Nonsteroidal Anti-inflammatory Drugs Group Research Articles

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.

NSAID PRESCRIPTION SURVEY IN INTEGRATED TRADITIONAL AND WESTERN MEDICINE TREATMENT: ASSESSING GASTROINTESTINAL AND CARDIOVASCULAR RISKS

Introduction: Non-steroidal anti-inflammatory drug (NSAID) usage should be carefully considered based on gastrointestinal (GI) and cardiovascular (CV) risks. In light of restricted evidence, this study aims to assess the prescription of NSAIDs concerning the GI and CV risks in the integrated treatment of Traditional medicine (TM) and Western medicine (WM). Materials and method: A retrospective cross-sectional study was conducted on 393 medical records of inpatients using NSAIDs in 2022 at the Traditional Medicine Hospital of Ho Chi Minh City. GI and CV risks, as well as information regarding NSAID prescriptions, were recorded. A multivariable regression model was employed to identify factors associated with the prescription of NSAID groups. Results: NSAIDs were primarily prescribed for musculoskeletal and connective tissue disorders (87.28%). Approximately half of the cases exhibited moderate to high GI risk (47.59%), while for CV risk, there were 68.95% with moderate to very high risk. COX-2 inhibitors were the most commonly prescribed (94.66%), even when considering GI and CV risks separately. In the majority, NSAID prescriptions aligned with both risks according to American College of Gastroenterology (ACG) guidelines (73.79%). The prescription of NSAID groups was significantly influenced by patient gender, ailment type, and physician education (p<0.05), but not by GI and CV risks (p>0.05). Conclusion: Patients receiving NSAIDs in integrated TM and WM treatment often faced an increased GI and CV risk, with the majority adhering to ACG guidelines. However, GI and CV risks were not significantly considered for NSAID group selections. Multi-center studies should be conducted.

Opioid-Sparing Nonsteroid Anti-inflammatory Drugs Protocol in Patients Undergoing Intramedullary Nailing of Tibial Shaft Fractures: A Randomized Control Trial.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective analgesics commonly used in fracture management. Although previously associated with delayed fracture healing, multiple studies have demonstrated their safety, with minimal risks of fracture healing. Given the current opioid crisis in the United States, alternate pain control modalities are essential to reduce opioid consumption. This study aims to determine whether the combination of oral acetaminophen and intravenous ketorolac is a viable alternative to opioid-based pain management in closed tibial shaft fractures treated with intramedullary nailing. We conducted a randomized controlled trial evaluating postoperative pain control and opioid consumption in patients with closed tibial shaft fractures who underwent intramedullary nailing. Patients were randomized into an NSAID-based pain control group (52 patients) and an opioid-based pain control group (44 patients). Visual analog scale (VAS) scores and morphine milligram equivalents (MMEs) were evaluated at 12-hour postoperative intervals during the first 48 hours after surgery. Nonunion and delayed healing rates were recorded for both groups. A statistically significant decrease in MMEs was noted at every measured interval (12, 24, 36, and 48 hours) in the NSAID group compared with the opioid group ( P -value 0.001, 0.001, 0.040, 0.024, respectively). No significant change in visual analog scale scores was observed at 12, 36, and 48 hours between both groups ( P -value 0.215, 0.12, and 0.083, respectively). A significant decrease in VAS scores was observed at the 24-hour interval in the NSAID group compared with the opioid group ( P -value 0.041). No significant differences in union rates were observed between groups ( P -value 0.820). Using an NSAID-based postoperative pain protocol led to a decrease in opioid consumption without affecting pain scores or union rates. Owing to the minimal risk of short-term NSAID use, their role in the perioperative management of tibia shaft fractures is justified, especially when they reduce opioid consumption markedly. Therapeutic Level I.

Triamcinolone Acetonide Subconjunctival Injection as Stand-alone Inflammation Prophylaxis after Phacoemulsification Cataract Surgery

