Nonsteroidal Anti-inflammatory Drugs Therapy Research Articles

Acetaminophen for Patent Ductus Arteriosus in Extremely Low-Birth-Weight Neonates.

Although non-steroidal anti-inflammatory drugs (NSAIDs) are the current standard therapy for the treatment of patent ductus arteriosus (PDA), many neonates have contraindications to receiving or may fail NSAID therapy. To avoid surgical ligation, these patients may benefit from an alternative therapy. The objective of this research is to report the efficacy and safety of acetaminophen for the treatment of PDA in a cohort of premature neonates. Demographics and clinical course were retrospectively evaluated for all neonates admitted during the study period who received acetaminophen for the treatment of PDA. Initial acetaminophen dosing was 15 mg/kg every 6 hours (88% intravenous). Efficacy was analyzed from ductal constriction on echocardiogram as well as need for further PDA treatment. Markers of hepatic and renal function as well as respiratory support and neonatal morbidities were evaluated to describe the safety of acetaminophen. Forty-one neonates were identified with a median birth weight of 760 g (IQR 614-948 g) and median gestational age of 25 weeks (IQR 24-27 weeks). Treatment was initiated at a median postnatal age of 15 days (IQR 8-19 days) for a median duration of 7 days (IQR 6-10 days). Twenty-seven neonates (66%) required no further PDA treatment, with echocardiographic PDA closure documented in 10 neonates (24%) and reduced ductal size in 15 neonates (37%). No clinically significant adverse effects attributable to acetaminophen therapy were detected. Most patients in this study responded to acetaminophen treatment for PDA, indicating that this therapy may be an option for extremely low-birth-weight neonates in order to avoid surgical ligation.

Epstein-Barr Virüs Enfeksiyonunun Nadir Görülen Bir Komplikasyonu: Miyoperikarditli Bir Olgu Sunumu

Acute myocarditis usually develops after viral infections and is often asymptomatic. However, pericarditis can accompany it. Myopericarditis due to Epstein-Barr virus (EBV) infection is very rare. A 16-year-old male presented with severe chest pain. Cardiac enzymes were elevated and electrocardiographic examination revealed widespread decreased voltage and ST-T changes on the DII, DIII, aVF, V5, and V6 leads. Left ventricular systolic functions were normal and pericardial effusion was present on echocardiographic evaluation. EBV-VCA IgM and EBV-PCR were positive; EBV myopericarditis was diagnosed in the patient. The patient responded well to intravenous immunoglobulin (IVIG) and nonsteroidal antiinflammatory therapy and recovered completely. Myopericarditis should be considered in the differential diagnosis while evaluating patients with chest pain. The Epstein-Barr virus should be kept in mind even though it rarely causes myopericarditis.

Treatment of orofacial granulomatosis: a case report

BackgroundOrofacial granulomatosis is a relatively recent term coined by Wiesenfield et al. in 1985 to define granulomatous lesions of oral mucosa without intestinal involvement. When it presents in a triad encompassing facial nerve palsy, lip swelling, and fissured or furrowed tongue it is called Melkersson–Rosenthal syndrome while monosymptomatic or oligosymptomatic forms are referred to as granulomatous cheilitis. It is an uncommon clinicopathologic entity which is distinct from classic Crohn’s disease. The NOD2 variant which is commonly associated with Crohn’s has not been shown to have any association with orofacial granulomatosis.Case presentationWe present a case of a 31-year-old white man who had painful swelling of the lip with oral ulcers and difficulty eating for 2 to 3 years. He was diagnosed as having granulomatous cheilitis based on characteristic biopsy findings. There was serologic evidence of Crohn’s disease with anti-Saccharomyces cerevisiae antibodies. However, he was not found to have any gastrointestinal involvement based on computed tomography enterography, and upper and lower endoscopies. He failed to respond to nonsteroidal anti-inflammatory drugs, steroids, and dapsone therapy but responded well to high doses of infliximab.ConclusionsOur case questions whether granulomatous cheilitis really exists or is it simply a variant of Crohn’s disease with only oral presentation. Our patient did not have symptoms of Crohn’s disease; moreover, endoscopic studies and computed tomography enterography were unremarkable for evidence of intestinal involvement. Our case is also the first reported case where high-dose infliximab alone has been used with sustained response for approximately 8 months. In conclusion, more research is needed to assess the underlying pathology as well as ideal treatment options for patients with orofacial granulomatosis. We propose that high-dose infliximab should be considered in patients who do not respond to traditional therapies.

Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study

ObjectiveTo assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use.DesignA phase 3, 24-week,...

Prescription audit of NSAIDs and gastroprotective strategy in elderly in primary care.

The use of non-steroidal anti-inflammatory drug (NSAIDs) is deemed amajor risk factor for peptic ulcer disease in elderly population that requires concomitant therapy with gastroprotective agents (GPAs). This study evaluated the rational prescribing of NSAIDs and GPAs, and extent of adherence to the guideline recommendations in primary care. Nationwide audit of prescriptions issued to elderly patients (≥65 years) with hypertension or diabetic hypertension in primary care. Among 2090 elderly, 45.9% were on low-dose aspirin, and 13.5% on other NSAIDs. Diclofenac-XR was the most frequently prescribed NSAIDs to three-quarter patients whereas naproxen, the safest NSAID for patients with high cardiovascular (CV) risk, was rarely prescribed. Among those on NSAID, 82.9% were on ascheduled dosing regimen; of these 78.8% received long-term NSAID therapy (3.9±0.9 months). The prescription rate of GPAs was low: 29.2% for aspirin and 33.3% for other NSAIDs. Aquarter of the patients on histamine type-2 receptor antagonists received ranitidine at subtherapeutic single-dose for gastroprotection. Approximately half of the patients on proton pump inhibitors (PPIs) were prescribed supra-therapeutic double-dose regimen: omeprazole and esomeprazole accounted for 63.2% of overall prescribed PPIs. The rational choice of NSAIDs and physicians' adherence to gastroprotective measures was suboptimal in primary care. The choice of NSAIDs and gastroprotective strategy in elderly be guided by the CV and gastrointestinal adverse events likelihood due to the NSAIDs and risk profile of patients for such adverse events.

Monofocal Chronic Nonbacterial Osteomyelitis in the Mandible Accompanied With Mucocutaneous Disease.

Chronic nonbacterial osteomyelitis (CNO) is a bone disease with nonbacteria osteitis of unknown etiology. Symptoms, including pain, swelling, fever, etc, always result in misdiagnosis and wrong therapy. This study aims to introduce the clinical features and the therapy of patients with CNO accompanied with mucocutaneous disease. The authors retrospectively reviewed the patients who presented to our hospital from 2000 to 2016, the final sample including 3 patients with CNO accompanied with mucocutaneous disease, who presented repeated severe pain of bone, swelling, tenderness, and fever during attack stage with no evidence of bacterial infections. One patient underwent surgery, and all of them took the therapy of nonsteroidal anti-inflammatory drugs and immunosuppressive agents. There was no significant effect after taken surgery, but good results with drugs. The study suggested us that medical therapy sometimes better than surgery in CNO accompanied with mucocutaneous disease.

Intercorrelation between MRI disease activity scores of the sacroiliac joints and the spine, and clinical disease activity indices in patients with axial spondyloarthritis

Intercorrelation between MRI disease activity scores of the sacroiliac joints and the spine, and clinical disease activity indices in patients with axial spondyloarthritis Hon Wai Lau,1 Chi Chiu Mok,2 Wun Cheung Samuel Chan,1 Ming Keung Yuen,1 On Chee Li1 1Department of Radiology, 2Department of Medicine, Tuen Mun Hospital, Tuen Mun, New Territories, Hong Kong Objective: To analyze the correlation between the magnetic resonance imaging (MRI) disease activity scores and the clinical disease activity indices (DAI) in Chinese patients with active axial spondyloarthritis (aSpA) that required biologics therapy. The correlation between MRI disease activity scores of the sacroiliac joints (SIJs) and the spine in these patients was also assessed.Methods: This was a cross-sectional study design in which adult patients who fulfilled the Assessment of SpondyloArthritis international Society classification criteria for aSpA and had active disease (Bath Ankylosing Spondylitis Disease Activity Index score ≥4, persistent spinal pain despite nonsteroidal anti-inflammatory drugs therapy >3 months) that required biologics therapy were included. The MRI disease activities were measured using the Spondyloarthritis Research Consortium of Canada (SPARCC) scores. Correlation between the SPARCC scores of the SIJs and the spine, and clinical DAI was calculated. Results: Fifty-seven patients (47 men and 10 women; mean age 37 ± 12 years) completed the study. There was no statistically significant correlation between the SPARCC scores and clinical DAI. The SPARCC score of the SIJs showed a positive correlation with the SPARCC score of the spine (r = 0.34, p < 0.05). The thoracic discovertebral units (57%) were found to be more frequently associated with significant disease activity than the other levels of the spine. Conclusion: MRI can detect active inflammation which may not be reflected by clinical DAI. MRI should be performed in patients with aSpA to provide a more comprehensive assessment and to better reflect disease activity and severity. MRI findings of more severe sacroiliitis should prompt the radiologist to look for involvement in the entire spine, particularly in the thoracic region. Keywords: magnetic resonance imaging, MRI, SPARCC score, axial spondyloarthritis, ankylosing spondylitis, spondyloarthropathies, sacroiliitis

