|
1
|
Fischbach W, Bornschein J, Hoffmann JC, Koletzko S, Link A, Macke L, Malfertheiner P, Schütte K, Selgrad DM, Suerbaum S, Schulz C. Update S2k-Guideline Helicobacter pylori and gastroduodenal ulcer disease of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:261-321. [PMID: 38364851 DOI: 10.1055/a-2181-2225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/18/2024]
Affiliation(s)
| | - Jan Bornschein
- Translational Gastroenterology Unit John, John Radcliffe Hospital Oxford University Hospitals, Oxford, United Kingdom
| | - Jörg C Hoffmann
- Medizinische Klinik I, St. Marien- und St. Annastiftskrankenhaus, Ludwigshafen, Deutschland
| | - Sibylle Koletzko
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU-Klinikum Munich, Munich, Deutschland
- Department of Paediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, 10-719 Olsztyn, Poland
| | - Alexander Link
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Magdeburg, Magdeburg, Deutschland
| | - Lukas Macke
- Medizinische Klinik und Poliklinik II Campus Großhadern, Universitätsklinikum Munich, Munich, Deutschland
- Deutsches Zentrum für Infektionsforschung, Standort Munich, Munich, Deutschland
| | - Peter Malfertheiner
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Magdeburg, Magdeburg, Deutschland
- Medizinische Klinik und Poliklinik II Campus Großhadern, Universitätsklinikum Munich, Munich, Deutschland
| | - Kerstin Schütte
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken Marienhospital Osnabrück, Osnabrück, Deutschland
| | - Dieter-Michael Selgrad
- Medizinische Klinik Gastroenterologie und Onkologie, Klinikum Fürstenfeldbruck, Fürstenfeldbruck, Deutschland
- Klinik für Innere Medizin 1, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Sebastian Suerbaum
- Universität Munich, Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Munich, Deutschland
- Nationales Referenzzentrum Helicobacter pylori, Pettenkoferstr. 9a, 80336 Munich, Deutschland
- Deutsches Zentrum für Infektionsforschung, Standort Munich, Munich, Deutschland
| | - Christian Schulz
- Medizinische Klinik und Poliklinik II Campus Großhadern, Universitätsklinikum Munich, Munich, Deutschland
- Deutsches Zentrum für Infektionsforschung, Standort Munich, Munich, Deutschland
| |
Collapse
|
|
2
|
Zhang J, Xie M. Graph regularized non-negative matrix factorization with
L
2
,
1
norm regularization terms for drug-target interactions prediction. BMC Bioinformatics 2023; 24:375. [PMID: 37789278 PMCID: PMC10548602 DOI: 10.1186/s12859-023-05496-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Accepted: 09/22/2023] [Indexed: 10/05/2023] Open
Abstract
BACKGROUND Identifying drug-target interactions (DTIs) plays a key role in drug development. Traditional wet experiments to identify DTIs are costly and time consuming. Effective computational methods to predict DTIs are useful to speed up the process of drug discovery. A variety of non-negativity matrix factorization based methods are proposed to predict DTIs, but most of them overlooked the sparsity of feature matrices and the convergence of adopted matrix factorization algorithms, therefore their performances can be further improved. RESULTS In order to predict DTIs more accurately, we propose a novel method iPALM-DLMF. iPALM-DLMF models DTIs prediction as a problem of non-negative matrix factorization with graph dual regularization terms andL 2 , 1 norm regularization terms. The graph dual regularization terms are used to integrate the information from the drug similarity matrix and the target similarity matrix, andL 2 , 1 norm regularization terms are used to ensure the sparsity of the feature matrices obtained by non-negative matrix factorization. To solve the model, iPALM-DLMF adopts non-negative double singular value decomposition to initialize the nonnegative matrix factorization, and an inertial Proximal Alternating Linearized Minimization iterating process, which has been proved to converge to a KKT point, to obtain the final result of the matrix factorization. Extensive experimental results show that iPALM-DLMF has better performance than other state-of-the-art methods. In case studies, in 50 highest-scoring proteins targeted by the drug gabapentin predicted by iPALM-DLMF, 46 have been validated, and in 50 highest-scoring drugs targeting prostaglandin-endoperoxide synthase 2 predicted by iPALM-DLMF, 47 have been validated.
Collapse
Affiliation(s)
- Junjun Zhang
- Key Laboratory of Computing and Stochastic Mathematics(LCSM) (Ministry of Education), School of Mathematics and Statistics, Hunan Normal University, Changsha, 410081 China
| | - Minzhu Xie
- Key Laboratory of Computing and Stochastic Mathematics(LCSM) (Ministry of Education), School of Mathematics and Statistics, Hunan Normal University, Changsha, 410081 China
- College of Information Science and Engineering, Hunan Normal University, Changsha, 410081 China
| |
Collapse
|
|
3
|
Aktualisierte S2k-Leitlinie Helicobacter
pylori und gastroduodenale Ulkuskrankheit der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – Juli 2022 – AWMF-Registernummer: 021–001. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:544-606. [PMID: 37146633 DOI: 10.1055/a-1975-0414] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/07/2023]
|
|
4
|
Del-Pino M, Sanz EJ. Analysis of deprescription strategies of proton pump inhibitors in primary care: a narrative review. Prim Health Care Res Dev 2023; 24:e14. [PMID: 36788753 PMCID: PMC9971848 DOI: 10.1017/s1463423623000026] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 11/14/2022] [Accepted: 12/19/2022] [Indexed: 02/16/2023] Open
Abstract
BACKGROUND Since the introduction of omeprazole in 1989, proton pump inhibitors (PPIs) have become the mainstream of treatment for acid-related pathologies, but nowadays, it is estimated that between 20% and 80% of people worldwide who are using PPIs are doing so without an approved indication. Overusing PPIs is known to involve a tremendous cost in financial terms, and many western countries have reported high spending on these medicines. OBJECTIVE We conducted a narrative review to evaluate PPI deprescription strategies carried out entirely or in collaboration with primary care and to identify factors that could influence the success of these strategies. METHOD This review was conducted in November 2022, following PRISMA guidelines. Four databases were searched: PubMed, Web of Science, Scopus and CINAHL Complete, using the MeSH terms 'proton pump inhibitors' AND 'deprescriptions'. RESULTS The search with the established criteria found eight studies. The different success rates obtained by the various studies analysed in this review may be due to the different methodologies used when establishing the protocols, sample selection and monitoring of the results. CONCLUSION We can conclude that the two factors related to the most successful strategies were a) the clarity and simplicity of the de-escalation protocols, in which patients were instructed on the measures to follow in the event of the reappearance of symptoms, and b) the training of the physicians responsible for deprescribing. Long-term conclusions cannot be drawn about the effectiveness of these protocols, given that the studies are limited in time. Other barriers to generalizing the results are the small sample size and the absence of control groups.
Collapse
Affiliation(s)
- Miguel Del-Pino
- Servicio Canario de la Salud, Tenerife, Spain. Canary Islands
| | - Emilio J. Sanz
- Facultad de Ciencias de la Salud. Universidad de La Laguna, La Laguna, Tenerife, Spain
- Complejo Hospital Universitario de Canarias, Tenerife, Spain
| |
Collapse
|
|
5
|
Predictors for inappropriate proton pump inhibitor use: observational study in primary care. Br J Gen Pract 2022; 72:e899-e906. [DOI: 10.3399/bjgp.2022.0178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 06/20/2022] [Indexed: 10/31/2022] Open
Abstract
Background: Proton pump inhibitor (PPI) indications are limited to gastrointestinal disorders and ulcer prophylaxis. Still, PPIs are among the most frequently prescribed drugs. Aim: To evaluate the appropriateness of PPI prescriptions and identify predictive factors for inappropriate PPI use. Design and Setting: Observational study using a Dutch primary care database with all new PPI prescriptions between 2016 and 2018. Methods: Individual patient data and details on PPI use were collected. Appropriateness of initiation and continuation of PPI prescriptions was evaluated using the applicable guidelines. Results: We evaluated 148,926 patients (≥ 18 years) from 27 general practices. A total of 23,601 (16%) patients started PPI therapy (mean age 57 ± 17 years, 59% female). Valid PPI indications at initiation were seen in 10,466 PPI users (44%). Predictors for inappropriately initiated PPI use were older age (OR 1.03, 95%CI 1.03-1.03), and use of non-selective NSAIDs (OR 5.15, 95%CI 4.70-5.65), ADP receptor inhibitors (OR 5.07, 95%CI 3.46-7.41), coxibs (OR 3.93, 95%CI 2.92-5.28) and low-dose aspirin (OR 3.83, 95%CI 3.07-4.77). Despite an initial valid indication, PPI use was inaccurately continued in 32% of patients on short-course therapy for dyspepsia and in 11% of patients on ulcer prophylaxis. Conclusion: More than half of PPI users in primary care seem to have an inappropriate indication with unnecessary ulcer prophylaxis related to drug use being one of the leading causes. Future initiatives to reduce PPI use for unnecessary ulcer prophylaxis and timely deprescription if PPI is no longer indicated, are needed.
Collapse
|
|
6
|
Mahdian-Shakib A, Hashemzadeh MS, Anissian A, Oraei M, Mirshafiey A. Evaluation of the acute and 28-day sub-acute intravenous toxicity of α-l-guluronic acid (ALG; G2013) in mice. Drug Chem Toxicol 2022; 45:151-160. [PMID: 31533489 DOI: 10.1080/01480545.2019.1665679] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
α-l-Guluronic acid (ALG; G2013) has been previously introduced as a new anti-inflammatory agent with promising therapeutic effects. Thus, in the present study, we aimed to evaluate the acute and sub-acute toxicity of ALG through intravenous (i.v.) administration in Balb/C mice. ALG was administrated i.v. to the mice with doses of 300, 600, and 1000 mg/kg of body weight to investigate acute toxicity (single dose) and with doses of 25, 50, and 100 mg/kg of body weight to sub-acute toxicity study (daily injections for a period of 28 days). The mortality rate, food and water intake, behavior, body weight, gross necropsy, hematological and biochemical parameters as well as histopathological presentations of the vital organs (kidneys, liver, lungs, spleen, and heart) were examined in treated groups and compared to the healthy controls. The results of both acute and sub-acute studies showed that i.v. administrations of ALG did not affect the investigated parameters in both sexes, indicating that the LD50 of ALG was higher than 1000 mg/kg of body weight. As no difference was observed in toxicity profiles of investigated doses, no-observed-adverse-effect-level for i.v. administration of ALG in the sub-acute study was greater than 100 mg/kg body weight in both female and male mice. According to the finding, i.v. administration of ALG did not lead to any clinical sign in abovementioned doses, suggesting that ALG was well tolerated up to 1000 mg/kg. These pre-clinical findings support the application of ALG in the future clinical trials.
