Impact Of Non-steroidal Anti-inflammatory Drugs Research Articles

Study on Impact of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) on Renal Function in Postpartum Period

A prospective, observational study was conducted in the Department of Obstetrics & Gynaecology of Combined Military Hospital (CMH), Dhaka, Bangladesh, to assess pre-delivery and post-delivery (5 days after administration of NSAID) change in renal function by determining the serum creatinine levels in pregnant women. The study was conducted on 120 purposively selected patients attending for their delivery purpose in the selected hospital from January to June of 2022. Following the delivery, tablet Paracetamol 500 mg thrice a day for 5 days have been prescribed to all the respondents. Diclofenac Sodium 100 mg suppository twice a day up to for 3 days had been prescribed with dosage adjusted as required. Serum creatinine levels were evaluated on two time points: the day before delivery and 5 days after delivery. Compared to the day before delivery, 53.3% of the respondents showed increased level of serum creatinine 5 days after delivery. Acute kidney injury (AKI) was identified in 9.17% patients with a change more than 0.3 mg/dL from the pre-delivery report. The change in the serum creatinine level pre-delivery to post delivery was statistically significant, which was also dependent on the NSAIDs dose with a positive linear association. Though NSAIDs regarded as a safe choice for postpartum pain management, yet apparently healthy mothers showed fluctuations in serum creatinine level in association to dosage of NSAIDs use. CBMJ 2024 July: vol. 13 no. 02 P: 141-147

Non-steroidal anti-inflammatory drugs in postoperative hand fracture management: Do they positively or negatively impact recovery?

This editorial explores the impact of non-steroidal anti-inflammatory drugs (NSAIDs) on postoperative recovery in hand fracture patients, amidst shifting pain management strategies away from opioids due to their adverse effects. With hand fractures being significantly common and postoperative pain management crucial for recovery, the potential of NSAIDs offers a non-addictive pain control alternative. However, the controversy over NSAIDs' effects on bone healing-stemming from their Cyclooxygenase-2 inhibition and associated risks of fracture non-union or delayed union-necessitates further investigation. Despite a comprehensive literature search, the study finds a lack of specific research on NSAIDs in postoperative hand fracture management, highlighting an urgent need for future studies to balance their benefits against possible risks.

Significantly Positive Impact of Nonsteroidal Anti-inflammatory Drugs Combined With Osmoprotectant (Osmolytes) in Cancer Treatment.

Osmoprotectant osmolyteand nonsteroidal anti-inflammatory drug (NSAID) coadministration can work synergistically in cancer chemotherapy since most tumors are inflammatory and cancer cells experience osmotic stress. NSAIDs have been shown to inhibit cyclooxygenase (COX) enzymes, which in turn reduces prostaglandin synthesis and prevents inflammation. They also encourage cell death to prevent tumor growth and its spread to other tissues and prevent the construction of new blood vessels, which contributes to the growth of cancer. Taurine belongs to the class of osmolytes since it has been shown to stabilize macromolecular structures and maintain cellular osmotic balance when combined with betaine and glycine. When these drugs are taken together, as opposed to separately, the effectiveness of cancer treatment is increased by increasing cancer cell death and suppressing tumor growth. Notable therapeutic benefits include the reduction of local inflammatory milieu by NSAIDs, which promotes tumor development, and the protection of surviving, normal cells and tissues from treatment-induced damage caused by cancer. By enhancing this synergy, side-effect risk can be decreased and treatment outcomes improved in terms of quality. Put another way, peptides can increase the therapeutic index of NSAIDs in cancer patients by preventing cell damage, which may lessen the gastrointestinal (GI), cardiovascular (CV), and renal side effects of the drug. However, there are drawbacks because using NSAIDs for an extended period of time is linked to serious side effects that call for strict supervision. More research is required because the usefulness and significance of osmolytes in cancer therapy are still very unclear, if not fragmented. In addition, people who live in places with limited resources may find it difficult to afford the possible expenditures associated with osmolytes and selective cyclooxygenase-2 (COX-2) inhibitors. Only the molecular mechanisms of the two drugs' interactions, the appropriate dosages for combination therapy, and clinical trials to validate the efficacy and safety of this dosage should be the focus of future research. The request is inviting because it presents hope for an extremely successful antiviral strategy; nevertheless, in order to implement this approach successfully, it is likely to be necessary to create affordable formulations and scalable solutions that do not necessitate excessive treatment regimen individualization. Due to their complementary capacities to demonstrate anti-inflammatory and cytoprotective effects, Akta and5-aminosalicylic acid (5-ASA) administration may thus represent a significant advancement in the treatment of cancer.