Relapsed and unresectable inflammatory myofibroblastic tumor responded to chemotherapy: A case report and review of the literature.

A 63-year-old female patient who had undergone cholecystectomy for inflammatory myofibroblastic tumor (IMT) in the gallbladder was referred to our hospital. The patient's disease relapsed, involving the pancreas, and was diagnosed as inoperable IMT 13 months after the cholecystectomy. The patient failed to respond to steroid and non-steroidal anti-inflammatory drug therapy, but subsequently exhibited a good response to vinorelbine and methotrexate combination chemotherapy. Little information is currently available on the efficacy of chemotherapy for adult-onset IMT. The present case suggests that chemotherapy with vinorelbine and methotrexate is a viable therapeutic option for adult patients with unresectable IMT.

Elixir for the aging mind: An empirical review of the neuroprotective effect of meditation in elderly

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the synthesis of prostaglandins, which comprise an important compensatory mechanism for maintaining renal blood flow, glomerular filtration, and water and electrolyte homeostasis in the setting of a number of pathophysiologic states including CKD. CKD patients are, therefore, at risk for adverse renal side-effects of NSAIDs, including acutely worsened renal function, hyperkalemia, hyponatremia, sodium retention, and exacerbation of hypertension. Although these effects are generally reversible upon discontinuation of the drugs, CKD patients must be monitored closely while taking NSAIDs.Evidence suggests that heavy cumulative NSAID consumption is capable of causing chronic kidney injury with manifestations similar to those seen in classic analgesic nephropathy, including chronic interstitial nephritis and papillary necrosis. The pathogenesis of this disorder is probably renal medullary ischemia resulting from diversion of blood flow to the cortex that occurs with suppression of prostaglandin synthesis. CKD due to NSAIDs is probably rare.Extra caution is indicated when (1) committing patients to high-dose, long-term NSAID therapy, or (2) recommending NSAID therapy of any duration to patients with CKD or other risk factors for adverse renal side-effects including advanced age, use of diuretics, congestive heart failure, cirrhosis, and hypertension.

THE EVOLUTION OF SPONDYLARTHRITIS – A THERAPEUTIC CHALLENGE

We are presenting the case of a 36 years old male diagnosed at the age of 20 with reactive arthritis and at 27 years with ankylosing spondylitis. During the course of the disease, the patient followed treatment with nonsteroidal anti-inflammatory drugs, Sulfasalazine and biological therapy. The first two anti-TNF had a very good response. During Adalimumab therapy the patient conceived a child without any teratogenic effect on it. The effect of the two anti-TNF has been long-lasting, but the effectiveness has decreased on the other two. The future of this patient lies in blocking a new molecule in ankylosing spondylitis named IL-17, so we are expecting the disease response to the new biological introduced into ankylosing spondylitis, named Secukinumab.

Nonsteroid anti-inflammatory therapy suppresses the development of proliferative vitreoretinopathy more effectively than a steroid one.

