Grisel's Syndrome After COVID-19 in a Pediatric Patient: A Case Report.

An eight-year-old female presenting with posterior neck pain and torticollis who had been diagnosed with coronavirus disease 2019 (COVID-19) three weeks earlier was radiographed and diagnosed with atlantoaxial rotatory fixation (AARF). Following treatment with non-steroidal anti-inflammatory drugs (NSAIDs), the posterior neck pain improved, and the torticollis was cured. Symptoms returned after two weeks, and computed tomography showed a 3.94 mm atlantodental interval and axis rotation. The patient was diagnosed with AARF relapse; symptoms resolved spontaneously prior to subsequent examination, and no further relapses were observed. This case highlights the need for clinicians to be aware that AARF may develop after COVID-19. Treatment options should be carefully considered.

Consumer awareness and knowledge regarding use of non-steroidal anti-inflammatory drugs (NSAIDs) in a metropolitan area.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) have well-known adverse effects, and numerous studies have shown inappropriate behaviors regarding their use. The primary aim of this study was to analyze the knowledge, attitudes, and behaviors regarding the use of NSAIDs simultaneously in one of the largest and most populated areas of Italy, Naples. Methods: From 2021 December 14th to 2022 January 4th, a cross-sectional survey study was conducted among community centers, working places, and universities using a snowball sampling method. For inclusion in the study, the participants were required to be at least 18 years old and residents in the metropolitan area of Naples. Three multiple linear regression analysis (MLRA) models were developed by including variables that could potentially be associated with the following outcomes of interest: knowledge (Model I), attitudes (Model II), and behavior (Model III) regarding the use of NSAIDs. Results: Data were acquired from 1,012 questionnaires administered to subjects evenly divided by gender with an average age of 36.8 years and revealed that only 7.9% of the participants self-admittedly did not take NSAIDs, while approximately half the participants (50%) admitted to occasionally using them. The results showed a statistically significant correlation between attitudes regarding the appropriate use of NSAIDs and less knowledge. The regression analyses indicated that behaviors regarding the appropriate use of NSAIDs were statistically significant in younger respondents, non-smokers, and those without children. These interesting results showed that behaviors regarding the appropriate use of NSAIDs were significantly higher among respondents with less knowledge and more positive attitudes. Conclusion: According to the collected data and statistical analysis results, it is possible to identify factors that can greatly affect inappropriate behaviors regarding the use of NSAIDs and establish targeted prevention programs.

Design of double-core-shell structural materials for the extraction of non-steroidal anti-inflammatory drugs.

In this work, core-shell material with a special structure was designed and applied in solid-phase extraction (SPE) for non-steroidal anti-inflammatory drugs (NSAIDs) combined with high-performance liquid chromatography. Based on the advantages of core-shell ZIF-8@ZIF-67 (Zeolite imidazole ester framework materials [ZIFs]), effective derivatization treatment was carried out to partially vulcanize the original ZIFs, resulting in a special and new double-core-shell structural material CoS/ZIF-67/ZnS/ZIF-8 (ZIFs@ZnS@CoS) with porous surface and center hollow. The multiple forces caused by the rich chemical structure, the large specific surface area caused by the special pore structure, and the effective protection of the ZIFs core by sulfide shell make the designed material have higher extraction efficiency and longer service life, compared with ZIF-8@ZIF-67 and ZIF-8. At the same time, the established analytical method for non-steroidal drugs had a high recovery rate (98.93%-102.10%), low detection limit (0.11-0.27 µg/L), and wide linear range (1-200 µg/L) within a good correlation coefficient R2 (0.9978-0.9993). Satisfactory results were also obtained from the extraction of NSAIDs from the Yellow River water samples. These results indicate that the designed double-core-shell structure material can effectively exert its structural advantages and become a promising extraction material.

