Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed drugs for cancer pain. We used Delphi methodology to evaluate the opinions of clinicians on NSAIDs and paracetamol, with a specific focus on their safety profile. Consensus was reached on 7 statements. High level of consensus was reached regarding use of NSAIDs and gastrointestinal, cardiovascular, and renal risk in patients taking low-dose aspirin and assessment of liver function during long-term treatment with paracetamol. Consensus was also reached that assessment and monitoring of eGFR is important in the elderly being administered NSAIDs. It was further agreed that NSAIDs can often play a key role in association with opioids in treatment of cancer pain and that paracetamol is the analgesic of first choice for patients with mild chronic pain. When NSAIDs are administered in combination with steroids, it was agreed that the risk of gastrointestinal damage is increased since steroids delay the healing of ulcers, and that paracetamol can be used during pregnancy and does not affect the health of the fetus. This Delphi study highlights that there is a poor agreement on how these drugs are routinely prescribed. However, the consensus was reached for 7 key statements and may represent a valid contribution to daily practice.

(1) Background: It is crucial to provide safe and knowledgeable healthcare practices because no research has been done on the knowledge and usage patterns of NSAIDs among the Hail population. (2) Method: Structured questionnaires were utilized to gather data from 399 individuals in Hail, Saudi Arabia for the cross-sectional analysis. The study assessed participants' knowledge regarding NSAIDs, patterns of use, reasons for use, and awareness of potential side effects. (3) Results: In the study, the gender distribution indicated that 170 participants (42.61%) were male, while 229 (57.39%) were female. Gender, occupation, and marital status showed non-significant associations (p>0.01), except for menstrual cycle and joint pain, where marital status displayed significant associations. Age had significant associations with muscle pain, menstrual cycle, and joint pain (p<0.01). Education and monthly income exhibited non-significant associations for all the reasons. The regression analysis demonstrated that gender played a significant role, with females having higher odds of knowledge (AOR = 1.75, 95% CI 1.10-2.88) than males. Age also had a notable impact, with individuals aged 50-59 (AOR = 0.21, 95% CI 0.07-0.66) exhibiting lower odds of knowledge. Education holding a Ph.D (AOR = 3.50, 95% CI 0.54-22.51) and business as an occupation (AOR = 6.12, 95% CI 1.10-35.10) had significantly higher odds of knowledge while housewives (AOR = 0.76, 95% CI 0.25-2.27) had lower odds. Meanwhile, >50% of the participants had knowledge of adverse events related to the use of NSAIDs while 25% had no knowledge. Moreover, 59 (25.766%) participants reported discomfort with the use of NSAIDs. In addition, 50% and >75% of participants’ considered NSAIDs can cause peptic ulcers and damage kidneys, respectively (4) Conclusions: This study shed light on the knowledge and patterns of NSAIDs use in the population of Hail, Saudi Arabia. While NSAIDs are commonly utilized for pain management, there exists a need for improved public awareness regarding potential risks and safe usage practices. Healthcare providers and policymakers should consider these insights to develop targeted educational initiatives and healthcare interventions to promote safe and informed NSAID utilization in the region.

Abstract: Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully un-derstood and causal treatment options are not available. Recently we demonstrated that Hepa-ranase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that As-pirin has inhibitory effect on Hpa. Another compound, which possesses a mild pan-creato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesize that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhib-itors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in ex-perimental model of AP induced by Cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the se-rum levels of Lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in heparanase transgenic (Hpa-Tg) mice vs wild-type (WT) mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.

Nonsteroidal anti-inflammatory drugs (NSAIDs), which block the activity of cyclooxygenase (COX) isoenzymes and inhibit the synthesis of prostaglandin, have been used for pain relief. We have developed a method to separate a mixture of three NSAIDs, such as aspirin, paracetamol, and naproxen, using reverse-phase high-performance liquid chromatography (RP-HPLC). An isocratic mobile phase consisting of acidic water and acetonitrile was selected to run at a low flow rate, such as 0.8 mL/min. The mixture of three NSAIDs was injected at a low volume into a C18 column that was 150 mm in length and characterized using a UV detector at 230 nm. We identified three peaks in the chromatogram indicating the three compounds. The elution time of the peaks was less than 10 minutes. To identify multiple peaks on the isocratic flow using a short column, further studies are required regarding the proposed method to generate microfluidic devices for nanoLC.