Effect of post-operative NSAID use on rotator cuff repair outcomes

BackgroundThe impact of non-steroidal anti-inflammatory drugs (NSAIDs) on rotator cuff repair is an ongoing area of study within orthopedics, with conflicting results in current literature. Despite concerns over the deleterious effects of NSAIDs on rotator cuff healing, they are becoming an integral part of a multimodal post-operative pain control regiment. The purpose of this study was to compare post-operative patient-reported outcomes (PROs), complications rates, and retear rates of arthroscopic rotator cuff repairs in patients using ibuprofen post-operatively to those who abstained from NSAIDs for six weeks after surgery. It was hypothesized that a short course of ibuprofen post-operatively would not lead to inferior PRO scores, increased retear rates, nor increased complication rates after arthroscopic rotator cuff repair. MethodsPatients of the primary surgeon who underwent arthroscopic rotator cuff repair between 2012 and 2022 were evaluated by retrospective chart review. In May 2017 the primary surgeon changed his protocol from avoiding NSAIDs for six weeks after surgery to routinely prescribing two weeks of Ibuprofen 800 mg TID post-operatively. Patients who avoided NSAIDs for six weeks were compared to patients who were prescribed NSAIDs post-operatively. Patient demographic data, pre-operative MRI results, pre-operative and post-operative PROs were collected from the EMR. Additionally, post-operative complications and repair failures requiring reoperation within one year were evaluated. Results125 patients met inclusion criteria for this study with 36 patients in the NSAID group and 89 in the no NSAID group. When comparing improvement in PROs, the NSAID group reached MCID at one year in 83.8 % of patients and the no NSAID group reached MCID at one year in 73.9 % of patients. There was no significant difference between the groups in reaching MCID improvement at one year (p = 0.471). Five post-operative complications were reported in the no NSAID group and two in the NSAID group (5.7 % vs 5.4 %, respectively, p = 0.827). Finally, there was no significant difference in the percentage of post-operative rotator cuff repair failures requiring revision in the first year between the groups (2.3 % vs 2.7 %, p = 1.000). ConclusionThere was no difference in percent of patients improving their PRO by the MCID between the groups that used ibuprofen and the group that did not. There was also no difference in post-operative complication rates and rates of symptomatic retear requiring reoperation between the groups. This supports that a short course of NSAIDs post-operatively, specifically ibuprofen, after rotator cuff repair does not increase reoperation rates nor lead to a clinically significant decrease in PROs at one year.

NSAIDs do not influence exercise effects on muscle size in rats or muscle protein synthesis signaling in humans