Exploring potential neuroimaging biomarkers for the response to non-steroidal anti-inflammatory drugs in episodic migraine.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are considered first-line medications for acute migraine attacks. However, the response exhibits considerable variability among individuals. Thus, this study aimed to explore a machine learning model based on the percentage of amplitude oscillations (PerAF) and gray matter volume (GMV) to predict the response to NSAIDs in migraine treatment. METHODS: Propensity score matching was adopted to match patients having migraine with response and nonresponse to NSAIDs, ensuring consistency in clinical characteristics and migraine-related features. Multimodal magnetic resonance imaging was employed to extract PerAF and GMV, followed by feature selection using the least absolute shrinkage and selection operator regression and recursive feature elimination algorithms. Multiple predictive models were constructed and the final model with the smallest predictive residuals was chosen. The model performance was evaluated using the area under the receiver operating characteristic (ROCAUC) curve, area under the precision-recall curve (PRAUC), balance accuracy (BACC), sensitivity, F1 score, positive predictive value (PPV), and negative predictive value (NPV). External validation was performed using a public database. Then, correlation analysis was performed between the neuroimaging predictors and clinical features in migraine. RESULTS: One hundred eighteen patients with migraine (59 responders and 59 non-responders) were enrolled. Six features (PerAF of left insula and left transverse temporal gyrus; and GMV of right superior frontal gyrus, left postcentral gyrus, right postcentral gyrus, and left precuneus) were observed. The random forest model with the lowest predictive residuals was selected and model metrics (ROCAUC, PRAUC, BACC, sensitivity, F1 score, PPV, and NPV) in the training and testing groups were 0.982, 0.983, 0.927, 0.976, 0.930, 0.889, and 0.973; and 0.711, 0.648, 0.639, 0.667,0.649, 0.632, and 0.647, respectively. The model metrics of external validation were 0.631, 0.651, 0.611, 0.808, 0.656, 0.553, and 0.706. Additionally, a significant positive correlation was found between the GMV of the left precuneus and attack time in non-responders. CONCLUSIONS: Our findings suggest the potential of multimodal neuroimaging features in predicting the efficacy of NSAIDs in migraine treatment and provide novel insights into the neural mechanisms underlying migraine and its optimized treatment strategy.

Corneal Melt and Perforation Associated With Prolonged Oral Non-Steroidal Anti-Inflammatory Drug (NSAID) Use: A Case Report.

Corneal melt and perforation can arise from various etiologies, including the use of toxic topical drops, particularly topical non-steroidal anti-inflammatory drugs (NSAIDs). The literature has frequently documented the association between the use of topical NSAIDs and the subsequent development of corneal ulcers. More recently, reports have emerged linking the use of oral NSAIDs and colchicine to impaired corneal wound healing and corneal perforation. This case report presents an instance of corneal melting and subsequent perforation in a medically unburdened patient who had been self-administering oral NSAIDs for one year. The evidence presented in this report suggests a plausible association between the prolonged administration of oral NSAIDs and corneal melt. Consequently, healthcare practitioners should be mindful of this potential risk when considering the prolonged use of oral NSAIDs.

NOSH-aspirin (NBS-1120) inhibits estrogen receptor negative breast cancer in vitro and in vivo by modulating redox-sensitive signaling pathways.

