Administration Of NSAIDs Research Articles

Dogs receiving cyclooxygenase-2-sparing nonsteroidal anti-inflammatory drugs and/or nonphysiologic steroids are at risk of severe gastrointestinal ulceration.

To report the incidence and characteristics of gastrointestinal ulceration lesions in dogs receiving an NSAID and/or corticosteroid. 33 dogs. Medical records of dogs with gastrointestinal ulceration receiving NSAIDs and/or corticosteroids within 30 days of diagnosis between January 2012 and July 2022 at multiple referral institutions were reviewed. Diagnosis was confirmed via endoscopy, surgery, or necropsy. Clinical data were collected from the medical record, including the dose and reason for administration of NSAIDs or steroids. Dogs received a single NSAID (n = 22, most commonly carprofen [9], meloxicam [4], and deracoxib [3]), 2 NSAIDs (5), a single steroid (5: prednisolone [2], prednisone [2], or dexamethasone SP [1]), or an NSAID and steroid (1). Eleven dogs receiving a single cyclooxygenase (COX)-2-sparing NSAID at an appropriate dose had ulcerations. All dogs receiving 2 NSAIDs concurrently experienced full-thickness perforation (5 of 5). The most common ulcer locations were duodenum (n = 18) and pylorus (11). Abdominal ultrasound correctly identified the site of ulceration in 5 of 24 dogs. Dogs receiving COX-2 sparing NSAIDs at recommended doses are at risk of severe GI ulceration. Carprofen was the most common NSAID resulting in ulceration; however, it is one of the most prescribed NSAIDs. Adding another NSAID and steroid could increase this risk. Careful monitoring is crucial for dogs on NSAIDs, regardless of duration.

A Complete Guide to Understand PMS (Pre-Menstrual Syndrome) in Women’s and its Effective Ayurvedic and Allopathic Treatment

Many women around the world are suffering from common physical discomfort just before their menstrual cycle. Symptoms may vary women to women which can be mild to severe such that it could affect their regular activities. Based on the diagnostic criteria, 2.5–3% of women of reproductive age have the severe form of PMS, while 40% of these women experience the moderate type. The symptoms seen were fluid retention, pain in pelvic region, mastalgia, psychological changes, behavioural changes, gastrointestinal problems, skin related problems and nervous system affecting problem. The targeting therapies to cure PMS includes allopathic as well as ayurvedic remedies. Allopathic includes mainly targeting brain SSRIs and some pharmacotherapies including administration of NSAIDs, anxiolytic agents, gonadotropin-releasing hormone (GnRH) agonists. etc. and recent studies shows combined oral contraceptives shows good effect to cure PMS prominently. And daily physical exercise can also overcome the PMS related problems wisely.

Prolonged administration of oral phenylbutazone and firocoxib in horses has no impact on selected cytokine and growth factor concentrations in platelet-rich plasma and autologous protein solution.

To determine the effects of prolonged administration of the oral NSAIDs phenylbutazone and firocoxib on concentrations of cytokines and growth factors in platelet-rich plasma (PRP) and autologous protein solution (APS). 6 adult University owned horses. Horses were randomized to receive phenylbutazone (1 g, orally, q 12 h) or firocoxib (57 mg, orally, q 24 h) for 6 days. Blood was obtained and processed for APS (Pro-Stride) and PRP (Restigen) before the administration of NSAIDs and at 7 days (1 day following cessation of NSAIDs). Horses underwent a two-week washout period, during which blood was obtained at 14 days and 21 days. The protocol was repeated with a crossover design. PRP and APS were analyzed for concentrations of platelets, leukocytes, and several cytokines (IL-1β, IL-10, IL-6, IL-8, and tumor necrosis factor-α) and growth factors (PDGF, FGF-2, and TGF-β1) using immunoassays. Plasma was evaluated for drug concentrations. No significant differences existed in concentrations of growth factors and cytokines before or after prolonged administration of NSAIDs. There were significant differences in concentrations of leukocytes and platelets in PRP compared to APS, with higher concentrations of leukocytes at the day 7 time point (T) in APS (phenylbutazone) and in concentrations of platelets in APS at T0 (firocoxib) and in APS at T7 (phenylbutazone). Veterinarians can recommend the administration of these oral NSAIDs prior to obtaining blood for PRP and APS provided a single-day washout period is instituted.

