Efficacy Of Non-steroidal Anti-inflammatory Drugs Research Articles

Effectiveness of the Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) for Postoperative Pain Management in Patients Undergoing Major Surgical Operations at Manokwari Hospital

Postoperative pain is a common complication in patients undergoing major surgical operations, interfering with comfort and recovery and increasing the risk of further complications. This study aimed to evaluate the effectiveness of NSAIDs in managing postoperative pain at Manokwari Regional Hospital. Utilizing qualitative research methods, data was collected through observation and literature study and analyzed via data reduction, data presentation, and conclusion drawing. The findings indicate that NSAIDs effectively alleviate postoperative pain by inhibiting cyclooxygenase (COX) enzymes responsible for prostaglandin production. However, their use is limited by potential systemic side effects, including gastrointestinal disorders, kidney impairment, increased blood pressure, heart attack, and heart failure. Consequently, topical NSAID formulations are recommended to mitigate these risks. The study suggests that while NSAIDs are effective, clinicians should consider their side effects and prefer topical alternatives. Future research should explore the efficacy and safety of topical NSAIDs and alternative pain management strategies to enhance clinical practice.

The Multifaceted Effects of Non-Steroidal and Non-Opioid Anti-Inflammatory and Analgesic Drugs on Platelets: Current Knowledge, Limitations, and Future Perspectives.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these drugs exhibit various other pleiotropic effects in several cells, including platelets. Within this article, the multifaceted properties of NSAIDs on platelet functions, activation and viability, as well as their interaction(s) with established antiplatelet medications, by hindering several platelet agonists' pathways and receptors, are thoroughly reviewed. The efficacy and safety of NSAIDs as adjunctive therapies for conditions involving inflammation and platelet activation are also discussed. Emphasis is given to the antiplatelet potential of commonly administered NSAIDs medications, such as ibuprofen, diclofenac, naproxen and ketoprofen, alongside non-opioid analgesic and antipyretic medications like paracetamol. This article delves into their mechanisms of action against different pathways of platelet activation, aggregation and overall platelet functions, highlighting additional health-promoting properties of these anti-inflammatory and analgesic agents, without neglecting the induced by these drugs' side-effects on platelets' functionality and thrombocytopenia. Environmental issues emerging from the ever-increased subscription of these drugs are also discussed, along with the need for novel water treatment methodologies for their appropriate elimination from water and wastewater samples. Despite being efficiently eliminated during wastewater treatment processes on occasion, NSAIDs remain prevalent and are found at significant concentrations in water bodies that receive effluents from wastewater treatment plants (WWTPs), since there is no one-size-fits-all solution for removing all contaminants from wastewater, depending on the specific characteristics of the wastewater. Several novel methods have been studied, with adsorption being proposed as a cost-effective and environmentally friendly method for wastewater purification from such drugs. This article also presents limitations and future prospects regarding the observed antiplatelet effects of NSAIDs, as well as the potential of novel derivatives of these compounds, with benefits in other important platelet functions.

Contribution of non-steroidal anti-inflammatory drugs to breast cancer treatment: In vitro and in vivo studies

Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E2 and tissue overexpression of cyclooxygenase-2 (COX-2) have been described in breast, urinary, colorectal, prostate, and lung cancers as being involved in tumor initiation, promotion, progression, angiogenesis, and immunosuppression. Non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for several medical conditions to not only decrease pain and fever but also reduce inflammation by inhibiting COX and its product synthesis. To date, significant efforts have been made to better understand and clarify the interplay between cancer development, inflammation, and NSAIDs with a view toward addressing their potential for cancer management. This review provides readers with an overview of the potential use of NSAIDs and selective COX-2 inhibitors for breast cancer treatment, highlighting pre-clinical in vitro and in vivo studies employed to evaluate the efficacy of NSAIDs and their use in combination with other antineoplastic drugs. Keywords: breast cancer, chemoprevention, COX-2, cyclooxygenase, experimental studies, NSAIDs.

Non-Opioid Analgesics and Adjuvants after Surgery in Adults with Obesity: Systematic Review with Network Meta-Analysis of Randomized Controlled Trials.

Background/Objectives: Managing postoperative pain in patients with obesity is challenging. Although using a combination of pain relief methods is recommended for these patients, the true effectiveness of various intravenous non-opioid analgesics and adjuvants in multimodal anesthesia needs to be better defined. Methods: A systematic review and network meta-analysis was performed to evaluate the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, ketamine, α-2 agonists, lidocaine, magnesium, and oral gabapentinoids in adult surgical patients with obesity. The analysis aimed to compare these treatments to a placebo/no treatment or alternative analgesics, with a primary focus on postoperative pain and secondary endpoints including rescue analgesia, postoperative nausea and vomiting (PONV), and recovery quality. English-language randomized controlled trials across PubMed, Scopus, Web of Science, CINAHL, and EMBASE were considered. Quality and evidence certainty were assessed with the RoB 2 tool and GRADE, and data was analyzed with R software. Results: NSAIDs, along with acetaminophen, lidocaine, α-2 agonists, ketamine, and oral gabapentinoids, effectively reduce early postoperative pain. NSAIDs, particularly ibuprofen, as well as acetaminophen, ketamine, and lidocaine, also show benefits in later postoperative stages. Intravenous non-opioid analgesics and adjuvants show some degree of benefit in reducing PONV and the need for rescue analgesic therapy when using α-2 agonists alone or combined with oral gabapentinoids, notably decreasing the likelihood of PONV. Ketamine, lidocaine, and α-2 agonists are shown to enhance postoperative recovery and care quality. Conclusions: Intravenous non-opioid analgesics and adjuvants are valuable in multimodal anesthesia for pain management in adult surgical patients suffering from obesity.

Evaluating Knowledge, Self-Reported Confidence Levels, and Prescription Patterns among Dental Practitioners Regarding Analgesics in Dentistry: A Cross-Sectional Study.

Background and Objectives: Dental pain is a common problem that often leads to unscheduled dental visits and requires a comprehensive understanding of analgesics, including their indications and contraindications. The aim of this study was to investigate dentists' knowledge, self-reported confidence levels, and prescribing patterns of analgesics in dentistry. Materials and Methods: A nationwide cross-sectional online survey was conducted, resulting in 379 responses. Of these, 68.6% were general dentists, and 31.4% were specialists. The collected data included sociodemographic information, levels of knowledge, and prescription patterns. The survey questionnaire explored self-perceived practices, patient information during prescription, and guiding factors. Descriptive statistics and a generalized linear model for regression were used for data analysis. Results: Higher levels of knowledge were observed in specific contexts such as secondary/tertiary healthcare (p = 0.022), specialization in endodontics (p = 0.003), and a higher number of working hours with patients (p = 0.038). Conversely, increased self-confidence was observed among endodontists (p = 0.008), oral surgeons (p = 0.011), and dentists with more than 6 h of patient interaction (p ≤ 0.001). Orthodontists and prosthodontists demonstrated lower knowledge levels, while specialists in family dentistry exhibited lower self-confidence. Self-confidence and knowledge displayed a significant positive correlation (r = 0.039, p < 0.001). The most frequently prescribed medication was ibuprofen (97.9%), primarily for surgical (83.9%) and endodontic procedures (60.9%), with the main indications being pulpal (85.8%), periradicular (57.3%), and postoperative pain (40.1%). Conclusions: This study reveals significant knowledge and confidence gaps among dentists, including limited awareness of the efficacy of nonsteroidal anti-inflammatory drugs for odontogenic pain, a lack of time for effective counseling, and perceived deficits in pharmacology education. To address these issues, targeted educational interventions are recommended to improve analgesic prescribing practice, close knowledge gaps, and increase dentists' confidence in more effective pain management.

Repurposing of non-steroidal anti-inflammatory drugs for combination therapies to combat multidrug-resistant S. aureus of bovine reproductive tract origin.

