Short-term Use Of Nonsteroidal Anti-inflammatory Drugs Research Articles

Opioid-Sparing Nonsteroid Anti-inflammatory Drugs Protocol in Patients Undergoing Intramedullary Nailing of Tibial Shaft Fractures: A Randomized Control Trial.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective analgesics commonly used in fracture management. Although previously associated with delayed fracture healing, multiple studies have demonstrated their safety, with minimal risks of fracture healing. Given the current opioid crisis in the United States, alternate pain control modalities are essential to reduce opioid consumption. This study aims to determine whether the combination of oral acetaminophen and intravenous ketorolac is a viable alternative to opioid-based pain management in closed tibial shaft fractures treated with intramedullary nailing. We conducted a randomized controlled trial evaluating postoperative pain control and opioid consumption in patients with closed tibial shaft fractures who underwent intramedullary nailing. Patients were randomized into an NSAID-based pain control group (52 patients) and an opioid-based pain control group (44 patients). Visual analog scale (VAS) scores and morphine milligram equivalents (MMEs) were evaluated at 12-hour postoperative intervals during the first 48 hours after surgery. Nonunion and delayed healing rates were recorded for both groups. A statistically significant decrease in MMEs was noted at every measured interval (12, 24, 36, and 48 hours) in the NSAID group compared with the opioid group (P-value 0.001, 0.001, 0.040, 0.024, respectively). No significant change in visual analog scale scores was observed at 12, 36, and 48 hours between both groups (P-value 0.215, 0.12, and 0.083, respectively). A significant decrease in VAS scores was observed at the 24-hour interval in the NSAID group compared with the opioid group (P-value 0.041). No significant differences in union rates were observed between groups (P-value 0.820). Using an NSAID-based postoperative pain protocol led to a decrease in opioid consumption without affecting pain scores or union rates. Owing to the minimal risk of short-term NSAID use, their role in the perioperative management of tibia shaft fractures is justified, especially when they reduce opioid consumption markedly. Therapeutic Level I.

Heart Failure Following Anti-Inflammatory Medications in Patients With Type 2 Diabetes Mellitus

BackgroundFluid retention and endothelial dysfunction have been related to use of nonsteroidal anti-inflammatory drugs (NSAIDs), and type 2 diabetes mellitus (T2DM) has been linked to both a decline in kidney function and subclinical cardiomyopathy. ObjectivesThe authors hypothesized that short-term use of NSAIDs could lead to subsequent development of incident heart failure (HF) in patients with T2DM. MethodsUsing nationwide Danish registers, we identified patients diagnosed with T2DM during 1998 to 2021 and included patients without previous HF, rheumatic disease, or use of NSAIDs 120 days before diagnosis. Associations between NSAIDs and first-time HF hospitalization were investigated using a case-crossover design with 28-day exposure windows, and ORs with 95% CIs were reported. ResultsIncluded were 331,189 patients with T2DM: 44.2% female, median age of 62 years (IQR: 52-71 years); 23,308 patients were hospitalized with HF during follow-up, and 16% of patients claimed at least 1 NSAID prescription within 1 year. Short-term use of NSAIDs was associated with increased risk of HF hospitalization (OR: 1.43; 95% CI: 1.27-1.63), most notably in subgroups with age ≥80 years (OR: 1.78; 95% CI: 1.39-2.28), elevated hemoglobin (Hb) A1c levels treated with 0 to 1 antidiabetic drug (OR: 1.68; 95% CI: 1.00-2.88), and without previous use of NSAIDs (OR: 2.71; 95% CI: 1.78-4.23). ConclusionsNSAIDs were widely used and were associated with an increased risk of first-time HF hospitalization in patients with T2DM. Patients with advanced age, elevated HbA1c levels, and new users of NSAID seemed more susceptible. These findings could guide physicians prescribing NSAIDs.