The current recommendation to avoid non-steroidal anti-inflammatory drugs (NSAIDs) in management of dengue virus disease is, as it was adopted earlier in COVID-19, scientifically considered of very low to low certainty. In this perspective I argue, for the first time globally, basing on real-life practice that NSAIDs might be lifesaving in early management of dengue virus disease as I originally argued and proved rightful in COVID-19. Moreover, I also argue that the Egyptian immune-modulatory Kelleni’s protocol, including nitazoxanide as an integral component, can be safely and effectively used to early manage COVID-19, human metapneumovirus, dengue virus disease, Zika virus separate or co-infections similar to what has already been experienced and published with separate or conjoined infections with SARS CoV-2, influenza, RSV and Norwalk viruses without the need of prior serological or molecular investigations to determine the causative agent.

The pharmacokinetics of salicylic acid (SA) in sheep was evaluated following intravenous (IV) and oral administration of sodium salicylate (sodium salt of salicylic acid) at different doses. Six healthy sheep were administered sodium salicylate (SS) IV at doses of 10, 50, 100 and 200 mg/kg body weight and another six sheep were drenched with 100 and 200 mg/kg of SS orally. Both studies were randomised crossover trials. A one-week washout period between each treatment was allowed in both studies. Blood samples were collected at 0, 15, 30 minutes and 1, 2, 4 and 6 hours after IV and oral SS administrations. Plasma SA concentrations were determined using high performance liquid chromatography with diode array detection method. Pharmacokinetic variables were calculated in a non-compartmental model. The elimination half-life (T_{1/2 el}) of SA after IV administration of 200 mg/kg SS was 1.16 ± 0.32 hours. Mean bioavailability of SA was 64%, and mean T_{1/2 el} was 1.90 ± 0.35 hours, after 200 mg/kg of oral SS. The minimum plasma SA concentration (16.8 µg/mL) required to produce analgesia in humans was achieved after IV administration of 100 and 200 mg/kg SS in sheep for about 0.17 hour in this study. Experiments on pharmacokinetic-pharmacodynamics modelling are required to determine the actual effective plasma concentration range of SA in sheep.

Chronic and non-healing wounds demand personalized and more effective therapies for treating complications and improve patient adherence. This work aims to develop a suitable chitosan-based scaffold to provide 24 hours controlled release of DKT, by taking advantage of chitosan’s thermo-responsive behavior as well as local hyperthermia in wounds. Three formulation prototypes were developed using chitosan (F1), 2:1 chitosan: PVA (F2), and 1:1 chitosan:gelatin (F3). Compatibility tests were done by DSC, TG, and IR spectroscopy. SEM was employed to examine the morphology of the surface and inner layers from the scaffolds. In vitro release studies were performed at 32 °C and 38 °C to evaluate the release profiles, which were later adjusted to different kinetic models for the best formulation. F3 showed the most controlled release of DKT at 32 °C for 24 hours (77.75 ± 2.72 %), and reduced the burst release in the initial 6 hours (40.18 ± 1.00 %), while at 38 °C the release reached 88.52 ± 2.07 % at 12 hours. The release profile for this formulation fits with Hixson-Crowell and Korsmeyer-Peppas kinetic models at both temperatures. Therefore, the developed chitosan/gelatin thermo-responsive scaffold provides a suitable system for wound healing with a controlled release of DKT for 24 hour-use, which can overcome adherence issues and wound complications.

COVID-19 pandemic represents an unprecedented sanitary threat: antiviral and host-directed medications to treat the disease are still urgently needed.A great effort has been paid to find drugs and treatments for hospitalized, severely ill patients. However, medications used for the domiciliary management of initial symptoms, notwithstanding their importance, have not been and are not presently regarded with the same attention. In analogy with other respiratory viral infections, COVID-19 patients in the early phase require specific antivirals (still lacking) and non-etiotropic drugs to lower pain, fever and control inflammation. Non-steroidal antinflammatory drugs (NSAIDs) and paracetamol (PAC) are widely used as non-etiotropic agents in these conditions and hence are both theoretically repurposable for COVID-19. However, a warning from some research reports and National Authorities raised NSAIDs safety concerns because of the supposed induction of ACE2 protein levels (the receptor used by SARS-CoV2 to enter host airways cells), the risk of bacterial superinfections and masking of disease symptoms. As a consequence, the use of NSAIDs was, and is, strongly discouraged while the alternative adoption of paracetamol is still preferred.On the basis of novel data and hypothesis on the possible role of scarce glutathione (GSH) levels in the exacerbation of COVID-19 and of the GSH depleting activity of PAC, this commentary raises the question of whether PAC may produce an oxidative imbalance which could be detrimental in COVID-19 clinical outcomes.

