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BACKGROUND: Literature comparing different alternatives for pain control in the immediate postoperative period of pediatric acute appendicitis (PAA) is scarce. MATERIALS AND METHODS: We prospectively compared the analgesic and emetogenic profile of intravenous ibuprofen and metamizole in the immediate postoperative period of PAA. For this purpose, we used a sample of patients operated on in 2021 in our center. Participants were recruited on arrival at the Emergency Department and histopathological confirmation of the diagnosis was obtained in all of them. Pain was evaluated every 8 hours after the surgery with validated visual analog scales ranging from 0 to 10 points. Repeated measures ANOVA was used to compare the evolution of pain in the 48 hours after surgery between the two groups. RESULTS: The sample included 95 patients (65% males) with a mean age of 9.7 years (sd: 3.14). 41 patients were treated with Ibuprofen (group 1) and 54 with metamizole (group 2). No significant differences were found in the level of pain either in the comparisons of point measurements or in its evolution in the 48 hours after surgery (p= 0.58). After adjusting for the received fluid therapy, children in the metamizole group had significantly more emetic episodes and needed significantly more doses of ondansetron. CONCLUSIONS: In our cohort, ibuprofen had a similar analgesic efficacy and a better emetogenic profile than metamizole in the immediate postoperative period of PAA. Future prospective, adequately controlled studies with larger sample sizes are needed to validate these findings.
INTRODUCCION: En la literatura existen pocas referencias que comparen las distintas alternativas disponibles para controlar el dolor en el postoperatorio inmediato de la apendicitis aguda pediátrica (AAP). MATERIAL Y METODOS: Comparación prospectiva del perfil analgésico y emético del ibuprofeno y el metamizol intravenosos en el postoperatorio inmediato de la AAP, para lo cual se recurre a una muestra de pacientes operados en 2021 en nuestro centro. Los participantes fueron reclutados a su llegada a Urgencias, obteniéndose confirmación histopatológica del diagnóstico en todos ellos. La evaluación del dolor se llevó a cabo cada 8 horas tras la cirugía mediante escalas analógicas visuales validadas, con valoraciones entre los 0 y los 10 puntos. Se realizó un ANOVA de las medidas repetidas entre los dos grupos para comparar la evolución del dolor en las 48 horas posteriores a la cirugía. RESULTADOS: La muestra estaba compuesta por un total de 95 pacientes (65% de ellos varones) con una edad media de 9,7 años (DT: 3,14). 41 pacientes fueron tratados con ibuprofeno (grupo 1) y 54 con metamizol (grupo 2). No se hallaron diferencias significativas en lo que respecta al dolor, ni en las comparaciones de las mediciones puntuales, ni en su evolución en las 48 horas posteriores a la cirugía (p= 0,58). Una vez realizado el ajuste correspondiente a la terapia de fluidos recibida, los niños del grupo metamizol tuvieron significativamente más episodios eméticos y necesitaron significativamente más dosis de ondansetrón. CONCLUSIONES: En nuestra cohorte, el ibuprofeno tuvo una eficacia analgésica similar y un mejor perfil emético que el metamizol en el postoperatorio inmediato de la AAP. Se hacen necesarios nuevos estudios prospectivos, adecuadamente controlados y con mayor tamaño muestral que validen estos hallazgos.
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Apendicitis , Ibuprofeno , Masculino , Humanos , Niño , Femenino , Ibuprofeno/efectos adversos , Dipirona , Apendicitis/tratamiento farmacológico , Apendicitis/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Analgésicos , Periodo PosoperatorioRESUMEN
OBJECTIVES: Pain management for infants undergoing cardiothoracic surgery primarily utilises opioid analgesics. There is a paucity of data available for the use of non-steroidal anti-inflammatory medications such as ketorolac in this patient population. MATERIALS AND METHODS: This retrospective study evaluated patients between 30 days and 6 months undergoing cardiothoracic surgery. The primary endpoint evaluates ketorolac on reducing post-operative opioid use. RESULTS: Of 243 evaluated patient, 145 met inclusion. Baseline demographics were similar amongst the cohorts. Patients administered ketorolac used less cumulative opiates, in morphine milligram equivalents, for post-op days (POD) 1-3 after surgery compared to patients not receiving ketorolac (9.47 versus 12.68; p = 0.002). The no-ketorolac group required more opiates on POD 1 (10.9 versus 5; p < 0.001) and POD 2 (4.2 versus 2.5; p = 0.006) with no difference found on POD 3 (2 versus 1.6; p = 0.2). There was a mean increase from baseline to highest serum creatinine level on POD 1-3 in the no-ketorolac group compared to the ketorolac group (0.15 versus 0.09 mg/dL; p < 0.014), with no difference in stage 1 or stage 2 acute kidney injury. There were no differences in average chest tube output in mL/kg/day (0.24 versus 0.32; p = 0.569) or need for transfusion (36% versus 24%; p = 0.125), respectively. DISCUSSION: Scheduled administration of ketorolac after cardiothoracic surgery resulted in a significant reduction in opioid exposure, with no difference in rates of acute kidney injury or bleeding.
