Nonsteroidal Anti-inflammatory Drugs Treatment Research Articles

Risks of serious adverse events associated with non-steroidal anti-inflammatory drugs in gastrointestinal surgery. A protocol for a systematic review with meta-analysis and trial sequential analysis.

Post-operative pain is frequent following gastrointestinal surgery and may result in prolonged hospitalisation, delayed recovery, and lower quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesics and recommended by Enhanced Recovery After Surgery guidelines as part of opioid-sparing multimodal treatment. However, perioperative NSAID treatment may be associated with increased risk of harm. We will investigate the risks of serious adverse events associated with perioperative NSAID treatment in patients undergoing gastrointestinal surgery. This protocol uses the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We wish to assess the effects of NSAIDs versus placebo, usual care, or no intervention on the incidence of serious adverse in patients undergoing gastrointestinal surgery. We will include all randomised trials. To identify trials, we will search the medical literature analysis and retrieval system online, excerpta medica database, cochrane central register of controlled trials, web of science core collection, and BIOSIS. Two authors will screen the literature and extract data. We will use the 'Risk of Bias 2 tool' to assess the risks of systematic errors. We will perform meta-analyses using R. We will use Trial Sequential Analysis to account for the risks of random errors. We will create a "Summary of Findings"-table in which we will present our primary and secondary outcome results. We will assess the certainty of the evidence using grading of recommendations assessment, development and evaluation. This systematic review can potentially elucidate the risks of perioperative NSAID treatment in gastrointestinal surgery and inform the already established non-opioid multimodal pain treatment regimen recommended by enhanced recovery after surgery guidelines.

Efficacy and safety of tanezumab, NSAIDs, and placebo in patients with moderate to severe hip or knee osteoarthritis and a history of depression, anxiety, or insomnia: post-hoc analysis of phase 3 trials

Objective: Treatment outcomes for chronic pain can be poor in patients with depression, anxiety, or insomnia. This analysis evaluated the efficacy and safety of subcutaneous tanezumab, nonsteroidal anti-inflammatory drugs (NSAIDs), and placebo in patients with osteoarthritis (OA) and a history of these conditions using data from three phase 3 studies. Methods: A post-hoc analysis of data from two pooled placebo-controlled studies and one NSAID-controlled study of subcutaneous tanezumab. All patients had moderate to severe knee or hip OA that was inadequately controlled with standard-of-care analgesics. Efficacy outcomes were least-squares mean change from baseline to Week 16 in Western Ontario McMaster Universities OA Index (WOMAC) Pain, WOMAC Physical Function, Patient’s global assessment of OA, and EQ-5D-5L scores. Results were summarized for patients with and without a history of depression, anxiety, or insomnia at baseline. Results: 1545 patients were treated in the pooled placebo-controlled studies (history of depression, 12%; anxiety, 8%; insomnia, 10%; any, 23%) and 2996 in the NSAID-controlled study (16%, 11%, 13%, 28%, respectively). In groups with positive histories, 38–80% took antidepressant or anxiolytic medications at baseline. Within treatments, largely similar improvements in efficacy outcomes were observed in patients with and without a history of depression, anxiety, or insomnia; the types of treatment-emergent adverse events were similar. Conclusions: Patients with OA and a history of depression, anxiety, or insomnia did not appear to experience reduced efficacy outcomes or an altered safety profile in response to tanezumab or NSAID treatment as compared with those without. NCT02697773; NCT02709486; NCT02528188

Cross-species comparisons reveal resistance of human skeletal stem cells to inhibition by non-steroidal anti-inflammatory drugs.

Fracture healing is highly dependent on an early inflammatory response in which prostaglandin production by cyclo-oxygenases (COX) plays a crucial role. Current patient analgesia regimens favor opioids over Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) since the latter have been implicated in delayed fracture healing. While animal studies broadly support a deleterious role of NSAID treatment to bone-regenerative processes, data for human fracture healing remains contradictory. In this study, we prospectively isolated mouse and human skeletal stem cells (SSCs) from fractures and compared the effect of various NSAIDs on their function. We found that osteochondrogenic differentiation of COX2-expressing mouse SSCs was impaired by NSAID treatment. In contrast, human SSCs (hSSC) downregulated COX2 expression during differentiation and showed impaired osteogenic capacity if COX2 was lentivirally overexpressed. Accordingly, short- and long-term treatment of hSSCs with non-selective and selective COX2 inhibitors did not affect colony forming ability, chondrogenic, and osteogenic differentiation potential in vitro. When hSSCs were transplanted ectopically into NSG mice treated with Indomethacin, graft mineralization was unaltered compared to vehicle injected mice. Thus, our results might contribute to understanding species-specific differences in NSAID sensitivity during fracture healing and support emerging clinical data which conflicts with other earlier observations that NSAID administration for post-operative analgesia for treatment of bone fractures are unsafe for patients.

