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

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

Nephroprotective and hepatoprotective effects of lemongrass essential oil and citral on diclofenac-induced toxicity in mice.

The present study was carried out to evaluate and compare the protective potential of two well-known antioxidants of herbal origin in a mouse model of acute DIC-induced nephro- and hepatotoxicity. The tested antioxidants included lemongrass essential oil (LO) and its predominant bioactive constituent citral (CIT). A third herbal product, silymarin (SILY), was used as a reference hepato-renal protective agent. DIC administration led to elevated serum urea and creatinine levels, and prompted oxidative stress along with histopathological changes in the kidney tissue. In parallel, DIC administration increased serum liver enzyme activity, decreased total protein, albumin, and globulin levels, and caused oxidative stress with associated histopathological changes in the liver tissue. Pre-treatment with LO or CIT mitigated DIC-induced alterations in all serum biochemical markers of kidney and liver health (except albumin). High-dose LO, like SILY, within kidney and liver tissues, counteracted DIC-induced oxidative stress and histomorphological alterations. By contrast, CIT failed to mitigate DIC-induced oxidative stress in the kidneys and provided only partial control of DIC-induced oxidative stress in the liver, resulting in less efficient preservation of kidney function and liver structural integrity than LO. Besides confirming the efficacy of SILY at protecting kidneys and liver against the toxicity of DIC in a rodent species different from the one tested so far (rat), this study demonstrated the preventive properties of LO and, to a lesser extent, of CIT against DIC-induced hepato-renal toxicity in mice, supporting their developmental potential as therapeutics.

Effectiveness of a Single Intra-articular Injection of High-Molecular-Weight Hyaluronic Acid Versus NSAIDs on the Visual Analog Pain Scale and Western Ontario and McMaster Universities Osteoarthritis Index Scores in Patients With Knee Osteoarthritis.

OBJECTIVE: This study aimed to determine the effectiveness of a single intra-articular injection of high-molecular-weight (HMW) hyaluronic acid (HA) at a dose of 4 mL/60 mg to reduce pain in people with knee osteoarthritis (OA) over 12 months. METHODOLOGY: This retrospective study was conducted after obtaining ethical approval from Dhaka Medical College and Hospital, Bangladesh. From July 2020 to June 2021, a medical professional conducted the investigation. The investigation encompassed patients aged 40 to 70 hospitalized at our facility and diagnosed with Grade 2 or Grade 3 knee OA according to the Kellgren-Lawrence grading method. We divided the patients into two categories based on the treatments they received. Patients in Group A received a single injection of HMW HA (60 mg/4 mL) into the joint, along with instructions on activities of daily living, exercise, and painkillers. Group B patients received conservative therapy, which involved the use of nonsteroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, therapeutic exercises, and a knee brace during physical activity. RESULTS: This study compared the efficacy of a single injection of HMW HA in the joint versus NSAIDs for managing OA-related symptoms over 12 weeks. The HA group initially scored similarly to the comparison group. By week three, however, the group receiving HA had considerably higher Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (p=0.019). This pattern continued through weeks 6 (p=0.044), 9 (p=0.016), and 12 (p<0.001). Similarly, by week 3 (p=0.029), the visual analog scale (VAS) scores, which were initially identical (p=0.120), demonstrated a significant preference for HA, and this preference persisted through weeks 6, 9, and 12 (all p<0.001). The results show that by the third week, HA is more effective than NSAIDs at relieving pain and improving symptoms. CONCLUSION: The study's results indicated that over 12 weeks, the use of HMW HA led to statistically significant reductions in pain intensity, as measured by the VAS. Furthermore, HMW HA demonstrated a more significant improvement in WOMAC ratings, which assess physical function, stiffness, and pain, compared to NSAIDs. The findings suggest that administering HMW HA injections can significantly reduce symptoms and improve functionality in individuals with knee OA.

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

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

Nonsteroidal anti-inflammatory drugs-associated vanishing bile duct syndrome: a real-world retrospective and disproportionality analysis.