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Mixed-mode reversed-phase/anion-exchange chromatography (RP/AEX) is an effective method for the chromatographic analysis of acidic drugs because it combines reversed-phase chromatography (RP) with anion-exchange chromatography (AEX). However, the result repeatability for the RP/AEX analysis of acidic drugs is frequently compromised by the detrimental effects of residual silanol groups in an RP/AEX stationary phase on peak separation and analyte retention. In this study, an RP/weak-AEX stationary phase with amino anion-exchange groups, Sil-AA, was prepared. Subsequently, an RP/strong-AEX stationary phase, Sil-PBQA, was prepared by replacing the amino groups in Sil-AA with a benzene ring and a benzyl-containing quaternary ammonium salt. The chromatographic behaviors of Sil-PBQA and Sil-AA were compared, and the effect of residual silanol groups on the chromatographic behavior of an RP/AEX stationary phase was evaluated. Residual silanol groups not only caused additional electrostatic interactions for acidic analytes, but also competed with the analytes for the anion-exchange sites in an RP/AEX stationary phase. The effects of different salt-containing mobile-phase systems on the analyte-retention behavior of Sil-PBQA were investigated to develop a method that enhanced the repeatability of the RP/AEX acidic-analyte-analysis results obtained using Sil-PBQA and facilitated the separation of nonsteroidal anti-inflammatory drugs on Sil-PBQA. The ideas presented in this paper can improve the separation of peaks and repeatability of results in the RP/AEX analysis of acidic drugs.
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Background: Enflicoxib is a COX-2 selective NSAID shown to be efficacious and safe in the treatment of pain and inflammation associated with canine osteoarthritis (OA) in clinical studies of 6 weeks duration. Objective: This prospective, multisite, blinded, randomized, placebo-controlled, parallel-group field study aimed to confirm the safety and efficacy of enflicoxib in long-term canine OA treatments. Animals: A total of 109 client owned dogs with clinical and radiographic signs of OA for at least 3 weeks were enrolled with 78 dogs completing all study visits. Methods: Dogs were randomized at a 3:1 ratio to receive enflicoxib (n = 83) or placebo (n = 26) once weekly during 6 months. Dogs underwent veterinary assessments from Day 0 to Day 189 using a clinical sum score (CSS). Efficacy was also assessed by the owners using the Canine Brief Pain Inventory (CBPI). Safety was assessed clinically and by repeated blood and urine sample analysis. The efficacy outcome measure was the treatment response according to the CSS and secondarily the treatment response according to the CBPI. The primary safety outcome was the incidence of adverse events (AEs) and secondarily the evolution of the clinical pathology parameters. Results: Percentages of CSS responders for enflicoxib were 71.6; 74.6 and 71.6% on Days 44, 135 and 189 respectively, always showing statistically significant differences (p < 0.05) vs. placebo (41.7, 33.3, and 20.8% respectively). Treatment response according to owner assessments followed the same pattern, achieving significant differences compared to placebo after 2 weeks of treatment. The incidence and type of AEs were as described in previous enflicoxib studies of shorter duration and as for other NSAIDs, with no tendency to increase over time. No relevant changes in hematology, biochemistry or urine parameters were observed. Conclusions and clinical relevance: Enflicoxib safety and efficacy profile is maintained after a long-term treatment, which together with its weekly administration, makes it a good alternative for the chronic treatment of dogs with naturally occurring OA.
