Combination Of Nonsteroidal Anti-inflammatory Drugs Research Articles

Outcomes after hip fracture surgery in patients receiving non-steroidal anti-inflammatory drugs alone, acetaminophen alone, or both.

The use of multimodal non-opioid analgesia in hip fractures, specifically acetaminophen combined with non-steroidal anti-inflammatory drugs (NSAIDs), has been increasing. However, the effectiveness and safety of this approach remain unclear. This study aimed to compare postoperative outcomes among patients with hip fractures who preoperatively received either acetaminophen combined with NSAIDs, NSAIDs alone, or acetaminophen alone. This nationwide retrospective cohort study used data from the Diagnosis Procedure Combination database. We included patients aged ≥ 18 years who underwent surgery for hip fractures and received acetaminophen combined with NSAIDs (combination group), NSAIDs alone (NSAIDs group), or acetaminophen alone (acetaminophen group) preoperatively, between April 2010 and March 2022. Primary outcomes were in-hospital mortality and complications. Secondary outcomes were opioid use postoperatively; readmission within 90 days, one year, and two years; and total hospitalization costs. We used propensity score overlap weighting models, with the acetaminophen group as the reference group. We identified 93,018 eligible patients, including 13,068 in the combination group, 29,203 in the NSAIDs group, and 50,474 in the acetaminophen group. Propensity score overlap weighting successfully balanced patient characteristics among the three groups, with no significant difference in in-hospital mortality rates observed among the groups (combination group risk difference 0.0% (95% CI -0.5 to 0.4%); NSAIDs group risk difference -0.2% (95% CI -0.5 to 0.2%)). However, the combination group exhibited a significantly lower risk of in-hospital complications than the acetaminophen group (risk difference -1.9% (95% CI -3.2 to -0.6%)) as well as a significantly lower risk of deep vein thrombosis (risk difference -1.4% (95% CI -2.2 to -0.7%)). Furthermore, total hospitalization costs were higher in the NSAIDs group than in the acetaminophen group (difference USD $438 (95% CI 249 to 630); p < 0.001). No significant differences in other secondary outcomes were observed among the three groups. The combination of acetaminophen with NSAIDs appears to be safe and advantageous in terms of reducing in-hospital complications.

Real-World Bleeding Risk of Anticoagulant and Nonsteroidal Anti-inflammatory Drugs Combotherapy versus Anticoagulant Monotherapy.

The incidence of acute gastrointestinal bleeding (GIB) increases with the utilization of anticoagulant and nonsteroidal anti-inflammatory drugs (NSAIDs). This study aimed to compare the risk of GIB between anticoagulant and NSAIDs combotherapy and anticoagulant monotherapy in real-world practice. We investigated the relative risk of GIB in individuals newly prescribed anticoagulant and NSAIDs combination therapy and that in individuals newly prescribed anticoagulant monotherapy at three hospitals using "common data model." Cox proportional hazard models and Kaplan-Meier estimation were employed for risk comparison after propensity score matching. A comprehensive analysis of 2,951 matched pairs showed that patients who received anticoagulant and NSAIDs combousers exhibited a significantly higher risk of GIB than those who received anticoagulant monousers (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.30 to 2.12; p<0.001). The risk of GIB associated with anticoagulant and NSAIDs combination therapy was also significantly higher than that associated with anticoagulant monotherapy in patients aged >65 years (HR, 1.53; 95% CI, 1.15 to 2.03; p=0.003) and >75 years (HR, 1.89; 95% CI, 1.23 to 2.90; p=0.003). We also found that the risk of GIB was significantly higher in the patients who received anticoagulant and NSAIDs combousers than that in patients who received anticoagulant monousers in both male (p=0.016) and female cohorts (p=0.010). The risk of GIB is significantly higher in patients who receive anticoagulant and NSAIDs combotherapy than that in patients who receive anticoagulant monotherapy. In addition, the risk of GIB associated with anticoagulant and NSAIDs combotherapy was much higher in individuals aged >75 years. Therefore, physicians should be more aware of pay more attention to the risk of GIB when they prescribe anticoagulant and NSAIDs.

