Non-steroidal anti-inflammatory drugs in postoperative hand fracture management:Do they positively or negatively impact recovery?

This editorial explores the impact of non-steroidal anti-inflammatory drugs(NSAIDs)on postoperative recovery in hand fracture patients,amidst shifting pain management strategies away from opioids due to their adverse effects.With hand fractures being significantly common and postoperative pain management crucial for recovery,the potential of NSAIDs offers a non-addictive pain control alternative.However,the controversy over NSAIDs'effects on bone healing—stemming from their Cyclooxygenase-2 inhibition and associated risks of fracture non-union or delayed union—necessitates further investigation.Despite a comprehensive literature search,the study finds a lack of specific research on NSAIDs in postoperative hand fracture management,highlighting an urgent need for future studies to balance their benefits against possible risks.

Systematic review and network meta-analysis of different nonsteroidal anti-inflammatory drugs for juvenile idiopathic arthritis

BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review and network meta-analysis to determine the optimal instructions.METHODS We searched for randomized controlled trials(RCTs)from PubMed,EMBASE,Google Scholar,CNKI,and Wanfang without restriction for publication date or language at August,2023.Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis.The surface under the cumulative ranking curve(SUCRA)analysis was used to rank the treatments.P value less than 0.05 was identified as statistically significant.RESULTS We included 8 RCTs(1127 patients)comparing 8 different instructions including meloxicam(0.125 qd and 0.250 qd),Celecoxib(3 mg/kg bid and 6 mg/kg bid),piroxicam,Naproxen(5.0 mg/kg/d,7.5 mg/kg/d and 12.5 mg/kg/d),inuprofen(30-40 mg/kg/d),Aspirin(60-80 mg/kg/d,75 mg/kg/d,and 55 mg/kg/d),Tolmetin(15 mg/kg/d),Rofecoxib,and placebo.There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response.The SUCRA shows that celecoxib(6 mg/kg bid)ranked first(SUCRA,88.9%),rofecoxib ranked second(SUCRA,68.1%),Celecoxib(3 mg/kg bid)ranked third(SUCRA,51.0%).There were no significant differences between any two NSAIDs regarding adverse events.The SUCRA shows that placebo ranked first(SUCRA,88.2%),piroxicam ranked second(SUCRA,60.5%),rofecoxib(0.6 mg/kg qd)ranked third(SUCRA,56.1%),meloxicam(0.125 mg/kg qd)ranked fourth(SUCRA,56.1%),and rofecoxib(0.3 mg/kg qd)ranked fifth(SUCRA,56.1%).CONCLUSION In summary,celecoxib(6 mg/kg bid)was found to be the most effective NSAID for treating JIA.Rofecoxib,piroxicam,and meloxicam may be safer options,but further research is needed to confirm these findings in larger trials with higher quality studies.

Roles of Community Pharmacists in Screening and Disseminating of Information about Non-Steroidal Anti-Inflammatory Drugs Risks: Implications for Drug Safety Assessment

Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no proper guidance is given by the health care provider. This study assessed the roles of community pharmacists in screening and disseminating information about the risks associated with NSAID use in Zambia. Methodology: This was a national cross-sectional study in which a structured self-administered questionnaire was administered to 245 registered community pharmacists in Zambia. Stata/BE, version 15.1 (Stata Corporation, College Station, Texas, USA) and multivariate logistic regression model was used to determine factors associated with information dissemination about ADRs of NS-NSAIDs. Results: 231 of the 245 distributed questionnaires were returned giving a response rate of 94.3%. All (100%) participating community pharmacists claimed to have practiced dispensing NSAIDs. However, only 26 (11.0%) and 71 (30.8%) regularly screened for risk factor of selective COX-2 NSAIDS (SC2-NSAIDS) and non-selective NSAIDS (NS-NSAIDs) respectively. Information dissemination on adverse drug reactions (ADRs) of SC2-NSAIDS was regularly provided by only 22 (9.5%) of pharmacists while that of NS-NSAIDs was regularly provided by 49 (21.2%). In the multivariate logistic regression model, being the owner of a pharmacy (AOR: 5.4, CI: 1.84 - 16.4) was significantly associated with information dissemination about ADRs of NS-NSAIDs while an hour increase in the working hours per day (AOR: 0.9, CI: 0.64 - 0.95) was associated with less likelihood of information dissemination. Conclusion: Pharmacists working in community pharmacies in Zambia did not regularly screen and disseminate information about the risks associated with NSAID use. Therefore, pharmacists should be able to screen and monitor patients at risk and be aware of the majority of risk factors while dispensing NSAIDs to minimize the associated complications.

