Use of gastroprotective agents in recommended doses in hospitalized patients receiving NSAIDs: a drug utilization study

OBJECTIVE: In recent years, studies investigated to what extend recommendations for co-prescribing gastroprotective agents in prevention of NSAID-induced gastrointestinal complications are followed in clinical practice. However, only a few studies have also taken into consideration the recommended dose of gastroprotectives prescribed in NSAID-induced ulcer prophylaxis. The aim of our study was to evaluate the prevalence of concomitant use of gastroprotectives with NSAIDs in hospitalized patients, with emphasis on the recommended dose of gastroprotectives for ulcer prophylaxis. - - - - - METHOD: This observational, cross-sectional, drug utilization study included all adult patients receiving NSAIDs hospitalized in the Clinical Hospital Center Zagreb on the day of the study. Data on age, sex, comorbidities, indications for NSAID use, type/dose of NSAIDs and gastroprotectives, history of gastrointestinal events, active gastrointestinal symptoms and risk factors were evaluated. - - - - - MAIN OUTCOME MEASURE: Study outcomes were: (1) prevalence of prescription of gastroprotectives among NSAID-users at risk; (2) prevalence of prescription of gastroprotective in recommended dose; (3) association between risk factors and prescription of GPAs. - - - - - RESULTS: The rates of gastroprotectives prescription were significantly higher in NSAID-users with concomitant risk factors as compared to patients without risk factors [47/70 (67.1%) and 8/22 (36.4%), respectively; p = 0.01072]. However, gastroprotection in recommended ulcer-preventive dose was low in both groups [8/70 (11.4%) and 9/92 (9.8%), respectively]. The number of concomitant risk factors did not increase the odds of receiving anti-ulcer therapy (odds ratio 0.7279). Thirty-three percent of patients with concomitant risk factors were not prescribed gastroprotectives. Ibuprofen, NSAID with the lowest risk of inducing gastrointestinal complications, was prescribed in only two patients. - - - - - CONCLUSION: The results indicate high awareness among hospital physicians about possible NSAID-induced gastrointestinal complications, but insufficient knowledge about risk factors related to NSAID-induced gastrointestinal toxicity, recommended dose of gastroprotectives in NSAID-induced ulcer prophylaxis and gastrointestinal toxicity of different types of NSAIDs

Randomised positive control trial of NSAID and antimicrobial treatment for calf fever caused by pneumonia

One hundred and fifty-four preweaning calves were followed between May and October 2015. Calves were fitted with continuous monitoring temperature probes (TempVerified FeverTag), programmed so a flashing light emitting diode (LED) light was triggered following six hours of a sustained ear canal temperature of ≥39.7°C. A total of 83 calves (61.9 per cent) developed undifferentiated fever, with a presumptive diagnosis of pneumonia through exclusion of other calf diseases. Once fever was detected, calves were randomly allocated to treatment groups. Calves in group 1 (NSAID) received 2 mg/kg flunixin meglumine (Allevinix, Merial) for three consecutive days and group 2 (antimicrobial) received 6 mg/kg gamithromycin (Zactran, Merial). If fever persisted for 72 hours after the initial treatment, calves were given further treatment (group 1 received antimicrobial and group 2 received NSAID). Calves in group 1 (NSAID) were five times more likely (P=0.002) to require a second treatment (the antimicrobial) after 72 hours to resolve the fever compared with the need to give group 2 (antimicrobial) calves a second treatment (NSAID). This demonstrates the importance of ongoing monitoring and follow-up of calves with respiratory disease. However, of calves with fever in group 1 (NSAID), 25.7 per cent showed resolution following NSAID-only treatment with no detrimental effect on the development of repeated fever or daily live weight gain. This suggests that NSAID alone may be a useful first-line treatment, provided adequate attention is given to ongoing monitoring to identify those cases that require additional antimicrobial treatment