Perspective of sarcoidosis in terms of rheumatology: a single-center rheumatology clinic experience.

Sarcoidosis may present with many rheumatological symptoms as well as mimic and/or may occur concomitantly with many other rheumatic diseases. We examined the demographic, clinical and laboratory characteristics of patients diagnosed with sarcoidosis in the rheumatology department. This study planned as retrospective cross-sectional study. Medical records of patients who applied to our rheumatology outpatient clinic due to complain of musculoskeletal problems and then diagnosed sarcoidosis were retrospectively investigated. Joint findings, extrapulmonary involvements, and coexisting rheumatic disease were evaluated. Fifty-six patients (41.21 ± 7.83years, 75% female) were included. The duration of the disease was 49.61 ± 29.11months, and the follow-up period was 26.66 ± 13.26months. All patients had pulmonary system involvement. Arthralgia was present in 91.10% of 56 patients and arthritis in 89.29% of patients. Examining the subtypes of the arthritis findings, mono-arthritis was found in 31/50 (62%) patients, oligo-arthritis in 15/50 (30%) patients, and polyarthritis in 4/50 (8%) patients. A total of 11 (19.60%) patients were diagnosed with uveitis. Excision of the mediastinal LAP was performed in a total of 37 patients (66.1%) and became the most commonly employed method. Considering the treatment distribution of the patients under followed-up, it is seen that non-steroidal anti-inflammatory treatments were used in 15 (26.8%) patients, corticosteroids in a total of 40 (71.4%) patients, methotrexate in a total of 15 patients (26.8%), azathioprine in six (10.7%) patients, hydroxychloroquine in 14 (25%) patients, and infliximab in one (1.8%) patient. As sarcoidosis is a mimicking disease, a good differential diagnosis should be made to avoid misdiagnosis and in order not to be late in diagnosis and treatment. Physicians, especially rheumatologists, should remember sarcoidosis more frequently as the disease may overlap with other rheumatological diseases and may occur with many rheumatological manifestations.

A new model to predict the risk of major gastrointestinal bleeding in patients on direct oral anticoagulants (dabigatran and rivaroxaban).

The aim of this study was to identify factors associated with gastrointestinal bleeding (GIB) in patients on direct oral anticoagulants (DOACs) and develop a risk score that would provide an effective tool for the clinical assessment of GIB. This was a multicentre retrospective analysis of clinical and follow-up data of patients treated with DOACs. The score was developed through logistic regression. The performance of score was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity and Hosmer-Lemeshow test. The 11 903 patients had a mean age of 65.1years. In multivariate analysis, age ≥65 years, alcohol use, history of peptic ulcer, history of major bleeding, abnormal liver function or renal function, cancer, platelet count <100 × 109 /L, anaemia, and concurrent antiplatelet agent or non-steroidal anti-inflammatory drug treatment were independent risk factors for GIB, and concurrent treatment with gastrointestinal protective agents were a protective factor. The Alfalfa-DOAC-GIB score was constructed using these 12 factors. The AUC of the Alfalfa-DOAC-GIB score was 0.77 (95% CI 0.74-0.81), which was higher than that of the HAS-BLED score (0.69; 95% CI 0.65-0.72) and the New score (0.65; 95% CI 0.61-0.68). Based on 12 factors, we developed a gastrointestinal bleeding risk score. The newly developed Alfalfa-DOAC-GIB score has better predictive value than the HAS-BLED score and the New score, and might be an effective tool to help reduce the occurrence of GIB in patients using DOACs.

