Efficacy Of Non-steroidal Anti-inflammatory Drugs Research Articles

The Efficacy of Non-Steroidal Anti-Inflammatory Drugs in Athletes for Injury Management, Training Response, and Athletic Performance: A Systematic Review

(1) Background: The purpose of this systematic review is to investigate the prevalent use of non-steroidal anti-inflammatory drugs (NSAIDs) in athletes and to comprehensively review the effectiveness and the results of these medications as it relates to injury management, training response, and overall sport performance. (2) Methods: An electronic literature search was performed in accordance with the recommendations and guidelines of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) protocol. A total of 7 randomized controlled studies met the review’s specific inclusion criteria from the 2250 studies initially identified within the PubMed database. (3) Results: In total, 346 adult female and male athletes from a variety of sporting activities and fitness levels were observed, of which 175 athletes were treated with either oral, topical, or local muscular infusion of an NSAID. Depending on study design, the outcomes focused on results obtained through physical exam findings, questionnaires, various performance metrics, and direct tissue sampling from microdialysis or biopsies. Across the 7 total studies, 2 articles focused on injured athletes and their varying pain responses with NSAIDs; 2 studies assessed the limited impact of NSAIDs on performance; and 3 articles revealed the use of NSAIDs correlating to no increases in either collagen synthesis or satellite cell activity after exercise. (4) Conclusions: The systematic review affirmed that NSAIDs can be effective for managing acute pain. However, their value appears to diminish when treating chronic injuries or if NSAIDs are expected to improve performance or have other ergogenic effects in athletes, as the aggregate data did not support such benefits. (5) Practical applications: NSAIDs can be beneficial for athletes in the right situation, but the fact that there are risks and possible disadvantageous results with their use highlights the importance of promoting appropriate expectations and the judicious use of these medications with the athletic community.

Risk of acute kidney injury after lower urinary tract reconstruction with early NSAID therapy: A propensity matched retrospective analysis

The opioid epidemic response led to increased use of postoperative, non-opioid analgesia. Some pediatric urologists do not routinely use non-steroidal anti-inflammatory drugs (NSAIDs) for fear of causing acute kidney injury (AKI). While previous studies have demonstrated the safety and efficacy of NSAIDs in children, safety after lower urinary tract reconstruction has not been well characterized. ptUsing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for AKI (increase in creatinine ≥0.3mg/dL or increase in creatinine ≥1.5x baseline or urine output <0.5mL/kg/hr for 6h), we hypothesized there would be a difference in the incidence of postoperative AKI between patients who did and did not receive NSAIDs following surgery. Patients 2-18 years old who underwent lower urinary tract reconstruction (i.e., bladder augmentation and/or creation of a catheterizable channel) from 2009 to 2021 and had documented urine output were retrospectively reviewed. Chronic kidney disease (CKD) stage was calculated from creatinine and cystatin C within 6 months of surgery using the CKiD U25 equations. Patients who received NSAIDs were propensity matched on 11 characteristics with patients undergoing similar surgeries who did not receive NSAIDs. The primary outcome was incidence of AKI within 48h of surgery. The unmatched cohorts included 243 patients. Propensity matching identified 166 patients in the NSAID arm and 41 in the no NSAID arm. 26 patients with CKD stage 2-3 were included. There was no significant difference in the incidence of postoperative AKI based on any KDIGO criteria (17.1% no NSAID versus 16.3% NSAID, p=0.87). Median postoperative opioids fell from 0.88mg/kg in the no NSAID arm to 0.37mg/kg morphine equivalents in the NSAID arm, although this was not statistically significant. Log-rank testing by Kaplan-Meier analysis demonstrated no difference in time to incidence of low urine output between the groups (p=0.32). In the whole population not stratified by NSAID use, no differences were seen in AKI between those with and without CKD (16.7% with versus 17.9% without CKD). There was no difference in the incidence of postoperative AKI among patients who did and did not receive NSAIDs after lower urinary tract reconstruction, excluding those with advanced CKD. These results support that postoperative NSAIDs were an unlikely source of AKI. However, AKI remained a risk following these surgeries, regardless of NSAID use, likely owing to underlying disease, longer operations, and fluid shifts.

Differential impacts of nonsteroidal anti-inflammatory drugs on lifespan and healthspan in aged Caenorhabditis elegans.

Aging and age-related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown their promise in mitigating age-related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age-related changes in drug metabolism and tolerance, which could result in age-dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans. The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk-1/skn-1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk-1 was knocked out in the pmk-1(km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age-dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population.

Efficacy and safety of topical NSAIDs combined with physiotherapy for frozen shoulder: a randomized controlled trial.

