Ibuprofen: The Hidden Culprit Behind Aseptic Meningitis.

Drug-induced aseptic meningitis represents a significant clinical entity characterized by an inflammatory response of the meninges triggered by specific pharmacological agents. This condition predominantly manifests as a delayed hypersensitivity reaction to a variety of drugs, most notably non-steroidal anti-inflammatory drugs, antibiotics, immune checkpoint inhibitors, and monoclonal antibodies. We report a case of aseptic meningitis in a 54-year-old male presenting with nausea and blurred vision two hours after taking ibuprofen. This case aims to highlight one underrecognized adverse event associated with one of the most commonly used over-the-counter medications worldwide.

Involvement of heparanase in the pathogenesis of acute pancreatitis: Implication of novel therapeutic approaches.

Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa-Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.

Multimodal Analgesia Approach in Acute Low Back Pain Management: A Phase III Study of a Novel Analgesic Combination of Etoricoxib/Tramadol.

INTRODUCTION: Pain and disability management are crucial for a speedy recovery. Combining analgesics with different mechanisms of action provides greater pain relief with lower doses, promoting efficient multimodal analgesia. This study evaluated the efficacy and safety between two fixed-dose combinations (FDC): etoricoxib/tramadol compared to paracetamol/tramadol for the management of acute low back pain (LBP) in a 7-day treatment. METHODS: We conducted a phase IIIb, prospective, randomized, and multicenter study in patients with acute LBP treated with etoricoxib 90 mg/tramadol 50 mg (one packet of granules diluted in 100 ml of water, once a day [QD], for 7 days) or paracetamol 975 mg/tramadol 112.5 mg (one tablet of 325 mg/37.5 mg, three times a day [TID], for 7 days) to assess the efficacy (in terms of pain and disability improvement) and safety. RESULTS: One hundred and twenty-four patients were randomized to receive either etoricoxib/tramadol QD (n = 61) or paracetamol/tramadol TID (n = 63). From the magnitude of change in pain evaluations, differences were observed between the treatment groups at 3 [p = 0.054, CI 95% - 0.648 (- 0.010 to 1.306)] and 5 days (p = 0.041). The proportion of patients with a 30% reduction in Visual Analogue Scale (VAS) score was statistically significant when comparing the treatment groups on the third day of follow-up [p = 0.008, CI 95% 0.241 (0.061-0.421)]. An improvement in LBP's disability to perform activities of daily routine (Oswestry and Roland-Morris questionnaires) was observed in both treatment groups. A total of 79 adverse events (AEs) (38 [48.1%] with etoricoxib/tramadol and 41 [51.9%] with paracetamol/tramadol) were reported. The most frequent AEs were nausea (17.7%) and dizziness (16.4%). CONCLUSIONS: The results show the clinical benefits of etoricoxib/tramadol FDC, such as the sparing effect of tramadol dose per day, early therapeutic response rate compared with paracetamol/tramadol; which translates into faster pain relief, better adherence, less tramadol drug dependency, and a reduction of related AEs incidence. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04968158.

Exploring the impact of curcumin on osteoarthritis symptomatology: correlations and insights from a Bulgarian cohort.

INTRODUCTION: Osteoarthritis is a prevalent degenerative joint disorder associated with pain and functional impairment. Curcumin, a natural anti-inflammatory compound, has garnered attention for its potential therapeutic benefits in osteoarthritis management.

A Review of Current Approaches to Pain Management in Knee Osteoarthritis with a Focus on Italian Clinical Landscape.

The global cases of knee osteoarthritis (KOA) are projected to increase by 74.9% by 2050. Currently, over half of patients remain dissatisfied with their pain relief. This review addresses unmet needs for moderate-to-severe KOA pain; it offers evidence and insights for improved management. Italian experts from the fields of rheumatology, physical medicine and rehabilitation, orthopedics, primary care, and pain therapy have identified several key issues. They emphasized the need for standardized care protocols to address inconsistencies in patient management across different specialties. Early diagnosis is crucial, as cartilage responds better to early protective and structural therapies. Faster access to physiatrist evaluation and reimbursement for physical, rehabilitative, and pharmacological treatments, including intra-articular (IA) therapy, could reduce access disparities. Concerns surround the adverse effects of oral pharmacological treatments, highlighting the need for safer alternatives. Patient satisfaction with corticosteroids and hyaluronic acid-based IA therapies reduces over time and there is no consensus on the optimal IA therapy protocol. Surgery should be reserved for severe symptoms and radiographic KOA evidence, as chronic pain post-surgery poses significant societal and economic burdens. The experts advocate for a multidisciplinary approach, promoting interaction and collaboration between specialists and general practitioners, to enhance KOA care and treatment consistency in Italy.