PurposeTo compare the effectiveness and safety of a single injection of subconjunctival triamcinolone acetonide (TA) to postoperative topical prednisolone acetate (PA) with and without nonsteroidal anti-inflammatory drug (NSAID) for cataract surgery prophylaxis DesignRetrospective comparative effectiveness cohort study ParticipantsPatients undergoing phacoemulsification cataract surgery at Kaiser Permanente Northern California from 2018 through 2021 InterventionAnti-inflammatory prophylaxis exposure groups included topical PA with or without NSAID, and subconjunctival injection of TA (Kenalog®) 10 mg/mL or 40 mg/mL in low (1.0 - 3.0 mg) or high dose (3.1 - 5.0 mg). Main Outcome MeasuresThe adjusted odds ratio (OR) and 95% confidence interval (CI) for the association of postoperative macular edema (ME) and iritis diagnoses 15 to 120 days following surgery (effectiveness measures) and a glaucoma-related event (safety measure) between 15 days to 1 year after surgery ResultsOf 69,832 eligible patient-eyes, postop ME, iritis, and a glaucoma-related event occurred, on average in 1.3%, 0.8% and 3.4% in the topical groups and 0.9%, 0.5% and 2.8% in the injection groups, respectively. In multivariate analysis, all injection groups had a trend of a lower OR of ME compared with the topical PA reference group, with the high dose TA 10 mg/mL group reaching statistical significance (OR 0.64, CI 0.43,0.97, P=0.033). The PA + NSAID group had higher odds (OR 0.88, CI 0.74,1.04, P =0.135). There was a trend of lower odds of a postop iritis diagnosis in the high strength (40 mg/mL) groups. For postop glaucoma-related events, compared with PA, the TA 10 mg/mL low dose group had lower odds (OR 0.69, CI 0.55,0.86, P=0.001), the TA 10 mg/mL high dose group had similar odds (OR 0.90, CI 0.70,1.15, P=0.40) and the TA 40 mg/mL low and high dose groups had higher odds (OR 1.46, CI 0.98,2.18, P=0.062), (OR 2.14, CI 1.36,3.37, P=0.001), respectively. ConclusionsThe TA 10 mg/mL high dose group, with an average dose of 4 mg, was associated with lower risk of postop macular edema and a similar risk of a glaucoma-related event compared with the topical groups.

Ultrasound guided injection with Collagen-based Medical Device: real-life evaluation of efficacy and safety in hip osteoarthritis.

Data regarding the treatment of hip osteoarthritis (OA) with collagen-based extracellular bio-scaffolds are lacking. We evaluated the treatment of hip OA with ultrasound guided intraarticular injections of Collagen-based Medical Device(CMD). Forty-four patients with Kellgren-Lawrence grade (KLG) I or II were selected, and 20/44randomly selected patients (CMD group), were treated with 2 weekly consecutive ultrasound guided intraarticular injections ofCMD (MD-HIP, Guna S.p.a. Milan, Italy). An additional 24/44 patients were treated with oral non-steroidal anti-inflammatorydrugs (NSAIDs) daily (NSAIDs group). Clinical assessment, X-rays and ultrasound evaluation were performed at baseline,and after 1 month in both groups, and after 3 months in the CMD group. Outcome measures were general pain VAS (0-10), thewhole WOMAC score, and the WOMAC specific subscores. CMD and NSAIDs group were homogenous for age,gender, VAS pain and WOMAC scores. The CMD group had significant improvement of the VAS pain (p<0.0001), globalWOMAC score (p<0.0001) and WOMAC function (p<0.0001) from baseline to the 1st month, with further improvementfrom the 1st to the 3rd month (p<0,001; p<0.01; p<0.03, respectively). Significant improvement in WOMAC pain (p<0.0001)and WOMAC stiffness (p<0.0001) was detected at 1st month, with no significant change at 3rd month. In the NSAIDs groupsignificant improvement in WOMAC function was detected after 1 month (p=0.021) only. No adverse events were recorded inthe CMD and NSAIDs group. The ultrasound guided intraarticular hip injections of CMD resulted in significantimprovement in VAS pain and WOMAC scores compared to treatment with oral NSAIDs.

Comparing Metabolic Preconditioning and Diabetes As Risk Factors in Knee Arthroplasty Complications.

Advanced osteoarthritis of the knee joint severely affects the patient's mobility, compounded by pre-existing comorbidities such as metabolic preconditioning (such as obesity, dyslipidemia, hyperuricemia, and insulin resistance syndrome) and both type I and type II diabetes. The success of total knee arthroplasty is influenced by knowledge and management of risk factors. The present study aims to evaluate differences in the evolution of risk factors such as obesity, injuries, and sedentary lifestyle, distinguishing those with metabolic preconditions and diabetes. The objectives of our study include (1) investigating the prevalence of obesity among patients, highlighting their proportion in the five categories of body weight; (2) analyzing statistically significant differences between research groups in terms of weight status and physical activity; (3) evaluating postoperative evolution based on the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and without NSAIDs (N-NSAIDs), with an emphasis on overweight patients and those with diabetes; and (4) examining changes in metabolic preconditioning and the incidence of postoperative injury depending on the administration of anti-inflammatory drugs. A cohort involving 730 patients diagnosed with gonarthrosis was divided into two groupsaccording to the administration of anti-inflammatory drugs in the first seven postoperative days:N-NSAIDs group (394 patients, 55.3%)and respectively NSAIDs group (319 patients, 44.7%). Theprospective, observational study was conducted in terms ofrisk factors and complications that occurred upon treatment administration in relation to each type of intervention andimplant used. The outcomes were assessed in terms of the influence on quality of life, the data beingcollected and interpreted for the entire cohort, and for each study year individually. The results indicate that almost 69% of them were overweight, while only 31% had a normal weight. Significant differences in weight status were observed between research groups, highlighting the association between obesity and metabolic preconditions or diabetes. Physical activity was absent in a significant proportion, having a notable impact on postoperative evolution, especially in the group without metabolic precondition. Administration of anti-inflammatory drugs influenced postoperative outcomes, with significant differences in overweight and diabetic patients. The findings suggest the need to manage body weight, promote physical activity, and personalize postoperative treatments, given the complex interactions between obesity, metabolic preconditions, and the administration of NSAIDs.