A Critical Review on the Pharmacodynamics and Pharmacokinetics of Non-steroidal Anti-inflammatory Drugs and Opioid Drugs Used in Reptiles

Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are analgesics used for moderate to severe pain in many animals, including reptiles. However, reptilian dosing regimens are often extrapolated from other animal species. This is not ideal as inter- and intra-species variability in physiology may result in varied drug disposition. Therefore, this critical review aims to collate data from pharmacological studies of selected NSAIDs and opioids performed in reptile and provide an analysis and discussion on the existing pharmacodynamic knowledge and pharmacokinetic data of NSAIDs and opioids use in reptiles. Additionally, key pharmacokinetic trends that may aid dosing of NSAIDs and opioids in reptiles will also be highlighted. Most of the existing reports of NSAID used in reptiles did not observe any adverse effects directly associated to the respective NSAID used, with meloxicam being the most well-studied. Despite the current absence of analgesic efficacy studies for NSAIDs in reptiles, most reports observed behavioural improvements in reptiles after NSAID treatment. Fentanyl and morphine were studied in the greatest number of reptile species with analgesic effects observed with the doses used, while adverse effects such as sedation were observed most with butorphanol use. While pharmacokinetic trends were drug- and species-specific, it was observed that clearance (CL) of drugs tended to be higher in squamates compared to chelonians. The half-life (t1/2) of meloxicam also appeared to be longer when dosed orally compared to other routes of drug administration. This could have been due to absorption-rate limited disposition. Although current data provided beneficial information, there is an urgent need for future research on NSAID and opioid pharmacology to ensure the safe and effective use of opioids in reptiles.

Electrochemical oxidation of Naproxen in aqueous matrices: Elucidating the intermediates’ eco-toxicity, by assessing its degradation pathways via experimental and density functional theory (DFT) approaches

The removal of the non-steroidal anti-inflammatory drug (NSAID) Naproxen (NAX) in water by hydroxyl radicals (•OH) was performed by electrochemical advanced oxidation processes either with Pt or BDD anodes and a 3D carbon felt cathode. The degradation of NAX by (•OH vs electrolysis time) was well fitted to a pseudo-first-order reaction rate kinetic. The detected reaction intermediates (aromatic compounds and carboxylic acids) were experimentally monitored during the process via LC, while density functional theory (DFT) was applied to uncover undetected intermediates, some for the first time in literature. The formation of toxic intermediates with higher toxicity than NAX were identified, such as IMS4b (6-Methoxy-1-[1-(6-methoxynaphthalen-2-yl) ethyl] naphthalen-2-ol), catechol, and glycolic acid. Based on these data, a detailed oxidation pathway of NAX by •OH was proposed. The evolution of solution toxicity indicated that the formed toxic intermediates were subsequently removed during the TOC removal process. Finally, almost complete mineralization of NAX was achieved in simulated urine or wastewater by the electro-Fenton treatment, with an optimized dose of iron as catalyst, showing the EAOPs’ potential to efficiently remove NAX even from challenging matrices. In extension, the strategies developed can be applied to the treatment of other NSAIDs.

Combination of Enzymes and Rutin to Manage Osteoarthritis Symptoms: Lessons from a Narrative Review of the Literature.

Osteoarthritis is the most common joint disorder affecting over 300 million people worldwide. It typically affects the knees and the hips, and is characterized by a loss in normal joint movement, stiffness, swelling, and pain in patients. The current gold standard therapy for osteoarthritis targets pain management using nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs are associated with several potentially serious side effects, the most common being gastrointestinal perforation and bleeding. Owing to the side effects, NSAID treatment doses need to be as low as possible and should be continued for the shortest duration possible, which is problematic in a chronic condition like osteoarthritis, which requires long-term management. Numerous clinical trials have examined oral enzyme combinations as a potential new approach in managing pain in patients with osteoarthritis. Oral enzyme combinations containing bromelain in combination with trypsin, both proteolytic enzymes, as well as the plant flavonoid rutin, may be an effective alternative to typical NSAIDs. The aim of this narrative review is to summarize and discuss the evidence on the efficacy of oral enzyme combinations compared to the gold standard (NSAID) in the management of osteoarthritis symptoms. Nine randomized controlled trials identified in this review assessed the efficacy and safety of the oral enzyme combination containing bromelain, trypsin, and rutin in patients with osteoarthritis. Most of the studies assessed the impact of the oral enzyme combination on the improvement of the Lequesne Algofunctional index score, treatment-related pain intensity alterations and adverse events compared to patients receiving NSAIDs. Although largely small scale, the study outcomes suggest that this combination is as effective as NSAIDs in the management of osteoarthritis, without the adverse events associated with NSAID use.Infographic

Maternal and infant outcomes in pregnancies of women with axial spondyloarthritis compared with matched controls: results from nationwide health insurance data

ObjectivesTo investigate pregnancy outcomes in women with axial spondyloarthritis (axSpA) under different pharmacological treatments in comparison with matched controls.MethodsUsing health insurance data from 2006 to 2019, pregnancy outcomes of women...