Design, classification, and adverse effects of NSAIDs: A review on recent advancements.

Inflammation is a hallmark of many diseases, including cancer, neurodegenerative diseases like Alzheimer's, type II diabetes, rheumatoid arthritis, and asthma. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been a cornerstone in the management of various inflammatory, pain, and fever-related conditions. As a result, NSAIDs have found their applications in new therapeutic areas. NSAIDs are known to act by inhibiting the cyclooxygenase (COX) pathway. In recent years, new strategies have been proposed to counter inflammation and develop safer COX inhibitors. This review discusses the design of new COX inhibitors, the derivatization of conventional NSAIDs, and their biological applications. The review also presents an integrated classification of NSAIDs incorporating both traditional chemical-based and function-based approaches, including a brief overview of the NSAIDs of natural origins. Additionally, the review addresses adverse effects associated with different NSAIDs, including effects associated with cardiovascular, renal, and hepatic complications emphasizing the need for the development of new and safer COX inhibitors.

Osteoarthritis: An Update on Diagnosis & Management.

Osteoarthritis (OA) is the most prevalent joint condition. It is a progressively degenerating disease that involves the entire joint, including the articular cartilage, subchondral bone, ligaments, capsule, synovial fluid, and periarticular muscles. Physicians understand that osteoarthritis is diagnosed late during the illness, which may be too late for patients to receive significant benefits from medications that change their condition. The goals of OA therapy are to preserve function while minimizing pain and stiffness. This article focuses on the current and potential treatments for osteoarthritis and various diagnostic methodologies for this disease. In the coming years, despite having numerous treatments for symptomatic relief, the treatment plan should be more specialized because everyone might experience improved outcomes.

Acute medications' intake for migraine: a one-year report in patients undergoing first evaluation at a third level Italian headache center.

Background: Headache disorders, particularly primary headaches like migraine and tension-type headache, still remain underdiagnosed and undertreated despite their high prevalence and significant impact on quality of life. In recent years, several specific medications targeting key pathways in the pathophysiology of migraine have been developed. Despite this advancement, numerous studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics remain the most commonly used drugs. This study focused on the use of NSAIDs and simple analgesics as acute treatments for migraine among patients at a tertiary headache center. Methods: A retrospective observational study was conducted at the Fondazione Policlinico Universitario Campus Bio-Medico throughout 2022. Data were collected on the type and frequency of headaches, the usage and dosage of NSAIDs and other medications, and changes in their use at follow-up visits. Statistical analyses were performed to evaluate the efficacy and determinants of NSAID consumption and headache frequency changes. Results: Two hundred and eightythree patients diagnosed with migraine undergoing their first examination at our center were enrolled. Initially, 58.7% of patients used NSAIDs or simple analgesics, which decreased to 46.6% 3 months after, while triptan use increased from 65.1 to 72.8%. Changes in prophylactic therapies were significantly associated with a decrease in NSAID intake (W = 834.000, p = 0.004) and in headache frequency (W = 5960.5, p = 0.003). Specifically, the addition of topiramate or amitriptyline was associated with a reduction in NSAID use and headache frequency. Even pain freedom after the intake of NSAIDs improved from 55.2 to 79.4% of cases at follow-up. Conclusion: The study highlights the importance of appropriate diagnosis and tailored treatment strategies in the management of primary headaches. It underscores the need for specialized care to enhance treatment efficacy and patient outcomes, demonstrating that adjustments in prophylactic therapy can significantly reduce NSAID intake and improve headache care. This reinforces the role of tertiary headache centers in providing specialized care that can adapt treatments to individual patient needs and improve overall headache management.

Case report of HIV associated arthritis.

Human immunodeficiency virus (HIV) infection is prevalent worldwide. Children living with HIV/AIDS form a vulnerable subsection and may frequently present with clinical symptoms in the first year of life itself. Besides its well-known signs and symptoms, HIV infection can have a wide spectrum of musculoskeletal manifestations. We report a case of a child with HIV infection with arthritis as a predominant presentation. The patient was anemic (Hb: 2.6 g/dl) and had features suggestive of inflammation, that is, highly elevated C-reactive protein (CRP) (161 mg/l), and erythrocyte sedimentation rate (ESR) (46 mm/h) values, accompanied with leukocytosis (12,100 cells/cu mm) and thrombocytoses (524,000 cells/ku mm). Urine culture showed Enterococcus spp. sensitive to linezolid and nitrofurantoin. A bone marrow aspiration and biopsy was done including culture for bacterial, mycobacterium and fungus. Treatment of arthritis in HIV-infected children can be challenging. It is crucial to recognize the arthritic manifestation of HIV infection in order to avoid delaying diagnosis and starting proper treatment.

Insights from pharmacovigilance and pharmacodynamics on cardiovascular safety signals of NSAIDs.

Background and Aim: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat fever, pain, and inflammation. Concerns regarding their cardiovascular safety have been raised. However, the underlying mechanism behind these events remains unknown. We aim to investigate the cardiovascular safety signals and receptor mechanisms of NSAIDs, employing a comprehensive approach that integrates pharmacovigilance and pharmacodynamics. Methods: This study utilized a pharmacovigilance-pharmacodynamic approach to evaluate the cardiovascular safety of NSAIDs and explore potential receptor mechanisms involved. Data were analyzed using the OpenVigil 2.1 web application, which grants access to the FDA Adverse Event Reporting System (FAERS) database, in conjunction with the BindingDB database, which provides target information on the pharmacodynamic properties of NSAIDs. Disproportionality analysis employing the Empirical Bayes Geometric Mean (EBGM) and Reporting Odds Ratio (ROR) methods was conducted to identify signals for reporting cardiovascular-related adverse drug events (ADEs) associated with 13 NSAIDs. This analysis encompassed three System Organ Classes (SOCs) associated with the cardiovascular system: blood and lymphatic system disorders, cardiac disorders, and vascular disorders. The primary targets were identified through the receptor-NSAID interaction network. Ordinary least squares (OLS) regression models explored the relationship between pharmacovigilance signals and receptor occupancy rate. Results: A total of 201,231 reports of cardiovascular-related ADEs were identified among the 13 NSAIDs. Dizziness, anemia, and hypertension were the most frequently reported Preferred Terms (PTs). Overall, nimesulide and parecoxib exhibited the strongest signal strengths of ADEs at SOC levels related to the cardiovascular system. On the other hand, our data presented naproxen and diclofenac as drugs of comparatively low signal strength. Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were identified as central targets. OLS regression analysis revealed that the normalized occupancy rate for either COX-1 or COX-2 was significantly inversely correlated with the log-transformed signal measures for blood and lymphatic system disorders and vascular disorders, and positively correlated with cardiac disorders and vascular disorders, respectively. This suggests that higher COX-2 receptor occupancy is associated with an increased cardiovascular risk from NSAIDs. Conclusion: Cardiovascular safety of NSAIDs may depend on pharmacodynamic properties, specifically, the percentage of the occupied cyclooxygenase isoenzymes. More studies are needed to explore these relations and improve the prescription process.

Treatment of Idiopathic Inflammatory Orbital Syndrome (IOIS) With Prominent Lacrimal Gland Involvement Using Oral Non-Steroidal Anti-Inflammatory Drugs (NSAIDs).

Idiopathic orbital inflammatory syndrome (IOIS) is a chronic inflammatory process of unknown etiology, which can either be localized or diffuse. In cases where there is isolated inflammation of the lacrimal gland, it is known as dacryoadenitis. This study focuses on the treatment of a patient with IOIS with prominent lacrimal gland involvement. The mainstay of treatment for idiopathic isolated dacryoadenitis is oral corticosteroids, but non-steroidal anti-inflammatory drug (NSAIDs) is known to be effective in treating idiopathic dacryoadenitis as well. There is no formal study yet to evaluate the use of NSAIDs in treating idiopathic dacryoadenitis. Here, we report a case of idiopathic isolated dacryoadenitis which was successfully treated with NSAIDs.

