Benefits Of Nonsteroidal Anti-inflammatory Drugs Research Articles

Nonsteroidal Anti-inflammatory Drugs for Chemoprevention in Patients With Familial Adenomatous Polyposis: A Systematic Review and Meta-Analysis.

Published literature shows mixed reports of the benefits of nonsteroidal anti-inflammatory drugs (NSAIDs) on reducing colorectal polyps in patients with familial adenomatous polyposis (FAP). We conducted a systematic review and performed a meta-analysis to assess the impact of NSAIDs on colorectal polyp burden in patients with FAP. We searched PubMed, EMBASE, and Cochrane for randomized controlled trials (RCTs) comparing the effect of NSAIDs vs placebo on the percent change in polyp number and polyp size in patients with FAP. Mean differences between the 2 study arms were pooled using RevMan. The risk of bias (RoB) was assessed using the Cochrane Risk of Bias tool for RCTs, and certainty in the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. The search strategy identified 1021 studies, out of which we included 8 RCTs with a total of 279 patients. Treatment for 6.4 ± 2.2 months with NSAIDs reduced polyp numbers by-17.4% (95% confidence interval-26.41%,-8.29%) (low certainty [I2 89%] due to imprecision and issues with RoB) and polyp size by-15.9% (95% confidence interval -24.98%,-6.73%) (very low certainty (I2 84%) due to imprecision, inconsistency, and issues with RoB). The most common gastrointestinal adverse events reported were stomatitis, diarrhea, and abdominal pain. Side effects leading to drug discontinuation were gastroenteritis and drug allergy. Short-term use of NSAIDs reduced polyp number and polyp size but with low to very low certainty of evidence. Further large multicenter studies are needed to further explore NSAIDs as a chemopreventive measure in patients with FAP.

Efficacy and safety profile of corticosteroids and non-steroidal anti-inflammatory drugs in COVID-19 management: A narrative review.

Due to the fact that coronavirus disease 2019 (COVID-19) is still prevalent, and current reports show that some parts of the world have seen increase in incidence, it is relevant that health professionals and scientists know about recent or novel trends, especially drug treatments. Additionally, the safety profiles of these drug treatments need to be documented and shared with the public. Some studies have demonstrated the clinical benefits of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids in COVID-19 treatment. On the contrary, others have also reported that NSAIDs and corticosteroids may worsen symptoms associated with COVID-19. While some researchers have suggested that corticosteroids may be helpful if used in the early stages of COVID-19, there are still some conflicting findings regarding the use of corticosteroids in certain viral infections. Our review suggests that methylprednisolone, dexamethasone, and ibuprofen have therapeutic potential in reducing mortality due to COVID-19 among hospitalized patients. This review also highlights the fact that the use of NSAIDs is not associated with adverse outcomes of COVID-19. In reality, evidence suggests that NSAIDs do not increase the risk of COVID-19 infections. Also, the literature reviewed suggests that corticosteroid treatment in COVID-19 was linked with a decrease in all-cause mortality and disease progression, without increase in adverse events when compared to no corticosteroid treatment.

Dairy cattle lameness: a roundtable discussion

Foreword Lameness in dairy cattle is a high prevalence condition with significant negative impact on the welfare and economics of the dairy herd. Most lameness is attributable to four main conditions: sole bruising (also referred to as sole haemorrhage), sole ulcer, white line disease and digital dermatitis. Understanding of the pathogenesis of major claw horn diseases has undergone a transformation in the last 20 years, with a shift from a primary nutritional aetiology to a biomechanical one. This has led to significant research into factors relating to claw biomechanics and interventions targeting the inflammatory process. Even for infectious conditions, the benefit of non-steroidal anti-inflammatory drugs to cow welfare and recovery cannot be underrated. In this roundtable discussion, the panel explore the clinical relevance of the findings of research exploring biomechanics and managing inflammation.

Amelioration of the hepatotoxic effects of nonsteroidal drugs using vitamin C and determination of their relationship with the lipid profile

ObjectiveDespite the various clinical benefits of nonsteroidal anti-inflammatory drugs, their frequent and prolonged use has led to numerous health risks, including hepatotoxicity. Hepatotoxicity mediated by oxidative stress can affect the lipid profile. The objective was to investigate whether post-treatment with vitamin C can ameliorate the effects of diclofenac and naproxen in the livers of prepubertal rats and to highlight their relationship with lipid profile. MethodsForty prepubertal female albino rats were distributed among the control group, the diclofenac-administered group (5 mg/kg/day), and the naproxen-administered group (50 mg/kg/day). This study included two phases. In Phase 1, only five rats from each group were dissected after 21 days of oral administration to assess the hepatotoxic effects of nonsteroidal drugs. In Phase 2, five of the remaining animals in each intervention group were post-treated with 25 mg/kg/day of vitamin C for an additional 21 days. After the administration and post-treatment, serum biochemical parameters and histopathological signs were evaluated. ResultsExtreme elevation in the levels of aspartate and alanine aminotransferases was observed in the diclofenac and naproxen groups compared with those in the control (p < 0.001). In addition, the levels of high- and low-density lipoproteins were significantly impacted in these drug groups (p < 0.01, p < 0.05 respectively). Several pathological signs in the liver histology were observed in both drug groups. After post-treatment with vitamin C, noticeable amelioration of these alterations was observed. There were slightly elevation in the liver enzymes and insignificant increase and decrease in the high and low-density lipoproteins respectively. ConclusionVitamin C post-treatment ameliorated the hepatotoxicity induced by diclofenac sodium and naproxen.

Modern Approaches to the Elimination of Visceral Pain

In modern medicine, one of the most common situations requiring emergency care is biliary or renal colic as a manifestation of abdominal pain syndrome. In both cases, smooth muscle spasm plays an important role in the pathogenesis of visceral pain syndrome. Taking into account the fact that, regardless of the chosen treatment tactics, at the first stage it is necessary to stop pain, the question arises about the choice of a drug strategy for the relief of these conditions. It used to be thought that the more intense the pain, the more indications for the prescription of narcotic drugs, which were considered reference analgesics. In recent years, the world has become embroiled in an «opioid crisis». This prompted clinicians to consider the use of drugs from other groups, namely, non-steroidal anti-inflammatory drugs and antispasmodics alone or in combination, which turned out to be no less effective and, often, safer in comparison with narcotic analgesics.&#x0D; New opportunities for effective treatment of visceral pain are opened by the drug Neospastil® (PJSC «Pharmaceutical Company «Darnitsa»), which combines the benefits of nonsteroidal anti-inflammatory drugs (ketorolac tromethamine) with antispasmodic effect of cholinolytics, ganglioblockers and phenytoin phenytoin. The drug increases the effectiveness of analgesia, as well as the control of muscle spasm.

Efficacy of local injection therapy for heel pain in rheumatic inflammatory diseases: Asystematic review.

Heel pain or achillodynia is one of the most common manifestations in patients with rheumatic inflammatory diseases (RID) and particularly spondyloarthritis (SpA). It can be associated with inflammation at the bone insertion of tendon, ligament, bursa or fascia. However, treatment is still achallenge for rheumatologists. Several findings highlighted the proven benefit of nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and recently, tumor necrosis factor (TNF)-α inhibitors. However, only limited data about the efficacy of local therapy such as glucocorticoid and anti-TNF injections are available. The aim of this systematic review was to assess the efficacy and safety of local therapies in heel pain and to make recommendations for further studies. Five studies discussing the effectiveness of local treatments of heel pain in RID were included. All studies recognized that the ultrasonography (US)-guided local corticosteroid or etanercept injections were effective and safe modalities for the treatment of inflammatory heel enthesitis, tendinitis, and retrocalcaneal bursitis (RCB) in patients with RID. Pain relief at the local site was associated with areversion of the acute inflammatory changes in the heel. Furthermore, US-guided injection in RCB with alateral approach was beneficial in terms of preventing side effects.

Clinicians’ attitudes to pain and the use of analgesia in cattle

There is now unequivocal evidence demonstrating the benefits of non-steroidal anti-inflammatory drugs (NSAIDs) in the management of bovine disease. This includes mastitis,1 respiratory disease2 and more recently lameness.3 However, there...