This study proves the possibility of targeted use of the nonsteroidal anti-inflammatory drug lornoxicam to prevent the development of proliferative vitreoretinopathy (PVR). Triamcinolone acetonide (TA) was selected as a reference substance. Wistar rats (N=400) were used. PVR was modeled by intravitreal injection of dispase or concanavalin A. Lornoxicam or TA intravitreal administration was performed 20min later. On the second and the third day, drugs were administrated systemic. Enucleation was performed on the first, third, seventh and 42nd or 56th day of the experiment. Pro-inflammatory substances led to the development of sub- and epiretinal membranes. Lornoxicam decreased the incidence of membrane formation by 43 and 31% in dispase and concanavalin models, respectively. Membranes, formed during its use, were smaller and contained less fibrotic components. At the end of the experiment, the thickness of retinal and choroidal layers among the animals which had received the therapy was the same as the thickness of the retina and choroid of intact rats. Lornoxicam administration normalized the cyclooxygenases (COXs) expression in the retina and the choroid at the early stages of the experiment. TA application was less effective in both models. COXs blocking during the development of PVR, overwhelming inflammation in the eye and reducing its consequences, is proved to be a much more effective and safe influence than the suppression of the entire cascade of arachidonic acid metabolism. Lornoxicam did not only improve the condition of the retina and the choroid but also significantly reduced the frequency of membrane formation.

Risk of nonsteroidal anti-inflammatory drug-associated renal dysfunction among neonates diagnosed with patent ductus arteriosus and treated with gentamicin.

To evaluate the risk of nonsteroidal anti-inflammatory drug (NSAID) therapy-associated acute kidney injury (AKI) among neonates diagnosed with patent ductus arteriosus (PDA) who are treated with gentamicin. Multicenter retrospective observational study of patients ⩽44 postmenstrual weeks of age diagnosed with PDA who received gentamicin during hospitalization between January 2006 and December 2014. Patients with and without NSAID exposure were matched on covariates associated with AKI and NSAID therapy. The primary end point, AKI, was defined according to Kidney Disease Improving Global Outcomes neonatal criteria. The rate of AKI for the entire cohort (n=594) was 12% (n=71). Among neonates receiving NSAIDS, 14.8% (n=44) experienced an AKI as compared to 9.1% (n=27) for those who were not exposed (relative risk, 1.6; 95% confidence interval, 1.0 to 2.6). Therefore, the attributable risk of NSAID use was 5.7% (95% confidence interval, 0.5 to 11.0). Among neonates with PDA and receiving gentamicin, NSAID therapy increases the risk of AKI by about 6%.

Evaluation of anti-inflammatory and ulcerogenic potential of zinc\u2013ibuprofen and zinc\u2013naproxen complexes in rats

Because of numerous indications and high availability, non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed and used medicines in the world. However, long-term therapy with and improper use of NSAIDs may lead to gastrointestinal damage. Therefore, improving the therapeutic index of the existing drugs has become a priority over the past decades. Considerable attention in the field has been concentrated on metal complexes of non-steroidal anti-inflammatory drugs. The aim of this study is to evaluate the effect of complexation with zinc on the anti-inflammatory and ulcerogenic effects of ibuprofen and naproxen after single and triple intragastric administration to rats. The anti-inflammatory effect was assessed in carrageenan-induced inflammatory edema in the hind paw of male albino Wistar rats. The mucosal lesions were inspected and evaluated for gross pathology. Single administration of both the investigated complexes, namely zinc–ibuprofen and zinc–naproxen (20 mg/kg equivalent to ibuprofen and naproxen, respectively) and their parent drugs and physical mixtures with zinc hydroaspartate (ZHA doses: 16.05 and 14.37 mg/kg), caused a significant reduction of the edema after the same time from the carrageenan injection in comparison to the control groups. However, no statistically significant differences between the investigated drugs were observed after their single administration. The mean ulceration score for the mixture of ibuprofen and ZHA was statistically lower than the mean score achieved in rats after treatment with ibuprofen alone. On the other hand, triple intragastric administration of the ZHA–ibuprofen and ZHA–naproxen combination showed substantial enhancement of the anti-inflammatory activity against control groups, as well as against the parent NSAIDs. The most potent anti-inflammatory activity was demonstrated after 2 h from the carrageenan injection in animals receiving ZHA together with naproxen. The edema growth was reduced in these animals by 80.9% as compared to the control group. This result was significantly higher than the results achieved in animals receiving zinc–naproxen (50.2%) or naproxen alone (47.9%). Both NSAID complexes with zinc and mixtures with ZHA alleviated ulcerations caused by parent NSAIDs; however, the mixtures of both ibuprofen and naproxen with ZHA after triple administration were the least damaging. In view of the above results, zinc supplementation during NSAID therapy may have a beneficial effect on ulcer prevention and healing by reducing the effective dose of the parent drug and increasing its potency.

