Use Of Nonsteroidal Anti-inflammatory Drugs Research Articles

Non-steroidal anti-inflammatory drug use and inflammatory markers associated with gallbladder dysplasia: A case-control analysis within a series of patients undergoing cholecystectomy.

Inflammation has been associated with the development of gallbladder cancer (GBC). However, little is known about the associations of both, inflammation and the use of non-steroidal anti-inflammatory drugs (NSAIDs), with preneoplastic lesions. We analyzed the association of NSAIDs and gallbladder dysplasia in 82 patients with dysplasia and 1843 patients with gallstones among symptomatic patients from a high-risk population. We also analyzed associations for 33 circulating immune-related proteins in a subsample of all 68 dysplasia cases diagnosed at the time of sample selection and 136 gallstone controls. We calculated age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). Biliary colic was reported among most cases (97.6%) and controls (83.9%). NSAID use was inversely associated with gallbladder dysplasia (OR: 0.48, 95%CI: 0.26-0.83). Comparing the highest versus lowest category of each immune-related protein, eight proteins were inversely associated with dysplasia with sex- and age-adjusted ORs ranging from 0.30 (95%CI: 0.12-0.77) for IL-33 to 0.76 (95%CI: 0.59-0.99) for MIP-1B. Of those, GRO remained associated with dysplasia (OR: 0.64, 95%CI: 0.45-0.91) and BCA-1 was borderline associated (OR: 0.74, 95%CI: 0.54-1.01) after adjusting the logistic regression model for sex, age, and NSAIDs. In conclusion, NSAID users were less likely to have gallbladder dysplasia, suggesting that NSAIDs might be beneficial for symptomatic gallstones patients. The inverse association between immune-related markers and dysplasia requires additional research, ideally in prospective studies with asymptomatic participants, to understand the role of the inflammatory response in the natural history of GBC and to address the biological effect of NSAIDs.

Uterine stromal but not epithelial PTGS2 is critical for murine pregnancy success.

Use of non-steroidal anti-inflammatory drugs that target prostaglandin synthase (PTGS) enzymes have been implicated in miscarriage. Further, PTGS2-derived prostaglandins are reduced in the endometrium of patients with a history of implantation failure. However, in the mouse model of pregnancy, peri-implantation PTGS2 function is controversial. Some studies suggest that Ptgs2 -/- mice display deficits in ovulation, fertilization, and implantation, while other studies suggest a role for PTGS2 only in ovulation but not implantation. Further, the uterine cell type responsible for PTGS2 function and role of PTGS2 in regulating implantation chamber formation is not known. To address this we generated tissue-specific deletion models of Ptgs2 . We observed that PTGS2 ablation from the epithelium alone in Ltf cre/+ ; Ptgs2 f/f mice and in both the epithelium and endothelium of the Pax2 cre/+ ; Ptgs2 f/f mice does not affect embryo implantation. Further, deletion of PTGS2 in the ovary, oviduct, and the uterus using Pgr cre/+ ; Ptgs2 f/f does not disrupt pre-implantation events but instead interferes with post-implantation chamber formation, vascular remodeling and decidualization. While all embryos initiate chamber formation, more than half of the embryos fail to transition from blastocyst to epiblast stage, resulting in embryo death and resorbing decidual sites at mid-gestation. Thus, our results suggest no role for uterine epithelial PTGS2 in early pregnancy but instead highlight a role for uterine stromal PTGS2 in modulating post-implantation embryo and implantation chamber growth. Overall, our study provides clarity on the compartment-specific role of PTGS2 and provides a valuable model for further investigating the role of stromal PTGS2 in post-implantation embryo development.

Making Sense of Topical Pain Relief Options: Comparing Topical Analgesics in Efficacy and Safety.