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Gout attacks are treated with uric-lowering and anti-inflammatory drugs. In patients with gout, non-steroidal anti-inflammatory drugs (NSAIDs) could be both cardiovascular beneficial, due to their anti-inflammatory actions, and cardiovascular hazardous, due to their prothrombotic, hypertensive, and proarrhythmic side effects. We, therefore, examined the risk of cardiovascular events associated with NSAID use in patients with gout. We conducted a nationwide, population-based case-crossover study of all Danes ≥ 18 years of age with first-time gout during 1997-2020, who experienced a cardiovascular event (myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation/flutter, or cardiovascular death) (n = 59,150). The exposure was use of NSAIDs, overall and according to type (ibuprofen, naproxen, or diclofenac). We used the dates 300, 240, 180, and 120 before the outcome date as reference dates. We used the Mantel-Haenszel method to calculate odds ratios (ORs) with 95% confidence intervals (CIs) of the association between NSAID use and cardiovascular events. NSAID use was overall associated with 12% decreased odds of a cardiovascular event (OR = 0.88, 95% CI: 0.85-0.91). This decreased odds ratio was observed for the use of ibuprofen (OR = 0.92, 95% CI: 0.88-0.97) and naproxen (OR = 0.85, 95% CI: 0.74-0.97), but not for the use of diclofenac (OR = 0.97, 95% CI: 0.90-1.05). Overall, use of NSAIDs was associated with decreased odds of all the individual components of the composite outcome. NSAIDs were not associated with an increased cardiovascular event rate when used in gout patients. Ibuprofen and naproxen appeared to have better cardiovascular risk profiles than diclofenac.
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Fixed drug eruption (FDE) is a well-recognized, non-immediate, drug hypersensitivity reaction, often attributed to the use of various medications, most commonly non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Cross-reactivity between related NSAIDs in FDE has been reported, but among chemically unrelated NSAIDs, is rare. Herein, we present a rare well-documented case where a patient initially displayed tolerance to etoricoxib after experiencing a nimesulide-induced FDE. Subsequently, the patient developed an etoricoxib-induced FDE, accompanied by the development of bullous lesions. This case report and the literature review on comparable FDE occurrences shed light on the intricate nature of FDEs, suggesting the possibility of cross-reactivity between chemically related and unrelated NSAIDs or the emergence of new drug-specific T cells without cross-reactivity after multiple exposures to a drug in a susceptible patient. Our case underscores the importance of increased awareness and vigilance among both physicians and patients in the realm of personalized medicine. Further research is needed to unravel the intricate mechanisms behind these drug eruptions, improve diagnostic approaches, and enhance patient care.
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Background: Smoking and the use of non-steroidal anti-inflammatory drugs (NSAIDs) acetylsalicylic acid (ASA), proton pump inhibitors (PPIs), serotonin reuptake inhibitors (SSRIs), and statins have been associated with microscopic colitis (MC). Objectives: We investigated whether these factors were associated with repeated budesonide treatments in patients diagnosed with MC. Design: Retrospective observational study. Methods: All patients with a histologically verified diagnosis of MC at our clinic between the years 2006 and 2022 were identified. Baseline factors and drugs prescribed before and after diagnosis were registered. The influence of risk factors on the odds of having a prescription of oral budesonide and the odds of having a second course of budesonide was studied. Results: Patients with MC (n = 183) with a mean age of 62.3 years [standard deviation (SD): 13.3 years] were followed for a median of 5 years (25th-75th percentile 4-10 years) after diagnosis. In all, 138 patients (75%) had at least one prescription of budesonide after diagnosis, and 90 patients (49%) had at least one clinical relapse treated with budesonide. Patients who had been prescribed NSAIDs within 1 year before clinical relapse had higher odds for clinical relapse [odds ratio (OR): 3.70, 95% confidence interval (CI): 1.06-12.9] but there was no increased risk for clinical relapse for the use of ASA (OR: 0.99, 95% CI: 0.39-2.90), PPIs (OR: 1.09, 95% CI: 0.45-2.63), SSRI (OR: 1.41, 95% CI: 0.82-2.44), or statins (OR: 0.83, 95% CI: 0.35-1.99). No association was seen between being a smoker and/or being prescribed NSAID, ASA, PPI, SSRI, and statins at baseline and the odds of having a prescription of oral budesonide within 1 year after diagnosis. Conclusion: The risk of being prescribed a second course of budesonide is associated with receiving a prescription of NSAIDs but not with the use of ASA, PPIs, SSRIs, and statins.