Estrogen receptor (ER)-negative breast cancers are known to be aggressive and unresponsive to anti-estrogen therapy, and triple negative breast cancers are associated with poor prognosis and metastasis. Thus, new targeted therapies are needed. FOXM1 is abundantly expressed in human cancers and implicated in protecting tumor cells from oxidative stress by reducing the levels of intracellular reactive oxygen species (ROS). Aspirin, a prototypical anti-cancer agent with deleterious side effects, has been modified to release nitric oxide and hydrogen sulfide, called NOSH-aspirin (NOSH-ASA), generating a 'safer' class of new anti-inflammatory agents. We evaluated NOSH-ASA against (ER)-negative breast cancer using cell lines and a xenograft mouse model. NOSH-ASA strongly inhibited growth of MDA-MB-231 and SKBR3 breast cancer cells with low IC50s of 90{plus minus}5 and 82{plus minus}5 nM, respectively, with marginal effects on a normal breast epithelial cell line. NOSH-ASA inhibited cell proliferation, caused G0/G1 phase arrest, increased apoptosis, and was associated with increases in ROS. In MDA-MB-231 cell xenografts, NOSH-ASA reduced tumor size markedly, which was associated with reduced proliferation (decreased PCNA expression), induction of apoptosis (increased TUNEL positive cells), and increased ROS, while NF-kB and FoxM1 that were high in untreated xenografts were significantly reduced. mRNA data for FoxM1, p21 and CyclinD1 corroborated with the respective protein expressions and arrest of cells. Taken together, these molecular events contribute to NOSH-ASA mediated growth inhibition and apoptotic death of (ER)-negative breast cells in vitro and in vivo. Additionally, as a ROS-inducer and FOXM1-inhibitor, NOSH-ASA has potential as a targeted therapy. Significance Statement In this investigation, we examined the cellular effects and xenograft tumor inhibitory potential of NOSH-aspirin, an NO and H2S-donating hybrid, against ER-negative breast cancer, which currently lacks effective therapeutic options. The induction of reactive oxygen species and subsequent downregulation of FOXM1 represents a plausible mechanism contributing to the observed decrease in cell proliferation and concurrent increase in apoptosis. NOSH-ASA demonstrated a remarkable reduction in tumor size by 90% without inducing any observable gross toxicity, underscoring its promising translational potential.

A Comprehensive Meta-Analysis on the Role of Analgesics and Anti-Inflammatories in Pan-retinal Photocoagulation.

PURPOSE: Pan-retinal photocoagulation (PRP) is the mainstay of treatment for proliferative diabetic retinopathy (PDR), reducing the risk of severe vision loss. Pain poses a potential obstacle to effective laser delivery and patient compliance. Therefore, implementing pain relief strategies can enhance both treatment efficacy and patient comfort. DESIGN: A systematic review and meta-analysis. METHODS: We conducted a systematic review and meta-analysis according to PRISMA guidelines. The PubMed, Embase and Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials (RCTs) that enrolled patients undergoing PRP due to DR and compared analgesics or non-steroidal anti-inflammatory drugs (NSAID) to placebo. Pain was evaluated with the visual analogue scale. The version 2 of the Cochrane Collaboration's Risk of Bias in Randomized Controlled Trials tool and its version for crossover trials were used to assess the risk of bias. The Grading of Recommendations, Assessment, Development, and Evaluation tool was used to measure the certainty of evidence. RESULTS: A total of 13 studies were included, comprising 1404 eyes from RCTs, nine of which were crossover. Patients who were administered analgesia reported a significantly lower pain sensitivity compared to those who received placebo (Standardized mean difference [SMD] -0.38; 95% confidence interval [CI] -0.58, -0.17; P<0.01; I2=69%). Subgroup analysis of systemic administration of analgesics/NSAIDs (metamizole, Entonox, acetaminophen, ibuprofen, caffeine, mefenamic acid, intramuscular ketorolac tromethamine, and potassium diclofenac) also showed a statistically significant reduction in pain when compared to placebo (SMD -0.28; 95% CI -0.50, -0.07; P<0.01; I2=43%). Exclusive eye drops administration (ketorolac tromethamine 0.5% and sodium diclofenac 0.1%) also showed a significant difference in pain sensitivity (SMD -0.46; 95% CI -0.88, -0.05; I2=83%), however with a more significant heterogeneity. CONCLUSION: The results of this meta-analysis including over 1000 patients demonstrated that the use of analgesics significantly reduced pain sensitivity during PRP, and systemic analgesia is potentially better than topical administration when compared to placebo.

Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury.