Nonsteroidal anti-inflammatory drugs before endoscopic ultrasound guided tissue acquisition to reduce the incidence of post procedural pancreatitis

Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst fluid.The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis,which is likely induced by the same pathophysiological mechanisms as after en-doscopic retrograde cholangiopancreatography(ERCP).According to the current European Society of Gastrointestinal Endoscopy guideline,nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate.A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition(TA)is harm-less in healthy adults.Since it is associated with low costs and,most important,may prevent a dreadsome complication,we strongly recommend the adminis-tration of 100 mg diclofenac rectally prior to EUS-TA.We will explain this recom-mendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.

Opinion on double strategy to fight against COVID-19:Vaccination and home treatment with non-steroidal anti-inflammatory drugs

The goals of global vaccination are to control,eliminate,or eradicate infectious diseases in a sustainable way that strengthens public health systems.Although the use of vaccines is essential for the control of epidemics,the vaccines against coronavirus disease 2019(COVID-19)proved to be inadequate to end the pandemic and thus are considered incomplete.These vaccines failed to prevent infection,so their primary purpose has been shifted to prevent severe disease and reduce hospitalizations and deaths.Therefore,we believe that all the strategies available to reduce transmission,hospitalizations and deaths due to COVID-19 will be put in place.It is reported that uncontrolled inflammation and thrombosis are the principal mechanisms for aggravation and death in patients with COVID-19.Unlike corticosteroids that should not be administered at the beginning of the symptoms for their immunosuppressive action,which could worsen the evolution of the disease,the usefulness of non-steroidal anti-inflammatory drugs in the early at-home treatment of the disease is becoming evident.

Efficacy and safety of rabeprazole in non-steroidal anti-inflammatory drug-induced ulcer in Japan

AIM: To investigate the effi cacy and safety of rabepra-zole under continuous non-steroidal anti-inflammatory drug (NSAID) administration for NSAID-induced ulcer in Japan. METHODS: Subjects comprised patients undergoing NSAID treatment in whom upper gastrointestinal en-doscopy revealed an ulcerous lesion (open ulcer) with diameter ≥ 3 mm, who required continuous NSAID treatment. Endoscopies were performed at the start of treatment, during the treatment period, and at the conclusion (or discontinuation) of treatment. Findings were evaluated as size (maximum diameter) and stage based on the Sakita-Miwa classifi cation. An ulcer was regarded as cured when the "white coating" was seen to have disappeared under endoscopy. As criteria for evaluating safety, all medically untoward symptoms and signs (adverse events, laboratory abnormalities, accidental symptoms, etc.) occurring after the start of rabeprazole treatment were handled as adverse events.RESULTS: Endoscopic cure rate in 38 patients in the efficacy analysis (endoscopic evaluation) was 71.1% (27/38). Among those 38 patients, 35 had gastric ulcer with a cure rate of 71.4% (25/35), and 3 had duodenal ulcer with a cure rate of 66.7% (2/3). Three adverse drug reactions were reported from 64 patients in the safety analysis (interstitial pneumonia, low white blood cell count and pruritus); thus, the incidence rate for adverse drug reactions was 4.7% (3/64).CONCLUSION: The treatment efficacy of rabeprazole for NSAID-induced ulcer under continuous NSAID ad-ministration was confi rmed.

Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease

The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.

Role of nonsteroidal anti-inflammatory drugs in the prevention of post-ERCP pancreatitis:a meta-analysis

BACKGROUND: The role of prophylactic nonsteroidal anti-inflammatory drugs (NSAIDs) for reduction of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) is debated. We performed a meta-analysis of all published randomized controlled trials to evaluate the efficacy of NSAIDs in the prevention of post-ERCP pancreatitis. DATA SOURCES: Searches were conducted in the databases PubMed, EMBASE and the Cochrane Library. Six randomized clinical trials that fulfilled the inclusion criteria and addressed the clinical questions of this analysis were further assessed. Data were extracted by two independent observers according to predetermined criteria. RESULTS: The risk of pancreatitis was lower in the NSAID group than in the placebo, group (OR: 0.46, 95% CI: 0.32 to 0.65, P < 0.0001). Two hours after ERCP, prophylactic administration of NSAIDs was associated with a lower serum amylase level (WMD: -91.09,95% CI: -149.78 to -32.40, P=0.002), but there was no difference in mean 24-hour serum amylase values (WMD: -379.00, 95% CI: -805.75 to 47.76, P=0.08). No deaths or NSAID-related complications were noted. CONCLUSIONS: Prophylactic administration of NSAIDs can reduce the incidence of post-ERCP pancreatitis; this administration in patients undergoing ERCP is recommended. Further randomized controlled trials are required before its introduction into routine care.

Prevention and management of non-steroidal anti-inflammatory drugs-induced small intestinal injury

Non-steroidal anti-inflammatory drug （NSAID）-induced small bowel injury is a topic that deserves attention since the advent of capsule endoscopy and balloon enteroscopy. NSAID enteropathy is common and is mostly asymptomatic. However, massive bleeding, stricture, or perforation may occur. The pathogenesis of small intestine injury by NSAIDs is complex and different from that of the upper gastrointestinal tract. No drug has yet been developed that can completely prevent or treat NSAID enteropathy. Therefore, a long-term randomized study in chronic NSAID users is needed.

Non-steroidal anti-inflammatory drugs in prevention of gastric cancer

Non-steroidal anti-inflammatory drugs （NSAIDs） including cydooxygenase 2 （COX-2） selective inhibitors, are potential agents for the chemoprevention of gastric cancer. Epidemiological and experimental studies have shown that NSAID use is associated with a reduced risk of gastric cancer although many questions remain unanswered such as the optimal dose and duration of treatment. The possible mechanisms for the suppressor effect of NSAIDs on carcinogenesis are the ability to induce apoptosis in epithelial cells and regulation of angiogenesis. Both COX-dependent and COX- independent pathways have a role in the biological activity of NSAIDs. Knowledge of how NSAIDs prevent neoplastic growth will greatly aid the design of better chemopreventive drugs and novel treatments for gastric cancer.

Effectiveness of nonsteroidal anti-inflammatory drugs in prevention of post-ERCP pancreatitis:A meta-analysis

AIM: To investigate the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). METHODS: Two independent reviewers searched Pub Med (1966 to October 2013), Embase (1984 to October 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 4, 2013) for relevant randomized controlled trials (RCTs) studying the effectiveness of prophylactic NSAID administration in the prevention of PEP. Using the Cochrane Collaboration Handbook, meta-analyses were conducted to evaluate the overall effect of NSAIDs in preventing the incidences of PEP and moderate to severe pancreatitis. RESULTS: Eight RCTs were identified from the literature search and included 1883 patients that underwent ERCP, with 971 patients in the NSAID group and 912 patients in the placebo group. Sixty-nine out of 971 (7.11%) patients developed PEP in the NSAID group in comparison to 143 out of 912 (15.68%) patients in the placebo group. The pooled RR of PEP incidence with prophylactic NSAID administration was 0.43 (95%CI: 0.33-0.56), which demonstrates that NSAID administration after ERCP significantly reduced the incidence of PEP when compared to the placebo group (P < 0.0001). Subgroup analysis was performed and revealed that the presence (NSAID group) or absence (placebo group) of NSAIDs had no significant effect on the development of moderate to severe pancreatitis (RR = 0.79, 95%CI: 0.52-1.18). Moreover, the administration of NSAIDs as a rectal suppository (RR = 0.35, 95%CI: 0.26-0.48; P < 0.0001) was more effective than oral administration (RR = 0.97, 95%CI: 0.53-1.80) or through infusion (RR = 0.43, 95%CI: 0.12-1.54). CONCLUSION: NSAIDs effectively reduce the incidence of PEP but not of moderate to severe pancreatitis. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: Old question new insights

Previous reports clearly demonstrated that Helicobacter pylori(H.pylori)infection,nonsteroidal anti-inflammatory drugs(NSAID)or low dose aspirin(ASA)use significantly and independently increased the risk for the development of peptic ulcer disease.Today,the presence of H.pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications.Whether NSAID intake in the presence of H.pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate.Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years.In addition,the interaction between H.pylori infection and low-dose ASA remains even more controversial.In real clinical practice,we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors.These huge variety of possible combinations greatly hinder the decision making process of physicians.

Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage

AIM:This study investigated the mechanisms of protection afforded by the proton pump inhibitor lansoprazole against gastric injury induced by different non-steroidal anti-inflammatory drugs (NSAIDs) in rats. METHODS: Male Sprague-Dawley rats were orally treated with indomethacin (100 μmol/kg), diclofenac (60 μmol/kg), piroxicam (150 μmol/kg) or ketoprofen (150 μmol/kg). Thirty minutes before NSAIDs, animals were orally treated with lansoprazole 18 or 90 umol/kg. Four hours after the end of treatments, the following parameters were assessed: gastric mucosal PGE2, malondialdehyde (MDA), myeloperoxidase (MPO) or non-proteic sulfhydryl compounds (GSH) levels; reverse transcription-polymerase chain reaction (RT-PCR) of mucosal COX-2 mRNA; gastric acid secretion in pylorus-ligated animals; in vitro effects of lansoprazole (1-300 μmol/L) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate. RESULTS: All NSAIDs elicited mucosal necrotic lesions which were associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels were detected in the gastric mucosa of indomethacin- or piroxicam-treated animals. Indomethacin enhanced mucosal cyclooxygenase-2 expression, while not affecting cyclooxygenase-1. At the oral dose of 18 μmol/kg lansoprazole partly counteracted diclofenac-induced mucosal damage, whereas at 90 μmol/kg it markedly prevented injuries evoked by all test NSAIDs. Lansoprazole at 90 μmol/kg reversed also the effects of NSAIDs on MPO, MDA and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced cyclooxygenase-2 expression. However, both lansoprazole doses markedly inhibited acid secretion in pylorus-ligated rats. Lansoprazole concentration-dependently reduced the oxidation of LDLs in vitro. CONCLUSION: These results suggest that, besides the inhibition of acid secretion, lansoprazole protection against NSAID-induced gastric damage depends on a reduction in mucosal oxidative injury, which is also responsible for an increment of sulfhydryl radical bioavailability. It is also suggested that lansoprazole does not influence the down-regulation of gastric prostaglandin production associated with NSAID treatment.

Helicobacter pylori-negative,non-steroidal anti-inflammatory drug:Negative idiopathic ulcers in Asia

Since the discovery of Helicobacter pylori(H.pylori)infection in the stomach,the bacteria infection and non-steroidal anti-inflammatory drugs(NSAIDs)use had been considered to be the 2 main causes of peptic ulcers.However,there have been recent reports of an increase in the proportion of peptic ulcers without these known risk factors;these are termed idiopathic peptic ulcers.Such trend was firstly indicated in 1990s from some reports in North America.In Asia,numerous studies reported that idiopathic ulcers accounted for a small percentage of all ulcers in the 1990s,but in the2000s,multiple studies reported that the proportion of idiopathic ulcers had reached 10%-30%,indicating that the incidence of idiopathic ulcers in Asia has also been rising in recent years.While a decline in H.pylori infection rates of general population in Asia is seen as the main reason for the increased incidence of idiopathic ulcers,it is also possible that the absolute number of idiopathic ulcer cases has increased.Advanced age,serious systemic complication,and psychological stress are considered to be the potential risk factors for idiopathic ulcers.Management of idiopathic ulcers is challenging,at present,because there is no effective preventative measure against recurrence in contrast with cases of H.pylori-positive ulcers and NSAIDs-induced ulcers.As it is expected that H.pylori infection rates in Asia will decline further in the future,measures to treat idiopathic ulcers will also likely become more important.

