BPB900 &gt; BPB800 &gt; BPB700 &gt; BPB600. A maximum removal efficiency of 72.67 ± 0.75% was observed at pH 9. Adsorption behavior was analyzed using isotherm and kinetic models, with the Freundlich isotherm model (R2 value 0.9620) indicating heterogeneous adsorption and the pseudo-second-order (PSO) kinetic model (R2 value 0.9969) suggesting that physicochemical interactions govern the process. FTIR analysis ensured the existence of functional groups (hydroxyl, carboxylic, carbonyl, and aromatic rings) responsible for adsorption. Machine learning algorithms, especially RF, demonstrated outstanding performance with 90.07% accuracy in predicting the experimental data. In comparison to other adsorbents, BPB demonstrated superior removal efficiency, underscoring its effectiveness. The study suggests that BPB, particularly at 900 °C, is effective in removing ibuprofen, and due to its sustainable production, it offers a potential solution for wastewater treatment.

Construction of biocatalysts based on P450BM3 for the degradation of non-steroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) are widespread pollutants in aquatic environments, posing significant risks to both ecosystems and human health due to their persistence and bioaccumulation. Effective and sustainable degradation methods are urgently required to address this environmental challenge. This study aims to design and optimize a cytochrome P450BM3-based biocatalyst for the rapid and efficient degradation of NSAIDs by direct chemical intervention and protein engineering. The novel biocatalyst achieved efficient biodegradation of four common NSAIDs. Notably, the F87I/T268D mutant achieved 99.22% degradation of diclofenac (DCF) within 10min, and degraded meloxicam (MEL) and phenylbutazone (PBZ) at rates of 98.86% and 90.51% within 5min, respectively. Furthermore, the F87G mutant accomplished 99.08% degradation of acetaminophen (APAP) within just 2min. The catalytic properties of P450BM3 and its mutants were evaluated through kinetic studies, and potential degradation pathways of the four NSAIDs were proposed in conjunction with UPLC-MS. This study provides a novel biocatalytic approach for the rapid degradation of NSAIDs in aquatic systems, offering considerable environmental benefits for pollution mitigation.

Low Frequency of Upper Gastrointestinal Bleeding Despite Non-Steroidal Anti-Inflammatory Drugs and Corticosteroids in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. It has been identified that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids can be essential risk factors for developing complications such as upper gastrointestinal bleeding (UGIB). This study aimed to describe the safety profile of drugs used to treat RA focused in UGIB. A cross-sectional study of patients with RA between 2015 and 2021, a description of the population, and an evaluation of the relationship with UGIB through bivariate analysis and logistic regression. Of 405 individuals, 16 presented UGIB (93.8% women, mean age was 65±13.6 years). No statistically significant differences were found regarding UGIB and medication use, except for the mean dose of corticosteroids. In the multivariate analysis, it was found that the presence of anemia in the last three months had an adjusted OR (AOR) of 16.1 (95% CI 2.74- 24.23) and higher HAQ values during the previous three months had an AOR of 6.17 (95% CI 1.79- 21.24). This study found a low frequency of UGIB in patients with RA. More significant disability and anemia in the previous months were independently associated with UGIB. The low frequency of NSAID use in this population is noteworthy. In general, reasonable medication use related to this complication is recommended.

Discovery of the synergy between sulindac and NO expands the application of NSAIDs in cardiac complications

Cardiac inflammation, a pathological cornerstone in cardiac dysfunction, triggers diastolic impairment, leading to profound myocardial hypoxia. This hypoxic state serves as a potent stimulus for the amplification of inflammatory mediator release, ultimately limiting the therapeutic potential of monotherapies. To address this challenge, compounds that integrate non-steroidal anti-inflammatory drugs (NSAIDs) with nitric oxide (NO) donors was synthesized. The in vitro screening unveiled the remarkable anti-hypoxic inflammatory injury activity of a sulindac derivative, despite its suboptimal COX-2 inhibition when comparing with other NSAIDs derivatives. This revelation propelled us to delve deeper into the intricate synergistic relationship between sulindac and NO. Employing two-way ANOVA and high-throughput screening technique, we incontrovertibly confirmed their synergism. Further, the underlying mechanism was unmasked through the detection of signal molecule release levels and western blot analysis. In a definitive step, we evaluated the therapeutic effects of sulindac and its derivatives in vivo, leveraging a rat model that recapitulates cardiac inflammation coupled with hypoxia. Our findings herald a promising drug candidate and establish a foundation for the expanded utilization of NSAIDs in the intricate landscape of cardiovascular diseases.

1,5- diaryl pyrazole-loaded chitosan nanoparticles as COX-2 inhibitors, mitigate neoplastic growth by regulating NF-κB pathway in-vivo zebrafish model

Non-steroidal anti-inflammatory drugs (NSAIDs) have been researched for their capacity to reduce cancer incidence, primarily due to their COX-2 inhibition properties. However, concerns have arisen regarding the precision of their targeting abilities. Nanoparticle approaches are revolutionizing cancer treatment by enabling targeted drug delivery, which enhances the efficacy and reduces the toxicity of chemotherapy. Particularly, chitosan-based nanoparticles are noteworthy for their biocompatibility, biodegradability, and ability to improve drug delivery. In this study, we synthesized folic acid-conjugated, 1,5-diaryl pyrazole-loaded chitosan (FA-CS-DP) nanoparticles using the ionic gelation method. The bioavailability and anti-neoplastic effects in a 7,12-dimethylbenzanthracene (DMBA)-exposed zebrafish model was investigated. MTT assay showed dose-dependent cytotoxicity of FA-CS-DP nanoparticles against MCF-7 breast cancer. The nanoparticles showed no toxicity to zebrafish embryos up to 100 μg/mL. The nanoparticle reduced oxidative stress and enhanced apoptosis in zebrafish exposed to DMBA. The morphological examination suggests that tumor growth was prevented in the zebrafish's surface and internal regions. The gene expression analysis confirmed the decrease in the expression of anti-inflammatory genes, such as cox-2 and nf-κb, and apoptosis inhibitor genes, such as bcl-2 and mdm2. By regulating the anti-inflammatory and apoptosis inhibitor genes, FA-CS-DP nanoparticle prevents neoplastic growth in the zebrafish model.

Quantitative Structure-activity Relationship (QSAR) Modelling of Indomethacin Derivatives using Regression Analysis.

Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) used for medication to reduce fever, spondylitis, or shoulder pain. It mainly works by the inhibition of prostaglandins, the endogenous signaling molecules. Fifteen indomethacin derivatives have been analyzed in relation to their physicochemical and molecular properties. Two-dimensional (2D) structures of fifteen indomethacin derivatives were drawn using the ACD Lab Chem Sketch version. Most of the topological parameters, such as wiener index (W), mean wiener index (Wa), Balaban indices (J), Balaban centric index (BAC), and molecular connectivity (χ), were calculated by using E Dragon software. The most common molecular file formats accepted in EDragon software were SMILES notations created online by Babel software and 2D structures of various derivatives, which were converted into 3D optimized structures using online CORINA, provided by Molecular Networks GMBH. 3D structures of compounds were also drawn on Gauss View software for calculations of various density functional theory (DFT) based quantum chemical descriptors, such as total energy (TE), softness (S), hardness (η), chemical potential (μ), highest occupied molecular orbital energy (HOMO), and lowest unoccupied molecular orbital energy (LUMO). All species were fully optimized in the gas phase with a 6-31+G* basis set. The harmonic vibrational frequency calculations were used to confirm that the optimized structures were minima, as characterized by positive vibrational frequencies. Combinations of various descriptors, such as D, ID, IOR, Log P, Mr, Mv, Mw, Pc, BAC, Pz, St, W, Wa, 0χ, 1χ, 2χ,3χ,4χ, 5χ, and Xeq have been found to be significant for modeling of activity. QSAR model no. 2: pIC50= -20.605 (±6.600) IOR - 0.747 (±0.454) I1 -5.083 (±3.478) Xeq + 51.647 optimized with empirical parameters with high statistical quality (R= 0.921, R2=0.848) was found to be the best model obtained. The QSAR model obtained suggests that substituents with a lesser value of the index of refraction and less electronegative groups were favourable for the activity, whereas indomethacin derivatives with a CH2CH2NHCONH(CH2)3ONO2 group at R1 position were unfavourable for the activity. The results were critically discussed based on regression data and cross-validation techniques. Pogliani factor Q and the results of the LOO (leave-one-out) method confirmed the reliability and predictability of the proposed models that could be highly beneficial for the future designing of new analogues with higher potency.