Changes in the serum concentrations of adhesion molecules and vascular endothelial growth factor in active ankylosing spondylitis patients taking amtolmetin guacil: Results of a 56-week prospective ореn-label controlled observational study

To estimate changes in the concentrations of adhesion molecules and vascular endothelial growth factor A after 30-day additional use of amtolmetin guacil (AMG) in patients with active ankylosing spondylitis (AS) who were unresponsive to previous one-year treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). 20 patients with active AS who had not reached a BASDAI score <4.0 at week 52 of NSAID therapy and 10 healthy individuals matched for cardiovascular risk factors were examined. After 52 weeks of NSAID therapy, AMG was administered orally at 1200 mg/day to patients with AS for 30 days. The concentrations of adhesion molecules (sICAM-1 and sVCAM-1) and VEGF-A were measured. BASDAI and ASDAS scores and C-reactive protein (CRP) levels were determined in AS patients. The concentrations of adhesion molecules and VEGF-A were investigated in patients with AS at baseline, at 52 weeks after NSAID treatment start, and at 30 days following AMH initiation (at week 56) and in healthy individuals at baseline and at 30 days. The concentration of sICAM-1 in patients with AS was 987.0±217.39, 938.98±293.31, and 364.25±363.3 ng/ml at weeks 0, 52, and 56, respectively; that in healthy individuals was 769.25±189.32 and 740.05±225.76 ng/ml at baseline and at 30 days, respectively. The differences from the baseline concentration were significant in patients with AS (p<0.05) and insignificant in healthy subjects (p≥0.05); the differences between the concentrations in patients with AS and the controls were significant at baseline and at 52 weeks (p<0.05). The concentration of sVCAM-1 in patients with AS was 364.25±160.49, 325.34±245.1, and 319.1±248.73 ng/ml at weeks 0, 52 and 56, respectively; that in healthy individuals was 245.13±40.4 and 248.73±34.42 ng/ml, respectively (p<0.05 vs baseline values and values in healthy subjects). The level of VEGF-A in AS patients was not different from that in healthy individuals, but decreased during treatment. Correlations were found between the concentration of adhesion molecules and the level of CRP (p<0.01). Elevated concentrations of adhesion molecules have been found in AS patients compared with healthy individuals. The study has demonstrated that AMG treatment is efficient in treating patients with AS. NSAID/AMG treatment is associated with lower concentrations of adhesion molecules. Decreased CRP levels serve as predictors for reduced concentration of adhesion molecules. The level of VEGF-A at baseline did not differ from that in healthy subjects, but was decreased during treatment with NSAIDs.

Primary hypertrophic osteoarthropathy due to a novel SLCO2A1 mutation masquerading as acromegaly

SummaryA 20-year-old man with an 8-year history of progressive enlargement of his hands and feet, coarsening facial features, painful joints and thickened, oily skin was referred for investigation of acromegaly. On examination, the subject was of normal height and weight. He had markedly increased skin thickness around the forehead, eyelids and scalp with redundant skin folds. Bilateral painful knee swelling was accompanied by enlargement of the extremities, and his fingers were markedly clubbed. Routine hematological, biochemical and hormonal blood tests, including GH and IGF-1 were normal. The clinical picture suggested primary hypertrophic osteoarthropathy (PHOA) rather than acromegaly and radiological studies were supportive of this, demonstrating increased subperiosteal bone formation and increased bone density and cortical thickening. There was widespread joint disease, with narrowing of joint spaces, whereas the knees demonstrated effusions and calcification. A skull X-ray revealed calvarial hyperostosis and a normal sellar outline. Family history was negative. Genetic studies were performed on peripheral blood leukocyte DNA for mutations in the two genes associated with PHOA, 15-hydroxyprostaglandin dehydrogenase (HPGD; OMIM: 601688) and solute carrier organic anion transporter family member 2A1 (SLCO2A1; OMIM: 601460). The sequence of HPGD was normal, whereas the subject was homozygous for a novel pathological variant in SLCO2A1, c.830delT, that predicted a frameshift and early protein truncation (p.Phe277Serfs*8). PHOA, also known as pachydermoperiostosis, is a rare entity caused by abnormal prostaglandin E2 metabolism, and both HPGD and SLCO2A1 are necessary for normal prostaglandin E2 handling. High prostaglandin levels lead to bone formation and resorption and connective tissue inflammation causing arthropathy, in addition to soft tissue swelling.Learning points:The differential diagnosis of enlarged extremities, coarsened facial features, skin changes and increased sweating in suspected acromegaly is quite limited and primary hypertrophic osteoarthropathy (PHOA) is one of the few conditions that can mimic acromegaly at presentation.PHOA is not associated with abnormalities in GH and IGF-1 secretion and can be readily differentiated from acromegaly by hormonal testing.Clubbing in the setting of diffuse enlargement of joints and extremities in addition to skin changes should alert the physician to the possibility of PHOA, as clubbing is not a usual feature of acromegaly. Underlying causes of secondary hypertrophic osteoarthroapthy (e.g. bronchial neoplasia) should be considered.PHOA is a very rare condition caused by abnormalities in prostaglandin metabolism and has two known genetic causes (HPGD and SLCO2A1 mutations). SLCO2A1 gene mutations lead usually to autosomal recessive PHOA; fewer than 50 SLCO2A1 mutations have been described to date and the current case is only the second in a Hispanic patient.Treatment of primary hypertrophic osteoarthropathy is focused on the management of joint pain usually in the form of non-steroidal anti-inflammatory drug therapy.