Collapse
Affiliation(s)
- Ahmad Mahdian-Shakib
- Applied Virology Research Centre, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | | | - Ali Anissian
- Veterinary Pathology Department, Islamic Azad University, Abhar, Iran
| | - Mona Oraei
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Mirshafiey
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
7
|
Magni A, Agostoni P, Bonezzi C, Massazza G, Menè P, Savarino V, Fornasari D. Management of Osteoarthritis: Expert Opinion on NSAIDs. Pain Ther 2021; 10:783-808. [PMID: 33876393 PMCID: PMC8586433 DOI: 10.1007/s40122-021-00260-1] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 03/27/2021] [Indexed: 12/13/2022] Open
Abstract
Osteoarthritis (OA) is a leading cause of disability among older adults worldwide. Treatment aims are to alleviate inflammatory pain and improve physical function through non-pharmacological and pharmacological interventions. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line therapy. However, selection is challenged by patient age, comorbidities and polypharmacy, and by the drug's benefit/risk balance, all of which together influence the risk of cardiovascular (CV), gastrointestinal (GI) and renal adverse events (AEs). While the efficacy profile of the various NSAIDs is delineated, the differences in their safety profile are not straightforward. This narrative review provides practical indications by a multidisciplinary Italian expert panel for general practitioners and specialists managing OA patients with chronic inflammatory pain; the goal is to maximize therapy efficacy while reducing untoward effects caused by inappropriate NSAID use. The discussion on the best approach to NSAIDs spanned the following topics: (1) patient evaluation: investigate pain origin, duration and components together with possible risk factors for CV, GI and renal AEs; (2) non-pharmacological interventions: the physiatrist provides a person-centered, holistic approach accounting for all patient aspects; (3) pharmacological interventions: patient profile and drugs' pharmacological properties affect NSAID selection, which drugs to be used in combination or to be avoided, formulation and therapy duration; (4) the pharmacologist's, general practitioner's and pain therapist's points of view; (5) NSAID safety: the individual baseline risk and the drug's safety profile are major determinants of CV, GI and renal risk; consider possible drug-drug interactions; (6) periodical re-evaluation of treatment response and adherence, using scales to assess pain and function.
Collapse
Affiliation(s)
- Alberto Magni
- Italian College of General Practitioners and Primary Care, Via Del Sansovino 179, Florence, Italy
| | - Piergiuseppe Agostoni
- Centro Cardiologico Monzino, IRCCS, Via Carlo Parea, 4, Milan, Italy ,Dipartimento di scienze cliniche e di comunità, Università degli Studi di Milano, Via Carlo Parea 4, Milan, Italy
| | - Cesare Bonezzi
- Unità di Terapia del dolore, Istituti Clinici Scientifici Maugeri, Via Salvatore Maugeri 10, Pavia, Italy
| | - Giuseppe Massazza
- Division of Physical Medicine and Rehabilitation, Department of Surgical Sciences, University of Turin, Via Zuretti 29, Turin, Italy ,“Città della Salute e della Scienza” University Hospital, Corso Bramante, 88, Turin, Italy
| | - Paolo Menè
- Division of Nephrology and Dialysis, Sant’Andrea University Hospital, “Sapienza” University of Rome, Via di Grottarossa, 1035/1039, Rome, Italy
| | - Vincenzo Savarino
- Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 6, Genoa, Italy
| | - Diego Fornasari
- Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Via Vanvitelli, 32, 20133, Milan, Italy.
| |
Collapse
|
|
8
|
Genetic variations and epigenetic modulations in CYP genes: Implications in NSAID-treatment of arthritis patients. THE NUCLEUS 2021. [DOI: 10.1007/s13237-021-00373-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
|
|
9
|
Domper Arnal MJ, Hijos-Mallada G, Lanas A. Gastrointestinal and cardiovascular adverse events associated with NSAIDs. Expert Opin Drug Saf 2021; 21:373-384. [PMID: 34376069 DOI: 10.1080/14740338.2021.1965988] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most prescribed pharmacological groups, especially in elderly patients. AREAS COVERED The main GI and CV adverse events associated with NSAID use are reviewed. Risk factors and prophylactic strategies are also covered. EXPERT OPINION COX-2 selective agents are safer to the GI tract but have a worst CV profile. On the contrary, naproxen seems safer for CV system, but it is one of the NSAIDs with higher GI toxicity. Co-therapy with aspirin reduces the GI benefits of COX-2 selective agents, whereas ibuprofen and naproxen may neglect the antiplatelet effect of aspirin. NSAIDs increase the risk of both upper and lower GI complications. Co-therapy with PPI reduces the risk of upper but not lower GI complications, and seems to induce dysbiosis in the small bowel, which may be implicated in the damage induced by NSAIDs. Celecoxib, a COX-2 selective agent, seems safer for both the upper and the lower GI tract. Prescription of type and dose of NSAIDs must be individualized based on the stratification of the CV and GI risk of patients.
Collapse
Affiliation(s)
- María-José Domper Arnal
- Service of Digestive Diseases, University Clinic Hospital, Zaragoza, Spain.,Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain
| | - Gonzalo Hijos-Mallada
- Service of Digestive Diseases, University Clinic Hospital, Zaragoza, Spain.,Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain
| | - Angel Lanas
- Service of Digestive Diseases, University Clinic Hospital, Zaragoza, Spain.,Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain.,University of Zaragoza, Zaragoza, Spain.,CIBERehd, Madrid, Spain
| |
Collapse
|
|
10
|
McEvoy L, Carr DF, Pirmohamed M. Pharmacogenomics of NSAID-Induced Upper Gastrointestinal Toxicity. Front Pharmacol 2021; 12:684162. [PMID: 34234675 PMCID: PMC8256335 DOI: 10.3389/fphar.2021.684162] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 05/11/2021] [Indexed: 12/19/2022] Open
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of drugs which are widely used globally for the treatment of pain and inflammation, and in the case of aspirin, for secondary prevention of cardiovascular disease. Chronic non-steroidal anti-inflammatory drug use is associated with potentially serious upper gastrointestinal adverse drug reactions (ADRs) including peptic ulcer disease and gastrointestinal bleeding. A few clinical and genetic predisposing factors have been identified; however, genetic data are contradictory. Further research is needed to identify clinically relevant genetic and non-genetic markers predisposing to NSAID-induced peptic ulceration.
Collapse
Affiliation(s)
- L McEvoy
- Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom
| | - D F Carr
- Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom
| | - M Pirmohamed
- Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom
| |
Collapse
|
|
11
|
Affiliation(s)
- Mohammad Bilal
- Center for Advanced Endoscopy, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Marwan S Abougergi
- Catalyst Medical Consulting, Simpsonville, South Carolina, USA; Division of Gastroenterology, Department of Internal Medicine, University of South Carolina School of Medicine, Columbia, South Carolina, USA
| |
Collapse
|
|
12
|
GİŞİ K, İSPİROĞLU M, KANTARÇEKEN B. NSAID Kullanan Her Hastada Gastrik Profilaksi Gerekli mi? KAHRAMANMARAŞ SÜTÇÜ İMAM ÜNIVERSITESI TIP FAKÜLTESI DERGISI 2020. [DOI: 10.17517/ksutfd.671049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
|
|
13
|
Khadem Azarian S, Jafarnezhad-Ansariha F, Nazeri S, Azizi G, Aghazadeh Z, Hosseinzadeh E, Mirshafiey A. Effects of guluronic acid, as a new NSAID with immunomodulatory properties on IL-17, RORγt, IL-4 and GATA-3 gene expression in rheumatoid arthritis patients. Immunopharmacol Immunotoxicol 2019; 42:22-27. [PMID: 31856612 DOI: 10.1080/08923973.2019.1702053] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Aim: Rheumatoid arthritis (RA) is a prevalent inflammatory, autoimmune diseases characterized by inflammation and destruction of joints. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can have modulatory interference in disease process. In this study, the effect of Guluronic Acid (G2013) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunomodulatory effects was evaluated on IL-17, RORγt, IL-4 and GATA-3 gene expression in RA patients.Methods: Fourteen patients with RA who had an inadequate response to conventional treatments were included in this clinical trial. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. G2013 was administered orally at dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected before and after treatment to evaluate the gene expression levels of IL-4, GATA-3, IL-17 and RORγt.Results: Primary and secondary efficacy endpoints and Disease Activity Score (DAS) 28 showed an improvement after 12 weeks of treatment. G2013 has a potent efficacy on gene expression of these molecules, so that it could decrease IL-17 and RORγt levels and increase IL-4 and GATA-3 levels after 12 weeks of treatment. Reduction of IL-17 was statistically non-significant whereas for its transcription factor (RORγt) was statistically significant. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments.Conclusion: G2013 as a natural novel drug showed a significant increase on IL-4 and GATA-3 and a significant decrease on RORγt gene expression after 12 weeks oral administration of this drug in RA patients. (Clinical trial identifier: IRCT2016092813739N5).
Collapse
Affiliation(s)
- Shahin Khadem Azarian
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.,Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | | | - Sepideh Nazeri
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Gholamreza Azizi
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Zahra Aghazadeh
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Elham Hosseinzadeh
- Department of Molecular Imaging, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Abbas Mirshafiey
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
14
|
Lanas-Gimeno A, Hijos G, Lanas Á. Proton pump inhibitors, adverse events and increased risk of mortality. Expert Opin Drug Saf 2019; 18:1043-1053. [DOI: 10.1080/14740338.2019.1664470] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
| | - Gonzalo Hijos
- Servicio de Aparato Digestivo, Hospital Clínico Universitario, Zaragoza, Spain
- Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain
| | - Ángel Lanas
- Servicio de Aparato Digestivo, Hospital Clínico Universitario, Zaragoza, Spain
- Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain
- CIBERehd, Madrid, Spain
- Department of Medicine, Universidad de Zaragoza, Zaragoza, Spain
| |
Collapse
|
|
15
|
Feuerherm AJ, Dennis EA, Johansen B. Cytosolic group IVA phospholipase A2 inhibitors, AVX001 and AVX002, ameliorate collagen-induced arthritis. Arthritis Res Ther 2019; 21:29. [PMID: 30665457 PMCID: PMC6341602 DOI: 10.1186/s13075-018-1794-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Accepted: 12/11/2018] [Indexed: 02/08/2023] Open
Abstract
Background Cytosolic phospholipase A2 group IVA (cPLA2α)-deficient mice are resistant to collagen-induced arthritis, suggesting that cPLA2α is an important therapeutic target. Here, the anti-inflammatory effects of the AVX001 and AVX002 cPLA2α inhibitors were investigated. Methods In vitro enzyme activity was assessed by a modified Dole assay. Effects on inhibiting IL-1β-induced release of arachidonic acid (AA) and prostaglandin E2 (PGE2) were measured using SW982 synoviocyte cells. In vivo effects were studied in prophylactic and therapetic murine collagen-induced arthritis models and compared to methotrexate (MTX) and Enbrel, commonly used anti-rheumatic drugs. The in vivo response to treatment was evaluated in terms of the arthritis index (AI), histopathology scores and by plasma levels of PGE2 following 14 and 21 days of treatment. Results Both cPLA2α inhibitors are potent inhibitors of cPLA2α in vitro. In synoviocytes, AVX001 and AVX002 reduce, but do not block, release of AA or PGE2 synthesis. In both CIA models, the AI and progression of arthritis were significantly lower in the mice treated with AVX001, AVX002, Enbrel and MTX than in non- treated mice. Several histopathology parameters of joint damage were found to be significantly reduced by AVX001 and AVX002 in both prophylactic and therapeutic study modes; namely articular cavity and peripheral tissue inflammatory cell infiltration; capillary and synovial hyperplasia; articular cartilage surface damage; and periostal and endochondral ossification. In comparison, MTX did not significantly improve any histopathology parameters and Enbrel only improved ossification. Finally, as a biomarker of inflammation and as an indication that AVX001 and AVX002 blocked the cPLA2α target, we determined that plasma levels of PGE2 were significantly reduced in response to the AVX inhibitors and MTX, but not Enbrel. Conclusions AVX001 and AVX002 display potent anti-inflammatory activity and disease-modifying properties in cellular and in vivo models. The in vivo effects of AVX001 and AVX002 were comparable to, or superior, to those of MTX and Enbrel. Taken together, this study suggests that cPLA2α inhibitors AVX001 and AVX002 are promising small molecule disease-modifying anti-rheumatic therapies.
