Nonsteroidal Anti-inflammatory Drugs Therapy Research Articles

Leflunomide with prednisone or nonsteroidal anti-inflammatory drug therapy is safe and tolerated for long-term treatment of immune-mediated polyarthritis in 27 dogs.

To retrospectively evaluate safety and tolerance of leflunomide for long-term treatment of canine idiopathic immune-mediated polyarthritis (IMPA). 27 dogs with clinical signs and synovial fluid cytology supportive of IMPA with ≥ 6 months' follow-up after starting leflunomide. Medical records were reviewed to identify dogs prescribed leflunomide for treatment of IMPA from February 2012 to May 2022. Initial leflunomide doses of 2 to 4 mg/kg once daily were prescribed and were titrated to the lowest effective dose with concurrent anti-inflammatory therapy. Complete blood count, serum chemistry, and clinical signs were monitored throughout the course of treatment. Adverse effects potentially attributable to leflunomide noted in 9 of 27 dogs (33%) included vomiting, diarrhea, lethargy, decreased or absent appetite, polyuria and polydipsia, and secondary antibiotic responsive infection and were self-limiting or resolved with outpatient therapy. Alkaline phosphatase (ALP) and alanine aminotransferase (ALT) elevation were documented in all dogs prescribed leflunomide plus prednisone, with persistent liver enzyme elevation in 6 of 9 dogs (67%) and normalization after antibiotic therapy in 3 of 9 dogs (33%). The majority of dogs prescribed leflunomide plus NSAID (11/17 [65%] dogs) did not experience liver enzyme elevation; 2 of 17 (12%) dogs developed transient antibiotic-responsive liver enzyme elevations, and 4 of 17 (23%) dogs had persistent liver enzyme elevation. Leflunomide was well tolerated for long-term management of IMPA. A significant difference in liver enzyme elevation was identified between dogs prescribed prednisone versus NSAID in combination with leflunomide. Leflunomide with NSAID therapy resulted in less hepatotoxicity compared with leflunomide with prednisone.

Outcomes of combined treatment of patients with acute lumbodynia

Introduction. Acute dorsalgia is a common reason to seek outpatient medical care in Russia. The clinical picture usually includes muscular-tonic and pain syndromes. The most common form of dorsalgia by localization is acute lumbar pain (lumbodynia).Aim. To evaluate the effectiveness of Spascuprel®, Traumeel S in the complex treatment of patients with acute lumbar pain in real-world clinical practice.Materials and methods. We conducted a non-interventional, prospective, observational study of 110 outpatients aged 26 to 65 years. Patients received a standard on-demand therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). In addition, Group 1 received Spascuprel® and Traumeel® C, and Group 2 received centrally acting muscle relaxants. The effectiveness of  treatment was assessed using the visual analogue scale (VAS) of pain intensity and the limitations of various activities in daily living were measured using the Roland – Morris questionnaire. Consideration was given to the exacerbation duration, the need for additional intake of NSAIDs, and the number of cases of pain exacerbation within 60 days from the start of participation in the observational study.Results. Under treatment, pain intensity showed statistically significant decreases in VAS scores (from 61.0 to 35.5 scores out of 100 according to VAS by Day 7 and to 19.5 scores by Day 14 of treatment in Group 1, from 61.2 to 41.1 and to 25.8 scores in Group 2, respectively (p < 0.05)). A more rapid decrease was observed in VAS pain intensity score from baseline in Group 1. Over 2-month observation period, group 1 had less exacerbations (p < 0.05) and fewer cases of need for additional intake of NSAIDs (p < 0.05). The frequency and severity of adverse events did not differ between two groups.Conclusion. A more rapid decrease in VAS pain intensity scores and reduction in the need for NSAIDs were noted in the group of patients with acute dorsalgia who used Traumeel® C and Spascuprel® in addition to standard NSAID therapy.