Frozen shoulder is a prevalent condition among individuals in their middle and later years. Invasive therapy has shown promising results in the treatment of frozen shoulders, but its widespread adoption has been hampered by high costs and the need for advanced medical technology. As a result, patients with frozen shoulders often turn to non-steroidal anti-inflammatory drugs (NSAIDs) for symptomatic relief. However, the oral administration of NSAIDs can lead to troublesome adverse effects on the gastrointestinal, cardiovascular, and urinary systems. In contrast, topical NSAIDs have gained attention for their excellent efficacy and lower adverse effects in various chronic pain conditions. Therefore, our study aimed to investigate the efficacy and safety of topical NSAIDs in improving pain and mobility among patients with frozen shoulders. A total of 108 patients experiencing moderate to severe pain and mobility impairment due to frozen shoulder were enrolled in this study. The participants were randomly assigned to either the experimental group (n=72) or the control group (n=36). The experimental group received daily treatment with the loxoprofen hydrogel patch (LOX-P) in addition to basic rehabilitation physiotherapy. The control group was treated with flurbiprofen cataplasm (FLU-C) twice a day, along with rehabilitation physiotherapy. The primary endpoint for evaluating the efficacy of the two patches was the Constant-Murley score (CMS). Clinical symptom data, adverse events, and patient satisfaction were also recorded. After 14 days of treatment, the effective rate was 66.67% (n=48) in the experimental group and 41.67% (n=15) in the control group. The overall difference in the effective rates was 25.00% (95% CI=5.20-42.52; p=0.013). The safety profiles of the two topical agents were similar, with only a few adverse events reported. The loxoprofen hydrogel patch demonstrates a significant ability to alleviate shoulder pain and restore shoulder function in the treatment of frozen shoulder, with minimal adverse reactions. Chictr.org.cn ID: ChiCTR2100052375.

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.

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.

Clinical efficacy of Osteoking in knee osteoarthritis therapy: a prospective, multicenter, non-randomized controlled study in China.

Osteoking has been extensively used for the treatment of knee osteoarthritis (KOA). However, it is lack of high-quality evidence on the clinical efficacy of Osteoking against KOA and the comparison with that of nonsteroidal anti-inflammatory drugs (NSAIDs). To evaluate the efficacy and safety of Osteoking in treating KOA. In the current study, a total of 501 subjects were recruited from 20 medical centers, and were divided into the Osteoking treatment group (n = 428) and the NSAIDs treatment group (n = 73). The Propensity Score Matching method was used to balance baseline data of different groups. Then, the therapeutic effects of Osteoking and NSAIDs against KOA were evaluated using VAS score, WOMAC score, EQ-5D-3L and EQ-VAS, while the safety of the two treatment were both assessed based on dry mouth, dizziness, diarrhea, etc. After 8weeks of treatment, the Osteoking group was compared with the NSAIDs group, the VAS score [2.00 (1.00, 3.00) vs. 3.00 (2.00, 4.00)], WOMAC pain score [10.00 (8.00, 13.00) vs. 11.00 (8.00, 16.00) ], WOMAC physical function score [32.00 (23.00, 39.00) vs. 39.07 ± 16.45], WOMAC total score [44.00 (31.00, 55.00) vs. 53.31 ± 22.47) ], EQ-5D-3L score [0.91 (0.73, 0.91) vs. 0.73 (0.63, 0.83) ] and EQ-VAS score [80.00 (79.00, 90.00) vs. 80.00 (70.00, 84.00) ] were improved by the treatment of Osteoking for 8weeks more effectively than that by the treatment of NSAIDs. After 8weeks of treatment with Osteoking, the VAS scores of KOA patients with the treatment of Osteoking for 8weeks were reduced from 6.00 (5.00, 7.00) to 2.00 (1.00, 3.00) (p < 0.05), which was better than those with the treatment of NSAIDs starting from 2weeks during this clinical observation. Importantly, further subgroup analysis revealed that the treatment of Osteoking was more suitable for alleviating various clinical symptoms of KOA patients over 65years old, with female, KL II-III grade and VAS 4-7 scores, while the clinical efficacy of NSAIDs was better in KOA patients under 65years old and with VAS 8-10 scores. Of note, there were no differences in adverse events and adverse reactions between the treatment groups of the two drugs. Osteoking may exert a satisfying efficacy in relieving joint pain and improving life quality of KOA patients without any adverse reactions, especially for patients with KL II-III grades and VAS 4-7 scores. https://www.chictr.org.cn/showproj.html?proj=55387, Identifier ChiCTR2000034475.

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.