Abstract: This work is part of the interest of solving the problems of water contamination with last generation pollutants, for which a novel and in an aqueous medium FeBTC material incorporated with magnetite nanoparticles was proposed. That material was synthesized by in situ solvothermal method, the Fe3O4 nanoparticles were added during the Fe-BTC MOF synthesis and used in the drug’s adsorption. The materials were characterized by XRD, FTIR and Raman spectroscopy, and N2-physisorption at 77 K. Fe3O4-FeBTC material showed a maximum adsorption capacity of 357.1 mg g−1 for diclofenac sodium, 70.9 mg g−1 for naproxen sodium, and 122.9 mg g−1 for Ibuprofen. A pseudo-second-order kinetic model can describe the adsorption process, and the thermodynamic study revealed that the adsorption of the three drugs was a feasible, spontaneous, and exothermic process. The incorporation of magnetite nanoparticles in the FeBTC considerably increased the adsorption capacity of pristine FeBTC. Also, hybridization of the FeBTC with magnetite nanoparticles reinforced the most vulnerable part of the MOF, increasing its thermal and aqueous media stability. The electrostatic interaction, H-bonding, and interactions in the open-metal sites played a vital role in drug adsorption. The competition of sites in the multicomponent mixture's adsorption showed selective adsorption at diclofenac sodium and naproxen sodium.

HCC is a highly aggressive malignancy with limited treatment options. In this study, novel conjugates, of NSAIDs - Ibuprofen and Ketoprofen with oleanolic acid oximes derivatives (OAO) were synthesized and their activity as modulators of signaling pathways involved in HCC pathogenesis was evaluated in normal THLE-2 liver cells and HCC derived HepG2 cells. The results demonstrated that conjugation with OAO derivatives reduces the cytotoxicity of parent compounds in both cell lines. In THLE-2 cells treatment with conjugates resulted in increased activation of the Nrf2-ARE pathway. An opposite effect was observed in HepG2 cells. In the later reduction of NF-κB was observed along with modulation of MAPK signaling pathways (AKT, ERK, p38, p70S6K, and JNK). Moreover, STAT3, STAT5, and CREB transcription factors on protein levels were significantly reduced as a result of treatment with IBU- and KET-OAO derivatives conjugates. The most active were conjugates with OAO-morpholide. Overall, the findings of this study demonstrate that IBU-OAO and KET-OAO derivatives conjugates modulate the key signaling pathways involved in hepatic cancer development. Their effect on specific signaling pathways varied depending on the structure of the conjugate. Since the conjugation of IBU and KET with OAO derivatives reduced their cytotoxicity, the conjugates may be considered good candidates for the prevention of liver cancer.

This perspective discusses the ongoing real-world practice using nitazxoanide, NSAIDs and/or azithromycin (Kelleni’s protocol) to manage the evolving manifestations of SARS CoV-2 Omicron EG.5.1, its descendant HV.1 as well as BA.2.86 and its descendant JN.1 subvariants in Egypt. These subvariants are well-known for their highly evolved immune-evasive properties and the manifestations include some peculiar manifestations as persistent cough besides high fever in young children as well as high fever, persistent severe cough, change of voice, loss of taste and smell, epigastric pain, nausea, vomiting, diarrhea, generalized malaise and marked bone aches in adults including the high risk groups. It’s suggested that the ongoing SARS CoV-2 evolution is continuing to mostly affect the high risk groups of patients, to some of whom we’ve also successfully prescribed nitazoxanide and/or NSAIDs for post-exposure prophylaxis of all household contacts. We also continue to recommend starting the immune-modulatory antiviral Kelleni’s protocol as soon as possible in the course of infection and adjusting it in a personalized manner to be more aggressive from the beginning for the high risk patients, at least until the currently encountered surge of infections subsides.