In patients with musculoskeletal (MSK) conditions, pain is the leading contributor to disability and significantly limits mobility and dexterity. This narrative review describes the efficacy and safety of topical analgesics in common use today. Secondary literature gained via a literature search using PubMed.gov and the Cochrane library were used. Recent literature (2000-2023) on several major classes of topical analgesics and topical delivery systems were reviewed to provide strength of recommendation taxonomy (SORT) levels. A total of 86 articles were reviewed. Level 2. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) and cabbage leaf wraps (CLW) appear to be best suited for multiple types of acute MSK pain, and topical nitroglycerin is helpful when used specifically for rotator cuff pain in patients seeking relief while performing activities of daily living and willing to treat for long periods of time. For compounded topical formulations, it may be better to offer single agent creams based on patient preferences. Little data support the use of cryotherapy. Traumeel could be a promising natural analgesic that compares with diclofenac. Topical lidocaine appears best suited for postherpetic neuropathic pain. O24 is a reasonable alternative with a low risk profile to treat pain in patients with fibromyalgia syndrome. Choice of topical agents should be guided by current evidence accounting for type of pain, medication side effects, patient comorbidities, as well as patient preference, convenience, and cost. Of the topical analgesics and modalities reviewed, SORT level A evidence was found for topical NSAID use in decreasing MSK pain, topical lidocaine for postherpetic neuralgia, and nitroglycerin patches for treating rotator cuff pain if used for prolonged periods of time. Alternative treatments such as CLW and Traumeel show promising results (SORT level B).

Prescription trends in Japanese advanced Parkinson's disease patients with non-motor symptoms: J-FIRST.

Non-motor symptoms (NMS) are important factors when selecting treatments for patients with advanced Parkinson's disease (PD). We sought to elucidate the prescribing practices for advanced PD patients with NMS in Japanese clinical practice. We examined the prescription rates and doses of anti-PD drugs, and the use of non-steroidal anti-inflammatory drugs (NSAIDs) in post hoc analyses of a 52-week observational study of 996 PD patients with wearing-off on levodopa-containing therapy and ≥1 NMS. Dopamine agonists were the most frequently prescribed drugs combined with levodopa-containing drugs, followed by entacapone, zonisamide, istradefylline, selegiline, and amantadine. The daily dose of levodopa-containing drugs, rotigotine, entacapone, istradefylline, and droxidopa, and the levodopa-equivalent dose increased during the observation period. In a subgroup analysis of patients stratified by NMS status (improved/unchanged/deteriorated), the deteriorated group had higher prescription rates of entacapone and istradefylline, whereas the improved group had higher prescription rates of NSAIDs and zonisamide at Week 52. Prescriptions varied by geographical region for anti-PD drugs and by NMS status for NSAIDs. There were significant changes in the prescriptions and dosing of selected anti-PD drugs, especially newer drugs. Anti-PD drug and NSAID prescriptions also varied by changes in NMS status and geographic region.

Does Nonsteroidal Anti-inflammatory Drug Use Modify All-Cause and Cause-Specific Mortality Associated with PM2.5 and Its Components? A Nationally Representative Cohort Study (2007–2017)

Does Nonsteroidal Anti-inflammatory Drug Use Modify All-Cause and Cause-Specific Mortality Associated with PM_2.5 and Its Components? A Nationally Representative Cohort Study (2007–2017)

Association of initial serum sodium change and clinical outcome in patients with diabetes receiving sodium-glucose cotransporter-2 inhibitor therapy: A multicentre database analysis in Taiwan.

The study aimed to assess the impact of varying degrees of initial serum sodium change among patients with type 2 diabetes (T2D) starting sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy and their subsequent clinical outcome. We used medical data from a multicentre health care provider in Taiwan and recruited 4400 patients with T2D with baseline normal serum sodium (135-145 mmol/L) and follow-up serum sodium measures available after 3 months of SGLT2i treatment from 1 June 2016 to 31 December 2021. After a median of 2.9 (2.4, 3.4) months of SGLT2i treatment, overall, there was a minimal change in serum sodium levels (from 139.6 ± 2.4 to 139.5 ± 3.7 mmol/L). Most patients (87.8%) maintained normal sodium levels, while 8.6% (n = 378) experienced hyponatraemia (<135 mmol/L) and 3.6% (n = 158) hypernatraemia (>145 mmol/L). Factors independently associated with hyponatraemia included cancer history, chronic lung disease, insulin use, higher glycated haemoglobin, impaired liver function, lower baseline sodium and greater initial decline in kidney function. Conversely, factors linked to hypernatraemia included older age, absence of cancer history, loop diuretic and non-steroidal anti-inflammatory drug use, higher baseline sodium and a lesser initial decline in kidney function. Over a median of 26.0 months of follow-up, hyponatraemia shortly after starting SGLT2i therapy was associated with significantly increased risks of major adverse cardiovascular events [hazard ratio (HR): 2.52; 95% confidence interval (CI): 1.83-3.48], heart failure for hospitalization (HR: 1.66; 95% CI: 1.16-2.37), major adverse renal events (HR: 2.27; 95% CI: 1.73-2.96) and all-cause death (HR: 2.98; 95% CI: 2.17-4.11) after adjusting for clinically relevant factors. Non-linear analysis indicated that a more pronounced initial decline in serum sodium levels correlated steeply with higher risks of these adverse events. While most patients with T2D maintain stable serum sodium homeostasis on SGLT2i therapy, a subset may experience dysnatraemic events with potential worse clinical consequences. Physicians should be vigilant about monitoring sodium levels and considering the associated risks when initiating SGLT2i therapy in patients with risk.