The treatment of desmoid tumors associated with familial adenomatous polyposis: the results of a Japanese multicenter observational study.

Familial adenomatous polyposis (FAP)-associated desmoid tumor (DT) is sometimes life threatening. However, the optimal treatment for DTs has not been established. The aim of this study was to analyze the outcomes of surgical and pharmacological treatments for DT in Japanese FAP patients. We retrospectively reviewed the data of 303 patients who underwent colectomy for FAP between 2000 and 2012. We analyzed 41 patients with DTs in which the location was apparent. The selection of treatment for intra-abdominal DTs was also evaluated according to Church's classification. Surgery was frequently used to treat extra-abdominal DTs. Multimodal treatments, including surgery, and the administration of non-steroidal anti-inflammatory drugs, hormonal therapy, and chemotherapy were widely used for intra-abdominal DTs. The most effective pharmacological treatment was cytotoxic chemotherapy, which was associated with a response rate of 45.5% and a disease control rate of 72.7%. After a median follow-up period of 53.0 months, the 5-year DT-specific survival rate in patients with stage IV disease was 71.4%; in contrast, the rate in patients with other stages was 100%. Four-stage IV patients died of DT due to uncontrollable rapid progression. No cytotoxic chemotherapy was administered; however, incomplete resection was performed in three cases. Our findings will provide clues that may help physicians in selecting the optimal strategy for this rare disease.

Risk factors for acute kidney injury associated with the treatment of bacterial endocarditis at a tertiary academic medical center

Background: Acute kidney injury (AKI) is a common complication of endocarditis.Objective: To determine risk factors for the development of AKI in patients treated for endocarditis.Methods: This single centre, retrospective univariate and multivariate analysis to determine risk factors for the development of AKI included patients diagnosed with endocarditis between January 2009 and October 2013.Results: Of 211 included patients, a total of 84 (39.8%) patients developed AKI. We identified multiple independent variables associated with the development of AKI, including: age ≥ 65 years, presence of hardware, chronic kidney disease, AKI on admission, infection with Staphylococcus spp, receipt of nafcillin or oxacillin or aminoglycoside and nafcillin or oxacillin or aminoglycoside and vancomycin, vancomycin trough level ≥ 20.0 mcg/ml, aminoglycoside total daily dose reduction, duration of vancomycin exceeding three days, receipt of loop diuretic or more than three concomitant nephrotoxins and duration of loop diuretic or non-steroidal anti-inflammatory drug therapy exceeding seven days.Conclusions: In patients treated for endocarditis, multiple risk factors for AKI were identified. Prospective studies are needed to evaluate these variables for causation of AKI in patients treated for endocarditis.