BACKGROUND: The aim of this project was to determine the impact of non-steroidal anti-inflammatory drugs (NSAIDs) on skeletal muscle adaptations to exercise. NSAIDs possess analgesic and anti‐inflammatory properties that occur by blocking cyclooxygenase (COX) enzymes, thereby inhibiting the production of prostaglandins. In the first study, we determined if low-dose chronic NSAID use affects muscle size in rodents exercising for six weeks. In the second study, we determined if a single high dose of NSAIDs effects the muscle protein synthetic signaling response to a bout of plyometric exercise. Our hypotheses were that NSAIDs would reduce both muscle size and muscle protein synthesis (MPS) signaling. METHODS: Study 1: 9-wk-old male Wistar rats (n=80) were randomized to placebo (PLA), naproxen (NAP), ibuprofen (IBU), or flurbiprofen (FLU) with or without exercise (EX) for six weeks. Exercise consisted of treadmill running at 25 m/min, for 30 minutes per day, five days per week. Soleus muscle was stained for myosin heavy chain (MHC) I or MHC IIA then analyzed for cross sectional area (CSA) and fiber type percentage. Rodent data were analyzed using a one-way ANOVA. Study 2: In a randomized, counter-balanced order, 12 participants (2 females, 10 males), performed four independent plyometric exercise bouts consisting of 10 sets of 10 plyometric jumps at 40% of their 1RM, separated by a minimum of one week. Prior to each session, participants consumed a single dose of celecoxib (CEL 200 mg), IBU (800 mg), FLU (100 mg) or PLA. Muscle biopsies were collected before (PRE) and 3-hours post (POST) exercise. Muscle was analyzed via immunoblot for the following: phospho(p)-AKT(S473), total AKT, p-mTOR (S448), total mTOR, p-S6 (S235/236), total S6, p-4EBP1, and total 4EBP1. Fold changes were calculated from PRE to POST. Data were analyzed using a repeated measures ANOVA. All data are presented as mean ± SD. RESULTS: Study 1: There was no significant difference (p<0.05) in muscle CSA (PLA: 4060±517; PLA+EX: 3965±605; IBU: 3720±804; IBU+EX:4129±477; FLU: 3743±671; FLU+EX: 3649±541; NAP: 4157±1011; NAP+EX: 4123±586) or MHC IIA percentage (PLA: 10±7; PLA+EX: 10±5; IBU: 7±5; IBU+EX:9±3; FLU: 11±4; FLU+EX: 11±6; NAP: 11±4; NAP+EX: 12±3) between groups. Study 2: There was no significant difference (p<0.05) in fold-change between groups for p-AKT/total AKT (PLA: 1.23±0.4; IBU: 1.13±0.3; CEL: 1.26±0.4; FLU: 1.31±0.4), p-mTOR/total mTOR (PLA: 1.21±0.2; IBU: 1.21±0.3; CEL:1.34±0.2; FLU: 1.49±0.3), p-S6/total S6 (PLA: 11.48±10.6; IBU: 10.9±6.8; CEL: 6.01±2.98; FLU: 25.25±19.38), or p-4EBP1/total 4EBP1 (PLA: 1.71± 1.35; IBU: 1.23±0.98; CEL: 1.07 ±0.64; FLU: 2.03±1.49). CONCLUSION: Chronic low-dose NSAID consumption does not influence muscle size or MHC in exercising rodents. Similarly, an acute high dose of an NSAID does not affect the MPS signaling response in exercising humans. Funding was provided by the Military Operational Medicine Research Program. The opinions or assertions contained herein are the private views of the author(s) and are not to be construed as offcial or as reflecting the views of the Army or the Department of Defense. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Nonsteroidal Anti-Inflammatory Drugs Decrease Coagulopathy Incidence in Severe Burn Patients

The study investigated the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on burn-induced coagulopathy in severely burned patients. Patients with a greater than 20% TBSA were identified in the TriNetX research network and categorized into receiving or not receiving NSAIDs in the first week after the burn. The statistical significance of the rate of burn-induced coagulopathy, mortality and sepsis in the week following injury was analysed. We observed 837 severely burned patients taking NSAIDS during the week following the burn and 1036 patients without. After matching for age, gender and race, the risk of burn-induced coagulopathy significantly decreased (p < 0.0001) in patients taking NSAIDs (17.7%) compared to those without (32.3%). Patients taking NSAIDs were also less likely to develop sepsis (p < 0.01) and thrombocytopenia (p < 0.001) or die the week following injury (p < 0.0001). In conclusion, the early protective effects of NSAIDs at reducing the risk of coagulopathy as well as sepsis and mortality occur during the acute phase of burns.