Celecoxib in rheumatic diseases: possibilities and prospects. Brief descriptive survey

Chronic pain is the main manifestation of rheumatic diseases (RD), it determines the main complaints and worsens the quality of life of patients. The problem of effective control of chronic pain in rheumatology remains a current issue despite the successes in the development of new drugs for pathogenetic therapy, especially in immunoinflammatory RD. For example, 40-50% of patients with rheumatoid arthritis (RA), even those receiving biologic disease-modifying antirheumatic drugs and Janus kinase inhibitors, require analgesics. According to several population studies, about 50% of patients with the most common RD, osteoarthritis (OA) are forced to take various analgesics on a regular basis.The most popular class of analgesics with proven efficacy in RA, spondyloarthritis (SpA) and OA are non-steroidal anti-inflammatory drugs (NSAIDs). As has been shown in several meta-analyses, NSAIDs are superior to placebo and paracetamol in their therapeutic effect, are not inferior to opioids and are better tolerated overall. However, the use of NSAIDs can be associated with the development of dangerous adverse events (AEs), which requires careful monitoring of the patient's condition, considering comorbid diseases and risk factors. It is very important to choose a drug with a balanced ratio of efficacy and low risk of gastrointestinal and cardiovascular AEs. One such drug is celecoxib, whose therapeutic potential and relative safety have been confirmed in RA, SpA and OA. A differentiated approach to celecoxib prescription makes it possible to achieve a maximum therapeutic result with a minimum risk of AEs. For severe pain, treatment starts with a dose of 400 mg/day, followed by a switch to a maintenance dose of 200 mg/day.

Risk Factors Associated with Gastritis among Adult Patients Attending at Capital Hospital in Mogadishu- Somalia

Background: Gastritis, an inflammatory disorder affecting the lining of the stomach, is a prevalent health concern across the globe, particularly in developing regions like Somalia. This study aims to investigate the primary risk factors linked to gastritis among adults receiving care at Capital Hospital in Mogadishu.  Methods: An unmatched case-control study was executed from June 1 to July 30, 2024, involving 63 adult participants, with 21 patients diagnosed with gastritis through endoscopic procedures and 42 controls. A semi- structured questionnaire was employed to gather data on socio-demographic characteristics, dietary patterns, lifestyle habits, medical histories, and medication usage. Statistical analysis was performed using SPSS version 26.  Results: The investigation revealed a gastritis prevalence of 78.8%, with acute cases constituting 48.9% and chronic cases 29.9%. Female participants were identified as having a protective effect against gastritis (Adjusted Odds Ratio [AOR]=0.05, p=0.023), whereas the routine use of non-steroidal anti-inflammatory drugs (NSAIDs) significantly raised the risk (Crude Odds Ratio [COR]=5.03, p=0.041). Interestingly, the presence of Helicobacter pylori was associated with a reduced risk of developing gastritis (COR=0.11, p=0.032). Other lifestyle and dietary factors did not show significant correlations.  Conclusions: The results underscore the protective influence of gender and the associated risks of NSAID intake regarding gastritis among Somali adults. The unexpected finding of H. pylori infection linked to lower gastritis risk deserves further exploration. There is an urgent need for targeted public health strategies to address the effects of gastritis in Somalia.