Self-Reported Gastrointestinal Symptoms Associated with NSAIDs and Caffeine Consumption in a Jordanian Subpopulation.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) and caffeine-containing beverages are widely consumed but their impact on gastrointestinal (GI) health requires further investigation. This cross-sectional study investigated the relationship between NSAIDs use, caffeinated drink consumption, and the prevalence of self-reported GI symptoms in a Jordanian subpopulation. Methods: An online survey was administered to 400 Jordanian individuals aged 18-65 years. Data on sociodemographics, NSAIDs use, caffeine consumption, peptic ulcer disease (PUD) history, and GI symptoms were collected. Contingency tables were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between exposures and outcomes. Results: The prevalence of self-reported PUD-related GI symptoms was 6.0%. NSAID users had higher odds of PUD (OR = 2.431) and related GI symptoms, including abdominal pain (OR = 4.688, p < 0.001) and discomfort (OR = 8.068, p < 0.001). Caffeine consumption was associated with self-reported burning stomach pain (OR = 14.104, p < 0.001), fullness (OR = 8.304, p = 0.010), and bloating (OR = 8.304, p = 0.010). Coffee, tea, soft drinks, and energy drinks were associated with increased odds of various GI symptoms (ORs 2.018-12.715, p < 0.05). Conclusions: NSAIDs use and caffeine consumption were independently associated with the increased prevalence of self-reported PUD and related GI symptoms. Despite the lack of adjustment for necessary confounders, our findings highlight the importance of considering the potential GI effects of NSAIDs and caffeine. Public health strategies promoting their safe use may help reduce the burden of GI disorders.

Oxymatrine alleviates NSAID-associated small bowel mucosal injury by regulating MIP-1/CCR1 signalling and gut microbiota.

Oxymatrine (OMT) as a quinazine alkaloid extracted from matrine has been shown to exhibit anti-inflammatory and anti-tumour effects. However, the protective mechanism of OMT on NSAID-associated small bowel mucosal injury remains unreported. We found that OMT could improve the clinical symptoms and pathological inflammation scoring, reduce the secretion of proinflammatory cytokines IL-1ß, IL-6 and TNF-α and cell apoptosis, promote cell proliferation and protect intestinal mucosal barrier as compared with the Diclofenac Sodium (DS) group. Further RNA-seq and KEGG analysis uncovered that the differentially expressed genes between DS and control groups were mainly enriched in immune regulation, of which MIP-1γ and its receptor CCR1 expression were validated to be repressed by OMTH. MAPK/NF-κB as the MIP-1 upstream signalling was also inactivated by OMT treatment. In this study, OMT regulated gut microbiota. Venn diagrams visualized and identified 1163 shared OTUs between DS group and OMTH group. The results showed that the α diversity index in the DS group was lower than that in the OMTH group, indicating that the complexity of the flora was reduced in the intestinal inflammatory state. ß diversity mainly includes Principal Component Analysis (PCA) and Principal Co-ordinates Analysis (PCoA). The differences between groups can be observed through PCA. The more similar the composition of the flora, the closer the samples are. We found that the difference was smaller in the DS group than in the OMTH group. The results of PcoA showed that the sample similarity between OMTH groups was the highest. Moreover, gut microbiota analysis unveiled that the abundances of Ruminococcus 1, Oscillibacter and Prevotellaceae at the genus level as well as Lactobacillus SP-L-Yj at the species level were increased in OMTH group as compared with the DS group but the abundance of Allobaculum, Ruminococceos-UCG-005, Ruminococceos-NK4A214 and Clostridium associated with DS-induced small bowel mucosal injury could be decreased by OMTH. MIP-1α and CCR1 were upregulated in human small bowel injury samples as compared with the normal ileal mucosa tissues. In conclusion, our findings demonstrated that OMT could alleviate NSAID-associated small bowel mucosal injury by inhibiting MIP-1γ/CCR1 signalling and regulating gut microbiota.

Treatment strategies for Spondyloarthritis: Implementation of precision medicine - Or "one size fits all" concept?