Risk of heart failure following short-term non-steroidal anti-inflammatory drug use in patients with type 2 diabetes mellitus

Abstract Background Fluid retention is a known but underappreciated side-effect of non-steroidal anti-inflammatory drug (NSAID) use. As type 2 diabetes mellitus (T2DM) has been linked to both subclinical cardiomyopathy and a decline in kidney function, short-term NSAID use could lead to subsequently development of heart failure (HF) due to aberrations in fluid balances. Purpose We investigated associations between short-term NSAID use and the risk of HF in a nationwide cohort of patients with T2DM. Methods Using nationwide Danish registers, we identified patients diagnosed with T2DM during 1998–2018. Follow-up began 120 days after first-time T2DM diagnosis among patients without prior heart failure or a rheumatological diagnosis indicating long-term NSAID use. To describe use of NSAID among patients with T2DM, we reported proportions of patients claiming at least 1, 2, 3 or 4 prescriptions of NSAID within one year of start of follow-up. We investigated associations between use of NSAIDs (celecoxib, diclofenac, ibuprofen and naproxen) and new-onset HF hospitalizations using a case-crossover design with 28-day exposure windows and reported odds ratios (OR) with 95% confidence intervals (CI). The case-crossover design uses each individual as his or her own control making it suitable to study the effect of short-term exposure on immediate events while mitigating unmeasured confounding. Sensitivity analyses using exposure windows of 14 and 42 days were performed as well. Results A total of 334,950 patients with T2DM was included (47.7% female, median age of 61 [interquartile range 50–70]). Celecoxib and naproxen were rarely used; on the contrary, prescriptions of diclofenac and ibuprofen were claimed at least once within one year from the beginning of follow-up by 4.9% and 15.5% of patients, respectively–0.9% and 2.7% claimed at least four prescriptions (Figure 1). The risk of new-onset HF hospitalization was increased following use of diclofenac or ibuprofen with corresponding ORs of 1.3 (95% CI 1.0 to 1.7) and 1.3 (95% CI 1.1 to 1.5) using 28-day exposure windows. An increased risk following use of celecoxib or naproxen was not found (Figure 2). Conclusion NSAIDs diclofenac and ibuprofen were both widely used and associated with an increased risk of new-onset HF hospitalization in patients with T2DM. This suggests a previously unknown and serious, clinically relevant concern of NSAID use in patients with T2DM. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Ib Mogens Kristiansens Almene FondHelsefonden

Nonsteroidal anti-inflammatory drugs for pain relief in case of injuries: Is there a risk of bone metabolism disorders and nonunion of bone fractures?

According to experimental studies, nonsteroidal anti-inflammatory drugs (NSAIDs) can affect the healing of bone tissue after fractures. The significance of this effect of NSAIDs for real clinical practice is the subject of discussion. We analyzed publications on the problem of nonunion or development of fractures against the background of taking NSAIDs presented in the PubMed and MEDLINE system. From 1976 to 2021, 75 papers on this topic were published, of which 19 were observational, cohort and randomized controlled trials, as well as case-control studies, 4 meta-analyses. According to meta-analyses, which included from 6 to 16 studies, there was an association between taking NSAIDs and nonunion of bones after fractures or postoperative trauma: the odds ratio ranged from 2.07 (95% CI: 1.19–3.61) to 5.27 (95% CI: 2.34–11.88). A number of large studies confirm an increased risk of nonunion of fractures and the development of “marching” fractures in patients treated with NSAIDs. The risk of nonunion was increased when using NSAIDs for more than 2 weeks and in high doses. With short-term use of NSAIDs (less than 2 weeks) and the use of these drugs in pediatric practice, the frequency of bone tissue repair disorders did not increase.

Non-steroidal anti-inflammatory drug-associated acute kidney injury: does short-term NSAID use pose a risk in hospitalized patients?