Multidrug-resistant bacteria have become the predominant etiology in bovine female reproductive tract infections and thus require effective treatment approaches. The main goal of this study was the molecular detection of mecA, blaZ, tetK, and aacA-aphD genes in Staphylococcus aureus (S. aureus) responsible for methicillin, beta-lactam, tetracycline, and aminoglycoside resistance respectively. Phylogenetic analysis was conducted to check the homology of staphylococcal genes with NCBI sequences. The in-vitro efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in combination therapies against MDR S. aureus was evaluated using well diffusion assay and checkerboard method. Vaginal swab samples (n = 384) collected from bovines suffering from endometritis, pyometra, and retained placenta were tested for S. aureus. Results showed a 17.96% overall prevalence. Both phenotypic and genotypic resistance was observed among S. aureus isolates with 50.72% and 37.68% isolates being confirmed as methicillin-resistant (MRSA), 36.23% and 18.84% isolates exhibiting beta-lactam, 40.58%, and 27.54% isolates showing tetracycline, and 33.33% and 36.23% isolates showing aminoglycosides resistance based on disc diffusion and gene confirmation, respectively. Phylogenetic analysis indicated homology with previously reported Pakistani isolates suggesting the possibility of MDR S. aureus transmission within and between animals. Synergy testing indicated that combinations of ceftriaxone-ketoprofen (153.77%), ceftriaxone-meloxicam (149.55%), amoxiclav-flunixin meglumine (106.06%), and oxytetracycline-flunixin meglumine (104.47%) showed synergy on well diffusion assay. Based on the fractional inhibitory concentration index by checkerboard method, oxytetracycline-meloxicam and gentamicin-ketoprofen combinations exhibited synergistic interaction. In conclusion, MDR S. aureus resistance was mitigated in-vitro through the combination of antibiotics (oxytetracycline, gentamicin) with NSAIDs (meloxicam, ketoprofen) that could be used to create therapeutic strategies for bovine reproductive issues.

Efficacy and Safety of Pharmacist-Managed NSAIDs Deprescribing: A Jordanian Outpatient Study

Background. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage pain, including chronic pain conditions. However, their prolonged use is associated with significant risks, particularly gastrointestinal (GI) adverse events. This study aimed to evaluate the effectiveness and safety of a pharmacist-managed deprescribing program for NSAIDs in a Jordanian outpatient population. Methods. A convenience sample of 100 participants who had been using NSAIDs for pain management was recruited. Participants underwent a structured deprescribing intervention in collaboration with physicians. Various effectiveness and safety outcomes were assessed before and after deprescribing. Descriptive statistics and chi-square test were used for data analysis. Results. The majority of participants reported chronic pain conditions, with rheumatoid arthritis (24%) and osteoarthritis (22%) being the most prevalent. Ibuprofen (28%) and diclofenac (22%) were the most commonly used NSAIDs. The deprescribing program was associated with a significant reduction in heartburn, stomach ulcer, kidney problems and fluctuation in blood pressure readings (p&lt;0.05), and pain exacerbation. Notably, the reduction in pain exacerbation was evident (p=0.003) in the 4-month follow-up. Conclusion. A pharmacist-managed NSAIDs deprescribing program demonstrated effectiveness in reducing the risk of GI adverse events and fluctuation in blood pressure readings without causing harm during a short-term follow-up. These findings support the feasibility of implementing such programs in outpatient settings. Further long-term investigations are necessary to confirm these results.

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.

Abnormal causal connectivity of anterior cingulate cortex-visual cortex circuit related to nonsteroidal anti-inflammatory drug efficacy in migraine.