Early drug treatment in preterm patients with large patent ductus arteriosus at 28 weeks or less gestational age: systematic review and meta-analysis.

Compare the use of nonsteroidal anti-inflammatory drugs (NSAIDs) with placebo/expectant management in preterm infants at 28 weeks or less gestational age with a large Patent Ductus (PDA). A meta-analysis of RCTs following PRISMA guidelines comparing the use of NSAIDs with placebo/expectant management in extremely preterm infants with a large PDA. There were no significant differences between the NSAIDs and placebo/expectant groups for all-cause mortality (RR 1.27; 95% CI 0.97-1.65; p = 0.081). However, the ibuprofen subgroup showed a significant difference in all-cause mortality (RR 1.36; 95% CI 1.03-1.80; p = 0.03) favoring the placebo/expectant group. In extremely preterm infants with a large PDA on ultrasound, early treatment with NSAIDs provides no additional clinical benefit compared to placebo/expectant treatment. Ibuprofen was associated with an increased risk ratio for all-cause mortality in the subgroup analysis.

Non-Steroidal Anti-Inflammatory Drugs: What Is the Actual Risk of Chronic Kidney Disease? A Systematic Review and Meta-Analysis.

Non-steroidal anti-inflammatory drugs (NSAIDs) are common cause of acute kidney injury, but chronic kidney disease (CKD) risk of NSAIDs is controversial. Prior systematic reviews are outdated with some methodological flaws. We conducted this systematic review to clarify the association between chronic NSAIDs use and occurrence and/or progression of CKD. MEDLINE, Cochrane Library, Web of Science and Science direct were searched for observational and interventional studies from inception to May 2023. Qualitative synthesis was performed. The meta-analysis used pooled odds ratios (OR) and hazard ratios (HR) to estimate the association between chronic NSAID use and CKD occurrence or progression. Forty studies with a total of 1757118 participants were included in the systematic review; of them 39 studies were suitable for meta-analysis. 56% of our included studies were recent, published within the last 10 years. The meta-analysis revealed a significant association between chronic NSAIDs use and CKD occurrence and progression. The pooled odds ratio was 1.24 (95% CI: 1.11-1.39, p <0.001, I² = 91.21%), and the pooled hazard ratio was 1.50 (95% CI: 1.31-1.7, p <0.001, I² = 90.77%). The pooled hazard ratio (HR) for individuals with no CKD at baseline was 1.31 (95% CI, 1.26-1.40), while for those with preexisting CKD, the HR was significantly higher at 1.67 (95% CI, 1.38-2.02). The HR for individuals with no specific chronic disease was 1.6 (95% CI, 1.32-1.94). For populations with diabetes mellitus (DM) and/or hypertension (HTN), the HR was 1.35 (95% CI, 1.27-1.43), and for those with rheumatic disease, the HR was 1.36 (95% CI, 0.88-2.10). Long-term NSAID use increases the risk of chronic kidney disease (CKD) occurrence and progression, especially in individuals with pre-existing CKD, who have a 67% risk compared to the general population's 60%. A patient-centered approach for safe and effective pain management is crucial, with special caution for those with pre-existing CKD.

Intraoperative Factors Affecting Pain Management and Postoperative Narcotic Use in Cranial Vault Remodeling: A Retrospective Review

Perioperative pain control in open cranial vault reconstruction (CVR) poses significant challenges. Narcotic use may confound signs of neurological deterioration and cause medication-induced complications. Previous studies have shown improved health outcomes in CVR with reduced narcotic use. The purpose of this study was to investigate the relationship between modifiable intraoperative factors on postoperative narcotic use. A retrospective cohort study was performed on 237 patients with craniosynostosis who presented to a tertiary pediatric hospital over a 10-year period for open CVR. There was a statistically significant relationship between total fluid volume infused intraoperatively (mL/kg) and total morphine equivalents (MEs, mL/kg) given throughout hospitalization (P&lt; 0.001). Longer operative times were associated with greater total hospitalization ME (P ≤ 0.006) and total intraoperative blood products transfused (P ≤ 0.001). Patients who received drains were given significantly higher total hospitalization ME compared with those who did not (P&lt; 0.001). Patients who received postoperative nonsteroidal anti-inflammatory drugs required significantly fewer total ME compared with children who did not (P&lt; 0.005) and patients who received intraoperative tranexamic acid were less likely to require postoperative blood transfusion (P&lt; 0.001). Postoperative nonsteroidal anti-inflammatory drug use is associated with decreased narcotic requirements during the immediate postoperative period whereas increased fluid requirements intraoperatively, longer operative durations, and drain placement are associated with higher narcotic use. Modifying intraoperative factors like these may lead to decreased postoperative pain, thus limiting narcotic use for patients, and improving overall outcomes.