While renal risk associated with short-term use of non-steroidal anti-inflammatory drugs (NSAID) has been anecdotally documented, no conclusive evidence is available on the renal safety, especially among hospitalized patients with reduced renal function. This study is to evaluate the risk of acute kidney injury (AKI) associated with NSAID use in hospital. A retrospective matched cohort study utilizing electronic health records from two large academic tertiary-care hospitals was conducted. We defined AKI based on changes in SCr according to published AKI criteria. The hospital acquired AKI risk associated with inpatient NSAID use was assessed using a time-dependent Cox proportional hazard regression in pooled cohort as well as two sub cohorts stratified by baseline renal function. A total of 18,794 admissions were included in the final cohort. Of 9397 admissions exposed to NSAIDs, 7914 and 1483 admissions were in the "without" and "with baseline renal impairment" cohort, with the same number of matching non-exposed admissions in each of the stratified cohort. The AKI incidences were 6 and 22 events per 1000 patient-days in "without" and "with preexisting renal impairment" cohort, respectively. The adjusted analyses suggested that NSAID use increased AKI risk in patients with preexisting renal impairment (hazard ratio [HR]: 1.38 [1.04-1.83]) but not in the patients without preexisting renal impairment (HR: 0.83 [95% CIs: 0.63-1.08]) or in the pooled cohort (HR: 1.01 [95% CIs: 0.83-1.24]). Our findings suggested that NSAID use is associated with an increased risk of AKI in the hospitalized patients with preexisting renal impairment but the association is not statistically significant in those who have preserved renal function. Further randomized controlled trials are needed to validate these observational findings.

Are NSAIDs Safe? Assessing the Risk-Benefit Profile of Nonsteroidal Anti-inflammatory Drug Use in Postoperative Pain Management.

In this article, we review controversies in assessing the risk of serious adverse effects caused by administration of nonsteroidal anti-inflammatory drugs (NSAIDs). Our focus is upon NSAIDs used in short courses for the management of acute postoperative pain. In our review of the literature, we found that the risks of short-term NSAID use may be overemphasized. Specifically, that the likelihood of renal dysfunction, bleeding, nonunion of bone, gastric complications, and finally, cardiac dysfunction do not appear to be significantly increased when NSAIDs are used appropriately after surgery. The importance of this finding is that in light of the opioid epidemic, it is crucial to be aware of alternative analgesic options that are safe for postoperative pain control.

Non-steroidal anti-inflammatory drugs for acute low back pain.

Non-steroidal anti-inflammatory drugs for acute low back pain.

Effects of nonsteroidal anti-inflammatory drug (NSAID) use upon male gonadal function: A national, population-based study.

Recent data have suggested that short-term NSAID use induces a state of compensated hypogonadism. Our aim was to investigate the association between chronic, regular NSAID use and compensated hypogonadism in a large, nationally representative cohort, the US National Health and Nutrition Examination Survey (NHANES) database. Men 20-80years who answered the analgesic use questionnaire and underwent hormonal testing were included. Multivariable regression was utilised to determine the relationship between NSAID use and serum testosterone (T), anti-Mullerian hormone (AMH) and T:AMH ratio. Among 3,749 men, 505 (13.5%) reported regular NSAID use and 3,244 (86.5%) did not. Regular users had lower T (440.7±27.0 vs. 557.0±24.9ng/dl, p=.005) and albumin (43.8±0.2 vs. 45.1±0.1, p<.001) compared to nonregular users. On multivariable analysis, only active smoking was significantly associated with T, AMH and T:AMH ratio (p<.001, p=.036 and p=.005 respectively). Regular NSAID use was not associated with T, AMH or T:AMH ratio (p=.523, p=.974, and p=.872 respectively). In this nationally representative sample of US men, regular and chronic NSAID use was not associated with alterations in T or compensated hypogonadism. These data should reassure patients and clinicians regarding the safety of NSAID use with respect to the risk of alteration in the hypothalamic-pituitary-gonadal axis.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Their Effect on Musculoskeletal Soft-Tissue Healing: A Scoping Review.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are being increasingly employed as a part of multimodal non-opioid strategies to treat postoperative pain. In the present study, we sought to review the effects of short-term NSAID use on musculoskeletal soft-tissue healing. We performed a scoping review of all studies that included the use of NSAIDs and their effect on healing of soft tissues, which for the purpose of this review refers to non-osseous musculoskeletal tissue such as ligament, tendon, labrum, and meniscus. The inclusion criteria encompassed all studies (human, animal, and in vitro) that evaluated the effect of NSAIDs on soft-tissue healing. Subgroup analyses, wherever applicable, were conducted on the basis of the type of NSAID (cyclooxygenase [COX]-specific or nonspecific) and the type of study (human, animal, or in vitro). Relevant metadata from each study were abstracted, and descriptive statistics were used to summarize the results. A total of 44 studies met the inclusion criteria, including 3 human studies, 33 animal studies, and 8 in vitro studies. These studies included 4 different NSAIDs in the human subgroup, 16 different NSAIDs in the animal subgroup, and 7 different NSAIDs in the in vitro subgroup. The majority of reported studies (including 1 of 2 human studies, 10 of 14 animal studies, and 3 of 3 in vitro studies) demonstrated that COX-2-selective inhibitors had negative impact on soft-tissue healing. In contrast, the majority of human and animal studies (2 of 2 and 19 of 30, respectively) demonstrated that nonselective COX inhibitors had no negative effect on the healing of labrum, tendons, and ligaments. The majority of in vitro studies demonstrated that NSAIDs have a harmful effect on biological processes involved in tendon-healing and regeneration (tenocyte proliferation, collagen and glycosaminoglycan synthesis). Current limited evidence demonstrates that selective COX-2 inhibitors can negatively affect healing of musculoskeletal soft tissue after surgical repair. In contrast, the majority of studies demonstrate that nonselective COX inhibitors have no negative effect on musculoskeletal soft-tissue healing. Additional high-quality human clinical trials are necessary to provide more definitive conclusions.