Manejo transfusional perioperatorio en craneotomías: encuesta nacional, un punto de partida para valorar la mejora asistencial

ObjectiveTo assess the perioperative management of haemostasis and transfusion practices in adult patients undergoing craniotomies. MethodOnline questionnaire addressed to Spanish anaesthesiologists and promoted by the Neurosciences and Haemostasis, Transfusion Medicine and Fluid Therapy Sections of SEDAR. The questionnaire was sent by email and social media, and was active between June and October 2022. ResultsWe obtained 155 responses from 67 centres; 59.4% perform >100 craniotomies per year. 61.7% were regularly involved in neuroanaesthesiology. Only 21.9% of respondents had pre-anaesthesia assessment performed by a member of that section, and in most of them (83.0%) the assessment was performed ≤3 weeks in advance. Of the respondents with Patient Blood Management programmes, 58.2% had no specific protocols for craniotomies. 90.3% reported that haemoconcentrates are systematically reserved. A lower platelet limit of 100,000/mcL is considered acceptable by 76.8%. 99.4% of respondents discontinued antiplatelet medication based on half-life. Only 23.9% respondents routinely discontinued non-steroidal anti-inflammatory drugs. The transfusion threshold for haemoglobin during surgical bleeding was <10g/dl in 18.7%, <9g/dl in 38.1%, <8g/dl in 38.7% and <7 g/dl in 4.5%. ConclusionsPreoperative anaemia screening and treatment programmes are not implemented and blood product reserves are systematised in patients scheduled for craniotomy. Anti-aggregation therapy is discontinued according to the half-life of the drug without checking platelet functionality.

Current Concepts and Medical Management for Patients with Radiographic Axial Spondyloarthritis.

Radiographic axial spondyloarthritis (r-axSpA), a chronic inflammatory disease, can cause significant radiographic damage to the axial skeleton. Regarding the pathogenic mechanism, association of r-axSpA with tumor necrosis factor (TNF) and the interleukin-23/17 (IL23/ IL17) pathway has been reported. Development of extraarticular manifestations, including uveitis, inflammatory bowel disease, and psoriasis, has been reported in some patients. The pivotal role of human leukocyte antigen-B27 in the pathogenesis of r-axSpA remains to be clarified. Symptoms usually start in late adolescence or early adulthood, and disease progression can vary in each patient, with clinical manifestations ranging from mild joint stiffness without radiographic changes to advanced manifestations including complete fusion of the spine, and severe arthritis of the hip, and could include peripheral arthritis and extraarticular manifestations. The modified New York criteria was used previously in diagnosis of r-axSpA. However, early diagnosis of the disease prior to development of bone deformity was required due to development of biological agents. As a result of Assessment of SpondyloArthritis international Society (ASAS), the classification was improved in part for diagnosis of spondyloarthritis prior to development of bone deformity. The diagnosis is based on comprehensive laboratory findings, physical examinations, and radiologic findings. Medical treatment for r-axSpA involves the use of a stepwise strategy, starting with administration of nonsteroidal anti-inflammatory drugs and physiotherapy, and progressing to sulfasalazine or methotrexate and biologics including TNF-α inhibitors or IL-17 inhibitors as needed. Use of Janus kinase inhibitors has been recently reported.

Comprehensive review on advanced antipyretic and anti-nociceptic agents: Efficacy; safety and emerging therapies

Fever; characterized by an increased core temperature; is a complex physiological reaction to illness involving acute-phase reactants and many physiological; endocrinological; and immunological systems. Antipyretics; chiefly non-steroidal anti-inflammatory Drugs (NSAIDs) and paracetamol; are essential for the management of fever and related discomfort. These medicines primarily function by inhibiting cyclooxygenase enzymes; so diminishing the production of prostaglandin E2 in the hypothalamus and subsequently decreasing the thermal set point. Although paracetamol is acknowledged for its safety when utilized correctly; it presents concerns of hepatic toxicity and overdose; requiring vigilant monitoring; especially in pediatric patients or those with concomitant conditions. Conversely; ibuprofen typically has greater antipyretic efficacy; particularly in pediatric populations; although its application may be constrained by gastrointestinal adverse effects and renal considerations. Recent breakthroughs in this domain concentrate on improving the safety and efficacy of antipyretic drugs; particularly for at-risk populations such as the elderly and children. Innovations like COX-2 selective inhibitors and advanced delivery technologies; including nanomedicine; offer exciting opportunities for enhancing pain management and fever therapy. Future study should emphasize the customization of therapy according to pharmacodynamics; possible drug interactions; and patient attributes to enhance therapeutic results. An interdisciplinary approach is crucial for the appropriate management of fever and pain; enhancing patient welfare and progressing clinical practices in antipyretic and antinociceptive therapies.