Quality of care for NSAID users: development of an assessment tool

Objective. Assessments of NSAID use based on authoritative guidelines typically overlook patients’ views and nuances of \ud medical history. Our objective was to develop an assessment tool that incorporates these aspects, and technical items, for quality of care assessments in NSAID users. \ud \ud Methods. Patients newly referred to a university hospital were interviewed by a nurse using an agreed template. A multidisciplinary group of rheumatologists, nurse specialists, primary care physicians and a pharmacist reviewed current guidance and systematic reviews on NSAID use, and a series of interview transcripts. The group agreed, by informal consensus, important determinants of effective and safe NSAID use. Technical aspects of medical care and items that reflected interpersonal care were included in an index for assessing quality of care for individual patients. Interview transcripts of 100 patients were scored by panel members and reliability of scores was tested by calculating weighted percentage agreement and the kappa statistic. \ud \ud Results. Our final index had five domains: medical risk factors; steps taken to reduce risk; knowledge of adverse effects; NSAID dose; and cost efficiency. Each item was scored 0, 1 or 2. Scores were summed, giving a maximum of 10 (low scores indicating low quality). Intra-rater agreement was >90%; kappa was 0.47–0.87 for individual domains and 0.59 for overall score. Inter-rater agreement for overall score was 95%; kappa was 0.25–0.78 for domains and 0.48 for overall score. Patients with especially low scores were identified using the mode of scores for five assessors; obvious clinical concerns were identified, supporting index face validity. \ud \ud Conclusions. A simple index to evaluate quality of care for NSAID users based on a patient interview is described. This may be used by one or more assessors to examine care standards and highlight deficiencies in relation to NSAID use in practice

Risk of myocardial infarction with use of selected nonsteroidal anti-inflammatory drugs in spondyloarthritis patients

BACKGROUND: Spondyloarthritis (SpA) is associated with increased risk of myocardial infarction (MI); the risk may be due to the underlying inflammatory disease, or also due to medications that increase MI risk, such as certain non-steroidal anti-inflammatory drugs (NSAIDs). OBJECTIVES: 1. To describe the risk of myocardial infarction (MI) among patients with spondyloarthritis who are prescribed NSAIDs 2. To compare the pattern of MI risk with specific NSAID use among spondyloarthritis patients with the pattern of risk among patients with osteoarthritis (OA) METHODS: Nested case-control studies were performed using 1994–2015 data from The Health Improvement Network (THIN). Underlying cohorts included adult patients with incident SpA or OA had >1 NSAID prescriptions and no history of MI. In each cohort, we matched cases of incident MI to four controls without MI. NSAID use was categorized as: (A) current (prescription end date 0–180 days prior to index date), (B) recent (181–365 days), or (C) remote (>365 days). We performed conditional logistic regression to compare the odds of current or recent NSAID use relative to remote use of any NSAID, considering diclofenac and naproxen specifically. RESULTS: Within the SpA cohort of 8140 and the OA cohort of 244,399, there were 115 and 6287 MI cases, respectively. After adjustment, among SpA subjects, current diclofenac use was associated with an OR of 3.05 (95% CI 1.48–6.29; Table 2) for MI. Naproxen use was not associated with any increase (adjusted OR 1.25, 95% CI 0.56–2.78). A ratio of ORs for SpA/diclofenac relative to OA/diclofenac was 2.35 (1.10–4.90).2019-06-12T00:00:00

The Misuse of Over-the-Counter NSAIDs

Over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most frequently used analgesics. The misuse of these medications occurs frequently and often without the patient’s realization. Inappropriate use can cause acute NSAID overdoses or contribute to serious adverse effects. Health care providers continue to play an important role in emphasizing the safe use of these medications. This article examines the impacts of NSAID misuse in our society and how health care professionals can help address these issues

In Silico screening of nonsteroidal anti-inflammatory drugs and their combined action on Prostaglandin H Synthase-1