Objective: To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury (DILI) caused by different drugs and their correlation with clinical indicators. Method: The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests (RUCAM) scoring criteria and clinically diagnosed with DILI. Based on Chinese herbal medicine, cardiovascular drugs, non-steroidal anti-inflammatory drugs (NSAIDs), anti-infective drugs, and other drugs, patients were divided into five groups. Cytokines were measured by Luminex technology. Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results: 73 patients were enrolled. Age among five groups was statistically different ( P = 0.032). Alanine aminotransferase (ALT) ( P = 0.033) and aspartate aminotransferase (AST) ( P = 0.007) in NSAIDs group were higher than those in chinese herbal medicine group. Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with Chinese herbal medicine (IL-6: P < 0.001; TNF-α: P < 0.001) and cardiovascular medicine (IL-6: P = 0.020; TNF-α: P = 0.001) were lower than those in NSAIDs group. There was a positive correlation between ALT ( r = 0.697, P = 0.025), AST ( r = 0.721, P = 0.019), and IL-6 in NSAIDs group. Conclusion: Older age may be more prone to DILI. Patients with NSAIDs have more severe liver damage in early stages of DILI, TNF-α and IL-6 may partake the inflammatory process of DILI.

Infectious Mononucleosis Revealed by Non-steroidal Anti-inflammatory Drug: A First Clinical Report.

Infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV), is a common viral illness among adolescents and young adults. IM typically presents with symptoms such as fever, lymphadenopathy, and pharyngitis. We present a case of a 32-year-old woman who developed a maculopapular rash following ibuprofen administration, revealing an underlying undiagnosed IM. Laboratory investigations confirmed EBV infection. This represents the first documented case linking non-steroidal anti-inflammatory drugs (NSAIDs) to IM presentation. Awareness of this association is crucial for timely diagnosis and management, especially when evaluating patients with unexplained skin reactions to medications.

[Expert consensus on the diagnosis and treatment of respiratory diseases exacerbated by nonsteroidal anti-inflammatory drugs （2024, Chengdu）].

Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease （N-ERD） is a chronic respiratory disease characterized by eosinophilic inflammation, featuring chronic rhinosinusitis （CRS）, asthma, and intolerance to cyclooxygenase 1 （COX-1） inhibitors. The use of these medications can lead to an acute worsening of rhinitis and asthma symptoms. This condition has not yet received sufficient attention in China, with a high rate of misdiagnosis and a lack of related research. The Chinese Rhinology Research Group convened a group of leading young experts in otolaryngology from across the country, based on the latest domestic and international evidence-based medical practices to formulate this consensus.The consensus covers the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies for N-ERD, including pharmacotherapy, surgery, biologic treatments, and desensitization therapy. The goal is to improve recognition of N-ERD, reduce misdiagnosis, and enhance treatment outcomes.

Inter-Semispinalis Plane Block Versus General Anesthesia for Postoperative Analgesia in Posterior Cervical Spine Surgery: A Randomized Controlled Trial.

Background: Postoperative pain management is crucial for improving patient outcomes following posterior cervical spine surgery. Opioids are effective but carry a risk of respiratory depression. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used but may not provide adequate pain relief and have potential complications. The inter-semispinalis plane (ISPB) block is a novel technique for postoperative analgesia in cervical spine surgery. Objectives: This study aims to evaluate and compare the efficacy of the ISPB with general anesthesia in terms of analgesia, postoperative Visual Analog Scale (VAS) pain scores, patient-surgeon satisfaction levels, and the occurrence of postoperative complications. Methods: This double-blind, randomized controlled trial was blinded to both the patient and the assessor. Fifty adult patients (18 - 60 years old) undergoing elective posterior cervical spine surgery were enrolled. The participants were divided into 2 groups: The ISPB group (receiving bilateral ultrasound-guided ISPB at the C5 level) and the control group (receiving general anesthesia only), with each group comprising 25 patients. The study assessed intraoperative fentanyl use, postoperative VAS pain levels, the need for rescue analgesia, and complications. Results: The ISPB group showed significantly lower intraoperative fentanyl consumption (median 100 vs. 100 - 150 µg, P = 0.022) and lower postoperative pain scores at 1, 8, 12, and 48 hours (P = 0.016, 0.009, 0.005, 0.016). Additionally, the ISPB group required less postoperative pethidine (20% vs. 64%, P = 0.002) and had a longer delay before requesting pethidine (hazard ratio 0.215, P = 0.001). Surgeon satisfaction was significantly higher in the ISPB group (P = 0.003). These results suggest that the ISPB can effectively reduce pain and analgesic requirements. Conclusions: The ISPB is an effective analgesic technique for posterior cervical spine surgery, reducing opioid consumption, providing better pain control, and enhancing surgeon satisfaction without increasing complications. This approach has the potential to improve postoperative care and patient outcomes in this surgical population.

Dexamethasone and chronic postsurgical pain: the pendulum meets reductionistic thinking.

Reductionist thinking results in the bulk of anaesthesia trial designs being a single intervention to address what are in fact complex processes. The Perioperative Administration of Dexamethasone and Infection (PADDI) trial assessed the safety of a single preoperative dose of dexamethasone. Surprising to most, in the original report, a single dose of dexamethasone increased the incidence of the secondary outcome chronic postsurgical pain. Was this a chance finding or does dexamethasone increase chronic postsurgical pain? In an attempt to address this question, the PADDI investigators have now analysed this prespecified secondary outcome in two ways: as a substudy published earlier in this Journal, and as a retrospective analysis of the ENIGMA-II chronic pain database in this issue of the Journal. The PADDI investigators have now presented enough data to convince us that indeed a single dose of dexamethasone is safe and effective. However, the increase in chronic postsurgical pain seen in the original PADDI publication highlights the complexities, and the possible immunologic mechanisms, behind the genesis of chronic postsurgical pain. These publications from the PADDI group raise questions about other anti-inflammatory agents we use regularly for long-term postoperative pain management, and highlights the need for well-designed clinical trials to address this critically important patient-centred adverse functional outcome.

Inflammation and cancer: friend or foe?

Chronic inflammation plays a crucial role in the onset and progression of pathologies like neurodegenerative and cardiovascular diseases, diabetes, and cancer, since tumor development and chronic inflammation are linked, sharing common signaling pathways. At least 20% of breast and colorectal cancers are associated with chronic inflammation triggered by infections, irritants, or autoimmune diseases. Obesity, chronic inflammation, and cancer interconnection underscore the importance of population-based interventions in maintaining healthy body weight, to disrupt this axis. Given that the dietary inflammatory index is correlated with an increased risk of cancer, adopting an anti-inflammatory diet supplemented with nutraceuticals may be useful for cancer prevention. Natural products and their derivatives offer promising antitumor activity with favorable adverse effect profiles; however, the development of natural bioactive drugs is challenging due to their variability and complexity, requiring rigorous research processes. It has been shown that combining anti-inflammatory products, such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and statins, with plant-derived products demonstrate clinical utility as accessible adjuvants to traditional therapeutic approaches, with known safety profiles. Pharmacological approaches targeting multiple proteins involved in inflammation and cancer pathogenesis emerge as a particularly promising option. Given the systemic and multifactorial nature of inflammation, comprehensive strategies are essential for long term success in cancer therapy. To gain insights into carcinogenic phenomena and discover diagnostic or clinically relevant biomarkers, is pivotal to understand genetic variability, environmental exposure, dietary habits, and TME composition, to establish therapeutic approaches based on molecular and genetic analysis. Furthermore, the use of endocannabinoid, cannabinoid, and prostamide-type compounds as potential therapeutic targets or biomarkers requires further investigation. This review aims to elucidate the role of specific etiological agents and mediators contributing to persistent inflammatory reactions in tumor development. It explores potential therapeutic strategies for cancer treatment, emphasizing the urgent need for cost-effective approaches to address cancer-associated inflammation.

