Nonsteroidal Anti-inflammatory Drugs Treatment Research Articles

A CLINICAL STUDY ON MANAGEMENT OF POST-OPERATIVE PAIN AND QUALITY OF LIFE OF OSTEOARTHRITIS PATIENTS AFTER TOTAL KNEE ARTHROPLASTY

Objective: The objective of this study is to assess the effect of pregabalin in the management of post-operative pain and the quality of life (QOL) of osteoarthritis (OA) patients after total knee arthroplasty.Methods: This prospective observational study was conducted in the Department of Orthopedics. A total of 96 patients were divided into two groups. Group A consists of 50 patients with the treatment of nonsteroidal anti-inflammatory drugs (NSAIDs) and Group B consists of 46 patients with the treatment of pregabalin with NSAIDs. The study subjects were followed once in 60 days for 6 months, and they were asked to answer the visual analog scale (VAS) and knee injury and OA outcome score (KOOS) questionnaire. The effect of the treatment was assessed by comparing the baseline score with follow-up score.Results: Our study result showed that the pain score of Group B in VAS at 2nd follow-up was 2.56±0.34 and KOOS pain score was 92.73±3.45 (p<0.01). The QOL score was improved significantly to 81.56±5.29 (p<0.01) as compared to Group A.Conclusion: The study concluded that pregabalin with NSAIDs group patients showed a better improvement in pain, symptoms, and QOL within short duration as compared to NSAIDs alone used group.

Effects of local anesthetic or systemic analgesia on pain associated with cautery disbudding in calves: A systematic review and meta-analysis

Disbudding is a common management procedure performed on dairy farms and, when done without pain mitigation, is viewed as a key welfare issue. Use of pain control has increased in recent years, but full adoption of anesthesia and analgesia by veterinarians or dairy producers has not been achieved. This may in part be due to the lack of a consistent recommendations of treatment protocols between studies examining pain control methods for disbudding. The objective of this systematic review was to examine the effects of these pain control practices for the most common method of disbudding, cautery, on outcomes associated with disbudding pain in calves. The outcomes were plasma cortisol concentrations, pressure sensitivity of the horn bud area, and validated pain behaviors (ear flick, head shake, head rub, foot stamp, and vocalization). Intervention studies describing cautery disbudding in calves 12 wk of age or younger were eligible, provided they compared local anesthesia, nonsteroidal anti-inflammatory drug (NSAID), or local anesthesia and NSAID to 1 or more of local anesthesia, NSAID, or no pain control. The search strategy used the Agricola, Medline (via OvidSP), and Web of Science databases, as well as the Searchable Proceedings of Animal Conferences (S-PAC), ProQuest Dissertations and Theses Database, and Open Access Theses and Dissertations. Meta-analysis was performed for all outcomes measured at similar time points with more than 2 studies. Local anesthetic was associated with reduced plasma cortisol until 2 h postdisbudding; however, a rise in cortisol was observed in the meta-analysis of studies reporting at 4 h postdisbudding. Heterogeneity was present in several of the analyses for this comparison. The addition of NSAID to local anesthetic showed reduction in plasma cortisol at 4 h, and a reduction in pressure sensitivity and pain behaviors in some analyses between 3 and 6 h postdisbudding. Heterogeneity was present in some meta-analyses, including several using pain behavior outcomes. This may reflect the variation in measurement time periods for behavioral measures between studies, as well as differences among NSAID treatments. Overall, a protective effect of local anesthetic was seen for the acute pain of cautery disbudding, and the delayed rise in cortisol was mitigated by the addition of an NSAID, which also reduced other signs of pain, including pressure sensitivity and pain behaviors. Based on these findings, we recommend use of local anesthetic and an NSAID as best practices for pain mitigation for cautery disbudding of calves 12 wk of age or less. The magnitude and duration of the effect of NSAID treatment was not possible to deduce from the literature because wide variation existed between studies. We recommend consideration of more standardized outcome measurements, especially for pain behaviors. Adherence to reporting guidelines by authors would help ensure more transparent and complete information is available to end users.