Spondyloarthritis (SpA) is a term to describe a group of chronic inflammatory rheumatic diseases, which have common pathophysiological, genetic, and clinical features. Under the umbrella term SpA, two main groups are subsumed: axial SpA (radiographic axSpA and non-radiographic axSpA) and peripheral SpA (with the leading representative being psoriatic arthritis (PsA) but also arthritis associated with inflammatory bowel disease (IBD), reactive arthritis, and undifferentiated pSpA). The key clinical symptom in axSpA is chronic back pain, typically with inflammatory characteristics, which starts in early adulthood, while the leading clinical manifestations of peripheral SpA (pSpA) are arthritis, enthesitis, and/or dactylitis. Furthermore, extra-musculoskeletal manifestations (EMMs) (acute anterior uveitis, psoriasis, and IBD) can accompany axial or peripheral symptoms. All these factors need to be taken into account when making treatment decisions in SpA patients. Despite the major advances in the treatment landscape over the past two decades with the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and most recently targeted synthetic DMARDs (tsDMARDs), a relevant proportion of patients still does not achieve the desired state of remission (=absence of disease activity). With this implementation of new treatment modalities, clinicians now have more choices to make in the treatment algorithms. However, despite generalized treatment recommendations, all factors need to be carefully considered when deciding on the optimal treatment strategy for an individual patient in clinical practice, aiming at an important first step towards personalized treatment strategies in SpA. In this narrative review, we focus on the efficacy of approved and emerging treatment options in axSpA and PsA as the main representative of pSpA and discuss their selective effect on the different manifestations associated with SpA to provide guidance on drivers of treatment decisions in specific situations.

Pain-free today, weak tomorrow: a case of electrolyte disorder due to diclofenac misuse.

BACKGROUND: The nephrotoxic effects of non-steroidal anti-inflammatory drugs (NSAIDs) are widely acknowledged. In particular, diclofenac is the most commonly prescribed NSAIDs, but no previous findings of electrolyte disturbances were reported following its administration. CASE REPORT: We presented the case of a man who experienced significant weakness associated with severe deficiencies in potassium, calcium, and magnesium after misusing diclofenac because of severe back pain. CONCLUSIONS: This case emphasizes the need of awareness about the electrolyte imbalances and electrolyte disturbances associated with the misuse of diclofenac, which is a widely available drug. This is a case report which does not need a Clinical Trial Number.

Current goals of NSAID-ERD management: patient-centered approaches involving NSAID desensitization with and without biologics.

Classic approach of non-steroidal anti-inflammatory drugs (NSAIDs) - exacerbated respiratory disease (NSAID-ERD) includes pharmaceutical and surgical treatments, as well as avoidance of COX-1-inhibitor NSAIDs. The introduction of biologics in the treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) represents an alternative therapeutic approach to the classical aspirin therapy after desensitization (ATAD) in some regions, and with convincing results. However, their use is limited due to approval and/or high-cost restrictions. NSAID-ERD is a mainly type 2 (T2) and highly eosinophilic disease, and monoclonal antibodies targeting IgE or interleukins (IL)-5, IL-4, and IL-13 have been shown to be effective for both severe asthma and severe CRSwNP. So far, dupilumab demonstrated greater efficacy in NSAID-ERD than in aspirin-tolerant patients with regards to several clinical outcomes. Patients with NSAID-ERD respond very rapidly to omalizumab also, with reduction in the release of prostaglandin D2 and cysteinyl leukotrienes. Patients favored biologic treatment over ATAD in multiple retrospective analyses, which must be acknowledged when choosing one or the other option. While this review will summarize ATAD in general, it will more prominently focus on when ATAD should be considered, even when T2 biologics are available. Additionally, there are conflicting studies as to whether patients on a T2 biologic become desensitized to NSAIDs, as omalizumab proved to restore tolerance to aspirin in only two thirds of patients. This goal of NSAIDs tolerance should be considered as part of disease control future approaches, representing one of many aspects in a patient-centered care approach.

Knee osteoarthritis: disease burden, available treatments, and emerging options.