Risk estimation of fetal adverse effects after short-term second trimester exposure to non-steroidal anti-inflammatory drugs: a literature review.

Non-steroidal anti-inflammatory drugs (NSAIDs) are not recommended in the 3rd trimester of pregnancy due to known fetal adverse effects in an advanced gestational age. This investigation was performed to assess whether there is a significant risk of NSAIDs being used as an analgesic or antipyretic medication in the 2nd trimester. A systematic search for publications reporting 2nd trimester NSAID exposure was performed in MEDLINE. The search focused on case descriptions reporting defined adverse effects including prenatal ductus arteriosus constriction, oligohydramnios, neonatal renal failure, and primary pulmonary hypertension. Original articles published until February 2018 were considered for evaluation. Out of 681 identified publications, 26 included relevant information on the defined adverse effects. Among these publications, premature labor was the major reason for 2nd trimester indomethacin treatment while other clinical indications and other NSAIDs were underrepresented. Narrowing or closure of the ductus arteriosus in the 2nd trimester was described in 33 fetuses. Only eight publications reported adverse effects after less than 7-day exposure during the 2nd trimester. Based on these results, short-term use of NSAIDs as analgesics or antipyretics in the 2nd trimester does not appear to pose a substantial risk for fetal adverse effects. Long-term use in the late 2nd trimester, however, should always be monitored.

Changing pattern of perforated PUD: Are NSAIDs to be blamed?

This study aimed to determine if there is association between gastric perforation and non-steroidal anti-inflammatory drugs (NSAIDs) abuse in patients presenting with perforated peptic ulcer disease (PPUD). The data were collected retrospectively from May 2011 to May 2015 and then prospectively until December 2017. Sixty patients diagnosed with PPUD on exploratory laparotomy were evaluated. Data were analyzed using SPSS (version 21.0). P value ≤ 0.05 was considered significant. A total of 60 patients were operated on for PPUD during the study period. Forty-five (75.0%) patients gave significant history of NSAIDs use, of which nine (20.0%) had medical prescription, while others were over the counter medications. None of the patients was on ulcer prophylaxis including those who were on long term use and with prior dyspeptic symptoms. Five patients (11.1%) were on the recommended dose of the NSAIDs, thus patients in this series showed irrational use of NSAIDs. Forty-two (93.3%) patients had gastric perforation, while only three of the patients had duodenal perforation. The association between significant NSAIDs use and gastric perforation was found to be significant (p= 0.002). There was no difference in the site of perforation when patients who were on long term NSAIDs were compared with short term NSAIDs use (10.0 vs. 35.0) (p= 0.061). In addition, long term NSAIDs use (p= 0.041), ignorance of proper dose of the medication (p= 0.003), and gastric ulcer perforations (p= 0.011) were independent causes of mortality in the studied patients when age and duration of the presentations were matched. NSAIDs use, including both long- and short-term use, was significant among patients with gastric perforation.