The anterior cingulate cortex (ACC) and visual cortex are integral components of the neurophysiological mechanisms underlying migraine, yet the impact of altered connectivity patterns between these regions on migraine treatment remains unknown. To elucidate this issue, we investigated the abnormal causal connectivity between the ACC and visual cortex in patients with migraine without aura (MwoA), based on the resting-state functional magnetic resonance imaging data, and its predictive ability for the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs). The results revealed increased causal connectivity from the bilateral ACC to the lingual gyrus (LG) and decreased connectivity in the opposite direction in nonresponders compared with the responders. Moreover, compared with the healthy controls, nonresponders exhibited heightened causal connectivity from the ACC to the LG, right inferior occipital gyrus (IOG) and left superior occipital gyrus, while connectivity patterns from the LG and right IOG to the ACC were diminished. Based on the observed abnormal connectivity patterns, the support vector machine (SVM) models showed that the area under the receiver operator characteristic curves for the ACC to LG, LG to ACC and bidirectional models were 0.857, 0.898, and 0.939, respectively. These findings indicate that neuroimaging markers of abnormal causal connectivity in the ACC-visual cortex circuit may facilitate clinical decision-making regarding NSAIDs administration for migraine management.

Novel sulindac derivatives for colorectal cancer chemoprevention that target cGMP phosphodiesterases to suppress Wnt/β-catenin transcriptional activity

&lt;p class="MsoNormal" style="margin-top: 6pt; line-height: 13pt; text-align: justify;"&gt;&lt;span lang="EN-US" style="font-size: 10pt; font-family: arial, helvetica, sans-serif;"&gt;Approximately 28 million individuals in the United States face the risk of developing precancerous colonic adenomas (polyps) and potentially progressing to colorectal cancer (CRC). While a promising strategy for CRC prevention involves pharmacological intervention, such as cancer chemoprevention or interception, currently, there are no FDA-approved drugs capable of preventing the formation or progression of adenomas to adenocarcinoma. Numerous clinical, epidemiological, and preclinical studies have offered compelling evidence supporting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in CRC chemoprevention. However, the prolonged use of NSAIDs is not FDA-approved due to potential life-threatening toxicities resulting from cyclooxygenase (COX) inhibition and the depletion of physiological prostaglandins. Despite indications that the COX inhibitory activity of NSAIDs may not be essential for their antineoplastic effects, the absence of a well-defined target impeded the development of derivatives that do not inhibit COX. Earlier research suggests that the inhibition of cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) may be responsible, at least in part, for the antineoplastic activity of the NSAID sulindac. This could potentially offer a novel target for CRC chemoprevention. To identify the cGMP PDE isozyme(s) contributing to the antineoplastic activity of sulindac, we synthesized a chemically diverse library of over 1500 compounds, all sharing the indene scaffold of sulindac. Subsequently, we screened these compounds for their impact on cancer cell growth and PDE inhibitory activity. From this screening, a series of lead compounds emerged. These compounds lacked COX-1 and COX-2 inhibitory activity, surpassing sulindac in potency to inhibit CRC cell growth. Importantly, they demonstrated greater selectivity by not affecting normal cell growth. Through chemical optimization, we identified several development candidates that selectively inhibit PDE5 and/or PDE10. These compounds activate cGMP/PKG signaling, suppressing Wnt/&amp;beta;-catenin transcription. This action counters the growth advantages resulting from APC or CTNNB1 mutations, which are responsible for most human CRCs. This review delves into the scientific literature supporting PDE5 and/or PDE10 as potential targets for CRC chemoprevention or interception. Our findings suggest a promising avenue for developing drugs that may effectively intervene in the progression of colorectal cancer, offering hope for improved preventive strategies in the future.&lt;/span&gt;&lt;/p&gt;

Novel sulindac derivatives for colorectal cancer chemoprevention that target cGMP phosphodiesterases to suppress Wnt/β-catenin transcriptional activity