Evaluation of Postoperative Pain When Adding a Tibial Nerve Block to the Femoral Nerve Block for Total Knee Arthroplasty.

Background: The aim of this study was to compare the postoperative analgesic efficacy when a tibial nerve block was added to the femoral nerve block for total knee arthroplasty (TKA). Methods: A total of 60 patients were randomly assigned to the experimental group (EG) or the control group (CG) in a 1:1 ratio. The thirty patients who formed the CG underwent an ultrasound-guided femoral nerve block together with neuraxial anaesthesia and the administration of opioids and NSAIDs through an intravenous elastomeric pump for the management of the postoperative pain; the other thirty, who formed the EG, underwent neuraxial anaesthesia together with femoral and tibial nerve blocks. The efficacy of the analgesic effect was evaluated based on the numerical pain rating scale (NPRS) and on the need for analgesic rescue at different time intervals within 48 h after surgery. Results: At 24 h, the mean NPRS score in the EG and CG at rest was 1.50 ± 1.19 and 1.63 ± 1.60 [U = 443.5, p = 0.113], respectively. With joint movement, the mean NPRS score was 2.80 ± 1.49 and 3.57 ± 1.79 [U = 345, p = 0.113], respectively. Ten patients in the EG [33.3%] and 24 in the CG [80%] required rescue analgesia [Phi = 0.471, p < 0.001]. At 48 h, the mean NPRS score in the EG and CG at rest was 0.33 ± 0.60 and 0.43 ± 0.72 [U = 428, p = 0.681], respectively. With movement, the mean NPRS score was 1.03 ± 0.99 in the EG and 1.60 ± 1.07 in the CG [U = 315, p = 0.038]. No patient in the EG group required rescue analgesia, while three patients in the CG [10%] did [Phi = 0.229, p = 0.076]. The mean opioid dosage in the CG was 300 mg, whereas in the EG it was 40 mg ± 62.14 [U < 0.05, p < 0.001]. Conclusions: Adding a tibial nerve block to the femoral nerve block in TKA may achieve the same analgesic efficacy within 48 h after surgery and would reduce the systematic use of opioids.

Unilateral nephrectomy in dogs is associated with a high rate of intraoperative and postoperative complications.

To determine the incidence of complications in the intraoperative and postoperative period for dogs undergoing nephrectomy for renal disease. 69 dogs. Medical records of dogs undergoing nephrectomies for renal disease were reviewed for signalment, date of surgery, results of blood analyses, and intra- and postoperative complications. Long-term follow-up was obtained via client telephone interview or referring veterinarian medical records. A Fisher exact test was used to assess the relationship between postoperative acute kidney injury and NSAID administration with long-term development of chronic kidney disease. Complications occurred in 44.9% and 42.6% of dogs in the intraoperative and postoperative periods, respectively. Most of these were lower-grade complications, though a total of 7 dogs died during the postoperative period. An acute kidney injury was diagnosed in 12 dogs postoperatively, with 2 dogs euthanized due to the severity of the injury. Long-term follow-up was available for 53 dogs, with 24 (45.3%) dogs developing chronic kidney disease. Postoperative acute kidney injury (P = .385) and NSAID administration (P = .519) were not statistically associated with the development of chronic kidney disease in this population. Unilateral nephrectomy is associated with high intraoperative and postoperative complication rates in dogs. Chronic kidney disease was diagnosed in almost 50% of the population with available long-term follow-up.

An update on nonsteroidal anti-inflammatory drug-induced urticaria.

Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (HR-NSAIDs) are common adverse events related to the widespread use of over-the-counter NSAIDs for the treatment of a variety of inflammatory conditions. Urticaria is the most commonly reported immediate cutaneous clinical sign of HR-NSAIDs, but it can be a manifestation of pathophysiologically different clinical entities that require different therapeutic strategies. The aim of this study is to ease the identification of the correct phenotype of HR-NSAIDs in patients reporting urticaria associated with the intake of NSAIDs and provide updated information about their diagnosis and management. The study is a narrative review conducted by collecting the most relevant and up-to-date data related to the classification, pathophysiology, severity, and prognosis of NSAID hypersensitivity reactions. PubMed and Embase scientific databases were used as search engines to select relevant articles. Patients developing HR-NSAIDs can be divided into two categories: selective responders (SR), who develop reactions after the administration of a single specific NSAID due to an underlying IgE or T-cell mediated hypersensitivity mechanism, or cross-intolerant (CI), who develop reactions to more than one chemically unrelated NSAIDs due to abnormalities in the biochemical pathways related with prostaglandin metabolism, independently from an underlying immunological mechanism. Five major different categories of HR-NSAIDs have been identified: NSAIDs-exacerbated cutaneous disease (NECD), NSAIDs-induced urticaria/angioedema with/without respiratory and systemic symptoms of anaphylaxis (NIUAA), and NSAIDs-exacerbated respiratory disease (NERD), which are developed by CI patients, and single NSAIDs-induced urticaria, angioedema and/ or anaphylaxis (SNIUAA) and single NSAIDs-induced delayed hypersensitivity reactions (SNIDHR), which are developed by CI patients. In vivo and in vitro diagnostic tests have rarely been shown to be reliable in all these entities and therefore are not routinely used in clinical practice. The management in SR patients consists of strict avoidance of the culprit drug, while for cross-intolerance reactions oral tolerance tests with safe alternative drugs (e.g. weak COX-1 inhibitors or selective COX-2 inhibitors) can be performed. HR-NSAIDs are being observed with increasing frequency, however, the pathogenesis behind some NSAIDS-associated clinical entities is still unclear. Diagnosis is mostly based on a thorough clinical history and confirmed by a drug challenge test. Clinical management is based on strict avoidance and use of alternative tolerated medications. Overall, all therapeutic decisions depend on the correct identification of the type of reaction the patient experienced.

Single-dose nonsteroidal anti-inflammatory drugs in horses have no impact on concentrations of cytokines or growth factors in autologous protein solution and platelet-rich plasma.

To determine the effects of a single dose of the NSAIDs phenylbutazone, firocoxib, flunixin meglumine, and ketoprofen on concentrations of growth factors and cytokines in autologous protein solution (APS) and platelet-rich plasma (PRP). 6 adult university-owned horses. For the first phase, 6 horses were randomized to receive ketoprofen (1,000 mg) or flunixin meglumine (500 mg) IV. Blood was obtained and processed for APS (Pro-Stride) and PRP (Restigen) before and 6 hours after administration of NSAIDs. Horses underwent a 2-week washout period, after which the protocol was repeated using a crossover design. For the second phase, following at least a 2-week washout period, the study protocol was repeated with phenylbutazone (1 g) or firocoxib (57 mg) administered orally. Plasma was collected 6 hours after administration for evaluation of drug concentrations, and APS and PRP were analyzed for concentrations of drug, platelets, leukocytes, and several growth factors and cytokines (PDGF, fibroblast growth factor, TGF-β1, IL-1β, IL-10, IL-6, IL-8, and tumor necrosis factor-α) before and 6 hours after administration of NSAIDs using immunoassays. There were no significant differences in concentrations of cytokines or growth factors before or after administration of any NSAID. There were significant differences in concentrations of leukocytes and platelets based on both product and time. NSAID concentrations in plasma were not significantly different from concentrations in APS and PRP. These results help guide clinicians on the appropriate use of these NSAIDs in conjunction with the processing of APS and PRP, which is unlikely to significantly alter the final product after single-dose administration.

Taste Masking of Dexketoprofen Trometamol Orally Disintegrating Granules by High-Shear Coating with Glyceryl Distearate.

