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INTRODUCTION: Overprescribing of acid suppressants is a common phenomenon in human and small animal patients, leading to potential deleterious gastrointestinal (GI) and non-GI consequences. The impact of consensus statements on veterinary prescribing habits in clinical practice have not been fully evaluated. This study aimed to compare the prescribing habits of the proton pump inhibitor (PPI), omeprazole, in dogs in an academic veterinary teaching hospital before and after the publication of the American College of Veterinary Internal Medicine (ACVIM) consensus statement on rational use of gastrointestinal protectants. METHODS: Evaluation of the prescribing habits of omeprazole in dogs during the years 2017 and 2021 was retrospectively compared. These years were selected to reflect a 12-month period prior to and following the publication of the consensus statement. One hundred dogs from each year were randomly selected. Dose, frequency of administration, duration of treatment, concurrent prescription of more than one gastroprotectant and indications for prescribing omeprazole were analyzed. RESULTS: A significant increase in the cases that received omeprazole q12h (p  0.0001) was detected after the publication of the 2018 ACVIM consensus statement. Considering the indications, there was also a significant increase in the appropriate prescription of omeprazole in the second compared to the first period of study (p

Staphylococcus aureus is a bacterial pathogen of considerable significance in public health, capable of inducing a diverse range of infectious diseases. One of the most notorious mechanisms used by S. aureus to survive and colonize the site of infection is its ability to form biofilms. Diflunisal, a non-steroidal antiinflammatory drug (NSAID), is a known inhibitor of the Agr system in S. aureus, which is key in regulating biofilm formation. This study evaluated the effect of broad-spectrum antibiotics in combination with diflunisal on S. aureus biofilm density. Eight antibiotics were tested independently at different concentrations and in combination with diflunisal to assess their effect on S. aureus biofilm formation. When using the antibiotics alone and with diflunisal, a significant control effect on biofilm formation was observed (p < 0.05), irrespective of diflunisal presence, but did not achieve a complete biofilm growth inhibition. Over time, diflunisal influenced biofilm formation; however, such an effect was correlated with antibiotic concentration and exposure time. With amikacin treatments, biofilm density increased with extended exposure time. In the case of imipenem, doripenem, levofloxacin, and ciprofloxacin, lower doses and absence of diflunisal showed higher control over biofilm growth with longer exposure. However, in all cases, diflunisal did not significantly affect the treatment effect on biofilm formation. In the absence of antibiotics, diflunisal significantly reduced biofilm formation by 53.12% (p < 0.05). This study suggests that diflunisal could be a potential treatment to control S. aureus biofilms, but it does not enhance biofilm inhibition when combined with antibiotics. [ABSTRACT FROM AUTHOR]

Copyright of Equine Veterinary Journal is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: With little to no regulation of the supplement markets and a paucity of quality information regarding clinical utility of individual marketed supplements, it is difficult for veterinarians to provide any evidence-based recommendations to owners. The current study aimed to provide clinically useful comparative efficacy data on certain marketed supplements. Methods: Using a prospective, block-randomized, double-blinded, placebo-controlled design, one hundred and one pet dogs with clinical hip OA-associated pain with one side worse than the other (index limb) were randomly assigned to one of four treatment groups: Green lipped Mussel plus Krill oil extracts (Antinol® Rapid, EAB-277); Biota orientalis extracts (4CYTE™ Epiitalis® Forte); an NSAID (meloxicam); or placebo (sunflower oil). Peak vertical force (PVF, expressed as a percentage of bodyweight) of the index limb, orthopedic assessment score (OAS) and hematology and blood chemistry values were evaluated before treatment (week 0), at 2, 4 and 6 weeks during treatment. Results: At 6 weeks, the changes from baseline in PVF of the index limb in the EAB-277 and meloxicam groups were significantly greater than the change in the placebo and 4CYTE™ groups, and the placebo and 4CYTE groups were not different from each other. At 6 weeks, there were significant differences between the groups for overall OAS scores with the lowest scores (least impairment) in the EAB-277 and meloxicam groups, followed by the 4CYTE group and then the placebo group. Discussion: Results of this study indicate that meloxicam and EAB-277 have significant objectively measured benefits in managing OA-related pain in dogs compared to placebo, but 4CYTE does not differ from placebo. [ABSTRACT FROM AUTHOR]

Background: Pseudophakic cystoid macular edema (PCME) is a known complication of cataract surgery that contributes to decreased visual acuity. Mechanical manipulation associated with the release of inflammatory mediators is the leading hypothesis for PCME. To date, no standardized prophylactic protocol has been established to effectively reduce the incidence of PCME. This study assessed the efficacy and safety of nonsteroidal anti-inflammatory drops (NSAIDs) and corticosteroids for the prevention of PCME. Method: We searched the following databases MEDLINE, EMBASE, and Cochrane Central. Register of Controlled Trials and included randomized controlled trials (RCTs) that studied the efficacy of NSAID vs. placebo, NSAID vs. steroid, or NSAID + steroid vs. placebo, reporting the incidence of PCME, macular thickness, and best-corrected visual acuity. The risk ratio (RR) with a 95% confidence interval (CI) and a random-effects model was used. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. Results: A total of 18 RCTs were included in this study (n = 2959). Nine RCT showed low risk of bias, 7 RCT showed unclear risk of bias, and 2 RCT had high risk of bias. The incidence of cystoid macular edema among patients treated with NSAIDs was significantly lower (RR = 0.33, P < 0.001). Subgroup analysis revealed a statistically significant low risk of edema among patients treated with NSAIDs alone (P < 0.001) compared to others. NSAIDs were associated with significantly low mean corrected visual acuity values using LogMar (P < 0.001). Conclusion: NSAID alone or in combination with steroids showed its efficacy in reducing the incidence of PCME post-operatively. Future double-blind randomized controlled trials are required to standardize the protocol for different patient population. [ABSTRACT FROM AUTHOR]