&lt;p class="MsoNormal" style="margin-top: 6pt; line-height: 13pt; text-align: justify;"&gt;&lt;span lang="EN-US" style="font-size: 10pt; font-family: arial, helvetica, sans-serif;"&gt;Approximately 28 million individuals in the United States face the risk of developing precancerous colonic adenomas (polyps) and potentially progressing to colorectal cancer (CRC). While a promising strategy for CRC prevention involves pharmacological intervention, such as cancer chemoprevention or interception, currently, there are no FDA-approved drugs capable of preventing the formation or progression of adenomas to adenocarcinoma. Numerous clinical, epidemiological, and preclinical studies have offered compelling evidence supporting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in CRC chemoprevention. However, the prolonged use of NSAIDs is not FDA-approved due to potential life-threatening toxicities resulting from cyclooxygenase (COX) inhibition and the depletion of physiological prostaglandins. Despite indications that the COX inhibitory activity of NSAIDs may not be essential for their antineoplastic effects, the absence of a well-defined target impeded the development of derivatives that do not inhibit COX. Earlier research suggests that the inhibition of cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) may be responsible, at least in part, for the antineoplastic activity of the NSAID sulindac. This could potentially offer a novel target for CRC chemoprevention. To identify the cGMP PDE isozyme(s) contributing to the antineoplastic activity of sulindac, we synthesized a chemically diverse library of over 1500 compounds, all sharing the indene scaffold of sulindac. Subsequently, we screened these compounds for their impact on cancer cell growth and PDE inhibitory activity. From this screening, a series of lead compounds emerged. These compounds lacked COX-1 and COX-2 inhibitory activity, surpassing sulindac in potency to inhibit CRC cell growth. Importantly, they demonstrated greater selectivity by not affecting normal cell growth. Through chemical optimization, we identified several development candidates that selectively inhibit PDE5 and/or PDE10. These compounds activate cGMP/PKG signaling, suppressing Wnt/&amp;beta;-catenin transcription. This action counters the growth advantages resulting from APC or CTNNB1 mutations, which are responsible for most human CRCs. This review delves into the scientific literature supporting PDE5 and/or PDE10 as potential targets for CRC chemoprevention or interception. Our findings suggest a promising avenue for developing drugs that may effectively intervene in the progression of colorectal cancer, offering hope for improved preventive strategies in the future.&lt;/span&gt;&lt;/p&gt;

Analgesic Efficacy of Non-Steroidal Anti-Inflammatory Drug Therapy in Horses with Abdominal Pain: A Systematic Review.

This systematic review aimed to identify the evidence concerning the analgesic efficacy of non-steroidal anti-inflammatory drugs to treat abdominal pain in horses, and to establish whether one non-steroidal anti-inflammatory drug could provide better analgesia compared to others. This systematic review was conducted following the "Systematic Review Protocol for Animal Intervention Studies". Research published between 1985 and the end of May 2023 was searched, using three databases, namely, PubMed, Embase, and Scopus, using the words equine OR horse AND colic OR abdominal pain AND non-steroidal anti-inflammatory drug AND meloxicam OR flunixin meglumine OR phenylbutazone OR firocoxib OR ketoprofen. Risk of bias was assessed with the SYRCLE risk of bias tool, and level of evidence scored according to the Oxford Centre for Evidence-based Medicine. A total of 10 studies met the inclusion criteria. From those only one study judged pain with a validated pain score, and a high risk of bias was identified due to the presence of selection, performance, and "other" types of bias. Therefore, caution is required in the interpretation of results from individual studies. To date, the evidence on analgesic efficacy to determine whether one drug is more potent than another regarding the treatment of abdominal pain in horses is sparse.

Nonsteroidal Anti-inflammatory Medications in Cranial Neurosurgery: Balancing Opioid-Sparing Analgesia with Bleeding Risk

Post-craniotomy pain is a common problem frequently encountered by neurosurgeons. This is typically managed with opioids; however, opioids have been shown to increase intracranial pressure by way of hypercapnia and straining from the associated constipation. Additionally, opioids can confound and mask the neurologic examination of post-craniotomy patients as well as be the nidus for a potential opioid addiction. Thus, alternative solutions for opioids have been a major topic of investigation within the neurosurgical community. Non-steroidal anti-inflammatory drugs (NSAIDs), present as a potential solution due to their non-addictive and analgesic properties, but utilization of NSAIDs in neurosurgical patients has been controversial given that NSAIDs alter platelet function. Whether the degree to which NSAIDs alter platelet function and bleeding time to clinically relevant manner has remained controversial; although, there have been several well-designed studies concluding that the utilization of NSAIDs in post-craniotomy patients does not increase the risk of postoperative bleeding. Herein, we review the pharmacology, efficacy, and safety of NSAIDs with a particular emphasis on NSAID use for post intracranial neurosurgical procedure pain management.