A clinical study on the risk and safety profiles of NSAIDs used for osteoporotic fractures in Chinese patients with rheumatoid arthritis

Purpose: To investigate the risk and safety profile of non-steroidal anti-inflammatory drugs (NSAIDs) for osteoporotic fractures in patients with rheumatoid arthritis (RA). &#x0D; Methods: 298 RA patients admitted to The First People's Hospital of Huzhou, Huzhou, China from August 2020 to September 2022, were investigated. Patients were assigned to groups based on drugs used viz: control group received anti-rheumatic drugs other than NSAIDs; corticosteroid group received dexamethasone, disease-modifying anti-rheumatic drugs (DMARDs) groups received sulfasalazine, NSAID group received either diclofenac or ibuprofen etc. Each group of patients received the respective treatment frequently for at least 3 years. The primary outcome in this study was the incidence of osteoporotic fracture resulting from fragile bone and deterioration of bone mass. &#x0D; Results: The incidence of osteoporotic fracture was highest in NSAID group (11.58 %) when compared to 5.44, 4.96, and 2.36 % in the corticosteroid, DMARD and control groups, respectively (p &lt; 0.05). This shows that users of NSAIDs had a 5-fold higher risk of osteoporotic fracture than patients in control group (OR = 1.26 (95 % CI: 1.22 - 1.81)) and 2-fold possibility of osteoporotic fracture when compared to corticosteroid users ((OR = 1.46 (95 % CI: 1.57 - 2.32)) and DMARD users (1.83 (95 % CI: 1.26 - 1.67)). &#x0D; Conclusion: Rheumatoid arthritis patients on NSAIDs such as celecoxib, diclofenac, ibuprofen, indomethacin, and oxaprozin are at risk of developing osteoporotic fracture. Therefore, NSAIDs must be used with proper counseling in RA patients to minimize the risk of osteoporotic fracture. In future, the study duration will need to be extended to determine the long-term effects and potential changes in bone properties.

Safety of the immediate use of nonsteroidal anti-inflammatory drugs after adult craniotomy for tumor.

Poor pain control has a negative impact on postoperative recovery and patient satisfaction. However, overzealous pain management, particularly with opioids, can confound serial neurological assessments, increase morbidity, and predispose patients to long-term dependence. Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in treating postoperative pain and can limit opioid intake, but their use has been limited in patients undergoing craniotomy for brain tumor resection due to concerns of an increased hemorrhage risk. Herein, the authors aim to 1) address the safety of NSAID use in the immediate postoperative setting and 2) determine whether NSAID administration decreases opioid use following craniotomy for tumor resection in adult patients. The authors conducted a retrospective cohort study of patients 18 years and older with an estimated glomerular filtration rate ≥ 60 ml/min/body surface area who had undergone craniotomy for tumor resection at their institution between 2019 and 2021. NSAID use in the first 48 hours following surgery was recorded. Primary outcomes were postoperative hemorrhage requiring a return to the operating room before hospital discharge and within 30 days of surgery. Secondary outcomes were more-than-minimal hemorrhage that did not require reoperation, acute kidney injury, and total opioid use within 48 hours after craniotomy. Among 1765 reviewed patient records, 1182 were eligible for inclusion in this analysis. Amid these records were 114 patients (9.6%) who had received at least one dose of an NSAID within 48 hours of their craniotomy. Four (0.3%) patients experienced bleeding requiring a return to operating room, one of whom was from the NSAID-treated group (RR 3.12, 95% CI 0.33-29.77, p = 0.30). No significant difference in nonoperative intracranial hemorrhage (RR 1.34, 95% CI 0.54-3.35, p = 0.53), postoperative acute kidney injury, or clinically significant extracranial bleeding was found between the NSAID and no-NSAID groups. Patients in the NSAID group had significantly higher oral morphine equivalent use (median 68 vs 30, p < 0.001). Postoperative NSAID use following craniotomy for tumor resection was not associated with an increased risk of hemorrhage requiring a return to the operating room. The authors noted higher opioid use in the patients treated with NSAIDs, which may reflect underlying reasons for the decision to treat patients with NSAIDs in the immediate postoperative period. These data warrant further investigation of NSAIDs as a safe, opioid-sparing postoperative pain management strategy in patients with normal kidney function who are undergoing intracranial tumor resection.