Pharmacogenomics (PGx) is the study of how variations of the patient genetic makeup could influence the selection and dosing of medications, including urate-lowering therapies (ULTs). Patients with gout present with several comorbidities, warranting the use of several long-term medications that increase their pill burden and the risk of adverse drug events. PGx testing can identify individuals who are more or less likely to benefit from a given treatment and ultimately improve adherence and reduce polypharmacy. Gout management involves using various ULTs associated with specific genetic variations that could modulate medication safety and efficacy. Individuals carrying the HLA-B*58:01 variant are at a higher risk of serious and life-threatening skin reactions from taking allopurinol. Besides, racial disparities in HLA-B distribution warrant testing for its status in high-risk populations, specifically some Asian subgroups and African Americans. G6PD-deficient individuals are prone to develop hemolytic anemia and methemoglobinemia with pegloticase and probenecid use. Patients with the less active form of the drug-metabolizing CYP2C9 are at higher risk for NSAID-related upper gastrointestinal (GI) bleeding. The drug-gene pair interactions among various gout therapies were also reviewed. Allopurinol-related genes included AOX, ABCG2, and SLC22A12. Febuxostat-related genes included UGT1A1. Benzbromarone- and probenecid- related genes included SLC22A12 and ABCB1. Colchicine-related genes included CYP2D6, ABCB1, rs6916345 G>A, and SEPHS1. Finally, the corticosteroid-related gene included HCG22; and the anakinra-related gene included IL1RA. This review synthesizes the most contemporary level of evidence for using PGx in gout pharmacotherapy, as referenced in the CPIC guidelines, FDA, PharmGKB, and current literature.

Perioperative acute pain management in pediatric patients is essential to reduce complications. Adenoidectomy-Tonsillectomy are surgical procedures requiring pain control, and risk minimization for postoperative bleeding, nausea, and vomiting. Despite their known secondary effects, the use of opioid analgesics remains preponderant in pediatric perioperative management. We present an updated review on perioperative pain management in children and describe the development and implementation of a multimodal analgesia protocol aimed to improve patients’ pain management while consistently reducing opioids use. Information from relevant articles was summarized, then compared to our clinical needs. Learnings were used to create and implement a multimodal analgesia protocol to be used in patients 3-9 years-old undergoing adenoidectomy/tonsillectomy. Analgesic strategies have emerged to reduce or avoid the use of opioids. Among these strategies, combining different non-opioid analgesics (Ibuprofen, Paracetamol, Metamizole) has been shown to be an effective and safe pharmacological strategy when implemented as part of postoperative multimodal analgesia protocols. Significant evidence associating the use of NSAIDs with a bigger risk of postoperative bleeding does not exist. Multimodal and preventive analgesia has shown to provide significantly more effective analgesia than some opioid regimens. Ibuprofen offers highly effective analgesia for postoperative pain, particularly when combined with acetaminophen.

Heel pain in the “funnel-shaped” space between the calcaneus, talus, and talocalcaneonavicular and subtalar joints may be representative of Sinus Tarsi syndrome. The pain is often characterized by a burning, numbness, or tingling sensation that can stem from strains and tears on the ligaments in that area. Injury treatment typically includes balance training, muscle exercises, bracing, foot orthosis, and non-steroidal anti-inflammatory drugs (NSAIDs). This study presents Wharton Jelly (WJ) tissue allografts as an alternative intervention for patients who fail standard-care treatments. WJ targets tissue defects, unlike other therapies, which aim to reduce swelling and symptomatic pain. This study includes five female patients who have previously failed standard-of-care treatment. Each received extracorporeal pulse-activated therapy (EPAT), WJ, laser therapy, and an orthotic. After an average of 80 days, the cohort had an overall 85.29% improvement in pain. The study's limitations include a small cohort size and a non-blinded design. Given the significant improvement in pain, WJ tissue allograft, combined with other techniques, presents an optimal patient care plan for tissue defects associated with Sinus Tarsi syndrome when standard-of-care treatments fail. These results provide evidence for a more extensive, randomized study to define dosage protocols further and confirm safety and efficacy.