Orally disintegrating granules (ODGs) are a pharmaceutical form commonly used for the administration of NSAIDs because of their easy assumption and fast dispersion. The development of ODGs is not easy for drugs like dexketoprofen trometamol (DXKT), which have a bitter and burning taste. In this work, high-shear coating (HSC) was used as an innovative technique for DKXT taste masking. This study focused on coating DXKT granules using the HSC technique with a low-melting lipid excipient, glyceryl distearate (GDS). The HSC technique allowed for the coating to be developed through the thermal rise resulting from the friction generated by the granules movement inside the equipment, causing the coating excipient to soften. The design of the experiment was used to find the best experimental coating conditions in order to gain effective taste masking by suitably reducing the amount of drug released in the oral cavity. The influence of the granule dimensions was also investigated. Coating effectiveness was evaluated using a simulated saliva dissolution test. It was found that low impeller speed (300 rpm) and a 20% coating excipient were effective in suitably reducing the drug dissolution rate and then in taste masking. The coated granules were characterized for their morphology and solid-state properties by SEM, BET, XRPD, DSC, and NIR analyses. A human taste panel test confirmed the masking of DXKT taste in the selected batch granules.

A Clinical Case Study on Janu Sandhivata (Knee Arthritis) to evaluate the effect of Combined Panchakarma procedure and Internal Traditional Ayurvedic Formulations

Being commonest form of articular disorders Janu Sandhivata (Knee Arthritis) causes a huge hindrance in day to day activities of the sufferer like walking, dressing, bathing etc. It is the disease of old age. It’s mainly effect the weight bearing joint of the body specially knee, hip, lumber spine. As per the Ayurvedic classical references Shula, Sotha, Vata- Poornadriti Sparsha and difficulty in flexion and extension of the Sandhi are the symptoms. There are lots of treatment available in contemporary fields includes NSAID Administration, Intra articular Steroids or eventually surgical intervention in the form of Knee replacement. With this regard there is a need of safe effective and affordable treatment options. In present case study it is tried to explode the Panchakarma procedure like Abhangya, Patra Pinda Shedana therapy, Kashaya Vasti along with few traditional Ayurvedic formulations particularly for Bilateral Knee Osteoarthritis for 30 days duration of treatment it can be concluded that symptoms of severe Osteoarthritis may also be merged with Ayurvedic interventions significantly.

Regulation of platelet proaggregant activity in cyclooxygenase inhibition in patients with nephrolithiasis

Aim of the study was to establish the possibility of synergism between the TP receptor for TxA2 and purinergic P2 receptors during COX inhibition, and the effect of the resulting remodeling of signaling pathways on aggregometry parameters in patients with nephrolithiasis (NLT). Materials and Methods. The study was prospective and included 30 patients with imaging evidence of urinary tract calculi who were treated with high doses of non-selective NSAIDs for analgesia. The severity of hematuria was assessed at the time of hospitalization and during 7 days of lithokinetic therapy (LKT). Analysis of functional activity of TR-receptors, purine P2X1and P2Yreceptors of platelets (Tc) was performed by turbidimetric method on ChronoLog analyzer (USA). Agonists (ATP, ADP and Arachidonic acid) were used at concentrations of EC50 and EC10. Statistical analysis was performed using MedCalc package. Results. Two waves of COX activity decrease were revealed 24h and 72h after the beginning of NSAID administration. On the 5th day of LKT, the compensatory reaction of Tc was switched on, which was reproduced at restoration of normoreactivity of TR-receptor. Purine P2X1 – and P2Y-receptor synergism had a more pronounced inducing effect on aggregation parameters compared with the interaction between P2Y-receptor and TR-receptor or TR-receptor and P2X -receptor. On the 7th day, the residual level of COX activity was reached and hyporeactivity of TR-receptor was registered; at the same time the preserved level of TxA2 synthesis did not provide limitation of hematuria. Conclusion. Upon COX inhibition, potentiation of Tc proaggregant activity is reproduced by purine P2-receptor and TR-receptor interaction due to an increase in the rate of intracellular signalling (Slope) and the number of aggregates formed (AUC).