Biologics Reduce Symptoms of Alcohol Intolerance Better than Aspirin Desensitization in Patients with N-ERD and Nasal Polyps.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and NSAID hypersensitivity. An overproduction of leukotrienes characterizes the pathomechanism of the disease. N-ERD patients often report breathing difficulties after consuming alcohol. These symptoms have been observed in patients receiving either aspirin therapy after desensitization (ATAD), therapy with the biologics dupilumab (anti-IL-4Ra antibody) and omalizumab (anti-IgE antibody), or intranasal corticosteroid treatment (INCS). METHODS: This retrospective, real-world study assessed the severity of alcohol-related and non-alcohol-related respiratory symptoms in CRSwNP/N-ERD patients 3-6 months after ATAD, biologic (dupilumab or omalizumab), or INCS therapy. A total of 171 patients (98 women and 73 men) were enrolled in the study. All groups received standard INCS therapy. Sixty-three patients were treated with ATAD; 48 received biologics (dupilumab n = 31; omalizumab n = 17); and 60 received INCS only and served as a control group. Alcohol-dependent symptoms and typical CRS symptoms (alcohol-independent) were quantified using visual analog scales (VAS). RESULTS: ATAD and biological therapy significantly reduced VAS scores for alcohol dependence and CRS symptoms. In the control group receiving INCS, only non-alcohol dependent CRS symptoms improved significantly (p < 0.05). The most significant differences in pre/post scores were observed in patients receiving dupilumab, with the most significant improvement in alcohol-dependent and CRS symptoms (dupilumab > omalizumab > ATAD). CONCLUSIONS: This real-world study shows that alcohol-related respiratory symptoms are a relevant parameter in CRSwNP/N-ERD patients. Patients benefit more from biologic therapy than from ATAD in terms of their alcohol-related symptoms and other CRS symptoms. Future studies should include placebo-controlled oral alcohol challenge.

Determinants of appropriate antibiotic and NSAID prescribing in unscheduled outpatient settings in the veterans health administration.

BACKGROUND: Despite efforts to enhance the quality of medication prescribing in outpatient settings, potentially inappropriate prescribing remains common, particularly in unscheduled settings where patients can present with infectious and pain-related complaints. Two of the most commonly prescribed medication classes in outpatient settings with frequent rates of potentially inappropriate prescribing include antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). In the setting of persistent inappropriate prescribing, we sought to understand a diverse set of perspectives on the determinants of inappropriate prescribing of antibiotics and NSAIDs in the Veterans Health Administration. METHODS: We conducted a qualitative study guided by the Consolidated Framework for Implementation Research and Theory of Planned Behavior. Semi-structured interviews were conducted with clinicians, stakeholders, and Veterans from March 1, 2021 through December 31, 2021 within the Veteran Affairs Health System in unscheduled outpatient settings at the Tennessee Valley Healthcare System. Stakeholders included clinical operations leadership and methodological experts. Audio-recorded interviews were transcribed and de-identified. Data coding and analysis were conducted by experienced qualitative methodologists adhering to the Consolidated Criteria for Reporting Qualitative Studies guidelines. Analysis was conducted using an iterative inductive/deductive process. RESULTS: We conducted semi-structured interviews with 66 participants: clinicians (N = 25), stakeholders (N = 24), and Veterans (N = 17). We identified six themes contributing to potentially inappropriate prescribing of antibiotics and NSAIDs: 1) Perceived versus actual Veterans expectations about prescribing; 2) the influence of a time-pressured clinical environment on prescribing stewardship; 3) Limited clinician knowledge, awareness, and willingness to use evidence-based care; 4) Prescriber uncertainties about the Veteran condition at the time of the clinical encounter; 5) Limited communication; and 6) Technology barriers of the electronic health record and patient portal. CONCLUSIONS: The diverse perspectives on prescribing underscore the need for interventions that recognize the detrimental impact of high workload on prescribing stewardship and the need to design interventions with the end-user in mind. This study revealed actionable themes that could be addressed to improve guideline concordant prescribing to enhance the quality of prescribing and to reduce patient harm.

Drug-Induced Pseudoporphyria: A Case Report.