Collapse
Affiliation(s)
- A J Feuerherm
- Department of Biology, Norwegian University of Science and Technology, N-7491, Trondheim, Norway
| | - E A Dennis
- Department of Chemistry and Biochemistry, University of California-San Diego, La Jolla, California, 92093-0601, USA.,Department of Pharmacology, School of Medicine, University of California-San Diego, La Jolla, California, 92093-0601, USA
| | - B Johansen
- Department of Biology, Norwegian University of Science and Technology, N-7491, Trondheim, Norway.
| |
Collapse
|
|
16
|
|
|
17
|
Savarino V, Marabotto E, Zentilin P, Furnari M, Bodini G, De Maria C, Pellegatta G, Coppo C, Savarino E. Proton pump inhibitors: use and misuse in the clinical setting. Expert Rev Clin Pharmacol 2018; 11:1123-1134. [PMID: 30295105 DOI: 10.1080/17512433.2018.1531703] [Citation(s) in RCA: 118] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION The introduction of proton pump inhibitors (PPIs) into clinical practice has greatly improved our therapeutic approach to acid-related diseases for their efficacy and safety. Areas Covered: The following evidence-based indications for PPI use are acknowledged by many scientific societies: treatment of the various forms and complications of gastroesophageal reflux disease, eradication of H. pylori infection in combination with two or more antibiotics, short- and long-term therapy of H. pylori-negative peptic ulcers, healing, and prevention of NSAID/COXIB-associated gastric ulcers, co-therapy with endoscopic procedures to control upper digestive bleeding and medical treatment of Zollinger Ellison syndrome. Expert Commentary: Despite the above well-defined indications, however, the use of PPIs continues to grow every year in both western and eastern countries and the endless expansion of the PPI market has created important problems for many regulatory authorities for two relevant features: the progressive increase of the costs of therapy and the greater potential harms for the patients. The major reasons for the misuse of PPIs are the prevention of gastro-duodenal ulcers in patients without risk factors and the stress ulcer prophylaxis in non-intensive care units, steroid therapy alone, anti-platelet or anti-coagulant treatment in patients without risk of gastric injury and the overtreatment of functional dyspepsia.
Collapse
Affiliation(s)
- Vincenzo Savarino
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Elisa Marabotto
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Patrizia Zentilin
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Manuele Furnari
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Giorgia Bodini
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Costanza De Maria
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Gaia Pellegatta
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Claudia Coppo
- a Gastrointestinal Unit, Department of Internal Medicine , University of Genoa , Genoa , Italy
| | - Edoardo Savarino
- b Gastrointestinal Unit, Department of Surgery , Oncology and Gastroenterology, University of Padua , Padua , Italy
| |
Collapse
|
|
18
|
Savarino V, Tosetti C, Benedetto E, Compare D, Nardone G. Appropriateness in prescribing PPIs: A position paper of the Italian Society of Gastroenterology (SIGE) - Study section "Digestive Diseases in Primary Care". Dig Liver Dis 2018; 50:894-902. [PMID: 30093304 DOI: 10.1016/j.dld.2018.07.004] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2018] [Revised: 07/04/2018] [Accepted: 07/09/2018] [Indexed: 02/06/2023]
Abstract
The introduction of proton pump inhibitors (PPIs) into clinical practice about thirty years ago has greatly improved our therapeutic approach to acid-related diseases for their well-recognized efficacy and safety. Despite the well-defined indications, however, the use of PPIs continues to grow every year in both western and eastern countries and this phenomenon poses serious queries that include the onset of potential adverse effects and the increase in health care costs. The major reason explaining this worrying market expansion is the inappropriate use of PPIs. In order to re-establish a correct use of these effective drugs in daily clinical practice, the Italian Society of Gastroenterology (SIGE), nominated a panel of experts who reviewed the available clinical literature and produced a series of updated position statements on the use of PPIs in clinical practice.
Collapse
Affiliation(s)
| | | | | | - Debora Compare
- Department of Clinical Medicine and Surgery, University Federico II of Naples, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, University Federico II of Naples, Italy.
| |
Collapse
|
|
19
|
Chi TY, Zhu HM, Zhang M. Risk factors associated with nonsteroidal anti-inflammatory drugs (NSAIDs)-induced gastrointestinal bleeding resulting on people over 60 years old in Beijing. Medicine (Baltimore) 2018; 97:e0665. [PMID: 29718891 PMCID: PMC6392961 DOI: 10.1097/md.0000000000010665] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 04/16/2018] [Indexed: 12/15/2022] Open
Abstract
Gastrointestinal (GI) bleeding is an unwanted side effect common to all chemical types of nonsteroidal anti-inflammatory drugs (NSAIDs), particularly in elderly people. However, the risk factors of GI bleeding associated with NSAIDs for elderly people remain unknown. This study aims to evaluate the risks of GI bleeding associated with NSAIDs in 4728 elderly people over 60 years old based on database from a hospital in Beijing.This retrospective hospital-based study included 4728 patients over 60 years old prescribed with NSAIDs, of which 928 patients had GI bleeding and 3800 did not have. Odds ratios (OR) for the risk of GI bleeding associated with NSAIDs were determined by logistic regression analysis. Mean Decrease Gini (MDG) involved in random forest algorithm was used to rank the associated factors with GI bleeding.In multivariate analysis, family history of GI bleeding (OR, 3.348; P = .000), history of peptic ulcers (OR, 4.068; P = .000), history of cardiovascular and cerebrovascular disease (OR, 1.476; P = .001), diabetes mellitus (OR, 1.408; P = .000), antiplatelet drugs (OR, 3.106; P = .000), Helicobacter pylori infection (OR, 1.312; P = .001), cholesterol level (OR, 0.516; P = .000), upper abdominal discomfort (OR, 3.467; P = .000), anorexia (OR, 2.038; P = .000), and NSAIDs used for 0.5 to 3 months (OR, 0.780; P = .000) were associated with GI bleeding. After ranked the MDG of each factor, the top 5 ranked factors associated with GI bleeding were melena, hematemesis, antiplatelet drugs, cholesterol level, and upper abdominal discomfort.We found that family history of GI bleeding, history of peptic ulcers, history of cardiovascular and cerebrovascular disease, diabetes mellitus, antiplatelet drugs, Helicobacter pylori infection, hypocholesterolemia, and NSAIDs used for 0.5 to 3 months were independent risk factors for GI bleeding on people over 60 years old. Meanwhile, upper abdominal discomfort might be the predictor of GI bleeding associated with NSAIDs elderly users.
Collapse
|
|
20
|
Abstract
Non-variceal upper gastrointestinal bleeding (NVUGIB) is bleeding that develops in the oesophagus, stomach or proximal duodenum. Peptic ulcers, caused by Helicobacter pylori infection or use of NSAIDs and low-dose aspirin (LDA), are the most common cause. Although the incidence and mortality associated with NVUGIB have been decreasing owing to considerable advances in the prevention and management of NVUGIB over the past 20 years, it remains a common clinical problem with an annual incidence of ∼67 per 100,000 individuals in the United States in 2012. NVUGIB is a medical emergency, and mortality is in the range ∼1-5%. After resuscitation and initial assessment, early (within 24 hours) diagnostic and therapeutic endoscopy together with intragastric pH control with proton pump inhibitors (PPIs) form the basis of treatment. With a growing ageing population treated with antiplatelet and/or anticoagulant medications, the clinical management of NVUGIB is complex as the risk between gastrointestinal bleeding events and adverse cardiovascular events needs to be balanced. The best clinical approach includes identification of risk factors and prevention of bleeding; available strategies include continuous treatment with PPIs or H. pylori eradication in those at increased risk of developing NVUGIB. Treatment with PPIs and/or use of cyclooxygenase-2-selective NSAIDs should be implemented in those patients at risk of NVUGIB who need NSAIDs and/or LDA.
Collapse
|
|
21
|
COELHO LGV, MARINHO JR, GENTA R, RIBEIRO LT, PASSOS MDCF, ZATERKA S, ASSUMPÇÃO PP, BARBOSA AJA, BARBUTI R, BRAGA LL, BREYER H, CARVALHAES A, CHINZON D, CURY M, DOMINGUES G, JORGE JL, MAGUILNIK I, MARINHO FP, MORAES-FILHO JPD, PARENTE JML, PAULA-E-SILVA CMD, PEDRAZZOLI-JÚNIOR J, RAMOS AFP, SEIDLER H, SPINELLI JN, ZIR JV. IVTH BRAZILIAN CONSENSUS CONFERENCE ON HELICOBACTER PYLORI INFECTION. ARQUIVOS DE GASTROENTEROLOGIA 2018; 55:97-121. [PMID: 30043876 DOI: 10.1590/s0004-2803.201800000-20] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 02/22/2018] [Indexed: 02/06/2023]
Abstract
ABSTRACT Significant progress has been obtained since the III Brazilian Consensus Conference on H. pylori infection held in 2012, in Bento Gonçalves, Brazil, and justify a fourth meeting to establish updated guidelines on the current management of H. pylori infection. Therefore, the Núcleo Brasileiro para Estudo do Helicobacter pylori e Microbiota (NBEHPM), association linked to Brazilian Federation of Gastroenterology (FBG) held its fourth meeting again in Bento Gonçalves, RS, Brazil, on August 25-27, 2017. Twenty-six delegates, including gastroenterologists, endoscopists, and pathologists from the five regions of Brazil as well as one international guest from the United States, participated in the meeting. The participants were invited based on their knowledge and contribution to the study of H. pylori infection. The meeting sought to review different aspects of treatment for infection; establish a correlation between infection, dyspepsia, intestinal microbiota changes, and other disorders with a special emphasis on gastric cancer; and reassess the epidemiological and diagnostic aspects of H. pylori infection. Participants were allocated into four groups as follows: 1) Epidemiology and Diagnosis, 2) Dyspepsia, intestinal microbiota and other afections, 3) Gastric Cancer, and, 4) Treatment. Before the consensus meeting, participants received a topic to be discussed and prepared a document containing a recent literature review and statements that should be discussed and eventually modified during the face-to-face meeting. All statements were evaluated in two rounds of voting. Initially, each participant discussed the document and statements with his group for possible modifications and voting. Subsequently, during a second voting in a plenary session in the presence of all participants, the statements were voted upon and eventually modified. The participants could vote using five alternatives: 1) strongly agree; 2) partially agree; 3) undecided; 4) disagree; and 5) strongly disagree. The adopted consensus index was that 80% of the participants responded that they strongly or partially agreed with each statement. The recommendations reported are intended to provide the most current and relevant evidences to management of H. pylori infection in adult population in Brazil.