Effectiveness and cost-effectiveness of duloxetine added to usual care for patients with chronic pain due to hip or knee osteoarthritis: protocol of a pragmatic open-label cluster randomised trial (the DUO trial)

IntroductionOsteoarthritis (OA) is a highly prevalent painful condition of the musculoskeletal system. The effectiveness of current analgesic options has proven to be limited and improved analgesic treatment is needed. Several...

Sessile Serrated Polyps and Colon Cancer Prevention.

Evidence suggests that up to one fifth of colorectal carcinomas develop from serrated polyps, named for their pattern of colonic crypts, and include the sessile serrated adenoma/polyp (SSA/P) that has malignant potential. SSA/Ps are typically located in the proximal colon and have molecular features of hypermethylation of CpG islands in gene promoters and activating point mutations (V600E) in the BRAF oncogene. Both of these features are seen in sporadic colorectal carcinomas with microsatellite instability (MSI) which is potentially consistent with an origin of these cancers from precursor SSA/Ps. Dysplasia is detected in a subset of SSA/Ps with a high risk of progression to carcinoma. An uncommon serrated polyp is the traditional serrated adenoma that is typically found in the left colon, has a tubulovillous architecture, and frequently harbors mutant KRAS To date, the epidemiology of these serrated lesions is poorly understood, and limited observational data suggest a potential chemopreventive benefit of nonsteroidal anti-inflammatory drugs. The current primary strategy to reduce the risk of colorectal carcinoma from serrated polyps is to enhance their detection at colonoscopy and to ensure their complete removal. This review provides insight into the epidemiologic, clinical, histopathologic, and molecular features of serrated polyps and includes data on their endoscopic detection and chemoprevention. Cancer Prev Res; 10(5); 270-8. ©2017 AACR.

Abstract B26: MiR-200 is involved in anti-invasive activity of sulindac in colon cancer

Abstract The chemopreventive benefits of nonsteroidal anti-inflammatory drugs (NSAIDs) are documented in various human cancers by numerous pre-clinical and clinical studies. However, the mechanisms accounting for NSAIDs' anticancer activity have not been well understood, given the controversial findings when determining the key role of cyclooxygenase 2 (COX-2) inhibition in the action. MicroRNA is a set of non-coding small RNA molecules showing the “master” role in regulation of human coding gene expression. We are interested in studying if microRNA is able to address the underlying mechanism of NSAIDs' anticancer activity. MiR-200 is a tumor suppressor microRNA and is well-known for its inhibitory effect on the epithelial-mesenchymal transition (EMT). Our previous study reported that the NSAID, sulidac sulfide (SS) can inhibit breast and colon tumor cell motility through a distinct mechanism from the known suppressive activity on tumor cell growth through COX-2 inhibition. In this study, we aim to study if miR-200 is involved in this underlying mechanism. By using human colon tumor cell lines, HCT116 and LIM2405, as the research models, we found that SS treatment could ultimately suppress the tumor cell invasion, while miR-200 was upregulated in parallel. When examining the expression levels of a panel of EMT related genes, we found the E-cadherin was upregulated but snail was downregulated inversely. E-cadherin was reported to be regulated by snail through the transcriptional repression; however, our results did not support the direct control of snail on E-cadherin in the colon tumor cells with miR-200 expression. When snail and miR-200 were forced to be overexpressed in HCT116 cells, E-cadherin was upregulated; when snail was knocked down by siRNAs in miR-200 overexpressed cells, E-cadherin maintained the static expression. These results suggest that the regulation of snail on E-cadherin in colon cancer cells may depend on miR-200 expression. To further support this hypothesis, we studied the interaction between snail and miR-200. The bioinformatics analysis suggested that several E-boxes on miR-200 gene promoter could serve as the binding sites of snail. By employing the chromatin immunoprecipitation (ChIP) and luciferase assays, we demonstrated that snail could directly bind to miR-200 promoter and regulate its expression at the transcriptional level. Our previous study showed that blockade NF-κB signaling is involved in SS inhibition of colon tumor cell motility. Given that snail was also reported to be regulated by NF-κB through the transcriptional modulation, these data suggest the NF-κB-snail-miR-200-E-cadherin axis may account for a novel mechanism to address the anti-metastatic activity of sulindac in colon cancer. Potentially, our results will provide insights into development of novel drugs in treatment of cancer patients with advanced diseases. This study is supported by the NIH/NCI R01 Grant (1R01CA192395) and the American Cancer Society Research Scholar Grant (RSG-13-265-01-RMC). Citation Format: Hong Chang, Xiangling Feng, Ruixia Ma, Yaguang Xi. MiR-200 is involved in anti-invasive activity of sulindac in colon cancer. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Cancer Cell Cycle - Tumor Progression and Therapeutic Response; Feb 28-Mar 2, 2016; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(11_Suppl):Abstract nr B26.