Pseudoporphyria is an uncommon dermatosis resembling porphyria cutanea tarda (PCT). The exclusion of true porphyria, especially PCT, is critically essential for diagnosing pseudoporphyria. It has an unknown underlying pathophysiology with a normal or near-normal porphyrin profile. Pseudoporphyria has been associated with chronic renal failure and hemodialysis, medications, and tanning beds. In drug-induced pseudoporphyria cases, eliminating the suspected photosensitizing drug improves the disease typically within weeks to months (on average eight weeks). In genetically predisposed individuals, phototoxic metabolites may trigger the development of skin fragility, bullae, milia, and scarring on the dorsum of the hands and other sun-exposed areas. Wearing a broad-spectrum sunscreen and maintaining strict ultraviolet protection is essential in cases of pseudoporphyria. We report the case of a 20-year-old male who presented to us with complaints of photosensitivity and multiple erosions with irregular scars over photo-exposed areas involving the dorsum of the hands and face predominantly. The patient was evaluated further to determine the underlying cause. A wood's lamp examination of the urine was done, which did not show fluorescence. Based on clinical and laboratory findings, the diagnosis of pseudoporphyria was made, and the patient was started on the oral antimalarial agent hydroxychloroquine sulfate with strict sun protection.

Clinical Outcomes of Topical Bevacizumab for the Treatment of Corneal Neovascularization.

Background and objective In corneal neovascularization, the peri-corneal vascular structure grows into a normally avascular cornea. This is due to an imbalance between the angiogenic and anti-angiogenic factors that sustain corneal transparency. There are various etiologies of this condition, and they can be divided into infective or non-infective causes, such as inflammation, trauma, or surgical causes. Corneal neovascularization has been shown to improve with the current treatments using steroids and anti-vascular endothelial growth factors. This study aimed to evaluate the effectiveness of topical bevacizumab as an anti-angiogenic agent in patients with corneal neovascularization. Methods This retrospective study included patients who suffered corneal neovascularization of various etiologies and completed six months of topical bevacizumab therapy between 2020 and 2022 at the Universiti Kebangsaan Malaysia Medical Centre. Results A total of 16 patients received treatment with topical bevacizumab over the three-year study period. Based on specified inclusion and exclusion criteria, 12 patients were eligible for inclusion in this study. Eight patients (66%) showed improvement in terms of either 'clock hours' of improvement, morphology, or regression of corneal neovascularization. All infective causes of corneal neovascularization showed improvement on completion of bevacizumab compared to other causes. Conclusion Topical bevacizumab can be one of the treatment choices for corneal neovascularization. As the outcome varies depending on the severity and chronicity of the condition, the attending ophthalmologist should treat each case differently. Although topical bevacizumab is more effective in mild and moderate cases, the indications for its use in chronic cases remain debatable as the results are unfavorable in such cases.

A blinded, randomized and controlled multicenter field study investigating the safety and efficacy of long-term use of enflicoxib in the treatment of naturally occurring osteoarthritis in client-owned dogs.

