Nonsteroidal Anti-inflammatory Drugs Group Research Articles

Early Experience with Diclofenac Topical Gel for Moderate to Severe Post-Ablation Phlebitis

ObjectiveOral (PO) non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat phlebitis and thrombus extension post-endovenous ablation. Few studies have evaluated diclofenac topical gel for treating post-ablation phlebitis. This study assesses diclofenac 1 percent (%) topical gel as a first-line treatment for patients with moderate to severe phlebitis post-ablation. MethodsFrom December 2021 to March 2024, a retrospective cohort study was performed to identify patients who developed post-ablation phlebitis and were treated with either diclofenac topical gel (with or without PO NSAIDs) versus PO NSAIDs alone. All patients were evaluated with a numeric pain rating scale (NPRS, 0-10) at four-time intervals (1, 7, 14, and 30 days) after initiating treatment. ResultsOverall, 45 patients were included in the study, with 38 in the Diclofenac +/- PO NSAIDs group (9 males and 29 females) and 7 in the PO NSAIDs alone group (all females). NPRS scores showed similar pain reduction trends at all time intervals. Topical diclofenac gel was non-inferior to PO treatments and resulted in partial to complete relief in most patients at 30 days. At the 30 day follow up interview, 57% of patients preferred the diclofenac topical gel due to its ease of use and immediate local pain reduction. ConclusionsPatients with moderate to severe post-ablation phlebitis respond well to diclofenac topical gel with or without PO NSAIDs. Moreover, patients often had significant pain relief without additional need for PO NSAIDs. Longitudinal studies are needed to support the use of diclofenac topical gel for post-ablation phlebitis.

Determination of some NSAIDs content in meat by liquid chromatography with tandem mass spectrometry (LC-MS/MS)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used group of drugs worldwide for pain relief, anti-inflammation, blood clot prevention, and fever reduction, but they can cause some side effects bad for health if used incorrectly. NSAIDs are on the list of drugs that must be monitored according to Council Directive 96/23/EC. The fact that NSAIDs are also used in animals for anti-inflammation, fever reduction, and pain relief raises concerns that animal products such as meat, eggs, and milk may be contaminated with NSAIDs, affecting human health if consumed like eating right. Therefore, developing a method to analyze NSAIDs in meat products is necessary, contributing to assessing the quality of meat products currently circulating on the market. In this study, 4 common substances in the NSAIDs group were studied and identified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) using a Symmetry C18 chromatographic column with an ESI (+) positive electron spray ionization source and multiple reaction monitoring (MRM) mode. The validity of the method was confirmed according to the guidelines of the Association of Official Analytical Chemists (AOAC). The results showed that the method has good specificity, the linearity range from 5.0 to 100 µg/kg, the detection limit of 1.5 µg/kg, the quantification limit of 5.0 µg/kg; precision and accuracy with relative standard deviation (RSD) less than 11% and recoveries ranging from 81.1 to 111%, meeting AOAC requirements. The method was used to analyze the content of NSAIDs in 15 meat samples in Hanoi. The results showed that 7 samples showed tolfenamic acid exceeding the quantitative limit of the method.

The effect of non-steroidal anti-inflammatory drugs on postoperative delirium: a meta-analysis.

Neuroinflammation is postulated as a potential mechanism underlying postoperative delirium. This study aimed to investigate the impact of non-steroidal anti-inflammatory drug (NSAID) use on postoperative delirium. We conducted a literature search in electronic databases, including PubMed, EMBASE, CENTRAL, and Web of Science, to identify eligible randomized controlled studies. The primary outcome was the incidence of postoperative delirium, and the secondary outcomes included pain scores and the amounts of opioid used at 24 h postoperatively. We estimated the effect size through calculating the odds ratios (ORs) or mean differences (MDs) with 95% CIs, as appropriate. In the analysis of eight studies involving 1,238 participants, the incidence of postoperative delirium was 11% and 19% in the NSAID and control groups, respectively, with a significant reduction in the NSAID group (OR: 0.54, 95% CI [0.38, 0.7], P = 0.0001, I2 = 0%). NSAID use had a significant effect on postoperative pain reduction (MD: -0.75, 95% CI [-1.37, -0.13], P = 0.0172, I2 = 88%). Significant lower postoperative opioid consumption was observed in the NSAID group (MD: -2.88, 95% CI [-3.54, -2.22], P = 0.0000; I2 = 0%). NSAID administration reduced the incidence of postoperative delirium, severity of pain, and opioid dose used.

Outcomes after hip fracture surgery in patients receiving non-steroidal anti-inflammatory drugs alone, acetaminophen alone, or both.

The use of multimodal non-opioid analgesia in hip fractures, specifically acetaminophen combined with non-steroidal anti-inflammatory drugs (NSAIDs), has been increasing. However, the effectiveness and safety of this approach remain unclear. This study aimed to compare postoperative outcomes among patients with hip fractures who preoperatively received either acetaminophen combined with NSAIDs, NSAIDs alone, or acetaminophen alone. This nationwide retrospective cohort study used data from the Diagnosis Procedure Combination database. We included patients aged ≥ 18 years who underwent surgery for hip fractures and received acetaminophen combined with NSAIDs (combination group), NSAIDs alone (NSAIDs group), or acetaminophen alone (acetaminophen group) preoperatively, between April 2010 and March 2022. Primary outcomes were in-hospital mortality and complications. Secondary outcomes were opioid use postoperatively; readmission within 90 days, one year, and two years; and total hospitalization costs. We used propensity score overlap weighting models, with the acetaminophen group as the reference group. We identified 93,018 eligible patients, including 13,068 in the combination group, 29,203 in the NSAIDs group, and 50,474 in the acetaminophen group. Propensity score overlap weighting successfully balanced patient characteristics among the three groups, with no significant difference in in-hospital mortality rates observed among the groups (combination group risk difference 0.0% (95% CI -0.5 to 0.4%); NSAIDs group risk difference -0.2% (95% CI -0.5 to 0.2%)). However, the combination group exhibited a significantly lower risk of in-hospital complications than the acetaminophen group (risk difference -1.9% (95% CI -3.2 to -0.6%)) as well as a significantly lower risk of deep vein thrombosis (risk difference -1.4% (95% CI -2.2 to -0.7%)). Furthermore, total hospitalization costs were higher in the NSAIDs group than in the acetaminophen group (difference USD $438 (95% CI 249 to 630); p < 0.001). No significant differences in other secondary outcomes were observed among the three groups. The combination of acetaminophen with NSAIDs appears to be safe and advantageous in terms of reducing in-hospital complications.

Nitroglycerin combined with NSAIDs for prevention of post-ERCP pancreatitis: A meta-analysis of prospective, randomized, controlled trials.

Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), with an incidence of approximately 9.7% according to some literature reviews. Recent clinical guidelines propose that glyceryl trinitrate (GTN) can reduce the incidence of post-ERCP pancreatitis (PEP). However, currently, no guidelines provide an exact opinion on GTN and nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent post-ERCP pancreatitis. A meta-analysis was performed of published, full-length, randomized controlled trials (RCTs) evaluating the effects of prophylactic use of GTN, including GTN alone or GTN in combination with NSAIDs, on the prevention of PEP. Literature searches were conducted using PubMed, Embase, Web of Science, and The Cochrane Library. Search terms included "endoscopic retrograde cholangiopancreatography" OR "ERCP," "OR 'PEP' OR 'post-endoscopic retrograde cholangiopancreatography pancreatitis', pancreatitis," "GTN" OR "glyceryl trinitrate" OR "nitroglycerin," "NSAIDs" OR "Nonsteroidal Anti-inflammatory Drugs" and limited to RCT. A total of 10 RCTs comprising 3240 patients undergoing ERCP were included. Meta-analysis revealed that the administration of GTN was associated with a significant reduction in the overall incidence of PEP. Moreover, PEP incidence was significantly lower in the GTN combined with the NSAIDs group than in the GTN alone group. GTN alone or GTN combined with NSAIDs may not reduce the severity of PEP (risk ratio = 0.64; 95% confidence interval: 0.41-0.99; P = .04). The difference in incidence between the 2 groups is 1.01% (6/594) in the GTN with NSAIDs group and 2.36% (14/592) in the placebo group. GTN has a significant benefit in preventing postoperative ERCP pancreatitis (P < .001). And neither GTN nor GTN plus NSAIDs reduces the incidence of non-mild ERCP postoperative pancreatitis. These conclusions need to be confirmed by high-quality randomized controlled studies with multicenter, large samples, and long-term follow-up.

Colchicine for cardiovascular and limb risk reduction in Medicare beneficiaries with peripheral artery disease: emulation of target trials.

Recent evidence from randomized trials demonstrates that colchicine can reduce the risk of major adverse cardiovascular events (MACE) in patients with coronary artery disease. Colchicine's effect on lower-extremity peripheral artery disease (PAD) is not known. To make inferences about the real-world effectiveness of colchicine in PAD, we emulated two target trials leveraging the variable prescribing practice of adding colchicine vs. a non-steroidal anti-inflammatory drug (NSAID) to urate-lowering therapy in patients with gout and PAD. Emulated Trial 1 compared colchicine initiators with NSAID initiators. Emulated Trial 2 compared long-term (indefinite) and short-term (3 months) treatment strategies after initiating colchicine. Eligible individuals were those continuously enrolled in Medicare receiving care at a multicentre academic health system between July 2007 and December 2019. The primary outcome for both trials was a 2 year composite of major adverse limb events (MALE), MACE, and all-cause mortality. Secondary outcomes included MALE and death, MACE and death, and individual components of the primary outcome. Inverse probability weighting was used to adjust for confounding. Percentile-based 95% confidence intervals (CIs) were estimated using non-parametric bootstrapping. A total of 1820 eligible patients were included; the mean age was 77 years [standard deviation (SD) 7], 32% were female, and 9% were non-White. The mean (SD) duration of colchicine and NSAID therapy was 247 (345) and 137 (237) days, respectively. In the emulation of Trial 1, the risk of the primary composite outcome of MALE, MACE, and death at 2 years was 29.9% (95% CI 27.2%, 32.3%) in the colchicine group and 31.5% (28.3%, 34.6%) in the NSAID group, with a risk difference of -1.7% (95% CI -6.5%, 3.1%) and a risk ratio of 0.95 (95% CI 0.83, 1.07). Similar findings were noted in the emulation of Trial 2, with a risk of the primary composite outcome at 2 years of 30.7% (95% CI 23.7%, 38.1%) in the long-term colchicine group and 33.4% (95% CI 29.4%, 37.7%) in the short-term group, with a risk difference of -2.7% (95% CI -10.3%, 5.4%) and risk ratio of 0.92 (95% CI 0.70, 1.16). In a real-world sample of patients with PAD and gout, estimates of the effect of colchicine were consistent across two analyses and provided no conclusive evidence that colchicine decreased the risk of adverse cardiovascular or limb events and death. The cardiovascular and limb benefits of colchicine in older, comorbid populations with PAD and advanced systematic atherosclerosis remain uncertain.

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&lt;0.05), but not by GI and CV risks (p&gt;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.

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.

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.

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.

The Inhibitory Effect of NSAIDs and Opioids on Spinal Fusion: An Animal Model.

Translational research. To evaluate the relative effects of NSAIDs, opioids, and a combination of the two on spinal fusion inhibition in a rodent model. Nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are common postoperative analgesic agents. Since NSAIDs inhibit the cyclooxygenase (COX) pathway, they are seldom prescribed following spinal fusion. Opioids may be given instead, but recent evidence suggests opioids also adversely affect spinal fusion quality and success. Eighty male Sprague-Dawley rats underwent L4-5 posterior lumbar fusion and were given one of the following analgesia regimens: saline, morphine (6mg/kg), ketorolac (4mg/kg), or morphine (3mg/kg) and ketorolac (2mg/kg). Serum samples were drawn to evaluate systemic pro-osteoblastic cytokines and vascular endothelial growth factor-A (VEGF-A) levels, which were measured through enzyme-linked immunosorbent assays (ELISA). After six weeks, the rats were sacrificed, and the operated spinal segments underwent manual palpation, microCT, and histologic analysis. Manual palpation scores were significantly diminished in the opioid, NSAID, and multimodal groups when compared with control ( P <0.001). MicroCT fusion scores ( P <0.001) and fusion rates (control: 75% vs . NSAID: 35% vs . opioid: 0% vs . combination: 15%, P <0.001) were significantly diminished in the treatment groups. The bone volume (BV) to tissue volume (TV) ratio (BV/TV) ( P <0.001) and bone mineral density (BMD) ( P <0.001) were all lower in the treatment groups, with the opioid and combined groups having the lowest BMD. Although statistically insignificant ( P <0.09), the concentration of VEGF-A was greater in the control group compared with opioids, NSAIDs, and the combined group. Opioids and NSAIDs, both independently and combined, inhibited spinal fusion and caused inferior bony callus. Administration of opioids resulted in the lowest rate of spinal fusion. We propose this may be due to the inhibition of VEGF-A, which limits angiogenesis to the burgeoning fusion mass.

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.