Collapse
|
|
22
|
Mohammed HA, Saboor-Yaraghi AA, Vahedi H, Yekaninejad MS, Panahi G, Hemmasi G, Lakzaei M, Mirshafiey A. Immunomodulatory effects of M2000 (β-D-Mannuronic acid) on TNF-α, IL-17 and FOXP3 gene expression in patients with inflammatory bowel disease. Int Immunopharmacol 2017; 51:107-113. [PMID: 28822915 DOI: 10.1016/j.intimp.2017.08.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Revised: 08/05/2017] [Accepted: 08/14/2017] [Indexed: 01/07/2023]
Abstract
INTRODUCTION Inflammatory bowel diseases (IBD) are immune-mediated disorders that result from an aberrant immunological response to the gut luminal antigen in genetically susceptible patients. IBD is categorized into two serotype, Crohn's diseases (CD) and ulcerative colitis (UC), both subtype are important cause of gastrointestinal diseases. The increasing rate of hospitalization, with the high economic burden experienced by the IBD patients, calls for more concerted research efforts to design a potent and affordable treatment option for the treatment of IBD. AIMS/OBJECTIVE This research was designed to test the efficacy and potency of β-D Mannuronic acid (M2000) and assess if it could serve as a better therapeutic option in the treatment of IBD. METHODOLOGY Ten (10)ml of blood was aseptically collected into an EDTA container, from 24 IBD patients and 24 normal healthy controls. PBMC was isolated and stimulated with 1μg/ml of LPS in cell culture plate and incubated for 4h. The cells were later treated with 10μg/ml and 50μg/ml of β-D Mannuronic acid (M2000) and incubated for 24h at 37°C under 5% CO2 and 100% humidity. The RNA extractions, cDNA synthesis, and QRT-PCR were performed. RESULTS Our findings showed a significant down-regulation of TNF-α and IL-17 gene expression, while the expression of FOXP3 gene was significantly up-regulated. CONCLUSION This result has indicated that β-D Mannuronic acid (M2000) have immunoregulatory and anti-inflammatory effects on these cytokines that are pivotal in the pathogenesis of IBD.
Collapse
Affiliation(s)
- Hussaini Alhassan Mohammed
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, International Campus, TUMS-, IC, Tehran, Iran; Department of Immunology, Faculty of Medical Laboratory Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria
| | - Ali Akbar Saboor-Yaraghi
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, International Campus, TUMS-, IC, Tehran, Iran
| | - Homayoun Vahedi
- Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mir Saeed Yekaninejad
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Ghodratollah Panahi
- Department of Medical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Gholamreza Hemmasi
- Department of Internal Medicine and Gastroenterology, Iran University of Medical Sciences, Tehran, Iran
| | - Mostafa Lakzaei
- Department of Medical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Mirshafiey
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, International Campus, TUMS-, IC, Tehran, Iran.
| |
Collapse
|
|
23
|
Abstract
BACKGROUND Rheumatoid arthritis is a systemic auto-immune disorder that causes widespread and persistent inflammation of the synovial lining of joints and tendon sheaths. Presently, there is no cure for rheumatoid arthritis and treatment focuses on managing symptoms such as pain, stiffness and mobility, with the aim of achieving stable remission and improving mobility. Celecoxib is a selective non-steroidal anti-inflammatory drug (NSAID) used for treatment of people with rheumatoid arthritis. OBJECTIVES To assess the benefits and harms of celecoxib in people with rheumatoid arthritis. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and clinical trials registers (ClinicalTrials.gov and the World Health Organization trials portal) to May 18, 2017. We also searched the reference and citation lists of included studies. SELECTION CRITERIA We included prospective randomized controlled trials (RCTs) that compared oral celecoxib (200 mg and 400 mg daily) versus no intervention, placebo or a traditional NSAID (tNSAID) in people with confirmed rheumatoid arthritis, of any age and either sex. We excluded studies with fewer than 50 participants in each arm or had durations of fewer than four weeks treatment. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS We included eight RCTs with durations of 4 to 24 weeks, published between 1998 and 2014 that involved a total of 3988 adults (mean age = 54 years), most of whom were women (73%). Participants had rheumatoid arthritis for an average of 9.2 years. All studies were assessed at high or unclear risk of bias in at least one domain. Overall, evidence was assessed as moderate-to-low quality. Five studies were funded by pharmaceutical companies. Celecoxib versus placeboWe included two studies (N = 873) in which participants received 200 mg daily or 400 mg daily or placebo. Participants who received celecoxib showed significant clinical improvement compared with those receiving placebo (15% absolute improvement; 95% CI 7% to 25%; RR 1.53, 95% CI 1.25 to 1.86; number needed to treat to benefit (NNTB) = 7, 95% CI 5 to 13; 2 studies, 873 participants; moderate to low quality evidence).Participants who received celecoxib reported less pain than placebo-treated people (11% absolute improvement; 95% CI 8% to 14%; NNTB = 4, 95% CI 3 to 6; 1 study, 706 participants) but results were inconclusive for improvement in physical function (MD -0.10, 95% CI 0.29 to 0.10; 1 study, 706 participants).In the celecoxib group, 15/293 participants developed ulcers, compared with 4/99 in the placebo group (Peto OR 1.26, 95% CI 0.44 to 3.63; 1 study, 392 participants; low quality evidence). Nine (of 475) participants in the celecoxib group developed short-term serious adverse events, compared with five (of 231) in the placebo group (Peto OR 0.87 (0.28 to 2.69; 1 study, 706 participants; low quality evidence).There were fewer withdrawals among people who received celecoxib (163/475) compared with placebo (130/231) (22% absolute change; 95% CI 16% to 27%; RR 0.61, 95% CI 0.52 to 0.72; 1 study, 706 participants).Cardiovascular events (myocardial infarction, stroke) were not reported. However, regulatory agencies warn of increased cardiovascular event risk associated with celecoxib. Celecoxib versus tNSAIDsSeven studies (N = 2930) compared celecoxib and tNSAIDs (amtolmetin guacyl, diclofenac, ibuprofen, meloxicam, nabumetone, naproxen, pelubiprofen); one study included comparisons of both placebo and tNSAIDs (N = 1149).There was a small improvement, which may not be clinically significant, in numbers of participants achieving ACR20 criteria response in the celecoxib group compared to tNSAIDs (4% absolute improvement; 95% CI 0% less improvement to 8% more improvement; RR 1.10, 95% CI 0.99 to 1.23; 4 studies, 1981 participants). There was a lack of evidence of difference between participants in the celecoxib and tNSAID groups in terms of pain or physical function. Results were assessed at moderate-to-low quality evidence (downgraded due to risk of bias and inconsistency).People who received celecoxib had a lower incidence of gastroduodenal ulcers ≥ 3 mm (34/870) compared with those who received tNSAIDs (116/698). This corresponded to 12% absolute change (95% CI 11% to 13%; RR 0.22, 95% CI 0.15 to 0.32; 5 studies, 1568 participants; moderate quality evidence). There were 7% fewer withdrawals among people who received celecoxib (95% CI 4% to 9%; RR 0.73, 95% CI 0.62 to 0.86; 6 studies, 2639 participants).Results were inconclusive for short-term serious adverse events and cardiovascular events (low quality evidence). There were 17/918 serious adverse events in people taking celecoxib compared to 42/1236 among people who received placebo (Peto OR 0.71; 95% CI 0.39 to 1.28; 5 studies, 2154 participants). Cardiovascular events were reported in both celecoxib and placebo groups in one study (149 participants). AUTHORS' CONCLUSIONS Celecoxib may improve clinical symptoms, alleviate pain and contribute to little or no difference in physical function compared with placebo. Celecoxib was associated with fewer numbers of participant withdrawals. Results for incidence of gastroduodenal ulcers (≥ 3 mm) and short-term serious adverse events were uncertain; however, there were few reported events for either.Celecoxib may slightly improve clinical symptoms compared with tNSAIDs. Results for reduced pain and improved physical function were uncertain. Particpants taking celecoxib had lower incidence of gastroduodenal ulcers (≥ 3 mm) and there were fewer withdrawals from trials. Results for cardiovascular events and short-term serious adverse events were also uncertain.Uncertainty about the rate of cardiovascular events between celecoxib and tNSAIDs could be due to risk of bias; another factor is that these were small, short-term trials. It has been reported previously that both celecoxib and tNSAIDs increase cardiovascular event rates. Our confidence in results about harms is therefore low. Larger head-to-head clinical trials comparing celecoxib to other tNSAIDs is needed to better inform clinical practice.
Collapse
Affiliation(s)
- Mahir Fidahic
- University of TuzlaMedical facultyUniverzitetska 1TuzlaCanton TuzlaBosnia and Herzegovina75000
| | - Antonia Jelicic Kadic
- Cochrane Croatia, University of Split School of MedicineSoltanska 2SplitCroatia
- University Hospital SplitDepartment of PediatricsSpinciceva 1SplitCroatia21 000
| | - Mislav Radic
- University Hospital Split, School of Medicine, Cochrane CroatiaDivision of Rheumatology and Clinical ImmunologyŠoltanska 2SplitCroatia21000
| | - Livia Puljak
- University of Split School of MedicineCochrane CroatiaSoltanska 2SplitCroatia21000
| | | |
Collapse
|
|
24
|
Barati A, Jamshidi AR, Ahmadi H, Aghazadeh Z, Mirshafiey A. Effects of β-d-mannuronic acid, as a novel non-steroidal anti-inflammatory medication within immunosuppressive properties, on IL17, RORγt, IL4 and GATA3 gene expressions in rheumatoid arthritis patients. Drug Des Devel Ther 2017; 11:1027-1033. [PMID: 28408801 PMCID: PMC5384716 DOI: 10.2147/dddt.s129419] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Rheumatoid arthritis (RA) is the most common form of chronic inflammatory arthritis characterized by pain, swelling and destruction of joints, with a resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can interfere with the disease process. In this study, the effect of β-d-mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive and anti-inflammatory effects together with antioxidant effects was evaluated on IL17, RORγt, IL4 and GATA3 gene expression in 12 RA patients. Previously, M2000 driven from sodium alginate (natural product; patented, DEU: 102016113018.4) has shown a notable efficacy in experimental models of multiple sclerosis, RA and nephrotic syndrome. This study was performed on 12 patients with RA who had an inadequate response to conventional treatments. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. M2000 was administered orally at a dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected before and after treatment to evaluate the expression levels of IL4, GATA3, IL17 and RORγt. The gene expression results showed that M2000 has a potent efficacy, so that it could not only significantly decrease IL17 and RORγt levels but also increase IL4 and GATA3 levels after 12 weeks of treatment. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments. In conclusion, M2000 as a natural novel agent has therapeutic and immunosuppressive properties on RA patients (identifier: IRCT2014011213739N2).