Association of long-term use of non-steroidal anti-inflammatory drugs with knee osteoarthritis: a prospective multi-cohort study over 4-to-5 years

This study examines the long-term impact of non-steroidal anti-inflammatory drugs (NSAIDs) on the progression of symptoms and structural deterioration of the joint in knee osteoarthritis. The study analyzes data from 4197 participants (8394 knees) across the Osteoarthritis Initiative (OAI), Multicenter Osteoarthritis Study (MOST), and Cohort Hip and Cohort Knee (CHECK) over 4-to-5 years. Adjustments were made for major covariates. We focussed on binary outcomes to assess the presence or absence of significant changes. We found that, relative to non-users, individuals using NSAIDs long-term were significantly more likely to experience aggravated symptoms exceeding the minimally clinically important difference, specifically, pain (OR: 2.04, 95% CI: 1.66–2.49), disability (OR: 2.21, 95% CI: 1.74–2.80), and stiffness (OR: 1.58, 95% CI: 1.29–1.93). Long-term users also faced a higher probability than non-users of having total knee replacement (OR: 3.13, 95% CI: 2.08–4.70), although no significant difference between long-term users and non-users was observed for structural deterioration in the knee joint (OR: 1.25, 95% CI: 0.94–1.65). While acknowledging the limitations of this study due to its observational design and the potential for bidirectional causality, these findings suggest that long-term NSAID use could accelerate the progression to total knee replacement by markedly exacerbating symptoms.

Impact of Non-steroidal Anti-inflammatory Drugs, Glucocorticoids, and Disease-Modifying Anti-Rheumatic Drugs on Cancer Response to Immune Checkpoint Inhibitor Therapy

Immune checkpoint inhibitor (ICI) therapy for advanced malignancies often leads to off-target adverse events. Rheumatic immune-related adverse events can often linger beyond the duration of ICI therapy and sometimes requires the use of immunomodulator therapy. A key question, therefore, is if the commonly used therapies affect cancer outcomes. In this review, the authors summarize the state of the data as it currently stands, taking into consideration the limitations of the various source studies. The most information is known about glucocorticoids, which appear to be harmful especially when used early and at high doses.

The Role of Early Treatment in the Management of Axial Spondyloarthritis: Challenges and Opportunities.

Axial spondyloarthritis (axSpA) is a chronic, inflammatory rheumatic disease that primarily affects the axial skeleton, often inflicting severe pain, diminished mobility, and a compromised quality of life. The advent of Assessment of SpondyloArthritis international Society (ASAS) classification criteria for spondyloarthritis (SpA) have enabled the classification of patients with axSpA in the non-radiographic stage but poorly perform if mistakenly used for diagnostic purposes. Despite notable progress in early diagnosis facilitated by referral strategies and extensive magnetic resonance imaging (MRI) utilization, diagnostic delays persist as a concerning issue. This underscores the urgency to narrow the diagnostic gap and highlights the critical role of early diagnosis in mitigating the long-term structural damage associated with this condition. Research into the impact of non-steroidal anti-inflammatory drugs (NSAIDs) and biologic disease-modifying antirheumatic drugs (bDMARDs) on inflammatory symptoms and radiographic progression has been extensive. A compelling body of evidence suggests that early intervention leads to superior disease outcomes. However, most of these studies have centered on patients with established diseases rather than those in the early stages. Consequently, findings from studies on early pharmacological intervention remain inconclusive, and the potential for modifying the disease trajectory is still debatable. Without precise data from clinical trials, insights from basic science regarding the pathogenic mechanisms might point toward potential targets that warrant early intervention in the disease process. This review underscores the urgency of early diagnosis and intervention in axSpA, highlighting ongoing research gaps and the need for further exploration to improve patient outcomes.

Diamine Oxidase Interactions with Anti-Inflammatory and Anti-Migraine Medicines in the Treatment of Migraine

Histamine intolerance arises when there is a disparity between the production of histamine and the body’s ability to break it down. In the gastrointestinal tract, the primary enzyme responsible for metabolizing ingested histamine is diamine oxidase (DAO), and a shortage of this enzyme has been associated with some diseases related to the respiratory, cardiovascular, nervous, muscular, and digestive systems, in addition to migraines. The treatment of migraines typically revolves around the utilization of both anti-migraine and anti-inflammatory drugs, but their interaction with DAO is not thoroughly understood. In this study, we examined the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) and anti-migraine medications on DAO activity through in vitro experiments. We also investigated their effects on the human intestinal cell line Caco-2, assessing changes in DAO expression (both at the mRNA and protein levels) as well as DAO activity. The tested drugs, including ibuprofen, acetylsalicylic acid, paracetamol, a combination of acetylsalicylic acid with paracetamol and caffeine, zolmitriptan, and sumatriptan, did not inhibit DAO activity or reduce their levels. However, naproxen reduced DAO protein levels in human enterocyte cultures while not affecting DAO activity. These results suggest that combining anti-inflammatory and anti-migraine drugs with DAO enzyme supplementation for migraine patients with DAO deficiency could be beneficial for healthcare professionals in their daily practice.