Association between gastroprotective agents and acute kidney injury in patients receiving non-steroidal anti-inflammatory drugs: Analysis of a Japanese hospital-based database.

The concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) potentially increases the risk of acute kidney injury (AKI). However, the risk of AKI has not been comprehensively assessed for the concomitant use of NSAIDs with gastroprotective agents such as misoprostol and PPIs. The objective of this study was to evaluate whether the use of various gastroprotective agents affects the risk of AKI in patients receiving NSAIDs. The data analyzed were obtained from the JMDC hospital-based administrative claims database between April 2014 and August 2022. Histamine-2 receptor antagonists (H2RAs) were compared with PPIs or misoprostol in patients receiving NSAIDs. The primary outcome was the incidence of AKI. The covariates considered were age and sex, admission to intensive care unit, presence of comorbidities based on the modified Charlson Comorbidity Index, and use of renin-angiotensin system inhibitors, loop diuretics, other diuretics, and lithium. AKI was identified by changes in serum creatinine. The distribution of AKI was analyzed using the log-rank test, and estimates of the incidence of AKI were compared among the groups using a Cox proportional hazards model with time-varying variables. Models were adjusted using a doubly robust method that accounts for the inverse probability of treatment weighting at baseline while adjusting for covariates. After screening, 11,688 patients were eligible for inclusion (1729 for H2RAs, 368 for misoprostol, and 9591 for PPIs). AKI occurred in 0.5% of H2RA recipients and 1.1% of PPI recipients; no AKI was observed in the misoprostol group. Compared with H2RAs, the risk of AKI tended to be higher with PPIs (adjusted hazard ratio 1.83, 95% confidence interval 0.92-3.63, p = 0.08). Compared with H2RAs, PPIs may increase the risk of AKI in patients receiving NSAIDs, although no statistically significant difference was observed. Further research is required to assess the risk trade-off with consideration of both peptic ulcer prevention and the increased risk of AKI in patients concurrently treated with NSAIDs and H2RAs, misoprostol, or PPIs.

Trends and hospital practice variation for analgesia for children with sickle cell disease with vaso-occlusive pain episodes: An 11-year analysis

This cross-sectional analysis of 86,111 visits for sickle cell disease and vaso-occlusive episodes (VOE) in U.S. pediatric emergency departments between 2013 and 2023 shows increased use of NSAIDs, ketamine, and acetaminophen, with unchanged opioid use. Hospitals with a higher volume of VOE visits more frequently administered opioids. BackgroundVaso-occlusive episodes (VOEs) are a hallmark of sickle cell disease (SCD), leading to frequent emergency department (ED) visits. Effective pain management is crucial, with guidelines recommending routine use of non-steroidal anti-inflammatory drugs (NSAIDs) with opioids, and emerging evidence supporting ketamine use. However, these recommendations are based on low-certainty evidence, and the impact of these guidelines on analgesia use over time remains unclear. ObjectiveThis study aimed to analyze trends in analgesia use over an 11-year period in pediatric SCD patients presenting to U.S. EDs with VOE and assess variations in treatment across hospitals. MethodsA cross-sectional study was conducted using data from the Pediatric Health Information System covering 34 U.S. children's hospitals from January 1, 2013, to December 31, 2023. The primary outcomes were the proportions of visits where opioids, NSAIDs, acetaminophen, and/or ketamine were administered on the first calendar day of the initial visit. Secondary outcomes included the co-administration of NSAIDs with opioids. Logistic and linear regression models were used to assess trends and hospital-level variations. ResultsA total of 86,111 ED visits for VOE were analyzed. Opioids were administered in 82 % of encounters, NSAIDs in 72 %, acetaminophen in 17 %, and ketamine in 1 %. Co-administration of NSAIDs with opioids occurred in 59 % of the visits. Among discharged patients, there was a positive trend for NSAID use (slope: 1.68 %/year, 95 % CI: 0.91 %, 2.45 %) and NSAID-opioid co-administration (slope: 1.03 %/year, 95 % CI: 0.37 %, 1.69 %) over time. Acetaminophen use also increased over the study period (slope: 0.99 %/year, 95 % CI: 0.80 %, 1.17 %). In hospitalized patients, there was a significant upward trend for acetaminophen (slope: 1.29 %/year, 95 % CI: 0.69 %, 1.89 %) and ketamine (slope: 0.36 %/year, 95 % CI: 0.27 %, 0.45 %), while opioid use remained unchanged. Significant hospital-level variations were observed, with larger hospitals more likely to administer opioids but less likely to co-administer NSAIDs with opioids compared to medium-volume hospitals. ConclusionOver the past decade, the use of NSAIDs, acetaminophen, and ketamine has increased in the management of VOE in pediatric SCD patients, while opioid use remains consistent. The co-administration of NSAIDs and opioids has also increased, reflecting guideline adherence. Variations in analgesia practices across hospitals underscore the need for standardizing pain management strategies in this population.

