Non-steroidal anti-inflammatory drugs and risk of acute adverse renal outcomes in diabetes and diabetic kidney disease

BACKGROUND: Individuals with diabetes mellitus (DM) may be susceptible to non-steroidal anti-inflammatory drug (NSAID) – induced acute kidney injury (AKI) but data on NSAID-related adverse renal events is sparse. We aimed to evaluate the risk of acute kidney injury and/or hyperkalemia after systemic NSAID among individuals with DM and diabetic chronic kidney disease (CKD). METHODS: Retrospective cohort study of 3896 adults with DM with incident prescriptions between July 2015 and December 2017 from Singapore General Hospital and SingHealth Polyclinics. Laboratory, hospitalization and medication data were retrieved from electronic medical records. The primary outcome was the incidence of AKI and/ or hyperkalemia within 30 days after prescription. RESULTS: AKI and/or hyperkalemia occurred in 13.5% of all DM and 15.8% of diabetic CKD. The association between systemic NSAID >14 days and 30-day risk of AKI and/or hyperkalemia failed to reach statistical significance in unselected DM (adjusted OR 1.62, 95% CI 0.99–2.65, p = 0.05) and diabetic CKD (adjusted OR 0.64, 95% CI 0.15–2.82, p = 0.64), but the odds of AKI and/or hyperkalemia were markedly and significantly increased when NSAID was prescribed with renin-angiotensin-aldosterone system (RAAS) blocker (adjusted OR 4.17, 95% CI 1.74–9.98, p = 0.001) or diuretic (adjusted OR 3.31, 95% CI 1.09–10.08, p = 0.04) and in the absence of diabetic CKD (adjusted OR 1.98, 95% CI 1.16–3.36, p = 0.01). CONCLUSION: NSAID prescription >14 days in individuals with DM with concurrent RAAS blockers or diuretics was associated with higher 30-day risk of AKI and/or hyperkalemia.

MO187NON-STEROIDAL ANTI-INFLAMMATORY DRUG PRESCRIPTION IN THE YOUNG-OLD AND VERY- OLD: TYPE, ROUTE AND BURDEN OF CARDIOVASCULAR RISK FACTORS

Background and Aims Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with cardiovascular and kidney adverse effects, especially in older adults. However, NSAIDs are still frequently prescribed to some at-risk groups. We aimed to evaluate the burden of traditional cardiovascular risk factors and pattern of NSAID prescription in the very-old and young-old. Method Cross-sectional study of older adults who received prescriptions over 3 years from a large healthcare cluster in Singapore. Individuals aged 65-79 years were the “young-old” and those ≥80 years were the “very-old”. Prescriptions and traditional cardiovascular risk factors were retrieved from electronic records. Results Among 197,932 older adults (including 41,079 very-old), 49.9% received at least 1 NSAID prescription. Topical NSAIDs were more frequently prescribed among the 19,979 very-old with NSAID prescriptions (91.5% versus 82.9% of the young-old), while oral non-selective (22.1% versus 38.5%) and selective NSAID (15.1% versus 24.9%) were less frequently prescribed compared to the young-old (all p<0.001). The very-old with NSAID prescriptions were more likely to have diabetes (38.2% vs. 32.8%), hypertension (19.3% vs. 14.0%), chronic kidney disease (51.4% vs. 23.6%) and cardiovascular disease (7.0% vs. 3.8%) than the young-old with NSAID prescriptions (all p<0.001). Table 1 shows that among the very-old, the odds of receiving oral non-selective NSAIDs was significantly lower in those with cardiovascular disease, while the odds of receiving oral COX II inhibitors was significantly higher in female and hypertension. Among the young-old, the odds of receiving oral non-selective NSAID was lower in those with cardiovascular disease, diabetes and chronic kidney disease, while the odds of receiving oral COX II inhibitors was higher in female, hypertension, cardiovascular disease and lower in diabetes and chronic kidney disease. Conclusion This study highlights that NSAIDs were frequently prescribed among older adults with comorbidities that may predispose to NSAID-associated adverse events. Physician education and policies are required to avoid potentially inappropriate prescriptions.

Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts

ObjectivesTo assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform.MethodsWe conducted two cohort studies from 1 March to 14 June 2020. Working on behalf of National Health Service England, we used routine clinical data in England linked to death data. In study 1, we identified people with an NSAID prescription in the last 3 years from the general population. In study 2, we identified people with rheumatoid arthritis/osteoarthritis. We defined exposure as current NSAID prescription within the 4 months before 1 March 2020. We used Cox regression to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region.ResultsIn study 1, we included 536 423 current NSAID users and 1 927 284 non-users in the general population. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, we included 1 708 781 people with rheumatoid arthritis/osteoarthritis, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, we observed a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with current use of NSAID versus non-use.ConclusionsWe found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.

OpenSAFELY: Do adults prescribed Non-steroidal anti-inflammatory drugs have an increased risk of death from COVID-19?

