Systemic Nonsteroidal Anti-inflammatory Drugs Research Articles

Selection of NSAIDs for rational pharmacotherapy of chronic musculoskeletal pain: a clinical pharmacologist's perspective

Chronic musculoskeletal pain (CMSP) is one of the most common pathological conditions that limits patients' physical activity and reduces their quality of life. The analgesic and anti-inflammatory effects of non-steroidal anti-inflammatory drugs (NSAIDs) make them the basis of pharmacotherapy for patients with chronic conditions affecting various parts of the musculoskeletal system. The main target of NSAIDs, cyclooxygenase (COX), exists in the form of two main isoforms, COX-1 and COX-2, the inhibition of each of which leads to a cascade of reactions at the cellular and tissue level that can cause both targeted pharmacological effects and side effects. The diversity of the chemical structures of NSAIDs leads to differences in their pharmacodynamic and pharmacokinetic parameters and correspondingly to differences in their efficacy and safety profile. Selective COX-2 inhibitors, coxibs, have shown an increased risk of cardiovascular side effects, which has led to significant restrictions on their use. Cardiotoxicity is not as pronounced with the non-selective COX inhibitors, but the range of their side effects is extremely wide. These side effects are dose-dependent and are characteristic, first of all, of systemic NSAIDs.The combination of systemic and topical NSAIDs makes it possible to reduce the dose of the former and improve the safety profile of anti-inflammatory therapy. Among the non-selective COX inhibitors with a satisfactory safety profile and high anti-inflammatory activity, the group of oxicams and especially tenoxicam should be emphasised, which are characterised by a maximum duration of action, which is an advantage in the treatment of patients with CMSP. This review addresses the issues of rational selection of NSAIDs based on comparative data on pharmacodynamics, pharmacokinetics and clinical trial results.

Blast Eye Injury After Mobile Phone Battery Explosion: A Case Report

Introduction : Injuries from mobile phone blasts have been on the rise in recent years. Mobile phone blasts cause serious ocular morbidity. We report a rare case of blast eye injury after mobile phone battery explosion.
 Case Illustration : A 16 years old woman presented with burning sensation on both the eyes, following a smartphone battery blast. Immediately, after disconnecting the phone from the charger, the battery exploded and the phone blew apart. Her presenting visual acuity was 1/300 and 1.0 in right eye and left eye. Examination revealed broad corneal haziness on right eye, charred lashes, circumciliary congestion, and multiple soot particles embedded over the cornea, conjunctiva, and the lid margins. The eyes were washed with copious ringer lactate and the debris was carefully removed. Topical preservative free lubricants, broad-spectrum antibacterial agent, corticosteroid, and cycloplegic agent were prescribed along with systemic nonsteroidal anti-inflammatory drug. The healing of epithelial defects started on the next day and was complete by the 14th day.
 Discussion : We describe an ocular blast injury due to mobile phone explosion. The mechanism of injury from battery blast could be a combination of mechanical (battery pieces), thermal, and chemical injuries. The vision can be saved if the ocular surface burns are treated promptly and properly.
 Conclusion : Mobile blast injury is emerging as a new mode of ocular trauma. Knowing proper management is very important to achieve the best result.

Trends in harmful drug exposure during pregnancy in France between 2013 and 2019: A nationwide cohort study.

Describe the trends of exposure to harmful drugs during pregnancy over recent years in France. Nationwide cohort study. The French National administrative health Data System (SNDS). Pregnancies starting between 2013 and 2019 and outcomes corresponding to live births, medical terminations of pregnancy, and stillbirths. Each pregnancy was divided into a preconceptional period of 90 days before conception and three trimesters from conception to birth. Harmful drugs were defined according to their risks to the fetus: teratogenicity or fetotoxicity. Exposure was defined using the critical period during pregnancy for each type of harmful drug: preconceptional period or first trimester for teratogenic drugs and second or third trimesters for fetotoxic drugs. Prevalence of pregnancies exposed to at least one harmful drug. Among 5,253,284 pregnancies, 204,402 (389 per 10,000) pregnancies were exposed to at least one harmful drug during the critical periods: 48,326 (92 per 10,000) pregnancies were exposed to teratogenic drugs during the preconceptional period or the first trimester, and 155,514 (299 per 10,000) pregnancies were exposed to fetotoxic drugs during the second or third trimesters. Teratogenic drugs were mainly retinoids for topical use (44 per 10,000 pregnancies), antiepileptics (13 per 10,000 pregnancies) and statins (13 per 10,000 pregnancies). Fetotoxic drugs were mainly non-steroidal anti-inflammatory drugs (NSAIDs), for systemic (128 per 10,000 pregnancies) and topical use (122 per 10,000 pregnancies). Exposure to teratogenic drugs decreased from the preconceptional period to the first trimester. Exposure to fetotoxic drugs decreased from the second to the third trimester. Between 2013 and 2019, we found a decrease in harmful drug exposure overall, mainly for topical and systemic NSAIDs and for topical retinoids. In this nationwide study, about one in 25 pregnancies was exposed to at least one harmful drug, mainly NSAIDs and topical retinoids. Although the prevalence of harmful drug exposure decreased over the study period, NSAID exposure in the second and third trimester remains of concern.

Surgically Induced Scleritis Associated With Suture Hypersensitivity Following Strabismus Surgery.

A 67-year-old woman with history of mild suture hyper-sensitivity presented with localized scleritis after strabismus surgery. After infection was ruled out, the patient was prescribed topical and systemic non-steroidal anti-inflammatory drugs and systemic steroids, which led to full clinical resolution. [J Pediatr Ophthalmol Strabismus. 2024;61(1):e4-e6.].

Drug Exposure During Pregnancy: A Case-Control Study from a Primary Care Database.

Drug exposure during pregnancy is frequent, even more during first trimester as pregnant women might not be aware of their condition. We used available electronic health records (EHRs) to describe the use of medications during the first trimester in pregnant women and to compare drug exposure between those women who had an abortion (either elective or spontaneous) compared to those who had live births. Case-control study of abortions, either elective or spontaneous (cases), and live birth pregnancies (controls) in Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària (Catalan Primary Health electronic health records) from 2012 to 2020. Exposure to drugs during first trimester of pregnancy was considered to estimate the association with abortion by conditional logistic regression and adjusted by health conditions and other drugs exposure. Sixty thousand three hundred fifty episodes of abortions were matched to 118,085 live birth pregnancy episodes. Cases had higher rates of alcohol intake (9.9% vs. 7.2%, p < 0.001), smoking (4.5% vs. 3.6%, p < 0.001), and previous abortions (9.9% vs. 7.8%, p < 0.001). Anxiety (30.3% and 25.1%, p < 0.001), respiratory diseases (10.6% and 9.2%, p < 0.001), and migraine (8.2% and 7.3%, p < 0.001), for cases and controls, respectively, were the most frequent baseline conditions. Cases had lower rate of drug exposure, 40,148 (66.5%) versus 80,449 (68.1%), p < 0.001. Association with abortion was found for systemic antihistamines (adjusted odds ratio [ORadj] 1.23, 95% confidence interval [CI] 1.19-1.27), antidepressants (ORadj 1.11, 95% CI 1.06-1.17), anxiolytics (ORadj 1.31, 95% CI 1.26-1.73), and nonsteroidal anti-inflammatory drugs (ORadj 1. 63, 95% CI 1.59-1.67). These high rates of drug exposures during the first trimester of pregnancy highlights the relevance of informed prescription to women with childbearing potential.

Comparison of drugs belonging to the group of ophthalmic non-steroidal anti-inflammatory drugs

Ophthalmic non-steroidal anti-inflammatory drugs are non-steroidal anti-inflammatory drugs used to treat or prevent eye inflammation. Their main action is to relieve symptoms such as pain, redness and swelling that can be caused by eye diseases, injuries or eye surgery. Non-steroidal anti-inflammatory drugs used in ophthalmology include substances such as diclofenac, ketorolac, bromfenac and nepafenac. So far, many studies have been published comparing the effectiveness of various systemic and local non-steroidal anti-inflammatory drugs. This work contains a comparative analysis of the above-mentioned substances in terms of their use and effectiveness in ophthalmology.

Moderate to Severe Osteoarthritis: What is the Economic Burden for Patients and the Health Care System? Insights from the "PONOS" Study.

To assess the economic burden of moderate to severe osteoarthritis (OA) management for patients and the health care system in Greece. A noninterventional, cross-sectional, prospective, epidemiological analysis of data from the medical records of patients with moderate to severe OA, recruited in a single visit from 9 sites in Greece. Outcomes included health care resource use (direct/indirect costs) associated with this patient population. A total of 164 patients were included in the analysis: mean age was 70.5 years, and the majority of participants were females (78.7%). The presence of comorbidities was reported by 87.2% of patients, with hypertension being the most frequently reported (53.7%). Paracetamol was the most commonly used analgesic treatment (96%), followed by systemic nonsteroidal anti-inflammatory drugs (NSAIDs) (75%) and opioids (50%). The mean overall annual direct costs per patient was estimated at 1,675.3€, with approximately half incurred by the National Health Insurance Fund, whereas the mean overall annual indirect cost (absenteeism of patients and informal caregivers) was estimated at 3,501.4€. Joint replacement (JR) procedures and paid care were the major drivers of annual direct costs in this patient population (4,326.3€ and 9,360.0€, respectively). This real-world analysis of direct and indirect costs confirmed the substantial economic burden imposed by moderate to severe OA to the health care system and the patients. Our findings emphasize the need for interventions to enhance disease management, to improve patients' health outcomes and reduce the global burden of OA on society.

A retrospective study of treatment, outcome, recurrence and concurrent diseases in 190 dogs with anal sacculitis.

Few studies report the treatment and recurrence rate in anal sacculitis (AS). Retrospective study reporting the management, recurrence and concurrent diseases in dogs with AS in a primary care practice. One hundred and ninety privately owned dogs in Sweden. Clinical records of dogs diagnosed with AS between 2018 and 2021 were reviewed, and management, time until clinical resolution, number of recurrent episodes and comorbidites were recorded. The 190 dogs developed 290 episodes of AS. The most common management, in 235 of 290 (81.0%) episodes, was flushing ± infusion of an antimicrobial product into the sacs ± prescription of a nonsteroidal anti-inflammatory drug (NSAID), providing resolution in 213 of 235 (90.6%) episodes. Median time to resolution was one week (range 1-16 weeks), with resolution seen within one week in 205 of 290 (70.7%) episodes. A single episode of AS developed in 126 of 190 (66.3%) dogs. Dogs with concurrent cutaneous allergic disease were more likely (p < 0.001) to have recurrence of AS when compared to dogs with other comorbidities. Cutaneous allergic disease occurred more often (p < 0.001) in dogs with AS than in the practice population. Local treatment of the anal sacs ± systemic NSAID was the most common treatment, inducing clinical resolution in the majority of dogs. Cutaneous allergic disease was the most common concurrent diagnosis, with higher recurrence rate of AS compared to other diseases and occurring in higher prevalence than in the practice population. Further studies are needed to determine if management of cutaneous allergic disease would reduce the risk of AS.

Retrospective evaluation of the incidence of gastrointestinal bleeding in dogs receiving ophthalmic nonsteroidal anti-inflammatory drugs.

To report the incidence of gastrointestinal (GI) bleeding and associated risk factors in a population of dogs receiving ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs). Medical records of dogs prescribed ophthalmic NSAIDs (cases), dogs receiving systemic NSAIDs alone and dogs receiving systemic prednisone alone (controls). Data were collected retrospectively from the medical records of 204 dogs prescribed ophthalmic NSAIDs (diclofenac, ketorolac, or flurbiprofen), which were subdivided based on if they received any concurrent systemic NSAIDs or glucocorticoids, 136 dogs receiving a systemic NSAID (carprofen or meloxicam) alone, and 151 dogs receiving a systemic glucocorticoid (prednisone) alone at a referral hospital from 2015 to 2019. Gastrointestinal bleeds developed in 8/79 (10.1%) of topical NSAID-only cases, 10/136 (7.4%) of systemic NSAID controls, and 14/151 (9.3%) of systemic glucocorticoid controls, with no significant difference between the three groups (p = .6103). There were no significant differences in GI bleed rates between cases treated with ketorolac, diclofenac, or flurbiprofen (p = .160), although severe GI bleeding was only seen in ketorolac-treated dogs. Presence of a known concurrent risk factor for GI bleeding was significantly associated with the development of GI bleed in dogs on ophthalmic NSAIDs (p = .032). Dogs treated with ophthalmic NSAIDs developed GI bleeding at a frequency comparable to dogs receiving systemic NSAIDs or systemic glucocorticoids alone, suggesting that dogs receiving ophthalmic NSAIDs may be at increased risk of GI bleeding.

Phenylbutazone concentrations in synovial fluid following administration via intravenous regional limb perfusion in the forelimbs of six adult horses.

Pain management is critical to equine welfare with non-steroidal anti-inflammatory drugs (NSAID) commonly used in horses. However, systemic NSAID use is limited by harmful gastrointestinal and renal side effects. Intravenous regional limb perfusion (IVRLP) is a technique used in horses that produces high, local antibiotic concentrations while limiting systemic circulation. NSAID-IVRLP would be a novel method of local pain management while limiting systemic NSAID side effects. To date, NSAID-IVRLP administration has not been reported in horses. This study aimed to identify the pharmacokinetics and local complications associated with using the NSAID phenylbutazone (PBZ) for IVRLP in six standing adult horses. PBZ-IVRLP, at a dose of 2.2 mg/kg PBZ, was performed in a randomly assigned forelimb cephalic vein in 6 standing, healthy adult horses. A placebo-IVRLP was performed in the contralateral forelimb for comparison. Systemic serum and radiocarpal joint synovial fluid PBZ concentrations were identified at various timepoints (before IVRLP T-0 h, just after tourniquet removal T-0.5, 1.5, 3, 5, 12, 16, and 24 h post IVRLP) for non-compartmental pharmacokinetic analysis and concentration over time curves. Local complications associated with PBZ-IVRP were evaluated for up to 7 days following PBZ-IVRLP using physical and ultrasonographic assessment. On day 7 horses were humanely euthanized with histology performed on both forelimbs at PBZ-IVRLP and placebo-IVRLP administration sites. Non-compartmental pharmacokinetics for PBZ, and its major metabolite oxyphenbutazone (OBZ), were determined for serum and synovial fluid. Synovial PBZ concentrations (mean ± SD; 1.9 ± 2.1 μg/mL) were significantly lower (p = 0.03; CI,0.46-7.36) than serum PBZ concentrations (5.8 ± 5.1 μg/mL) at any time point. Physical and ultrasonographic measurements were not significantly different between PBZ- and placebo-IVRLP forelimbs. The most common histologic findings included focal deep dermal/subcutaneous hemorrhage and edema. Two horses showed perivasculitis and one horse showed a resolving thrombus in the cephalic vein of the PBZ-IVRLP limb. This horse also had severe perivasculitis and fibrinosuppurative dermatitis/panniculitis in the placebo-IVRLP limb. PBZ-IVRLP pharmacokinetics at a 2.2 mg/kg dose showed no benefit compared to systemic PBZ administration in standing adult horses. Local complications associated with PBZ-IVRLP were similar to placebo-IVRLP on physical and ultrasonographic evaluation.

Resolution of the Council of Experts of May 20, 2023 "Issues of safety in the treatment of a rheumatological patient"

At the meeting of the Expert Council on May 20, the safety of treatment for patients with osteoarthritis (OA), the most common form of joint disease, was discussed. The first step in the treatment of OA should be the administration of symptomatic delayed-acting agents (SYSADOA) and nonsteroidal anti-inflammatory drugs (NSAIDs). However, given the current understanding of the pathogenesis of inflammation, as well as the fact that it is an active process involving multiple proinflammatory and pro-resolving mediators, it is reasonable to limit the cyclooxygenase-2 suppressive treatment and to include medications with multipurpose effects that contribute to the resolution of inflammation, in particular Zeel® T and Traumeel® S. Traumeel® S affects all stages of inflammation, mostly on the pro-resolving mediators synthesis, and Zeel® T affects chondrogenesis, inflammation, metabolic processes in cartilage tissue and prevents angiogenesis.It was found that it is advisable to use Traumeel® S when it is not possible to prescribe systemic NSAIDs for pain relief. The combination of the proven therapeutic efficacy of Zeel® T and Traumeel® S with a minimal number of adverse events and the absence of interactions with other drugs allows them to be used as an independent treatment regimen for OA.

Systemic Diclofenac Sodium Reduces Postoperative rhBMP-2 Induced Neuroinflammation: A Rodent Model Study.

This is a basic science, animal research study. This study aims to explore, in rodent models, the effectiveness of systemic nonsteroidal anti-inflammatory drugs in reducing recombinant human bone morphogenetic protein-2 (rhBMP-2) induced neuroinflammation. rhBMP-2 is increasingly used to augment fusion in lumbar interbody fusion surgeries, although it can cause complications including postoperative radiculitis. Eighteen 8-week-old Sprague-Dawley rats underwent Hargreaves testing to measure the baseline thermal withdrawal threshold before undergoing surgical intervention. The L5 nerve root was exposed and wrapped with an Absorbable Collagen Sponge containing rhBMP-2. Rats were randomized into 3 groups: (1) Low dose (LD), (2) high dose (HD) diclofenac sodium, and (3) saline, receiving daily injection treatment. Hargreaves testing was performed postoperatively on days 5 and 7. Seroma volumes were measured by aspiration and the nerve root was then harvested for hematoxylin and eosin, immunohistochemistry, Luxol Fast Blue staining, and real-time quantitative polymerase chain reaction. The Student t test was used to evaluate the statistical significance among groups. The intervention groups showed reduced seroma volume, and a general reduction of inflammatory markers (MMP12, MAPK6, GFAP, CD68, and IL18) compared with controls, with the reduction in MMP12 being statistically significant ( P = 0.02). Hematoxylin and eosin and immunohistochemistry of the nerve roots showed the highest macrophage density in the saline controls and the lowest in the HD group. Luxol Fast Blue staining showed the greatest extent of demyelination in the LD and saline groups. Lastly, Hargreaves testing, a functional measure of neuroinflammation, of the HD group demonstrated a minimal change in thermal withdrawal latency. In contrast, the thermal withdrawal latency of the LD and saline groups showed a statistically significant decrease of 35.2% and 28.0%, respectively ( P < 0.05). This is the first proof-of-concept study indicating that diclofenac sodium is effective in alleviating rhBMP-2-induced neuroinflammation. This can potentially impact the clinical management of rhBMP-2-induced radiculitis. It also presents a viable rodent model for evaluating the effectiveness of analgesics in reducing rhBMP-2-induced inflammation.

Pharmacological approaches to pulmonary fibrosis following COVID-19.

Background: In the past few years, COVID-19 became the leading cause of morbidity and mortality worldwide. Although the World Health Organization has declared an end to COVID-19 as a public health emergency, it can be expected, that the emerging new cases at the top of previous ones will result in an increasing number of patients with post-COVID-19 sequelae. Despite the fact that the majority of patients recover, severe acute lung tissue injury can in susceptible individuals progress to interstitial pulmonary involvement. Our goal is to provide an overview of various aspects associated with the Post-COVID-19 pulmonary fibrosis with a focus on its potential pharmacological treatment options. Areas covered: We discuss epidemiology, underlying pathobiological mechanisms, and possible risk and predictive factors that were found to be associated with the development of fibrotic lung tissue remodelling. Several pharmacotherapeutic approaches are currently being applied and include anti-fibrotic drugs, prolonged use or pulses of systemic corticosteroids and non-steroidal anti-inflammatory and immunosuppressive drugs. In addition, several repurposed or novel compounds are being investigated. Fortunately, clinical trials focused on pharmacological treatment regimens for post-COVID-19 pulmonary fibrosis have been either designed, completed or are already in progress. However, the results are contrasting so far. High quality randomised clinical trials are urgently needed with respect to the heterogeneity of disease behaviour, patient characteristics and treatable traits. Conclusion: The Post-COVID-19 pulmonary fibrosis contributes to the burden of chronic respiratory consequences among survivors. Currently available pharmacotherapeutic approaches mostly comprise repurposed drugs with a proven efficacy and safety profile, namely, corticosteroids, immunosuppressants and antifibrotics. The role of nintedanib and pirfenidone is promising in this area. However, we still need to verify conditions under which the potential to prevent, slow or stop progression of lung damage will be fulfilled.

Analysis of the development dynamics of cough syndrome in acute nasopharyngitis with intoxication syndrome

Introduction. Although acute cough in acute inflammatory diseases of the upper respiratory tract seems to be a minor problem and can be stopped on its own, it holds the leading position among all reasons for population receiving health care due to significant decrease in life quality.Purpose. To analyze the cough severity in patients with acute nasopharyngitis with intoxication syndrome in the treatment of systemic non-steroidal anti-inflammatory drugs (NSAIDs) and local interferon therapy.Materials and methods. The study included 62 patients with acute nasopharyngitis with intoxication syndrome, in the period from the onset of the first symptoms to the visit to the doctor was no more than 24 hours. They were divided into 2 groups: group 1 − 32 people (14 men, 18 women, age 34.4 ± 10.3 years) received traditional systemic therapy with NSAIDs, group 2 − 30 people (13 men, 17 women, age 41.1 ± 13.7 years) received interferon-α2b intranasally. Cough severity was assessed using a 3-point visual analog scale (VAS) on the day of admission and for the next 7 days.Results. On the 1st day dry cough was observed in 62.5–63.3% of cases. Starting from the 3rd day of observation, there were statistically significant differences in the intensity of this symptom between the groups. In the traditional therapy of NSAIDs, an increase in the number of patients with a complaint of cough, and an increase in its severity compared with the first day of observation was revealed. They lasted until the 6th day of illness, which was explained by the spread of the inflammatory process to the trachea and bronchi. In the treatment of local interferon therapy, cough regression was noted on day 4 in 83.3% of cases, with its complete disappearance in this group on day 6. The total duration of cough in group 1 was 6.0 (5.0; 8.0) days, in group 2 – 2.0 (1.0; 3.0) days.Conclusion. In acute inflammatory diseases of the upper respiratory tract, cough in the absence of prescribing drugs that affect this symptom persists on the eighth day of observation in 56.2% of patients with traditional therapy with systemic NSAIDs.

Selective sensory nerve blocks for effective pain management in the emergency department for a term pregnant cobra snake envenomation patient.

Sir, Snake bites with envenomation are a rare life-threatening emergency during pregnancy.[1] We report a case of a young full-term parturient who reported intense localized pain at the cobra (Naza Naza) bite site which was managed successfully by selective sensory nerve blocks. She subsequently underwent a caesarean section under spinal anaesthesia and had an uneventful post-partum course. A 26-year-old eight month pregnant patient presented to the emergency department (ED) post-cobra bite. The patient was taken to a local hospital within 30 min of the event. The bite mark was present on the right foot near the 4th toe [Figure 1]. There was minimal localized swelling but intense pain in the bite area. She had an episode of vomiting 45 min post-snake bite (suggesting the onset of systemic symptoms) and was administered 10 vials of anti-snake venom and referred to our tertiary care set-up.Figure 1: Distribution of superficial peroneal nerve (a); Probe placement for USG-guided block (b); USG image showing the superficial peroneal nerve (c); Snake bite mark on foot of the patient (d)When she presented to our ED 3h post-bite, the swelling had increased considerably and 10 more vials of anti-snake venom were infused. The investigations revealed leucocytosis with mild thrombocytopenia and anaemia. Local site pain was unbearable even after intravenous paracetamol and diclofenac. A superficial peroneal nerve and sural nerve blocks to cover the dorsolateral aspect of the foot was planned. The nerves were localized using a linear transducer (8–13 MHz) and a 3.5 ml of 0.75% ropivacaine was deposited. [Figures 1 and 2] Within 5 mins, the numeric rating scale (NRS) fall to 2 from the initial score of 10. At 10h, the patient reported an NRS score of 6, and the same blocks were repeated and effective pain relief was reported. The patient underwent a caesarean section under spinal anaesthesia at 18h post-admission given foetal distress. The baby was kept on nasal continuous positive airway pressure for 18h in view of respiratory distress and both of them were discharged in stable condition on the 3rd day of admission.Figure 2: Distribution of sural nerve (a); Probe placement for USG-guided block (b); USG image showing the sural nerve (c)Snake bites are rare in pregnancy but maternal mortality and foetal loss remain high.[1] An early presentation and rapidity of treatment with anti-snake venom probably led to a good outcome in this case. Acute localized moderate-to-severe pain is often documented as the first sign of a venomous snake bite (VSB).[2,3] The presynaptic and postsynaptic neurotoxins may directly interact with the nerve endings or indirectly cause severe pain secondary to ischemia due to local oedema.[1] Antivenom treatment fails to alleviate the local pain which may last for 48–72 h.[3] Weak opioids such as tramadol or paracetamol often provide inadequate analgesia.[4] Systemic opioids and non-steroidal anti-inflammatory drugs may be harmful to the foetus in term pregnancy. Furthermore, opioids can increase the risk of respiratory depression in neurotoxic envenomation cases as seen in cobra bite.[4] Untreated pain can have adverse consequences on foeto-maternal circulation.[5] In our case, the patient had intense pain with an NRS of 10 despite analgesics and responded well to nerve blocks. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

β-D-mannuronic Acid (M2000) and Inflammatory Cytokines in COVID-19; An In vitro Study.

coronavirus disease of 2019 (COVID-19) can be complicated by acute respiratory distress syndrome (ARDS) and may be associated with cytokine storm and multiorgan failure. Anti-inflammatory agents, such as systemic corticosteroids, monoclonal antibodies, and nonsteroidal anti-inflammatory drugs (NSAIDs) can be used for this purpose. In this study, we evaluated the immunomodulatory effect of mannuronic acid (M2000), which is a novel NSAID, on COVID-19-related cytokine storms. This study was conducted in vitro on blood samples of 30 COVID-19 patients who presented with ARDS to a referral center. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples and incubated with phorbol myristate acetate for 24 hours. M2000 was administered with the dosages of 25 µg/well and 50 µg/well after 4 hours of incubation at 37°C. The quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to assess mRNA gene expression. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the supernatant PBMC levels of interleukin (IL)-6, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Both mRNA expression and the supernatant PBMC levels of IL-17, TNF-α, IL‑6, and IFN‑γ were decreased in PBMCs of COVID-19 patients treated with M2000 compared with the control group. For the first time, it was observed that M2000 could be effective in alleviating the inflammatory cascade of COVID-19 patients based on an in vitro model. After further studies in vitro and in animal models, M2000 could be considered a novel NSAID drug in COVID-19 patients.

Scleritis as the harbinger of Granulomatosis with polyangiitis.

Ocular and orbital involvement in Granulomatosis with polyangiitis (GPA) is common. GPA can lead to life and sight threatening complications due to necrosis and tissue melting. We report four cases presenting with ocular pain and redness for varied durations. One had diminution of vision. All of them had deep sectoral/diffuse congestion with one having scleral thinning. All were diagnosed with anterior necrotizing/non-necrotizing scleritis. One had associated penetrating ulcerative keratitis. Topical steroids and systemic non-steroidal anti-inflammatory drugs were started in all cases and rheumatology consultation was taken. Pertinent investigations were sent, and GPA was diagnosed. Intravenous immunosuppressive regimens and oral steroid were started and significant improvements were seen, preventing untoward complications. Scleritis could be manifesting feature of GPA so cautious history taking and evaluation is important. Management often requires multidisciplinary care and ocular features could be the reference guidelines to adjust dose of systemic medications of GPA.

Antinociceptive Effect of a Sacro-Coccygeal Epidural of Morphine and Lidocaine in Cats Undergoing Ovariohysterectomy.

A commonly described analgesic protocol for ovariohysterectomy (OHE) combines systemic opioids, sedatives, and non-steroidal anti-inflammatory drugs. However, systemic analgesia does not fully prevent perioperative visceral and somatic pain triggered by the surgical stimulus. To compare the analgesic effects and quality of recovery of systemic analgesia with those of a sacrococcygeal epidural injection of lidocaine and morphine in cats undergoing elective OHE. Methods: Twenty domestic female cats were premedicated with dexmedetomidine (0.01 mg kg-1 IM) and alfaxalone (1.5 mg kg-1 IM) and randomly assigned to one of two analgesic protocols: methadone (0.2 mg kg-1 IM) in the control group CTR (n = 10) and methadone (0.1 mg kg-1 IM) + epidural (lidocaine 2% (0.3 mL kg-1) + morphine 1% (0.1 mg kg-1) diluted with NaCl 0.9% to a total volume of 1.5 mL in the SCC-E group (n = 10). General anaesthesia was induced with alfaxalone (1 mg kg-1 IV) and maintained with sevoflurane in 100% oxygen. Non-invasive blood arterial pressure and cardiorespiratory variables were recorded. The quality of recovery was assessed using a simple descriptive scale. Before surgery and 1, 2, 3, 4, 6, and 8 h post-op pain was assessed using the UNESP-Botucatu multidimensional composite pain scale (MCPS) and mechanical nociception thresholds (MNT). The repeated measures analysis of variance (ANOVA) was used to compare groups over time. Comparison between groups was performed using independent samples t-test if the assumption of normality was verified, or the Mann-Whitney test. The chi-square test of independence and exact Fisher's test were used to compare groups according to recovery quality. Heart rate and systolic arterial pressure increased significantly from baseline values in the CTR group and did not change in the SCC-E group. In the CTR group, MNT and UNESP-Botucatu-MCPS scores increased significantly from baseline for all assessment points and the first 3 h, respectively, whereas this did not occur in the SCC-E group. Based on our results, the SCC-E administration of lidocaine 2% with morphine 1% is a reasonable option to provide perioperative analgesia in cats submitted to OHE, compared to a systemic protocol alone.

Management of Pain after Photorefractive Keratectomy: A Report by the American Academy of Ophthalmology

To evaluate current best practices for postoperative photorefractive keratectomy (PRK) pain control. Literature searches in the PubMed database were last conducted in October 2021 and were restricted to publications in English. This search identified 219 citations, of which 84 were reviewed in full text for their relevance to the scope of this assessment. Fifty-one articles met the criteria for inclusion; 16 studies were rated level I, 33 studies were rated level II, and 2 studies were rated level III. Systemic opioid and nonsteroidal anti-inflammatory drugs (NSAIDs); topical NSAIDs; postoperative cold patches; bandage soft contact lenses (BCLs), notably senofilcon A contact lenses; and topical anesthetics were demonstrated to offer significantly better pain control than comparison treatments. Some other commonly reported pain mitigation interventions such as systemic gabapentinoids, chilled intraoperative balanced salt solution (BSS) irrigation, cycloplegia, and specific surface ablation technique strategies offered limited improvement in pain control over control treatments. Systemic NSAIDs and opioid medications, topical NSAIDs, cold patches, BCLs, and topical anesthetics have been shown to provide improved pain control over alternative strategies and allow PRK-associated pain to be more tolerable for patients.

Nodular Posterior Scleritis Masquerading as Amelanotic Choroidal Melanoma

We report a patient of choroidal mass, masquerading as amelanotic choroidal melanoma. A 48 years old male presented in outpatient department (OPD) with painless decrease in vision of left eye. Fundus examination revealed a two disc diameter, non-pigmented, sub-retinal lesion with approximately 3mm basal diameter, superior to the disc with no choroidal folds, retinal detachment or pigmentation over the lesion. B scan revealed a small nodular thickening superior to the optic nerve head with moderate to low internal reflectively and no choroidal excavation. Swept-Source optical coherence tomography (SS OCT) showed massive elevation of retina due to underlying scleral thickening. He was diagnosed as nodular posterior scleritis (NPS). The lesion regressed completely after treatment with topical and systemic Non-steroidal anti-inflammatory drugs (NSAIDs). Despite its low prevalence, NPS should be kept in differential diagnosis of an amelanotic choroidal mass.