Collapse
MESH Headings
- Administration, Oral
- Anti-Inflammatory Agents, Non-Steroidal/administration & dosage
- Anti-Inflammatory Agents, Non-Steroidal/pharmacology
- Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
- Antioxidants/administration & dosage
- Antioxidants/pharmacology
- Antioxidants/therapeutic use
- Arthritis, Rheumatoid/drug therapy
- Arthritis, Rheumatoid/genetics
- Female
- GATA3 Transcription Factor/antagonists & inhibitors
- GATA3 Transcription Factor/genetics
- GATA3 Transcription Factor/metabolism
- Gene Expression Profiling
- Hexuronic Acids/administration & dosage
- Hexuronic Acids/pharmacology
- Hexuronic Acids/therapeutic use
- Humans
- Immunosuppressive Agents/administration & dosage
- Immunosuppressive Agents/pharmacology
- Immunosuppressive Agents/therapeutic use
- Interleukin-17/antagonists & inhibitors
- Interleukin-17/genetics
- Interleukin-17/metabolism
- Interleukin-4/antagonists & inhibitors
- Interleukin-4/genetics
- Interleukin-4/metabolism
- Male
- Middle Aged
- Nuclear Receptor Subfamily 1, Group F, Member 3/antagonists & inhibitors
- Nuclear Receptor Subfamily 1, Group F, Member 3/genetics
- Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism
Collapse
Affiliation(s)
- Anis Barati
- Department of Immunology, School of Public Health
| | - Ahmad Reza Jamshidi
- Iranian Institute for Health Sciences Research, Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | | | | | | |
Collapse
|
|
25
|
Scarpignato C, Gatta L, Zullo A, Blandizzi C. Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression. BMC Med 2016; 14:179. [PMID: 27825371 PMCID: PMC5101793 DOI: 10.1186/s12916-016-0718-z] [Citation(s) in RCA: 274] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2016] [Accepted: 10/14/2016] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The introduction of proton pump inhibitors (PPIs) into clinical practice has revolutionized the management of acid-related diseases. Studies in primary care and emergency settings suggest that PPIs are frequently prescribed for inappropriate indications or for indications where their use offers little benefit. Inappropriate PPI use is a matter of great concern, especially in the elderly, who are often affected by multiple comorbidities and are taking multiple medications, and are thus at an increased risk of long-term PPI-related adverse outcomes as well as drug-to-drug interactions. Herein, we aim to review the current literature on PPI use and develop a position paper addressing the benefits and potential harms of acid suppression with the purpose of providing evidence-based guidelines on the appropriate use of these medications. METHODS The topics, identified by a Scientific Committee, were assigned to experts selected by three Italian Scientific Societies, who independently performed a systematic search of the relevant literature using Medline/PubMed, Embase, and the Cochrane databases. Search outputs were distilled, paying more attention to systematic reviews and meta-analyses (where available) representing the best evidence. The draft prepared on each topic was circulated amongst all the members of the Scientific Committee. Each expert then provided her/his input to the writing, suggesting changes and the inclusion of new material and/or additional relevant references. The global recommendations were then thoroughly discussed in a specific meeting, refined with regard to both content and wording, and approved to obtain a summary of current evidence. RESULTS Twenty-five years after their introduction into clinical practice, PPIs remain the mainstay of the treatment of acid-related diseases, where their use in gastroesophageal reflux disease, eosinophilic esophagitis, Helicobacter pylori infection, peptic ulcer disease and bleeding as well as, and Zollinger-Ellison syndrome is appropriate. Prevention of gastroduodenal mucosal lesions (and symptoms) in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or antiplatelet therapies and carrying gastrointestinal risk factors also represents an appropriate indication. On the contrary, steroid use does not need any gastroprotection, unless combined with NSAID therapy. In dyspeptic patients with persisting symptoms, despite successful H. pylori eradication, short-term PPI treatment could be attempted. Finally, addition of PPIs to pancreatic enzyme replacement therapy in patients with refractory steatorrhea may be worthwhile. CONCLUSIONS Overall, PPIs are irreplaceable drugs in the management of acid-related diseases. However, PPI treatment, as any kind of drug therapy, is not without risk of adverse effects. The overall benefits of therapy and improvement in quality of life significantly outweigh potential harms in most patients, but those without clear clinical indication are only exposed to the risks of PPI prescription. Adhering with evidence-based guidelines represents the only rational approach to effective and safe PPI therapy. Please see related Commentary: doi: 10.1186/s12916-016-0724-1 .
Collapse
Affiliation(s)
- Carmelo Scarpignato
- Clinical Pharmacology & Digestive Pathophysiology Unit, Department of Clinical & Experimental Medicine, University of Parma, Maggiore University Hospital, Cattani Pavillon, I-43125, Parma, Italy.
| | - Luigi Gatta
- Clinical Pharmacology & Digestive Pathophysiology Unit, Department of Clinical & Experimental Medicine, University of Parma, Maggiore University Hospital, Cattani Pavillon, I-43125, Parma, Italy
- Gastroenterology & Endoscopy Unit, Versilia Hospital, Azienda USL Toscana Nord Ovest, Lido di Camaiore, Italy
| | - Angelo Zullo
- Division of Gastroenterology & Digestive Endoscopy, Nuovo Regina Elena Hospital, Rome, Italy
| | - Corrado Blandizzi
- Division of Pharmacology, Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy
| |
Collapse
|
|
26
|
Wang P, Tao JH, Pan HF. Probiotic bacteria: a viable adjuvant therapy for relieving symptoms of rheumatoid arthritis. Inflammopharmacology 2016; 24:189-196. [PMID: 27581587 DOI: 10.1007/s10787-016-0277-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Accepted: 08/23/2016] [Indexed: 01/05/2023]
Abstract
The burgeoning use of probiotics has proliferated during the past two decades. However, the effect of probiotic administration for either the prevention or treatment of rheumatoid arthritis (RA) has been investigated in a limited number of studies. Randomized controlled clinical trials have provided evidences that specific probiotics supplementation exhibit anti-inflammatory effects, help to increase daily activities and alleviate symptoms in patients with RA. Therefore, using probiotic bacteria as an adjuvant therapy may be considered as a promising treatment option for RA. This review summarizes the available data about the therapeutic and preventive effect of probiotics in RA, together with probiotic supplement as a possible therapy in clinical treatment.
Collapse
Affiliation(s)
- Peng Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China
- Anhui Provincial Laboratory of Population Health & Major Disease Screening and Diagnosis, Hefei, Anhui, China
| | - Jin-Hui Tao
- Department of Rheumatology, Anhui Provincial Hospital, Hefei, Anhui, China
| | - Hai-Feng Pan
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China.
- Anhui Provincial Laboratory of Population Health & Major Disease Screening and Diagnosis, Hefei, Anhui, China.
| |
Collapse
|
|
27
|
Bauman JE, Zang Y, Sen M, Li C, Wang L, Egner PA, Fahey JW, Normolle DP, Grandis JR, Kensler TW, Johnson DE. Prevention of Carcinogen-Induced Oral Cancer by Sulforaphane. Cancer Prev Res (Phila) 2016; 9:547-57. [PMID: 27339168 PMCID: PMC4930727 DOI: 10.1158/1940-6207.capr-15-0290] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2015] [Accepted: 04/28/2016] [Indexed: 12/28/2022]
Abstract
Chronic exposure to carcinogens represents the major risk factor for head and neck squamous cell carcinoma (HNSCC). Beverages derived from broccoli sprout extracts (BSE) that are rich in glucoraphanin and its bioactive metabolite sulforaphane promote detoxication of airborne pollutants in humans. Herein, we investigated the potential chemopreventive activity of sulforaphane using in vitro models of normal and malignant mucosal epithelial cells and an in vivo model of murine oral cancer resulting from the carcinogen 4-nitroquinoline-1-oxide (4NQO). Sulforaphane treatment of Het-1A, a normal mucosal epithelial cell line, and 4 HNSCC cell lines led to dose- and time-dependent induction of NRF2 and the NRF2 target genes NQO1 and GCLC, known mediators of carcinogen detoxication. Sulforaphane also promoted NRF2-independent dephosphorylation/inactivation of pSTAT3, a key oncogenic factor in HNSCC. Compared with vehicle, sulforaphane significantly reduced the incidence and size of 4NQO-induced tongue tumors in mice. A pilot clinical trial in 10 healthy volunteers evaluated the bioavailability and pharmacodynamic activity of three different BSE regimens, based upon urinary sulforaphane metabolites and NQO1 transcripts in buccal scrapings, respectively. Ingestion of sulforaphane-rich BSE demonstrated the greatest, most consistent bioavailability. Mucosal bioactivity, defined as 2-fold or greater upregulation of NQO1 mRNA, was observed in 6 of 9 evaluable participants ingesting glucoraphanin-rich BSE; 3 of 6 ingesting sulforaphane-rich BSE; and 3 of 9 after topical-only exposure to sulforaphane-rich BSE. Together, our findings demonstrate preclinical chemopreventive activity of sulforaphane against carcinogen-induced oral cancer, and support further mechanistic and clinical investigation of sulforaphane as a chemopreventive agent against tobacco-related HNSCC. Cancer Prev Res; 9(7); 547-57. ©2016 AACR.
Collapse
Affiliation(s)
- Julie E Bauman
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania
| | - Yan Zang
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Malabika Sen
- Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Changyou Li
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Lin Wang
- Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Patricia A Egner
- Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Jed W Fahey
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Daniel P Normolle
- University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Jennifer R Grandis
- Department of Otolaryngology-Head and Neck Surgery, University of California at San Francisco, San Francisco, California
| | - Thomas W Kensler
- University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland. Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Daniel E Johnson
- Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
| |
Collapse
|
|
28
|
Sostres C, Lanas Á. Prescripción apropiada, adherencia y seguridad de los antiinflamatorios no esteroideos. Med Clin (Barc) 2016; 146:267-72. [DOI: 10.1016/j.medcli.2015.09.022] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Revised: 09/30/2015] [Accepted: 09/30/2015] [Indexed: 12/29/2022]
|
|
29
|
Seddighi R, Lee L. Complications Associated with Nonsteroidal Antiinflammatory Drugs. COMPLICATIONS IN SMALL ANIMAL SURGERY 2016:97-109. [DOI: 10.1002/9781119421344.ch15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
|
|
30
|
Anti-Inflammation Property of Syzygium cumini (L.) Skeels on Indomethacin-Induced Acute Gastric Ulceration. Gastroenterol Res Pract 2015; 2015:343642. [PMID: 26633969 PMCID: PMC4655050 DOI: 10.1155/2015/343642] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Revised: 02/23/2015] [Accepted: 03/11/2015] [Indexed: 12/19/2022] Open
Abstract
Indomethacin, nonsteroidal anti-inflammatory drug (NSAIDs), induced gastric damage and perforation through the excess generation of reactive oxygen species (ROS). Syzygium cumini (L.) Skeels is commonly used as a medicinal plant and is claimed to have antioxidant activities. The effects of Syzygium cumini (L.) Skeels aqueous extract (SCC) on antifree radical, anti-inflammation, and antiulcer of SCC on indomethacin induced acute gastric ulceration were determined in our study. Scavenging activity at 50% of SCC is higher than ascorbic acid in in vitro study. Mice treated with indomethacin revealed mucosal hemorrhagic lesion and inhibited mucus content. Pretreatment with SCC caused discernible decrease in indomethacin induced gastric lesion and lipid peroxide content. In addition, oxidized glutathione (GSSG), glutathione peroxidase (GPx), nitric oxide (NO) levels, and gastric wall mucus were restored on acute treated mice model. Indomethacin induced inflammation by activated inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) proinflammatory cytokines to release large amount of ROS/RNS which were ameliorated in mice pretreatment with SCC. SCC showed restoration of the imbalance of oxidative damage leading to amelioration of cyclooxygenase enzyme (COX). In conclusion, SCC acts as an antioxidant, anti-inflammation, and antiulcer against indomethacin.
Collapse
|
|
31
|
Abstract
Use of nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin is accompanied by risk of upper and lower gastrointestinal (GI) complications, some of which can be serious or even fatal. Management strategies to reduce this risk include gastroprotective pharmacotherapy, use of safer NSAIDs, and eradication of Helicobacter pylori infection. In this article, Dr Lanas summarizes the GI risks associated with NSAID and low-dose aspirin therapy and weighs the efficacy of current risk management strategies.
Collapse
Affiliation(s)
- Angel Lanas
- Service of gastroenterology, University Hospital, Institute of Health Sciences of Aragon, Zaragoza, Spain
| |
Collapse
|
|
32
|
Sheth SH, Johnson DE, Kensler TW, Bauman JE. Chemoprevention targets for tobacco-related head and neck cancer: past lessons and future directions. Oral Oncol 2015; 51:557-64. [PMID: 25868717 DOI: 10.1016/j.oraloncology.2015.02.101] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2014] [Revised: 01/21/2015] [Accepted: 02/25/2015] [Indexed: 11/26/2022]
Abstract
Progress toward identifying an effective chemopreventive agent to reduce the incidence of head and neck squamous cell carcinoma (HNSCC) has been limited by poor efficacy and intolerable toxicity profiles. In this review, we summarize the biological basis of HNSCC chemoprevention, and outline challenges associated with identifying appropriate high-risk HNSCC populations for chemoprevention studies. We discuss findings and lessons learned from clinical trials that have investigated micronutrient and molecular targeting interventions. Finally, we introduce the concept of green chemoprevention, interventions based upon whole plant foods or simple extracts that may represent a safe and cost-conscious option for the next generation of studies. As our scientific understanding of HNSCC reaches new levels, the field is poised to develop chemoprevention studies based on rigorous biological validation with accessibility to all affected individuals regardless of socioeconomic barriers.