Short-Term Non-Steroid Anti-Inflammatory Drug Use in Spondyloarthritis Patients Induces Subclinical Acute Kidney Injury: Biomarkers Study

Background: Non-steroid anti-inflammatory drug (NSAID) usage is associated with kidney injury. Rise in serum creatinine (sCr) often represents irreversible process. Thus to assess the early effects of regular NSAID use, we studied sensitive serum and urine biomarkers of kidney injury. Methods: In a protocol-based intervention study, 103 subjects were enrolled in 3 mutually exclusive groups. Group 1 included 37 healthy controls having minimal baseline NSAID exposure as per a definition, and group 2 had 41 spondyloarthritis (SpA) patients on regular NSAID therapy for >3 months. Group 3 included 25 SpA patients having minimal NSAID exposure at baseline. Blood and urine samples were collected from all the 3 groups at baseline. Furthermore, group 3 was started on 6-week regular NSAID therapy, and blood and urine samples were re-collected at 1, 6, and 12 weeks. Baseline normal kidney function as per the definition was ensured in all the subjects. Creatinine, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin-C, and microalbumin were measured in urine and serum samples to assess kidney injury. Results: Kidney injury biomarkers were 2-3-fold higher in SpA patients using regular NSAID therapy compared to healthy controls and SpA patients having minimal NSAID exposure (uKIM-1 and uNGAL p < 0.0001, sKIM-1 and sNGAL p = 0.001). There was no difference in sCr and estimated glomerular filtration rate using Cockcroft-Gault equation between the groups. In SpA patients started on 6 weeks of regular NSAID (group 3), biomarker levels started rising at week 1 and showed a significant rise at week 6. The levels in the patients that stopped NSAID use at 6 weeks showed reversibility at 12 weeks. Conclusions: Regular NSAID use in SpA patients induces subclinical kidney injury represented by rise in biomarkers. These levels start rising as early as 7 days of regular NSAID use and are reversible on stopping the drug.

A Critical Look into the 2016 NICE Guidelines: Acupuncture for Low-Back Pain and Sciatica

Abstract Background: In November of 2016, the National Institute for Health and Care Excellence (NICE) Guidelines for low-back pain (LBP) and sciatica were published. According to the NICE Guidelines Development Group (GDG), acupuncture is no longer a recommended treatment for LBP and sciatica, while other therapies including nonsteroidal anti-inflammatory drugs, exercise, epidurals, and manual therapy are recommended as treatments. Objective: The aim of this article is to discuss how the GDG decision-making process behind the recommendations against acupuncture—while supporting common conventional treatments for LBP and sciatica—is inconsistent and lacks sufficient evidence-based justification. Methods: The evidence used to develop the 2016 NICE Guidelines for LBP and sciatica were critically appraised using the Grading of Recommendations, Assessment, Development, and Evaluation framework, and examined for their limitations. Results: There is predominantly moderate-quality evidence favoring acupuncture o...

Inhibition of Methotrexate Uptake via Organic Anion Transporters OAT1 and OAT3 by Glucuronides of Nonsteroidal Anti-inflammatory Drugs.

Combination therapy of non-steroidal anti-inflammatory drugs (NSAIDs) and methotrexate (MTX) sometimes triggers adverse effects, such as liver injury, renal failure, gastrointestinal disorders, and myelosuppression, owing to the reduction of MTX clearance. Previous reports have suggested that NSAIDs inhibit renal MTX uptake via organic anion transporters (OATs) and reduced folate transporter (RFC)-1 and efflux via multidrug resistance-associated proteins (MRPs). Recently, our laboratory found inhibitory effects of NSAIDs-glucuronide (NSAIDs-Glu), a major metabolite of NSAIDs, on MRP-mediated MTX transport as a new site of interaction between MTX and NSAIDs. However, it remains unclear that whether NSAIDs-Glu inhibit renal uptake of MTX. Therefore, the present study aimed to evaluate inhibitory effects of several NSAIDs-Glu (diclofenac, R- and S-ibuprofen, R- and S-flurbiprofen, and R- and S-naproxen) on human OAT1 and OAT3-mediated MTX transport. In this study, [3H]MTX uptake was observed by using human OAT1 and OAT3-overexpressing HEK293 cells in the presence or absence of NSAIDs-Glu. All examined NSAIDs-Glu exhibited concentration-dependent inhibitory effects on MTX uptake via OAT1 and OAT3. Our results indicated that NSAIDs-Glu are more potent (5- to 15-fold) inhibitors of OAT3 than OAT1. Moreover, stereoselective inhibitory effects of NSAIDs-Glu on OATs-mediated MTX uptake were not observed, unlike on MRPs-mediated transport. These findings suggest that inhibition of OAT1 and OAT3-mediated renal uptake of MTX by plasma NSAIDs-Glu may be one of the competitive sites underlying complex drug interaction between MTX and NSAIDs.