The use of drugs and the odds for patients with microscopic colitis of having a second course of budesonide Microscopic colitis is a common cause of chronic diarrhea. Previous studies have shown that the use of non-steroidal anti-inflammatory drugs, acetylsalicylic acid, proton-pump inhibitors, serotonin reuptake inhibitors and statins are used more often in patients who later develop microscopic colitis. We aimed to study if these drugs also had an association to an increased risk of disease flares treated with budesonide in 183 patients with known microscopic colitis. Oral budesonide for 6-8 weeks are recommended for disease flares of microscopic colitis. In our study, 90 patients (49%) were prescribed a second course of budesonide probably due to a disease flare. We found a higher odds for being prescribed a second course of budesonide in patients with microscopic colitis who were prescribed non-steroidal anti-inflammatory drugs but no higher risk for the other 'risk drugs' for microscopic colitis.
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Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) constitute an important class of pharmaceuticals acting on cyclooxygenase COX-1 and COX-2 enzymes. Due to their numerous severe side effects, it is necessary to search for new selective, safe, and effective anti-inflammatory drugs. In silico design of novel therapeutics plays an important role in nowadays drug discovery pipelines. In most cases, the design strategies require the use of molecular docking calculations. The docking procedure may require case-specific condition for a successful result. Additionally, many different docking programs are available, which highlights the importance of identifying the most proper docking method and condition for a given problem. Methods: In the current work, the performances of five popular molecular docking programs, namely, GOLD, AutoDock, FlexX, Molegro Virtual Docker (MVD) and Glide to predict the binding mode of co- crystallized inhibitors in the structures of known complexes available for cyclooxygenases were evaluated. Furthermore, the best performers, Glide, AutoDock, GOLD and FlexX, were further evaluated in docking-based virtual screening of libraries consisted of active ligands and decoy molecules for cyclooxygenase enzymes and the obtained docking scores were assessed by receiver operating characteristics (ROC) analysis. Results: The results of docking experiments indicated that Glide program outperformed other docking programs by correctly predicting the binding poses (RMSD less than 2 Å) of all studied co-crystallized ligands of COX-1 and COX-2 enzymes (i.e., the performance was 100%). However, the performances of the other studied docking methods for correctly predicting the binding poses of the ligands were between 59% to 82%. Virtual screening results treated by ROC analysis revealed that all tested methods are useful tools for classification and enrichment of molecules targeting COX enzymes. The obtained AUCs range between 0.61-0.92 with enrichment factors of 8 - 40 folds. Conclusion: The obtained results support the importance of choosing appropriate docking method for predicting ligand-receptor binding modes, and provide specific information about docking calculations on COXs ligands.
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Preterm infants often experience frequent intermittent hypoxia (IH) episodes which are associated with neuroinflammation. We tested the hypotheses that early caffeine and/or non-steroidal inflammatory drugs (NSAIDs) confer superior therapeutic benefits for protection against IH-induced neuroinflammation than late treatment. Newborn rats were exposed to IH or hyperoxia (50% O2 ) from birth (P0) to P14. For early treatment, the pups were administered: 1) daily caffeine (Caff) citrate (Cafcit, 20 mg/kg IP loading on P0, followed by 5 mg/kg from P1-P14); 2) ketorolac (Keto) topical ocular solution in both eyes from P0 to P14; 3) ibuprofen (Ibu, Neoprofen, 10 mg/kg loading dose on P0 followed by 5 mg/kg/day on P1 and P2); 4) Caff+Keto co-treatment; 5) Caff+Ibu co-treatment; or 6) equivalent volume saline (Sal). On P14, animals were placed in room air (RA) with no further treatment until P21. For late treatment, pups were exposed from P0 to P14, then placed in RA during which they received similar treatments from P15-P21 (Sal, Caff, and/or Keto), or P15-P17 (Ibu). RA controls were similarly treated. At P21, whole brains were assessed for histopathology, apoptosis, myelination, and biomarkers of inflammation. IH caused significant brain injury and hemorrhage, inflammation, reduced myelination, and apoptosis. Early treatment with Caff alone or in combination with NSAIDs conferred better neuroprotection against IH-induced damage than late treatment. Early postnatal treatment during a critical time of brain development, may be preferable for the prevention of IH-induced brain injury in preterm infants.