Efficiency of the combination of physical therapy modalities with topical nonsteroidal anti-inflammatory drugs for treatment of pain in rheumatology

Pain is the most common syndrome in rheumatology. NSAIDs are often used in its treatment. But they have limitations associated with side effects. An advantage of topical drugs and physical factors (electrophoresis, phonophoresis) combination is the use of low doses of the drug and a decrease in time, to achieve a therapeutic effect, reduce the risk of adverse reactions, increase the concentration of the drug in the inflammation focus, prolonged action (creating a drug depot in tissues). Ketoprofen gel (“Artrocol gel”) is one of the representatives of this pharmacological group. Physicochemical properties help ketoprofen to penetrate easily through the skin and create a therapeutic concentration in the underlying tissues. 
 Objective. 
 To assess the effectiveness of ketoprofen gel (“Arthrocol gel”) electrophonophoresis in the treatment of pain in rheumatological patients. 
 Materials and methods. 
 The study was carried out on the basis of Physiotherapy Department of Vinnytsia Regional Clinical Hospital named after M. I. Pirogov. All patients treated according to the unified clinical protocols were divided into experimental group (EG) and control group (CG). Patients of EG (98 persons) underwent electrophonophoresis with ketoprofen gel once a day for a week. In CG (43 persons) ketoprofen gel was used without electrophonophoresis. The intensity of the pain syndrome is monitored using a visual analog scale (VAS) of Huskisson at rest and during movement. A week later, the patient and the doctor evaluated satisfaction with the results of treatment on the scale: not effective, insufficient, satisfactory, good, excellent. 
 Results. 
 There was a persistent decrease in the intensity of pain syndrome in patients of both groups. The VAS scores were lower in the EG starting from the 3rd day of treatment. The intensity of the acute pain syndrome after 1-week treatment at rest (t = 4.71, p < 0.001) and during the movement (t = 3.84, p < 0.001) more decrease in EG. Satisfaction with the results of treatment was higher in EG.

Predictive value of microRNA-132 and its target gene NAG-1 in evaluating therapeutic efficacy of non-steroidal anti-inflammatory drugs treatment in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a common chronic rheumatic disorder, accompanied by the differential expression of various microRNAs (miRNAs) in patients suffering from the condition, some of which have the potential to serve as novel complementary AS biomarkers. During this study, AS patients were recruited in connection with our investigation into the correlation of microRNA-132 (miR-132) in peripheral blood and its target gene NAG-1 expressions in relation with the clinical efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) treatment in patients with AS. A total of 218 AS patients who had been previously treated with oral diclofenac sodium and were placed into either the response (n = 175) or non-response groups (n = 43) following a 16-week period of therapeutic evaluation. An additional 113 healthy patients were also recruited for the purposes of the study. AS patient peripheral blood samples were obtained at the 0th, 8th, and 16th week, with the corresponding samples of the healthy patients collected at week 0. The expressions of miR-132 and NAG-1 were detected by RT-qPCR and analyzed using a ROC curve for the elucidation of the diagnostic value of peripheral blood miR-132 expressions as well as their predictive value among AS patients undergoing NSAIDs treatment. The targeting relations of miR-132 and NAG-1 were validated by microRNA.org and luciferase assay. Greater levels of peripheral blood miR-132 expression were observed among AS patients prior to treatment, in comparison to the healthy patients in the study. Prior to treatment, the area under the miR-132 ROC curve (AUC) of AS patients was 0.965, with a critical point of 2.605. The sensitivity and specificity of miR-132 were 91.7 and 97.3%, respectively, in regard to the AS diagnostic clinical efficacy. In comparison with the non-response group, the miR-132 expression of patients in the response group exhibited descended levels while the mRNA expression of NAG-1 increased. The ROC results indicated that the AUC of miR-132 was 0.876 with its sensitivity and specificity observed to be 95.3 and 80.0%, respectively. The AUC of NAG-1 was 0.912 with its sensitivity and specificity observed to be 76.6 and 79.1%, respectively. In comparison with the high miR-132 expression group and the low NAG-1 mRNA expression group, significantly improved blood biochemistry indexes, sign indexes, blood indexes, and adverse reaction rate were observed among the low miR-132 expression group and the high NAG-1 mRNA expression group. The microRNA.org and luciferase assay revealed NAG-1 to be a target of miR-132. Based on the results of this study, it was concluded that the expressions of MiR-132 and NAG-1 could serve as biological markers in the prediction of the therapeutic efficiency of NSAID treatment in AS patients.