Selection of NSAIDs for rational pharmacotherapy of chronic musculoskeletal pain: a clinical pharmacologist's perspective

Chronic musculoskeletal pain (CMSP) is one of the most common pathological conditions that limits patients' physical activity and reduces their quality of life. The analgesic and anti-inflammatory effects of non-steroidal anti-inflammatory drugs (NSAIDs) make them the basis of pharmacotherapy for patients with chronic conditions affecting various parts of the musculoskeletal system. The main target of NSAIDs, cyclooxygenase (COX), exists in the form of two main isoforms, COX-1 and COX-2, the inhibition of each of which leads to a cascade of reactions at the cellular and tissue level that can cause both targeted pharmacological effects and side effects. The diversity of the chemical structures of NSAIDs leads to differences in their pharmacodynamic and pharmacokinetic parameters and correspondingly to differences in their efficacy and safety profile. Selective COX-2 inhibitors, coxibs, have shown an increased risk of cardiovascular side effects, which has led to significant restrictions on their use. Cardiotoxicity is not as pronounced with the non-selective COX inhibitors, but the range of their side effects is extremely wide. These side effects are dose-dependent and are characteristic, first of all, of systemic NSAIDs.The combination of systemic and topical NSAIDs makes it possible to reduce the dose of the former and improve the safety profile of anti-inflammatory therapy. Among the non-selective COX inhibitors with a satisfactory safety profile and high anti-inflammatory activity, the group of oxicams and especially tenoxicam should be emphasised, which are characterised by a maximum duration of action, which is an advantage in the treatment of patients with CMSP. This review addresses the issues of rational selection of NSAIDs based on comparative data on pharmacodynamics, pharmacokinetics and clinical trial results.

Non-steroidal anti-inflammatory drugs, renin-angiotensin system blockade or diuretics and risk of acute kidney injury: A case-crossover study

BackgroundAging-related physiological changes, such as decline in renal function, not only exacerbates pre-existing comorbidities but also escalate the susceptibility to adverse events. Previous studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI), and the concomitant use of renin-angiotensin system blockade or diuretics may further potentiate the risk. However, studies evaluating the risk of AKI associated with NSAIDs (including routes, concomitant use of different NSAIDs, categories (traditional NSAIDs or COX-2 inhibitors), and cumulative doses of NSAIDs) are limited, particularly the risk of AKI associated with the dual or triple combination of NSAIDs with renin-angiotensin system blockade (RAS blockades) and/or diuretics. MethodsA case-crossover study utilized two sets of longitudinal data from Taiwan's National Health Insurance Research Database (NHIRD). Newly admitted patients with a primary AKI diagnosis were included, with the index date defined as the first admission date. The 1–7 days and 181–187 days prior to the index date served as the case and control periods. Exposure to NSAIDs and co-exposures of RAS blockade and/or diuretics were assessed in both periods. Multivariable conditional logistic regression models, adjusting for potential confounders, estimated adjusted odds ratios (aORs) and 95 % confidence intervals (CIs) for AKI associated with NSAIDs, dual, or triple combinations. Sensitivity analyses explored result robustness by varying case and control period lengths. ResultsThe study included 1,284 newly diagnosed AKI patients. NSAIDs showed a 3.55-fold increased risk of AKI (aOR: 3.55; 95 % CI 2.70–4.65), with similar risks for traditional NSAIDs and COX-2 inhibitors. Use of multiple NSAIDs, parenteral dosage forms, and higher cumulative doses increased AKI risk. Dual combination with either RAS blockade or diuretics resulted in a 2.90-fold (aOR: 2.90; 95 %CI 1.47–5.70) and 12.68-fold (aOR: 12.68; 95 %CI 6.15–26.12) risk, respectively. The highest risk occurred with triple combination (aOR: 29.22; 95 %CI 12.82–66.64). ConclusionsNSAIDs, including both non-selective NSAIDs and COX2 inhibitors, elevate the risk of AKI. Increased AKI risk is linked to using multiple NSAIDs, the parenteral dosage form, and higher cumulative doses. Dual combination of RAS blockade with NSAIDs or diuretics with NSAIDs, as well as triple therapy, heightens the risk, with the latter associated with the highest risk of AKI.

An evidence-based guideline on treating lumbar disc herniation with traditional Chinese medicine.