Cox-2 inhibitors and cardiovascular disease: considerable heat, but not much light

This editorial refers to ‘Effects of Celecoxib On Restenosis after Coronary Intervention and Evolution of Atherosclerosis (Mini-COREA) trial: celecoxib, a double-edged sword for patients with angina’, by H.-J. Kang et al. , doi:10.1093/eurheartj/ehs001 We are now in the second decade of controversy regarding the cardiovascular effects of cycloxygenase-2 (COX-2) inhibitors. The introduction of this class of drugs occurred on 31 December 1998, when the US Food and Drug Administration (FDA) approved the sale of celecoxib, followed shortly by the approval of rofecoxib on 20 May 1999. The market acceptance of these two drugs was extraordinary, and both rapidly achieved more than a billion dollars in annual sales. The science leading to the discovery of COX-2 inhibitors is a fascinating story and illustrates the creativity of the pharmaceutical industry in medicinal chemistry. By targeting the COX-2 enzyme, these drugs offered the hope for agents that would preserved the clinical benefits of non-steroidal anti-inflammatory drugs (NSAIDs) without the gastrointestinal (GI) adverse effects attributable to inhibition of the COX-1 isoform. By any reasonable assessment, this targeted therapeutic approach was initially a tremendous success. Studies showed that both COX-2 inhibitors possessed anti-inflammatory and analgesic effects comparable with conventional NSAIDs, but produced fewer symptomatic GI adverse effects. Then, in November 2000, a pivotal study, the VIGOR trial, showed that rofecoxib, compared with naproxen, also produced fewer complicated upper GI adverse events including severe bleeding, ulceration, and perforation.1 However, artfully concealed within the VIGOR manuscript was a dark secret about rofecoxib—although this drug enhanced GI safety, there were significantly more adverse thrombotic cardiovascular events, particularly myocardial infarctions. This safety issue received little public attention until we published an independent analysis of the VIGOR trial in August 2001.2 The rest of the story is now a matter of history and has been fully described in both …

Practical Approaches to Pharmacologic Management of Pain in Older Adults With Cancer

To identify appropriate strategies for pharmacotherapeutic agents in the management of pain in older adults with cancer. PubMed literature searches, personal reference collection, and clinical experience. To make good decisions about pain management when developing treatment plans for older adults, healthcare providers should focus on the pharmacokinetic and pharmacodynamic properties of drugs in the context of the physiologic changes that occur with aging. Unrelieved pain can have a detrimental effect on older adults; conversely, overmedicating can lead to an increased risk of adverse events. With advancing age, physiologic changes alter the pharmacokinetic and pharmacodynamic properties of drugs by reducing their absorption, changing their distribution, and modifying their metabolism and elimination. Also, common comorbidities increase the risk of pharmacologic toxicity and narrow the therapeutic window. In addition, polypharmacy-an issue more common in older adults-increases the complexity of prescribing and risk of adverse events. Consequently, older adults require individualization of their pharmacotherapies. Healthcare providers should consider carefully the risks and benefits of nonsteroidal anti-inflammatory drugs, opioids, and adjuvants before initiating an analgesic trial. The 2009 guidelines published by the American Geriatrics Society described several key principles for prescribing analgesics to older adults and offered specific recommendations and caveats for each drug class. Current guidelines support appropriate management of cancer pain in older adults with specific recommendations for each class of analgesics as well as general prescribing principles.