Changes in feeding, social, and lying behaviors in dairy cows with metritis following treatment with a nonsteroidal anti-inflammatory drug as adjunctive treatment to an antimicrobial

Dairy cows with metritis display sickness behaviors, and nonsteroidal anti-inflammatory drugs (NSAID) have the potential to reduce these responses. The objective of this study was to investigate changes in feeding, social, and lying behaviors in dairy cows with metritis that had been treated with the NSAID meloxicam. After parturition, cows were housed in a dynamic, mixed-parity group of 20 animals with access to 12 electronic feed bins, 2 electronic water bins, and 24 lying stalls in a freestall pen. Every third day after parturition, vaginal discharge was evaluated to diagnose metritis based on the presence of foul smell and characteristic visual appearance. When diagnosed with metritis, animals (n = 87) were randomly allocated to receive either a single dose of meloxicam (0.5 mg/kg of body weight subcutaneously) or a placebo solution. All metritic animals received an antimicrobial (ceftiofur) for 5 d. We measured feeding and social behaviors at the feed bunk, as well as lying behaviors, and assessed within-cow changes from the day before to the day of (d 0) NSAID treatment, and from the day before to d 1 to 5 after treatment. Generally, behaviors changed around the day of diagnosis of metritis. Compared with the placebo group, cows that received meloxicam had a greater increase in the number of visits to the feeder, but tended to show less of an increase in dry matter intake and feeding time. These differences did not persist beyond 24 h after NSAID treatment. We observed no differences in changes in number of meals and feeding rate on d 0, but from d 1 to 5 cows treated with meloxicam had a lesser decrease in the number of meals and tended to have a greater decrease in feeding rate than did placebo-treated cows. In multiparous cows on d 0 and from d 1 to 5, meloxicam treatment was associated with decreased lying times. In primiparous cows, lying time changes were similar between treatments on d 0, but lying times increased more on d 1 to 5 for meloxicam than for placebo cows. Overall, cows changed the number of lying bouts on d 0, and this increase tended to be smaller for the meloxicam cows. There were no treatment differences in changes of social behavior. In summary, we observed inconsistent and generally small effects of a single dose of meloxicam in addition to antimicrobial therapy on the behavior of cows with metritis.

Efficacy and safety of combined treatment of miniscalpel acupuncture and non-steroidal anti-inflammatory drugs: an assessor-blinded randomized controlled pilot study

BackgroundChronic neck pain is a common musculoskeletal disease during the lifespan of an individual. With an increase in dependence on computer technology, the prevalence of chronic neck pain is expected to rise and this can lead to socioeconomic problems. We have designed the current pilot study to evaluate the efficacy and safety of miniscalpel acupuncture treatment combined with non-steroidal anti-inflammatory drugs (NSAIDs) in patients with chronic neck pain.MethodsThis seven-week clinical trial has been designed as an assessor-blinded, randomized controlled trial with three parallel arms. Thirty-six patients will be recruited and randomly allocated to three treatment groups: miniscalpel acupuncture treatment; NSAIDs; and miniscalpel acupuncture treatment combined with NSAIDs. Patients in the miniscalpel acupuncture and combined treatment groups will receive three sessions of miniscalpel acupuncture over a three-week period. Patients in the NSAIDs and combined treatment groups will receive zaltoprofen (one oral tablet, three times a day for three weeks). Primary and secondary outcomes will be measured at weeks 0 (baseline), 1, 2, 3 (primary end point), and 7 (four weeks after treatment completion) using the visual analogue scale and the Neck Disability Index, EuroQol 5-dimension questionnaire, and Patients’ Global Impression of Change scale, respectively. Adverse events will also be recorded.DiscussionThis pilot study will provide a basic foundation for a future large-scale trial as well as information about the feasibility of miniscalpel acupuncture treatment combined with NSAIDs for chronic neck pain.Trial registrationKorean Clinical Research Information Service registry, KCT0002258. Registered on 9 March 2017.

Effects of nonsteroidal anti-inflammatory drugs on serum proinflammatory cytokines in the treatment of ankylosing spondylitis.