Predicting the efficacy of non-steroidal anti-inflammatory drugs in migraine using deep learning and three-dimensional T1-weighted images

Deep learning (DL) models based on individual images could contribute to tailored therapies and personalized treatment strategies. We aimed to construct a DL model using individual 3D structural images for predicting the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in migraine. A 3D convolutional neural network model was constructed, with ResNet18 as the classification backbone, to link structural images to predict the efficacy of NSAIDs. In total, 111 patients were included and allocated to the training and testing sets in a 4:1 ratio. The prediction accuracies of the ResNet34, ResNet50, ResNeXt50, DenseNet121, and 3D ResNet18 models were 0.65, 0.74, 0.65, 0.70, and 0.78, respectively. This model, based on individual 3D structural images, demonstrated better predictive performance in comparison to conventional models. Our study highlights the feasibility of the DL algorithm based on brain structural images and suggests that it can be applied to predict the efficacy of NSAIDs in migraine treatment.

Topical non-steroidal anti-inflammatory drugs for central serous chorioretinopathy: A systematic review and meta-analysis.

Central serous chorioretinopathy (CSC) is a prevalent exudative maculopathy and the ongoing verteporfin shortage restricts current treatment possibilities. Topical non-steroidal anti-inflammatory drugs (NSAID) have previously been proposed as a treatment for CSC, although its exact efficacy remains unclear. In this systematic review and meta-analysis, we outlined the efficacy of topical NSAIDs for the treatment of CSC. We searched 11 literature databases on 13 December 2022, for any study describing topical NSAID treatment for CSC. Thirteen eligible studies were included with a total of 1001 eyes of 994 patients with CSC. Six studies were case reports, two were cohort studies and five were non-randomized comparative studies. Where specified, topical NSAIDs used were bromfenac 0.09%, diclofenac 0.1%, ketorolac 0.4% and 0.5%, pranoprofen 0.1%, and nepafenac 0.1% and 0.3%. Studies were predominantly of cases with acute CSC and several case studies reported treatment outcomes simultaneously with discontinuation of corticosteroid use, which complicated treatment evaluation. Meta-analyses of comparative studies revealed a statistically significant but clinically irrelevant best-corrected visual acuity improvement of -0.04 logMAR (95% CI: -0.07 to -0.01 logMAR; p = 0.01) at 1-month follow-up, which became statistically insignificant at 3-month follow-up (-0.03 logMAR; 95% CI: -0.06 to 0.003 logMAR; p = 0.08). Further, we found no benefit in complete subretinal fluid resolution at 1-month follow-up (OR: 1.20; 95% CI: 0.81-1.76; p = 0.37) or 3-month follow-up (OR: 1.17; 95% CI: 0.86 to 1.59; p = 0.33). Taken together, available evidence does not support the use of topical NSAIDs for the treatment of CSC.

Circulating miR-222-3p is associated with ankylosing spondylitis development and predicts therapeutic efficacy of nonsteroidal anti-inflammatory drugs.

Ankylosing spondylitis (AS) is a chronic rheumatic disease, and some microRNAs (miRNAs) in AS have been identified. This study aimed to measure miR-222-3p expression in AS patients, investigate the association of miR-222-3p with AS disease activity, and explore the clinical value of miR-222-3p in diagnosing AS and predicting therapeutic efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) on AS patients. This study included 96 patients with AS, 58 patients with rheumatoid arthritis (RA), and 90 healthy controls. miR-222-3p expression was detected by reverse-transcription quantitative polymerase chain reaction (PCR). The ability of miR-222-3p to discriminate between different groups was evaluated by receiver operating characteristic analysis. The predictive value of miR-222-3p on the efficacy of NSAID treatment for AS was assessed by logistic regression analysis. AS patients treated with oral NSAIDs diclofenac sodium were divided into response (n = 76) and no-response (n = 20) groups after 16 weeks of treatment. miR-222-3p in AS patients was higher than that in healthy subjects and RA patients. miR-222-3p had high diagnostic value in distinguishing patients with AS from RA patients and healthy controls. miR-222-3p, increased in active AS patients, had the ability to screen active AS patients from inactive AS patients. miR-222-3p was decreased in the response group, and had high accuracy in predicting the therapeutic efficiency of NSAIDs. The findings indicate that increased miR-222-3p in AS patients may function as a diagnostic biomarker for AS, and predictive biomarker for the therapeutic efficacy of NSAIDs in patients with AS. In addition, miR-222-3p is associated with AS disease activity.