Lumbar disc herniation (LDH), as one of the most common causes of lower back pain, imposes a heavy economic burden on patients and society. Conservative management is the first-line choice for the majority of LDH patients. Traditional Chinese medicine (TCM) is an important part of conservative treatment and has attracted more and more international attention. Evidence-based guideline. We formed a guideline panel of multidisciplinary experts. The clinical questions were identified on the basis of a systematic literature search and a consensus meeting. We searched the literature for direct evidence on the management of LDH and assessed its certainty-generated recommendations using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. The guideline panel made 20 recommendations, which covered the use of Shentong Zhuyu decoction, Shenzhuo decoction, Simiao San decoction, Duhuo Jisheng decoction, Yaobitong capsule, Yaotongning capsule, Osteoking, manual therapy, needle knife, manual acupuncture, electroacupuncture, Chinese exercise techniques (Tai Chi, Baduanjin, or Yijinjing), and integrative medicine, such as combined non-steroidal anti-inflammatory drugs, neural nutrition, and traction. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. This is the first LDH treatment guideline for TCM and integrative medicine with a systematic search, synthesis of evidence, and using the GRADE method to rate the quality of evidence. We hope these recommendations can help support healthcare workers caring for LDH patients.

Quantitative sensory testing, psychological factors, and quality of life as predictors of current and future pain in patients with knee osteoarthritis.

Substantial interindividual variability characterizes osteoarthritis (OA) pain. Previous findings identify quantitative sensory testing (QST), psychological factors, and health-related quality of life as contributors to OA pain and predictors of treatment outcomes. This exploratory study aimed to explain baseline OA pain intensity and predict OA pain after administration of a nonsteroidal anti-inflammatory drug in combination with paracetamol for 3 weeks. The Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score was used to estimate OA pain presentation. One hundred one patients were assessed at baseline and follow-up using QST (pressure pain thresholds and temporal summation of pain [TSP]), symptoms of depression and anxiety, pain catastrophizing scales (PCSs), and health-related quality of life. Linear regression with backward selection identified that PCS significantly explained 34.2% of the variability in baseline KOOS pain, with nonsignificant contributions from TSP. Pain catastrophizing score and TSP predicted 29.3% of follow-up KOOS pain, with nonsignificant contributions from symptoms of anxiety. When assessed separately, PCS was the strongest predictor (32.2% of baseline and 24.1% of follow-up pain), but QST, symptoms of anxiety and depression, PCS, and quality of life also explained some variability in baseline and follow-up knee OA pain. Further analyses revealed that only TSP and PCS were not mediated by any other included variables, highlighting their role as unique contributors to OA pain presentation. This study emphasizes the importance of embracing a multimodal approach to OA pain and highlights PCS and TSP as major contributors to the baseline OA pain experience and the OA pain experience after OA treatment.

Synergistic effect of a nonsteroidal anti-inflammatory drug in combination with topotecan on small cell lung cancer cells.

The topoisomerase I inhibitor topotecan (TPT) is used in the treatment of recurrent small cell lung cancer (SCLC). However, the drug has a limited success rate and causes distress to patients due to its side effects, such as hematologic toxicities, including anemia and thrombocytopenia. Due to these pharmacokinetic limitations and undesirable side effects of chemotherapeutic drugs, the development of combination therapies has gained popularity in SCLC. Meclofenamic acid (MA), a nonsteroidal anti-inflammatory drug, has demonstrated anticancer effects on various types of cancers through different mechanisms. This study aims to investigate the potential synergistic effects of MA and TPT on the small cell lung cancer cell line DMS114. To assess the cytotoxic and apoptotic effects of the combined treatment of MA and TPT, trypan blue exclusion assay, Annexin V, acridine orange/propidium iodide staining, western blot, and cell cycle analysis were conducted. The results demonstrated that the combination of MA and TPT elicited synergistic effects by enhancing toxicity in DMS114 cells (P < 0.01) without causing toxicity in healthy epithelial lung cells MRC5. The strongest synergistic effect was observed when the cells were treated with 60 µM MA and 10 nM TPT for 48h (CI = 0,751; DRI = 10,871). This study, for the first time, furnishes compelling evidence that MA and TPT synergistically reduce cellular proliferation and induce apoptosis in SCLC cells. Combinations of these drugs holds promise as a potential therapeutic strategy to improve efficacy and reduce the side effects associated with TPT.

Transdermal buprenorphine patch as an adjunct to multimodal analgesia after total joint arthroplasty: a retrospective cohort study.