Experience of preputiotomy performing in bull with acroposthitis and fibrous affect of penis’ S-shaped curve

The aim of this study was to perform a preputiotomy with the formation of an artificial opening in a breeding bull to realize his reproductive potential. Scientific and production research was conducted in the spring of 2024. In a 3.5-year-old Holstein breeding bull, kept at a breeding station for keeping breeding bulls, acroposthitis and fibrous lesion of the penis in the area of the S-shaped bend were detected due to the developed infectious process caused by Pseudomonas aeruginosa. The resulting pathology prevented the penis from fully extending beyond the preputial sac when collecting sperm for an artificial vagina (the last sperm collection was performed on 02/07/2024). The operation performed consisted of the following stages: insertion of a thick-walled tube into the preputial sac for better orientation in the tissues; making a V-shaped incision of all layers of the prepuce near its fornix; excision of the prepuce section necessary for free removal of the penis when collecting sperm; formation of an artificial opening by connecting the parietal preputial layer to the skin with an interrupted suture. The postoperative period included daily monitoring of the animal's condition, antibiotic therapy (amoxicillin (0.15 g), three injections every 48 hours), and the use of non-steroidal anti-inflammatory drugs (meloxicam (0.002 g), 3 days). A month after the operation, sperm was collected (06.05.2024, three months later) and the presence of all unconditioned reflexes was noted. At the same time, the copulatory reflex was full, painless and ended in ejaculation. The obtained volume of sperm after two mountings was 2.5 ml, the concentration was 1.3x108, the activity was 8 points. Thus, preputiotomy is an effective method for surgical correction of lesions of the preputial sac and adhesions in the area of the S-shaped bend of the penis in breeding bulls.

Prospective study of risk factors for community-acquired acute kidney injury

Background and hypothesisCauses and risk factors for community-acquired acute kidney injury (CA-AKI) have not been thoroughly studied. The aim of this study was to examine the risk factors for CA-AKI. MethodsIn this prospective study, we examined serum creatinine from all individuals visiting a university hospital's emergency department (ED) over an 11-month period for the presence of AKI defined according to the KDIGO criteria. Patients with AKI were invited to participate. Randomly selected controls (1:2) were paired according to age, sex, and date of admission. Participants answered questions about their medical history and medication use, including over-the-counter (OTC) drugs. Conditional logistic regression was used to identify factors associated with AKI. ResultsOf 602 AKI cases identified, 512 participated in the study. AKI cases were significantly more likely than controls to have used nonsteroidal anti-inflammatory drugs (NSAIDs) (26.0 % vs 18.0 %, p = 0,001) in the week preceding the ED visit, particularly OTC NSAIDs (23.3 % vs 15.9 %, p < 0.001). AKI was associated with a recent history of vomiting (OR 2.52 [95 %CI 1.87–3.39]), diarrhea (1.30 [1.00–1.70]) and urinary retention (1.92 [1.36–2.72]), use of non-selective NSAIDs (1.84, [1.37–2.48]), RAAS blockers (1.63 [1.21–2.19]), and diuretics (1.53 [1.13–2.08]), and a history of diabetes (1.42 [1.04–1.94]), CKD (1.36 [1.01–1.83]) and smoking (1.72 [1.24–2.37]). ConclusionsEvents in the setting of acute illness and medication use, including OTC NSAIDs, may play a greater role in the development of CA-AKI than comorbid conditions. Frequent use of OTC NSAIDs is a concern and should be addressed in view of serious adverse effects.