Effect of Transdermal Microneedle Patch Plus Nonsteroidal Anti-Inflammatory Drug in Knee Osteoarthritis: A Randomized, Double-Blind Study

Purpose: No recent clinical study has shown the efficacy of transdermal microneedle patch (TDM) plus nonsteroidal antiinflammatory drug (NSAID) in early knee osteoarthritis (OA). This study aimed to determine the effect of TDM plus NSAID on synovial hypertrophy, knee pain, and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score in osteoarthritic knees. Methods: A randomized, controlled, double-blind trial was conducted. One hundred participants, aged 40–70 years, with painful knee OA and radiographic nonstructural changes were randomly assigned into two groups to undergo TDM plus NSAID (ketorolac 30 mg) or TDM (placebo) at the medial joint line of the knee twice (once weekly). The synovial thickness was measured using ultrasonography at pretreatment, weeks 1, 2, and 4. The visual analog scale (VAS) for pain, WOMAC score, and adverse events (AEs) were also recorded. Results: The TDM plus NSAID group demonstrated a significant reduction in synovial thickness and VAS at weeks 2 and 4 compared with the placebo group (P&lt;0.05). At week 4, the mean synovial thickness reduction was 1.1 and 0.3 mm, and the mean VAS reduction was 3.2 and 1.7 for the TDM plus NSAID and placebo groups, respectively. The mean WOMAC scores at week 4 were significantly reduced (5.7 and 0.9 for the TDM plus NSAID and placebo groups, respectively). No complication and treatment-related AEs occurred. Conclusions: TDM plus NSAID significantly reduced synovitis and improved the pain score in knee OA after 2 weeks. The WOMAC score improved at week 4 without any AEs. Thai Clinical Trials Registry (TCTR), TCTR identification number is TCTR20200613001.

Leaky gut and inflammatory biomarkers in a medication overuse headache model in male rats.

Medication overuse is common among chronic migraine patients and nonsteroidal antiinflammatory drugs (NSAIDs) are the most frequently overused drugs. The pathophysiological mechanisms underlying medication overuse headache (MOH) are not completely understood. Intestinal hyperpermeability and leaky gut are reported in patients using NSAIDs. The aim of the study is to investigate the role of leaky gut and inflammation in an MOH model MOH model in male rats. The study was conducted in male Sprague Dawley rats. There were two experimental groups. The first group was the chronic NSAID group in which the rats received mefenamic acid (n = 8) for four weeks intraperitoneally (ip) and the second group was the vehicle group (n = 8) that received 5% dimethyl sulfoxide+sesame oil (ip) for 4 weeks. We assessed spontaneous pain-like behavior, periorbital mechanical withdrawal thresholds, and anxiety-like behavior using an elevated plus maze test. After behavioral testing, serum levels of occludin and lipopolysaccharide-binding protein (LBP) and brain levels of IL-17, IL-6, and high mobility group box 1 protein (HMGB1) were evaluated with ELISA.Results: Serum LBP and occludin levels and brain IL-17 and HMGB1 levels were significantly elevated in the chronic NSAID group compared to its vehicle (p = 0.006, p = 0.016, p = 0.016 and p = 0.016 respectively) while brain IL-6 levels were comparable (p = 0.67) between the groups. The chronic NSAID group showed pain-like and anxiety-like behavior in behavioral tests. Brain IL-17 level was positively correlated with number of head shakes (r = 0.64, p = 0.045), brain IL-6 level was negatively correlated with periorbital mechanical withdrawal thresholds (r = -0.71, p = 0.049), and serum occludin level was positively correlated with grooming duration (r = 0.73, p = 0.032) in chronic NSAID group. Elevated serum occludin and LBP levels and brain IL-17 and HMGB1 levels indicate a possible role of leaky gut and inflammation in an MOH model in male rats. Additionally, a significant correlation between pain behavior and markers of inflammation and intestinal hyperpermeability, supports the role of inflammation and leaky gut in MOH pathophysiology.