Total hip arthroplasty or total knee arthroplasty (THA/TKA) is often associated with varying degrees of pain. In recent years, transdermal buprenorphine (TDB) patch has shown encouraging results for acute postoperative pain control in orthopedic surgery. The aim of our study was to investigate the efficacy and safety of the combination of TDB patch and nonsteroidal anti-inflammatory drugs (NSAIDs) as a multimodal analgesic regimen after THA/TKA. Patients who underwent THA and TKA between January 2022 and January 2023 were reviewed. Three postoperative analgesic regimens were selected: Group A (flurbiprofen 50mg and tramadol 37.5mg/acetaminophen 325mg), Group B (flurbiprofen 50mg and TDB 5mg), and Group C (Parecoxib 40mg and TDB 5mg). The primary outcomes were the Wong-Baker face pain scale revision (FPS-R) scores and the rate of sleep disturbances. Secondary outcomes of the study included the proportion of patients with postoperative pain relief rates categorized as 0%, <50%, ≥50%, and 100%. The dynamic FPS-R pain scores on day 3 after surgery in Group B were significantly lower than those in Group A for THA (P < 0.017). The dynamic FPS-R pain scores were lowest in Group C on day 2 and 3 after THA and TKA (P < 0.017). Rate of sleep disturbances was significantly lower in Group B for THA and in Group C for TKA, respectively, compared with that in Group A (P < 0.017). The proportion of dynamic pain relief rate ≥50% in Group C was statistically higher than that in Group A for THA (P < 0.017). Rate of adverse reactions among three groups for THA and TKA was not statistically different (P > 0.05). This study suggests that the combination of TDB patch and NSAIDs is safe and effective for postoperative analgesia after THA/TKA.

Paracetamol versus Non-Steroidal Anti-Inflammatory Drugs in Acute Pain in Trauma Management: Systemic Review

Background: Effective pain management is essential for patient recovery and quality of life. Paracetamol (Acetaminophen) and Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are commonly used analgesics, but their comparative efficacy remains debated. Objective: To systematically review and compare the efficacy of paracetamol and NSAIDs in various pain scenarios. Methods: A comprehensive search was conducted across major databases, primarily using PubMed. The search yielded studies that compared paracetamol to any NSAID in human trials. Following strict inclusion and exclusion criteria, 11 studies with 3,038 participants were finally included in the review. Results: Paracetamol demonstrated comparable efficacy to NSAIDs in multiple scenarios such as post-trauma, post-partial Mastectomy Pain, and migraine in children. While, in certain situations like postoperative pain after Day-Case Operative Hysteroscopy, Pain Post-Total Hip Arthroplasty, and Pain during Rapid Maxillary Expansion, NSAIDs showcased superior efficacy. In some cases, however, such as renal colic, conflicting study evidence was presented. Moreover, in acute settings when administered I.V., paracetamol was slightly more effective. Finally, the combination of NSAIDs with paracetamol did not always offer enhanced analgesic effects. Conclusion: The choice between paracetamol and NSAIDs should be based on the specific clinical scenario and patient needs. While paracetamol is often seen as a safer option, NSAIDs play a vital role in pain management in certain conditions. Generally, due to its safety profile and less GIT and CVS complications, paracetamol should be preferred in pain management as first-line agent, especially in mild cases before moving to NSAIDS in more moderate to severe cases. The route of administration can also affect the analgesic\&amp;apos;s efficacy with the IV route showing higher efficacy. The findings highlight the potential for reducing opioid use by optimizing the use of non-opioids.

Treatment patterns and characteristics of headache in patients in Japan: A retrospective cross-sectional and longitudinal analysis of health insurance claims data.

The present study aimed to investigate prescription patterns for patients aged over 17 years with headaches in the REZULT database. We conducted a cross-sectional study (Study 1) of the proportion of over-prescription of acute medications (≥30 tablets/90 days for triptans, combination non-steroidal anti-inflammatory drugs (NSAIDs) and multiple types; ≥45 tablets/90 days for single NSAIDs) among patients with headache diagnosed in 2020. We longitudinally studied (Study 2) patients for >2 years from initial headache diagnosis (July 2010 to April 2022). The number of prescribed tablets was counted every 90 days. In Study 1, headache was diagnosed in 200,055 of 3,638,125 (5.5%) patients: 13,651/200,055 (6.8%) received acute medication. Single NSAIDs were prescribed to 12,297/13,651 (90.1%) patients and triptans to 1710/13,651 (12.5%). Over-prescription was found in 2262/13,651 (16.6%) patients and 1200/13,651 (8.8%) patients received prophylactic medication. In Study 2, 408,183/6,840,618 (6.0%) patients were first diagnosed with headaches, which persisted for ≥2 years. Over time, the proportion of patients over-prescribed acute medications increased. Over 2 years, 37,617/408,183 (9.2%) patients were over-prescribed acute medications and 29,313/408,183 (7.2%) patients were prescribed prophylaxis at least once. According to real-world data, prophylaxis remains poorly prescribed, and both acute and prophylactic treatment rates for headaches have increased over time.