Osteoarthritis (OA) is a prevalent condition that affects nearly 528 million people worldwide, including 23% of the global population aged ⩾40, and is characterized by progressive damage to articular cartilage, which often leads to substantial pain, stiffness, and reduced mobility for affected patients. Pain related to OA is a barrier to maintaining physical activity and a leading cause of disability, accounting for 2.4% of all years lived with disability globally, reducing the ability to work in 66% of US patients with OA and increasing absenteeism in 21% of US patients with OA. The joint most commonly involved in OA is the knee, which is affected in about 60%-85% of all OA cases. The aging population and longer life expectancy, coupled with earlier and younger diagnoses, translate into a growing cohort of symptomatic patients in need of alternatives to surgery. Despite the large number of patients with knee OA (OAK) worldwide, the high degree of variability in patient presentation can lead to challenges in diagnosis and treatment. Multiple society guidelines recommend therapies for OAK, but departures from guidelines by healthcare professionals in clinical settings reflect a discordance between evidence-based treatment algorithms and routine clinical practice. Furthermore, disease-modifying pharmacotherapies are limited, and treatment for OAK often focuses solely on symptom relief, rather than underlying causes. In this narrative review, we summarize the patient journey, analyze current disease burden and nonsurgical therapy recommendations for OAK, and highlight emerging and promising therapies-such as cryoneurolysis, long-acting corticosteroids, and gene therapies-for this debilitating condition.

Efficacy of different medications in the treatment of gynaecological tumours: a clinical meta-analysis.

Background: A gynaecological tumour is one of the world's leading causes of death for women globally. Among women, cancer is the 8th most common cause of death. Since there are no such programmes, the majority of women who are diagnosed with the condition are either in advanced stages or do not respond well to current treatments. Even if patients react to the treatments, they still risk having the cancer return, at which point any further medical intervention is met with resistance. Method: For this study, we selected the systemic reviews and articles that have the use of different medications used for the treatment of gynaecological tumours. Results: Regarding metformin use, this study found a positive relationship between higher survival and metformin use. Five of the studies that examined the use of statins revealed a link between statin use and higher overall and/or progression-free survival rates. Individuals on lipophilic and hydrophilic statins would do better. Research evaluating beta-blocker use during neoadjuvant treatment revealed a time-varying effect, with improved survival seen across all users early in the follow-up period. However, only non-selective beta-blocker users demonstrated a correlation with higher survival after five years. One study found that the benefits of aspirin use were significant, but the advantage for continuous users (both before and after diagnosis) was minimal. Conclusion: Conclusions on the association between gynaecological tumour survival and NA-NSAIDs, metformin, beta-blockers, and aspirin cannot be drawn due to insufficient evidence. However, the vast majority of statin studies have demonstrated that users had higher rates of survival. Bias, however, bias may affect the results of the studies.

Do NSAIDs affect bone healing rate, delay union, or cause non-union: an updated systematic review and meta-analysis.

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) may potentially delay or cause non-union of fractures by inhibiting prostaglandin synthesis. However, studies have shown conflicting results. This systematic review and meta-analysis aim to synthesize current evidence on the potential influence of NSAIDs on bone healing. Methods: We conducted a comprehensive search of PubMed, Embase, and Cochrane CENTRAL databases for studies published up to 25 July 2023. Specific keywords included "NSAID," "nonsteroidal anti-inflammatory drug," "cyclooxygenase-2 inhibitor," "bone healing," "non-union," "pseudoarthrosis," "delayed union," and "atrophic bone." Eligible studies included prospective, retrospective, and case-controlled studies assessing the correlation between NSAID use and bone healing outcomes. The leave-one-out approach was used to test the robustness of the meta-analysis results. Results: A total of 20 studies with 523,240 patients were included in the analysis. The mean patient age ranged from 6.7 to 77.0 years, with follow-up durations from 3 to 67 months. The meta-analysis revealed no significant difference in non-union or delayed union between NSAID users and non-users [pooled adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 0.99-1.23]. Initial analysis identified a significant association between NSAID usage and an increased risk of reoperation, but this association became insignificant upon sensitivity analysis (crude OR = 1.42; 95% CI: 0.88-2.28). Discussion: NSAIDs may have a minimal impact on non-union or delayed union risks. However, caution is advised due to the limited number of studies and the absence of a specific focus on NSAID types and dosages. Further research is necessary to better understand the implications of NSAID use on bone healing.