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      Association between NSAID use and mortality risk in patients with end-stage renal disease: a population-based cohort study

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          Abstract

          Background: Pain is one of the most common symptoms experienced by patients with end-stage renal disease. Although NSAIDs may lead to adverse events, NSAID use appears to be considerably high in patients with end-stage renal disease. However, whether NSAID use is associated with an increased risk of mortality in this population remains unknown.

          Aim: This study aimed to investigate the association between the use of NSAIDs and the risk of mortality in patients with end-stage renal disease.

          Patients and methods: We used the population-based Taiwan National Health Insurance Research Database to investigate the association between the use of NSAIDs and the risk of mortality in patients with end-stage renal disease receiving dialysis. A total of 3,383 patients with newly diagnosed end-stage renal disease requiring long-term dialysis between 1998 and 2012 were included in the current study, and the study outcome was evaluated until December 31, 2013. Time-dependent Cox regression models were applied to examine the association between NSAID use and mortality risk.

          Results: In the study cohort, 2,623 (78%) patients used NSAIDs during the follow-up period. The median follow-up period was 4.0 years, during which 1,515 patients died. The results of multivariable analysis demonstrated that compared with NSAID nonuse, the use of any NSAIDs, nonselective NSAIDs, and selective cyclooxygenase-2 inhibitors was associated with a significantly increased risk of all-cause mortality with an adjusted HR (95% CI) of 1.39 (1.21–1.60), 1.36 (1.19–1.55), and 1.61 (1.42–1.83), respectively.

          Conclusion: The results suggest that NSAID use was associated with an increased risk of mortality in the patients with end-stage renal disease. Future randomized controlled trials are needed to validate these observational findings.

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          Most cited references30

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          Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis

          Objective To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs. Design Network meta-analysis. Data sources Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data. Study selection All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility. Data extraction The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data. Data synthesis 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death. Conclusions Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.
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            The prevalence of symptoms in end-stage renal disease: a systematic review.

            Symptoms in end-stage renal disease (ESRD) are underrecognized. Prevalence studies have focused on single symptoms rather than on the whole range of symptoms experienced. This systematic review aimed to describe prevalence of all symptoms, to better understand total symptom burden. Extensive database, "gray literature," and hand searches were undertaken, by predefined protocol, for studies reporting symptom prevalence in ESRD populations on dialysis, discontinuing dialysis, or without dialysis. Prevalence data were extracted, study quality assessed by use of established criteria, and studies contrasted/combined to show weighted mean prevalence and range. Fifty-nine studies in dialysis patients, one in patients discontinuing dialysis, and none in patients without dialysis met the inclusion criteria. For the following symptoms, weighted mean prevalence (and range) were fatigue/tiredness 71% (12% to 97%), pruritus 55% (10% to 77%), constipation 53% (8% to 57%), anorexia 49% (25% to 61%), pain 47% (8% to 82%), sleep disturbance 44% (20% to 83%), anxiety 38% (12% to 52%), dyspnea 35% (11% to 55%), nausea 33% (15% to 48%), restless legs 30% (8%to 52%), and depression 27% (5%to 58%). Prevalence variations related to differences in symptom definition, period of prevalence, and level of severity reported. ESRD patients on dialysis experience multiple symptoms, with pain, fatigue, pruritus, and constipation in more than 1 in 2 patients. In patients discontinuing dialysis, evidence is more limited, but it suggests they too have significant symptom burden. No evidence is available on symptom prevalence in ESRD patients managed conservatively (without dialysis). The need for greater recognition of and research into symptom prevalence and causes, and interventions to alleviate them, is urgent.
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              Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes.

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                Author and article information

                Journal
                Clin Epidemiol
                Clin Epidemiol
                CLEP
                clinepid
                Clinical Epidemiology
                Dove
                1179-1349
                31 May 2019
                2019
                : 11
                : 429-441
                Affiliations
                [1 ] Department of Anesthesiology, Taipei Medical University Hospital , Taipei, Taiwan
                [2 ] Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University , Taipei, Taiwan
                [3 ] Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University , Taipei, Taiwan
                [4 ] Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital , Taipei, Taiwan
                [5 ] Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University , Taipei, Taiwan
                Author notes
                Correspondence: Yuan-Wen LeeDepartment of Anesthesiology, Taipei Medical University Hospital, No. 252, Wuxing St., Taipei11031, TaiwanTel +88622737 2181 ext. 8310Fax +886 2 2736 7344Email m102093020@ 123456tmu.edu.tw
                Article
                204322
                10.2147/CLEP.S204322
                6549765
                31213924
                cb589897-39f7-44f9-aec6-95bd42124804
                © 2019 Lai et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 06 February 2019
                : 02 May 2019
                Page count
                Figures: 2, Tables: 4, References: 40, Pages: 13
                Categories
                Original Research

                Public health
                end-stage renal disease,nsaids,mortality
                Public health
                end-stage renal disease, nsaids, mortality

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