Acute Corneal Melting Induced by the Concomitant Use of a Non-steroidal Anti-inflammatory Agent with an Antiseptic Eye Drop.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed perioperatively to reduce intraoperative prostaglandin release, diminishing pain, preventing miosis, modulating postoperative inflammation, and reducing the incidence of cystoid macular edema (CME). A 70-year-old female patient without previous history of ocular or systemic disease was urgently referred to our hospital because of a sudden corneal perforation concerning her left eye (OS). The patient had instilled bromfenac eye drops and antiseptic eye drops twice and four times daily, respectively, for 2days only, in preparation of scheduled cataract surgery. Slit-lamp examination revealed diffuse inferior corneal melting with a 1 × 2 mm area of full-thickness perforation and a very shallow anterior chamber. Both topical agents were immediately discontinued. Cyanoacrylate glue was applied to seal the perforation and a bandage contact lens was applied together with a topical antibiotic given hourly. Two hours later, the anterior chamber started to reform. The following day, the anterior chamber was fully reformed with a negative Seidel test. At her next follow-up appointment, 1month later, the glue was detached and the cornea was seen to have successfully healed with only some corneal thinning remaining inferiorly. Perioperative use of topical NSAIDs in combination with antiseptic eye drops may rarely elicit corneal perforation in certain susceptible elderly individuals. Their use should therefore be carefully monitored.

Effects of low-dosage radiotherapy for knee osteoarthritis on the incidence of knee arthroplasty: Results of a randomized controlled trial with 9-year follow-up

The aim. To compare the incidence of knee arthroplasty in patients receiving standard treatment with non-steroidal anti-inflammatory drugs (NSAIDs) in combination with symptomatic slow acting drugs for osteoarthritis (SYSADOA), or combination of NSAIDs and SYSADOA with low-dose radiation therapy (LDRT) in patients with stage 0–2 knee osteoarthritis (OA). Materials and methods. The article presents the results of randomized controlled study of 292 patients with confirmed knee OA according to Altman’s criteria (1991) and Kellgren – Lawrence radiographic stages 0–2 who were randomized into two groups. The control group (n = 146) received standard therapy of NSAIDs + SYSADOA. Patients of the study group (n = 146) received combination of standard therapy and LDRT up to a total dose of 4.5 Gy. The cumulative risk of knee arthroplasty was assessed using actuarial analysis and the Kaplan – Meier method. Attributable (AF) and population attributable (PAF) fractions were calculated to assess LDRT preventive potential. Results. The total observation period was 2131.2 person-years. Knee arthroplasty was performed in 4.1 % (n = 6) of patients in the study group against 7.5 % (n = 11) in the control group. The incidence density ratio was 0.60 (95% CI: 0.18–1.88), which corresponds to a risk reduction by 67 %, but the differences were not statistically significant due to the small number of cases (p = 0.340). The AF was 40 % while the PAF was 21 %. Conclusions. The use of LDRT reduces the risk of knee arthroplasty by two-thirds and has the potential to prevent 21 % cases of knee arthroplasty in patients with knee OA. A study on a larger sample is required.

Cholinesterase inhibitors and non-steroidal anti-inflammatory drugs and the risk of peptic ulcers: A self-controlled study.

Non-steroidal anti-inflammatory drugs (NSAIDs) should be used with caution in adults aged 65 years and older. Their gastrointestinal adverse event risk might be further reinforced when using concomitant cholinesterase inhibitors (ChEIs). We aimed to investigate the association between NSAIDs and ChEI use and the risk of peptic ulcers in adults aged 65 years and older. Register-based self-controlled case series study including adults ≥65 years with a new prescription of ChEIs and NSAIDs, diagnosed with incident peptic ulcer in Sweden, 2007-2020. We identified persons from the Total Population Register individually linked to several nationwide registers. We estimated the incidence rate ratio (IRR) of peptic ulcer with a conditional Poisson regression model for four mutually exclusive risk periods: use of ChEIs, NSAIDs, and the combination of ChEIs and NSAIDs, compared with the non-treatment in the same individual. Risk periods were identified based on the prescribed daily dose, extracted via a text-parsing algorithm, and a 30-day grace period. Of 70,060 individuals initiating both ChEIs and NSAIDs, we identified 1500 persons with peptic ulcer (median age at peptic ulcer 80 years), of whom 58% were females. Compared with the non-treatment periods, the risk of peptic ulcer substantially increased for the combination of ChEIs and NSAIDs (IRR: 9.0, [6.8-11.8]), more than for NSAIDs alone (5.2, [4.4-6.0]). No increased risks were found for the use of ChEIs alone (1.0, [0.9-1.2]). We found that the risk of peptic ulcer associated with the concomitant use of NSAIDs and ChEIs was over and beyond the risk associated with NSAIDs alone. Our results underscore the importance of carefully considering the risk of peptic ulcers when co-prescribing NSAIDs and ChEIs to adults aged 65 years and older.