This study was conducted to investigate the correlation between serum levels of proinflammatory cytokines and the clinical efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with ankylosing spondylitis (AS). A total of 148 patients with AS were selected and received NSAID treatment. ELISA was used to assess cytokine levels, and patients were assigned into the following groups: positively effective; effective; moderately effective; and ineffective. Spearman and Pearson correlation analyses were used for correlation analysis. The erythrocyte sedimentation rates (ESR), C-reactive protein (CRP) levels, and immunoglobulin A (IgA) levels of the case group after NSAID treatment were markedly lower than those before NSAID treatment. After treatment, the levels of interleukin (IL)-6, IL-17, and tumor necrosis factor (TNF)-α were markedly reduced, while IL-10 levels increased in the positively effective, effective, and moderately effective groups, and IL-12 levels decreased in the positively effective and effective groups. In addition, the levels of IL-6 and TNF-α were correlated with a greater number in the efficacy indexes and clinical parameters, followed by IL-10 levels, while the levels of IL-17 and IL-12 had relatively weaker correlations with these indexes and parameters. NSAIDs could promote the clinical efficacy of treatment for ankylosing spondylitis by regulating serum levels of proinflammatory cytokines.

Prostaglandin antagonist relieves blood-retinal barrier breakdown induced by anterior segment intraocular surgery in a rat model.

To evaluate the efficacy of prostaglandin antagonists on blood-retinal barrier breakdown induced by anterior segment intraocular simulated surgery. Rats were randomly assigned to a negative control group, model group, nonsteroidal anti-inflammatory drugs prophylactic treatment group, nonsteroidal anti-inflammatory drugs treatment group, corticosteroid prophylactic treatment group, and corticosteroid treatment group. Four hours and 48h after modeling, the concentrations of PGE1, PGE2, and PGF2 α in the aqueous humor and vitreous body of the rat model were visualized using ELISA. The integrity of the blood-retinal barrier was quantitatively measured using Evan's blue as a tracer. Four hours after modeling, the concentrations of PGE1, PGE2, and PGF2α in the aqueous humor and vitreous body in the negative control group and the nonsteroidal anti-inflammatory drugs prophylactic treatment group were significantly lower than those in the model group. The concentrations of PGE1, PGE2, and PGF2α in the aqueous humor and vitreous body in the corticosteroid prophylactic treatment group were higher than those in the negative control group and the nonsteroidal anti-inflammatory drugs prophylactic treatment group. Forty-eight hours after modeling, the concentrations of PGE1, PGE2, and PGF2α in the aqueous humor and vitreous body in the nonsteroidal anti-inflammatory drugs prophylactic treatment group, nonsteroidal anti-inflammatory drugs treatment group, corticosteroid prophylactic treatment group, and corticosteroid treatment group were lower than those in the model group, but higher than those in the negative group. Retinal Evan's blue leakage in the nonsteroidal anti-inflammatory drugs prophylactic treatment group was higher than that in the negative control group, and lower than those in the nonsteroidal anti-inflammatory drugs treatment group, corticosteroid prophylactic treatment group, corticosteroid treatment group, and model group. Retinal Evan's blue leakage in the nonsteroidal anti-inflammatory drugs treatment group, corticosteroid prophylactic treatment group, and corticosteroid treatment group were lower than those in the model group. This study confirms that prostaglandin antagonists can relieve blood-retinal barrier breakdown in a rat model and that nonsteroidal anti-inflammatory drugs prophylactic treatment can achieve better efficacy.

Role of Nonsteroidal Anti-inflammatory Drug in Treatment of Extra-abdominal Desmoid Tumors.

BackgroundWe retrospectively reviewed the outcomes of patients who had been treated with meloxicam for the extra-abdominal desmoid tumors and evaluated the correlation between clinical outcome and clinic pathological variables.MethodsTwenty patients treated with meloxicam were followed up every 3 to 6 months. Meloxicam administration was planned at 15 mg/day orally for 6 months.ResultsOf the 20 patients evaluated, according to Response Evaluation Criteria in Solid Tumors criteria, there were five patients with partial response (25.0%), eight with stable disease (40.0%), and seven with tumor progression (35.0%). The cumulative probability of dropping out from our nonsurgical strategy using meloxicam was 35.0% at 1 year and 35.0% at 5 years.ConclusionsThe present study suggests that conservative treatment would be a primary treatment option for this perplexing disease even though we were not able to determine that the use of a cyclooxygenase-2 inhibitor would have an additional influence on the natural course of a desmoid tumor.

Critical Literature Review of the Homeopathic Compound Traumeel for Treatment of Inflammation

Traumeel is a compound that is utilized by a wide variety of healthcare practitioners to treat inflammatory states. It is utilized extensively in Germany for multiple inflammatory conditions. The purpose of this document is to review and critique publications written about Traumeel and Traumeel S, a proprietary formulation. Furthermore, this review will determine if the literature supports substituting Traumeel for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and corticosteroids or if adding Traumeel to NSAID and corticosteroid treatment protocols benefits patients with inflammation. Long-term use of NSAIDs and corticosteroids causes significant pathology leaving many patients without an effective treatment to manage their inflammatory condition. Traumeel does not have the severe side effect profile of NSAIDs and corticosteroids. There are important implications of the studies included in this review. The literature supports Traumeel as an effective alternative to NSAIDS and corticosteroids in preventing stomatitis for patients undergoing chemotherapy. Traumeel also provides pain-free outcomes following musculoskeletal and tissue injuries.

Biomarkers of bone remodeling in ankylosing spondylitis patients using nonsteroidal anti-inflammatory drugs: results of an ETHICS research program

To evaluate changes in the concentration of biomarkers for osteoproliferation and bone resorption in ankylosing spondylitis (AS) patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs) in different regimens. Forty patients with AS (according to the modified New York criteria), who had BASDAI ≥ 4.0 at baseline and at 52 weeks of on-demand NSAID treatment were examined and randomized into 2 groups: 1) 30 patients who used continuously oral tenoxicam 20 mg daily (a study group); 2) 10 patients who continued previous therapy (a comparison group). BASDAI and ASDAS were calculated; the serum levels of C-reactive protein, C-terminal type I procollagen propeptide (PICP), and C-terminal telopeptide of type I collagen (CTX-I) were measured at baseline and at 52 and 56 weeks of treatment. A control group consisted of 19 healthy volunteers. The continuous use of NSAIDs (tenoxicam) decreased higher baseline BASDAI and ASDAS scores. There were no changes in the indicators of AS activity in the patients who took on-demand NSAIDs. Baseline CTX-I levels did not differ between the patients with AS and the healthy individuals; those declined during continuous intake of tenoxicam and remained unchanged during on-demand administration. In the patients with AS, baseline PICP levels exceeded those in the healthy individuals. In the tenoxicam-treated patients, the concentrations of PICP at baseline and at 52 and 56 weeks were 17.1±9.0, 16.8±9.9, and 13.29±6.7 ng/ml, respectively (p=0.0001 for differences between the baseline and week 56 levels); in the comparison group, PICP levels did not change statistically significantly (p≥0.05 for all intergroup comparisons). Changing the inefficient long-term on-demand use of NSAIDs to their continuous intake is associated with a rapid decrease in clinical AS activity (within 4 weeks) with a reduction in the higher baseline concentration of the marker for osteoproliferation and in the normal level of the marker for bone resorption.

A rare case of nasal osteoma in a dog: a case report

A 35-month-old female German shepherd weighing 33.2 kg was referred to our department with a 10-month history of sneezing and left nasal swelling. On clinical examination, the dog showed deformity of the left nasal plane in the absence of any cutaneous lesions or nasal discharge, and presented with nasal snoring noises during both the inspiratory and expiratory phases. The patency of nasal cavities was evaluated using the cotton swab test, and was found to be preserved only on the right side. Endoscopic, radiographic and computed tomographic examination revealed an osteoproductive lesion that distorted the nasal, maxillar and frontal bones, completely occupying the left nasal cavity and frontal sinuses, resulting in destruction of the nasal septum and invasion of the contralateral nasal cavity. Five bioptic samples of the mass were collected from the cutaneous surface using a 9G Jamshidi bone marrow bioptic instrument. Histologically, the lesion consisted of a non-encapsulated, multilobulated mass composed of dense coalescing trabeculae of well-differentiated bone, which was lined by osteogenic cells. The morphology was suggestive of nasal osteoma. Due to the large size of the mass, evidenced by computed tomography, chronic systemic nonsteroidal anti-inflammatory treatment with carprofen was proposed instead of surgery. The description of this case is useful for veterinarians, who should consider osteoma as a possible differential diagnosis for nasal tumours.