Collapse
Affiliation(s)
| | - Daniel E Johnson
- Department of Medicine, University of Pittsburgh, United States; Departments of Pharmacology and Chemical Biology, University of Pittsburgh, United States
| | - Thomas W Kensler
- Departments of Pharmacology and Chemical Biology, University of Pittsburgh, United States
| | - Julie E Bauman
- Department of Medicine, University of Pittsburgh, United States.
| |
Collapse
|
|
33
|
Goldstein JL, Cryer B. Gastrointestinal injury associated with NSAID use: a case study and review of risk factors and preventative strategies. DRUG HEALTHCARE AND PATIENT SAFETY 2015; 7:31-41. [PMID: 25653559 PMCID: PMC4310346 DOI: 10.2147/dhps.s71976] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
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.
Collapse
Affiliation(s)
- Jay L Goldstein
- Department of Medicine, NorthShore University HealthSystem, Evanston, IL, USA
| | - Byron Cryer
- Division of Gastroenterology, University of Texas Southwestern Medical Center and Dallas VA Medical Center, Dallas, TX, USA
| |
Collapse
|
|
34
|
Laine L. NSAID-associated gastrointestinal bleeding: assessing the role of concomitant medications. Gastroenterology 2014; 147:730-3. [PMID: 25167988 DOI: 10.1053/j.gastro.2014.08.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Loren Laine
- Yale School of Medicine, New Haven and VA Connecticut Healthcare System, West Haven, Connecticut.
| |
Collapse
|
|
35
|
Gargallo CJ, Sostres C, Lanas A. Prevention and Treatment of NSAID Gastropathy. ACTA ACUST UNITED AC 2014; 12:398-413. [DOI: 10.1007/s11938-014-0029-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
|
|
36
|
Sostres C, Gargallo CJ, Lanas A. Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: Old question new insights. World J Gastroenterol 2014; 20:9439-9450. [PMID: 25071338 PMCID: PMC4110575 DOI: 10.3748/wjg.v20.i28.9439] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Revised: 01/15/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
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.
Collapse
|
|
37
|
Richards BL, Whittle S, Buchbinder R, Barrett C, Lynch N, Major G, Littlejohn G, Taylor A, Zochling J. Australian and New Zealand evidence-based recommendations for pain management by pharmacotherapy in adult patients with inflammatory arthritis. Int J Rheum Dis 2014; 17:738-48. [PMID: 24889411 DOI: 10.1111/1756-185x.12388] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
AIM To develop Australian and New Zealand evidence-based recommendations for pain management by pharmacotherapy in adult patients with optimally treated inflammatory arthritis (IA). METHODS Four hundred and fifty-three rheumatologists from 17 countries including 46 rheumatologists from Australia and New Zealand participated in the 2010 3e (Evidence, Expertise, Exchange) Initiative. Using a formal voting process, rheumatologists from 15 national scientific committees selected 10 clinical questions regarding the use of pain medications in IA. Bibliographic fellows undertook a systematic literature review for each question, using MEDLINE, EMBASE, Cochrane CENTRAL and 2008-09 EULAR/ACR abstracts. Relevant studies were retrieved for data extraction and risk of bias assessment. Rheumatologists from Australia and New Zealand used the evidence to develop a set of national recommendations. These recommendations were then formulated and assessed for agreement and the potential impact on clinical practice. The Oxford Levels of Evidence and Grade of Recommendation were applied to each recommendation. RESULTS The systematic reviews identified 49 242 references, from which 167 studies which met the pre-specified inclusion criteria. Combining this evidence with expert opinion led to the development of 10 final Australian and New Zealand recommendations. The recommendations relate to pain measurement, and the use of analgesic medications in patients with and without co-morbidities and during pregnancy and lactation. The recommendations reflect the clinical practice of the majority of the participating rheumatologists (mean level of agreement 7.24-9.65). CONCLUSIONS Ten Australian and New Zealand evidence-based recommendations regarding the management of pain by pharmacotherapy in adults with optimally treated IA were developed. They are supported by a large panel of rheumatologists, thus enhancing their utility in everyday clinical practice.
Collapse
Affiliation(s)
- Bethan L Richards
- Department of Rheumatology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Department of Medicine, University of Sydney, Sydney, New South Wales, Australia
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
38
|
Risk factors associated with NSAID-induced upper gastrointestinal bleeding resulting in hospital admissions: A cross-sectional, retrospective, case series analysis in valencia, spain. CURRENT THERAPEUTIC RESEARCH 2014; 68:107-19. [PMID: 24678124 DOI: 10.1016/j.curtheres.2007.03.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/25/2007] [Indexed: 11/22/2022]
Abstract
UNLABELLED Abstract. BACKGROUND NSAIDs are a significant cause of drug-related hospital admissions and deaths. The therapeutic effects of NSAIDs have been associated with the risk for developing adverse events, mainly in the gastrointestinal tract. OBJECTIVES The focus of this study was to identify the most common risk factors associated with NSAID-induced upper gastrointestinal bleeding (UGIB) resulting in hospital admissions. A secondary end point was the relationship between use of gastroprotective treatment and relevant risk factors to NSAID-induced UGIB in the selected population. METHODS This study was a cross-sectional, retrospective, case-series analysis of NSAID-induced UGIB resulting in hospital admission to the Requena General Hospital, Valencia, Spain, occurring from 1997 to 2005. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify UGIB admissions associated with NSAIDs. To estimate the probability of association between UGIB and the use of NSAIDs, the Naranjo adverse drug reaction probability was used. Patients were categorized as high-risk to develop UGIB if they met ≥1 of the following risk criteria (relevant risk factors): aged ≥65 years (age risk factor); peptic ulcer disease or NSAID gastropathy occurring in the year before their hospital admission (history risk factor); and concomitant use of other NSAIDs, systemic corticoids, oral anticoagulants, or platelet aggregation inhibitors (concomitant medication risk factor). Patients were categorized as candidates to use gastroprotections if they met ≥1 of the relevant risk factors. Patients were categorized as users of gastroprotective treatment if they used proton pump inhibitors, histamine H2-receptor antagonists, or misoprostol at hospital admission. RESULTS This study comprised 209 cases of NSAID-induced UGIB (129 men, 80 women: mean [SD] age, 71.5 [13.8] years; 128 [61.2%] receiving acetyl salicylic acid [ASA], with 72 [34.4%] receiving low-dose [80-325 mg] ASA). Prevalence of relevant risk factors for UGIB were as follows: age, 158 (75.6%) patients; history, 37 (17.7%); and concomitant medication, 35 (16.7%). One hundred seventy-eight (85.2%) patients met ≥1 criterion for using a gastroprotective agent; 28 (15.6%) were actually using one. Only the history risk factor was significantly associated with the use of gastroprotective treatment (P = 0.007; odds ratio = 3.17). CONCLUSIONS In this study of NSAID-induced UGIB resulting in hospital admission, age was the most common risk factor. However, this criterion was not associated with the use of gastroprotective agents. A large number of cases were associated with the use of ASA, primarily in those receiving low doses. A significant lack of gastroprotective agent use was observed in patients who met the criteria to use them.
Collapse
|
|
39
|
Han JB, Keller EE, Grothe RM. Postoperative gastrointestinal bleeding in orthognathic surgery patients: its estimated prevalence and possible association to known risk factors. J Oral Maxillofac Surg 2014; 72:2043-51. [PMID: 24997023 DOI: 10.1016/j.joms.2014.02.039] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2013] [Revised: 02/22/2014] [Accepted: 02/25/2014] [Indexed: 12/26/2022]
Abstract
PURPOSE To assess the prevalence of gastrointestinal (GI) bleeding in patients after orthognathic surgery and its relation to known risk factors. PATIENT AND METHODS With institutional review board approval, a single-center case series was conducted with data collected retrospectively from orthognathic surgical patients' medical records from 1990 to 2010. All patients were treated by 1 primary surgeon, were limited to 21 years or younger at the time of surgery, and had no coagulopathy. The authors' hypothesis was that patients concurrently exposed to mechanical ventilation and dual anti-inflammatory drugs in the postoperative period would be at a greater risk for clinically significant GI bleeding according to the American Society of Health-System Pharmacists guideline compared with those exposed to fewer risk factors. Its prevalence and relation to known risk factors were analyzed. RESULTS In total 498 orthognathic cases consisting of 220 male patients (median age, 17 yr; age range, 3 to 21 yr) and 262 female patients (median age, 17 yr; age range, 10 to 21 yr) were reviewed. Of 17 patients admitted to intensive care unit level of care postoperatively, 4 patients were exposed to concomitant administration of ketorolac and steroids while being mechanically ventilated. Two of these 4 patients developed esophagogastroduodenoscopy-confirmed upper GI bleeding (UGIB). There was no incidence of UGIB in patients not exposed to all 3 risk factors concurrently. CONCLUSIONS Postoperative GI bleeding complication is rare in orthognathic surgical patients, with an estimated prevalence of 0.4%. Based on these observations, orthognathic surgical patients who require mechanical ventilation and are receiving anti-inflammatory medications may have an increased risk of GI bleeding. In the absence of active bleeding from the surgical site, persistent decrease in hemoglobin concentration should alert one to consider the possibility of UGIB.
Collapse
Affiliation(s)
- James B Han
- Resident, Division of Oral and Maxillofacial Surgery, Department of Surgery, Mayo Clinic, Rochester, MN.
| | - Eugene E Keller
- Consultant, Division of Oral and Maxillofacial Surgery, Department of Surgery; Professor of Surgery, Mayo Clinic College of Medicine, Rochester, MN
| | - Rayna M Grothe
- Chair, Pediatric Gastroenterology, Pediatric and Adolescent Medicine; Assistant Professor of Pediatrics, Mayo Clinic College of Medicine, Rochester, MN
| |
Collapse
|
|
40
|
Recomendaciones para una prescripción segura de antiinflamatorios no esteroideos: documento de consenso elaborado por expertos nominados por 3 sociedades científicas (SER-SEC-AEG). GASTROENTEROLOGIA Y HEPATOLOGIA 2014; 37:107-27. [DOI: 10.1016/j.gastrohep.2013.11.014] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/17/2013] [Accepted: 11/12/2013] [Indexed: 12/17/2022]
|
|
41
|
Watanabe T, Tanigawa T, Shiba M, Nadatani Y, Nagami Y, Sugimori S, Yamagami H, Watanabe K, Tominaga K, Fujiwara Y, Koike T, Arakawa T. Anti-tumour necrosis factor agents reduce non-steroidal anti-inflammatory drug-induced small bowel injury in rheumatoid arthritis patients. Gut 2014; 63:409-14. [PMID: 23697473 DOI: 10.1136/gutjnl-2013-304713] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVE The role of tumour necrosis factor α (TNFα) in the pathogenesis of non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal damage remains unclear. We evaluated the preventive effect of anti-TNF therapy against NSAID-induced enteropathy in rheumatoid arthritis (RA) patients. DESIGN Capsule endoscopy was performed in 95 consecutive RA patients who received NSAID for more than 3 months, with or without anti-TNF therapy over a period of 3 months. The findings were scored from 0 to 4: 0, normal; 1, red spots; 2, one to four erosions; 3, more than four erosions; and 4, large erosions/ulcers. The relationship between the use of anti-TNF therapy and the risk of severe damage (scores 3 or 4) or the most severe damage (score 4) was assessed using multiple logistic regression analysis. Furthermore, a propensity score matching analysis was performed to reduce the effects of TNF selection bias. RESULTS By stratifying the patients on the basis of anti-TNF therapy, we obtained crude OR of 0.23 for severe damage (95% CI 0.09 to 0.65) and 0.37 for the most severe damage (95% CI 0.16 to 0.86). This protective effect of anti-TNF therapy remained robust to adjustments for baseline characteristics, with the adjusted OR for severe damage and the most severe damage ranging from 0.23 to 0.26 and 0.06 to 0.41, respectively. Propensity score matching yielded similar results and showed the protective effects of anti-TNF therapy against severe and most severe damage. CONCLUSIONS Anti-TNF therapy may protect against NSAID-induced small intestinal damage in RA patients.