INTRODUCTION: Vanishing bile duct syndrome (VBDS) is a potentially fatal adverse reaction triggered by certain medications. The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and VBDS is based on case reports. We explored the reporting prevalence and evaluated the clinical features of NSAID-related VBDS. RESEARCH DESIGN AND METHODS: Adverse event reports of VBDS associated with NSAIDs from 2004 to 2023 in the FAERS database were retrieved, and disproportionality analyses were conducted to detect risk signals. Case reports from 2000 to 2023 on NSAID-induced VBDS were retrieved for retrospective analysis. RESULTS: We obtained 87 VBDS reports from the FAERS database. Ibuprofen had the greatest proportion of VBDS (63.2%), while loxoprofen had the highest positive signal value. Sixteen case reports showed evidence of VBDS, with 37.5% of children. The median age was 29 years; typical initial symptoms included rash (60.0%), jaundice (53.3%), fatigue/asthenia (33.3%), and SJS/TEN (53.3%). The median onset time of VBDS was 4 weeks. All cases had abnormal liver function tests, with the median level of TBIL being 20.0 mg/dl. The overall prognosis is poor, with 50% of patients achieving clinical remission. CONCLUSION: Four NSAID agents had significant reporting associations with VBDS. Prescribers should be more aware of this risk and identify signs/symptoms earlier.

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

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

Molecular Thumbprints: Biological Signatures That Measure Loss of Identity.

Each life is challenged to adapt to an ever-changing environment with integrity-simply put, to maintain identity. We hypothesize that this mission statement of adaptive homeostasis is particularly poignant in an adaptive response, like inflammation. A maladaptive response of unresolved inflammation can seed chronic disease over a lifetime. We propose the concept of a molecular thumbprint: a biological signature of loss of identity as a measure of incomplete return to homeostasis after an inflammatory response. Over time, personal molecular thumbprints can measure dynamic and precise trajectories to chronic inflammatory diseases and further loss of self to cancer. Why is this important? Because the phenotypes and molecular signatures of established complex inflammatory diseases are a far cry from the root of the complex problem, let alone the initial seed. Understanding the science behind key germinating seeds of disease helps to identify molecular factors of susceptibility, resilience, and early dietary or drug intervention. We pilot this hypothesis in a rat colitis model that is well-established for understanding molecular mechanisms of colonic health, disease, and transition of colitis to cancer.

Diaphragm Disease of the Terminal Ileum: The Great Imitator.

Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an array of intestinal injuries: erosions, ulcers, enteropathy, strictures and diaphragm disease. The diagnosis of diaphragm disease is challenging. Diaphragm disease can cause thin, concentric and stenosing strictures, which can induce intermittent or complete bowel obstruction. NSAID-induced lesions are reversible following discontinuation of the offending agent. Treatment of diaphragm disease can be conservative, endoscopic or surgical through stricturoplasty and/or segmental resection. We report a case of a 59-year-old female presenting with intermittent right lower quadrant pain diagnosed with diaphragm disease upon combined ileo-colonoscopy and histopathological analysis. Her diaphragm disease was successfully treated conservatively through drug cessation, avoiding more invasive procedures like endoscopic and surgical interventions. LEARNING POINTS: The incidence of diaphragm disease has been soaring due to the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs).Diaphragm disease is characterized by diaphragm-like mucosal projections and annular constrictions that induce luminal narrowing and result in bowel obstruction.Physicians should get acquainted with diaphragm disease and include it in their differential diagnosis when approaching a patient with obstruction-like symptoms or non-specific and vague abdominal pain in the setting of chronic NSAIDs usage.

Knowledge, attitude, and practice toward nonsteroidal anti-inflammatory drugs among osteoarthritis patients: a cross-sectional study.

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are common drugs in patients with osteoarthritis (OA). NSAIDs are generally used at home by patients, without supervision, requiring proper knowledge and attitudes for correct practice. This study investigated the knowledge, attitude, and practice (KAP) of patients with OA toward NSAIDs. Methods This cross-sectional study enrolled patients with OA at the Qingpu Branch of Zhongshan Hospital of Fudan University between January and March 2024. The KAP scores and demographic information of respondents were collected through a self-designed questionnaire. Results There were 645 participants, with 579 (89.8%) over 45 years old and 394 (61.1%) females. The average scores for knowledge, attitude, and practice were 16.26 ± 3.79 (possible range: 0-24), 18.12 ± 1.99 (possible range: 5-35), and 29.20 ± 5.52 (possible range: 10-50), respectively. The structural equation model (SEM) found that for individuals currently using NSAIDs, the attitude had a direct effect on practice (ß = 0.978, P < 0.001). For individuals not using NSAIDs, the attitude had a direct effect on practice (ß = 0.936, P < 0.001). Conclusion This study suggested that adequate NSAID knowledge is the prerequisite for correct NSAID-related medical decisions, while attitude has a crucial intermediary effect. Healthcare professionals and society should strengthen education regarding the relevant knowledge of NSAIDs and guide the cultivation of positive attitudes toward NSAIDs.

Are Environmental Levels of Nonsteroidal Anti-Inflammatory Drugs a Reason for Concern? Chronic Life-Cycle Effects of Naproxen in Zebrafish.

The nonsteroidal anti-inflammatory drug naproxen (NPX) is among the most consumed pharmaceuticals worldwide, being detected in surface waters within the ng to µg/L range. Considering the limited chronic ecotoxicity data available for NPX in aquatic ecosystems, the present study aimed at evaluating its impact in the model organism Danio rerio, following a full life-cycle exposure to environmentally relevant concentrations (0.1 to 5.0 µg/L). An integration of apical endpoints, i.e., survival, growth, and reproduction, with gonad histopathology and gene transcription (RNA-seq) was performed to provide additional insights into the mode of action (MoA) of NPX. NPX decreased zebrafish growth and reproduction and led to histopathological alterations in gonads at concentrations as low as 0.1 µg/L. At the molecular level, 0.7 µg/L of NPX led to a disruption in gonads transcription of genes involved in several biological processes associated with reproduction, mainly involving steroid hormone biosynthesis and epigenetic/epitranscriptomic machineries. Collectively, these results show that environmentally realistic concentrations of NPX affect zebrafish reproduction and associated signaling pathways, indicating that current hazard and risk assessment data for NPX underestimate the environmental risk of this pharmaceutical.

Dual Role of Ibuprofen and Indomethacin in Promoting Peripheral Nerve Regeneration In Vitro.

Peripheral nerve injuries (PNI) can result in significant losses of motor and sensory function. Although peripheral nerves have an innate capacity for regeneration, restoration of function after severe injury remains suboptimal. The gold standard for peripheral nerve regeneration (PNR) is autologous nerve transplantation, but this method is limited by the generation of an additional surgical site, donor-site morbidity, and neuroma formation at the site of harvest. Although targeted drug compounds have the potential to influence axonal growth, there are no drugs currently approved to treat PNI. Therefore, we propose to repurpose commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) to enhance PNR, facilitating easier clinical translation. Additionally, calcium signaling plays a crucial role in neuronal connectivity and regeneration, but how specific drugs modulate this process remains unclear. We developed an in vitro hollow channel collagen gel platform that successfully supports neuronal network formation. This study evaluated the effects of commonly used NSAIDs, namely ibuprofen and indomethacin, in our in vitro model of axonal growth, regeneration, and calcium signaling as potential treatments for PNI. Our results demonstrate enhanced axonal growth and regrowth with both ibuprofen and indomethacin, suggesting a positive influence on PNR. Further, these drugs showed enhanced calcium signaling dynamics, which we posit is a crucial aspect for nerve repair. Taken together, these findings highlight the potential of ibuprofen and indomethacin to be used as treatment options for PNI, given their dual capability to promote axonal growth and enhance calcium signaling.

The Addition of a Non-Steroidal Anti-Inflammatory Drug (NSAID) in Local Infiltration Analgesia During Total Knee Arthroplasty Increases the Risk of Acute Kidney Injury in Patients Who Have Renal Impairment: A Propensity-Matched Retrospective Cohort Study.