A Novel Sulindac Derivative Lacking Cyclooxygenase-Inhibitory Activities Suppresses Carcinogenesis in the Transgenic Adenocarcinoma of Mouse Prostate Model

Nonsteroidal anti-inflammatory drugs including sulindac are well documented to be highly effective for cancer chemoprevention. However, their cyclooxygenase (COX)-inhibitory activities cause severe gastrointestinal, renal, and cardiovascular toxicities, limiting their chronic use. Recent studies suggest that COX-independent mechanisms may be responsible for the chemopreventive benefits of nonsteroidal anti-inflammatory drugs and support the potential for the development of a novel generation of sulindac derivatives lacking COX inhibition for cancer chemoprevention. A prototypic sulindac derivative with a N,N-dimethylammonium substitution called sulindac sulfide amide (SSA) was recently identified to be devoid of COX-inhibitory activity yet displays much more potent tumor cell growth-inhibitory activity in vitro compared with sulindac sulfide. In this study, we investigated the androgen receptor (AR) signaling pathway as a potential target for its COX-independent antineoplastic mechanism and evaluated its chemopreventive efficacy against prostate carcinogenesis using the transgenic adenocarcinoma of mouse prostate model. The results showed that SSA significantly suppressed the growth of human and mouse prostate cancer cells expressing AR in strong association with G(1) arrest, and decreased AR level and AR-dependent transactivation. Dietary SSA consumption dramatically attenuated prostatic growth and suppressed AR-dependent glandular epithelial lesion progression through repressing cell proliferation in the transgenic adenocarcinoma of mouse prostate mice, whereas it did not significantly affect neuroendocrine carcinoma growth. Overall, the results suggest that SSA may be a chemopreventive candidate against prostate glandular epithelial carcinogenesis.

Lower limb tendinopathy in athletes

Tendinopathy is a common and debilitating problem especially affecting athletes. Understanding of the disease has increased over the past two decades with the most notable change being in the perception that the pathology of tendinopathy is of a noninflammatory origin. The most prevalent aetiological factors implicated in the development of tendinopathy in athletes are overuse and training errors. The commonest lower limb tendinopathy affects the achilles tendon closely followed by patella tendinosis. Achilles tendinopathy is usually seen in running sports whereas patella tendinopathy is commoner in sports that involve jumping. The diagnosis can be confirmed by taking a good history and clinical examination and supported by appropriate radiological imaging. The investigations of choice are ultrasonography and magnetic resonance imaging with each of the investigations having some benefit over the other depending on the questions needing to be answered for the clinician. Treatment of lower limb tendinopathy is mainly conservative and includes activity modification, correction of training errors and eccentric exercises. To date, there have not been any conclusive studies to prove the benefits of nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids which are currently used to help in the management of pain. Surgical treatment has a variable success rate (45—100%) and is normally reserved as the last option if conservative modalities fail. Novel therapies like infection of sclerosing agent, Traumeel®, platelet-derived growth factors (PDGF) or autologous blood injections into diseased tendons are showing promising results but need more multicentre clinical trials to evaluate their efficacy.

Effects of Indomethacin on Viral Replication Markers in Asymptomatic Carriers of Hepatitis B: A Randomized, Placebo-Controlled Trial

Previous studies have suggested some benefits of nonsteroidal antiinflammatory drugs (NSAIDs) use in patients with chronic viral hepatitis. We evaluated potential effects of indomethacin in asymptomatic carriers of hepatitis B surface antigen (HBsAg). Randomized, placebo-controlled, double-masked clinical trial. One hundred and twelve patients who were confirmed to be HBsAg carriers for at least 6 months and had normal liver function tests, normal abdominal sonography, and no sign of cirrhosis were randomly assigned into two groups. One group (56 participants, mean age (+/-SD) 31.7 (+/-9.6) yr, 29 male, mean serum alanine aminotransferase (ALT) (+/-SD) 24.9 (+/-9.2)) received indomethacin capsules (25 mg) three times daily and the other group (56 participants, mean age (+/-SD) 33.8 (+/-10.2) yr, 33 male, mean serum ALT (+/-SD) 24.5 (+/-8.7)) took placebo capsules with identical package and appearance. All participants were under treatment for 6 months and were followed 3 months thereafter. Statistical analyses were performed both by intention-to-treat and on-treatment methods. Nine participants in the indomethacin group (16%) and 8 in the placebo group (14%) did not complete the trial. HBsAg seroconversion did not differ by treatment group (2 subjects in each group became seronegative). Hepatitis B virus DNA (HBV-DNA) became negative in sera of 7 participants in the indomethacin group but only in 1 in the placebo group (intention-to-treat p= 0.06; on-treatment p= 0.03). Seroconversion of HBeAg to anti-HBe occurred only in 5 participants in the indomethacin group (intention-to-treat p= 0.06; on-treatment p= 0.03). Adverse events included one case of hepatotoxicity and two cases of gastritis in the indomethacin group and one suspected gastritis in the placebo group. We suggest use of indomethacin only in the subgroup of asymptomatic HBsAg carriers who have detectable HBV-DNA or HBeAg in their sera.