Non-steroidal anti-inflammatory drugs and statins in relation to colorectal cancer risk

AIM： To investigate the association between individual or combined use of non-steroidal anti-inflammatory drugs （NSAIDs） or statins and colorectal cancer risk.METHODS： In a population-based case-control study in women, we examined the association between NSAIDs and statin use and the risk of colorectal cancers. We further investigated whether the use of statins modifies the protective effect of NSAIDs. Female cases （n = 669）of colorectal cancer aged 50-74 years were identified from a storewide registry in Wisconsin during 1999-2001. Community control women （n = 1375） were randomly selected from lists of licensed drivers and Medicare beneficiaries. Medication use and risk factor information were gathered during a structured telephone interview. A multivariable logistic regression model was used to calculate odds ratio （OR） and 95% confidence interval （CI）.RESULTS： Overall, NSAIDs users had a 30% reduction in risk of colorectal cancer （95% CI： 0.56-0.88）. Statin use was not associated with colorectal cancer risk （OR = 1.17, 95% CI： 0.74-1.85）, regardless of structural type （lipophilic or hydrophilic）, duration of use, or recency. There was no evidence of an interaction between NSAIDs and statins and colorectal cancer risk （P-interaction = 0.28）.CONCLUSION： Although our results confirm the inverse association between NSAIDs use and colorectal cancer risk, they do not support a risk reduction in statin users, or an interaction effect of combined NSAIDs and statin use.

Characteristics and clinical outcome of nonsteroidal anti-inflammatory drug-induced acute hepato-nephrotoxicity among Chinese patients

AIM: To determine the clinicopathological characteristics of nonsteroidal anti-inflammatory drug (NSAID)-induced acute hepato-nephrotoxicity among Chinese patients.

Non-steroidal anti-inflammatory drugs-induced small intestinal injury and probiotic agents

Intestinal bacteria play a role in the development of non-steroidal anti-inflammatory drugs （NSAID）-induced small intestinal injury. Agents such as probiotics, able to modi~ the gut ecology, might theoretically be useful in preventing small intestinal damage induced by NSAIDs. The clinical studies available so far do suggest that some probiotic agents can be effective in this respect.

Muscovite is protective against non-steroidal anti-inflammatory drug-induced small bowel injury

AIM: To evaluate the effect of muscovite in preventing small bowel injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs).

Impact of topical nonsteroidal anti-inflammatory drugs in prevention of macular edema following cataract surgery in diabetic patients

AIM： To evaluate the efficacy of prophylactic administration of topical non-steroidal anti-inflammatory drugs（NSAIDs） on macular edema following cataract surgery in diabetic patients, and to compare between types of NSAIDs（ketorolac tromethamine 0.4% and nepafenac 0.1%）. METHODS： Group 1（control） received artificial tears substitute as a placebo group, group 2（nepafenac） received topical nepafenac 0.1%, and group 3（ketorolac） received topical ketorolac tromethamine 0.4%. Patients were examined postoperatively after completing one week, one month, two months and three months＇ intervals for evaluating cystoid macular edema（CME） development. The main study outcomes were achieving the best corrected visual acuity（BCVA） and change in the central macular thickness（CMT） measured with optical coherence topography（OCT）.RESULTS： Eighty eyes of 76 patients were included in this study. BCVA showed a statistically significant difference at the third month postoperative follow up between the control group and the NSAIDs groups（P=0.04）. There was an increase in the CMT in all cases starting from postoperative first week until third month. CMT showed a statistically significant difference between control group and NSAIDs groups from postoperative first month until third month（P=0.008, 0.027, 0.004）. There was no statistically significant difference between nepafenac and ketorolac groups in BCVA and OCT CMT. CONCLUSION： Prophylactic preoperative and postoperative NSAIDs may have a role in reducing the frequency and severity of CME in diabetic eyes following cataract surgery.

Exacerbation of inflammatory bowel disease by nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors:Fact or fiction?

The existence of a possible link between inflammatory bowel disease （IBD） and nonsteroidal anti-inflammatory drugs （NSAIDs） has been repeatedly suggested. Recently, a few studies have addressed the issue of a possible, similar effect by selective cyclooxygenase-2 inhibitors （COXIBs）. The present article reviews the available scientific evidence for this controversial subject.