#5576 SYSTEMATIC REVIEW AND META-ANALYSIS OF THE SAFETY AND EFFICACY OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS FOR THE MANAGEMENT OF POSTPARTUM PAIN

Abstract Background and Aims Effective pain management is critical for postpartum recovery. While commonly prescribed, systematically-reviewed data regarding efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) are limited. Moreover, guidelines suggest avoiding NSAIDs in women with hypertensive disorders of pregnancy (HDP) due to risks of hypertension and adverse events (AE). However, these AE have not been consistently observed in cohort studies and randomised controlled trials (RCTs) following postpartum NSAID use. This systematic review aims to provide further insight into the postpartum safety and efficacy of NSAIDs. Method A systematic review of eight databases and four clinical trial registries was conducted in July 2020 (PROSPERO Protocol CRD42020196054). RCTs which assessed the safety and/or efficacy of NSAIDs in postpartum women after the year 2000 were included. The primary outcome was incidence of hypertension, with secondary outcomes categorised into three groups: hypertension, secondary safety and efficacy. Data were tabulated and analysed using R (version 4.0.2). Due to heterogeneity in study design, NSAIDs were analysed in a single group and compared with other medications (including paracetamol, opioids, and local anaesthetics) grouped based on mechanism to facilitate meta-analysis. Risk of bias was assessed using the RoB 2 tool with a plan to assess quality of evidence for the primary outcome. Results 12,172 records were identified with the inclusion of 92 RCTs. Eight studies, with four that included women with HDP, reported hypertension-related data (Table 1). The primary outcome was included in one RCT. Secondary safety outcomes such as acute kidney injury or eclampsia were not reported. The odds of nausea, vomiting and sedation were similar between groups. NSAIDs were effective when compared with placebo, as assessed by mean differences (MD) in visual assessment scores (VAS) at 12 hours (MD -1.57, 95% confidence intervals (CI) -2.47 to -0.66), 24 hours (MD -0.82, 95% CI -1.42 to -0.22) and need for additional analgesia (odds ratio 0.17, 95% CI 0.05 to 0.61). There were no significant differences in VAS between NSAIDs and other comparators at 12 and 24 hours. Further interpretation of results is limited due to heterogeneity in intervention and comparator groups, inclusion criteria and reported outcomes. Conclusion Our study confirms the efficacy of NSAIDs for postpartum pain, but current data are inconclusive regarding the risk of developing hypertension. Available data do not demonstrate trends toward AE although further research is required to determine long term, clinically-relevant outcomes to guide decision making.

Topical nonsteroidal anti-inflammatory drugs in the prevention of pseudophakic cystoid macular edema following phacoemulsification: A systematic review

Introduction: The goal of surgeons to avoid Pseudophakic Cystoid Macular Edema (PCMO) has led to the widespread use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) after cataract surgery, although current research into the best anti-inflammatory drugs to avoid PCMO is still underway. This review aimed to determine the efficacy of topical NSAIDs in preventing PCMO following phacoemulsification. Methods: This systematic review was built on the recommended reporting items for systematic reviews and meta-analyses (PRISMA) and PICO criteria for papers during the previous 10 years. The keywords was searched by Boolean operator: “NSAIDs” AND “Prevention” AND “Cystoid Macular Edema” AND “Optical Coherence Tomography” AND “Phacoemulsification”. According to STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist, the quality of each chosen article was evaluated. Results: We have selected five articles of prospective cohort studies, which involved 756 patients whom received topical NSAIDs (Nepafenac 0.3%, Ketorolac Tromethamine 0.4%Nepafenac 0.1%, , and Diclofenac 0.1%) in treatment group and 700 patients received Placebo (Artificial tears) in control group. There was significant difference of central macular thickness based on OCT results between NSAIDs and control (placebo) group after uneventful phacoemulsification. Additionally, NSAIDs used as a preventative before phacoemulsification procedure exhibited a significantly reduced rise in central foveal thickness compared to placebo. There were changes of central macular thicknes postoperatively, and were significantly different from preoperative. Conclusion: It has been demonstrated that topical NSAIDs successfully lower the incidence of Pseudophakic Cystoid Macular Edema following phacoemulsification.