Do disease-modifying antirheumatic drugs and non-steroidal anti-inflammatory drugs increase the burden on ankylosing spondylitis patients with mild-moderate COVID-19? evidence from a retrospective cohort study

Objectives: The impact of non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumor necrosis factor inhibitors (TNFi) on the outcomes of mild-moderate COVID-19 in patients with ankylosing spondylitis (AS) remains unclear. This study aimed to evaluate the effects of NSAIDs, csDMARDs, and TNFi on AS patients with mild-moderate COVID-19.Methods: This cohort study utilized patient-reported PCR/antigen tests to determine the occurrence of COVID-19 and assessed clinical manifestations to determine its severity. The study focused on two primary outcomes: an increased number of COVID-19 symptoms and a prolonged disease course (longer than 10 or 28 days). Modified Poisson regression was performed to analyze the association between exposures and outcomes.Results: A total of 521 patients were included in the analysis. The median age was 34.8 (inter-quartile range: 27.2–46.7), with 420 (80.6%) being men. Among the patients, 52 (10.0%) had comorbidities and 443 (85%) had been vaccinated. After adjusting for confounding factors, there was no significant association between csDMARDs or TNFi and the presence of more than 5 symptoms in mild-moderate COVID-19 (adjusted relative risk (RRa) 1.08, 95% CI: 0.84–1.40 or 1.09, 0.92–1.29 for csDMARDs or TNFi, respectively), whereas the prevalence of experiencing more than 5 symptoms increased in patients with NSAID monotherapy (RRa 1.22, 95% CI: 1.01–1.46). Similarly, there was no significant association with having more than 10 symptoms (RRa 0.65, 95% CI: 0.26–1.64; 0.95, 0.36–2.54; and 1.01, 0.53–1.91 for NSAIDs, csDMARDs, and TNFi, respectively). Patients who had pre-existing use of NSAIDs, csDMARDs and TNFi had similar odds of experiencing a disease course longer than 10 days (RRa 1.17, 95% CI: 0.82–1.66; 1.18, 0.78–1.77; and 1.22, 0.92–1.63 for NSAIDs, csDMARDs, and TNFi, respectively) and longer than 28 days (RRa 0.94, 95% CI: 0.31–2.81; 0.97, 0.25–3.74 and 1.05, 0.44–2.49, respectively) compared to those not using medication.Conclusion: AS patients treated with csDMARDs or TNFi did not show inferior outcomes in terms of symptom burden or recovery compared to those not using medication in mild-moderate COVID-19. The observed inverse association between pre-existing NSAIDs use and COVID-19 symptom burden in AS deserves further investigation.

Modulation of the Immune Response to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination by Nonsteroidal Anti-Inflammatory Drugs.

Evidence is scarce to guide the use of nonsteroidal anti-inflammatory drugs (NSAIDs) to mitigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-related adverse effects, given the possibility of blunting the desired immune response. In this pilot study, we deeply phenotyped a small number of volunteers who did or did not take NSAIDs concomitant with SARS-CoV-2 immunizations to seek initial information on the immune response. A SARS-CoV-2 vaccine-specific receptor binding domain (RBD) IgG antibody response and efficacy in the evoked neutralization titers were evident irrespective of concomitant NSAID consumption. Given the sample size, only a large and consistent signal of immunomodulation would have been detectable, and this was not apparent. However, the information gathered may inform the design of a definitive clinical trial. Here we report a series of divergent omics signals that invites additional hypotheses testing. SIGNIFICANCE STATEMENT: The impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on the immune response elicited by repeat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunizations was profiled by immunophenotypic, proteomic, and metabolomic approaches in a clinical pilot study of small sample size. A SARS-CoV-2 vaccine-specific immune response was evident irrespective of concomitant NSAID consumption. The information gathered may inform the design of a definitive clinical trial.