Non-steroidal anti-inflammatory drug related upper gastrointestinal bleeding: types of drug use and patient profiles in real clinical practice

Background: The best available evidence regarding non-steroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) bleeding comes from randomized controlled trials including patients who use NSAIDs to manage chronic rheumatic diseases; however, patients with varying background profiles commonly take NSAIDs for many other reasons, often without prescription, and such usage has not been well studied.Objectives and methods: To define the characteristics of patients hospitalized for upper GI bleeding in clinical practice, we conducted a case–control study among patients with endoscopy-proven major upper GI bleeding due to gastroduodenal peptic lesions and control subjects. We used adjusted logistic regression models to estimate bleeding risks. Data analysis was performed using SPSS 22.0.Results: Our analysis included 3785 cases and 6540 controls, including 1270 cases (33.55%) and 834 controls (12.75%) reporting recent use (<30 days) of NSAIDs including high-dose acetylsalicylic acid (ASA). NSAID use was associated with increased risk of upper GI bleeding, with an adjusted relative risk of 4.86 (95% CI, 4.32–5.46). Acute musculoskeletal pain (36.1%), chronic osteoarthritis (13.5%), and headache (13.6%) were the most common reasons for NSAID use. Among cases, only 17.31% took NSAIDs and 6.38% took high dose ASA due to chronic osteoarthritis. Demographic characteristics significantly differed between subjects with chronic vs. acute musculoskeletal pain. Proton pump inhibitor use was significantly higher in patients who used NSAIDs due to chronic osteoarthritis compared to patients with acute musculoskeletal pain. NSAID (65.15%) or high-dose ASA use (65.83%) preceding upper GI bleeding was most often short-term. In over half of cases (63.62%), the upper GI bleeding event was not preceded by dyspeptic warning symptoms.Conclusions: The majority of patients hospitalized due to NSAID-related upper GI bleeding reported short-term NSAID use for reasons other than chronic rheumatic disease. These findings suggest that current prevention strategies may not reach a wide population of short-term NSAID users.

The effect of NSAIDs on spinal fusion: a cross-disciplinary review of biochemical, animal, and human studies.

Non-steroidal anti-inflammatory drugs (NSAIDs) play an important role in postoperative pain management. However, their use in the setting of spine fusion surgery setting has long been a topic of controversy. In this review we examined relevant research, including in vivo, animal, and clinical human studies, with the aim of understanding the effect of NSAIDs on spinal fusion. Systematic review of study designs of all types from randomized controlled trials and meta-analyses to single-institution retrospective reviews. A search of PubMed and Embase was conducted using the keywords: "spine," "spinal fracture," NSAIDs, anti-inflammatory non-steroidal agents, bone, bone healing, fracture, fracture healing, yielding a total of 110 studies. Other 28 studies were identified by cross-referencing, resulting in total 138 studies. There is no level I evidence from human studies regarding the use of NSAIDs on spinal fusion rates. The overall tone of the spine literature in the early 2000s was that NSAIDs increased the rate of non-union; however, nearly all human studies published after 2005 suggest that short-term (<2weeks) postoperative use have no such effect. The dose dependency that is seen with a 2-week postoperative course is not present when NSAIDs are only used for 48h after surgery. NSAID appear to have dose-dependent and duration-dependent effects on fusion rates. The short-term use of low-dose NSAIDs around the time of spinal fusion surgery is reasonable. Spine surgeons can consider the incorporation of NSAIDs into pain control regimens for spinal fusion patients with the goal of improving pain control and reducing the costs and complications associated with opioids.