Pharmacokinetics and clinical efficacy of acetaminophen (paracetamol) in adult horses with mechanically induced lameness.

Acetaminophen has been used clinically in horses alone or combined with traditional non-steroidal anti-inflammatory drugs for treatment of musculoskeletal pain in horses. To determine the pharmacokinetics and efficacy of acetaminophen at two doses in horses with mechanically induced lameness compared with phenylbutazone or placebo control. In vivo experiment. Nine healthy mares with mechanical lameness induced via a reversible sole pressure horseshoe model were treated with acetaminophen (20 mg/kg PO; A20), acetaminophen (30 mg/kg PO; A30), phenylbutazone (2.2 mg/kg, PO; PB) and oral placebo (C) in a randomised four-way Latin square model. Plasma concentrations for A20 and A30 were analysed via LC-MS/MS and noncompartmental pharmacokinetic analysis. Heart rate and heart rate variability were measured using a portable telemetry. Lameness was scored by three blinded boarded equine surgeons using the AAEP and 10-point scales. Mean maximum plasma concentration (Cmax ) for A20 was 20.01 μg/ml within 0.66 h (Tmax ) after administration; The mean Cmax for A30 was 30.02 μg/ml with a Tmax of 0.43 h. Post-treatment heart rate for A30 was significantly lower than A20 at 1 and 7h; lower than PB at 2, 3, 4.5 and 7h; lower than C at 2, 3.5, 4.5, 6, 7 and 8h. 10-point Lameness scores were significantly improved for A30 than C at 2 and 4h post-treatment; PB was significantly improved than C at 8h post treatment. There were no significant differences in lameness between A20, A30 and PB. Small sample size, lack of objective lameness measurement. Acetaminophen at 30 mg/kg produced a more rapid improvement in lameness scores and heart rate compared with other treatments in this model. Further evaluation of the pharmacokinetics and safety of repeated oral dosing of acetaminophen at 30 mg/kg is needed to determine clinical utility.

All-Cause Health Care and Work Loss Burden Associated With Nonsteroidal Anti-Inflammatory Drug and Opioid Treatment in Employed Patients With Osteoarthritis.

This study estimated all-cause health care resource utilization (HRU) and costs and work loss outcomes associated with pain management of employed patients with osteoarthritis of the hip and/or knee. Optum Health Care Solutions data were analyzed for employed patients prescribed nonsteroidal anti-inflammatory drugs, tramadol, or nontramadol opioids following diagnoses of osteoarthritis of the hip and/or knee. A pre-post design was used to evaluate changes in all-cause HRU and costs, and work loss days and associated costs. Costs rose for patients in all three cohorts (up to 198.3% for health care costs [tramadol] and up to 178.7% for work loss costs [tramadol]). Greatest increases in all-cause HRU included inpatient visits (237.9% [nonsteroidal anti-inflammatory drugs]; 600% [tramadol]). Study results provide evidence of increases in all-cause HRU and costs and work loss days and associated costs.

Does coprescribing nonsteroidal anti-inflammatory drugs and oral anticoagulants increase the risk of major bleeding, stroke and systemic embolism?

To examine the risk of gastrointestinal (GI) bleeding, major bleeding, stroke and systemic embolism associated with prescribing nonsteroidal anti-inflammatory drugs (NSAIDs) to adults receiving oral anticoagulant (OAC) therapy. We conducted a population-based cohort study in adults receiving OAC therapy using linked primary care (Clinical Practice Research Datalink GOLD) and hospital (Hospital Episodes Statistics) electronic health records. We used cause-specific Cox regression models with time-dependent NSAID treatment in a propensity score matched population to estimate the increased risk of GI bleeding, stroke, major bleeding and systemic embolism associated with NSAID use. The matched cohort contained 3177 patients with OAC therapy alone and 3177 with at least 1 concomitant NSAID prescription. Compared with OAC therapy alone, concomitant prescription of NSAIDs with OACs was associated with increased risk of GI bleeding (hazard ratio [HR] 3.01, 95% confidence interval [CI] 1.63 to 5.55), stroke (HR 2.71, 95% CI 1.48 to 4.96) and major bleeding (HR 2.77, 95% CI 1.84 to 4.19). The association with systemic embolism did not reach statistical significance (HR 3.02, 95% CI 0.82 to 11.07). Sensitivity analyses indicated that the results were robust to changes in exclusion criteria and the choice of potential confounding variables. When OACs are coprescribed with NSAIDs, the risk of adverse bleeding events increases and, simultaneously, the protective effect of OACs to prevent strokes reduces. There is a need for interventions that reduce hazardous prescribing of NSAIDs in people receiving OAC therapy.