Nonsteroidal Anti-inflammatory Drugs Are Not Associated With Increased Bleeding in Blunt Solid Organ Injury.

Nonsteroidal anti-inflammatory drugs are an effective nonopiate option for pain control. However, the antiplatelet aggregation of cyclooxygenase-1 (COX-1) inhibitors presents a concern in that they may exacerbate bleeding in patients with solid organ injuries. The aim of the study is to evaluate the impact of nonsteroidal anti-inflammatory drugs on blunt solid organ injury. We hypothesized that nonsteroidal anti-inflammatory drugs would not contribute to intra-abdominal bleed progression. This is a retrospective cohort study of blunt solid organ injury evaluated from June 1, 2015, to June 30, 2019, at an urban midwestern Level I trauma center. Patients receiving and those not receiving nonsterioidal anti-inflammatory drugs were compared on intra-abdominal bleeding progression as assessed by surgical intervention, angioembolization, and blood transfusions. We analyzed 706 patients, of whom 206 were given nonsteroidal anti-inflammatory drugs during their hospital course. Compared with those who were not given nonsteroidal anti-inflammatory drugs, patients given nonsteroidal anti-inflammatory drugs were less likely to have an operation (odds ratio, OR 0.46, 95% confidence interval, CI [0.25, 0.85], p = .012) and were less likely to have an embolization (OR 0.27, 95% CI [0.11, 0.70], p = .004). There was no difference in the need for packed red blood cell transfusion between the nonsteroidal anti-inflammatory drug and non- nonsteroidal anti-inflammatory drug groups (95% CI [0.91, 1.99], p = .13). Patients given nonsteroidal anti-inflammatory drugs had a decreased likelihood of receiving an organ-specific procedure or needing a blood transfusion and had no difference in mortality. Our findings indicate that nonsteroidal anti-inflammatory drugs in patients with blunt solid organ injuries were not associated with an increased risk of adverse events related to intra-abdominal bleeding.

Influence of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) on Photosynthetic Parameters and Secondary Metabolites of Plants from Fabaceae Family

Nonsteroidal anti-inflammatory medications (NSAIDs) are commonly used painkillers, anti-inflammatory agents, and fever reducers. They arrive in the environment from municipal wastewater and/or agriculture waste, affecting growing plants. In our study, the impact of NSAIDs, namely, diclofenac, indomethacin, naproxen, and paracetamol, on four plant species from the Fabaceae family (Cicer arietinum, Pisum sativum, Lens culinaris, and Vicia faba) was tested. The assimilation rate and stomatal conductance decreased for all plants treated with NSAIDs. Chlorophyll and carotenoid contents in the leaves of plants under stress declined by more than 15% compared with the control plants, while the flavonoids and total phenols decreased to a lesser extent. In contrast, the plants treated with NSAIDs emit terpenes and green leaf were volatile, at a level of some nmol m−2 s−1, which could influence the atmospheric reaction and ozone formation.

Impact of nonsteroidal anti-inflammatory drugs on efficacy of anti-PD-1 therapy for primary liver cancer

To assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical outcomes of patients receiving anti-PD-1 immunotherapy for hepatocellular carcinoma. We conducted a retrospective study among 215 patients with primary liver cancer receiving immunotherapy between June, 2018 and October, 2020. The patients with balanced baseline characteristics were selected based on propensity matching scores, and among them 33 patients who used NSAIDs were matched at the ratio of 1∶3 with 78 patients who did not use NSAIDs. We compared the overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) between the two groups. There was no significant difference in OS between the patients using NSAIDs (29.7%) and those who did not use NSAIDs (70.2%). Univariate and multivariate analyses did not show an a correlation of NSAIDs use with DCR (univariate analysis: OR=0.602, 95% CI: 0.299-1.213, P=0.156; multivariate analysis: OR=0.693, 95% CI: 0.330-1.458, P=0.334), PFS (univariate analysis: HR=1.230, 95% CI: 0.789-1.916, P=0.361; multivariate analysis: HR=1.151, 95% CI: 0.732-1.810, P=9.544), or OS (univariate analysis: HR=0.552, 95% CI: 0.208-1.463, P=0.232; multivariate analysis: HR=1.085, 95% CI: 0.685-1.717, P=0.729). Our results show no favorable effect of NSAIDs on the efficacy of immunotherapy in patients with advanced primary liver cancer, but this finding still needs to be verified by future prospective studies of large cohorts.