Collapse
Affiliation(s)
- Toshio Watanabe
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, , Osaka, Japan
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
42
|
The rate of prescribing gastrointestinal prophylaxis with either a proton pump inhibitor or an H2-receptor antagonist in Nova Scotia seniors starting nonsteroidal anti-inflammatory drug therapy. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2014; 24:481-8. [PMID: 20711527 DOI: 10.1155/2010/397610] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used agents that can cause serious gastrointestinal (GI) side effects. For patients at increased risk of NSAID-related GI complications, prophylaxis with either a nonselective NSAID plus gastroprotective agent (GPA) or, alternatively, therapy with a cyclooxygenase-2 selective inhibitor with or without a GPA such as a proton pump inhibitor (PPI), is recommended. AIM To describe the rate, timing and duration of GI prophylaxis in Nova Scotia seniors receiving nonselective NSAIDs. METHODS The Nova Scotia Seniors' Pharmacare Program beneficiaries for the years 1998 to 2002 were studied. A cohort of incident NSAID and GPA users was selected from all nonselective NSAID users (no prescribed NSAID dispensed 12 months before the index month and no GPA dispensed two months before the index prescription). Monthly coprescribing rates were calculated by dividing the number of patients in the cohort using GPAs by the number of NSAID users. GI prophylactic coprescribing was defined as the coprescribing rate present at the first month (index month) of prescribing an NSAID. RESULTS The cohort consisted of 12,906 patients. Seventy-five per cent of the nonselective NSAID prescriptions dispensed were for up to two months duration, with only 2.3% longer than one year. GI prophylaxis was given to only 3.8% of patients starting NSAIDs who were not on a GPA in the two months before starting NSAIDs. Of this 3.8%, 92.7% of the patients received H2-receptor antagonists (H2RAs), and 7% received PPIs. The rate of H2RA coprescribing increased with the number of consecutive months on an NSAID from 3.5% in the first month to 24.1% at 48 months. For PPIs, the coprescribing rate increased from 0.3% to 1.9% of all NSAID users in the cohort. The rate of gastroprophylaxis coprescribing for patients receiving NSAIDs did not rise with increasing age. CONCLUSION In Nova Scotian seniors using nonselective NSAIDs, the rate of GI prophylaxis was low. Most patients received H2RAs as GPAs despite evidence that they offer insufficient protection.
Collapse
|
|
43
|
de Groot NL, Hagenaars MP, Smeets HM, Steyerberg EW, Siersema PD, van Oijen MGH. Primary non-variceal upper gastrointestinal bleeding in NSAID and low-dose aspirin users: development and validation of risk scores for either medication in two large Dutch cohorts. J Gastroenterol 2014; 49:245-53. [PMID: 23609946 DOI: 10.1007/s00535-013-0817-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2012] [Accepted: 03/24/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND Non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose acetylsalicylic acid (ASA) have several adverse gastrointestinal (GI) effects, including upper GI bleeding. We aimed to develop a simple risk score to identify high risk NSAID and ASA users for primary upper GI bleeding. METHODS Using data from two large anonymized health insurance databases, we defined a development and validation cohort with NSAID and ASA users which were followed-up for the occurrence of a primary upper GI bleeding. Cox regression analyses identified risk factors which were combined into simple risk scores. C-statistics were used to evaluate the discriminative ability of these scores in a validation cohort. RESULTS In total, 421 cases of upper GI bleeding were identified in the initial cohort of 784,263 NSAID users (incidence rate 54.2 per 10,000 person-years), while 1,295 cases of upper GI bleeding were identified in 235,531 ASA users (incidence rate 37.9 per 10,000 person-years). The risk of upper GI bleeding increased with a higher risk score, which for NSAID users included age, male gender, anemia and concomitant use of ASA or anticoagulants. For ASA users, age, anemia, diabetes and concomitant use of other antiplatelet drugs or anticoagulants were included in the risk score. The C-statistics in the validation cohort were 0.68 and 0.63 or NSAID and ASA users, respectively. CONCLUSION Risk factors for primary upper GI bleeding are to a large extent similar for NSAID and ASA users. Using a risk score based on these risk factors, patients at the highest risk can be identified with moderate accuracy.
Collapse
Affiliation(s)
- Nicolette L de Groot
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, P.O. Box 85500, (Internal Code F02.618), 3508 GA, Utrecht, The Netherlands,
| | | | | | | | | | | |
Collapse
|
|
44
|
Lanas A, Benito P, Alonso J, Hernández-Cruz B, Barón-Esquivias G, Perez-Aísa Á, Calvet X, García-Llorente JF, Gobbo M, Gonzalez-Juanatey JR. Safe prescription recommendations for non steroidal anti-inflammatory drugs: consensus document ellaborated by nominated experts of three scientific associations (SER-SEC-AEG). ACTA ACUST UNITED AC 2014; 10:68-84. [PMID: 24462644 DOI: 10.1016/j.reuma.2013.10.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2013] [Revised: 10/22/2013] [Accepted: 10/23/2013] [Indexed: 02/06/2023]
Abstract
This article outlines key recommendations for the appropriate prescription of non steroidal anti-inflammatory drugs to patients with different musculoskeletal problems. These recommendations are based on current scientific evidence, and takes into consideration gastrointestinal and cardiovascular safety issues. The recommendations have been agreed on by experts from three scientific societies (Spanish Society of Rheumatology [SER], Spanish Association of Gastroenterology [AEG] and Spanish Society of Cardiology [SEC]), following a two-round Delphi methodology. Areas that have been taken into account encompass: efficiency, cardiovascular risk, gastrointestinal risk, liver risk, renal risk, inflammatory bowel disease, anemia, post-operative pain, and prevention strategies. We propose a patient management algorithm that summarizes the main aspects of the recommendations.
Collapse
Affiliation(s)
- Angel Lanas
- Servicio de Aparato Digestivo, Hospital Clínico Lozano Blesa, Universidad de Zaragoza, IIS Aragón, CIBERehd, Zaragoza, España.
| | - Pere Benito
- Servicio de Reumatología, Hospital del Mar, Universidad Autónoma de Barcelona, Barcelona, España
| | - Joaquín Alonso
- Servicio de Cardiología, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España
| | - Blanca Hernández-Cruz
- i+D+I, Unidad de Gestión Clínica de Reumatología, Servicio de Reumatología, Hospital Universitario Virgen Macarena, Sevilla, España
| | - Gonzalo Barón-Esquivias
- Servicio de Cardiología, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, España
| | - Ángeles Perez-Aísa
- Unidad de Digestivo, Agencia Sanitaria Costa del Sol, Marbella, Málaga, España
| | - Xavier Calvet
- Servei de Digestiu, Hospital de Sabadell, Universidad Autónoma de Barcelona, CIBERehd, Sabadell, Barcelona, España
| | | | - Milena Gobbo
- Unidad de Investigación, Sociedad Española de Reumatología, Madrid, España
| | - José R Gonzalez-Juanatey
- Servicio de Cardiología y Unidad Coronaria, Hospital Clínico Universitario, Santiago de Compostela, La Coruña, España
| |
Collapse
|
|
45
|
Sommerfelt RM, Feuerherm AJ, Jones K, Johansen B. Cytosolic phospholipase A2 regulates TNF-induced production of joint destructive effectors in synoviocytes. PLoS One 2013; 8:e83555. [PMID: 24349530 PMCID: PMC3861525 DOI: 10.1371/journal.pone.0083555] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2013] [Accepted: 11/06/2013] [Indexed: 11/18/2022] Open
Abstract
INTRODUCTION Rheumatoid arthritis (RA) is an inflammatory disease of the joint characterized by chronic synovitis causing pain, swelling and loss of function due to destruction of cartilage and bone. The complex series of pathological events occurring in RA is largely regulated via excessive production of pro-inflammatory cytokines, the most prominent being tumor necrosis factor (TNF). The objective of this work was to elucidate possible involvement of group IVA cytosolic phospholipase A2 (cPLA2α) in TNF-induced regulation of synovitis and joint destructive effectors in RA, to evaluate the potential of cPLA2α as a future therapeutic target. METHODS The involvement of cPLA2α in tumor necrosis factor (TNF)-induced intracellular signaling cascades in synoviocytes (synovial fibroblast-like cells) was analyzed by arachidonic acid (AA) release assay, synoviocyte enzyme activity assay, gene expression analysis by real-time PCR and ELISA immunoassay for the detection of prostaglandin E2 (PGE2), interleukin 8 (IL8) and stromelysin-1 (MMP3), respectively. RESULTS Inhibitors of cPLA2α enzyme activity (AVX002, ATK) significantly reduced TNF-induced cellular release of AA, PGE2, IL8 and MMP3. This reduction was evident both at transcriptional, protein or metabolite levels. Interestingly, cPLA2α inhibition affected several key points of the arachidonyl cascade; AA-release, cyclooxygenase-2 (COX2) expression and PGE2 production. Furthermore, the results suggest that cPLA2α is subject to transcriptional auto-regulation as inhibition of cPLA2α resulted in reduced PLA2G4A gene expression in TNF-stimulated synoviocytes. CONCLUSIONS cPLA2α appears to be an important regulator of central effectors of inflammation and joint destruction, namely MMP3, IL8, COX2, and PGE2. Decreased transcription of the PLA2G4A and COX2 genes in response to cPLA2α enzyme inhibition further suggest a self-reinforcing effect of cPLA2α inhibition in response to TNF. Collectively, these results support that cPLA2α is an attractive therapeutic target candidate as its inhibition reduces the production of multiple key pro-inflammatory factors involved in RA pathogenesis.