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Fibromatosis is a rare locally aggressive benign tumour which arises from the musculoaponeurotic structures throughout the body. In the oral and maxillofacial region, It has been described under a variety of synonyms, including 'extra articular desmoids', 'desmoids tumours', 'grade-1 fibrosarcomas','non metastasizing fibrosarcoma'and 'aggressive fibromatosis'. The pecularity of this entity in paranasal sinuses is that it is rare in this location and are locally aggressive with higher rates of recurrence in a relatively restricted area.The purpose of this study is to present a rare case report and reviewing the literature of this entity.
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Purpose: Chronic inflammatory pain is usually treated with oral non-steroidal anti-inflammatory drugs (NSAIDs). However, oral NSAIDs can cause some adverse events, and local preparation is an important alternative drug. Currently, small sample clinical studies show that loxoprofen sodium hydrogel patch (LX-P) has good analgesic and anti-inflammatory effects; however, there is a lack of real-world clinical research data. Patients and Methods: This study included 60 patients with chronic inflammatory pain. They were treated with LX-P without affecting their real-world treatment for two weeks. Results: After 2 weeks of continuous medication, 93.33% of the patients stated that the treatment was effective. Only 3.33% of the patients had a relapse after 4 weeks. Moreover, the swelling range and degree of swelling decreased markedly and the dysfunction of the pain site was markedly alleviated. The total satisfaction of patients after treatment reached 90.00%. Conclusion: In this real-world observational study, LX-P showed good efficacy and safety in patients with chronic inflammatory pain.
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Purpose: Patients with chronic kidney disease (CKD) are particularly vulnerable to the risks of polypharmacy, largely owing to various comorbid conditions. This vulnerability is further compounded by an escalated risk of renal function deterioration when exposed to nephrotoxic medications. As part of the national health insurance program in Taiwan, the pre-end-stage kidney disease patient care and education plan has included pharmaceutical care since October 2021. This study aims to explore the effect of pharmacist involvement in a multidisciplinary care team for patients with kidney disease in outpatient settings. Patients and Methods: This retrospective observational study was conducted at a single center. It analyzed data from May 2022 to May 2023, focusing on patients who received medication therapy management in the kidney disease pharmacist-managed clinic. The study assessed changes in patient medication adherence, non-steroidal anti-inflammatory drugs (NSAIDs) usage, CKD stage, and urine protein-to-creatinine ratio (UPCR) after pharmacist intervention. It also documented pharmacists' medication recommendations and the rate of acceptance by physicians. Results: A total of 202 patients who had at least two clinic visits were included in the study. After pharmacist intervention, the proportion of poor medication adherence reduced significantly from 67.8% to 43.1% (p<0.001). The proportion of NSAID users also decreased significantly from 19.8% to 8.4% (p=0.001). CKD stage showed a significant reduction (p=0.007), and the average UPCR improved from 2828.4 to 2111.0 mg/g (p<0.001). The pharmacists provided a total of 56 medication recommendations, with an acceptance rate of 86%. Conclusion: The involvement of pharmacists in the multidisciplinary care team can effectively provide medication-related recommendations, ensuring the effectiveness and safety of patients' medication use, and lead to better kidney function and lower proteinuria.
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Peptic ulcers are a common condition that arises from an imbalance between acid production and gastroduodenal protective factors. Various drugs, including non-steroidal anti-inflammatory drugs (NSAIDs), potassium supplements, bisphosphonates, and doxycycline, can increase the development of peptic ulcers. NSAIDs are one of the most common medications prescribed for pain relief, and they also inhibit the formation of cyclooxygenase-1 (COX-1). COX-1 helps in the production of mucus that lines the stomach, so by inhibiting COX-1, NSAIDs reduce the mucus produced by the stomach and increase the likelihood of gastric ulcer formation. Additionally, NSAIDs are acidic, and increasing the amount of any acid in the stomach can result in promoting ulcer development. Potassium supplements are used to reduce the effects of hypertension, decrease the development of kidney stones, and treat hypokalemia. The various types of transporters and channels used to move potassium across cell membranes increase hydrogen being pumped, increasing gastric acid production and ulcer formation. Bisphosphonates are used to treat a variety of skeletal disorders that require inhibition of osteoclast activity. Nitric oxide (NO) has been shown to have a therapeutic effect on gastric ulcers, and some bisphosphonates have been shown to decrease the production of nitric oxide, resulting in increased damage to the gastric mucosa. Finally, doxycycline is a broad-spectrum tetracycline antibiotic that is typically used to treat anthrax poisoning, skin lesions, and sexually transmitted diseases. A harmful adverse effect of doxycycline is the formation of peptic and gastric ulcers related to the drug being highly acidic once it has dissolved.