Comparison of Colchicine Monotherapy Versus Nonsteroidal Anti-Inflammatory Drugs Monotherapy or Combination Therapy for the Prevention of Recurrent Pericarditis in Patients With Heart Failure With Reduced Ejection Fraction and/or Coronary Artery Disease

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.

Ketoprofen, lysine and gabapentin co-crystal magnifies synergistic efficacy and tolerability of the constituent drugs: Pre-clinical evidences towards an innovative therapeutic approach for neuroinflammatory pain

Chronic pain is an enormous public health concern, and its treatment is still an unmet medical need. Starting from data highlighting the promising effects of some nonsteroidal anti-inflammatory drugs in combination with gabapentin in pain treatment, we sought to combine ketoprofen lysine salt (KLS) and gabapentin to obtain an effective multimodal therapeutic approach for chronic pain. Using relevant in vitro models, we first demonstrated that KLS and gabapentin have supra-additive effects in modulating key pathways in neuropathic pain and gastric mucosal damage. To leverage these supra-additive effects, we then chemically combined the two drugs via co-crystallization to yield a new compound, a ternary drug-drug co-crystal of ketoprofen, lysine and gabapentin (KLS-GABA co-crystal). Physicochemical, biodistribution and pharmacokinetic studies showed that within the co-crystal, ketoprofen reaches an increased gastrointestinal solubility and permeability, as well as a higher systemic exposure in vivo compared to KLS alone or in combination with gabapentin, while both the constituent drugs have increased central nervous system permeation. These unique characteristics led to striking, synergistic anti-nociceptive and anti-inflammatory effects of KLS-GABA co-crystal, as well as significantly reduced spinal neuroinflammation, in translational inflammatory and neuropathic pain rat models, suggesting that the synergistic therapeutic effects of the constituent drugs are further boosted by the co-crystallization. Notably, while strengthening the therapeutic effects of ketoprofen, KLS-GABA co-crystal showed remarkable gastrointestinal tolerability in both inflammatory and chronic neuropathic pain rat models. In conclusion, these results allow us to propose KLS-GABA co-crystal as a new drug candidate with high potential clinical benefit–to–risk ratio for chronic pain treatment.

Upturn Strategies for Arachidonic Acid-Induced MC3T3-E1—625 nm Irradiation in Combination with NSAIDs: Dissipating Inflammation and Promoting Healing

Oral surgery, such as tooth extractions and dental implantations, can cause inflammation in the surrounding tissue, especially in bones. Anti-inflammatory drugs are crucial for pain relief and wound healing. Nonsteroidal anti-inflammatory drugs (NSAIDs) and light-emitting diode irradiation (LEDI) at 625 nm have been used as therapies to reduce inflammation, which ultimately promotes wound healing. The mechanism of these two methods, however, is different, which possibly makes the combined use of the two approaches effective. Therefore, the efficacy of 625 nm LEDI, NSAIDs, or a combination of both on anti-inflammatory and wound healing effects were analyzed in MC3T3-E1. In this study, piroxicam, ibuprofen, indomethacin, and celecoxib were selected as the NSAIDs. The effect of LEDI at 625 nm was investigated by cell viability, prostaglandin E2 (PGE2) release, and the expression of inflammation-related proteins and cell migration-related proteins were evaluated. Additionally, alkaline phosphatase staining with activity, cell migration assay and BrdU cell proliferation assays were performed. Both LEDI and NSAIDs reduced cyclooxygenase-2 (COX-2) and PGE2. Additionally, LEDI promoted cell migration, proliferation, and bone formation as well, but not by NSAIDs. Thus, a combination of LEDI and NSAIDs can benefits the cells in inflammation, which provides upturn strategies for bone healing after tooth extraction.