735 Early Treatment with NSAIDs Improves Blood Clotting Function in Severely Burned Patients

IntroductionThe risk of coagulopathy is increased in severe burns. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed in burn patients to relieve pain and reduce inflammation. This study investigates the impact of NSAIDs on burn induced coagulopathy in severely burned patients.MethodsSevere burn patients (total body surface area [TBSA] >20%) were identified with TriNetX, a North American federated health research network from 51 health-care organizations (HCOs) and categorized for those receiving NSAIDs during the first week following injury; those with NSAID use prior to injury were excluded. NSAIDs included in this study were ibuprofen, oxaprozin, indomethacin, aspirin, diclofenac, celecoxib, and naproxen. Burn induced coagulopathy was defined as international normalized ratio (INR) levels ≥1.5. Statistical significance of the rate of burn-induced coagulopathy in the week following injury among the two groups was analyzed with measures of association using chi-squared tests.ResultsWe identified 709 severely burned patients receiving NSAIDS during the week after burn and 1,032 severely burned patients without NSAID use. Among those receiving NSAIDs, ibuprofen and aspirin were the most prescribed at rates of 80% and 36%, respectively. After cohort matching, the risk of burn induced coagulopathy was significantly decreased in patients taking NSAIDs (17.7%) compared to patients not receiving NSAIDs (32.3%) (p< 0.0001). The protective nature of NSAIDs was greatest on the same day (p=0.0002) and first day following burn injury (p=0.0026). On average, those not taking NSAIDs had an elevated risk of developing coagulopathy compared to those who did as %TBSA increased in 10% intervals. This observation was confirmed in a linear regression analysis with slopes of 0.0453 and 0.0293, respectively. Furthermore, patients taking NSAIDs were less likely to develop sepsis (p=0.0046) and thrombocytopenia (p=0.0003) and die the first week following injury (p< 0.0001).ConclusionsThe early protective effects of NSAIDs at reducing the risk of coagulopathy occurs during the acute phase of burns, though selection bias cannot be excluded. The potential risk of burn induced coagulopathy increased more with %TBSA in patients without NASIDs.

NSAID Use and Effects on Pediatric Bone Healing: A Review of Current Literature.

This systematic review evaluates and synthesizes the available peer-reviewed evidence regarding the impact of non-steroidal anti-inflammatory drugs (NSAIDs) on fracture healing in skeletally immature patients. Evidence supports the use of NSAIDs in this patient population for adequate pain control without increasing the risk of nonunion, particularly in long bone fractures and pseudoarthrosis after spine fusion. However, further clinical studies are needed to fill remaining gaps in knowledge, specifically with respect to the spectrum of available NSAIDs, dosage, and duration of use, in order to make broad evidence-based recommendations regarding the optimal use of NSAIDs during bone healing in skeletally immature patients.

Association of Kidney-Related Safety Events with Incident Chronic Kidney Disease in Veterans