Pediatric Research Challenge, Alignment with the National Research Agenda

Pediatric Research Challenge, Alignment with the National Research Agenda

Factors affecting recurrence in subacute granulomatous thyroiditis.

This study aimed to evaluate the factors affecting recurrence in subacute granulomatous thyroiditis (SAT). A total of 137 patients with SAT were enrolled in the study; 98 (71.5%) were women and 39 (28.5%) were men. The patients received either steroid or nonsteroidal anti-inflammatory drug (NSAID) for eight weeks. Erythrocyte sedimentation rate (ESR), C-reactive protein, serum thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine (FT4), anti-thyroid peroxidase antibodies and thyroglobulin antibodies, neutrophil, lymphocyte, platelet, neutrophil to lymphocyte ratio, and platelet to lymphocyte ratio levels were evaluated. In addition, recurrence rates were compared between patients who received NSAID treatment and those who received steroid therapy. Treatment modality and pretreatment TSH, FT4, and ESR were significantly different between patients with and without recurrence (p = 0.011, 0.001, 0.004, and 0.026, respectively). Compared with patients without recurrence, those with recurrence had higher pretreatment TSH levels, but lower FT4 and ESR levels. On logistic regression analysis, treatment modality was found to be an independent risk factor for recurrence. The risk of recurrence was higher in those taking steroids than in those taking NSAIDs (p = 0.015). The optimal TSH cutoff value for recurrence was 0.045 µIU/mL, with a sensitivity of 83.3% and specificity of 76% (AUC 0.794, 95% CI 0.639-0.949). The risk of SAT recurrence was higher with steroid therapy than with NSAIDs. Patients who had mild thyrotoxicosis had relatively high recurrence rate and may need a relatively longer duration of treatment.

Stevens-Johnson Syndrome Following Non-steroidal Anti-inflammatory Drugs: A Real-World Analysis of Post-marketing Surveillance Data.

Background:The Stevens-Johnson syndrome (SJS) is a severe skin reaction to non-steroidal anti-inflammatory drugs (NSAIDs), and can even be life-threatening. However, there are still few real-world studies to compare the specific differences in the adverse effects of skin and mucosal invasion.MethodsDisproportionality analysis and Bayesian analysis were devoted to data-mining of the suspected SJS after using NSAIDs based on the FDA's Adverse Event Reporting System (FAERS) from January 2004 to March 2021. The times to onset, fatality, and hospitalization rates of antipyretic analgesic-associated SJS were also investigated.ResultsA total of 1,868 reports of SJS adverse events were identified with NSAIDs. Among 5 NSAIDs monotherapies we studied (acetaminophen, ibuprofen, aspirin, diclofenac and celecoxib), ibuprofen had the highest association with SJS based on the highest reporting odds ratio (ROR = 7.06, 95% two-sided CI = 6.59–7.56), proportional reporting ratio (PRR = 6.98, χ2 = 4201.14) and empirical Bayes geometric mean (EBGM = 6.78, 95% one-sided CI = 6.40). However, ibuprofen-associated SJS had the lowest fatality rate (6.87%, p < 0.0001) and the highest hospitalization rate (79.27%, p < 0.0001). Celecoxib-associated SJS had the latest time to onset (317.56 days, p < 0.0001). Diclofenac-associated SJS cases appeared to be associated with the highest risk of death (25.00%, p < 0.0001).ConclusionsThe analysis of FAERS data provides a more accurate profile of the incidence and prognosis of SJS after NSAIDs treatment, enabling continued surveillance and timely intervention in patients at risk of SJS following these NSAIDs.