Vertebral osteoporotic fractures: differential diagnosis, therapeutic approaches

Osteoporotic vertebral fractures (OVF) are a severe complication of osteoporosis associated adverse outcomes, acute and chronic pain syndrome. If vertebral fractures (deformities) are detected, osteoporosis is diagnosed regardless of bone mineral density and the 10-year absolute fracture risk scale of the Fracture Risk Assessment Tool, but subject to the exclusion of other metabolic osteopathies. The article presents differential diagnosis of OVF with osteopathies such as osteomalacia, tumors or metastatic lesions of the spine, Paget»s disease, myeloma, hyper parathyroid osteodystrophy, post-traumatic vertebral deformities, Scheuermann-Mau disease. Differential diagnosis between different types of osteopathies is based on features of the clinical picture, history, changes in laboratory parameters (calcium, phosphorus, alkaline phosphatase, parathyroid hormone, vitamin D3 and on data from X-ray of the skeleton examination. It is necessary to take into account conditions under which the vertebral fracture occurred, its localization, prevalence, peculiarities of changes in bone structures, presence or absence of osteoporotic background, degenerative-dystrophic changes in the spine. The tactics of managing the patients with OVF is determined by the time after the fracture, its severity, nature of the pain syndrome and includes non-drug and medical measures. Among non-pharmaceutical measures in the acute period of OVF, there are unloading of the spinal column, use of a corset, and physical therapy. Medical measures are aimed at pain relief using injectable and oral forms of nonsteroidal anti-inflammatory drugs, central acting muscle relaxants and anti-osteoporotic therapy. Dexketoprofen (Dexalgin) is the first-line drug for relief of acute pain in OVF which has a rapid and pronounced analgesic effect. For the anti-osteoporotic therapy, the drugs of choice are parenteral bisphosphonates, denosumab and teriparatide.

NSAID exposure delays time-to-pregnancy in patients with spondyloarthritis: an analysis of the GR2 prospective cohort

BackgroundThe impact of disease activity and treatment on fertility outcomes in patients with spondyloarthritis (SpA) has been little explored. This study aimed to describe median time to pregnancy (TTP) in...

Validity evaluation of a rat model of monoiodoacetate-induced osteoarthritis with clinically effective drugs

BackgroundKnee osteoarthritis (KOA) is the most common type of joint disease in elderly people and is characterized by pain and dysfunction. Although the monoiodoacetate (MIA)-induced model is widely used as a rodent KOA model, it is important to acknowledge the inherent limitations of this model, as the MIA model develops complex pathological phases on a daily basis. An accurate understanding of this model and the selection of an appropriate time point according to the target for drug candidates can lead to the development of clinically effective drugs.MethodsChanges in the pathological state of the MIA model were assessed via histopathological evaluation. Clodronate, a bisphosphonate, and diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), were selected as models of clinically effective drugs due to their different mechanisms of action. The analgesic effects of both drugs on the MIA model were evaluated. The long-term effect of clodronate on subchondral bone osteoclasts was also evaluated.ResultsHistopathological evaluation revealed that MIA-induced symptomatic behavior occurred in the early and late phases and was accompanied by synovial inflammation and osteoclast-related joint degeneration, respectively. Although clodronate inhibited symptomatic behavior and prevented cartilage degeneration from the early to late phases, diclofenac inhibited symptomatic behavior only in the early phase. Clodronate acted locally and inhibited the activation of subchondral osteoclasts.ConclusionsPathological changes, such as synovial changes in the early phase and knee joint degeneration in the late phase, in the MIA model are similar to those in human KOA. Our results indicate that the early phase in the MIA model is appropriate for evaluating the effects of anti-inflammatory agents such as NSAIDs and corticosteroids. The late phase in the MIA model is appropriate for evaluating the effects of drugs that act on cartilage and subchondral bone.