EFFICACY OF VIRECHANA IN AMLAPITTA (GASTRO ESOPHAGEAL REFLUX DISEASE): A SINGLE CASE STUDY

Amlapitta is very common disease encountered in present population. Due to lifestyle changes and changes in food habits people are mainly suffering from GIT disorders. Agniwhich is considered as root cause of all diseases is vitiate in Amlapittaleading to Mandagni (mildness of gastric fire) and food remains in Amashaya (abdomen) inShukta Avastha due to improper digestion. Its symptoms include heart burn, acid eructation, sour taste in the mouth, nausea, vomiting and loss of appetite. Conventional medical knowledge states that H. pylori infections, prolonged use of non-steroidal anti-inflammatory drug therapy, and infections are the most common causes of GERD. In AyurvedShodhanChikita is the best way to treat the root cause of disease by eliminating toxic substances from body. Amlapitta is Pitta Dosha Pradhan disease and VirechanaKarma is best for Pitta vitiate disorder. This article is case study of 32 Yr. male patient with sign and symptoms of Amlapitta registered from the O.P.D, P.G. Department of Kayachikitsa, Gurukul Campus, Haridwar.

The Effect of Nonsteroidal Anti-inflammatory Drugs on Union Rates Following Joint Arthrodesis: A Meta-Analysis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used and prescribed medications because of their important role in reducing inflammation and pain, in addition to their non-addictive properties and safety profiles. However, some studies have documented an association between NSAIDs and delayed union or nonunion of joint arthrodesis procedures due to a potential inhibition of the bone's inflammatory healing response. As a result, some orthopedic surgeons hesitate to prescribe NSAIDs after an arthrodesis procedure. The purpose of this meta-analysis is to review all relevant literature regarding the effect of NSAIDs on union rates after arthrodesis and determine if NSAID therapy increases the risk of non-union in the setting of arthrodesis procedures. The study hypothesis was that NSAIDs would not have a significant effect on therisk of nonunion after arthrodesis. A thorough systematic review of Medline, Embase, the Cochrane Database of Systematic Reviews, and the Web of Science identified 3,050 articles to be screened. The variables of interest encompassed demographic factors, procedural details, type and administration of NSAIDs, the number of patients exposed to NSAIDs with and without successful union (case group), as well as the number of patients who did not receive NSAIDs with and without successful union (control group). All the data were analyzed using a maximum likelihood random-effects model. The number of non-union events versus routine healing from each study was used to calculate the odds ratio (OR) of successful healing after arthrodesis procedures with versus without NSAID therapy. Thirteen articles met the inclusion criteria for the meta-analysis. NSAID exposure showed an increased risk of nonunion, delayed union, or both following arthrodesis procedures; however, this did not meet statistical significance (OR, 1.48; confidence interval [CI], 0.96 to 2.30). A sub-analysis of pediatric and adult studies showed a significant increase in non-union risk in adults (OR, 1.717; CI, 1.012 to 2.914) when removing the pediatric cohort (p = 0.045). This meta-analysis provides evidence that NSAIDs can increase the risk of nonunion, delayed union, or both following arthrodesis procedures in adults. However, the study did not identify a risk of nonunion, delayed union, or both following arthrodesis procedures in the pediatric population.

Pericarditis. Causes, Mechanisms of Development, Variants of Course and Therapeutic Approaches in Modern Conditions

Under physiological conditions, the pericardial cavity contains serous fluid (15-50 ml), which belongs to the plasma ultrafiltrate and is visualized during echocardiography only in systole. The thickness of the pericardium in an adult averages 2 mm (1-3 mm). Inflammatory lesions of the pericardium with or without effusion into its cavity can act as an independent disease, and as a secondary manifestation of another pathological condition. Pericarditis of infectious (14-16%) and non-infectious (15-20%) nature, primary and secondary, acute, chronic and recurrent are commonly distinguished. The prevalence of acute and idiopathic recurrent pericarditis is 27.7 per 100,000 population and 5.4-8.1 per 100,000 population, respectively. Currently, idiopathic recurrent pericarditis belongs to polygenic autoinflammatory diseases, where an important role in the initiation of the pathologic process belongs to the inflammatory cytokine — interleukin-1 (β and α). The most characteristic manifestations of acute pericarditis are chest pain, dyspnea and fever. The article summarizes the main aspects of etiology, clinical manifestations, diagnosis and therapy of pericarditis, including the peculiarities of its treatment taking into account specific conditions. A clinical case demonstrated a case of acute effusion pericarditis with recurrence, which was characterized by rapid progression of heart failure symptoms, as well as systemic manifestations (anemia, hypercytokinemia, marked muscle weakness). The results of echocardiography allowed to identify the presence of pericardial effusion. Steroid and non-steroidal anti-inflammatory, anticoagulant and antibacterial therapy led to the disappearance of pericardial effusion and normalization of the activity of inflammatory markers in serum. However, in the dynamics of observation the attempt to suspend glucocorticoid therapy again led to fluid accumulation in the pericardium, which required continuation of steroidal and non-steroidal anti-inflammatory drugs.

Celecoxib to improve scar quality following acute burn injury: Lessons learned after premature termination of a randomised trial

BackgroundPre-clinical studies suggest that non-steroidal anti-inflammatory therapy may reduce acute inflammation and modulate scar formation after burn injury. The objective of this trial was to determine if celecoxib administered soon after acute burn improved scar quality. MethodsA single centre, parallel group, placebo-controlled, randomised, superiority trial. Adults with non-major acute burn injury were eligible for recruitment. Participants within 48 h of admission for acute burn injury received either six weeks of celecoxib 200 mg twice daily or identically packaged placebo capsules. The primary outcome was participant-reported Patient Observer Scar Assessment Scale (POSAS) at day 42 following burn injury. The best possible score using this assessment is 7 and the worst 70. Key safety outcomes included study drug side effects. ResultsRestrictions imposed during the COVID-19 pandemic resulted in slow recruitment and early termination after 59 of the 150 planned participants were enrolled. The primary outcome was available for 21/30 (70 %) participants in the celecoxib arm and for 23/29 (79 %) who received placebo. There was no significant difference in the primary outcome between treatment groups with a mean POSAS of 33.4 (standard deviation 12.7) in the celecoxib arm and 36.9 (13.7) in the control arm giving a difference of −3.49 (95 % CI [-11.57, 4.59], p =.39). Gastrointestinal symptoms occurred in 3/30 (10 %) allocated celecoxib and in none allocated placebo. Secondary outcomes including graft loss and delayed healing were similar between groups. ConclusionsAnti-inflammatory therapy did not improve scar quality. Due to early trial termination and significant loss to follow up these findings should be interpreted cautiously. To improve generalisability and to attain recruitment targets, future trials should apply different approaches to improve participant retention as well as including patients with larger burn injuries and an older population.Trial registration: ACTRN12618000732280.

Fetal circular shunt in Ebstein's anomaly and non-steroidal anti-inflammatory treatment.

A circular shunt is a poor prognostic factor associated with Ebstein's anomaly. Targeting the constriction of the ductus arteriosus (DA) in order to limit or resolve the circular shunt, has been shown to improve fetal outcomes. Prenatal non-steroidal anti-inflammatory drugs (NSAIDs) have been known to constrict the DA. Recently, prenatal NSAIDs have been used for that purpose in the treatment of circular shunt. Limited research shows that it may be an effective treatment leading to improved fetal outcomes. In this article, we did an extensive review of literature to describe this therapy's effectiveness and outcomes. 82% of fetuses were able to achieve ductal constriction with prenatal NSAID therapy. For fetuses who achieved ductal constriction, fetal demise was less likely (6%) when compared to those who were unable to achieve the same (50%). Of all the fetuses with hydrops, 50% had resoluation of hydrops with prenatal NSAID treatment.

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

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

A systematic literature review of randomised controlled trials evaluating colchicine for cardiovascular prevention: There is an elephant in the room

ObjectivesTo review randomised controlled trials (RCT) investigating colchicine (COL) for cardiovascular (CV) prevention in patients at high to very high CV risk aiming to extract data that could be useful in rheumatology practice. MethodsA systematic search of multiple databases according to the PICO framework was performed from inception to April 3, 2023. Three researchers independently screened abstracts/titles and reviewed full texts reviewed. Data extraction was performed using a pilot‐tested data extraction form. ResultsA total of 14,096 references were retrieved by the search and 30 articles, describing 28 RCTs, were included in the review (Total number of patients 16,795, of which 8,463 randomised to COL; dose 0.5–2 mg/day, treatment duration 1day-29 months). Only one of the 28 RCTs provided clear information on whether patients with rheumatic diseases (more specifically gout) were enrolled in the study cohorts and previous use of COL was an exclusion criterion only in 14 (50 %) RCTs. Previous therapy with glucocorticoids and/or non-steroidal anti-inflammatory drugs and/or immune suppressive therapies was an exclusion criterion only in 9 (32 %) RCTs. ConclusionOur results highlight the need to redefine the eligibility criteria as well as the reporting of results in future RCTs in order to minimise bias or previous exposure to COL and also obtain data that could be useful in rheumatology practice.

Effects of low-dosage radiotherapy for knee osteoarthritis on the incidence of knee arthroplasty: Results of a randomized controlled trial with 9-year follow-up

The aim. To compare the incidence of knee arthroplasty in patients receiving standard treatment with non-steroidal anti-inflammatory drugs (NSAIDs) in combination with symptomatic slow acting drugs for osteoarthritis (SYSADOA), or combination of NSAIDs and SYSADOA with low-dose radiation therapy (LDRT) in patients with stage 0–2 knee osteoarthritis (OA). Materials and methods. The article presents the results of randomized controlled study of 292 patients with confirmed knee OA according to Altman’s criteria (1991) and Kellgren – Lawrence radiographic stages 0–2 who were randomized into two groups. The control group (n = 146) received standard therapy of NSAIDs + SYSADOA. Patients of the study group (n  =  146) received combination of standard therapy and  LDRT up to a total dose of 4.5  Gy. The  cumulative risk of knee arthroplasty was assessed using actuarial analysis and the Kaplan – Meier method. Attributable (AF) and population attributable (PAF) fractions were calculated to assess LDRT preventive potential. Results. The total observation period was 2131.2 person-years. Knee arthroplasty was performed in 4.1 % (n = 6) of patients in the study group against 7.5 % (n = 11) in the control group. The  incidence density ratio was 0.60 (95%  CI: 0.18–1.88), which corresponds to a risk reduction by 67 %, but the differences were not statistically significant due to the small number of cases (p = 0.340). The AF was 40 % while the PAF was 21 %. Conclusions. The use of LDRT reduces the risk of knee arthroplasty by two-thirds and has the potential to prevent 21 % cases of knee arthroplasty in patients with knee OA. A study on a larger sample is required.

Use of non-steroidal anti-inflammatory drugs in renal transplant patients: A retrospective study.

Renal transplanted patients are often prescribed non-steroidal anti-inflammatory drugs (NSAIDs) for analgesic purposes. Considering the dearth of data, we carried out the present study to evaluate the use of various NSAIDs and the incidence of acute kidney injury (AKI) in transplant patients. A retrospective study amongst renal transplant patients prescribed at least one dose of NSAID was carried between January and December 2020 at the Department of Nephrology, Salmaniya Medical Complex, Kingdom of Bahrain. The patients' demographic details, serum creatinine values, and drug-related details were obtained. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used for defining AKI. Eighty-seven patients were included. Forty-three patients were prescribed diclofenac, 60 received ibuprofen, six received indomethacin, 10 were administered mefenamic acid, and 11 received naproxen. Due to multiple courses of NSAID prescription, a total of 70 prescriptions were identified for diclofenac, 80 for ibuprofen, six for indomethacin, 11 for mefenamic acid, and 16 for naproxen. No significant differences were observed in the absolute (p =0.08) and percent changes in serum creatinine (p =0.1) between the NSAIDs. Twenty-eight (15.2%) courses of NSAID therapy met the KDIGO criteria for AKI. Age (OR: 1.1, 95% CI: 1.007, 1.2; p =0.02), concomitant everolimus (OR: 483, 95% CI: 4.3, 54407; p =0.01), and mycophenolate + cyclosporine + azathioprine (OR: 63.4E+006, 95% CI: 203.2157 to 19.8E+012; p =0.005) administration were observed with significant risk of NSAID-induced AKI. We observed possible NSAID-induced AKI to an extent of around 15.2% in our renal transplant patients. No significant differences were observed in the incidence of AKI between various NSAIDs and none of them had either graft failure or death.

Analgesic Efficacy of Non-Steroidal Anti-Inflammatory Drug Therapy in Horses with Abdominal Pain: A Systematic Review.

This systematic review aimed to identify the evidence concerning the analgesic efficacy of non-steroidal anti-inflammatory drugs to treat abdominal pain in horses, and to establish whether one non-steroidal anti-inflammatory drug could provide better analgesia compared to others. This systematic review was conducted following the "Systematic Review Protocol for Animal Intervention Studies". Research published between 1985 and the end of May 2023 was searched, using three databases, namely, PubMed, Embase, and Scopus, using the words equine OR horse AND colic OR abdominal pain AND non-steroidal anti-inflammatory drug AND meloxicam OR flunixin meglumine OR phenylbutazone OR firocoxib OR ketoprofen. Risk of bias was assessed with the SYRCLE risk of bias tool, and level of evidence scored according to the Oxford Centre for Evidence-based Medicine. A total of 10 studies met the inclusion criteria. From those only one study judged pain with a validated pain score, and a high risk of bias was identified due to the presence of selection, performance, and "other" types of bias. Therefore, caution is required in the interpretation of results from individual studies. To date, the evidence on analgesic efficacy to determine whether one drug is more potent than another regarding the treatment of abdominal pain in horses is sparse.

SHORT-TERM CELECOXIB PROMOTES BONE FORMATION WITHOUT COMPROMISING ANTIBIOTIC EFFICACY IN EARLY ORTHOPAEDIC DEVICE-RELATED INFECTION: EVIDENCE FROM A RAT MODEL

We investigated the effects of non-steroidal anti-inflammatory drugs (NSAIDs) with different cyclooxygenase (COX) selectivity on orthopaedic device-related infections (ODRIs) in a rat model. We aimed to measure the impact of NSAID therapy on bone changes, bacterial load, and cytokine levels after treatment with antibiotics. We also compared the effects of long vs short-term celecoxib (a COX-2 inhibitor) treatment on the same outcomes.Skeletally mature female Wistar rats were implanted with Staphylococcus epidermidis- contaminated polyetheretherketone (PEEK) screws in the proximal right tibia and monitored for 7 days. All animals received subcutaneous antibiotics (rifampicin plus cefazolin) for two weeks from day 7 to 21. In phase I of the study, rats were randomly assigned to receive 28 days of oral treatment with acetylsalicylic acid, ibuprofen, celecoxib, or vehicle control. In phase II, an additional group received seven days of celecoxib treatment from day 0 to 7. Bone changes were monitored using in vivo micro-CT and histology. Quantitative bacteriology was performed at euthanasia. Plasma samples were collected to measure cytokine levels on days 0, 6, 20, and 28.Combination antibiotic therapy resulted in treatment success in 85.71% of cases, while the addition of long-term celecoxib treatment reduced it to 45.45%. Long-term celecoxib treatment significantly reduced bone loss (33.85% mean difference [95% CI 14.12–53.58], p=0.0004 on day 6 bone fraction) and periosteal reaction (0.2760 μm mean difference [95% CI 0.2073–0.3448], p&lt;0.0001 on day 14 periosteal thickness) during early infection compared to the control group. Short- term celecoxib treatment showed similar radiological results without a reduction in treatment success (88.9%). No differences in the inflammatory markers were observed.Our findings highlight the potential benefits of short-term use of celecoxib in improving bone fraction during the early post-infection period without impairing the efficacy of antibiotic therapy

Transplacental non-steroidal anti-inflammatory drugs versus expectant management in fetal Ebstein anomaly with circular shunt: Systematic review and meta-analysis.

Ebstein anomaly (EA) is a rare congenital cardiac malformation associated with high perinatal mortality. In this systematic review and meta-analysis, we aimed to investigate the outcomes of pregnancies affected by EA or tricuspid valve dysplasia (TVD) with circular shunt, focusing on two prenatal management approaches: (1) expectant management (EM) and (2) transplacental non-steroidal anti-inflammatory drugs (NSAID) therapy. We searched PubMed, Scopus, and Web of Science systematically from its inception until June 2023. The random-effect model was used to pool the data. Heterogeneity was assessed using the I2 value. Twenty-one studies with a total of 610 fetuses with EA/TVD with circular shunt were included in the synthesis, of which 17 studies (583 fetuses) were on EM and 4 studies (27 fetuses) used transplacental NSAID therapy. The NSAID group had higher rates of moderate to severe tricuspid regurgitation, hydrops, and pericardial effusion on prenatal ultrasound compared with the EM group. However, ductal constriction was achieved in 81% of NSAID cases, mitigating the disease pathophysiology, although 65% of them experienced oligohydramnios. Notably, the NSAID group showed significantly higher rates of live birth (86%) and survival to hospital discharge (89%) compared with the EM group (67% and 43%, respectively). Despite these promising results, it's important to acknowledge that the number of cases treated with NSAIDs was small, with limited safety data. Therefore, caution is advised in interpreting these findings, and patients considering NSAID therapy should be informed about these limitations. Future multicenter studies are necessary to further explore the safety and effectiveness of NSAID therapy in this particular population.

Results of a clinical study of Traumeel® S and Zeel® T in patients with knee osteoarthritis and concomitant cardiovascular disease

   Objective: to evaluate the efficacy and safety of simultaneous intramuscular administration of Traumeel® S and Zeel® T followed by therapy with the tablet medication Zeel® T in patients with knee osteoarthritis (OA) and concomitant cardiovascular diseases.   Material and methods. The analysis included 119 patients aged 45–79 years (78.2 % women and 21.8 % men) with confirmed diagnosis of knee OA according to Altman criteria, stage II–III according to Kellgren–Lawrence and confirmed cardiovascular disease. The main indicator of efficacy was the change in pain intensity in the target knee joint according to the “Pain” subscale of the WOMAC questionnaire (A) at the final examination compared to the baseline. Other criteria were the dynamics of each symptom of knee OA according to the WOMAC questionnaire (pain, stiffness, and functional impairment, total score) on each visit, pain intensity in the target joint on a visual analogue scale (VAS), time it takes to travel 15 m, and the patient's overall disease assessment on the VAS. In addition, duration of use and dose of paracetamol (if used) were assessed, as well as quality of life by EuroQol and adverse events (AEs). Treatment safety was also analyzed in patients who had received at least one dose of the study drug.   Results and discussion. WOMAC pain intensity decreased by on average of 3.8 points: from 7.6 to 3.8 points (95 % confidence interval, CI from -4.3 to -3.3). Data on changes in knee OA symptoms (pain, stiffness, and functional impairment) for each WOMAC subscale and the total score showed significant improvement at each follow-up visit (p &lt; 0.0001). The VAS pain level decreased by 52%. An improvement in joint function was noted: the time it takes to travel 15 m fell from 19.5 to 16.4 s (p &lt; 0.0001). The EuroQol quality of life score also improved from 57.1 ± 16.2 points at baseline to 71.1 ± 14.8 points on the 84&lt;sup&gt;th&lt;/sup&gt; day of therapy. Thirty (25.2 %) patients had AEs, mainly neurological: headache (7.6 %) and hypoesthesia (1.7 %). No serious AEs were recorded. An association between AEs and study drug use was noted in 4 patients (headache, hypoesthesia, muscle cramps, and injection site pain).   Conclusion. The results of the study confirm the efficacy and safety of the use of Traumeel® S and Zeel® T in patients with knee OA who have concomitant cardiovascular disease. During therapy, a significant decrease in pain and other clinical signs of OA (stiffness, limitation of physical activity) was observed, which allows us to recommend this treatment regimen for patients with comorbid pathology, as well as with the risk of developing of AEs during non-steroidal anti-inflammatory drugs therapy.

Predictors of treatment failure of non-steroidal anti-inflammatory drugs in patients with axial spondyloarthritis with focus on haptoglobin, haptoglobin polymorphism and zonulin.

According to the Assessment of SpondyloArthritis International Society-European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axial spondyloarthritis (axSpA), patients should undergo at least two courses of non-steroidal anti-inflammatory drugs (NSAIDs) therapy. In our study, we enrolled axSpA patients both at onset and in a flare who had already been treated with NSAIDs ineffectively. Subsequently, according to the recommendations, they received modified NSAID treatment as another attempt to the first-line drug therapy and were monitored from there. We aimed to identify risk factors for treatment failure after 4weeks (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4) especially amongst zonulin and haptoglobin concentrations, and haptoglobin polymorphism. Treatment failure was observed in 71% of patients, and the following variables were contributed for occurrence of this state: higher zonulin levels, ankylosing spondylitis, X-ray sacroiliitis, magnetic resonance imaging sacroiliitis, long duration of symptoms, high BASDAI, and high value of spinal pain intensity on visual analogue scale. In addition, the following positive correlations were found: haptoglobin concentration with C-reactive protein (r = 0.56; p = 0.0004), and erythrocyte sedimentation rate (r = 0.62; p < 0.0001), as well as between zonulin levels and white blood count (r = 0.5; p = 0.0003). The results of the study presented the identified factors related to the standard treatment failure in axSpA, amongst them zonulin levels. They might be applied to point out the patients for whom the search for a more appropriate method of treatment should be considered.

The Role of Quercetin for the Treatment of Endometriosis and Endometrial Cancer: A Comprehensive Review.

Endometrial glands and stroma can be seen outside the uterine cavity in endometriosis, a gynecological disorder linked to estrogen dependency. Hormonal therapies, surgical excision, and non-steroidal anti-inflammatory drug therapy are among the traditional endometriosis treatments, however, various side effects limit their efficacy. Therefore, it is vital to research complementary and alternative therapeutic modalities to decrease the side effects of conventional therapies. While the search for the best endometriosis treatment continues, the focus is being paid to the assistance provided by polyphenols, notably quercetin. A broad spectrum of health-improving benefits of quercetin includes interactions with endometriosis-related molecular targets such as cell proliferation, apoptosis, invasiveness, inflammation, and oxidative stress. According to already-known research, medicines that mimic the physiological effects of quercetin are good candidates for creating novel endometriosis therapies. This review aims to comprehensively review quercetin's potential as a non-pharmacological treatment for endometriosis by interacting with several cellular and molecular targets.

Differential Diagnostic Indicators for the Appointment of Non-Steroidal Anti-Inflammatory Therapy in the Treatment of Red Eye Syndrome at the Stage of Primary Outpatient Admission. Part 2

In recent years, the Delphi method (DMt) has been widely used in scientific practice. It is based on an expert assessment of the object under study, which is formed on the basis of a survey of a group of experts in a particular field. The application of the Delphi method in various areas of ophthalmological practice has made it possible to develop practical recommendations for the diagnosis of visual stress, methods for diagnosing and treating keratoconus, to develop clinical guidelines for the diagnosis and treatment of patients with Sjögren’s syndrome, to classify the signs and symptoms of dry eye syndrome in accordance with the main mechanism of its occurrence and etc. A survey ophthalmologist expert conducted during the study, performed in accordance with the Delphi method, aimed at developing a differential algorithm in the treatment of patients with one of the most common pathologies among diseases belonging to the category of “red eye syndrome” — conjunctivitis, allowed identify key symptoms for prescribing different groups of drugs. In accordance with the clinical guidelines developed by the Russian Association of Ophthalmologists, the following groups of drugs are recommended for use: antibacterial, antiseptic, antihistamine, non-steroidal anti-inflammatory drugs, steroidal anti-inflammatory drugs, antiviral drugs. This article presents the results obtained in determining the indications for the use of non-steroidal anti-inflammatory therapy in the treatment of conjunctivitis. These include: the presence of a history of systemic diseases, the duration of inflammation for more than 7 days, the absence or presence of mucous discharge, complaints of a feeling of pain, discomfort in the eyes, their redness, as well as biomicroscopic signs of inflammation, which manifest themselves as mild to moderate conjunctival hyperemia expressiveness. The result obtained is of fundamental practical importance for primary outpatient ophthalmologists for choosing rational drug therapy in the treatment of one of the most common pathologies encountered in ophthalmic practice — conjunctivitis. A differentiated approach in choosing the volume and type of drug therapy based on the severity of the inflammatory process will reduce the drug load on the ocular surface. In accordance to the data presented in the first part of this article, it will lead to a decrease the risk of developing signs of dry eye syndrome against the background of a stopped inflammatory process in the long-term period and improving the quality of life in patients.

Conjugation with Tris Decreases the Risk of Ketoprofen-Induced Mucosal Damage and Reduces Inflammation-Associated Methane Production in a Rat Model of Colitis.

We have designed a new compound from the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (Ket) and 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) precursors, with the aim to reduce the gastrointestinal (GI) side effects of NSAID therapies. We investigated mucosal reactions in a standard rat model of colitis together with methane generation as a possible indicator of pro-inflammatory activation under this condition (approval number: V./148/2013). Whole-body methane production (photoacoustic spectroscopy) and serosal microcirculation (intravital videomicroscopy) were measured, and mucosal damage was assessed (conventional histology; in vivo laser-scanning endomicroscopy). Inflammatory markers were measured from tissue and blood samples. Colitis induced an inflammatory response, morphological colonic damage and increased methane output. Ket treatment lowered inflammatory activation and colonic mucosal injury, but macroscopic gastric bleeding and increased methane output were present. Ket-Tris reduced inflammatory activation, methane emission and colonic mucosal damage, without inducing gastric injury. Conjugation with Tris reduces the GI side effects of Ket and still decreases the inflammatory response in experimental colitis. Methane output correlates with the mucosal inflammatory response and non-invasively demonstrates the effects of anti-inflammatory treatments.

Comparison of Colchicine Monotherapy Versus Nonsteroidal Anti-Inflammatory Drugs Monotherapy or Combination Therapy for the Prevention of Recurrent Pericarditis in Patients With Heart Failure With Reduced Ejection Fraction and/or Coronary Artery Disease.

Objective: Guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin for 2-4 weeks with colchicine for 3 months for the treatment of acute pericarditis. In patients with HFrEF and/or CAD, the adverse effect profile of NSAIDs pose concern. While previous studies evaluated colchicine as adjunctive therapy, colchicine monotherapy has never been assessed. This study aims to compare the efficacy of colchicine monotherapy to NSAID monotherapy or combination therapy for the prevention of recurrent pericarditis in patients with HFrEF and/or CAD. Methods: This was a single health-system, retrospective, observational cohort study. Patients were 18 years or older, had a diagnosis of acute pericarditis and HFrEF and/or CAD, and were discharged on colchicine and/or NSAID therapy. Patients were excluded if they had an episode of pericarditis within the previous 12 months. The primary outcome was the incidence of pericarditis recurrence or documentation of incessant symptoms within 12 months of the index hospitalization. Results: Of the 77 patients included, 43 (55.8%) were treated with colchicine monotherapy, 7 (9.1%) were treated with NSAID monotherapy, and 27 (35.1%) were treated with combination therapy. Pericarditis recurrence or documentation of incessant symptoms occurred in 16.3% of patients treated with colchicine monotherapy, 28.6% of those treated with NSAID monotherapy, and 18.5% of those treated with combination therapy (P = .740). Conclusion: In this study, no difference in the primary outcome was observed between groups. However, a prospective, randomized trial is needed to further elucidate the efficacy of colchicine monotherapy for the treatment of acute pericarditis in patients with HFrEF and/or CAD.