Introduction: With rapidly growing interest in the use of cannabidiol (CBD) in the management of pain and other conditions, more information is needed on the safety and efficacy of this supplement, particularly its co-administration with commonly used pharmaceuticals such as non-steroidal anti-inflammatory drugs (NSAIDs). This study sought to assess the effect of CBD in dogs with mobility impairments, as well as evaluate the clinical tolerance of CBD used together with NSAIDs. Materials and methods: Forty-two client-owned dogs with diagnosed mobility impairments were enrolled in this prospective, double-blind, crossover, placebo-controlled study. Baseline data were collected for 10-14 days followed by random allocation to either placebo or CBD oil for 45 days with a 30-day washout period in between. CBD was dosed at 5 mg/kg orally every 12 h with masked placebo administered at equal volume. Outcome measures included objective gait analysis, accelerometry, and clinical metrology instruments. CBD plasma levels and serum biochemistry were also collected along with hepatic ultrasound if warranted. Results: Thirty-eight dogs finished the study with thirty-nine included for at least partial analysis. Compared to baseline, dogs receiving CBD showed evidence of improved outcomes based on blinded veterinary assessments and accelerometer data. Compared to placebo, dogs receiving CBD showed some evidence of improved outcomes on CBPI, CSOM, and blinded veterinary assessments, but not for objective outcome measures. There was evidence of increased ALP when CBD was co-administered with NSAIDs compared to CBD administration alone. Additionally, there was evidence of ALT elevations with CBD and NSAID co-administration, but this elevation did not show evidence of an increase over CBD use alone. Discussion: These results suggest a potential therapeutic benefit in the administration of CBD for the management of mobility impairments, but greater ALP elevations were seen when administered with NSAIDs. While the sample size of dogs that received further hepatic work-up for liver enzyme elevations is small, chosen diagnostics varied, and liver biopsies were not performed, there did not appear to be clinically apparent liver damage. Further research is needed to better understand the efficacy of CBD in a larger population of dogs and patient tolerance and safety when administered with NSAIDs or other medications long term. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Our objectives were to compare the efficacy of ketoprofen or ceftiofur for treatment of metritis in dairy cows considering subsequent health, production, and reproduction. Cows from 2 commercial dairy farms in Ontario, Canada were examined with a Metricheck device 3 times per week from 2 to 14 DIM. Cows with metritis (fetid vaginal discharge; n = 193) were blocked by parity and fever (rectal temperature ≥39.5°C or <39.5°C) and within each block per farm, randomly assigned to receive 3 mg/kg BW of ketoprofen (KET) or 2.2 mg/kg of ceftiofur hydrochloride (CEF), once a day for 3 d. Day of enrollment was considered study d 0. Rectal temperature and attitude were evaluated in cows with metritis on study d 0, 3, 4, 7, 10, and 13, and vaginal discharge was evaluated on study d 4, 7, 10, and 13. Body condition was scored at enrollment and at 35 DIM, and serum concentration of haptoglobin was measured at d 0, 2, 4, and 7. Cows with rectal temperature ≥39.5°C or a depressed attitude on d 3 were classified as clinical failure and received treatment with ceftiofur for 3 d (KET), or 2 additional days (CEF), to a maximum of 5 d of treatment with ceftiofur. At 35 ± 3 DIM cows were examined for uterine involution via transrectal palpation, purulent vaginal discharge (PVD) via Metricheck, and endometritis via endometrial cytology. Time to onset of cyclicity was assessed by serum progesterone (P4) measurements at 28, 42, and 56 DIM. Contemporary cows from the same farms without metritis (NOMET; n = 1,043) were used for comparison. Data were analyzed with mixed linear or logistic regression or Cox's proportional hazard models, including herd as a random effect. The proportion of clinical resolution of metritis on d 3 (96% vs. 92%), of cows with fever (from d 3 to d 13 after enrollment) or fetid discharge (from d 4 to d 13 after enrollment), and the number of medical treatments (3.1 vs. 3.3) were not different between CEF and KET, respectively. Cows in KET received fewer antibiotic treatments than cows in CEF (0.3 vs. 3.1). Uterine involution, prevalence of PVD (50% vs. 47%) and subclinical endometritis (6.6% vs. 4.3%), and proportion of cyclic cows (82% vs. 86%) did not differ between CEF and KET. Cows in KET had greater serum haptoglobin concentration from d 2 to 7 after enrollment. The incidence of mastitis, lameness, or displaced abomasum to 60 DIM and subclinical ketosis to 21 DIM did not differ among CEF, KET, and NOMET. There were no differences in median time to first AI (CEF = 68 d, 95% CI: 65–70; KET = 69 d, 95% CI: 68–72; NOMET = 69 d, 95% CI: 68–70), median time to pregnancy (CEF = 118 d, 95% CI: 92–145; KET = 113 d, 95% CI: 90–135; NOMET = 105 d, 95% CI: 101–109), pregnancy at first AI at 33 d after insemination (CEF = 42%; KET = 41%; NOMET = 41%), pregnancy loss after first AI (CEF = 8%; KET = 11%; NOMET = 8%), hazard of pregnancy, or hazard of culling up to 300 DIM. Milk yield was not different between CEF and KET during the first 10 wk, but was lesser in KET at wk 2 and 4 and CEF at wk 2, 4, and 6 than in NOMET. In this pilot-scale study, given early detection, we did not detect differences in subsequent health, milk yield, or reproductive performance in cows with metritis initially treated for 3 d with CEF or KET. Additional, larger studies are warranted. [ABSTRACT FROM AUTHOR]

Copyright of Medicina Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Diclofenac is a hepatotoxic non-steroidal anti-inflammatory drug (NSAID) that affects liver histology and its protein expression levels. Here, we studied the effect of diclofenac on rat liver when co-administrated with either Yersinia enterocolitica strain 8081 serotype O:8 biovar 1B (D*Y) or Lactobacillus fermentum strain 9338 (D*L). Spectroscopic analysis of stool samples showed biotransformation of diclofenac. When compared with each other, D*Y rats lack peaks at 1709 and 1198 cm−1, while D*L rats lack peaks at 1411 cm−1. However, when compared to control, both groups lack peaks at 1379 and 1170 cm−1. Assessment of serum biomarkers of hepatotoxicity indicated significantly altered activities of AST (D*Y: 185.65 ± 8.575 vs Control: 61.9 ± 2.607, D*L: 247.5 ± 5.717 vs Control: 61.9 ± 2.607), ALT (D*Y: 229.8 ± 6.920 vs Control: 70.7 ± 3.109, D*L: 123.75 ± 6.068 vs Control: 70.7 ± 3.109), and ALP (D*Y: 276.4 ± 18.154 vs Control: 320.6 ± 9.829, D*L: 298.5 ± 12.336 vs Control: 320.6 ± 9.829) in IU/L. The analysis of histological alterations showed hepatic sinusoidal dilation with vein congestion and cell infiltration exclusively in D*Y rats along with other histological changes that are common to both test groups, thereby suggesting more pronounced alterations in D*Y rats. Further, LC–MS/MS based label-free quantitation of proteins from liver tissues revealed 74.75% up-regulated, 25.25% down-regulated in D*Y rats and 51.16% up-regulated, 48.84% down-regulated in D*L experiments. The proteomics-identified proteins majorly belonged to metabolism, apoptosis, stress response and redox homeostasis, and detoxification and antioxidant defence that demonstrated the potential damage of rat liver, more pronounced in D*Y rats. Altogether the results are in favor that the administration of lactobacilli somewhat protected the rat hepatic cells against the diclofenac-induced toxicity. [ABSTRACT FROM AUTHOR]

The impact of non-steroidal anti-inflammatory drugs (NSAIDs) on rotator cuff repair is an ongoing area of study within orthopedics, with conflicting results in current literature. Despite concerns over the deleterious effects of NSAIDs on rotator cuff healing, they are becoming an integral part of a multimodal post-operative pain control regiment. The purpose of this study was to compare post-operative patient-reported outcomes (PROs), complications rates, and retear rates of arthroscopic rotator cuff repairs in patients using ibuprofen post-operatively to those who abstained from NSAIDs for six weeks after surgery. It was hypothesized that a short course of ibuprofen post-operatively would not lead to inferior PRO scores, increased retear rates, nor increased complication rates after arthroscopic rotator cuff repair. Patients of the primary surgeon who underwent arthroscopic rotator cuff repair between 2012 and 2022 were evaluated by retrospective chart review. In May 2017 the primary surgeon changed his protocol from avoiding NSAIDs for six weeks after surgery to routinely prescribing two weeks of Ibuprofen 800 mg TID post-operatively. Patients who avoided NSAIDs for six weeks were compared to patients who were prescribed NSAIDs post-operatively. Patient demographic data, pre-operative MRI results, pre-operative and post-operative PROs were collected from the EMR. Additionally, post-operative complications and repair failures requiring reoperation within one year were evaluated. 125 patients met inclusion criteria for this study with 36 patients in the NSAID group and 89 in the no NSAID group. When comparing improvement in PROs, the NSAID group reached MCID at one year in 83.8 % of patients and the no NSAID group reached MCID at one year in 73.9 % of patients. There was no significant difference between the groups in reaching MCID improvement at one year (p = 0.471). Five post-operative complications were reported in the no NSAID group and two in the NSAID group (5.7 % vs 5.4 %, respectively, p = 0.827). Finally, there was no significant difference in the percentage of post-operative rotator cuff repair failures requiring revision in the first year between the groups (2.3 % vs 2.7 %, p = 1.000). There was no difference in percent of patients improving their PRO by the MCID between the groups that used ibuprofen and the group that did not. There was also no difference in post-operative complication rates and rates of symptomatic retear requiring reoperation between the groups. This supports that a short course of NSAIDs post-operatively, specifically ibuprofen, after rotator cuff repair does not increase reoperation rates nor lead to a clinically significant decrease in PROs at one year. [ABSTRACT FROM AUTHOR]

Introduction: Upper gastrointestinal bleeding (UGIB) is among the most common causes of morbidity and mortality worldwide, accounting for major resource allocation and increasing incidence. This study aimed to evaluate the severity of non-variceal bleeding in patients at risk of bleeding through the use of NSAIDs, oral anticoagulants, and antiplatelet therapy. Material and Method: The study included 296 patients admitted in the Gastroenterology Department of the Municipal County Emergency University Hospital, Timisoara, between 01.01.2018 and 01.04.2020, and diagnosed via gastroscopy with non-variceal gastrointestinal bleeding. The patients were divided among four groups based on their use of different drugs known to induce UGIB, i.e., aspirin and clopidogrel, NOACs, NSAIDs, and anti-vitamin K drugs, respectively. Statistical analyses were performed based on ANOVA one-way tests for continuous variables and Chi-square tests for categorical variables with pairwise comparisons based on Bonferroni adjusted significance tests. Results: The results showed several parameters having statistical significance among the different groups of patients. Patients on NOACs had statistically significant lower hemoglobin levels, lower hematocrit values, lower erythrocytes, lower RDW and higher fibrinogen levels compared to patients on VKA. Discussion: Surprisingly, the results from our study suggest that the use of NOACs was associated with a higher risk of bleeding when compared to VKA, which differs from the existing literature. Conclusions: One of the important factors causing upper non-variceal bleeding can be iatrogenic, either due to antiplatelet drugs or anticoagulants, to which NSAID treatment is additionally associated for various reasons. In our study, the use of NOACs seemed to have a more severe bleeding spectrum with higher morbidity compared to VKA. [ABSTRACT FROM AUTHOR]