Electronic health record intervention to increase use of NSAIDs as analgesia for hospitalised patients: a cluster randomised controlled study

BackgroundPrescribing non-opioid pain medications, such as non-steroidal anti-inflammatory (NSAIDs) medications, has been shown to reduce pain and decrease opioid use, but it is unclear how to effectively encourage multimodal pain...

Factors Affecting Gastric Perforation Patient Outcome with History of Arthritis and Long Term Use of NSAIDs in Dr. Kariadi Semarang Period 2020 – 2022

Background: The incidence of gastric perforation gives a high mortality outcome. The second most common cause of gastric perforation is long-term use of NSAIDs. In cases of arthritis during the COVID-19 pandemic, a conservative therapeutic approach and administration of NSAIDs are preferred. Due to this, researchers want to know the factors affecting gastric perforation cause by NSAIDs. Method: An analytic descriptive study with a retrospective cohort study design, using electronic medical records of patients at RSUP Dr. Kariadi Semarang from January 2020 - December 2022. Data collected was in the form of demographics, diagnoses, procedures, preoperative conditions, scoring system, and outcome. Results: PULP score, one of prognostic factor, has a good level of significance compared to other scoring systems in determining the prognostic mortality of patients with gastric perforation. The combination of variables between the type of NSAIDs and the type of arthritis has a direct correlation with a positive inter-variable power of 86.7% and a significance of 0.049 on patient outcome. Conclusion: NSAIDs pose a risk of gastric perforation in long-term use. tNSAIDs carry a higher risk inducing gastric perforation than selective NSAIDs.

Efficacy of stepped care treatment for chronic discogenic low back pain patients with Modic I and II changes

ObjectiveThis study investigated whether patients with Modic changes (MC) of types I, I/II, and II would respond to an anti-inflammatory-based, stepped care treatment with three treatment steps: first, oral administration of NSAIDs, 2 × 200 mg celecoxib daily for two weeks; second, an intradiscal steroid injection (ID) with dexamethasone and cefazolin; and third, oral treatment with antibiotics (AB), 3 × 1 g amoxicillin daily for 100 days. DesignThis was an observational clinical study based on analyses of categorical data of patient-reported outcome measurements. SubjectsSubjects were consecutive patients with chronic low back pain (CLBP), diagnosed by assessment of anamnestic signs of inflammation; a pain score ≥6 on the Numeric Pain Rating Scale (NPRS); a mechanical assessment; MC I, I/II, or II based on MRI; and lack of response to conservative treatment. MethodsFrom January 1, 2015, to December 31, 2021, 833 eligible patients were selected for the stepped care treatment. A total of 332 patients completed requested follow-up questionnaires at baseline and 12 months (optional at 3 and 6 months). Primary outcomes were pain (at least 50 % pain relief) and/or a minimum of 40 % improvement in functionality as measured by the Roland Morris Disability Questionnaire (RMDQ) or the Oswestry Disability Questionnaire (ODI). Secondary outcome measures were use of pain medication and return to work. ResultsAt 1 year of follow-up, 179 (53.6 %) of 332 patients reported improvement according to the responder criteria. Of the 138 patients that had received only NSAIDs, 88 (63.8 %) had improved. In addition, 50 (56.8 %) of the 183 patients that had received ID had improved, and 41 (38.7 %) of the 106 patients treated with AB had improved. None of the patients reported complications. 12.0 % of patients using AB stopped preterm due to undesirable side effects. ConclusionTreatment with a stepped care model for inflammatory pain produced clinically relevant, positive reported outcomes on pain and/or function. Our stepped care model appears to be a useful, safe, and cost-saving treatment option that is easily reproducible. Further studies, including randomized controlled trials and analyses of subgroups, may help to develop a more patient-tailored approach and further avoidance of less-effective treatments and costs.

Simultaneous Multifocal Intracranial Haemorrhages Associated with Staphylococcus Aureus Endocarditis: A Plausible Role for Diclofenac Administration.