Collapse
Affiliation(s)
- Randi M. Sommerfelt
- Department of Biology, Norwegian University of Science and Technology, Trondheim, Norway
| | - Astrid J. Feuerherm
- Department of Biology, Norwegian University of Science and Technology, Trondheim, Norway
| | - Kymry Jones
- Department of Biology, Norwegian University of Science and Technology, Trondheim, Norway
| | - Berit Johansen
- Department of Biology, Norwegian University of Science and Technology, Trondheim, Norway
- * E-mail:
| |
Collapse
|
|
46
|
Watanabe T, Tanigawa T, Nadatani Y, Nagami Y, Sugimori S, Okazaki H, Yamagami H, Watanabe K, Tominaga K, Fujiwara Y, Koike T, Arakawa T. Risk factors for severe nonsteroidal anti-inflammatory drug-induced small intestinal damage. Dig Liver Dis 2013; 45:390-5. [PMID: 23333664 DOI: 10.1016/j.dld.2012.12.005] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2012] [Revised: 12/07/2012] [Accepted: 12/10/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Few studies have assessed the risk factors associated with nonsteroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal damage. AIMS To evaluate the risk factors for NSAID-induced enteropathy in patients with rheumatoid arthritis. METHODS A cross-sectional study using capsule endoscopy was conducted. A total of 113 patients who took NSAIDs for over 3 months underwent capsule endoscopies. Endoscopic findings were scored as (0) normal, (1) red spots, (2) 1-4 erosions, (3) >4 erosions, or (4) large erosions/ulcers. Initial scores were grouped into 3 categories: No damage (0-1), mild damage (2), and severe damage (3-4), and the potential risk factors for damage development were assessed. RESULTS Five patients were excluded because of incomplete visualization of the entire small intestine. Fifty-two (47.2%) and 27 (25%) patients had no damage and mild damage, respectively, while the remaining 30 patients (27.8%) had severe damage and significantly decreased hemoglobin levels. In a multivariate logistic regression analysis, ages of 65 years or more (odds ratio [OR], 4.16; 95% confidence interval [CI], 1.51-11.47), proton pump inhibitor usage (OR, 5.22; 95% CI, 1.36-20.11), and histamine H2 receptor antagonist usage (OR, 3.95; 95% CI, 1.28-12.25) were independent risk factors for severe damage. CONCLUSIONS Elderly patients and acid suppressant users are more likely to develop severe NSAID-induced enteropathy.
Collapse
Affiliation(s)
- Toshio Watanabe
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Patrignani P, Tacconelli S, Bruno A, Sostres C, Lanas A. Managing the adverse effects of nonsteroidal anti-inflammatory drugs. Expert Rev Clin Pharmacol 2012; 4:605-21. [PMID: 22114888 DOI: 10.1586/ecp.11.36] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Conventional medical treatment for rheumatoid arthritis and osteoarthritis includes the use of NSAIDs (traditional and selective inhibitors of cyclooxygenase [COX]-2), because they provide unmistakable and significant health benefits in the treatment of pain and inflammation. However, they are associated with an increased risk of serious gastrointestinal (GI) and cardiovascular (CV) adverse events. Both beneficial and adverse effects are due to the same mechanism of action, which is inhibition of COX-dependent prostanoids. Since CV and GI risk are related to drug exposure, a reduction in the administered dose is recommended. However, this strategy will not eliminate the hazard owing to a possible contribution of individual genetic background. Further studies will be necessary to develop genetic and/or biochemical markers predictive of the CV and GI risk of NSAIDs.
Collapse
Affiliation(s)
- Paola Patrignani
- Department of Medicine and Center of Excellence on Aging, G. d'Annunzio University, and CeSI, Via dei Vestini 31, 66100 Chieti, Italy.
| | | | | | | | | |
Collapse
|
|
48
|
Whittle SL, Colebatch AN, Buchbinder R, Edwards CJ, Adams K, Englbrecht M, Hazlewood G, Marks JL, Radner H, Ramiro S, Richards BL, Tarner IH, Aletaha D, Bombardier C, Landewé RB, Müller-Ladner U, Bijlsma JWJ, Branco JC, Bykerk VP, da Rocha Castelar Pinheiro G, Catrina AI, Hannonen P, Kiely P, Leeb B, Lie E, Martinez-Osuna P, Montecucco C, Ostergaard M, Westhovens R, Zochling J, van der Heijde D. Multinational evidence-based recommendations for pain management by pharmacotherapy in inflammatory arthritis: integrating systematic literature research and expert opinion of a broad panel of rheumatologists in the 3e Initiative. Rheumatology (Oxford) 2012; 51:1416-25. [PMID: 22447886 PMCID: PMC3397467 DOI: 10.1093/rheumatology/kes032] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2011] [Revised: 01/25/2012] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE To develop evidence-based recommendations for pain management by pharmacotherapy in patients with inflammatory arthritis (IA). METHODS A total of 453 rheumatologists from 17 countries participated in the 2010 3e (Evidence, Expertise, Exchange) Initiative. Using a formal voting process, 89 rheumatologists representing all 17 countries selected 10 clinical questions regarding the use of pain medications in IA. Bibliographic fellows undertook a systematic literature review for each question, using MEDLINE, EMBASE, Cochrane CENTRAL and 2008-09 European League Against Rheumatism (EULAR)/ACR abstracts. Relevant studies were retrieved for data extraction and quality assessment. Rheumatologists from each country used this evidence to develop a set of national recommendations. Multinational recommendations were then formulated and assessed for agreement and the potential impact on clinical practice. RESULTS A total of 49,242 references were identified, from which 167 studies were included in the systematic reviews. One clinical question regarding different comorbidities was divided into two separate reviews, resulting in 11 recommendations in total. Oxford levels of evidence were applied to each recommendation. The recommendations related to the efficacy and safety of various analgesic medications, pain measurement scales and pain management in the pre-conception period, pregnancy and lactation. Finally, an algorithm for the pharmacological management of pain in IA was developed. Twenty per cent of rheumatologists reported that the algorithm would change their practice, and 75% felt the algorithm was in accordance with their current practice. CONCLUSIONS Eleven evidence-based recommendations on the management of pain by pharmacotherapy in IA were developed. They are supported by a large panel of rheumatologists from 17 countries, thus enhancing their utility in clinical practice.
Collapse
Affiliation(s)
- Samuel L Whittle
- Rheumatology Unit, The Queen Elizabeth Hospital, Woodville South, South Australia 5011, Adelaide, Australia.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
49
|
Boike JR, Kao R, Meyer D, Markle B, Rosenberg J, Niebruegge J, Stein AC, Berkes J, Goldstein JL. Does concomitant use of paracetamol potentiate the gastroduodenal mucosal injury associated with aspirin? A prospective, randomised, pilot study. Aliment Pharmacol Ther 2012; 36:391-7. [PMID: 22742578 DOI: 10.1111/j.1365-2036.2012.05200.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2012] [Revised: 06/09/2012] [Accepted: 06/11/2012] [Indexed: 12/14/2022]
Abstract
BACKGROUND Paracetamol is commonly prescribed for first-line symptomatic treatment in patients with osteoarthritis and aspirin is often co-administered for cardiovascular prophylaxis. It is not known if an interaction exists between aspirin and paracetamol in regards to gastroduodenal mucosal injury. AIM To investigate whether or not co-administered aspirin with paracetamol results in an increased rate of endoscopic gastroduodenal mucosal injury as compared to either agent alone. METHODS In this prospective, double-blind, randomised, three-arm, placebo- and active-controlled, parallel-group pilot study healthy adult subjects (18-75 years old) with a normal baseline trans-nasal oesophagogastroduodenoscopy (TN-EGD), received oral paracetamol 4000 mg q.d.s. (n = 21), aspirin 325 mg q.d.s. (n = 19) or paracetamol 4000 mg q.d.s. and aspirin 325 mg q.d.s. (n = 20). Upper gastrointestinal mucosal injury was evaluated after 7 days of treatment with TN-EGD. RESULTS The rate of gastric ulcers in subjects receiving paracetamol (0/21, 0%) alone or aspirin (3/19, 16%) or both (2/20, 10%) was not different. There were, however, significantly more subjects with one or more lesions (erosion or ulcer) per subject in the paracetamol and aspirin (16/20, 80%) treated subjects as compared to the aspirin (8/19, 42%, P < 0.001) or the paracetamol (3/21, 14%, P < 0.01) exposed subjects. The mean number of lesions per subject was also greater (7.9 vs. 0.7, P < 0.01) in those treated with aspirin and paracetamol compared to paracetamol alone. CONCLUSIONS Co-administration of paracetamol and aspirin was not associated with a significant difference in endoscopic ulcer rates compared to either drug alone. There was a strong signal for increased endoscopic erosions and ulcers in the combined group compared to either aspirin or paracetamol alone.
Collapse
Affiliation(s)
- J R Boike
- Department of Digestive Diseases and Nutrition, University of Illinois at Chicago, 3731 N Clifton Ave, Chicago, IL 60613, USA.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Radner H, Ramiro S, Buchbinder R, Landewé RBM, van der Heijde D, Aletaha D. Pain management for inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and other spondylarthritis) and gastrointestinal or liver comorbidity. Cochrane Database Syst Rev 2012; 1:CD008951. [PMID: 22258995 PMCID: PMC8950811 DOI: 10.1002/14651858.cd008951.pub2] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Even with optimal disease-modifying treatment and good control of disease activity, persistent pain due to structural damage is common in people with inflammatory arthritis and therefore additional treatment for pain might be required. Because comorbidity is highly prevalent in people with inflammatory arthritis, it is important to consider comorbidities such as gastrointestinal or liver diseases in deciding upon optimal pharmacologic pain therapy. OBJECTIVES To assess the efficacy and safety of pharmacological pain treatment in patients with inflammatory arthritis who have gastrointestinal or liver comorbidities, or both. SEARCH METHODS We searched MEDLINE, EMBASE and Cochrane CENTRAL for studies to June 2010. We also searched the 2007-2010 ACR and EULAR abstracts and performed a hand search of reference lists of articles. SELECTION CRITERIA All randomised or quasi-randomised controlled trials (RCTs or CCTs) were considered for inclusion for assessment of efficacy. For safety we also considered single arm trials, controlled before-after studies, interrupted time series, cohort and case-control studies, and case series of 10 or more consecutive cases. Pain therapy comprised paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, opioid-like drugs (tramadol) and neuromodulators (anti-depressants, anticonvulsants and muscle relaxants). The study population comprised adults (>18 years) with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or other spondyloarthritis who had gastrointestinal and/or hepatic comorbid conditions. Outcomes of interest were pain, adverse effects, function and quality of life. Studies that included a mixed population of inflammatory arthritis and other conditions were included only if results for inflammatory arthritis were reported separately. DATA COLLECTION AND ANALYSIS Two review authors independently selected trials for inclusion, assessed risk of bias and extracted data. MAIN RESULTS Out of 2869 articles only one single arm open trial was identified that fulfilled our inclusion criteria. This trial assessed the safety and efficacy of naproxen (dosage not specified) in 58 patients with active rheumatoid arthritis and gastrointestinal comorbidities for up to 52 weeks. Thirteen participants (22%) remained on gold therapy, four participants (10%) remained on hydroxychloroquine, 27 (47%) remained on corticosteroids, 12 (21%) remained on salicylates and all participants continued on antacids and bland diet. The presence of faecal occult blood was reported in 1/58 participants tested between weeks 1 to 26 and 2/32 participants tested between weeks 27 to 52. Over the course of the study, seven participants (12.1%) withdrew due to adverse events but of these, only two participants withdrew due to gastrointestinal side effects (abdominal pain n=1, nausea n=1) and no serious adverse events were reported. Noteable, out of 14 studies excluded due to inclusion of mixed population (osteoarthritis or other rheumatic conditions) or intervention already withdrawn, five trials reported higher risk of developing gastrointestinal events in patients with prior gastrointestinal events when treated with NSAIDs. AUTHORS' CONCLUSIONS On the basis of the current review, there is scant evidence to guide clinicians about how gastrointestinal or liver comorbidities should influence the choice of pain treatment in patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or other spondylarthritis. Based upon additional studies that included a mixed population of participants with a range of rheumatic conditions, NSAIDs should be used cautiously in patients with inflammatory arthritis and a history of gastrointestinaI comorbidity as there is consistent evidence that they may be at increased risk.
Collapse
Affiliation(s)
- Helga Radner
- Division of Rheumatology,Department of InternalMedicine 3,MedicalUniversityVienna,Vienna,
| | | | | | | | | | | |
Collapse
|