After understanding the biological signaling roles of hydrogen sulfide and its involvement in various physiological processes, there has been enormous interest in exploring its therapeutic utility in areas such as cancer, inflammation, cardiovascular diseases, etc. There is also growing interest in using suitable H2S donors in combination with other drugs to improve the treatment outcome through the modulation of multiple pathways. The premature release of H2S from small molecule donors and the difficulty in controlling its spatio‐temporal distribution are the major challenges during these efforts. Hence the development of appropriate carriers that can release this gasotransmitter along with the therapeutic entity of interest in a controlled manner has high significance. In this regard, this report presents a novel drug delivery system from oxanorbornane‐based synthetic lipids that carries a H2S‐releasing 1,2‐dithiole‐3‐thione moiety as part of the head group. Nanoaggregates of the resulting conjugate are not only capable of efficiently entrapping a non‐steroidal anti‐inflammatory drug such as ibuprofen, but also release this drug and H2S in a controlled and sequential manner. [ABSTRACT FROM AUTHOR]

Parenteral ketorolac and intravenous (IV) acetaminophen have been used for prehospital analgesia, yet limited data exist on their comparative effectiveness. To evaluate the comparative effectiveness of IV acetaminophen and parenteral ketorolac for analgesia in the prehospital setting. We conducted a retrospective cross-sectional evaluation of patients receiving IV acetaminophen or parenteral ketorolac for pain management in a large suburban EMS system between 1/1/2019 and 11/30/2021. The primary outcome was change in first to last pain score. Subgroup analysis was performed on patients with traumatic pain. We used inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) to estimate the treatment effect of acetaminophen versus ketorolac among all patients and the subgroup of those with traumatic pain. Of 2178 patients included, 856 (39.3%) received IV acetaminophen and 1322 (60.7%) received parenteral ketorolac. The unadjusted mean change in pain score was −1.9 (SD 2.4) for acetaminophen group and −2.4 (SD 2.4) for ketorolac. In the propensity score analyses, there was no statistically significant difference in pain score change for the acetaminophen group versus ketorolac among all patients (mean difference, IPTW: 0.11, 95% confidence interval [CI] −0.16, 0.37; PSM: 0.15, 95% CI −0.13, 0.43) and among those with traumatic pain (unadjusted: 0.18, 95% CI −0.35, 0.72; IPTW: 0.23, 95% CI −0.25, 0.71; PSM: −0.03, 95% CI −0.61, 0.54). We found no statistically significant difference in mean pain reduction of IV acetaminophen and parenteral ketorolac for management of acute pain. [ABSTRACT FROM AUTHOR]

This study aimed to assess the anti-inflammatory properties of a bioactive glutamic-alanine rich glycoprotein (GP) derived from Undaria pinnatifida on both LPS-stimulated RAW264.7 cells, peritoneal macrophages, and mouse models of carrageenan- and xylene-induced inflammation, investigating the underlying molecular mechanisms. In both in-vitro and in-vivo settings, GP was found to reduce the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) while also inhibiting the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in response to lipopolysaccharide (LPS) stimulation. GP treatment significantly impeded the nuclear translocation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by blocking the phosphorylation of IKKα and IκBα, leading to a reduction in proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Additionally, GP effectively inhibited the activation of mitogen-activated protein kinases (MAPKs), with specific inhibitors of p38 and extra-cellular signal regulated kinase (ERK) enhancing GP's anti-inflammatory efficacy. Notably, GP administration at 10 mg/kg/day (p.o.) markedly reduced carrageenan-induced paw inflammation and xylene-induced ear edema by preventing the infiltration of inflammatory cells into targeted tissues. GP treatment also downregulated key inflammatory markers, including iNOS, COX-2, IκBα, and NF-κB, by suppressing the phosphorylation of p38 and ERK, thereby improving the inflammatory index in both carrageenan- and xylene-induced mouse models. These findings suggest that marine resources, particularly seaweeds like U. pinnatifida, could serve as valuable sources of natural anti-inflammatory proteins for the effective treatment of inflammation and related conditions. [ABSTRACT FROM AUTHOR]

The aim of this paper was to present a rapid, simple, and straightforward high-performance liquid chromatography (HPLC) method for the determination of robenacoxib in plasma. Robenacoxib is a member of the COXIB group of nonsteroidal anti-inflammatory drugs developed for veterinary use. The method was validated based on the FDA Guidance for Industry: Bioanalytical Method Validation for selectivity, linearity, accuracy, precision, stability, and recovery. Methylene chloride was used in a liquid–liquid extraction that produced an average recovery of 97%. Chromatographic separation occurred on a Sunfire C18 column (4.6 × 150 mm) using an isocratic combination of 0.025% trifluoroacetic acid in water and acetonitrile (50:50, v/v). Ultraviolet absorbance was measured at 275 nm and the flow rate was 1.1 mL/min. The method was linear in the concentration range of 0.1 to 50 µg/mL. The assay variability ranged from 2.2% to 9.2% while the accuracy was 100%. The lower limit of quantification for a 0.1 mL sample size was 0.1 µg/mL. The method was used for the determination of robenacoxib in plasma samples. [ABSTRACT FROM AUTHOR]

Abstract Background Pseudophakic cystoid macular edema (PCME) is a known complication of cataract surgery that contributes to decreased visual acuity. Mechanical manipulation associated with the release of inflammatory mediators is the leading hypothesis for PCME. To date, no standardized prophylactic protocol has been established to effectively reduce the incidence of PCME. This study assessed the efficacy and safety of nonsteroidal anti-inflammatory drops (NSAIDs) and corticosteroids for the prevention of PCME. Method We searched the following databases MEDLINE, EMBASE, and Cochrane Central. Register of Controlled Trials and included randomized controlled trials (RCTs) that studied the efficacy of NSAID vs. placebo, NSAID vs. steroid, or NSAID + steroid vs. placebo, reporting the incidence of PCME, macular thickness, and best-corrected visual acuity. The risk ratio (RR) with a 95% confidence interval (CI) and a random-effects model was used. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. Results A total of 18 RCTs were included in this study (n = 2959). Nine RCT showed low risk of bias, 7 RCT showed unclear risk of bias, and 2 RCT had high risk of bias. The incidence of cystoid macular edema among patients treated with NSAIDs was significantly lower (RR = 0.33, P

ABSTRACT: Our objectives were to compare the efficacy of ketoprofen or ceftiofur for treatment of metritis in dairy cows considering subsequent health, production, and reproduction. Cows from 2 commercial dairy farms in Ontario, Canada were examined with a Metricheck device 3 times per week from 2 to 14 DIM. Cows with metritis (fetid vaginal discharge; n = 193) were blocked by parity and fever (rectal temperature ≥39.5°C or

AbstractOur study aimed to evaluate the effect of different treatments for BRD on health and welfare in fattening bulls. A total of 264 bulls were enrolled. Welfare was assessed on day 2 (T0) and day 15 (T1) after arrival. A decrease in the welfare level was observed from T0 to T1. All bulls were inspected clinically at T0 and T1 revealing an increase of skin lesions and lameness in T1. In both periods, a high incidence of respiratory disease was observed. A prevalence of 79.55% and 95.45% of Mycoplasma bovis using RT-PCR and culture at T0 and T1 respectively was observed. Blood samples were collected for haematology at T0 and T1. At T0, 36 animals were individually treated for BRD with an antimicrobial (IT), 54 received a metaphylactic treatment with tulathromycin (M), 150 received a metaphylactic treatment with tulathromycin plus a second antimicrobial (M + IT) whereas 24 were considered healthy and therefore not treated (NT). Additionally, 128 were treated with a non-steroid anti-inflammatory (NSAID). Neutrophils of M + IT were significantly higher than groups NT and M and the lymphocytes of M + IT were significantly lower than that of IT. White blood cells, neutrophils and N/L ratio of animals treated with an NSAID was significantly higher than that not treated. Lung inspection of 172 bulls at the abattoir indicated that 92.43% presented at least one lung lesion. A statistically significant effect of the NSAID treatment on the lung lesions was observed. Our findings indicate that BRD was a major welfare and health concern and evidence the difficulties of antimicrobial treatment of M. bovis.