COX-1 and COX-2 in health and disease.

Nearly 30 years ago, cyclooxygenase (COX) was identified as an enzyme that initiates the biotransformation of arachidonic acid to prostanoids. It is now known that COX exists as two distinct but similar isozymes, COX-l and COX-2. Prostaglandins (PGs) formed by the enzymatic activity of COX-l are primarily involved in the regulation of homeostatic functions throughout the body, whereas PGs formed by COX-2 primarily mediate pain and inflammation. Based on structural differences in the active sites of COX-l and COX-2, a new class of drugs has been developed that specifically inhibits COX-2 but not COX-l activity. By preserving the synthesis of homeostatic PGs, these specific inhibitors of COX-2 provide the clinical benefits of nonsteroidal anti-inflammatory drugs and minimize the consequences of nonspecific inhibition of PG synthesis.

Use and Benefits of Nonsteroidal Anti-inflammatory Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) continue to be used very widely in the community. Their use reflects the significant burden of rheumatic disease on the general population, and they form a basis for the treatment of inflammation in and around the joint. Furthermore, NSAIDs are also being used increasingly for nonrheumatic conditions, including acute and chronic pain, biliary and ureteric colic, and dysmenorrhea. Recent studies in osteoarthritis have suggested that a significant number of patients previously maintained on NSAIDs can be equally well treated using analgesic agents, such as paracetamol. In noninflammatory rheumatic diseases, analgesics and physical therapies should be the initial treatment of choice and, even in inflammatory rheumatic diseases, NSAID use may be reduced by the addition of pure analgesics to the treatment regimen. A large number of NSAIDs now exist, and there is variability in clinical response to NSAIDs among individual patients. Concern over the widespread use of NSAIDs is largely related to their side-effects. These include adverse reactions in the gastrointestinal tract, kidney, liver, dermis, and central nervous system, as well as hematologic problems. The potential for drug interactions with NSAIDs is also large, as they are often administered to a population with significant co-morbidities. NSAIDs play a major role in the management of acute and chronic rheumatic diseases, but their use needs to be tempered with the realization that they can cause potentially serious adverse reactions. These side-effects can be reduced by careful attention to the dose and duration of therapy, concomitant risk factors, and the combined use of more specific drugs to reduce disease activity. Furthermore, the gastrointestinal side-effects of NSAIDs may be treated and prevented by using appropriate therapy in combination with NSAIDs.

Peri-operative use of nonsteroidal anti-inflammatory drugs in children: analgesic efficacy and bleeding.

Nonsteroidal anti-inflammatory drugs are effective in the management of mild to moderate postoperative pain in children. They can decrease or even eliminate the need for opioid analgesics, thus reducing or eliminating opioid-induced side-effects. The increasing peri-operative use of nonsteroidal anti-inflammatory drugs in children has, however, raised concerns about complications secondary to impaired haemostasis. To examine the extent of this unwanted side-effect, this paper reviews the published literature on analgesic efficacy and bleeding following the peri-operative use of nonsteroidal anti-inflammatory drugs in children. The reviewed literature confirms that haemorrhagic events in the postoperative period occur, but results remain inconclusive regarding the association between peri-operative use of nonsteroidal anti-inflammatory drugs and disordered haemostasis. In order to maximise the benefit of nonsteroidal anti-inflammatory drugs in children, the risks must be recognised and patients, clinical indications, the individual drug, timing and route of administration must be selected carefully. Nonsteroidal anti-inflammatory drugs appear to play a valuable role in the further improvement of postoperative pain management in children.