Objective: The impact of Nonsteroidal Anti-Inflammatory Drugs (NSAID) and iodine-based contrast exposures on developing Chronic Kidney Disease (CKD) is controversial. We examined the association of these exposures with the development of CKD in a Veteran population. Methods: A retrospective case-control study of 154,448 veterans from the Veterans Affairs (VA) Corporate Data Warehouse (CDW) database between 2005 and 2014 was conducted to assess the association between incident stage 3 CKD with Acute Kidney Injury (AKI), NSAID use, iodine-based contrast exposures, and comorbid conditions. Stepwise logistic regression was used to determine multivariable adjusted Odds Ratios (OR). Results: The mean age was 59 (SD±13), and the median eGFR was 84 (IQR: 73, 96). AKI was associated with increased odds of CKD (inpatient: OR=3.76, 95% CI: 3.44, 4.11; outpatient: OR=4.73, 95% CI: 4.09, 5.46) and demonstrated escalated odds with &gt;1 episode (inpatient: OR=5.72, 95% CI: 4.71, 6.95; outpatient: OR=8.36, 95% CI: 6.32, 11.06). Months of NSAID prescriptions was associated with CKD, with ORs at &gt;0-6 months, &gt;6-12 months, and &gt;12 months of 1.27 (95% CI: 1.23, 1.32), 1.54 (95% CI: 1.46, 1.63), and 1.69 (95% CI: 1.62, 1.77) respectively. Iodine-based contrast exposure was associated with increased odds of CKD, with ORs for 1-2 Computed Tomography (CT) scans, ≥3CT scans, and left heart catheterization of 1.29 (95% CI: 1.24, 1.35), 1.29 (95% CI: 1.20, 1.28), and 1.38 (95% CI: 1.17, 1.63) respectively. Conclusion: AKI events, NSAID use, and iodine-based contrast exposures are associated with increased odds for developing stage 3 CKD in veterans.

Non-steroidal anti-inflammatory drugs, polygenic risk score and colorectal cancer risk.

The regular use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced colorectal cancer (CRC) risk. To explore whether this association varies according to background polygenic risk for CRC. Data were collected from a large population-based case-control study on CRC in Germany. A polygenic risk score (PRS) based on 140 CRC-related risk loci was used to quantify the genetic risk. The associations of regular use of NSAIDs (≥2times per week for at least 1year) with CRC risk were estimated in the whole population and in subgroups according to PRS levels using multivariable logistic regression. The impact of NSAIDs on CRC risk was compared to PRS using the 'genetic risk equivalent' (GRE), a recently developed metric for effective risk communication. In total 5129 CRC cases and 4093 controls were included in this analysis. The regular use of NSAIDs (including aspirin) was associated with reduced CRC risk [odds ratio (OR) 0.66, 95% confidence interval (CI) 0.59, 0.74], as was regular use of aspirin only (OR 0.73, 95% CI 0.65, 0.83), without indication of interaction with the PRS (P=0.10 and 0.22 respectively). The effect of NSAID use was equivalent to the effect of having a 32 percentiles lower PRS (GRE -32, 95% CI -41, -22). The regular use of NSAIDs is associated with greatly reduced CRC risk regardless of individual genetic profile. With an equivalent reduction of relative risk across all polygenic risk groups, absolute risk reduction would be expected to be strongest among those with the highest polygenic risk score.

Impact of non-steroidal anti-inflammatory drugs on the efficiency of enhanced recovery programmes after colorectal surgery: a retrospective study of the GRACE database

BackgroundMultimodal analgesia is considered a key element of enhanced recovery programmes (ERPs) after colorectal surgery. We investigated the effects of NSAIDs, a major component of multimodal analgesia on adherence to ERP, incidence of postoperative complications, and length of hospital stay (LOS). MethodsThis was a retrospective study of the GRACE database that included 8611 patients scheduled for colorectal surgery with an ERP between February 2016 and November 2019. Primary endpoints were adherence to the postoperative protocol, the rate and type of postoperative complications, and LOS. Data are median [IQR] and number (per cent). Multivariate models were used to assess the effects of NSAIDs on these variables taking into account potential confounding factors. ResultsData from 8258 patients were analysed and classified into four groups according to whether NSAIDs had been given intra- and/or postoperatively or not at all; 4578 patients were given NSAIDs intra- and/or postoperatively and 3680 patients received no NSAIDs. Use of NSAIDs was significantly (P<0.001) associated with improved adherence to the postoperative protocol (4.0 [3.0−4.0] vs. 3.0 [2.0−4.0] items), a reduced incidence of complications (21.1% vs. 29.2%), and a shortened LOS (5.0 [3.0−7.0] vs. 6.0 [4.0−9.0] days) compared to the no-NSAIDs group. Multivariate analyses adjusted for the confounding factors confirmed a significant (P<0.001) beneficial impact of NSAIDs on these three primary endpoints. ConclusionThis study suggests that perioperative NSAID use results in better adherence to the postoperative protocol, fewer postoperative in-hospital complications, and shorter LOS after colorectal surgery.