Importance: There has been speculation that non-steroidal anti-inflammatory drugs (NSAIDs) may negatively affect coronavirus disease 2019 (COVID-19) outcomes, yet clinical evidence is limited. Objective: To assess the association between NSAID use and deaths from COVID-19 using OpenSAFELY, a secure analytical platform. Design: Two cohort studies (1st March-14th June 2020). Setting: Working on behalf of NHS England, we used routine clinical data from >17 million patients in England linked to death data from the Office for National Statistics. Participants: Study 1: General population (people with an NSAID prescription in the last three years). Study 2: people with rheumatoid arthritis/osteoarthritis. Exposures: Current NSAID prescription within the 4 months before 1st March 2020. Main Outcome and Measure: We used Cox regression to estimate hazard ratios (HRs) for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, adjusting for age, sex, comorbidities and other medications. Results: In Study 1, we included 535,519 current NSAID users and 1,924,095 non-users in the general population. The crude HR for current use was 1.25 (95% CI, 1.07-1.46), versus non-use. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR, 0.95, 95% CI, 0.80-1.13) in the fully adjusted model. In Study 2, we included 1,711,052 people with rheumatoid arthritis/osteoarthritis, of whom 175,631 (10%) were current NSAID users. The crude HR for current use was 0.43 (95% CI, 0.36-0.52), versus non-use. In the fully adjusted model, we observed a lower risk of COVID-19 related death (HR, 0.78, 95% CI, 0.65-0.94) associated with current use of NSAID versus non-use. Conclusion and Relevance: We found no evidence of a harmful effect of NSAIDs on COVID-19 related deaths. Risks from COVID-19 do not need to influence decisions about therapeutic use of NSAIDs.

AB0635 HOW ARE NON STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAID) PRESCRIBED IN AXIAL SPONDYLOARTHRITIS?

Background:For decades, NSAID have been used as the first-line drugs to treat axial spondyloarthritis (ax-SpA). However, the NSAID prescription strategy is not clearly detailed and it varies from one clinician to another.Objectives:The aim of this study was to assess the NSAID prescription modalities adopted in ax-SpA and the differences between these modalities.Methods:This is a descriptive study including 200 cases of ax-SpA fulfilling the ASAS 2009 criteria and diagnosed between January 2000 and October 2019. The demographic and clinical features of the ax-SpA were collected and the modalities of prescription of NSAID were retrospectively assessed.Results:Our population consists of 138 men and 62 women with a mean age of 43,3 ± 11,2 years. The HLA B-27 antigen was present in 50,8% of cases. The ax-SpA was a pure axial form in 67% of patients, associated with peripheral arthritis, enthesitis and dactylitis in 19%, 21,5% and 1,5% respectively.One hundred eighty patients (90%) had been treated with NSAIDs. The NSAIDs used were: the Diclofenac (57.5%), Indomethacin (37.5%), Piroxicam (36%), clecoxib (34%), Naproxen (29.5%) and ketoprofen (13%). Seventy-three patients (36.5%) had used at least 3 NSAIDs.Among the 180 patients treated with NSAID, 88 patients (48,8%) were treated with conventional synthetic DMARDs (csDMARDs) in association with NSAID: Salazopyrine (43,3%) and Methotrexate (13,3%). Seventy-one patients (39,4%) had necessitated the use of anti-TNF alpha.NSAIDs were used continuously in 115 patients (63.8%) and the maximum dose of NSAIDs was used in 78 patients (43.3%). By comparing patients who used maximum doses of NSAIDs and those who used NSAID continuously with other patients, we noticed that the use of biological treatments was more frequent in those groups (p = 0,01 and p=0,004 respectively).In addition, while comparing the group of patients co-treated with csDMARDs with other patients treated with NSAID on monotherapy, we noted that this group of patients had more arthritis (p<0,0001), enthesitis (p=0,02), psoriasis (p=0,04) and necessitated more biological treatments (p=0,01).Conclusion:Our results suggest that maximal doses and/or continuous prescription of NSAID were mainly used if there was no response to that treatment. The csDMARDs were more prescribed if there were peripheral manifestations or psoriatic arthritis and those forms were also more candidates to biological treatments.References:[1]Wang R, et al. Arthritis Rheumatol Hoboken NJ. 2019;Disclosure of Interests:None declared

Details of the Use of Non-steroidal Anti-inflammatory Drugs in Comorbid Patients. Ways to Minimise the Risks of NSAID-induced GIT Complications

Objective of the Review: to discuss the most common adverse events from the use of non-steroidal anti-inflammatory drugs (NSAID) for GIT: NSAID-induced esophago-, gastroduodeno- and enteropathy, possible management and the use of various therapies in order to minimize the risks of this pathology. Key Points. NSAIDs are efficient analgetics and anti-inflammatory products widely used in clinical setting. NSAIDs are prescribed mostly to patients with chronic joint and spine conditions. As a lot of patients who take NSAIDs are comorbid, they have frequent adverse reactions to drugs, including NSAIDs, and need stricter control if this is a therapy of choice. Selective NSAIDs (nimesulide) are characterised by good bioavailability; they are efficient pain killers, possess marked anti-inflammatory properties and are relatively safe, thus making it possible to minimise the rate of adverse reactions for GIT. Conclusion. It should be emphasised that the issue of NSAID-induced GIT disorders is still challenging and can be aggravated in comorbid patients. Of prime importance are timely prevention and diagnosis of NSAID-induced GIT disorders and sustainable and individuated NSAID prescription. Keywords: non-steroidal anti-inflammatory drugs, comorbidity, NSAID-induced gastroduodenopathy, NSAID-induced enteropathy, nimesulide, Nise