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There is a high global prevalence of NSAIDs during pregnancy. However, current evidence is largely conflicting regarding the safety of gestational NSAIDs use both for the pregnancy and offspring health. The aim of this study is to systematically review the relationship between NSAIDs use during pregnancy and the risk of adverse pregnancy outcomes and congenital abnormalities. Cohort studies and case control studies on congenital malformations, miscarriage and preterm birth in infants born to mothers who were exposed to NSAIDs during pregnancy were identified via PubMed, Medline, Embase, the Cochrane Library databases and the Reprotox® database from inception to 26 March 2021, and updated on 6 April 2023. On the whole, compared with the unexposed group, infants exposed to NSAIDs during early pregnancy showed a 28% increased risk of overall congenital anomalies (OR 1.28, 95%CI 1.16-1.40), and 19% for major birth defects (OR 1.19, 95%CI 1.08-1.30). Contrary to previous beliefs, there appeared to be a trend towards a higher risk of miscarriage among women who were exposed to NSAIDs during pregnancy, but the association was not statistically significant (OR 1.20, 95%CI 0.93-1.55). According to our study findings, the use of NSAIDs by pregnant women has been linked to a higher risk of congenital anomalies and a negative impact on preterm birth. Therefore, we advise pregnant women to carefully consider the potential benefits and risks before using NSAIDs during pregnancy.
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Aborto Espontáneo , Complicaciones del Embarazo , Nacimiento Prematuro , Femenino , Embarazo , Recién Nacido , Humanos , Resultado del Embarazo/epidemiología , Aborto Espontáneo/inducido químicamente , Aborto Espontáneo/epidemiología , Nacimiento Prematuro/epidemiología , Antiinflamatorios no Esteroideos/efectos adversos , Complicaciones del Embarazo/tratamiento farmacológicoRESUMEN
BACKGROUND: Pain is common in patients with cancer. The World Health Organisation recommends paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) for mild pain and combined with other agents for moderate/severe pain. This study estimated associations of NSAIDs with recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and the incidence of immune-related adverse events (irAEs) in high-risk patients with resected melanoma in the EORTC 1325/KEYNOTE-054 phase III clinical trial. PATIENTS AND METHODS: Patients with AJCC7 stage IIIA, IIIB or IIIC resected melanoma were randomized to receive 200 mg of adjuvant pembrolizumab (N = 514) or placebo (N = 505) 3-weekly for one year or until recurrence. As previously reported, pembrolizumab prolonged RFS and DMFS. NSAID use was defined as administration between 7 days pre-randomization and starting treatment. Multivariable Cox and Fine and Gray models were used to estimate hazard ratios (HRs) for associations of NSAIDs with RFS, DMFS and irAEs. RESULTS: Of 1019 patients randomized, 59 and 44 patients in the pembrolizumab and placebo arms, respectively, used NSAIDs. NSAIDs were not associated with RFS (HR 0.91, 95% CI 0.58-1.43) or DMFS in the pembrolizumab (HR 1.03, 95% CI 0.65-1.66) or placebo arms (for RFS, HR 0.76, 95% CI 0.48-1.20; for DMFS, HR 0.80, 95% CI 0.49-1.31). NSAIDs were associated with the incidence of irAEs in the placebo arm (HR 3.06, 95% CI 1.45-6.45) but not in the pembrolizumab arm (HR 0.94, 95% CI 0.58-1.53). CONCLUSION: NSAIDs were not associated with efficacy outcomes nor the risk of irAEs in patients with resected high-risk stage III melanoma receiving adjuvant pembrolizumab.