BACKGROUND: Local infiltration analgesia (LIA) is a crucial component of pain management during total knee arthroplasty (TKA). Various formulations of the LIA drug cocktail have been described, with non-steroidal anti-inflammatory drugs (NSAIDs) commonly included. Although NSAIDs are highly effective in improving postoperative pain, they are associated with adverse renal, gastrointestinal, and cardiovascular effects. This study aimed to investigate whether the addition of an NSAID in LIA affects the incidence of acute kidney injury (AKI) in TKA patients, especially those who have pre-existing renal impairment. The secondary aim was to determine overall AKI incidence. METHODS: A retrospective cohort study was conducted on elective, primary TKA patients in a single tertiary institution between January 2020 and April 2024. Data was obtained from a prospectively collected institutional knee arthroplasty registry. Patients were administered LIA intraoperatively, with or without an NSAID (30 mg of ketorolac). The study population was divided into two subpopulations, patients who did or did not have chronic kidney disease (CKD), and analyzed separately. Propensity matching was performed on the CKD group, correcting for age, sex, BMI, ASA score, and presence of diabetes mellitus/hypertension. The outcome of interest was the incidence of AKI. A t-test or Chi-square test was used, where appropriate, to determine the statistical significance of the results. RESULTS: In patients who had CKD (n = 114), the presence of ketorolac in LIA was associated with a higher AKI incidence (12.7 versus 2.0%, P = 0.041). In patients who did not have CKD (n = 870), the presence of ketorolac in LIA was not associated with a higher AKI incidence (2.0 versus 1.9%, P = 1.0). Overall AKI incidence was 2.6%. CONCLUSION: In patients who have CKD, orthopaedic surgeons should be highly cautious of administering ketorolac in LIA during TKA, as it is associated with a higher risk of AKI. Patients who have normal renal function can be safely given ketorolac in LIA without an elevated risk of AKI. Further studies are needed to examine AKI incidence when other NSAIDs are used in LIA.

Floppy iris. How is floppy iris syndrome managed? What do urologists and ophthalmologists say?

Introduction: This study focuses on the effect of chronic treatment on the eye, regarding the so-called Intraoperative Floppy Iris Syndrome (IFIS) or Floppy Iris Syndrome, which can occur during cataract surgery. Aim: The study aimed to establish the influence of tamsulosin, used in benign prostatic hyperplasia (BPH) treatment on the iris, during cataract surgery, considering the increased incidence of both conditions in older age. Methods: This study included one hundred male patients, operated on for cataracts at the Ofta Total Clinic and Dr. Stanila Medical Centre, in Sibiu, out of 601 patients operated on for cataracts between February and October 2022. Of the 100 patients, 24 used medication for BPH. 5 patients used prostamol, a phytotherapeutic preparation, which is an extract from Serenoarepens, and the remaining 19 used tamsulosin, which is an alpha-blocker, most commonly used in the treatment of BPH, considered the first-line treatment option. Results: In 15 patients, we intraoperatively managed, a medium mydriasis through pharmacological dilation, including intracameral administration of phenocaine and mechanical dilation or stripping. In 4 patients it was necessary to apply iris dilators. Due to the small pupil in 2 patients, we caught the iris in the phacoemulsification probe, and a small, incomplete iris coloboma was formed. Sometimes, there was a turnover of Descemet in 4 patients. The pupil remained semi-dilated and slightly areflective in the patients to whom we applied iris hooks. The patients' visual acuity was satisfactory, between 0.9 and 0.6. Discussions: The topic gives rise to many discussions. It seems that stopping the administration of tamsulosin for a short time does not help the occurrence of IFIS, because the iris lesions seem irreversible. Patients at risk of developing cataracts should be evaluated and possibly referred to an ophthalmologist to determine surgery before starting treatment for BPH and to competently assess the administration of this medication. Conclusions: Collaboration between urologists and ophthalmologists is required for patients prone to the appearance of cataracts since both conditions are frequently encountered in elderly patients.

The effect of macrophage-cardiomyocyte interactions on cardiovascular diseases and development of potential drugs.