Isolated posterior cruciate ligament calcification: A case report

Calcification around the knee joint is a rare condition in athletes. Medial collateral ligament (MCL) calcification is the most frequent post-traumatic ligament calcification. There is very limited information about the calcification of cruciate ligaments. In this study, we aimed to present a management scheme for the diagnosis and treatment process of a veteran athlete with isolated posterior cruciate ligament (PCL) calcification. A 59-year-old female patient, who was formerly an athlete, admitted to emergency department with generalized right knee pain that aggravated with sports activities. Radiographic images revealed a calcification in line with the PCL contours. It was decided to perform arthroscopic debridement. After the operation, the patient's symptoms regressed rapidly. Tendon calcifications may cause post-exercise pain in athletes with concomitant chronic diseases. Conservative treatment and non-steroidal antiinflammatory treatment should be tried first in all calcific tendinopathies. Although conservative treatment appears to be frequently satisfactory, arthroscopic excision may be a better option for the refractory or severe cases.

Retrospective comparison of outcomes following tibial plateau levelling osteotomy and lateral fabello-tibial suture stabilisation of cranial cruciate ligament disease in small dogs with high tibial plateau angles

ABSTRACT Aims To compare short and long-term outcomes after tibial plateau levelling osteotomy (TPLO) and lateral fabello-tibial suture (LFTS) techniques for the management of cranial cruciate ligament disease in small dogs with high tibial plateau angles (TPA). Methods In this retrospective study, the medical records of two veterinary specialist practices in the United Kingdom were searched for dogs (<20 kg) that underwent TPLO or LFTS between 2000 and 2010, and had a preoperative radiographic TPA >30° with either short-term (6 weeks) and/or long-term (>3 months) follow-up data. Data collected at a 6-week post-surgical re-examination was derived from orthopaedic examination and radiographic assessment and included the incidence of major and minor complications and scoring of the short-term outcome. Long-term outcome was scored based on results of a subjective owner questionnaire and veterinary orthopaedic examination. Results A total of 61 (84 stifles) dogs were included in the study: 24 (30 stilfes) and 37 (54 stifles) dogs underwent LFTS and TPLO, respectively. Long-term clinical outcome was different (p = 0.017) between groups; 15/15 stifles in the TPLO group had a good or excellent long-term clinical outcome, compared to 4/8 (50%) in the LFTS group. There was no evidence of a difference in short-term post-operative outcome or owner subjective long-term outcome between treatment groups. Stifles in the LFTS group were more likely (p = 0.027) to have palpable stifle pain at long-term follow-up. Owners reported that 5/16 (31.3%) dogs in the LFTS group required oral non-steroidal anti-inflammatory drug (NSAID) treatment at least monthly (4/5 required daily treatment), whereas no dogs in the TPLO group required treatment with NSAID more frequently than three times per year (p = 0.011). No correlation was found between short-term outcome and owner subjective long-term outcome but there was a positive correlation between short-term outcome and long-term clinical outcome. There was no evidence of a difference in overall major complication rates between treatment groups. The occurrence of complications was associated with heavier body weight at the time of surgery. No other variables were shown to be risk factors for complications. Conclusion and clinical relevance Small breed dogs with high TPA that underwent TPLO had better long-term clinical outcomes and were less likely to require NSAID administration than those that underwent LFTS. The risk of complication increased with the weight of the dog at surgery. There was a positive correlation between short-term outcome and long-term clinical outcome.

Different changes in the biomarker C-terminal telopeptides of type II collagen (CTX-II) following intra-articular injection of high molecular weight hyaluronic acid and oral non-steroidal anti-inflammatory drugs in patients with knee osteoarthritis: a multi-center randomized controlled study