Enhancing Acute Migraine Treatment: Exploring Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for the Nose-to-Brain Route.

Migraine has a high prevalence worldwide and is one of the main disabling neurological diseases in individuals under the age of 50. In general, treatment includes the use of oral analgesics or non-steroidal anti-inflammatory drugs (NSAIDs) for mild attacks, and, for moderate or severe attacks, triptans or 5-HT1B/1D receptor agonists. However, the administration of antimigraine drugs in conventional oral pharmaceutical dosage forms is a challenge, since many molecules have difficulty crossing the blood-brain barrier (BBB) to reach the brain, which leads to bioavailability problems. Efforts have been made to find alternative delivery systems and/or routes for antimigraine drugs. In vivo studies have shown that it is possible to administer drugs directly into the brain via the intranasal (IN) or the nose-to-brain route, thus avoiding the need for the molecules to cross the BBB. In this field, the use of lipid nanoparticles, in particular solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), has shown promising results, since they have several advantages for drugs administered via the IN route, including increased absorption and reduced enzymatic degradation, improving bioavailability. Furthermore, SLN and NLC are capable of co-encapsulating drugs, promoting their simultaneous delivery to the site of therapeutic action, which can be a promising approach for the acute migraine treatment. This review highlights the potential of using SLN and NLC to improve the treatment of acute migraine via the nose-to-brain route. First sections describe the pathophysiology and the currently available pharmacological treatment for acute migraine, followed by an outline of the mechanisms underlying the nose-to-brain route. Afterwards, the main features of SLN and NLC and the most recent in vivo studies investigating the use of these nanoparticles for the treatment of acute migraine are presented.

Patterns of pain medication usage and self-reported pain in older Irish adults with osteoarthritis: A latent class analysis of data from the Irish Longitudinal Study on Ageing

BackgroundThis study aimed to identify and describe links between pain medication use and self-reported pain among people aged ≥ 50 years with osteoarthritis (OA) in an Irish population, and to examine the relationships between pain, medication usage and socioeconomic and clinical characteristics.MethodsSecondary data analysis of wave 1 cross-sectional data from The Irish Longitudinal Study on Ageing (TILDA) was undertaken of 1042 people with self-reported doctor-diagnosed OA. We examined use of medications typically included in OA clinical guidelines, including non-opioid analgesics (e.g. paracetamol), topical and oral non-steroidal anti-inflammatory drugs (NSAIDs), opioids and nutraceuticals. Latent Class Analysis (LCA) was used to identify underlying clinical subgroups based on medication usage patterns, and self-reported pain severity. Multinomial logistic regression was used to explore sociodemographic and clinical characteristic links to latent class membership.ResultsA total of 358 (34.4%) of the 1042 people in this analysis were taking pain medications including oral NSAIDs (17.5%), analgesics (11.4%) and opioids (8.7%). Nutraceutical (glucosamine/chondroitin) use was reported by 8.6% and topical NSAID use reported by 1.4%. Three latent classes were identified: (1) Low medication use/no pain (n = 382, 37%), (2) low medication use/moderate pain (n = 523, 50%) and (3) moderate medication use/high pain (n = 137, 13%). Poorer self-rated health and greater sleep disturbance were associated with classes 2 and 3; depressive symptoms and female gender were associated with class 2, and retirement associated with class 3.ConclusionsWhilst pain medication use varied with pain severity, different medication types reported broadly aligned with OA guidelines. The two subgroups exhibiting higher pain levels demonstrated poorer self-rated health and greater sleep disturbance.

Topical nonsteroidal anti-inflammatory drugs for management of pain after PRK: systematic review and network meta-analysis.