Nonsteroidal Anti-Inflammatory Drug-Induced Leaky Gut Modeled Using Polarized Monolayers of Primary Human Intestinal Epithelial Cells

The intestinal epithelium provides a critical barrier that separates the gut microbiota from host tissues. Nonsteroidal anti-inflammatory drugs (NSAIDs) are efficacious analgesics and antipyretics and are among the most frequently used drugs worldwide. In addition to gastric damage, NSAIDs are toxic to the intestinal epithelium, causing erosions, perforations, and longitudinal ulcers in the gut. Here, we use a unique in vitro human primary small intestinal cell monolayer system to pinpoint the intestinal consequences of NSAID treatment. We found that physiologically relevant doses of the NSAID diclofenac (DCF) are cytotoxic because they uncouple mitochondrial oxidative phosphorylation and generate reactive oxygen species. We also find that DCF induces intestinal barrier permeability, facilitating the translocation of compounds from the luminal to the basolateral side of the intestinal epithelium. The results we outline here establish the utility of this novel platform, representative of the human small intestinal epithelium, to understand NSAID toxicity, which can be applied to study multiple aspects of gut barrier function including defense against infectious pathogens and host-microbiota interactions.

Pericarditis aguda

EpidemiologyThis is the most common pericardial syndrome, and appears to be most frequent in young adults. Aetiology/aetiopathogenesisMost of the cases in our environment are viral or idiopathic, although it can be associated with systemic and neoplastic disease. The most common aetiology in developing countries is tuberculosis. Clinical manifestationsThe principal clinical manifestation is chest or precordial pain of mechanical characteristics. Low-grade fever can be associated. DiagnosisTwo of these 4 criteria need to be present to establish a diagnosis: pericardial chest pain, pericardial rub, new ST segment elevation or PR segment depression on ECG and pericardial effusion. PrognosisThe course of the condition is usually benign and symptoms disappear when treatment is started. However, complications can appear in some cases such as myopericarditis or cardiac tamponade, especially in cases that are not viral in aetiology. TreatmentNon-steroidal anti-inflammatory drugs are the treatment of choice for acute idiopathic pericarditis, associated with colchicine to prevent recurrence. Other aetiologies require specific treatment of the cause.

Changes of Interleukin-1β and Testosterone Concentration after Nonsteroidal Anti-Inflammatory Drug Treatment at Different Times Relative to Endotoxin Administration in an Equine Model

Changes of Interleukin-1β and Testosterone Concentration after Nonsteroidal Anti-Inflammatory Drug Treatment at Different Times Relative to Endotoxin Administration in an Equine Model

Effects of anti-inflammatory (NSAID) treatment on human tendinopathic tissue.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat tendinopathy, but evidence for this treatment is lacking, and little is known regarding effects of NSAIDs on human tendinopathic tendon. This study investigated the effects of NSAID treatment (ibuprofen) on human tendinopathic tendon, with changes in gene expression as the primary outcome, and tendon pain, function, and blood flow as secondary outcomes. Twenty-six adults (16 men, 10 women), diagnosed with chronic Achilles tendinopathy, were randomized to 1-wk treatment with ibuprofen (600 mg ×3/day) (n = 13) or placebo (n = 13) (double-blinded). Ibuprofen content in blood, visual analog scale score for tendon pain at rest and activity, Victorian Institute of Sports Assessment-Achilles (VISA-A) scores for tendon function, tendon thickness (with ultrasonography), and color Doppler were measured before and 1 h after treatment. After the last posttreatment test, a full-width tendon biopsy was taken from the affected area. Real-time-RT-PCR was used to assess expression of collagen I, collagen III, transforming growth factor (TGF-β) isoforms, cyclooxygenase-2 (COX-2), angiopoietin-like 4 (ANGPTL4), and cyclic AMP-dependent transcription factor (ATF3) in tendon tissue. Expression of collagens and TGF-β isoforms showed relatively low variation and was unaffected by ibuprofen treatment. Further, no changes were seen in tendon thickness or VISA-A score. The placebo treatment reduced the color Doppler (in tendon plus surrounding tissue) compared with the ibuprofen group and also increased the perception of pain at rest. In conclusion, there was no indication that short-term ibuprofen treatment affects gene expression in human chronic tendinopathic tendon or leads to any clear changes in tendon pain or function.NEW & NOTEWORTHY Nonsteroidal anti-inflammatory drugs are widely used in the treatment of tendinopathy, but little is known of the effects of these drugs on tendon tissue. We find that 1 wk of ibuprofen treatment has no effect on gene expression of collagen and related growth factors in adult human tendinopathic tendon in vivo (in spite of relatively low levels of variation in gene expression), suggesting that tendinopathic cells are not responsive to ibuprofen.