Intracranial haemorrhage may complicate infective endocarditis, caused by ruptured mycotic aneurysms or haemorrhagic transformation of brain septic emboli. The risk of intracranial bleeding may increase with the use of non-steroidal anti-inflammatory agent (NSAIDs). We report on a 53-year-old male patient with a past history of intravenous drug abuse, who was treated with diclofenac (75 mg IM) for a few hours of preceding fever and arthralgia. Seven hours later he was hospitalised with impaired consciousness and hemiparesis. Evaluation revealed multiple intracranial haemorrhages, at least one originating from a mycotic aneurysm. Repeated blood cultures grew methicillin-resistant Staphylococcus aureus (MRSA), and echocardiography revealed a vegetation on the mitral valve, establishing the diagnosis of bacterial endocarditis. The abrupt simultaneous multifocal intracranial bleeds shortly following the administration of NSAIDs for a few hours of febrile disease, one clearly originating from a mycotic aneurism, are exceptional. This raises a possibility of a role for diclofenac the intracranial bleeding diathesis in this unique clinical presentation. Intracranial haemorrhage in the set-up of undiagnosed infective endocarditis (IE) might be added to the long list of potential adverse outcomes of NSAID administration, and the possibility of IE should be considered before their administration for febrile disease of undetermined cause. Intracranial haemorrhage in the set-up of undiagnosed infective endocarditis might be added to the long list of potential adverse outcomes of NSAID administration.The possibility of infective endocarditis should be considered before the administration of NSAIDs for febrile disease of an undetermined cause.

Randomised Control Trial Investigating the Efficacy of Meloxicam and Sodium Salicylate Non-Steroidal Anti-Inflammatory Drugs for Calf Cautery Disbudding.

Disbudding calves using hot iron cautery is a routine management procedure to destroy the germinal cells around the horn bud in calves. It is recommended that NSAIDs are used in conjunction with local anaesthesia to reduce pain in calves during and after the procedure. In this study, two treatment groups were examined; calves in the positive control MEL group received subcutaneous meloxicam, and SAL calves received sodium salicylate orally for three days, both in addition to a local anaesthesia. Tri-axis accelerometers were attached to the calves, and DLWG (Daily Live Weight Gain) was measured. There was no significant difference between the treatment groups with regard to DLWG (p = 0.52), MI (motion index (p = 0.66)), lying bouts (p = 0.96) or lying times (p = 0.54). Given these findings, sodium salicylate may offer a lower-cost option for farmers when given at licensed doses compared to meloxicam, as well as providing a reduced-stress method of NSAID administration via an oral route. In addition, this study identified significant differences in activity in the time periods before and after disbudding, with MI (p < 0.01), lying bouts (p = 0.002) and lying times (p < 0.001) indicating changes in behaviour which extended to five days post disbudding.

Abstract 5112: Immune biomarkers of clinical response after NSAID treatment in combination with vaccination targeting EGFR-COX2-CDC25B in the APC(Min/+) mouse model