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Anticuerpos Monoclonales Humanizados , Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/tratamiento farmacológico , Melanoma/cirugía , Melanoma/patología , Pronóstico , Estadificación de Neoplasias , Supervivencia sin Enfermedad , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Adyuvantes Inmunológicos/uso terapéutico , Dolor , Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios/uso terapéuticoRESUMEN
Non-specific low back pain (LBP) represents a challenging and prevalent condition that is one of the most common symptoms leading to primary care physician visits. While established guidelines recommend prioritizing non-pharmacological approaches as the primary course of action, pharmacological treatments are advised when non-pharmacological approaches are ineffective or based on patient preference. These guidelines recommend non-steroidal anti-inflammatory drugs (NSAIDs) or skeletal muscle relaxers (SMRs) as the first-line pharmacological options for acute or subacute LBP, while NSAIDs are the exclusive first-line pharmacological option for chronic LBP. Although SMRs are generally effective for acute LBP, the available evidence does not support the view that they improve functional recovery, and their comparative efficacy to NSAIDs and other analgesics remains unknown, while studies have shown them to introduce adverse events without significantly reducing LBP. Moreover, opioids continue to be widely prescribed for LBP, despite limited evidence for effectiveness and known risks of addiction and overdose. Broader use of non-opioid pharmacotherapy, including the appropriate use of OTC options, is critical to addressing the opioid crisis. The balance of evidence indicates that NSAIDs have a favorable benefit-risk profile when compared to other available pharmacological treatment options for non-specific LBP, a condition that is primarily acute in nature and well-suited for self-treatment with OTC analgesics. While clinical guidelines do not differentiate between NSAIDs, evidence indicates that OTC naproxen sodium effectively relieves pain across multiple types of pain models, and furthermore, the 14-h half-life of naproxen sodium allows sustained, all day pain relief with reduced patient pill burden as compared to shorter acting options. Choosing the most appropriate approach for managing LBP, including non-pharmacological options, should be based on the patient's condition, severity of pain, potential risks, and individual patient preference and needs.
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Dolor de la Región Lumbar , Naproxeno , Humanos , Naproxeno/uso terapéutico , Antiinflamatorios no Esteroideos/efectos adversos , Analgésicos , Analgésicos Opioides , Dolor de la Región Lumbar/tratamiento farmacológico , Dolor de la Región Lumbar/inducido químicamenteRESUMEN
The presence of micropollutants in water bodies has become a growing concern due to their persistence, bioaccumulation and potential toxicological effects on aquatic life and humans. In this study, the performance of a column system consisting of zero-valent iron nanoparticles (nZVI) incorporated into a cationic resin and synthesized from green tea extract with the addition of persulfate for the elimination of selected pharmaceuticals and endocrine disruptors from wastewater is evaluated. Ibuprofen, naproxen, diclofenac and ketoprofen were the target pharmaceuticals from non-steroidal anti-inflammatory drugs group, while bisphenol A was the target endocrine disruptor. In this context, different real wastewater effluent matrices were investigated: anaerobic membrane bioreactor (AnMBR), upflow anaerobic sludge blanket reactor (UASB) after microfiltration, tertiary treated by conventional activated sludge system and saturated vertical constructed wetland followed by a sand filtration unit effluent (hybrid). The transformation products of diclofenac and bisphenol A were also identified. The experimental results indicated that the performance of the R-nFe/PS system towards the removal efficiency of the target compounds was enhanced in the order of effluents: tertiary > AnMBR ≈ hybrid > UASB. More than 70% removal was obtained for almost all target compounds when conventional tertiary effluent was used, while the maximum removal efficiency was about 50% in the case of filtered UASB. As far as we know, this is the first time that nZVI has been assessed in combination with persulfate for the removal of micropollutants in a continuous flow system receiving various types of real wastewater with different matrix characteristics.