An interpretable machine-learning model for predicting the efficacy of nonsteroidal anti-inflammatory drugs for closing hemodynamically significant patent ductus arteriosus in preterm infants.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used in the closure of ductus arteriosus in premature infants. We aimed to develop and validate an interpretable machine-learning model for predicting the efficacy of NSAIDs for closing hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. We assessed 182 preterm infants ≤ 30 weeks of gestational age first treated with NSAIDs to close hsPDA. According to the treatment outcome, patients were divided into a "success" group and "failure" group. Variables for analysis were demographic features, clinical features, as well as laboratory and echocardiographic parameters within 72 h before medication use. We developed the machine-learning model using random forests. Model performance was assessed by the area under the receiver operating characteristic curve (AUC). Variable-importance and marginal-effect plots were constructed to explain the predictive model. The model was validated using an external cohort of two preterm infants who received ibuprofen (p.o.) to treat hsPDA. Eighty-three cases (45.6%) were in the success group and 99 (54.4%) in the failure group. Infants in the success group were associated with maternal chorioamnionitis (p = 0.002), multiple births (p = 0.007), gestational age at birth (p = 0.020), use of indometacin (p = 0.007), use of inotropic agents (p < 0.001), noninvasive ventilation (p = 0.001), plasma albumin level (p < 0.001), PDA size (p = 0.038) and Vmax (p = 0.013). Multivariable binary logistic regression analysis showed that maternal chorioamnionitis, multiple births, use of indomethacin, use of inotropic agents, plasma albumin level, and PDA size were independent risk factors influencing the efficacy of NSAIDs (p < 0.05). The AUC of the random forest model was 0.792. The top-three features contributing most to the model in the variable-importance plot were the plasma albumin level and platelet count 72 h before treatment and 24-h urine volume before treatment. In the external cohort, treatment succeeded in one case and failed in the other. The probabilities of success and failure predicted by the random forest model were 60.2% and 48.4%, respectively. Based on clinical, laboratory, and echocardiographic features before first-time NSAIDs treatment, we constructed an interpretable machine-learning model, which has a certain reference value for predicting the closure of hsPDA in premature infants under 30 weeks of gestational age.

Effects of Non-steroidal Anti-inflammatory Drugs (NSAIDs) and Gastroprotective NSAIDs on the Gastrointestinal Tract: A Narrative Review.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for their anti-inflammatory, antipyretic, and analgesic properties. However, their use is often associated with gastrointestinal tract (GIT) side effects due to the inhibition of both cyclooxygenase (COX)-1 and COX-2 enzymes, leading to a decrease in gastroprotective prostaglandins (PG). To minimize these adverse effects, various approaches have been explored, including selective COX-2 inhibitors, NO-NSAIDs (nitric oxide-releasing NSAIDs), and dual COX/LOX (lipoxygenase) NSAIDs. However, the effects of these gastroprotective NSAIDs on the GIT and their efficacy remains uncertain. This review aims to provide an overview of the current understanding of the effects of traditional NSAIDs and gastroprotective NSAIDs on GIT. We discuss the underlying mechanisms of GIT damage caused by NSAIDs, including mucosal injury, ulceration, and bleeding, and the potential of gastroprotective NSAIDs to mitigate these effects. We also summarize recent studies on the efficacy and safety of various gastroprotective NSAIDs and highlight the limitations and challenges of these approaches. The review concludes with recommendations for future research in this field.