The detailed kinetic model of Prostaglandin H Synthase-1 (PGHS-1) was applied to in silico screening of dose-dependencies for the different types of nonsteroidal anti-inflammatory drugs (NSAIDs), such as: reversible/irreversible, nonselective/selective to PGHS-1/PGHS-2 and time dependent/independent inhibitors (aspirin, ibuprofen, celecoxib, etc.) The computational screening has shown a significant variability in the IC50s of the same drug, depending on different in vitro and in vivo experimental conditions. To study this high heterogeneity in the inhibitory effects of NSAIDs, we have developed an in silico approach to evaluate NSAID action on targets under different PGHS-1 microenvironmental conditions, such as arachidonic acid, reducing cofactor, and peroxide concentrations. The designed technique permits translating the drug IC50, obtained in one experimental setting to another, and predicts in vivo inhibitory effects based on the relevant in vitro data. For the aspirin case, we elucidated the mechanism underlying the enhancement and reduction (aspirin resistance) of its efficacy, depending on PGHS-1 microenvironment in in vitro/in vivo experimental settings. We also present the results of the in silico screening of the combined action of sets of two NSAIDs (aspirin with ibuprofen, aspirin with celecoxib), and study the mechanism of the experimentally observed effect of the suppression of aspirin-mediated PGHS-1 inhibition by selective and nonselective NSAIDs. Furthermore, we discuss the applications of the obtained results to the problems of standardization of NSAID test assay, dependence of the NSAID efficacy on cellular environment of PGHS-1, drug resistance, and NSAID combination therapy

Older patients' prescriptions screening in the community pharmacy: development of the Ghent Older People's Prescriptions community Pharmacy Screening (GheOP3S) tool

Background: Ageing of the population often leads to polypharmacy. Consequently, potentially inappropriate prescribing (PIP) becomes more frequent. Systematic screening for PIP in older patients in primary care could yield a large improvement in health outcomes, possibly an important task for community pharmacists. In this article, we develop an explicit screening tool to detect relevant PIP that can be used in the typical community pharmacy practice, adapted to the European market. Methods: Eleven panellists participated in a two-round RAND/UCLA (Research and Development/University of California, Los Angeles) process, including a round zero meeting, a literature review, a first written evaluation round, a second face-to-face evaluation round and, finally, a selection of those items that are applicable in the contemporary community pharmacy. Results: Eighteen published lists of PIP for older patients were retrieved from the literature, mentioning 398 different items. After the two-round RAND/UCLA process, 99 clinically relevant items were considered suitable to screen for in a community pharmacy practice. A panel of seven community pharmacists selected 83 items, feasible in the contemporary community pharmacy practice, defining the final GheOP3S tool. Conclusion: A novel explicit screening tool (GheOP3S) was developed to be used for PIP screening in the typical community pharmacy practice

Risk of acute myocardial infarction with nonselective non-steroidal anti-inflammatory drugs: a meta-analysis

The use of cyclo-oxygenase 2 selective nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of acute myocardial infarction (AMI). The association between the risks of AMI with nonselective NSAIDs is less clear. We reviewed the published evidence and assessed the risk of AMI with nonselective NSAIDs. We performed a meta-analysis of all studies containing data from population databases that compared the risk of AMI in NSAID users with that in non-users or remote NSAID users. The primary outcome was objectively confirmed AMI. Fourteen studies met predefined criteria for inclusion in the meta-analysis. Nonselective NSAIDs as a class was associated with increased AMI risk (relative AMI risk 1.19, 95% confidence interval [CI] 1.08 to 1.31). Similar findings were found with diclofenac (relative AMI risk 1.38, 95% CI 1.22–1.57) and ibuprofen (relative AMI risk 1.11, 95% CI 1.06 to 1.17). However, this effect was not observed with naproxen (relative AMI risk 0.99, 95% CI 0.88–1.11). In conclusion, based on current evidence, there is a general direction of effect, which suggests that at least some nonselective NSAIDs increase AMI risk. Analysis based on the limited data available for individual NSAIDs, including diclofenac and ibuprofen, supported this finding; however, this was not the case for naproxen. Nonselective NSAIDs are frequently prescribed, and so further investigation into the risk of AMI is warranted because the potential for harm can be substantial

Use of Non-Steroidal Anti-Inflammatory Drugs That Elevate Cardiovascular Risk: An Examination of Sales and Essential Medicines Lists in Low-, Middle-, and High-Income Countries

PMCID: PMC3570554This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited