Use Of Nonsteroidal Anti-inflammatory Drugs Research Articles

A MISLEADING FORM OF IDIOPATHIC CAPILLARY LEAKAGE SYNDROME (CLARKSONS DISEASE): A CASE REPORT

The idiopathic capillary leak syndrome, commonly referred to as Clarksons disease, is an uncommon and severe disorder that frequently necessitates intensive care intervention due to recurring episodes of shock.With no established treatment available during the acute phase, the primary approach to management revolves around symptom relief. It seems that the use of vascular fluid resuscitation has an adverse effect on patient outcomes in intensive care, and therefore, there should be endeavors to restrict its usage.As an illustrative case, this article describes the case of a 53-year-old patient who presented to the emergency department with edema following the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and was initially misdiagnosed as anaphylaxis.Laboratory tests revealed hypoproteinemia in contrast to hemoconcentration, and the absence of serum albumin, which raised suspicion of Clarksons syndrome. This suspicion was confirmed through serum protein electrophoresis, ruling out other diagnoses.

КЛИНИЧЕСКИЕ ПОКАЗАТЕЛИ КРОВИ КРЫС С ХРОНИЧЕСКИМ ВОСПАЛЕНИЕМ МЯГКИХ ТКАНЕЙ СПИНЫ ПРИ КУРСОВОМ ВНУТРИМЫШЕЧНОМ ВВЕДЕНИИ РАСТВОРОВ ЯДА ГЮРЗЫ ЗАКАВКАЗСКОЙ (MACROVIPERA LEBETINA OBTUSA)

An relevant task of modern pharmacology is the search for drugs for the treatment of chronic inflammatory processes. The use of nonsteroidal anti-inflammatory drugs and drugs of the glucocorticoid group has a number of limitations due to pronounced negative effects. The use of herbal anti-inflammatory drugs often has a delayed effect. In this case, the anti-inflammatory effect is manifested in the later stages of the pathological process. For this reason, it seems interesting to us to use a solution of poison obtained from gyurza (Macrovipera lebetina obtusa) as an alternative therapy for chronic inflammatory processes. Earlier in our work, the ability of solutions of these poisons to reduce inflammation was shown. This effect was found both in native venom solutions and in those heated to 55оС. In this work, the effect of venom solutions was studied after a course of intramuscular administration. The criteria for anti-inflammatory action were blood counts in experimental chronic inflammation caused by acetic acid. Inflammation was modeled by injecting 0.5 ml of 9% acetic acid solution under the skin of the back and intraperitoneal administration of 1 ml of 10% Rheopolyglukin solution to white outbred male rats. Diclofenac in injections was chosen as a comparison drug. The assessment of clinical blood parameters was carried out on an automatic hematology analyzer BC 2800vet (Mindray). The positive dynamics of the course of the chronic aseptic inflammatory process has been revealed. A more positive dynamics of the course of the chronic aseptic inflammatory process was revealed in groups of animals receiving solutions of native venom.

Non-steroidal anti-inflammatory drugs, renin-angiotensin system blockade or diuretics and risk of acute kidney injury: A case-crossover study

BackgroundAging-related physiological changes, such as decline in renal function, not only exacerbates pre-existing comorbidities but also escalate the susceptibility to adverse events. Previous studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI), and the concomitant use of renin-angiotensin system blockade or diuretics may further potentiate the risk. However, studies evaluating the risk of AKI associated with NSAIDs (including routes, concomitant use of different NSAIDs, categories (traditional NSAIDs or COX-2 inhibitors), and cumulative doses of NSAIDs) are limited, particularly the risk of AKI associated with the dual or triple combination of NSAIDs with renin-angiotensin system blockade (RAS blockades) and/or diuretics. MethodsA case-crossover study utilized two sets of longitudinal data from Taiwan's National Health Insurance Research Database (NHIRD). Newly admitted patients with a primary AKI diagnosis were included, with the index date defined as the first admission date. The 1–7 days and 181–187 days prior to the index date served as the case and control periods. Exposure to NSAIDs and co-exposures of RAS blockade and/or diuretics were assessed in both periods. Multivariable conditional logistic regression models, adjusting for potential confounders, estimated adjusted odds ratios (aORs) and 95 % confidence intervals (CIs) for AKI associated with NSAIDs, dual, or triple combinations. Sensitivity analyses explored result robustness by varying case and control period lengths. ResultsThe study included 1,284 newly diagnosed AKI patients. NSAIDs showed a 3.55-fold increased risk of AKI (aOR: 3.55; 95 % CI 2.70–4.65), with similar risks for traditional NSAIDs and COX-2 inhibitors. Use of multiple NSAIDs, parenteral dosage forms, and higher cumulative doses increased AKI risk. Dual combination with either RAS blockade or diuretics resulted in a 2.90-fold (aOR: 2.90; 95 %CI 1.47–5.70) and 12.68-fold (aOR: 12.68; 95 %CI 6.15–26.12) risk, respectively. The highest risk occurred with triple combination (aOR: 29.22; 95 %CI 12.82–66.64). ConclusionsNSAIDs, including both non-selective NSAIDs and COX2 inhibitors, elevate the risk of AKI. Increased AKI risk is linked to using multiple NSAIDs, the parenteral dosage form, and higher cumulative doses. Dual combination of RAS blockade with NSAIDs or diuretics with NSAIDs, as well as triple therapy, heightens the risk, with the latter associated with the highest risk of AKI.

Cataract surgery in patients with diabetes mellitus. Prevention and optimisation of the diabetic macular edema therapy

Diabetes mellitus (DM) is a major public health problem, with approximately one third having signs of diabetic retinopathy (DR). In such patients, cataracts develop at an earlier age and 2–5 times more frequently. The incidence of macular edema (ME) after phacoemulsification of cataracts (FEC) in patients with diabetes has been shown to increase by 1.80 times and, in the presence of DR by 6.23. The critical period for retinal deterioration is 2 months after FEC, which requires an active therapy and monitoring. For patients with pre-existing diabetic macular edema (DME), If the cataract does not affect daily activities of patients with a pre-existing DME and the optical clarity is adequate, it is preferable to postpone surgical treatment in order to maximize retinal stabilization on OCT at two consecutive visits with a month’s interval between. In the case of severe impairment of lens transparency, FEC with an intravitreal injection of anti-VEGF 28 days or steroids 1 month before surgery under strict monitoring of the retinal condition using OCT is recommended. If macular changes are absent and there is a risk of developing DME, the use of nonsteroid anti-inflammatory drugs is necessary. Prophylactic intravitreal therapy is unacceptable in the absence of MO.

Postinjection protocols following platelet-rich plasma administration for knee osteoarthritis: A systematic review.

Platelet-rich plasma (PRP) use in treating orthopedic conditions has increased, yet evidence of its clinical efficacy is inconsistent and limited by heterogeneity in osteoarthritis (OA) severity, PRP preparations and protocols, and clinical outcome measurement. This review aims to characterize the variations in postinjection protocols in studies assessing the clinical efficacy of PRP for knee OA. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A literature search from database inception to February 2023 of CINAHL, MEDLINE, and EMBASE was conducted. Article screening, data extraction, and risk of bias assessments were completed in duplicate by two reviewers. Primary outcomes were presence/absence and timing of the following postinjection protocol components: nonsteroidal anti-inflammatory drug (NSAID) restrictions, non-NSAID analgesic and cryotherapy use, immediate knee flexion/extension, immediate rest, activity restriction, return-to-activity guidelines, and rehabilitation protocols. A descriptive analysis was used to analyze the data. Given study heterogeneity, a meta-analysis was not performed. A total of 187 studies were included for analysis. Half of all studies (51.9%) excluded patients due to preinjection NSAID use, most often within 5 days of blood sampling or injection. Postinjection NSAID restriction was included in 42.8% of studies, ranging from 1 to 1800 days. Few studies (19.4%) that permitted non-NSAID analgesia restricted their use prior to clinical assessments. Postinjection immediate flexion, extension, and immobilization were rarely (8.6%) mentioned. Activity restriction was included in a third of studies (35.3%), with the most frequent length of restriction being 1 day. Postinjection return-to-activity protocols were less common (20.3%), usually with a "gradual" and/or "as tolerated" recommendation. A minority of studies (16.0%) reported physical therapy protocols and the vast majority (93.3%) were home based. Significant heterogeneity remains in post-PRP injection protocols, with unclear consensus regarding optimal recommendations and limited rationale for the protocols outlined. Further study is necessary to compare protocols directly and to determine which pre- and postinjection recommendations can result in optimal outcomes.

Abstract 3446: Associations of non-steroidal anti-inflammatory drug use and circulating inflammatory proteins with gallbladder dysplasia

Abstract Background: Most gallbladder cancer (GBC) cases arise from the metaplasia-dysplasia-GBC sequence, and chronic inflammation has been associated with its development. The use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk of GBC; however, little is known about these associations with preneoplastic lesions. We thus aimed to study the associations of the use of NSAIDs and inflammatory proteins with gallbladder dysplasia, a precursor to GBC. Methods: Associations of NSAIDs and gallbladder dysplasia were evaluated in 1,925 Chilean cholecystectomy patients, 82 with dysplasia and 1,843 with gallstones but not dysplasia. In addition, we measured 33 circulating inflammatory proteins in a subsample of 68 dysplasia cases diagnosed at the time of sample selection and 136 gallstone controls. Age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated, and associations of inflammatory proteins and gallbladder dysplasia were analyzed. Results: 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 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) in the multivariable logistic regression model additionally adjusted for sex, age and NSAID use. Conclusion: NSAID users were less likely to have gallbladder dysplasia, suggesting that NSAIDs might be beneficial for gallstones patients. Prospective studies are needed to understand the inverse association of immune-related markers and dysplasia, and to evaluate the biological effect of NSAIDs in GBC. Research supported by general funds from the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and the Office of Research on Women’s Health, National Institutes of Health. Citation Format: Lorena Rosa, Paz Cook, Ruth M. Pfeiffer, Troy J. Kemp, Allan Hildesheim, Burcin Pehlivanoglu, Volkan Adsay, Enrique Bellolio, Juan Carlos Araya, Ligia Pinto, Catterina Ferreccio, Gloria Aguayo, Eduardo Viñuela, Jill Koshiol. Associations of non-steroidal anti-inflammatory drug use and circulating inflammatory proteins with gallbladder dysplasia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3446.

Resveratrol and Neuroinflammation: Total-Scale Analysis of the Scientific Literature

Neuroinflammation plays a crucial role in the development of various neurological diseases, including neurodegenerative disorders, leading to significant neuronal dysfunction. Current treatments involve the use of non-steroidal anti-inflammatory drugs and steroids; however, they are associated with serious adverse effects, limiting their efficacy. Exploring natural products with anti-inflammatory properties appears promising, with resveratrol, a polyphenol found in various plants, standing out for its potential benefits. Studies on resveratrol and its anti-inflammatory properties have been increasing in recent years, and analyzing the profile of this knowledge area can bring benefits to the scientific community. Therefore, this study conducted bibliometric analyses, using “resveratrol AND neuroinflammation” as search terms in the Web of Science Core Collection database. The analysis, performed with VOSviewer software version 1.6.18, encompasses 323 publications. Key terms in the studies include “resveratrol”, “neuroinflammation”, and “oxidative stress”, with China leading in the number of publications. The Federal University of Rio Grande do Sul in Brazil emerges as the institution with the highest contribution, and a phase 2 clinical study on resveratrol was the most cited. These results provide an overview of the global research landscape related to resveratrol and neuroinflammation, aiding decision making for future publications and advancing scientific understanding in this field.

Investigating the risk factors for nonadherence to analgesic medications in cancer patients: Establishing a nomogram model

ObjectiveThe substantial prevalence of nonadherence to analgesic medication among individuals diagnosed with cancer imposes a significant strain on both patients and healthcare resources. The objective of this study is to develop and authenticate a nomogram model for assessing nonadherence to analgesic medication in cancer patients. MethodsClinical information, demographic data, and medication adherence records of cancer pain patients were gathered from the Affiliated Hospital of Chengde Medical University between April 2020 and March 2023. The risk factors associated with analgesic medication nonadherence in cancer patients were analyzed using the least absolute selection operator (LASSO) regression model and multivariate logistic regression. Additionally, a nomogram model was developed. The bootstrap method was employed to internally verify the model. Discrimination and accuracy of the nomogram model were evaluated using the Concordance index (C-index), area under the receiver Operating characteristic (ROC) curve (AUC), and calibration curve. The potential clinical value of the nomogram model was established through decision curve analysis (DCA) and clinical impact curve. ResultsThe study included a total of 450 patients, with a nonadherence rate of 43.33%. The model incorporated seven factors: age, address, smoking history, number of comorbidities, use of nonsteroidal antiinflammatory drugs (NSAIDs), use of opioids, and PHQ-8. The C-index of the model was found to be 0.93 (95% CI: 0.907–0.953), and the ROC curve demonstrated an AUC of 0.929. Furthermore, the DCA and clinical impact curves indicate that the built model can accurately predict cancer pain patients' medication adherence performance. ConclusionsA nomogram model based on 7 risk factors has been successfully developed and validated for long-term analgesic management of cancer patients.

The Effect of Murottal and Lavender Aromatherapy on Post-Circumition Pain in Pediatric Patients at Oerip Putra Brebes Clinic

Background: Circumcision is a medical procedure involving the removal of the prepuce, resulting in wound and significant postoperative pain that disrupts daily activities. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) to manage pain has associated side effects, prompting the exploration of non-pharmacological therapies such as murottal and aromatherapy as alternatives for pain management in post-circumcision pediatric patients. Method: This quantitative study utilized a pre-experimental design with a one-group pre-and-post-test approach. A sample of 20 respondents was selected using non-probability purposive sampling at Oerip Putra Brebes Clinic. Pain level was measured using the Wong-Baker Faces Pain Rating Scale. The respondents were being asked three times for the pain scale before the intervention, to make sure the pain scale is not temporarily but it’s their final answer. Data analysis employed the Wilcoxon Signed Rank Test. Data collection was condcuted between December 2022 and February 2023. Results: The average pain scale value before intervention was 4,20, and after intervention, it was 4,70. The Wilcoxon test yielded a p-value of 0,197, indicating no significant impact from murottal and lavender aromatherapy on post-circumcision pediatric patients. Conclusion: The administration of murottal and lavender aromatherapy did not yield a significant impact on post-circumcision pain in pediatric patients.

Association of long-term use of non-steroidal anti-inflammatory drugs with knee osteoarthritis: a prospective multi-cohort study over 4-to-5 years

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.

Comparison of the effect of erector spinae plane block for postoperative analgesia on neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in patients operated for breast cancer

Objectives: It was seen that recurrence and metastasis after breast cancer surgery are related to the immune response of the host. Anesthetic agents modulate the surgical stress response or directly impair the functions of immune system cells. In our study, we aimed to compare the effects of nonsteroidal anti-inflammatory drugs and erector spinae plane block, which are among the methods we use for postoperative analgesia, on the neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in patients undergoing breast cancer surgery. Methods: One hundred female patients aged 18-75 years, scheduled for unilateral breast cancer surgery, and who agreed to participate were included in our study. These cases were divided into two groups of the analgesia method: Those with erector spinae plane block (Group E) and those who were administered nonsteroidal anti-inflammatory drugs (Group N). According to the results, preoperative and postoperative neutrophil/lymphocyte ratio and platelet/lymphocyte ratio values were calculated and recorded. Results: Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were statistically higher in both groups in the postoperative period. No statistically significant difference was found when the preoperative and postoperative measurement changes of the laboratory parameters between the groups were compared. Postoperative VAS scores were statistically significantly lower in Group E. Conclusions: We concluded that when erector spinae plane block and nonsteroidal anti-inflammatory drug use were compared in managing postoperative analgesia in breast cancer surgery, their effects on the neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were not superior to each other. However, the erector spinae plane block was superior for adequate pain control.

NSAID-induced gastropathy in a comorbid patient in a multidisciplinary hospital

The purpose of this case report is to demonstrate the importance of outpatient management of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients, especially those at risk (elderly patients, alcohol abusers, patients with a history of peptic ulcer disease, patients taking glucocorticoids or anticoagulants) to avoid life-threatening complications. The following clinical case shows the association between gastric and duodenal mucosal barrier disruption and the use of nonsteroidal anti-inflammatory drugs. Methods: a complete blood count, blood biochemistry test, ultrasound, and abdominal radiography. Results. The clinical case describes a patient with coronary heart disease, ischemic cardiomyopathy, hypertension, permanent atrial fibrillation, impaired glucose tolerance, obesity, and a long history of smoking who had been taking 1–2 tablets of Nimesulide per day for a long time without doctor’s prescription; the intake of NSAIDs was not controlled on an outpatient basis. The reason for hospitalization was sharp pain in the epigastrium; the plain abdominal radiography in the emergency room revealed free gas below both domes of the diaphragm, and ultrasound examination of the abdominal cavity showed a level of inhomogeneous free fluid detected in all sloping areas and pneumatosis intestinalis. In this regard, the patient was urgently hospitalized to the department of surgery, where surgical intervention was performed, including upper-middle laparotomy, abdominoscopy, suture repair of the perforated gastric ulcer, and sanitation and drainage of the abdominal cavity. Conclusion. This clinical case draws attention to the problem of NSAID gastropathy in clinical practice. The task of a clinician is to prevent the development of NSAID-induced gastropathy, identify patients with risk factors for NSAID gastropathy at the earliest possible time, and carry out preventive and therapeutic measures. Patient management at the outpatient stage according to the clinical recommendations could have prevented the development of gastrointestinal bleeding associated with NSAID gastropathy.

Trends in Opioid and Nonsteroidal Anti-Inflammatory Drug Use for Patients with Kidney Stones in United States Emergency Departments from 2015 to 2021.

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.

Drug-induced liver injury (DILI) ascribed to non-steroidal anti-inflammatory drugs (NSAIDs) in the USA-Update with genetic correlations.

To describe patients with NSAID-DILI, including genetic factors associated with idiosyncratic DILI. In DILIN, subjects with presumed DILI are enrolled and followed for at least 6 months. Causality is adjudicated by a Delphic approach. HLA sequencing of multiethnic NSAID-DILI patients and HLA allele imputation of matching population controls were performed following overall, class and drug-based association analysis. Significant results were tested in a non-Hispanic White (NHW) case-control replication cohort. Between September 2004 and March 2022, causality was adjudicated in 2498, and 55 (41 [75%] women) were assessed as likely due to NSAIDs. Median age at onset was 55 y (range 22-83 y). Diclofenac was the causative drug in 29, celecoxib in 7, ibuprofen in 5, etodolac and meloxicam each in 4. Except for meloxicam and oxaprozin (n = 2), the liver injury was hepatocellular with median R 15-25. HLA-DRB1*04:03 and HLA-B*35:03 were significantly more frequent in NSAID-DILI patients than in non-NSAID DILI controls. Interestingly, 85% of the HLA-DRB1*04:03 carriers developed DILI due to the use of acetic acid derivative NSAIDs, supporting the hypothesis that HLA-DRB1*04:03 could be a drug and/or class risk factor. HLA-B*35:03 but not HLA-DRB1*04:03 association was confirmed in the independent NHW replication cohort, which was largely driven by diclofenac. Despite prevalent use, NSAID-DILI is infrequent in the United States. Diclofenac is the most commonly implicated, and adherence to warnings of risk and close observation are recommended. The increased frequency of HLA-B*35:03 and DRB1*04:03, driven by diclofenac, suggests the importance of immune-mediated responses.

Abstract A089: Influence of pre-diagnosis aspirin use on epithelial ovarian cancer tumor immune microenvironment markers: results from the Nurses’ Health Study (NHS) and NHSII

Abstract Background: Daily aspirin use versus never use is associated with a 10-20% lower risk of developing epithelial ovarian cancer (EOC). Among women with EOC, aspirin use after diagnosis compared with never use is associated with a 30% improvement in ovarian cancer-specific survival. Inhibition of enzymes in prostaglandin synthesis is a key mechanism responsible for the anti-inflammatory and anti-neoplastic effects of aspirin. Prostaglandins influence immune inflammatory cells in the tumor microenvironment therefore our objective was to evaluate how aspirin use may influence the EOC tumor immune microenvironment. Methods: Tissue microarrays (TMAs) representing EOC tumor tissues from participants in the Nurses’ Health Study (NHS) and NHSII were assessed for total T cells, T cell activation and T cell exhaustion markers within the tumor (epithelium) area using multiplex immunofluorescence. Data on aspirin use and information on EOC risk factors and lifestyle variables were collected by questionnaire every two years. Beta-binomial models were used to estimate odds ratios (ORs) and 95% CIs; these models estimate the odds that a cell was positive for the marker(s) of interest comparing recent regular aspirin use (2+ times per week in the questionnaire cycle prior to diagnosis) versus never use, accounting for the total tumor cells in each core. Former users of aspirin were excluded. Multivariable models were adjusted for cohort, histotype (type 1 versus type 2), age and year of cancer diagnosis, number of CD3+ T cells (in tertiles), hysterectomy, tubal ligation, duration of oral contraceptive use, family history of breast or ovarian cancer, parity and body mass index (as fixed effects) and the participant (random effect) to account for multiple tissue cores per case. Results: We compared tumor tissues from 209 participants with recent pre-diagnosis use of aspirin with 88 participants who never used aspirin. Compared with cases who never used aspirin, recent aspirin users had higher odds of having tumors with recently activated cytotoxic T cells (CD3+CD8+CD69+, OR=1.69, 95% CI: 1.10, 2.59) and T cells expressing exhaustion markers (CD3+Lag-3+, OR=1.63, 95% CI: 1.09, 2.43; CD3+Tim-3+, OR= 1.62, 95% CI: 0.96, 2.72). In contrast, there was no association between recent aspirin use versus never use and odds of a tumor being positive for total T cells (CD3+, OR=1.20, 95% CI: 0.80, 1.79). Conclusions: Our data suggest that recent aspirin use before diagnosis was associated with higher odds of having EOC tumors expressing both recently activated cytotoxic T cells and T cell exhaustion markers. By improving our biological understanding of how aspirin use influences the ovarian tumor immune microenvironment, these results will assist to inform the optimal use of aspirin to improve EOC patient outcomes. Future work will focus on additional immune markers, assess non-aspirin nonsteroidal anti-inflammatory drug (NSAID) use and evaluate associations between aspirin/NSAID use with EOC survival considering the context of tumor immune microenvironment biomarkers. Citation Format: Nicola S. Meagher, Cassandra Hathaway, Mary K. Townsend, Mollie E. Barnard, Jose R. Conejo-Garcia, Brooke L. Fridley, Daryoush Saeed-Vafa, Britton Trabert, Shelley S. Tworoger, Melissa A. Merritt. Influence of pre-diagnosis aspirin use on epithelial ovarian cancer tumor immune microenvironment markers: results from the Nurses’ Health Study (NHS) and NHSII [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A089.

Prospective Evaluation of Dental Practitioners' Knowledge, Attitude, and Practice Toward Adult Dental Pain Management: A Cross-Sectional Multicenter Study.

Background Dental pain among adults is a prevalent concern impacting oral health and quality of life. Dental pain management presents a significant challenge for dental practitioners in effectively alleviating patient discomfort. Among the medications available, non-steroidal anti-inflammatory drugs (NSAIDs) are considered the most effective analgesics in dental care. While numerous studies have been conducted to assess the role of antibiotics in dental practice, there is a scarcity of studies specifically examining the prescription patterns of analgesics. The primary aim of this study was to evaluate the knowledge, attitudes, and practices of dental practitioners (DPs) in India concerning the management of adult dental pain. Method This survey utilized a computer-aided questionnaire-based approach. A total of 110 dentists, including 16 from metropolitan areas and 84 from non-metropolitan cities practicing at dental healthcare setups, clinics, and hospitals, were interviewed as part of the survey. The participants comprised dental professionals specializing in prosthodontics, endodontics, orthodontics, periodontics, oral surgery, pedodontics, and oral medicine. The study was conducted between September 2022 and January 2023. Results The primary reason patients seek dental consultation, as reported by 95% of dentists, is tooth cavities, followed by tooth sensitivity, post-root canal treatment, and pulpitis. All surveyed dentists prescribed NSAIDs to their patients for managing dental pain. Local anesthesia (LA) was the second choice for 75% of dentists, prescribed to 23% of their patients. The primary use of NSAIDs was for patients experiencing severe pain and to manage post-procedure pain. Eighty percent of DPs recognized ketorolac as a fast-acting molecule, providing immediate relief within 10-15 minutes. Overall, analysis indicated that 98% of DPs are satisfied and 67% are extremely satisfied with ketorolac among monotherapies for dental pain management due to its quick onset of action, fast pain relief, and usefulness in post-surgical pain management. Conclusion NSAIDs like ketorolac, diclofenac, and aceclofenacwere the preferred prescriptions for overall dental pain management. Dental practitioners associated ketorolac with fast pain relief, quick onset of action, and effectiveness in post-surgical pain management, emphasizing its lasting effects. The insights from the study contribute to enhancing dental pain management strategies.

Determinants of pressure injury development in patients with COVID-19.

Pressure injuries (PIs) often develop in critically ill patients due to immobility, and underlying comorbidities that decrease tissue perfusion and wound healing capacity. This study sought to provide epidemiological data on determinants and current managements practices of PI in patients with COVID-19. A US national insurance-based database consisting of patients with coronavirus or COVID-19 diagnoses was used for data collection. Patients were filtered by International Classification of Diseases (ICD) codes corresponding to coronavirus or COVID-19 diagnosis between 2019-2020. Diagnosis of PI following COVID-19 diagnosis was queried. Demographic data and comorbidity information was compared. Logistic regression analysis was used to determine predictors for both PI development and likelihood of operative debridement. A total of 1,477,851 patients with COVID-19 were identified. Of these, 15,613 (1.06%) subsequently developed a PI, and 8074 (51.7%) of these patients had an intensive care unit (ICU) admission. The average and median time between diagnosis of COVID-19 and PI was 39.4 and 26 days, respectively. PI was more likely to occur in patients with COVID-19 with: diabetes (odds ratio (OR): 1.39, 95% confidence interval (CI): 1.29-1.49; p<0.001); coronary artery disease (OR: 1.11, 95% CI: 1.04-1.18, p=0.002), hypertension (OR: 1.43, 95% CI: 1.26-1.64; p<0.001); chronic kidney disease (OR: 1.18, 95% CI: 1.10-1.26; p<0.001); depression (OR: 1.45, 95% CI 1.36-1.54; p<0.001); and long-term non-steroidal anti-inflammatory drug use (OR: 1.21, 95% CI: 1.05-1.40; p=0.007). They were also more likely in critically ill patients admitted to the ICU (OR: 1.40, 95% CI: 1.31-1.48; p<0.001); and patients requiring vasopressors (OR:1.25, 95% CI: 1.13-1.38; p<0.001), intubation (OR: 1.21, 95% CI 1.07-1.39; p=0.004), or with a diagnosis of sepsis (OR: 2.38, 95% CI 2.22-2.55; p<0.001). ICU admission, sepsis, buttock and lower back PI along with increasing Charlson Comorbidity Index (CCI) (OR: 1.04, 95% CI 1.00-1.08; p=0.043) was associated with surgical debridement. The vast majority of patients with COVID-19 did not undergo operative debridement or wound coverage. PIs are widely prevalent in patients with COVID-19, especially in those who are critically ill, yet the vast majority do not undergo operative procedures. The authors have no conflicts of interest to declare.

A retrospective cohort study on early antibiotic use in vaccinated and unvaccinated COVID-19 patients.

The bacteriophage behavior of SARS-CoV-2 during the acute and post-COVID-19 phases appears to be an important factor in the development of the disease. The early use of antibiotics seems to be crucial to inhibit disease progression-to prevent viral replication in the gut microbiome, and control toxicological production from the human microbiome. To study the impact of specific antibiotics on recovery from COVID-19 and long COVID (LC) taking into account: vaccination status, comorbidities, SARS-CoV-2 wave, time of initiation of antibiotic therapy and concomitant use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). A total of 211 COVID-19 patients were included in the study: of which 59 were vaccinated with mRNA vaccines against SARS-CoV-2 while 152 were unvaccinated. Patients were enrolled in three waves: from September 2020 to October 2022, corresponding to the emergence of the pre-Delta, Delta, and Omicron variants of the SARS-CoV-2 virus. The three criteria for enrolling patients were: oropharyngeal swab positivity or fecal findings; moderate symptoms with antibiotic intake; and measurement of blood oxygen saturation during the period of illness. The use of antibiotic combinations, such as amoxicillin with clavulanic acid (875 + 125 mg tablets, every 12 h) plus rifaximin (400 mg tablets every 12 h), as first choice, as suggested from the previous data, or azithromycin (500 mg tablets every 24 h), plus rifaximin as above, allows healthcare professionals to focus on the gut microbiome and its implications in COVID-19 disease during patient care. The primary outcome measured in this study was the estimated average treatment effect, which quantified the difference in mean recovery between patients receiving antibiotics and those not receiving antibiotics at 3 and 9 days after the start of treatment. In the analysis, both vaccinated and unvaccinated groups had a median illness duration of 7 days (interquartile range [IQR] 6-9 days for each; recovery crude hazard ratio [HR] = 0.94, p = 0.700). The median illness duration for the pre-Delta and Delta waves was 8 days (IQR 7-10 days), while it was shorter, 6.5 days, for Omicron (IQR 6-8 days; recovery crude HR = 1.71, p < 0.001). These results were confirmed by multivariate analysis. Patients with comorbidities had a significantly longer disease duration: median 8 days (IQR 7-10 days) compared to 7 days (IQR 6-8 days) for those without comorbidities (crude HR = 0.75, p = 0.038), but this result was not confirmed in multivariate analysis as statistical significance was lost. Early initiation of antibiotic therapy resulted in a significantly shorter recovery time (crude HR = 4.74, p < 0.001). Concomitant use of NSAIDs did not reduce disease duration and in multivariate analysis prolonged the disease (p = 0.041). A subgroup of 42 patients receiving corticosteroids for a median of 3 days (IQR 3-6 days) had a longer recovery time (median 9 days, IQR 8-10 days) compared to others (median 7 days, IQR 6-8 days; crude HR = 0.542, p < 0.001), as confirmed also by the adjusted HR. In this study, a statistically significant reduction in recovery time was observed among patients who received early antibiotic treatment. Early initiation of antibiotics played a crucial role in maintaining higher levels of blood oxygen saturation. In addition, it is worth noting that a significant number of patients who received antibiotics in the first 3 days and for a duration of 7 days, during the acute phase did not develop LC.

Prolonged Non-Steroidal Anti-Inflammatory Drug Exposure After Pleurodesis Increases Pneumothorax Recurrence: A Retrospective Cohort Study

The use of non-steroidal anti-inflammatory drugs (NSAID) in patients undergoing pleurodesis remains controversial. Although many surgeons are comfortable prescribing NSAIDs post-operatively, some oppose this practice due to concerns of suppressing the inflammatory response and quality of pleurodesis. Only a small body of inconsistent publications exists with respect to guiding therapy in this common clinical scenario. A retrospective cohort study was undertaken assessing effect of NSAID exposure on pleurodesis outcomes. An institutional thoracic surgery database was reviewed yielding 147 patients who underwent pleurodesis for pneumothorax between 2010 and 2018. Medical records and imaging were reviewed for patient characteristics, NSAID exposure, recurrent pneumothorax and other adverse events. There was no overall difference between rates of recurrence and procedural failure of pleurodesis (Relative Risk [RR] 1.67 [95% CI 0.74-3.77]). However, NSAID exposure of >48 hours was associated with increased risk of recurrent pneumothorax (RR 2.16 [95% CI 1.05-4.45]). There was no increased rate of other adverse events related to NSAID usage. NSAID exposure does not increase failure rates or other adverse events following pleurodesis for pneumothorax. However, prolonged NSAID exposure post-pleurodesis may increase procedural failure rates. Further large volume randomised control trials are required.

Identifying Risk Factors for Cardiovascular Events Among Active-Duty Service Members and Veterans Prescribed Nonsteroidal Anti-Inflammatory Drugs (NSAIDs).

Oral NSAIDs are widely used analgesic medications for the treatment of musculoskeletal and inflammatory conditions. NSAIDs are associated with adverse effects that arise from COX enzyme inhibition including cardiovascular events. The combined role of patient and prescription factors associated with NSAID use on cardiovascular risk is not well characterized. The purpose of this study is to identify the risk factors with cardiovascular events among NSAID users. This study is a retrospective, nested case-control study, within the DAVINCI database, among active-duty service members and veterans with at least one NSAID pharmacy claim between fiscal year (FY) 2015-FY2020. Inclusion criteria individuals ≥18 years of age received a prescription NSAID for ≥7-day supply and a duration ≥1 month overall. Cases experienced nonfatal myocardial infarction, nonfatal stroke, or new onset heart failure. Ten controls were selected per case. Risk factors were identified through logistic regression modeling. The risk factors with strongest association to the primary outcome included age starting at 45 up to 75 and older, the first 90 days of NSAID exposure, cerebrovascular disease, cardiomyopathy, and history of myocardial infarction. Cox-selectivity and dose did not appear to be clinically significant in their association with cardiovascular events. The results of this study indicate that age, initial NSAID exposure, and comorbidities are more predictive than NSAID-specific factors such as COX-selectivity and dose. The results provide the framework for development of a risk score to improve prediction of NSAID-associated cardiovascular events.