Abstract Studies from our group have shown that administration of NSAIDs in mouse models of Familial Adenomatous Polyposis (FAP) results in a decrease in the development in small intestinal polyps with a significant increase in CD8 tumor infiltrating lymphocytes (TIL) and downregulation of PD-L1 on tumors. Furthermore, we have demonstrated that NSAIDs could be used in combination with vaccination to even further reduce the development of intestinal polyps. We questioned what tissue specific biomarkers could define the efficacy of response with the combination treatment. APC(Min/+) male and female mice (4-6 weeks old) were immunized with a multi-antigen (EGFR, COX2, CDC25B) peptide vaccine with CFA/IFA as an adjuvant. Control mice received immune adjuvant alone. Regular chow or chow containing 400 ppm naproxen was provided intermittently (3 weeks on, 3 weeks off for 3 cycles) or continuously (18 weeks on) at the initiation of the vaccine regimen. Animals were euthanized at 22 weeks and tumors quantified. TIL were evaluated by flow cytometry. Since intermittent naproxen treatment was just as effective at inhibiting tumor development as continuous naproxen treatment, with or without vaccine, we did not differentiate between NSAID regimens. We observed an increase in CD8+ (83%; p&amp;lt;0.0001), Tbet+CD4+ (94%; p&amp;lt;0.001), effector memory (EM) CD4+ (76%; p&amp;lt;0.0001) and EM CD8+ (94%; p&amp;lt;0.0001) TIL in the tumors that did develop in the mice treated with the combination NSAID and vaccination as compared to control. There was increased CD8+ (Pearson correlation coefficient: −0.506, p&amp;lt;0001), Tbet+CD4+ (Pearson correlation coefficient: -0.6222, p&amp;lt;0.001), EM CD4+ (Pearson correlation coefficient: 0.-6074, p&amp;lt;0.001) and EM CD8+ (Pearson correlation coefficient: -0.7155, p&amp;lt;0.001) in mice with greater tumor inhibition than those with less protection. Receiver operator curves revealed that CD8+ (AUC: 0.7623; p=0.002), Tbet+CD4+ (AUC 0.7273; p=0.008), EM CD4+ (AUC 0.6782; p=0.04) and EM CD8 (AUC 0.7897; p&amp;lt;0.001) TIL can differentiate mice receiving the combination of NSAID and vaccination as compared to either monotherapy alone. These data define potential biomarkers of response that can guide human clinical trials of NSAIDs +/- vaccination in patients with FAP. Citation Format: Denise L. Cecil, Ying Liu, Lauren Corulli, Mary L. Disis. Immune biomarkers of clinical response after NSAID treatment in combination with vaccination targeting EGFR-COX2-CDC25B in the APC(Min/+) mouse model. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5112.

Opioid-Sparing Effects of Flurbiprofen Axetil as an Adjuvant to Ropivacaine in Pre-Emptive Scalp Infiltration for Post-Craniotomy Pain: Study Protocol for a Multicenter, Randomized Controlled Trial.

Pain after craniotomy remains a poorly controlled problem that is mainly caused by the inflammatory reaction at the incision site. Nowadays, systemic opioids use, as first-line analgesics, is often limited because of adverse effects. Flurbiprofen axetil (FA) is a non-steroidal anti-inflammatory drug merged into emulsified lipid microspheres, which represent a strong affinity to inflammatory lesions. Local administration of flurbiprofen into a surgical wound has induced enhanced analgesic efficacy and few systemic or local adverse effects after oral surgery. However, the impact of local FA, as a non-opioid pharmacologic alternative, remains elusive on postoperative pain in craniotomy. In this study, we presume that pre-emptive infiltration of scalp with FA as an adjuvant to ropivacaine can lead to less sufentanil consumption postoperatively in patient controlled intravenous analgesia (PCIA) compared with ropivacaine alone. We design a multicenter, randomized controlled study that will enroll 216 subjects who are planned to receive supratentorial craniotomy. Patients will receive pre-emptive infiltration of scalp either with 50 mg FA and 0.5% ropivacaine, or with 0.5% ropivacaine alone. Primary outcome is total consumption of sufentanil with PCIA device at 48 h postoperatively. This is the first study attempting to explore the analgesic and safety profile of local FA as an adjuvant to ropivacaine for incisional pain in patients undergoing craniotomy. It will provide additional insights into the opioid-sparing analgesia pathways by local administration of NSAIDs for neurosurgery.

Pharmacokinetics and efficacy of orallyadministered acetaminophen (paracetamol) in adult horses with experimentally induced endotoxemia.