Abstract The objective of this study was to investigate the association between a Parkinson’s disease (PD)-specific polygenic score (PGS) and protective lifestyle factors on age at onset (AAO) in PD. We included data from 4367 patients with idiopathic PD, 159 patients with GBA1-PD, and 3090 healthy controls of European ancestry from AMP-PD, PPMI, and Fox Insight cohorts. The association between PGS and lifestyle factors on AAO was assessed with linear and Cox proportional hazards models. The PGS showed a negative association with AAO (β = − 1.07, p = 6 × 10–7) in patients with idiopathic PD. The use of one, two, or three of the protective lifestyle factors showed a reduction in the hazard ratio by 21% (p = 0.0001), 44% (p 0.05). In our cohort, coffee, tobacco, aspirin, and PGS are independent predictors of PD AAO. Additionally, lifestyle factors seem to have a greater influence on AAO than common genetic risk variants with aspirin presenting the largest effect.

Abstract Background The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and postoperative acute kidney injury (AKI) remains controversial, with limited studies specifically examining flurbiprofen. Therefore, this research aimed to investigate the association between intraoperative flurbiprofen administration and postoperative AKI. Methods We retrospectively identified a cohort of patients at the Third Xiangya Hospital of Central South University. A total of 3882 adult patients undergoing spinal surgery between January 1, 2012, and July 31, 2018, were included and classified into two groups: those receiving flurbiprofen (50 or 100 mg once, 5 min after anesthesia start) and those not receiving flurbiprofen. The primary endpoint was the incidence of AKI. Result The flurbiprofen group (4.4%) had a lower incidence of AKI compared to the non-flurbiprofen group (6.5%, P

Osteoarthritis (OA) is a chronic and progressive degenerative disease that affects joint structures, such as the hips, knees, and hands, involving the articular cartilage, subchondral bone, ligaments, capsule, and synovium. OA is characterized by a progressive degeneration of the joint structures, resulting in pain and decreased quality of life. Local and systemic risk factors pave the way for OA development. Different phenotypes may be identified, but three main molecular mechanisms define the endotypes: the bone-driven endotype, the synovitis-driven endotype, and the cartilage-driven endotype. The hallmark of OA pathophysiology involves more than just mechanical degradation; it includes the release of pro-inflammatory mediators, such as interleukins and TNF-a, which elucidates the significant roles of metabolic syndrome, diabetes, and cellular senescence in its development. OA is distinguished by a clinical presentation that varies significantly between people and is marked by pain, stiffness, and functional impairments. The clinical course can be split into Pre-OA, Early OA, Evident OA, and End-Stage. Depending on the stage of the disease, OA diagnosis frequently necessitates a complex strategy that combines clinical evaluation to detect joint tenderness, range of motion, and joint swelling or abnormalities, medical history assessment, imaging modalities, and laboratory investigations. There is no known treatment for OA, and different therapies are usually evaluated based on the stage of the disease to minimize pain and stiffness while maintaining joint function. Treatments are divided into the reduction of modifiable risk factors, pharmacologic therapies, rehabilitation, complementary therapies, interventional pain procedures, and surgery. OA clinical heterogeneity underlines the importance of prevention, early diagnosis, and identifying the phenotype and endotype to tailor the treatment. [ABSTRACT FROM AUTHOR]

Background:Hand foot mouth disease (HFMD), a disease of childhood is also reported in adults caused by Coxsackie virus A type 16. Clinical condition is characterized by vesicular eruptive lesion in mouth, hand, foot, buttock, or genitalia. Coxsackie virus is a member of picoranaviridae family that includes non-enveloped SSRNA viruses. Spread in humans in the case of HFMD is through oral route, by the shed virus from intestine of infected person or through upper respiratory tract by the secretions or vesicle fluid of the diseased individual. Incubation period is 3 to 6 days. Diagnosis of HFMD most of the time is based clinically depending on the patient’s age, symptoms and clinical presentation of rash. Samples include stool, oral samples, biopsy & vesicular scrapings. Viral culture is the gold standard. Treatment is mainly supportive, to maintain hydration, acetaminophen and NSAIDS to reduce temperature. Novel agents like pleconaril play a vital role in the management of viral infection cases. Hand hygiene is the main stay of prevention. [ABSTRACT FROM AUTHOR]

Objectives: This systematic review was designed to summarize randomized controlled trials of intra-articular administration of non-steroidal anti-inflammatory drugs (NSAIDs) for temporomandibular disorders. Methods: Randomized controlled trials regarding intra-articular injections of non-steroidal anti-inflammatory drugs for temporomandibular disorders were included in the review. The final search was conducted on 16 June 2024 in the Bielefeld Academic Search Engine, PubMed, and Scopus databases. Results: Of the 173 identified studies, 6 were eligible for review. In trials comparing arthrocentesis alone to arthrocentesis with NSAIDs, slight differences in joint pain were noted. For tenoxicam, differences were under 1 point on a 0–10 scale after 4 weeks, with inconsistent results. Piroxicam showed no significant difference, and pain levels were minimal in both groups. For maximum mouth opening (MMO), tenoxicam showed no significant difference. Piroxicam increased MMO by nearly 5 mm, based on one small trial with bias concerns. Conclusions: Currently, there is no strong scientific evidence supporting the injection of NSAIDs into the temporomandibular joint to relieve pain or increase jaw movement. Preliminary reports on piroxicam with arthrocentesis and tenoxicam or diclofenac without rinsing justify further research. [ABSTRACT FROM AUTHOR]

Mares enrolled in assisted reproductive technologies (ARTs) programs are often treated with non-steroidal anti-inflammatory drugs (NSAIDs), particularly phenylbutazone (Bute), due to chronic lameness. The current study was performed to determine the effect of Bute administration on the developmental competence of in vitro -matured equine oocytes subjected to Intracytoplasmic Sperm Injection (ICSI). In a Preliminary Study, immature cumulus-oocyte complexes (COCs) recovered by post-mortem ovary harvested from two healthy mares (n = 2) treated for 10 days with Bute (4.4 mg/kg, PO, BID), and four non-treated healthy mares (n = 4), were matured in vitro and subjected to Piezo-driven ICSI. Lower oocyte in vitro maturation [Bute: 25% (3/12) vs. Control: 61% (28/46)] and blastocyst rates [Bute: 0% (0/12) vs. Control: 18% (5/28)] were observed in the Bute-treated when compared to the Control mares (P < 0.05). In the Main Experiment, a group of healthy mares (n = 9) received a daily dose of Bute (4.4 mg/kg, orally, SID) for 10 days. A control group of mares (n = 10) was treated with an equal volume of placebo. Mares in both groups were subjected to ultrasound-guided transvaginal oocyte aspiration (TVA) on days 3, 33, and 77 following the last dose of Bute (PT). Recovered COCs from both mare groups were matured in vitro and subjected to Piezo-driven ICSI. By day-3 PT, oocyte in vitro maturation rate was similar between mare groups [Bute: 65% (36/55) vs. Control: 67% (78/116); P > 0.05], while oocyte recovery [Bute: 53% (55/103) vs. Control: 70% (116/166)], cleavage [Bute: 31% (11/36) vs. Control: 62% (48/78)] and blastocyst rates [Bute: [0%] (0/36) vs. Control: 28% (22/78)] were significantly different (P < 0.05). By day 33 PT and 77 PT, differences on oocyte recovery, in vitro maturation, cleavage, and blastocyst rates were not observed between mare groups. In summary, the administration of Bute for 10 consecutive days (4.4 mg/kg, PO, SID, or BID) is associated with a decrease in the ability of immature equine oocytes to undergo in vitro -maturation (Preliminary Study) and develop to the blastocyst stage following ICSI (Preliminary Study and Main Experiment). This negative effect appeared to be transient, as 30- and 77-days post-treatment, no differences on in vitro maturation, cleavage or blastocyst rates were observed. • Oral phenylbutazone impaired in vitro competence of equine oocytes. • Highest dose of phenylbutazone resulted in no blastocyst production after ICSI. • Recommended dose of phenylbutazone had a transient negative effect on blastocyst production after ICSI. • Embryo production was similar to non-treated mares after one month post-treatment with phenylbutazone. [ABSTRACT FROM AUTHOR]

• Rare unique clinical-radiological entity with a common treatment that can be diagnosed in the Emergency Department for a patient presenting with acute neck pain. • Diagnosis can usually be made with clinical findings and secondary laboratory tests including ESR and CRP. • Classic imaging findings includes enhancing soft tissue surrounding the common carotid artery without luminal involvement. • Response to NSAIDs or short course of corticosteroids is usually confirmatory for the diagnosis. • Awareness is critical to avoid unnecessary procedures. Idiopathic carotidynia, also known as transient perivascular inflammation of the carotid artery (TIPIC) syndrome, is a rare, self-limited, clinical-radiologic entity. Over the years, the diagnosis of carotidynia has been controversial, but recent pathologic, radiologic, clinical, and laboratory findings support an inflammatory etiology. A 61-year-old woman with a history of hypertension, left lower extremity liposarcoma, and right internal jugular port placement 2 weeks prior with initiation of chemotherapy presented to the emergency department with right neck pain and swelling of the lateral neck and lower face for the past 3 days. Computed tomography–neck with IV contrast revealed marked mural thickening of the right common carotid artery, which can be seen with carotidynia (Fay syndrome and TIPIC syndrome) and vasculitis. The patient had elevated inflammatory markers and was treated clinically for carotidynia with ibuprofen, evaluated by vascular surgery, and discharged home. The causes of acute neck pain are diverse, ranging from nonemergent to surgically emergent etiologies. As radiologists and emergency physicians, we believe TIPIC syndrome is a rare entity with important clinical impact deserving attention, as it is not typically included in medical training and is usually learned only through years of clinical experience and practice. TIPIC syndrome requires a unique combination of both clinical and radiologic findings to diagnose accurately and appropriately. It is important to be familiar with this diagnosis because treatment is focused on symptomatic relief without the need for invasive procedures. Our goal was to increase awareness of this uncommon diagnosis to improve patient care by preventing unnecessary invasive procedures and aid in timely and accurate diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: In 2005, the Food and Drug Administration (FDA) issued a decision memorandum regarding nonsteroidal anti-inflammatory drugs (NSAIDs). The memorandum recommended the withdrawal of certain NSAIDs due to potential cardiovascular adverse effects. It highlighted the issue of cardiovascular risk associated with NSAIDs as a class. The NSAID medication guide includes a wide range of adverse drug reactions (ADRs), such as increased blood pressure, liver failure, allergic reactions, heart attack, and intestinal bleeding. Although both sexes have an increased risk of ADRs with NSAID use, females have a greater risk than males due to differences in pharmacodynamics and higher medication concentrations (mg/kg). In particular, females with high blood pressure, coronary heart, kidney, and liver disease are at an additional risk of harm from NSAID ADRs. This study quantifies sex-specific differences and other factors associated with prescription NSAID use. Method: The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES), a complex survey conducted by the Centers for Disease Control and Prevention (CDC) in two-year cycles. A survey-weighted logistic regression model was utilized to investigate potential sex differences with prescription NSAIDs in the context of other factors, including kidney disease, hypertension, liver disease, insurance status, coronary heart disease, and age, within the 2011–2018 NHANES survey data. Results: Females reported a slightly higher percentage of high blood pressure and kidney disease than males, while males reported a slightly higher percentage of coronary heart and liver disease than females. Last, the model indicated that females were 58% more likely to have used a prescription NSAID than males. Conclusion: The results confirm that women and people with medical conditions, who would potentially suffer greater harm from NSAID ADRs, are more likely to use a prescription NSAID than individuals without these conditions. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate systemic absorption and gastrointestinal (GI) adverse effects of topical ketorolac 0.5% and diclofenac 0.1% ophthalmic solutions. ANIMALS 11 healthy purpose-bred Beagles. METHODS Dogs were randomly assigned to receive either ketorolac (n = 6) or diclofenac (5), 1 drop in both eyes 4 times daily for 28 days. Upper Gl endoscopy was performed on days 0 and 29 with mucosal lesion scores (0 to 7) assigned to each region evaluated. Plasma samples were collected on days 14, 21, and 28 for measurement of diclofenac and ketorolac using high-performance liquid chromatography-mass spectrometry. RESULTS Gl erosions and/or ulcers developed in all ketorolac-treated dogs and 1 of 5 diclofenac-treated dogs. Post-treatment mucosal lesion score for the antrum was higher in the ketorolac group than in the diclofenac group (P = .006) but not significantly different for any other region. Post-treatment antral mucosal lesion scores were significantly related to plasma ketorolac concentrations (P<.001). Ketorolac and diclofenac were detected in the plasma at all time points (median ketorolac day 14, 191 ng/mL; day 21, 173.5 ng/mL; and day 28, 179.5 ng/mL; and median diclofenac day 14, 21.1 ng/mL; day 21, 20.6 ng/mL; day 28, 27.5 ng/mL). Vomiting and decreased appetite events were observed uncommonly and were not significantly different between treatment groups. CLINICAL RELEVANCE Gl ulceration and erosion developed after ophthalmic administration of ketorolac and diclofenac, with higher plasma concentrations and more severe Gl lesions associated with ketorolac. Clients should be alerted to this potential risk with ophthalmic use and informed to watch for systemic clinical signs that would warrant veterinary reevaluation. [ABSTRACT FROM AUTHOR]

Background: The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and postoperative acute kidney injury (AKI) remains controversial, with limited studies specifically examining flurbiprofen. Therefore, this research aimed to investigate the association between intraoperative flurbiprofen administration and postoperative AKI. Methods: We retrospectively identified a cohort of patients at the Third Xiangya Hospital of Central South University. A total of 3882 adult patients undergoing spinal surgery between January 1, 2012, and July 31, 2018, were included and classified into two groups: those receiving flurbiprofen (50 or 100 mg once, 5 min after anesthesia start) and those not receiving flurbiprofen. The primary endpoint was the incidence of AKI. Result: The flurbiprofen group (4.4%) had a lower incidence of AKI compared to the non-flurbiprofen group (6.5%, P < 0.001). After adjusting for potential confounding variables, the multivariable regression analysis showed that the flurbiprofen group had a 49% reduced risk of postoperative AKI (OR 0.51; 95% CI 0.31 to 0.82) compared to the non-flurbiprofen group. Subgroup analysis indicated that flurbiprofen injection was associated with a reduced incidence of postoperative AKI in patients without diabetes (OR 0.61; 95% CI 0.19 to 0.74), surgical times of 2–5 h (OR 0.54; 95% CI 0.23 to 0.75), and preoperative anemia (OR 0.57; 95% CI 0.21 to 0.74). Conclusion: The study concluded that perioperative flurbiprofen treatment was associated with a lower risk of postoperative AKI in adult patients undergoing spinal surgery. [ABSTRACT FROM AUTHOR]

Objective: To determine the effectiveness of oral Theophyline compared to Non-Steroidal Anti-Inflammatory Drugs in the management of postdural puncture headache in obstetric patients. Study Design: Quasi-experimental Study. Place and Duration of Study: Anaesthesia Department, Combined Military Hospital, Kharian Pakistan, from Apr to Sep 2018. Methodology: Our study enroled 60 pregnant women suffering from postdural puncture headache. The were divided in to two groups, NSAID-Group (Group-A) who received 30mg of Ketorolac in three divided doses in 24 hours and Theophyline-Group (Group-B) who received 750mg of oral Theophyline in three divided doses in 24 hours after which effects of both drugs were noted. Results: Pregnant women were enroled in NSAID-Group and in Theophyline Group. Mean baseline Visual Analogue Scale score was 7.500±0.97 in NSAID-Group and 7.33±0.92 in Theophyline Group. Mean weight was 66.86±5.25 kg in NSAID-Group and 67.16±7.01 Kg in Theophyline-Group. In NSAID-Group efficacy was noted in 7(23.3%) patients as compared to 25(83.3%) patients in Theophyline-Group, (p<0.001). Conclusion: Theophyline when given oraly in the management of postdural puncture headache proved to be a superior alternative to NSAID medication. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage pain, fever, and inflammation. Although most are usually classified as prescription-only medicines, in many countries they are frequently purchased for self-medication purposes. This study explores NSAID-usage patterns in Kosovo, aiming for a safer and more effective medicinal use. The study employed a dual approach to collect data. First, NSAID sales were analyzed in a convenience sample of ten community pharmacies across diverse regions in Kosovo in 2023. Second, data on NSAID-usage patterns and patient awareness were systematically gathered from 410 patients during routine pharmacist–patient interactions. The four most commonly purchased NSAIDs according to sales analysis were diclofenac (33.1%), ketoprofen (27.6%), ibuprofen (17.0%) and nimesulide (12.7%). A significant 74.8% of NSAIDs were bought without prescriptions, particularly among younger adults (20–39 years), who accounted for 82.8% of such purchases. The predominant reason for NSAID use was headache (43.8%). Although many of the patients suffered from occasional (33.7%) or frequent (12.6%) stomachaches and took acid-lowering medicines, the majority (85.9%) could not recall any NSAID adverse reactions. This study exposes widespread self-medication and a significant lack of awareness regarding potential risks of NSAIDs, particularly among young adults. To address these issues, it is critical to improve dispensing practices through increased pharmacist awareness and stricter law enforcement. [ABSTRACT FROM AUTHOR]

Therapeutic effect of non-steroidal anti-inflammatory drugs (NSAIDs) has been related with gastrointestinal injury. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (PUFA), can prevent gastric and small intestinal damage. Nonetheless, contribution of antioxidative action in the protective effect of DHA has not been evaluated before in the small intestine injury after indomethacin treatment. Pathogenesis of NSAID-induced small intestinal injury is multifactorial, and reactive oxidative species have been related to indomethacin's small intestinal damage. The present work aimed to evaluate antioxidative activity in the protective action of DHA in the indomethacin-induced small intestinal damage. Female Wistar rats were gavage with DHA (3 mg/kg) or omeprazole (3 mg/kg) for 10 days. Each rat received indomethacin (3 mg/kg, orally) daily to induce small intestinal damage. The total area of intestinal ulcers and histopathological analysis were performed. In DHA-treated rats, myeloperoxidase and superoxide dismutase activity, glutathione, malondialdehyde, leukotriene, and lipopolysaccharide (LPS) levels were measured. Furthermore, the relative abundance of selective bacteria was assessed. DHA administration (3 mg/kg, p.o.) caused a significant decrease in indomethacin-induced small intestinal injury in Wistar rats after 10 days of treatment. DHA's enteroprotection resulted from the prevention of an increase in myeloperoxidase activity, and lipoperoxidation, as well as an improvement in the antioxidant defenses, such as glutathione levels and superoxide dismutase activity in the small intestine. Furthermore, we showed that DHA's enteroprotective effect decreased significantly LPS levels in indomethacin-induced injury in small intestine. Our data suggest that DHA's enteroprotective might be attributed to the prevention of oxidative stress. [ABSTRACT FROM AUTHOR]

Birds use their legs and wings when transitioning from aerial to ground locomotion during landing. To improve our understanding of the effects of footpad dermatitis (FPD) and keel bone fracture (KBF) upon landing biomechanics in laying hens, we measured ground-reaction forces generated by hens (n = 37) as they landed on force plates (Bertec Corporation, Columbus, OH) from a 30 cm drop or 170 cm jump in a single-blinded placebo-controlled trial using a cross-over design where birds received an anti-inflammatory (meloxicam, 5 mg/kg body mass) or placebo treatment beforehand. We used generalized linear mixed models to test for effects of health status, treatment and their interaction on landing velocity (m/s), maximum resultant force (N), and impulse (force integrated with respect to time [N s]). Birds with FPD and KBF tended to show divergent alterations to their landing biomechanics when landing from a 30 cm drop, with a higher landing velocity and maximum force in KBF compared to FPD birds, potentially indicative of efforts to either reduce the use of their wings or impacts on inflamed footpads. In contrast, at 170 cm jumps fewer differences between birds of different health statuses were observed likely due to laying hens being poor flyers already at their maximum power output. Our results indicate that orthopedic injuries, apart from being welfare issues on their own, may have subtle influences on bird mobility through altered landing biomechanics that should be considered.

An episode of the common cold can have a significant negative impact on quality of life, mood, and daily activities. In line with this fact, there is a growing demand for health care and treatments associated with the common cold. Current treatments aim to (1) inhibit symptom severity and (2) shorten the duration of an episode of the common cold. These products include analgesics, antihistamines, and decongestants. In addition, various supplements, including vitamins, minerals, and herbs, are marketed to treat the common cold. The current products marketed for treating the common cold may reduce the severity of some (but not all) common cold symptoms, but they usually do not shorten the common cold episode. The recent indication that phenylephrine is not effective means that it will ultimately need to be removed from the over-the-counter monograph. Manufacturers will consequently need to reformulate their products and withdraw oral phenylephrine-containing products. Several newly developed common cold products are currently under investigation. These clinical trials should evaluate their efficacy and safety, as there remains a clear need for common cold products that significantly reduce both the symptom severity and the duration of episodes of the common cold.

IntroductionWith rapidly growing interest in the use of cannabidiol (CBD) in the management of pain and other conditions, more information is needed on the safety and efficacy of this supplement, particularly its co-administration with commonly used pharmaceuticals such as non-steroidal anti-inflammatory drugs (NSAIDs). This study sought to assess the effect of CBD in dogs with mobility impairments, as well as evaluate the clinical tolerance of CBD used together with NSAIDs.Materials and methodsForty-two client-owned dogs with diagnosed mobility impairments were enrolled in this prospective, double-blind, crossover, placebo-controlled study. Baseline data were collected for 10–14 days followed by random allocation to either placebo or CBD oil for 45 days with a 30-day washout period in between. CBD was dosed at 5 mg/kg orally every 12 h with masked placebo administered at equal volume. Outcome measures included objective gait analysis, accelerometry, and clinical metrology instruments. CBD plasma levels and serum biochemistry were also collected along with hepatic ultrasound if warranted.ResultsThirty-eight dogs finished the study with thirty-nine included for at least partial analysis. Compared to baseline, dogs receiving CBD showed evidence of improved outcomes based on blinded veterinary assessments and accelerometer data. Compared to placebo, dogs receiving CBD showed some evidence of improved outcomes on CBPI, CSOM, and blinded veterinary assessments, but not for objective outcome measures. There was evidence of increased ALP when CBD was co-administered with NSAIDs compared to CBD administration alone. Additionally, there was evidence of ALT elevations with CBD and NSAID co-administration, but this elevation did not show evidence of an increase over CBD use alone.DiscussionThese results suggest a potential therapeutic benefit in the administration of CBD for the management of mobility impairments, but greater ALP elevations were seen when administered with NSAIDs. While the sample size of dogs that received further hepatic work-up for liver enzyme elevations is small, chosen diagnostics varied, and liver biopsies were not performed, there did not appear to be clinically apparent liver damage. Further research is needed to better understand the efficacy of CBD in a larger population of dogs and patient tolerance and safety when administered with NSAIDs or other medications long term.

Staphylococcus aureus is a bacterial pathogen of considerable significance in public health, capable of inducing a diverse range of infectious diseases. One of the most notorious mechanisms used by S. aureus to survive and colonize the site of infection is its ability to form biofilms. Diflunisal, a non-steroidal anti-inflammatory drug (NSAID), is a known inhibitor of the Agr system in S. aureus, which is key in regulating biofilm formation. This study evaluated the effect of broad-spectrum antibiotics in combination with diflunisal on S. aureus biofilm density. Eight antibiotics were tested independently at different concentrations and in combination with diflunisal to assess their effect on S. aureus biofilm formation. When using the antibiotics alone and with diflunisal, a significant control effect on biofilm formation was observed (p

This article discusses a case of acute photoallergic contact dermatitis in a 56-year-old man who developed a severe rash on his right shoulder and knee. Initially, the rash was thought to be bullous pemphigoid, an autoimmune blistering skin disease, but further examination revealed that the patient had used a diclofenac-based gel on his left knee prior to the onset of the rash. Photopatch tests were performed, which confirmed a photoallergic reaction to diclofenac and etofenamate. The patient was also found to have multiple contact allergies to other substances. The article highlights the potential for photocontact allergies to topical NSAIDs like diclofenac and etofenamate. [Extracted from the article]

Objective(s): Prescription of ibuprofen as a non-steroidal anti-inflammatory drug is limited by its gastrointestinal side effects and poor aqueous solubility. It was shown that phospholipid-association (PA) can lead to assembling assembly of the micellar form, thereby improving solubility of non-steroidal anti-inflammatory drugs solubility and reducing their gastrointestinal side effects. Materials and Methods: Ibuprofen in PA form was prepared and its interaction, crystallinity, and particle size were evaluated. Conventional ibuprofen and PA pellets in different drug contents were prepared by extrusion-spheronization. The mMorphology, shape factors, mechanical strength, and drug content of pellets were investigated. The dissolution test also was conducted in an intestinal-simulated medium and a gastric-simulated medium. Results: The results showed that PA micelles of ibuprofen were demonstrated to be formed, amorphous, and in an acceptable size range. Using a suitable composition of solid components and granulation fluid, pellets with desirable size, shape, and sphericity could be produced. All pellets have had plastic mechanical properties and the strength of formulations were decreased with increasing PA ratio. The PA-pellet formulation had faster drug release compared to conventional ibuprofen pellets, via increasing ibuprofen solubility by reducing crystallinity in solid state and micelle formation in dissolution media. Moreover, ibuprofen solubility in a gastric-simulated medium was decreased and might result in reduced gastrointestinal side effects.Conclusion: Due to the demonstrated bioavailability advantages of PA-pellets, they can be considered for further studies.

Alzheimer’s disease (AD) is a neurological condition that is much more common as people get older. It may start out early or late. Increased levels of pro-inflammatory cytokines and microglial activation, both of which contribute to the central nervous system’s inflammatory state, are characteristics of AD. As opposed to this, periodontitis is a widespread oral infection brought on by Gram-negative anaerobic bacteria. By releasing pro-inflammatory cytokines into the systemic circulation, periodontitis can be classified as a “low-grade systemic disease.” Periodontitis and AD are linked by inflammation, which is recognized to play a crucial part in both the disease processes. The current review sought to highlight the effects of pro-inflammatory cytokines, which are released during periodontal and Alzheimer’s diseases in the pathophysiology of both conditions. It also addresses the puzzling relationship between AD and periodontitis, highlighting the etiology and potential ramifications.

Abstract Background The objective of this study was to investigate the trends and prescribing patterns of antimigraine medicines in China. Methods The prescription data of outpatients diagnosed with migraine between 2018 and 2022 were extracted from the Hospital Prescription Analysis Cooperative Project of China. The demographic characteristics of migraine patients, prescription trends, and corresponding expenditures on antimigraine medicines were analyzed. We also investigated prescribing patterns of combination therapy and medicine overuse. Results A total of 32,246 outpatients who were diagnosed with migraine at 103 hospitals were included in this study. There were no significant trend changes in total outpatient visits, migraine prescriptions, or corresponding expenditures during the study period. Of the patients who were prescribed therapeutic medicines, 70.23% received analgesics, and 26.41% received migraine-specific agents. Nonsteroidal anti-inflammatory drugs (NSAIDs; 28.03%), caffeine-containing agents (22.15%), and opioids (16.00%) were the most commonly prescribed analgesics, with corresponding cost proportions of 11.35%, 4.08%, and 19.61%, respectively. Oral triptans (26.12%) were the most commonly prescribed migraine-specific agents and accounted for 62.21% of the total therapeutic expenditures. The proportion of patients receiving analgesic prescriptions increased from 65.25% in 2018 to 75.68% in 2022, and the proportion of patients receiving concomitant triptans decreased from 29.54% in 2018 to 21.55% in 2022 (both P

Triple‐negative breast cancer (TNBC) is a leading cause of cancer mortality and lacks modern therapy options. Modulated electro‐hyperthermia (mEHT) is an adjuvant therapy with demonstrated clinical efficacy for the treatment of various cancer types. In this study, we report that mEHT monotherapy stimulated interleukin‐1 beta (IL‐1β) and interleukin‐6 (IL‐6) expression, and consequently cyclooxygenase 2 (COX‐2), which may favor a cancer‐promoting tumor microenvironment. Thus, we combined mEHT with nonsteroid anti‐inflammatory drugs (NSAIDs): a nonselective aspirin, or the selective COX‐2 inhibitor SC236, in vivo. We demonstrate that NSAIDs synergistically increased the effect of mEHT in the 4T1 TNBC model. Moreover, the strongest tumor destruction ratio was observed in the combination SC236 + mEHT groups. Tumor damage was accompanied by a significant increase in cleaved caspase‐3, suggesting that apoptosis played an important role. IL‐1β and COX‐2 expression were significantly reduced by the combination therapies. In addition, a custom‐made nanostring panel demonstrated significant upregulation of genes participating in the formation of the extracellular matrix. Similarly, in the B16F10 melanoma model, mEHT and aspirin synergistically reduced the number of melanoma nodules in the lungs. In conclusion, mEHT combined with a selective COX‐2 inhibitor may offer a new therapeutic option in TNBC.

Abstract This study examines the long-term impact of non-steroidal anti-inflammatory drugs (NSAIDs) on the progression of symptoms and structural deterioration of the joint in knee osteoarthritis. The study analyzes data from 4197 participants (8394 knees) across the Osteoarthritis Initiative (OAI), Multicenter Osteoarthritis Study (MOST), and Cohort Hip and Cohort Knee (CHECK) over 4-to-5 years. Adjustments were made for major covariates. We focussed on binary outcomes to assess the presence or absence of significant changes. We found that, relative to non-users, individuals using NSAIDs long-term were significantly more likely to experience aggravated symptoms exceeding the minimally clinically important difference, specifically, pain (OR: 2.04, 95% CI: 1.66–2.49), disability (OR: 2.21, 95% CI: 1.74–2.80), and stiffness (OR: 1.58, 95% CI: 1.29–1.93). Long-term users also faced a higher probability than non-users of having total knee replacement (OR: 3.13, 95% CI: 2.08–4.70), although no significant difference between long-term users and non-users was observed for structural deterioration in the knee joint (OR: 1.25, 95% CI: 0.94–1.65). While acknowledging the limitations of this study due to its observational design and the potential for bidirectional causality, these findings suggest that long-term NSAID use could accelerate the progression to total knee replacement by markedly exacerbating symptoms.

Boron nanoparticles have numerous medical, industrial, and environmental applications as potential nanomaterials. Given the inevitable release of these particles in aquatic environments, they can combine with other pollutants like pharmaceuticals. Therefore, it is necessary to investigate their combined detrimental effects on freshwater biota. This study examined the joint impacts of Boron nitride nanoparticles (BNNPs) and Diclofenac (DCF) on freshwater microalgae Scenedesmus obliquus. Three different concentrations of BNNPs (0.1, 1, and 10 mg L−1) were mixed with 1 mg L−1 of DCF and were treated with algal cells, and biochemical analyses were performed. A concentration-dependent decrease in algal cell viability was observed after a 72-h interaction period with BNNPs and their binary combinations. The maximum toxic effects were observed for the highest combination of BNNPs + DCF, i.e., 10 mg L−1 BNNPs + 1 mg L−1 DCF. Similarly, an increase in the oxidative stress parameters and antioxidant enzyme activity was observed, which correlated directly to the decline in cell viability. The algal cells also showed reduced photosynthetic efficiency and electron transfer rate upon interaction with BNNPs. The results of this research emphasize the importance of considering the negative consequences of emerging pollutants and their combinations with other pollutants, BNNPs, and DCF as part of a thorough evaluation of ecotoxicity in freshwater algal species.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of analgesics that inhibit the activity of cyclooxygenase isoenzymes, which drive tissue inflammation pathways. Caution should be exercised when taking these drugs during pregnancy as they increase the risk of developmental defects. Due to the high rates of NSAID use by individuals, possibilities for in utero exposure to NSAIDs are high, and it is vital that we define the potential risks these drugs pose during embryonic development. In this review, we characterize the identified roles of the cyclooxygenase signaling pathway components throughout pregnancy and discuss the effects of cyclooxygenase pathway perturbation on developmental outcomes.

Neoplasm arising from the keratinocytes or melanocytes in the skin is the most prevalent type of cancer in the United States and worldwide. Since ultraviolet (UV) radiation may be a causing factor for several types of skin cancer, effective strategies to manage skin cancer include preventive measures such as minimizing exposure to UV and applying sunscreens. However, the effect of sunscreen in reducing skin cancer incidence remains uncertain. An alternative approach to prevent skin cancer is chemoprevention, which is defined as using either natural products or synthetic compounds to inhibit, delay, or reverse the development of cancer. Preclinical studies have demonstrated the effectiveness of multiple pharmacological agents and dietary supplements. However, whether preclinical findings can be translated into clinical application is unknown. This review evaluates the state of recent clinical trials investigating chemopreventive agents focusing on skin cancer to compare the target populations, interventions, endpoints, and outcomes of these trials. The ClinicalTrials and PubMed databases were searched for their available literature using the key words "skin cancer" and "chemoprevention". The objective of this review is to provide updated information on the effectiveness and side effects of promising chemopreventive agents in human subjects and to identify research gaps.