Glucocorticoids added to paracetamol and NSAIDs for post-operative pain: A systematic review with meta-analysis and trial sequential analysis.

Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as the basic pain treatment regimen for most surgeries. Glucocorticoids have well-known anti-inflammatory and anti-emetic properties and may also demonstrate analgesic effects. We assessed benefit and harm of adding glucocorticoids to a combination of paracetamol and NSAIDs for post-operative pain management. We searched Embase, Medline and CENTRAL for randomised clinical trials investigating the addition of glucocorticoids versus placebo/no intervention to paracetamol and an NSAID in adults undergoing any type of surgery. We assessed three primary outcomes: cumulative opioid consumption at 24 h postoperatively, serious adverse events and pain at rest at 24 h postoperatively. We performed meta-analysis and trial sequential analysis (TSA), assessed risk of bias using the Risk of Bias 2 tool and used the Grading of Recommendations Assessment, Development and Evaluation approach to evaluate the certainty of the evidence. We identified 12 relevant trials of which nine trials randomising 804 participants were included in quantitative analysis. When added to paracetamol and NSAIDs, we found no evidence of a difference of glucocorticoids versus placebo/no intervention in cumulative opioid consumption at 24 h postoperatively (mean difference [MD] -0.28, TSA-adjusted 95% confidence interval [CI] -1.90 to 1.33, p=.68, moderate certainty of evidence), serious adverse events (risk ratio (RR) 0.99, TSA-adjusted 95% CI 0.27-3.63, p=.93, very low certainty of evidence) or pain on the Numeric Rating Scale at 24 h postoperatively (MD -0.39, TSA-adjusted 95% CI -0.84 to 0.17, p=.10, moderate certainty of evidence). All outcomes were assessed to be at high risk of bias and TSA showed that we had insufficient information for most outcomes. Glucocorticoids added to a baseline therapy of paracetamol and an NSAID likely result in little to no difference in cumulative opioid consumption and pain at rest at 24 h postoperatively. In addition, the evidence is very uncertain about the effect on serious adverse events. For most outcomes we did not have sufficient information to draw firm conclusions and the certainty of the evidence varied from moderate to very low. Multimodal approaches for post-operative analgesia are favoured, including paracetamol and nonsteroidal anti-inflammatory drugs. In this meta-analysis, pooled results from clinical trials are assessed to describe possible benefit of addition of glucocorticoid treatment for analgesia. The findings did not identify additional benefit, though the certainty of the evidence was not high.

Dressler syndrome: a literature review

Gabrielė Žūkaitė1, Rasa Šimoniūtytė2 1Lithuanian University of Health Sciences, Faculty of Medicine, Kaunas, Lithuania 2Vilnius City Clinical Hospital, Department of Internal Medicine, Vilnius, Lithuania Abstract Background. Dressler syndrome (DS) occurs as a result of injury to the heart or pericardium, usually 1 to 6 weeks after a myocardial infarction. The incidence is decreasing due to advanced treatment methods. Pathogenesis still remains unclear, but it is associated with autoimmune processes. Clinical DS symptoms are fever, pleuritic chest pain, and fluid in pericardial and/or pleural space (pericardial rub and murmurs may be heard). Aim: to select and analyze the latest diagnostic and treatment recommendations for DS based on the experience of researchers and to discuss the etiology, pathogenesis and clinical symptoms. Material and methods. A review of medical literature was performed using databases of PubMed, Elsevier, Google Scholar, and guidelines of European Society of Cardiology. The search was performed using the following keywords and combinations in English: Dressler syndrome, pericarditis, post-cardiac injury syndrome. Results. DS can be diagnosed if two of the five diagnostic criteria are present (fever without other alternative causes, pericardial or pleural pain, pericardial or pleural effusion, fluid in pericardium or pleura, and/or increased C-reactive protein). The first-line treatment is non-steroidal anti-inflammatory drugs in combination with colchicine. In treatment-resistant DS, glucocorticoids are given without discontinuing colchicine. If recovery is not achieved even with second-line treatment, immunomodulators or intravenous immunoglobulin are prescribed, and as a last resort, pericardiectomy is performed. Conclusion. DS has favorable prognosis if diagnosed in time, but there is a possibility of recurrence of the syndrome (colchicine is an approved medication for prevention). Keywords: Dressler syndrome, pericarditis, post–cardiac injury syndrome. Full article https://doi.org/10.53453/ms.2023.2.20

Nonopioid pharmacological management of acute low back pain: A level I of evidence systematic review.