Results of a non-interventional observational multicenter study of the management of patients with axial psoriatic arthritis in real-life clinical practice (NiSaXPA)

Psoriatic arthritis (PsA) is a chronic immunoinflammatory disease of the joints, spine and entheses from the group of spondyloarthritis, which is usually observed in patients with psoriasis. In recent years, the axial form of PsA (axPsA) has been actively researched. However, there is insufficient data on approaches to the diagnosis and treatment of patients with axPsA in real-life clinical practice. This article presents the results of an interim analysis of data from a non-interventional multicenter observational study on the treatment of patients with axPsA in real-life clinical practice (NiSaXPA) in Russian centers.Objective: to identify patients with axPsA, their characteristics and describe treatment tactics in real-life clinical practice.Material and methods. Patients with PsA who met the inclusion criteria were prospectively followed up during routine visits to a rheumatologist. Participants' axial radiographs were uploaded to a database in order for it to be confirmed the presence or absence of axPsA by two independent experts, a rheumatologist and a radiologist. Patients with a confirmed axPsA diagnosis participated in a further data collection phase (Visit 2, week 24).Results and discussion. Six hundred patients were enrolled into the study. At the time of analysis, 386 (64.3%) of them (209 men and 177 women) were screened for axPsA. The diagnosis of axPsA was confirmed in 241 (62.4%) cases; these patients formed the Per Protocol (PP) population. The mean age of patients with axPsA in the PP population was 46.30±12.6 years and the body mass index (BMI) was 27.4±5.2 kg/m2 . In 14.9% of patients, the duration of psoriasis was less than 1–5 years, in 21.5% – 5–10 years and in 63.6% – more than 10 years. The duration of PsA symptoms was less than 1–5 years in 31.2 % of patients, 5–10 years in 31.6 % and more than 10 years in 37.2 %. Low disease activity (BASDAI ˂ 4) was achieved in 33.3 % of patients with axPsA at visit 1 and in 64.3 % at visit 2; the BASDAI index declined on average from 4.67±1.95 to 3.31±1.89 points.In real-life clinical practice, patients were most frequently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) – 88.7% and 71.7% (visits 1 and 2, respectively), and synthetic disease-modifying antirheumatic drugs (sDMARDs) –79.1% and 70.7%, respectively; therapy with biologic disease-modifying antirheumatic drugs (bDMARDs) was initiated in 40.2% and 60.6% of patients, respectively.Conclusion. The results of the interim analysis of this observational study showed that in 87.2% of patients who met the CASPAR criteria for PsA there was a suspicion of axial manifestations of PsA on the primary care level. However, only 62.4% of them had a confirmed diagnosis of axPsA on centralized expert assessment, which may indicate a possible overdiagnosis of axial lesions in real-life practice and emphasizes the importance of collaboration between a rheumatologist and a radiologist when analyzing the results of imaging studies. 33.3% of patients with axPsA had low disease activity according to BASDAI at baseline and 64.3% after 24 weeks, meaning that the disease was only adequately controlled in one third of cases despite therapy; the number of these patients doubled after a change in therapy. In real-world clinical practice, patients with axPsA are most commonly prescribed drugs from the NSAID and sDMARD groups; the frequency of use of biologic drugs varied between 40.2 and 60.6% by the end of the observation period.

Effect of nonsteroidal anti-inflammatory drugs on pelvic floor muscle regeneration in a preclinical birth injury rat model

BackgroundPelvic floor muscle (PFM) injury is a common consequence of vaginal childbirth. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used postpartum analgesics. Multiple studies report negative effects of these drugs on limb muscle regeneration. The impact of NSAIDs on PFM recovery following birth injury has not been explored. ObjectiveUsing the validated rat model, we assessed the effects of NSAIDs on acute and longer-term PFM recovery following simulated birth injury (SBI). Study DesignThree-month old Sprague-Dawley rats were randomly assigned to (1) controls; (2) SBI; (3) SBI + NSAID; or (4) NSAID group. SBI was induced using a well-established vaginal balloon distention protocol. Ibuprofen was administered in drinking water (0.2 mg/ml) ad lib. Animals were sacrificed at 1,3,5,7,10,28 days post birth injury/ibuprofen administration. The pubocaudalis portion of the rat levator ani, which, like the human pubococcygeus, experiences larger parturition-associated strains, was harvested (N=3-9/timepoint/group). The cross-sectional areas of regenerating (embryonic myosin heavy chain (eMyHC)+) and mature myofibers were assessed at the acute and 28-day timepoints, respectively. The intramuscular collagen content was assessed at the 28-day timepoint. Myogenesis was evaluated using anti-Pax7 and anti-myogenin antibodies to identify activated and differentiated muscle stem cells, respectively. The overall immune infiltrate was assessed using anti-CD45 antibody. Expression of genes coding for pro- and anti-inflammatory cytokines was assessed by qRT-PCR at 3,5,10 days post-injury. ResultsThe pubocaudalis fiber size was significantly smaller in the SBI+NSAID compared to SBI group at 28 days post-injury, P<0.0001. The median size of eMyHC+ fibers was also significantly reduced, with fiber area distribution enriched with smaller fibers in SBI+NSAID compared to SBI group at 3 days post-injury (P<0.0001), suggesting a delay in the onset of regeneration in the presence of NSAIDs. By 10 days post-injury, the median eMyHC+ fiber size in the SBI group decreased from 7 days post-injury (P<0.0001) with a tight cross-sectional area distribution, indicating nearing completion of this state of regeneration. However, in the SBI+NSAID group, the size of eMyHC+ fibers continued to increase (P<0.0001) with expansion of the cross-sectional area distribution, signifying a delay in regeneration in these animals. NSAID decreased the muscle stem cell pool at 7 days post-injury (P<0.0001) and delayed muscle stem cell differentiation, as indicated by persistently elevated number of myogenin+ cells 7 days post-injury (P<0.05). In contrast, the proportion of myogenin+ cells returned to baseline by 5 days post-injury in the SBI group. The analysis of expression of genes coding for pro- and anti-inflammatory cytokines demonstrated only transient elevation of Tgfb1 in SBI+NSAID group at 5 but not at 10 days post-injury. Consistent with previous studies, SBI+NSAID resulted in increased deposition of intramuscular collagen compared to uninjured animals. There were no significant differences in any outcomes of interest between the NSAID group and the unperturbed controls. ConclusionsNSAIDs negatively impact PFM regeneration in the preclinical SBI model. The above appears to be driven by the negative impact of NSAIDs on pelvic muscle stem cell function, resultant in delayed temporal progression of PFM regeneration following birth injury. These novel findings provide impetus to investigate the impact of postpartum NSAID administration on muscle regeneration in women at high risk for PFM injury.