Cardiovascular safety of hydroxypropyl-β-cyclodextrin–diclofenac in the management of acute postsurgical pain: a pooled analysis of 2 randomized, double-blind, placebo- and active comparator–controlled phase III clinical trials

Study ObjectiveLong-term use of nonsteroidal anti-inflammatory drugs, including selective and nonselective cyclooxygenase inhibitors, has been suggested to be associated with cardiovascular (CV) safety risks. Data are limited regarding CV risks associated with short-term nonsteroidal anti-inflammatory drug use, including injectable formulations, although it has been suggested that even a single dose may increase CV adverse event (AE) risk. The objective of this study was to examine the CV safety of an injectable diclofenac formulation solubilized with hydroxypropyl-β-cyclodextrin (HPβCD) when given for ≤5days postoperatively. DesignA pooled analysis of CV AEs from 2 pivotal phase III clinical trials examining the efficacy and safety of intravenous (IV) HPβCD-diclofenac vs placebo and the active comparator ketorolac was conducted. SettingPostoperative, with treatment initiated in the postanesthesia care unit ≤6hours postsurgery. PatientsOverall, 608 abdominal/pelvic and orthopedic surgery patients met inclusion criteria and received ≥1 study medication dose. InterventionsPatients received either HPβCD-diclofenac, ketorolac, or placebo via IV bolus injection every 6hours, for ≤5days postsurgery. MeasurementsCV AEs, reported by study investigators, were evaluated through the treatment period and follow-up (≤37days after last study medication dose), and relative CV AE risks were estimated. Main ResultsIV HPβCD-diclofenac was not associated with increased treatment-emergent CV AE incidence vs placebo (11.6% vs 12.2%; relative risk, 0.96 [95% confidence interval, 0.56-1.62]). Serious CV AEs as well as treatment-related AEs were uncommon, and there were no reports of myocardial infarction or cerebrovascular accident. CV AEs were uncommon during the follow-up period, occurring in 1.3%, 0%, and 1.4% of patients in the HPβCD-diclofenac, ketorolac, and placebo groups, respectively. ConclusionsAlthough a longer duration follow-up study in a larger patient population would expand our understanding of potential CV risks, the present analysis suggests that postoperative use of HPβCD-diclofenac does not present an added CV safety risk over placebo.

Non-steroidal anti-inflammatory drugs for chronic low back pain

Chronic back pain is an important health problem. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat people with low back pain, especially people with acute back pain. Short term NSAID use is also recommended for pain relief in people with chronic back pain. Two types of NSAIDs are available and used to treat back pain: non-selective NSAIDs and selective COX-2 NSAIDs. In 2008, a Cochrane review identified a small but significant effect from NSAIDs compared to placebo in people with chronic back pain. This is an update of the Cochrane review published in 2008 and focuses on people with chronic low back pain. To determine if NSAIDs are more efficacious than various comparison treatments for non-specific chronic low back pain and if so, which type of NSAID is most efficacious. We searched CENTRAL, MEDLINE, EMBASE, PubMed and two clinical trials registry databases up to 24 June 2015 for randomized controlled trials (RCTs) published in English, German or Dutch. We also screened references cited in relevant reviews. We included RCTs (double-blind and single-blind) of NSAIDs used to treat people with chronic low back pain. Two review authors independently screened trials for inclusion in this Cochrane review according to the inclusion criteria. One review author extracted the data, and a second review author checked the data. Two review authors independently evaluated the risk of bias of all included trials. If data were clinically homogeneous, we performed a meta-analysis and assessed the quality of evidence using the GRADE approach. We included 13 trials in this Cochrane review. Ten studies were at 'low' risk of bias. Six studies compared NSAIDs with placebo, and included 1354 participants in total. There is low quality evidence that NSAIDs are more effective than placebo, with a mean difference in pain intensity score from baseline of -3.30 (95% CI -5.33 to -1.27) on a 0 to 100 visual analogue scale (VAS) with a median follow-up of 56 days (interquartile range (IQR) 13 to 91 days). Four studies measured disability using the Roland Morris Disability Questionnaire. There is low quality evidence that NSAIDs are more effective than placebo on disability, with a mean difference from baseline of -0.85 (95% CI -1.30 to -0.40) on a scale from 0 to 24 with a median follow-up of 84 days (IQR 42 to 105 days). All six placebo controlled studies also reported adverse events, and suggested that adverse events are not statistically significant more frequent in participants using NSAIDs compared to placebo (RR 1.04, 95% CI 0.92 to 1.17). Due to the relatively small sample size and relatively short follow-up in most included trials, it is likely that the proportion of patients experiencing an adverse event is underestimated.Two studies compared different types of non-selective NSAIDs, namely ibuprofen versus diclofenac and piroxicam versus indomethacin. The trials did not find any differences between these NSAID types, but both trials had small sample sizes. One trial reported no differences in pain intensity between treatment groups that used selective or non-selective NSAIDs. One other trial compared diflunisal with paracetamol and showed no difference in improvement from baseline on pain intensity score. One trial showed a better global improvement in favour of celecoxib versus tramadol.One included trial compared NSAIDs with 'home-based exercise'. Disability improved more in participants who did exercises versus participants receiving NSAIDs, but pain scores were similar. Six of the 13 included RCTs showed that NSAIDs are more effective than placebo regarding pain intensity. NSAIDs are slightly more effective than placebo regarding disability. However, the magnitude of the effects is small, and the level of evidence was low. When we only included RCTs at low risk of bias, differences in effect between NSAIDs and placebo were reduced. We identified no difference in efficacy between different NSAID types, including selective versus non-selective NSAIDs. Due to inclusion of RCTs only, the relatively small sample sizes and relatively short follow-up in most included trials, we cannot make firm statements about the occurrence of adverse events or whether NSAIDs are safe for long-term use.