Acute low back pain (LBP) imposes a significant socioeconomical burden as it is the condition that, worldwide, cause the most disability. Nonetheless, the literature regarding the best pharmacological management of acute LBP is limited, and the indications available in the literature are conflicting. This work investigates whether the pharmacological management of acute LBP can effectively reduce pain and disability, and aims to identify which drugs show the highest efficacy. This systematic review was conducted according to the 2020 PRISMA statement. In September 2022, PubMed, Scopus, and Web of Science were accessed. All the randomized controlled trials investigating the efficacy of myorelaxants, nonsteroidal anti-inflammatory drugs (NSAIDs), and paracetamol for acute LPB were accessed. Only studies that investigated the lumbar spine were included. Only studies reporting on patients with acute LBP with symptom duration of less than 12 weeks were included. Only patients older than 18 years and with nonspecific low back pain were included. Studies that investigated the use of opioids in acute LBP were not considered. Data from 18 studies and 3478 patients were available. Myorelaxants and NSAIDs were effective in reducing pain and disability in acute LBP at approximately one week. The combination of NSAIDs and paracetamol was associated with a greater improvement than the use of NSAIDs alone, but paracetamol alone did not induce any significant improvement. Placebo was not effective in reducing pain. Clinical Significance: Myorelaxants, NSAIDs, and NSAIDs with paracetamol could reduce pain and disability in patients with acute LBP.

EFFECT OF DIFFERENT TREATMENTS ON SYNOVIAL FLUID PARAMETERS IN EXPERIMENTAL OSTEOARTHRITIS IN RABBITS

Veterinary specialists are actively studying the problem of osteoarthritis in animals (horses, dogs, cats, rabbits) and methods of overcoming it. At present, there are classical treatment regimens that give positive results, and the use of platelet-rich plasma (PRP) is being actively introduced into veterinary practice. In this regard, the studies described in this article were aimed at applying the effectiveness and evaluating changes in animals with experimental knee osteoarthritis of non-steroidal anti-inflammatory drugs in combination with chondroitin and glucosamine (classical treatment regimen) and platelet-rich plasma. The material of the study was synovial fluid obtained from animals with experimentally formed osteoarthritis of the knee joint on days 7, 14, 21 and 28 after the start of treatment using two different methods. In the animals of the experimental group (classical treatment regimen), on the 7th day, a decrease in the number of neutrophils by 31%, eosinophils by 12.5%, the number of lymphocytes increased by 31.3%, and macrophages decreased by 7% was observed. The number of lymphocytes increased by 7.3% compared to the baseline. On the 14th day, the number of neutrophils decreased by 61.5%, eosinophils by 45%, macrophages by 37.9%, and the number of lymphocytes increased by 4.5% compared to the 7th day. On the 21st day, the number of neutrophils decreased by 46.7%, eosinophils by 39.4%, macrophages by 51%, and the number of lymphocytes increased by 10.9% compared to the 14th day. On the 28th day, single neutrophils, eosinophils, and macrophages were observed in the synovial fluid samples, which corresponds to the physiological norm of synovial fluid composition. At the same time, the number of lymphocytes increased by 14.9% compared to the values of 21 days, but remained within the reference values. In animals treated with platelet-rich plasma on day 7, the number of neutrophils decreased by 54.7%, eosinophils by 33.7%, macrophages by 34% compared to the baseline, and the number of lymphocytes increased by 34% compared to the baseline. On the 14th day of the experiment, the number of neutrophils decreased by 60.5%, eosinophils by 37%, macrophages by 44.6%, and the number of lymphocytes increased by 10.5% compared to the 7th day, but were within the range of acceptable reference values. On day 21, single neutrophils, eosinophils, and macrophages were observed in the synovial fluid samples of animals of this group. It should be noted that the number of lymphocytes increased by 9.8 % compared to the values of day 14, which corresponds to the physiological norm of synovial fluid composition. On the 28th day of the experiment, single neutrophils and eosinophils were observed in the synovial fluid. At the same time, the number of lymphocytes increased by 19.5 % compared to day 21, which corresponds to the physiological norm of synovial fluid composition. The scientific material of experimental studies is of practical value for the use of platelet-rich plasma in the treatment of animals with osteoarthritis.