Bleeding risk from nonsteroidal anti‐inflammatory drugs after functional endoscopic sinus surgery: Analysis of the TriNetX database

AbstractObjectivesPostoperative pain medications and aspirin before undergoing functional endoscopic sinus surgery (FESS) are managed carefully due to concern for bleeding. Little is known regarding the increase in the risk of bleeding for patients unable to stop aspirin as trials are limited in this area. We compared outcomes for patients undergoing FESS who were managed postoperatively with nonsteroidal anti‐inflammatory drugs (NSAIDs) versus opioids. We also determined the epistaxis rate for patients on aspirin at the time of surgery compared to those who were not on aspirin.Data SourceRetrospective analysis of patients undergoing FESS using the TriNetX database.MethodsPatients were propensity‐matched, and the odds of bleeding complications between the patients prescribed postoperative NSAIDs were compared to those prescribed opioids. We also compared postoperative odds of bleeding in patients unable to halt aspirin use at the time of surgery to those who were not on aspirin before surgery.ResultsA total of 51,361 patients received opioids after FESS compared to 1923 patients who received NSAIDs. After propensity matching, 1918 patients were in each group and odds of epistaxis were similar between the NSAID group and the opioid group (odds ratio [OR]: 1.32, 95% confidence interval (CI): 0.90–1.94); 7.67% of the NSAID group required rescue opioids. Patients on aspirin who were unable to hold aspirin at surgery showed bleeding rates of 14.67% compared to 9.00% in propensity‐matched controls who were not on aspirin (OR: 1.74, 95%CI: 1.20–2.51).ConclusionsNSAID use appears to be a safe alternative to opioids for patients without pre‐existing risk factors for bleeding. Patients who remained on aspirin in the week before FESS had an increased risk of postoperative epistaxis.

Associations between the use of common nonsteroidal anti-inflammatory drugs, genetic susceptibility and dementia in participants with chronic pain: A prospective study based on 194,758 participants from the UK Biobank

ObjectiveTo investigate the potential relationship between common nonsteroidal anti-inflammatory drugs (NSAIDs), genetic susceptibility and all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VD) among individuals experiencing chronic pain. MethodsThis study was based on 194,758 chronic pain participants form UK biobank with a median follow-up of 13.7 years. Participants were categorized into different NSAIDs painkiller regimen groups: No NSAIDs group, Aspirin group, Ibuprofen group, Paracetamol group, and 2–3 NSAIDs group. Cox proportional risk models were used to examine the correlation between regular NSAIDs usage and the risk of ACD, AD, and VD. In addition, we further performed subgroup analyses and sensitivity analyses. Results1) Compared to the No NSAIDs group, the aspirin group (HR = 1.12, 95% CI:1.01–1.24, P < 0.05), the paracetamol group (HR = 1.15, 95% CI:1.05–1.27, P < 0.01), and the 2–3 NSAIDs group (HR = 1.2, 95% CI:1.08–1.33, P < 0.05) showed a higher risk of ACD. Furthermore, the 2–3 NSAIDs group was also associated with a higher risk of VD (HR = 1.39, 95% CI: 1.08–1.33, P < 0.05). 2) At high dementia GRS participants with chronic pain, the paracetamol group (HR = 1.2, 95% CI: 1.03–1.43, P < 0.05) and the NSAIDs group (HR = 1.3, 95% CI: 1.07–1.59, P < 0.05) were associated with a higher risk of ACD compared to the no painkiller group. 3) There was no significant association between ibuprofen use and higher risk of dementia. ConclusionIn individuals with chronic pain, the use of aspirin and paracetamol was associated with a higher risk of ACD, whereas the use of ibuprofen was not significantly associated with a higher risk of ACD.