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) for management of pain in patients after photorefractive keratectomy (PRK). Pain after PRK is a major concern for both patients and surgeons. Although evidence supports the use of NSAIDs postoperatively, no consensus exists regarding the preferred regimen. The study aimed to compare the efficacy and safety of different topical NSAIDs. This study was prospectively registered with PROSPERO (ID: CRD42023417651). A systematic search of electronic databases was performed, for randomized controlled trials reporting topical NSAIDs' outcomes of corneal re-epithelization, rescue analgesics intake, and pain in days 0 to 3 after PRK (postoperative days [PODs] 0 to 3). Studies were graded for risk of bias. Data were extracted, and standardized mean differences (SMDs) were evaluated in a network meta-analysis in accordance with the Cochrane's guidelines, to which a frequentist approach model was fitted. Transitivity was assessed using the net split method. Treatment effectiveness was ranked using forest plots based on comparison with placebo. P-scores (P) and league tables were used to examine combined direct and indirect comparisons. Of 1540 studies identified, 27 were included. These encompassed 2286 patients across 11 countries, evaluating 7 distinct topical NSAIDs. At POD0, ketorolac (P 0.764), flurbiprofen (P 0.763), and bromfenac (P 0.717) were the most efficient drugs overall and displayed significantly lower pain scores than placebo. Other than that, flurbiprofen held the highest rank for reported pain throughout, significantly outperforming placebo on POD1 (P 0.874, SMD -1.19, 95% CI -1.86 to -0.52), POD2 (P 0.882, SMD -1.05, 95% CI -1.82 to -0.27), and POD3 (P 0.939, SMD -1.14, 95% CI -2.1 to -0.18). Other NSAIDs were significantly better than placebo only on POD1 and POD0. Rescue analgesic intake analysis favored indomethacin (P 0.834, SMD -0.8, 95% CI -1.33 to -0.27), ketorolac, and diclofenac. Compared with placebo, re-epithelization was slowed to different significances with all NSAIDs but flurbiprofen (P 0.991, SMD -0.7, 95% CI -1.38 to -0.03). Flurbiprofen was favorable in pain scores on typically painful postoperative days and re-epithelization times. However, analgesics intake, a more objective outcome, suggested superiority of other NSAIDs. Inconsistencies may be explained by the small sample size. For clinical interpretation, NSAID effect sizes should be taken into consideration.

Troxerutin effect on gastric ulcers induced by ketorolac in rats: Relation with oxidative stress

Gastric ulcers are an essential side effect associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs). Free radicals are one of the important mechanisms contributing to the development of gastric ulcers caused by NSAIDs. This prompted us to choose troxerutin, which has antioxidant and anti-inflammatory effects, especially with a lack of studies investigating the preventive effect of troxerutin on gastric ulcers. Twenty-nine rats were divided into five groups: A Vehicle group, a Keto group (30 mg/kg of ketorolac), and two troxerutin groups (150 mg/kg or 200 mg/kg of troxerutin, respectively). A Miso group was used as a reference with (100 μg/kg of misoprostol). Troxerutin and misoprostol were administered orally 1 h before ketorolac. The ulcer index was determined considering the numbers and severity of ulcerations. Gastric tissue inflammation was evaluation microscopically. Both thiobarbituric acid reactive substance levels and catalase activity were measured as markers of oxidative stress in gastric tissue. Our data showed an improvement in ulcer indices with troxerutin and misoprostol compared with ketorolac, with improvement in gastric inflammation observed with misoprostol but not with troxerutin. These results were accompanied by a reduction in gastric oxidative stress induced by ketorolac with both troxerutin and misoprostol. This study highlights, for the first time, the antioxidant effect of troxerutin on gastric ulcers. This effect may contribute to the good prevention of ketorolac-induced gastric ulcers.

Baseline and 2-year differences in spinal symptoms and spinal and hip mobility in early axial spondyloarthritis and non-axial spondyloarthritis chronic back pain patients

ObjectiveTo compare spinal symptoms and spinal/hip mobility at baseline and 2 years in early axial spondyloarthritis (axSpA) and non-axSpA chronic back pain (BP) patients.MethodsBaseline and 2 years data of the...