Conhecimentos dos Pacientes da Clínica Escola de Fisioterapia Sobre o Uso de Anti-Inflamatórios Não Esteroidais (AINE)

Atualmente, observa-se que os medicamentos estão presentes praticamente no cotidiano de todos os indivíduos, presentes não somente nos consultórios e hospitais, mas também nos lares, sendo que a maioria destes não precisam de prescrições médicas. Os anti-inflamatórios não esteroides (AINE) estão entre as classes medicamentosas mais utilizadas no mundo, sobretudo para tratar inflamação, dor e edema, osteoartrites, artrite reumatoide e distúrbios musculoesqueléticos. O objetivo deste estudo foi identificar a utilização e o nível de conhecimento sobre as possíveis reações adversas dos AINE, pelos pacientes da Clínica Escola de Fisioterapia da Faculdade Anhanguera de Sorocaba. Foi realizado um estudo transversal, quantitativo, por meio da aplicação de um questionário investigativo. Foram incluídos no estudo pacientes adultos, homens e mulheres, que deram início ao tratamento de fisioterapia. No estudo, 88,33% dos pacientes acreditam que os AINE aliviam a dor e 85% responderam que receberam uma prescrição de AINE durante o atual tratamento. Quando indagados quanto a eficácia do uso de AINE concomitante com a fisioterapia, 65% responderam que os anti-inflamatórios ajudaram no tratamento com o alívio da dor. Sobre os problemas de saúde relacionados ao uso prolongado de AINEs, 61,66% responderam que possuem conhecimento. O uso crônico de AINE é acompanhado de diversos efeitos colaterais e adversos, os quais devem ser sempre alertados aos usuários, fato esse não observado neste estudo de acordo com as respostas dos participantes do estudo. Palavras-chave: Inflamação. Sistema Osteomuscular. Automedicação. AbstractCurrently, it is observed that medicines are present almost on a daily basis of all individuals, present not only in clinics and hospitals, but also in homes, being that most of these do not require medical prescriptions. The non-steroid anti-inflammatory drugs (NSAIDS) are among the most widely used drug classes in the world, especially to treat inflammation, pain and edema, osteoarthritis, rheumatoid arthritis and musculoskeletal disorders. The objective of this study was to identify the use and the level of knowledge about the possible adverse reactions of NSAIDS, by patients of the Clinic School of Physiotherapy at Faculdade Anhanguera Sorocaba. A cross-sectional, quantitative study was conducted, through the application of an investigative questionnaire. Patients included in the study were adults, men and women, who started the physiotherapy treatment. In the study, 88.33% of patients believe that NSAIDS relieve pain and 85% responded that they received an NSAID prescription during the current treatment. When asked about the effectiveness of the use of NSAID concomitantly with physiotherapy, 65% responded that the anti-inflammatories helped in dealing with the pain relief. About the health problems concerning the prolonged use of NSAIDS, 61.66% answered that they are aware of. The chronic use of NSAIDS is accompanied by various adverse and side effects, which should always be alerted to the users, fact which was not observed in this study, according to the study participants’ answers. Keywords: Inflammation. Musculoskeletal System. Self-Medication.

Further effort is needed to improve management of chronic pain in primary care. Results from the Arkys project

Treatment of chronic pain is challenging. The Arkys project was initiated in Italy to assist general practitioners (GPs) in the management of chronic pain. The main objective of this study was to determine the usefulness of Arkys for selecting new therapeutic strategies. An online interactive questionnaire for assessing pain and guiding therapeutic decisions was made available to GPs participating to Arkys. The GPs were invited to complete the questionnaire for each patient who presented moderate-severe chronic pain, and to decide on a new analgesic treatment based on the information provided by the questionnaire. Two hundred and forty four GPs participated with a total of 3035 patients. Patients (mean age 68.9 years) had mostly chronic non-cancer pain (87.7%). In 42.3%, pain had neuropathic components. Only 53.6% of patients were in treatment with analgesics (strong opioids, 38.9%; NSAIDs, 32.6%; weak opioids, 25.6%; anti-epileptics, 17.3%; paracetamol, 14.9%). Use of the questionnaire resulted in the prescription of analgesics to all patients and in increased prescription of strong opioids (69.7%). NSAID prescription decreased (12.8%), while anti-epileptics use remained stable. These findings show that current management of chronic pain in primary care is far from optimal and that efforts are needed to educate GPs and improve guideline implementation.