Drug-drug salts of Naftopidil with non-steroidal anti-inflammatory drugs for potential multi-drug therapy

Drug-drug cocrystals (DDCs) are a subclass of pharmaceutical cocrystals in which both the components of a cocrystal are active drugs. DDCs are the recent advancement based on the crystal engineering approach to overcome the problems associated with conventional combination therapy. They also allow the modulation of the physicochemical properties of parent drugs. Four new drug-drug salts of Naftopidil (NFPD), a BCS class IV anti-cancer drug, were prepared by liquid-assisted grinding and solvent evaporation technique, with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as Aspirin (ASP), Tolfenamic acid (TFA), Mefenamic acid (MFA) and Niflumic acid (NIFA) as coformers. The solids obtained were characterized by Single Crystal X-Ray diffraction (SCXRD), Powder X-ray Diffraction (PXRD), Thermo Gravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC). Furthermore, the solubility of NFPD in the solids was determined by the shake flask method. SCXRD analysis showed that O–H···N hydrogen bond interactions found in the pure NFPD crystal structure are replaced by the N+–H···O- and O–H···O hydrogen bond interactions in the drug-drug solids. Additionally, the transfer of a proton from the carboxylic group of NSAIDs to piperazine nitrogen of NFPD is observed in all the drug-drug crystal structures, which suggests the nature of the solids as salts. NFPD-ASP salt exhibited improved solubility (33.2 µg/ml), which is eight-fold higher than the pure NFPD solubility (4.3 µg/ml). NFPD-MFA (0.6 µg/ml), NFPD-TFA (0.17 µg/ml), and NFPD-NIFA (1.35 µg/ml) showed reduced solubility than the pure NFPD. We anticipate that the current research will provide an alternate strategy to overcome the solubility issue of NFPD and provide potential candidates for designing combination therapy to treat complications in Benign Prostatic Hypertrophy (BPH), which involves pain and inflammation.

Postoperative NSAIDs use and the risk of anastomotic leakage after restorative resection for colorectal cancer.

Although non-steroidal anti-inflammatory drugs (NSAIDs) are useful options for multimodal opioid-sparing analgesia, their effect on anastomotic leakage (AL) after colorectal surgery remains unclear. We aimed to investigate the association between early postoperative NSAID use and AL occurrence in patients who underwent colorectal cancer surgery at a high-volume tertiary care center. This retrospective observational study included all adult patients who underwent elective colorectal cancer resection surgery during 2011-2021at a tertiary teaching hospital. Based on NSAID use within five postoperative days, patients were classified into either NSAID or no NSAID groups. We performed multivariable logistic regression analysis for the primary outcome, AL, within the first 30 postoperative days, before and after propensity score analysis using stabilized inverse probability of treatment weighting (sIPTW). Among the 7928 patients analyzed, 0.6% experienced AL after surgery. The occurrence rates of AL were 1.7% (12/714) and 0.5% (37/7214) in the NSAID and no NSAID groups, respectively. Multivariable logistic regression analysis revealed that early postoperative NSAID use was significantly associated with AL [odds ratio (OR), 3.41; 95% confidence interval (CI), 1.76-6.60; P<0.001]. Significance was maintained after sIPTW (OR, 3.65; 95% CI, 1.86-6.72; P<0.001). Early postoperative NSAID use was significantly associated with AL in patients undergoing colorectal cancer surgery at a high-volume tertiary care center. Further prospective studies are required to investigate NSAIDs' clinically meaningful unfavorable effects following colorectal cancer surgery.

Under what conditions is the intra-articular steroid injection superior to nonsteroidal anti-inflammatory drugs for treating sacroiliac joint pain?

The purpose of this prospective study was to determine the conditions under which intra-articular injection therapy may be superior to nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with sacroiliac joint pain in the outpatient setting at our hospital. Patients with sacroiliac pain were divided into two groups: NSAID and the sacroiliac injection group. The NSAID group received 25 mg of indometacin orally once a day and 750 mg of naproxen orally once a day. In the sacroiliac injection group, 5 mg of betamethasone were injected into the sacroiliac joint. The patients' history of lumbar surgery, whether they had sacroiliitis, and the duration of pain were recorded. The patients' VAS (Visual analogue scale) scores at week 1 and month 1 were evaluated. VAS scores were decreased after the first week and first month in the sacroiliac injection group compared to the NSAID group (p<0.001). Sacroiliac steroid injection was found to be superior to NSAIDs in reducing VAS scores in patients with sacroiliitis, a history of lumbar surgery, and pain lasting more than 30 days (p<0.001). In patients without sacroiliitis, without a history of lumbar surgery, and with less than 30 days of pain, no difference was observed between the groups in reducing VAS scores at the end of the first month. In patients with sacroiliac joint pain, sacroiliac joint injection is superior to NSAIDs in pain relief in patients with pain for more than 30 days, those with MRI-diagnosed sacroiliitis, and those who have undergone lumbar surgery.