Effect of Early and Prophylactic Nonsteroidal Anti-Inflammatory Drugs on Flare Duration in Pediatric Acute-Onset Neuropsychiatric Syndrome: An Observational Study of Patients Followed by an Academic Community-Based Pediatric Acute-Onset Neuropsychiatric Syndrome Clinic.

Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is characterized by the sudden onset of severe obsessive-compulsive symptoms and/or eating restriction along with at least two coinciding neuropsychiatric symptoms. When associated with group A Streptococcus, the syndrome is labeled Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS). An abnormal immune response to infection and subsequent neuroinflammation is postulated to play an etiologic role. We evaluated the impact of nonsteroidal anti-inflammatory drug (NSAID) treatment on flare duration in PANS/PANDAS. Patient inclusion criteria: Patients were included if they had at least one neuropsychiatric deterioration ("flare") that met strict PANS/PANDAS research criteria and for which flare duration could be assessed. Flare inclusion criteria: Any flare that started before October 15, 2016 was included and followed until the flare resolved or until the end of our data collection (November 1, 2016). Flare exclusion criteria: Flares were excluded if they were incompletely resolved, treated with aggressive immunomodulation, or treated with NSAIDs late (>30 days of flare onset). Ninety-five patients met study inclusion criteria and collectively experienced 390 flares that met flare criteria. Data were analyzed using multilevel linear models, adjusting for demographics, disease, and treatment covariates. NSAID use was associated with a significantly shorter flare duration. Flares not treated with NSAIDs had a mean duration of approximately 12.2 weeks (95% CI: 9.3-15.1). Flares that occurred while the child was on NSAID maintenance therapy were approximately 4 weeks shorter than flares not managed with NSAIDs (95% CI: 1.85-6.24; p < 0.0001). Flares treated with NSAIDs within 30 days of flare onset were approximately 2.6 weeks shorter than flares not managed with NSAIDs (95% CI: 0.43-4.68; p = 0.02). Flares treated prophylactically and those treated early with NSAIDs did not differ in duration (p = 0.26). Among the flares that received NSAID treatment within the first 30 days, earlier intervention was modestly associated with shorter flare durations (i.e., for each day that NSAID treatment was delayed, flare duration increased by 0.18 weeks; 95% CI: 0.03-0.33; p = 0.02), though it was not statistically significant after controlling for covariates (p = 0.06). NSAIDs given prophylactically or within 30 days of flare onset may shorten neuropsychiatric symptom duration in patients with new-onset and relapsing/remitting PANS and PANDAS. A randomized placebo-control clinical trial of NSAIDs in PANS is warranted to formally assess treatment efficacy.

Inhaled nitric oxide prevents NSAID-induced renal impairment in pseudo-normovolaemic piglets.

ObjectiveInhaled nitric oxide (iNO) is commonly used as a treatment of pulmonary hypertension. Its action is purported to be specific to the lung, but extrapulmonary effects have been reported. The objective of this study was to evaluate if iNO could compensate the renal impairment induced by ketoprofen, a conventional non-steroidal anti-inflammatory drug (NSAID), during general anaesthesia.MethodsUnder pseudo-normovolaemic condition, thirty piglets were randomly assigned into 5 equal groups and equipped for renal and systemic parameters measurements. A first experiment was carried out to validate methods and reproduce the renal effects of iNO (40 ppm) in comparison with a placebo (100% oxygen). In a second experiment, iNO was inhaled for 120 minutes right after NSAID treatment (ketoprofen 2 mg×kg-1 IV, and 40 ppm iNO; group KiNO) and its effects were compared to ketoprofen alone (2 mg×kg-1 IV; group K) and placebo (saline; group C).ResultsIn this model, iNO increased significantly renal blood flow measured by ultrasonic (RBFUL: +53.2±17.2%; p = 0.008) and by PAH clearance (RBFPAH:+78.6±37.6%; p = 0.004) methods, glomerular filtration rate (GFR: +72.6±32.5%; p = 0.006) and urinary output (UO: +47.4±24.2%; p = 0.01). In the second experiment, no significant temporal variation was noted for renal parameters in groups KiNO and C, whereas a significant and constant decrease was observed in the group K for RBFUL (max -19.0±7.1%), GFR (max -26.6±10.4%) and UO (max -30.3±10.5%).Clinical significanceOur experiments show that iNO, released from its transport forms after its inhalation, can improve renal safety of NSAIDs. This result is promising regarding the use of NSAIDs in critical conditions, but needs to receive clinical confirmation.