Increased Risk of End-Stage Renal Disease (ESRD) Requiring Chronic Dialysis is Associated With Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Nationwide Case-Crossover Study.

It is known that many medical adverse events can be caused by nonsteroidal anti-inflammatory drugs (NSAIDs); however, epidemiologic evidence has not granted an affirmative relationship between NSAID use and the risk of end-stage renal disease (ESRD). We aimed to investigate the relationship in a Chinese population between short-term NSAID use and development of ESRD requiring chronic dialysis. A retrospective case-crossover design was used in this study. Using the Taiwanese National Health Insurance database, we identified 109,400 incident chronic ESRD patients with dialysis initiation from 1998 to 2009. For each patient, we defined the case period as 1 to 14 days and the control period as 105 to 118 days, respectively, before the first dialysis date. The washout period was 90 days between the case and control period. Detailed information about NSAID use was compared between the case and control periods. We calculated odds ratios (ORs) and their 95% confidence intervals (CIs) using a conditional logistic regression model. NSAID use was found to be a significant risk factor associated with dialysis commencement. The adjusted OR was 2.73 (95% CI: 2.62-2.84) for nonselective NSAIDs and 2.17 (95% CI: 1.83-2.57) for celecoxib. The OR reached 3.05 for the use of acetic acid derivatives. Compared with the oral forms, significantly higher risks were seen in parenteral NSAID use (OR: 8.66, 95% CI: 6.12-20.19). NSAIDs should be prescribed with caution, especially for those in ESRD high-risk groups.

Gastrointestinal injury associated with NSAID use: a case study and review of risk factors and preventative strategies.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective anti-inflammatory and analgesic agents and are among the most commonly used classes of medications worldwide. However, their use has been associated with potentially serious dose-dependent gastrointestinal (GI) complications such as upper GI bleeding. GI complications resulting from NSAID use are among the most common drug side effects in the United States, due to the widespread use of NSAIDs. The risk of upper GI complications can occur even with short-term NSAID use, and the rate of events is linear over time with continued use. Although gastroprotective therapies are available, they are underused, and patient and physician awareness and recognition of some of the factors influencing the development of NSAID-related upper GI complications are limited. Herein, we present a case report of a patient experiencing a gastric ulcer following NSAID use and examine some of the risk factors and potential strategies for prevention of upper GI mucosal injuries and associated bleeding following NSAID use. These risk factors include advanced age, previous history of GI injury, and concurrent use of medications such as anticoagulants, aspirin, corticosteroids, and selective serotonin reuptake inhibitors. Strategies for prevention of GI injuries include anti-secretory agents, gastroprotective agents, alternative NSAID formulations, and nonpharmacologic therapies. Greater awareness of the risk factors and potential therapies for GI complications resulting from NSAID use could help improve outcomes for patients requiring NSAID treatment.

CT enteroclysis/enterography findings in drug-induced small-bowel damage.