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Compuestos de Bencidrilo , Fenoles , Aguas Residuales , Contaminantes Químicos del Agua , Humanos , Aguas del Alcantarillado , Eliminación de Residuos Líquidos/métodos , Diclofenaco , Hierro , Anaerobiosis , Reactores Biológicos , Preparaciones FarmacéuticasRESUMEN
As excellent crystalline materials, covalent organic frameworks (COFs) are widely used in drug adsorption. In this work, a defective engineering strategy was proposed for designing and preparing the functionalized end-capping monomer and missing-linker COFs. The missing-linker COF 2,4,6-trihydroxybenzene-1,3,5-tricarbaldehyde compound with glycidyltrimethyl ammonium chloride modified benzene-1,4-diamine (TpPa-GTA) was synthesized through Schiff base reaction with wide pore size distribution for adsorption of four nonsteroidal anti-inflammatory drugs (NSAIDs). The adsorption process follows pseudo-second-order kinetics, and the four drugs reached adsorption equilibrium within 10 min. The sunflower-like structure helps to promote intraparticle diffusion during the adsorption process, thereby realizing the rapid adsorption of TpPa-GTA. The equilibrium isotherms fit well with both the Freundlich and Langmuir models, with a maximum adsorption capacity of 83.3-315 mg g-1 calculated from the Langmuir model. Based on the detection results of Zeta potential and XPS, the adsorption mechanism was inferred, and the rapid capture of NSAIDs in the wide pH range of 4.0 to 7.5 was realized under electrostatic interaction, hydrogen bonding, and π-π interaction. The detection of lake and river samples using the missing adapter TpPa-GTA has a recovery rate of 84.2-117%, which provides a new approach to the adsorption of pollutants with COFs.
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Helianthus , Estructuras Metalorgánicas , Estructuras Metalorgánicas/química , Antiinflamatorios no Esteroideos , Adsorción , CinéticaRESUMEN
We evaluated the effect of administration timing of meloxicam and robenacoxib on renal function, platelet cyclo-oxygenase and perioperative analgesia in 60 cats undergoing ovariohysterectomy, in a prospective randomized blinded controlled study. Twelve cats were randomly allocated to one subcutaneous treatment group: meloxicam (0.2 mg/kg) or robenacoxib (2 mg/kg) at admission (MA, RA), at induction (MI, RI) and robenacoxib at the end of surgery (RE). All cats received the same anaesthesia protocol. Plasma renin activity (PRA), plasma creatinine, drug concentrations and serum thromboxane (TxB2 ) were measured sequentially. Anaesthesia significantly increased PRA, as activity at end of the surgery was higher than 2 h later (mean ± SD: 26.6 ± 2.8 versus 10.0 ± 3.9 ng/mL/h). PRA remained higher at 2 h post-surgery in admission groups compared to induction groups (p = .01). Serum TxB2 was lower with meloxicam than robenacoxib (p = .001), and was lower in the MA than each robenacoxib group at catheter placement. Admission groups (16/24 from RA and MA groups) received earlier rescue analgesia than other groups (p = .033). In conclusion, the renin-angiotensin system was activated during anaesthesia despite cyclo-oxygenase inhibition, possibly due to hypotension or surgical stimulation. There was no effect of drug or timing on the markers of renal function but one cat receiving meloxicam at induction had suspected IRIS grade II acute kidney injury.
RESUMEN
Objective: To examine the relationship between long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence and progression of radiographic hip osteoarthritis (RHOA), as well as the degeneration of individual radiographic features. Methods: We analyzed data from the Osteoarthritis Initiative (OAI) and the Cohort Hip and Cohort Knee (CHECK) study. Our exposure was the number of years of NSAID use over a 4-to-5-year follow-up period. Our outcomes were the incidence and progression of RHOA over a 4-to-5-year follow-up as assessed using a modified Croft grade in OAI and the Kellgren-Lawrence (K/L) grade in CHECK. The incidence of RHOA was defined as having RHOA (grade ≥2) at follow-up and investigated in "incidence cohorts" of hips without RHOA at baseline (grade <2). The progression of RHOA was defined as an increase of ≥1 grade at follow-up from baseline and investigated in "progression cohorts" of hips with RHOA at baseline (grade ≥2). Additionally, we assessed the degeneration of nine specific radiographic features, such as joint space narrowing and osteophytes, defined by a grade increase of ≥1 âat follow-up from baseline, in all cohorts. Results: In the incidence cohorts, there were 5153 hips in OAI and 1011 in CHECK; in the progression cohorts, there were 285 and 106 hips, respectively. There was no association between NSAID use and the outcomes investigated. Conclusion: Over 4-to-5 years, long-term NSAID use showed no association with the incidence or progression of RHOA, or with the degeneration of individual radiographic features.