Meloxicam is a nonsteroidal anti-inflammatory analgesic drug that is often used in mice. However, doses of 1 to 5 mg/kg given twice daily were recently reported to provide inadequate analgesia. Some studies suggest that doses of up to 20 mg/kg may be necessary for adequate pain management. We investigated the analgesia provided by a high-dose of meloxicam in female CD1 mice. Pharmacokinetic analyses demonstrated that a subcutaneous injection of 10 mg/kg or 20 mg/kg of meloxicam produced therapeutic plasma concentrations for at least 12 h. Ovariectomies via ventral laparotomy were performed to assess analgesic efficacy. Mice were treated immediately before surgery with a high-dose of 10 mg/kg, a low-dose of 2.5 mg/kg, or saline, followed by every 12 h for 36 h. At 3, 6, 12, 24, and 48 h after surgery, mice were assessed for pain based on the following behaviors: distance traveled, time mobile, grooming, rearing, hunched posture, orbital tightening, and von Frey. Initially, some mice received a 20-mg/kg loading dose followed by 10 mg/kg every 12 h. This regimen caused severe morbidity and mortality in 2 mice. Subsequently, this regimen was abandoned, and mice assigned to the high-dose group received 10 mg/kg every 12 h. Mice that received the 10-mg/kg dose after surgery showed less orbital tightening between 3 to 6 h and reduced frequency of hunched posture for 48 h compared with mice that received either the low-dose or saline. However, mice were significantly less mobile for 6 to 12 h after surgery regardless of treatment. These data indicate that a meloxicam dose of 10 mg/kg every 12 h provides better analgesia than a 2.5-mg/kg dose but does not completely alleviate pain.

Introduction: Pain mostly arises because specialized cells called nociceptors detect harmful or potentially harmful stimuli. In lower animals with less convoluted nervous system, these responses are believed to be purely nociceptive. Amongst invertebrate animal models, planarians are becoming popular in a wide range of pharmacological and behavioral studies beyond the field of regeneration. Recent publications led the way on pain studies by focusing on nociceptive behaviors such as the 'scrunching' gait displayed under various noxious stimuli, as opposed to the 'gliding' gait planarians usually adopt in normal conditions. Methods: In this study, we adapted commonly used nociceptive tests to further explore nociception in planarians of the species Girardia dorotocephala. By using behavioral analysis in open fields and place preferences, we managed to set up chemical, thermal and mechanical nociceptive tests. We also adapted RNA interference protocols and explored the effects of knocking down TRPA1 ion channels, one of the main effectors of chemically and thermally-induced nociceptive responses in vertebrates. Results: Consequently, we demonstrated the reliability of the scrunching gait in this planarian species, which they displayed in a dose-dependent manner when exposed to the irritant AITC. We also showed that suppressing the expression of TRPA1 ion channels completely suppressed the scrunching gait, demonstrating the involvement of TRPA1 nociceptors in this nociceptive reaction. Besides, we also explored the effects of two common analgesics that both displayed strong antinociceptive properties. First, morphine reduced the chemically-induced nociceptive scrunching gaits by more than 20% and shifted the EC50 of the dose-response curve by approximately 10 µM. Secondly, the NSAID meloxicam drastically reduced chemically-induced scrunching by up to 60% and reduced heat avoidance in place preference tests. Discussion: Thus, we managed to characterize both behavioral and pharmacological aspects of G. dorotocephala's nociception, further developing the use of planarians as a replacement model in pain studies and more globally the study of invertebrate nociception. [ABSTRACT FROM AUTHOR]

Introduction: Renal colic is frequently treated with opioids; however, narcotic analgesic use can lead to dependence and abuse. We evaluated use trends of opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) for pain management of kidney stones in United States emergency departments (EDs) from 2015 to 2021. Methods: Kidney stone encounters were identified using National Hospital Ambulatory Medical Care Survey data. We applied a multistage survey weighting procedure to account for selection probability, nonresponse, and population weights. Medication use trends were estimated through logistic regressions on the timing of the encounter, adjusted for selected demographic and clinical characteristics. Results: Between 2015 and 2021, there were an estimated 9,433,291 kidney stone encounters in United States EDs. Opioid use decreased significantly (annual odds ratio [OR]: 0.87, p = 0.003), and there was no significant trend in NSAID use. At discharge, male patients were more likely than females (OR: 1.93, p = 0.001) to receive opioids, and Black patients were less likely than White patients (OR: 0.34, p = 0.010) to receive opioids. Regional variation was also observed, with higher odds of discharge prescriptions in the West (OR: 3.15, p = 0.003) and Midwest (OR: 2.49, p = 0.010), compared with the Northeast. Thirty-five percent of patients received opioids that were stronger than morphine. Conclusion: These results suggest improved opioid stewardship from ED physicians in response to the national opioid epidemic. However, regional variation as well as disparities in discharge prescriptions for Black and female patients underscore opportunities for continued efforts. [ABSTRACT FROM AUTHOR]

The transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) has the potential to overcome some of the major disadvantages relating to oral NSAID usage, such as gastrointestinal adverse events and compliance. However, the poor solubility of many of the newer NSAIDs creates challenges in incorporating the drugs into formulations suitable for application to skin and may limit transdermal permeation, particularly if the goal is therapeutic systemic drug concentrations. This review is an overview of the various strategies used to increase the solubility of poorly soluble NSAIDs and enhance their permeation through skin, such as the modification of the vehicle, the modification of or bypassing the barrier function of the skin, and using advanced nano-sized formulations. Furthermore, the simple yet highly versatile microemulsion system has been found to be a cost-effective and highly successful technology to deliver poorly water-soluble NSAIDs. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to investigate the trends and prescribing patterns of antimigraine medicines in China. Methods: The prescription data of outpatients diagnosed with migraine between 2018 and 2022 were extracted from the Hospital Prescription Analysis Cooperative Project of China. The demographic characteristics of migraine patients, prescription trends, and corresponding expenditures on antimigraine medicines were analyzed. We also investigated prescribing patterns of combination therapy and medicine overuse. Results: A total of 32,246 outpatients who were diagnosed with migraine at 103 hospitals were included in this study. There were no significant trend changes in total outpatient visits, migraine prescriptions, or corresponding expenditures during the study period. Of the patients who were prescribed therapeutic medicines, 70.23% received analgesics, and 26.41% received migraine-specific agents. Nonsteroidal anti-inflammatory drugs (NSAIDs; 28.03%), caffeine-containing agents (22.15%), and opioids (16.00%) were the most commonly prescribed analgesics, with corresponding cost proportions of 11.35%, 4.08%, and 19.61%, respectively. Oral triptans (26.12%) were the most commonly prescribed migraine-specific agents and accounted for 62.21% of the total therapeutic expenditures. The proportion of patients receiving analgesic prescriptions increased from 65.25% in 2018 to 75.68% in 2022, and the proportion of patients receiving concomitant triptans decreased from 29.54% in 2018 to 21.55% in 2022 (both P < 0.001). The most frequently prescribed preventive medication classes were calcium channel blockers (CCBs; 51.59%), followed by antidepressants (20.59%) and anticonvulsants (15.82%), which accounted for 21.90%, 34.18%, and 24.15%, respectively, of the total preventive expenditures. Flunarizine (51.41%) was the most commonly prescribed preventive drug. Flupentixol/melitracen (7.53%) was the most commonly prescribed antidepressant. The most commonly prescribed anticonvulsant was topiramate (9.33%), which increased from 6.26% to 12.75% (both P < 0.001). A total of 3.88% of the patients received combined therapy for acute migraine treatment, and 18.63% received combined therapy for prevention. The prescriptions for 69.21% of opioids, 38.53% of caffeine-containing agents, 26.61% of NSAIDs, 13.97% of acetaminophen, and 6.03% of triptans were considered written medicine overuse. Conclusions: Migraine treatment gradually converges toward evidence-based and guideline-recommended treatment. Attention should be given to opioid prescribing, weak evidence-based antidepressant use, and medication overuse in migraine treatment. [ABSTRACT FROM AUTHOR]