The interaction between macrophages and cardiomyocytes plays an important role not only in maintaining cardiac homeostasis, but also in the development of many cardiovascular diseases (CVDs), such as myocardial infarction (MI) and heart failure (HF). In addition to supporting cardiomyocytes, macrophages and cardiomyocytes have a close and complex relationship. By studying their cross-talk, we can better understand novel mechanisms and target pathogenic mechanisms, and improve the treatment of CVDs. We review macrophage-cardiomyocyte communication through connexin 43 (Cx43)-containing gap junctions (GJs) directly, secreted protein factors indirectly, and discuss the implications of these interactions in cardiac homeostasis and the development of various CVDs, including MI, HF, arrhythmia, cardiac fibrosis and myocarditis. In this section, we review various drugs that work by modulating cytokines or other proteins to reduce inflammation in CVDs. The clinical findings from targeting inflammation in CVDs are also discussed. Additionally, we examine the challenges and opportunities for improving our understanding of macrophage-cardiomyocyte coupling as it relates to pathophysiological disease processes, extending our research scope, and helping identify new molecular targets and improve the effectiveness of existing therapies.

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

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

Core-shell tablets designed for modified and sequential release of ibuprofen and rabeprazole.

In this study, core-shell tablets comprising an ibuprofen (IBU) enteric-coated core for modified release and a rabeprazole (RAB) shell for immediate release were developed using wet granulation method. The primary aim was to produce a sequential release of RAB and IBU with pharmacokinetic profiles comparable to those of the respective single tablets, thereby reducing the potential for IBU-associated gastrointestinal (GI) side effects. The composition of the IBU/RAB core-shell tablets was finalized on a comparative basis by evaluating various trial formulations. IBU/RAB core-shell tablets (400/20 mg) were assessed for physicochemical attributes, storage stability, and in vivo pharmacokinetics in beagle dogs. IBU/RAB core-shell tablets showed immediate RAB release (99.5 % in 1 h at pH 1.2) and delayed IBU release (3.4 % and 88 % in the acid and buffer stages, respectively). IBU/RAB core-shell tablets produced either comparable or improved plasma concentrations in dogs (Cmax; 1163.3 vs. 1160.0 ng/mL for RAB and 27,370 vs. 24,170 ng/mL for IBU) compared to those of the respective single tablets. The IBU/RAB core-shell tablets also demonstrated long-term and accelerated storage stability. In conclusion, the core-shell design could be a promising strategy for the co-administration and sequential release of IBU and RAB to relieve inflammatory conditions and reduce GI complications.

Response of crop seed germination and primary root elongation to a binary mixture of diclofenac and naproxen.

Non-steroidal anti-inflammatory drugs, diclofenac (DCF) and naproxen (NPX), represent a group of environmental contaminants often detected in various water and soil samples. This work aimed to assess possible phytotoxic effects of DCF and NPX in concentrations 0.1, 1 and 10 mg/L, both individually and in binary mixtures, on the seed germination and primary root elongation of crops, monocots Allium porrum and Zea mays, and dicots Lactuca sativa and Pisum sativum. Results proved that the seed germination was affected by neither individual drugs nor their mixture. The response of primary root length in monocot and dicot species to the same treatment was different. The Inhibition index (%) comparing the root length of drug-treated plants to controls proved to be approximately 10% inhibition in the case of dicots lettuce and pea, and nearly 20% inhibition in monocot leek, but almost 20% stimulation in monocot maize. Assessment of the binary mixture effect confirmed neither synergistic nor antagonistic interaction of DCF and NPX on early plant development in the applied concentration range.

Do NSAIDs affect bone healing rate, delay union, or cause non-union: an updated systematic review and meta-analysis.

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) may potentially delay or cause non-union of fractures by inhibiting prostaglandin synthesis. However, studies have shown conflicting results. This systematic review and meta-analysis aim to synthesize current evidence on the potential influence of NSAIDs on bone healing. Methods: We conducted a comprehensive search of PubMed, Embase, and Cochrane CENTRAL databases for studies published up to 25 July 2023. Specific keywords included "NSAID," "nonsteroidal anti-inflammatory drug," "cyclooxygenase-2 inhibitor," "bone healing," "non-union," "pseudoarthrosis," "delayed union," and "atrophic bone." Eligible studies included prospective, retrospective, and case-controlled studies assessing the correlation between NSAID use and bone healing outcomes. The leave-one-out approach was used to test the robustness of the meta-analysis results. Results: A total of 20 studies with 523,240 patients were included in the analysis. The mean patient age ranged from 6.7 to 77.0 years, with follow-up durations from 3 to 67 months. The meta-analysis revealed no significant difference in non-union or delayed union between NSAID users and non-users [pooled adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 0.99-1.23]. Initial analysis identified a significant association between NSAID usage and an increased risk of reoperation, but this association became insignificant upon sensitivity analysis (crude OR = 1.42; 95% CI: 0.88-2.28). Discussion: NSAIDs may have a minimal impact on non-union or delayed union risks. However, caution is advised due to the limited number of studies and the absence of a specific focus on NSAID types and dosages. Further research is necessary to better understand the implications of NSAID use on bone healing.

Treatment of Idiopathic Inflammatory Orbital Syndrome (IOIS) With Prominent Lacrimal Gland Involvement Using Oral Non-Steroidal Anti-Inflammatory Drugs (NSAIDs).

Idiopathic orbital inflammatory syndrome (IOIS) is a chronic inflammatory process of unknown etiology, which can either be localized or diffuse. In cases where there is isolated inflammation of the lacrimal gland, it is known as dacryoadenitis. This study focuses on the treatment of a patient with IOIS with prominent lacrimal gland involvement. The mainstay of treatment for idiopathic isolated dacryoadenitis is oral corticosteroids, but non-steroidal anti-inflammatory drug (NSAIDs) is known to be effective in treating idiopathic dacryoadenitis as well. There is no formal study yet to evaluate the use of NSAIDs in treating idiopathic dacryoadenitis. Here, we report a case of idiopathic isolated dacryoadenitis which was successfully treated with NSAIDs.

Acute medications' intake for migraine: a one-year report in patients undergoing first evaluation at a third level Italian headache center.

Background: Headache disorders, particularly primary headaches like migraine and tension-type headache, still remain underdiagnosed and undertreated despite their high prevalence and significant impact on quality of life. In recent years, several specific medications targeting key pathways in the pathophysiology of migraine have been developed. Despite this advancement, numerous studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics remain the most commonly used drugs. This study focused on the use of NSAIDs and simple analgesics as acute treatments for migraine among patients at a tertiary headache center. Methods: A retrospective observational study was conducted at the Fondazione Policlinico Universitario Campus Bio-Medico throughout 2022. Data were collected on the type and frequency of headaches, the usage and dosage of NSAIDs and other medications, and changes in their use at follow-up visits. Statistical analyses were performed to evaluate the efficacy and determinants of NSAID consumption and headache frequency changes. Results: Two hundred and eightythree patients diagnosed with migraine undergoing their first examination at our center were enrolled. Initially, 58.7% of patients used NSAIDs or simple analgesics, which decreased to 46.6% 3 months after, while triptan use increased from 65.1 to 72.8%. Changes in prophylactic therapies were significantly associated with a decrease in NSAID intake (W = 834.000, p = 0.004) and in headache frequency (W = 5960.5, p = 0.003). Specifically, the addition of topiramate or amitriptyline was associated with a reduction in NSAID use and headache frequency. Even pain freedom after the intake of NSAIDs improved from 55.2 to 79.4% of cases at follow-up. Conclusion: The study highlights the importance of appropriate diagnosis and tailored treatment strategies in the management of primary headaches. It underscores the need for specialized care to enhance treatment efficacy and patient outcomes, demonstrating that adjustments in prophylactic therapy can significantly reduce NSAID intake and improve headache care. This reinforces the role of tertiary headache centers in providing specialized care that can adapt treatments to individual patient needs and improve overall headache management.