Synthesis and pharmacological characterization of new curcumin ester pro-drugs with enhanced anti-inflammatory, anti-ulcerogenic and improved tissue distribution

In this work, curcumin- Non steroidal anti-inflammatory drugs (NSAIDs) conjugates were synthesized by esterification of the phenolic group of curcumin with the acid group of NSAIDs using the Steglich esterification method to enhance the anti-inflammatory activity of curcumin and to reduce the gastrointestinal side effects of NSAIDs. A set of bis C-NSAIDs conjugates was prepared by direct coupling of curcumin with Aceclofenac and Diflunisal respectively in good yield and characterized by Fourier-transform infrared spectra (FTIR) and Proton Nuclear Magnetic Resonance Spectra (1HNMR). In vivo, studies were performed to evaluate the toxicity, anti-inflammatory activity, bio-distribution, and anti-ulcerogenic studies of selected conjugates using different animal models. In Vivo, studies reveal enhanced biological activity with better tissue distribution of conjugates than that of parent curcumin and it could be a curcumin-based therapeutic molecule that might be explored further for its efficacy in managing inflammatory diseases.

Transplacental non-steroidal anti-inflammatory drugs versus expectant management in fetal Ebstein anomaly with circular shunt: Systematic review and meta-analysis.

Ebstein anomaly (EA) is a rare congenital cardiac malformation associated with high perinatal mortality. In this systematic review and meta-analysis, we aimed to investigate the outcomes of pregnancies affected by EA or tricuspid valve dysplasia (TVD) with circular shunt, focusing on two prenatal management approaches: (1) expectant management (EM) and (2) transplacental non-steroidal anti-inflammatory drugs (NSAID) therapy. We searched PubMed, Scopus, and Web of Science systematically from its inception until June 2023. The random-effect model was used to pool the data. Heterogeneity was assessed using the I2 value. Twenty-one studies with a total of 610 fetuses with EA/TVD with circular shunt were included in the synthesis, of which 17 studies (583 fetuses) were on EM and 4 studies (27 fetuses) used transplacental NSAID therapy. The NSAID group had higher rates of moderate to severe tricuspid regurgitation, hydrops, and pericardial effusion on prenatal ultrasound compared with the EM group. However, ductal constriction was achieved in 81% of NSAID cases, mitigating the disease pathophysiology, although 65% of them experienced oligohydramnios. Notably, the NSAID group showed significantly higher rates of live birth (86%) and survival to hospital discharge (89%) compared with the EM group (67% and 43%, respectively). Despite these promising results, it's important to acknowledge that the number of cases treated with NSAIDs was small, with limited safety data. Therefore, caution is advised in interpreting these findings, and patients considering NSAID therapy should be informed about these limitations. Future multicenter studies are necessary to further explore the safety and effectiveness of NSAID therapy in this particular population.

Evaluation of the efficacy and safety of various non-steroidal anti-inflammatory drugs in postmenopausal women with an inflammatory phenotype of osteoarthritis

Introduction. Non-steroidal anti-inflammatory drugs (NSAIDs) are currently the mainstay of the management for relieving pain syndrome in osteoarthritis (OA). NSAIDs are characterized by an individual reaction to medication, as well as a quite high frequency of gastrointestinal side effects. The issue of the disadvantages and advantages of a particular group of NSAIDs is still open.Aim. To evaluate the safety and efficacy of Meloxicam at a dose of 15 mg/day as compared with Nimesulide and placebo in postmenopausal women with an inflammatory phenotype of OA.Results and discussion. The frequency of all adverse events was comparable among the group of patients receiving meloxicam (40.0%), and lower than in the nimesulide group (48.0%), but higher than in the placebo group. A decrease in pain syndrome was observed as early as at 2 weeks of treatment in the group of patients receiving meloxicam. A significant decrease in WOMAC scores (overall result, pain syndrome, stiffness, function) was observed in the group of patients receiving meloxicam, and in the group of patients receiving nimesulide, after 3 weeks of treatment. meloxicam and nimesulide demonstrated high efficacy at 3 weeks compared with the initial VAS scores. The placebo group showed no efficacy.Conclusion. The frequency of all adverse events was lower while taking meloxicam as compared to nimesulide. Our results substantiate the concept to prescribe meloxicam at a dose 15 mg once daily for the treatment of pain and stiffness in post-menopausal women with OA.