Background: Enflicoxib is a COX-2 selective NSAID shown to be efficacious and safe in the treatment of pain and inflammation associated with canine osteoarthritis (OA) in clinical studies of 6 weeks duration. Objective: This prospective, multisite, blinded, randomized, placebo-controlled, parallel-group field study aimed to confirm the safety and efficacy of enflicoxib in long-term canine OA treatments. Animals: A total of 109 client owned dogs with clinical and radiographic signs of OA for at least 3 weeks were enrolled with 78 dogs completing all study visits. Methods: Dogs were randomized at a 3:1 ratio to receive enflicoxib (n = 83) or placebo (n = 26) once weekly during 6 months. Dogs underwent veterinary assessments from Day 0 to Day 189 using a clinical sum score (CSS). Efficacy was also assessed by the owners using the Canine Brief Pain Inventory (CBPI). Safety was assessed clinically and by repeated blood and urine sample analysis. The efficacy outcome measure was the treatment response according to the CSS and secondarily the treatment response according to the CBPI. The primary safety outcome was the incidence of adverse events (AEs) and secondarily the evolution of the clinical pathology parameters. Results: Percentages of CSS responders for enflicoxib were 71.6; 74.6 and 71.6% on Days 44, 135 and 189 respectively, always showing statistically significant differences (p < 0.05) vs. placebo (41.7, 33.3, and 20.8% respectively). Treatment response according to owner assessments followed the same pattern, achieving significant differences compared to placebo after 2 weeks of treatment. The incidence and type of AEs were as described in previous enflicoxib studies of shorter duration and as for other NSAIDs, with no tendency to increase over time. No relevant changes in hematology, biochemistry or urine parameters were observed. Conclusions and clinical relevance: Enflicoxib safety and efficacy profile is maintained after a long-term treatment, which together with its weekly administration, makes it a good alternative for the chronic treatment of dogs with naturally occurring OA.

A mixed-mode reversed-phase/strong-anion-exchange stationary phase: Analyte-retention stability and application in the analysis of nonsteroidal anti-inflammatory drugs.

Mixed-mode reversed-phase/anion-exchange chromatography (RP/AEX) is an effective method for the chromatographic analysis of acidic drugs because it combines reversed-phase chromatography (RP) with anion-exchange chromatography (AEX). However, the result repeatability for the RP/AEX analysis of acidic drugs is frequently compromised by the detrimental effects of residual silanol groups in an RP/AEX stationary phase on peak separation and analyte retention. In this study, an RP/weak-AEX stationary phase with amino anion-exchange groups, Sil-AA, was prepared. Subsequently, an RP/strong-AEX stationary phase, Sil-PBQA, was prepared by replacing the amino groups in Sil-AA with a benzene ring and a benzyl-containing quaternary ammonium salt. The chromatographic behaviors of Sil-PBQA and Sil-AA were compared, and the effect of residual silanol groups on the chromatographic behavior of an RP/AEX stationary phase was evaluated. Residual silanol groups not only caused additional electrostatic interactions for acidic analytes, but also competed with the analytes for the anion-exchange sites in an RP/AEX stationary phase. The effects of different salt-containing mobile-phase systems on the analyte-retention behavior of Sil-PBQA were investigated to develop a method that enhanced the repeatability of the RP/AEX acidic-analyte-analysis results obtained using Sil-PBQA and facilitated the separation of nonsteroidal anti-inflammatory drugs on Sil-PBQA. The ideas presented in this paper can improve the separation of peaks and repeatability of results in the RP/AEX analysis of acidic drugs.

Moderators of treatment effect of non-steroidal anti-inflammatory drugs for patients with (sub) acute low back pain: Protocol for a systematic review with individual participant data meta-analysis.

A Cochrane review found that non-steroidal anti-inflammatory drugs (NSAIDs) are slightly more effective than placebo on acute and subacute low back pain (LBP) outcomes (pain intensity, disability, and global improvement). Our objectives are: (1) to assess the overall treatment effect of NSAIDs in adults with acute and subacute LBP; (2) to identify the moderation of baseline patients' characteristics on treatment effect. We will conduct a systematic search of RCTs on effectiveness of NSAIDs compared with placebo in adults with non-chronic LBP in Medline ALL, Embase, Cochrane Central Register of Controlled Trials*. We will screen the records after January 2020, and include eligible RCTs before January 2020 screened by the Cochrane review mentioned above. Our primary outcomes are pain intensity, disability, and health-related quality of life, secondary outcomes are adverse events. Our IPD dataset will consist of the information on each eligible trial characteristics and included variables according to a predefined coding scheme. We will assess risk-of-bias of included RCTs with the Cochrane Risk Of Bias (RoB)-2 assessment tool. We will perform power calculations with closed-form solutions and prioritize a one-stage approach for IPD-MA. For reporting the results, we will adhere to the PRISMA-IPD statement.