Acetaminophen has been evaluated in horses for treatment of musculoskeletal pain but not as an antipyretic. To determine the pharmacokinetics and efficacy of acetaminophen compared to placebo and flunixin meglumine in adult horses with experimentally induced endotoxemia. Eight university owned research horses with experimentally induced endotoxemia. Randomized placebo controlled crossover study. Horses were treated with acetaminophen (30 mg/kg PO; APAP), flunixin meglumine (1.1mg/kg, PO; FLU), and placebo (PO; PLAC) 2hours after administration of LPS. Plasma APAP was analyzed via LC-MS/MS. Serial CBC, lactate, serum amyloid A, heart rate and rectal temperature were evaluated. Serum IL-1β, IL-6, IL-8, IL-10, and TNF-α were evaluated by an equine-specific multiplex assay. Mean maximum plasma APAP concentration was 13.97 ± 2.74 μg/mL within 0.6± 0.3hour after administration. At 4 and 6hours after treatment, both APAP (P= <.001, P= .03, respectively) and FLU (P= .0045 and P< .001, respectively) had a significantly greater decrease in rectal temperature compared to placebo. FLU caused greater heart rate reduction than APAP at 4 and 6hours (P= .004 and P= .04), and PLAC at 4hours (P= .05) after treatment. The pharmacokinetics of acetaminophen in endotoxemic horses differ from thosereportedbyprevious studies in healthy horses. Acetaminophen is an option for antipyresis in clinical cases, particularly when administration of traditional NSAIDs is contraindicated.

Study on the Effect of Topical Pre-operative Nonsteroidal Anti-inflammatory Drugs in Maintaining Mydriasis during Small Incision Cataract Surgery

A prospective, randomized, double masked, single centered comparative study done in the Bangladesh Naval Ship Patenga, Chattogram, Bangladesh, from July 2021 to June 2022, to assess the clinical benefits and effectiveness of prophylactic pre-operative topical administration of NSAIDs in maintaining mydriasis during small incision cataract surgery. Thirty patients underwent small incision cataract surgery with intra ocular lens implantation were randomized to compare the efficacy of topical NSAIDs drops (Group-A) and placebo drops (Group-B) in maintaining peroperative mydriasis. Balanced salt solution containing non preservative adrenaline was used in all patients. Pupil size was measured prior to the corneal incision and after the completion of the operation. The two groups were analyzed with respect to the changes in pupillary diameter at the beginning and at the end of the operation. The change in pupil size was significantly different among the two groups at the end of the surgery. The mean vertical and horizontal diameter of the two groups were near about similar at the beginning of the surgery. Significant differences were seen after IOL implantation with the NSAIDs group having the larger mean diameter in both vertical (P=0.003) and horizontal (P=0.008) pupillary measurements at the conclusion of surgery. Topical NSAIDs has been shown to be a more effective inhibitor of meiosis during per operative uncomplicated small incision cataract surgery and provides a more stable mydriatic effect during surgery compared to the placebo group.&#x0D; CBMJ 2023 January: Vol. 12 No. 01 P: 22-26

Polymorphisms of the Proinflammatory Cytokine Genes Modulate the Response to NSAIDs but Not to Triptans in Migraine Attacks.

Migraine is a common neurovascular disorder characterized by recurrent episodes of headache and associated neurological symptoms. At present, a significant portion of patients do not obtain a satisfactory response to acute pain-relieving therapies, including NSAIDs and triptans. In this context, pharmacogenetics plays a key role in the understanding of such a diverse response. In order to investigate whether functional polymorphisms in proinflammatory cytokine genes (IL-1α, IL-1β, IL-1RN; IL-6 and TNF-α) may influence the response to acute treatment, 313 consecutive patients with episodic migraine without aura were enrolled. Pain relief by administration of NSAIDs or triptans for three consecutive migraine attacks was evaluated. We found a significant association between A allele of the TNF-α promoter (-308 A/G) and a lack of efficacy after NSAID administration (p &lt; 0.01, OR 2.51, 95% CI: 1.33 &lt; OR &lt; 4.75 compared to the G allele). Remaining polymorphisms had no significant effect on pain relief. Our study showed that a functional polymorphism in the TNF-α gene significantly modulates the clinical response to NSAID administration in acute attacks. Patients with higher production of the active cytokine during stress showed a significantly lower anti-migraine effect. Our results further support a role for TNF-α in the pathophysiological mechanisms of migraine attack.