Evaluation of the Effect of a Single Intra-articular Injection of Allogeneic Neonatal Mesenchymal Stromal Cells Compared to Oral Non-Steroidal Anti-inflammatory Treatment on the Postoperative Musculoskeletal Status and Gait of Dogs over a 6-Month Period after Tibial Plateau Leveling Osteotomy: A Pilot Study.

Compare the clinical and pressure walkway gait evolution of dogs after a tibial plateau leveling osteotomy (TPLO) for a cranial cruciate ligament rupture (CrCLR) and treatment with either a 1-month course of non-steroidal anti-inflammatory drugs (NSAIDs) or a single postoperative intra-articular (IA) injection of allogeneic neonatal mesenchymal stromal cells (MSCs). Prospective, double-blinded, randomized, controlled, monocentric clinical study. Sixteen client-owned dogs. Dogs with unilateral CrCLR confirmed by arthroscopy were included. Allogeneic neonatal canine MSCs were obtained from fetal adnexa retrieved after C-section performed on healthy pregnant bitches. The dogs were randomly allocated to either the "MSCs group," receiving an IA injection of MSCs after TPLO, followed by placebo for 1 month, or the "NSAIDs group," receiving IA equivalent volume of MSCs vehicle after TPLO, followed by oral NSAID for 1 month. One of the three blinded evaluators assessed the dogs in each group before and after surgery (1, 3, and 6 months). Clinical score and gait and bone healing process were assessed. The data were statistically compared between the two groups for pre- and postoperative evaluations. Fourteen dogs (nine in the MSCs group, five in the NSAIDs group) completed the present study. No significant difference was observed between the groups preoperatively. No local or systemic adverse effect was observed after MSCs injection at any time point considered. At 1 month after surgery, bone healing scores were significantly higher in the MSCs group. At 1, 3, and 6 months after surgery, no significant difference was observed between the two groups for clinical scores and gait evaluation. A single IA injection of allogeneic neonatal MSCs could be a safe and valuable postoperative alternative to NSAIDs for dogs requiring TPLO surgery, particularly for dogs intolerant to this class of drugs.

Gastric Ulcer Complications after the Introduction of Proton Pump Inhibitors into Clinical Routine: 20-Year Experience

Background: The aim of this study was to analyze the admissions and the management of peptic ulcer disease (PUD) in a tertiary care surgical center. Methods: We evaluated the medical records of all patients admitted to the University Hospital of Tübingen, Germany, for treatment of PUD during 1989-2008. Patients were included into the study if the diagnosis was verified endoscopically or surgically. Annual number of admissions, length of hospitalization, mortality rate, age, rate of non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitor (PPI) medication, rate of Helicobacter pylori infection, and complications of PUD and surgery performed were recorded. Data were analyzed by descriptive analyses, Pearson's chi-square test, and regression analysis. Results: This study included 614 admissions. The number of annual admissions (31 ± 12), the length of hospitalization (9 ± 3 days), and the mortality rate (5 ± 4% per year) remained constant, whereas the age increased (1989: 52 ± 14 years vs. 2008: 67 ± 16 years). The rates of patients with H. pylori infection (47 ± 28% per year), NSAIDs treatment (29 ± 15% per year), and PPI treatment (31 ± 27% per year) remained constant. The most frequent PUD complication was hemorrhage (42 ± 16% per year), followed by perforation (9 ± 8% per year). During 1999-2008, more hemorrhages (125 vs. 121; p < 0.05) and perforations (40 vs. 21; p < 0.05) were registered than during 1989-1998. The rate of emergency surgery increased from 70% during 1989-1998 to 87% during 1999-2008. In contrast, elective surgery decreased from 21% during 1989-1998 to 7% during 1999-2008. Ulcer excision and oversewing was the most frequent surgical procedure performed (59%), with decreasing rates of acid-reducing surgery. Conclusion: Despite recent advances in PUD management, ulcer hemorrhage and perforation remain a significant health burden and a surgical disease.