To evaluate the CT enteroclysis (CTE)/enterography findings of patients with small-bowel mucosal damage induced by aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) and to compare these findings with the duration of drug use and endoscopic findings. CTE findings of 11 patients (22 lesions) with drug-induced small-bowel damage were reviewed, including 8 NSAID users and 3 aspirin users. Three patients were short-term users (6 months or shorter) and eight were long-term users (3 years or longer). Nine patients also underwent videocapsule endoscopy (VCE) or double-balloon enteroscopy (DBE). Small-bowel abnormalities were visible in 8 of 11 patients (73%) on CTE. Multiple lesions were seen in five patients, including all short-term users. Lesions were classified into three types. Type 1 (mucosal patchy enhancement) was found in four of eight patients (50%, 12 lesions) all were short-term users. Small erosions with mild oedema/redness were shown by DBE. Type 2 (homogeneous hyperenhancement) was found in two of eight patients (25%, four lesions) who were long-term users. Large ulcers with marked oedema/redness were shown by DBE. Type 3 (stratification enhancement) was found in four of eight patients (50%, six lesions), both short-term and long-term users. Annular or large ulcers with strictures were shown by VCE or DBE. On CTE, Type 1 lesions in patients with mostly short-term aspirin or NSAID use, Type 2 lesions in patients with long-term use and Type 3 lesions in both types of patients were detected. CTE may have usefulness for the detection of mild damage. Small-bowel abnormalities owing to aspirin or NSAID present with three different patterns on CTE.

Nonsteroidal anti-inflammatory drugs and antihypertensives: how do they relate?

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely available as over-the-counter medications, despite their numerous side effects and drug interactions. The aim of this article is to increase awareness of the hypertensive potential of NSAIDs and their interference with antihypertensives. Patients with hypertension appear to be more susceptible than normotensive individuals to the blood pressure-increasing effect of NSAIDs. Most studies have found that short-term use of NSAIDs does not pose a major risk for hypertension or increase in cardiovascular disease in healthy individuals. The calcium channel blockers and β-blockers seem to be least affected by the concomitant use of NSAIDs. A dentist must weigh the benefits and disadvantages of using NSAIDs in patients taking antihypertensive drugs. For those who may be at greater risk, such as patients with hypertension and the elderly, careful selection of the class of NSAID and close monitoring are appropriate measures, especially if long-term use is anticipated.

Exposure to phototoxic NSAIDs and quinolones is associated with an increased risk of melanoma

Ultraviolet radiation exposure is the most important exogenous risk factor for cutaneous malignancies. It is possible that phototoxic drugs promote the development of cutaneous melanoma (CM) by intensifying the effect of ultraviolet light on the skin. We investigated the association between the use of common systemic phototoxic drugs and development of CM. This study was a case-control study in a Dutch population-based cohort. The drug dispensing data was obtained from PHARMO, a Dutch drug dispensing and hospital admissions registry, and linked to PALGA, the nationwide pathology network of the Netherlands. The cases were patients diagnosed with pathologically confirmed primary CM between 1991 and 2004. Controls were sampled from the PHARMO population. Exposure to systemic phototoxic drugs was measured and included antimicrobial agents, diuretics, antipsychotic drugs, antidiabetic drugs, cardiac drugs, antimalarials and nonsteroidal anti-inflammatory drugs (NSAIDs). A multivariate conditional logistic regression analysis was performed to study the association between exposure to phototoxic drugs and CM. The study population included 1,318 cases and 6,786 controls. Any phototoxic drug during the study period was dispensed for 46 % of the cases and 43 % of the controls (p = 0.012). The use of quinolones [odds ratio (OR) 1.33, 95 % confidence interval (CI) 1.01-1.76] and propionic acid derivative NSAIDs (OR 1.33, 95 % CI 1.14-1.54) had a positive association with CM. Our study shows that the use of phototoxic drugs is associated with an increased risk of developing CM. Even a short-term use of phototoxic quinolones and propionic acid derivative NSAIDs may increase the risk for CM. Patient education to promote sun-protective behaviour is essential to avoid immediate adverse effects and possible long-term effects of phototoxic drugs.