We previously reported, based on a multicenter randomized-control study, that the efficacy of intra-articular injections of hyaluronic acid (IA-HA) was not inferior to that of oral non-steroidal anti-inflammatory drugs (NSAIDs) in patients with knee osteoarthritis (OA). However, the molecular effects on the pathophysiology of knee OA remain unclear. C-terminal telopeptides of type II collagen (CTX-II) is reported to primarily originate from the interface between articular cartilage and subchondral bone, which is a site of potential remodeling in OA. We performed a predefined sub-analysis of the previous study to compare the changes of urinary CTX-II (uCTX-II) in response to IA-HA to those in response to NSAID for knee OA. A total of 200 knee OA patients were registered from 20 hospitals and randomized to receive IA-HA (2,700kDa HA, 5 times at 1-week intervals) or NSAID (loxoprofen sodium, 180mg/day) for 5weeks. The uCTX-II levels were measured before and after treatment. The uCTX-II levels were significantly increased by IA-HA treatment (337.7±193.8 to 370.7±234.8ng/μmol Cr) and were significantly reduced by NSAID treatment (423.2±257.6 to 370.3±250.9ng/μmol Cr). The %changes of uCTX-II induced by IA-HA (11.6±29.5%) and NSAID (-9.0±26.7%) was significantly different (between-group difference: 20.6, 95% confidence intervals: 10.6 to 30.6). While both IA-HA and NSAID improved symptoms of knee OA, uCTX-II levels were increased by IA-HA and reduced by NSAIDs treatment, suggesting these treatments may improve symptoms of knee OA through different modes of action.

Érythème noueux compliquant une maladie des griffes du chat : une association et des implications thérapeutiques à connaître

IntroductionCat-scratch disease is a zoonosis caused by Bartonella henselae and transmitted mostly through a break in the skin. This infectious disease is commonly characterized by a benign lymphadenitis. However, more unusual presentations have been observed. Case reportWe report the case of a 44-year-old woman with cat-scratch disease who developed subsequently an erythema nodosum. The non-steroidal anti-inflammatory treatment of the erythema nodosum may have led to worsening of cat-scratch disease with an abscess requiring surgical treatment. ConclusionCat-scratch disease is an uncommon and poorly known cause of erythema nodosum, and must be systematically ruled out. As non-steroidal anti-inflammatory drug are usually prescribed as a treatment of erythema nodosum, it should be used cautiously to reduce the risk of complications in the cat-scratch disease.

Presence of subclinical inflammation in axial spondyloarthritis patients with NSAID/anti-TNF-α drug-induced clinical remission.

To investigate the rate of subclinical inflammation in patients with axial spondyloarthritis (axSpA) with nonsteroidal anti-inflammatory drug (NSAID)/anti-tumor necrosis factor (TNF)-α drug-induced clinical remission and to explore factors influencing clinical and imaging remission. One hundred twenty-five patients with axSpA followed up for at least 6months were enrolled in this prospective study and randomly divided into two groups. Ninety patients were treated with anti-tumor necrosis factor (TNF)-α or anti-TNF-α combined with nonsteroidal anti-inflammatory drugs (NSAIDs) (anti-TNF-α treatment group), and thirty-five patients were treated with only NSAIDs (non anti-TNF-α treatment group). The improvements in the clinical remission rate, imaging remission rate, and disease parameters before and after the different treatments were compared. Risk factors for clinical and imaging remission were analyzed by multivariate logistic regression analysis. The clinical and imaging remission rate was increased after treatment especially in the anti-TNF-α group (P < 0.001). The remission rate of imaging in the group with clinical remission was higher than that in the group with clinical non-remission (P < 0.05). After treatment, the remission rates of imaging in the clinical remission and non-remission group were significantly higher than those before treatment (P < 0.0001). The results of multivariate logistic regression analysis showed that higher CRP was a risk factor for failure of clinical remission in axSpA (OR = 2.034, 95% CI:1.595 ~ 2.617, P < 0.001), while higher ASDAScrp was a risk factor for failure of imaging remission (OR = 1.306, 95% CI:1.026 ~ 1.688, P < 0.05). Anti-TNF-α treatment was a protective factor for both clinical (OR = 0.234, 95% CI:0.091 ~ 0.605, P < 0.05) and imaging remission (OR = 0.511, 95% CI:0.286 ~ 0.914, P < 0.05). Even after regular treatment, some clinical remission patients continued to have evidence of subclinical inflammation. Higher CRP and ASDAScrp are risk factors for clinical and imaging non-remission in axSpA respectively, Continuous NSAID treatment (more than 1year) can effectively improve clinical and MRI inflammation in patients, but anti-TNF-α treatment is more beneficial for clinical and imaging remission. Key Points • Some patients achieving ASDAScrp remission status continue to have inflammation when assessed with objective imaging techniques. • MRI can sensitively measure bone marrow inflammation and may provide a more accurate assessment of remission. • Controlling inflammation, especially reducing CRP and ASDAScrp levels, is a key factor for achieving clinical and imaging remission in patients with axSpA.