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1 NSAID Induced Gastropathy & Enteropathy 서울의대내과학교실 분당서울대학교병원 내과이동호
2 Table of contents Mechanism Gastropathy NSAIDs, Coxibs & H. pylori NSAIDs and Lower GI Safety Diagnosis/ Management for GI Complications of NSAIDs Treatment & Prevention
3 Mechanism
4 Mechanism of action of Cox-1 and Cox-2 Celecoxib, NSAIDs and the skeleton; Drugs of Today 2008, 44(9): ; J. Patrick O Connor and Thomas Lysz
5 Mechanism of action of NSAIDS: New concept
6 COX-1 & COX-2
7 COX-2 selectivity of NSAIDs (In vitro) 1
8 In Vivo COX-1 inhibition % In Vivo 60 COX-1 Inhibition Placebo Refecoxib 12.5 mg qd Refecoxib 25 mg qd Diclofenac 50 mg qd Meloxicam 15 mg qd Ibuprofen 800 mg tid Naproxen Sodium 550 mg bid J Clin Pharmacol 2000;40:1109
9 Gastropathy
10 What s the NSAID gastropathy? Acute gastric mucosal erosions, subepithelial hemorrhages A predilection for fundus and body Sleisenger & Fordtran s. 7 th ed. 2002:
11 Epidemiology of NSAID-induced GI complications 10~20% of NSAID user; dyspepsia 5~15% of RA patients using NSAID; stop medication within 6 months 1.3% of RA patients taking NSAID; serious GI complications Mortality of NSAID-induced bleeding; 5~10% Sleigenser and Fordtran s Gastrointestinal and Liver disease 8th ed. Pp
12 US mortality data in ,000 15th cause of death in USA 20,000 20,197 16,685 16,500 Hospitalization : 100,000/ year and Number of deaths 15,000 10,000 5,000 10, % of them die 5,338 4,441 1,437 0 Singh et al. J Rheumatol 1999
13 ns-nsaid-induced ulcers Incidence of gastric ulcer; 10~40% Incidence of duodenal ulcer; 4~15% Asymptomatic in most cases Risk of clinically significant NSAID-induced ulceration; 1% Sleisenger & Fordtran s. 7 th ed. 2002:
14 Most patients with ns-nsaid-related GI complications are asymptomatic Asymptomatic Symptomatic 42% 58% 81% 19% UK epidemiological study 1 Armstrong, Blower, 1987 US observational cohort study 2 Singh et al, Armstrong CP, Blower AL. Gut. 1987;28: Singh G et al. Arch Intern Med. 1996;156:
15 Reasons for NSAID-induced asymptomatic ulceration NSAIDs... Induce analgesia Exacerbate a previously existing silent ulcer perforate or bleed Anticoagulants (antiplatelet actions) increase bleeding tendency Continue NSAID consumption continued risk of asymptomatic ulcerations ulcer complication Sleisenger & Fordtran s Gastrointestinal and Liver Disease, 7th ed. 413
16 NSAID-induced ulcer complications: Risk factors Prior complicated ulcer Use of multiple NSAIDs (including aspirin) High-dose of NSAIDs Anticoagulant therapy Prior uncomplicated ulcer Age > 70 years H. pylori infection Glucocorticoid therapy * Numbers at ends of shaded bars denote odds ratios. Sleisenger and Fortran s Gastrointestinal and Liver disease, 8 th edition,, p.20
17 GI risk factors in Korean population taking NSAIDs 2008 GI risk assessment study 대상 : 병원을방문한, 현재 NSAIDs 를복용중인 20 세이상의성인환자 (N=3,140) Data on file (presented at 2008 fall congress of Korean Orthopaedic Aassociation on Oct 16, 2008)
18 1 out of 2 Koreans who take NSAIDs is on very high/ high GI risk 대상 : 병원을방문한, 현재 NSAIDs 를복용중인 20 세이상의성인환자 (N=3,140) 45% 55% 49% 51% High/ Very high group Mild/ Moderate group Cox-2 inhibitor 처방 Nonselective NSAIDs 처방 Data on file (presented at 2008 fall congress of Korean Orthopaedic Aassociation on Oct 16, 2008)
19 Age as a risk factors of upper GI bleeding Age Case N=1,457 Controls N=10,000 RR (95% CI) ( ) ( ) ( ) Rodriguez LAG et al, Lancet 1994;343:769
20 Age > 60, the most important GI risk factor in Korean population taking NSAIDs Lee HL, Han DS, Kim JB, et al. Korean J Gastroenterol 2004;44:
21 Low dose aspirin is safe? Daily aspirin use for >= one month OR (95% CI) Any dose 3.2 ( ) 75 mg 2.3 ( ) 105 mg 3.2 ( ) 300 mg 3.9 ( ) Low dose aspirin (usually 325 mg daily): very commonly prescribed for the prevention of cardiovascular diseases Weil J et al, BMJ 1995;310:827
22 Endoscopic upper GI ulcers in low-dose ASA users Goldstein et al 1999 Pooled analysis of randomized trials ulcers (%) Incidence of % 10.4% Placebo + ASA (n=20) Celecoxib + ASA (n=105) 22.2% Ns- NSAIDs + ASA (n=108) Goldstein JL et al. Gastroenterol ;116:A174. Abstract G0759.
23 How many patients are taking aspirin? 60 세이상의골관절염환자의약 60% 가 저용량아스피린복용 1 40 세이상성인 ( 미국 ) 의약 41% 가 심혈관계질환예방목적으로저용량아스피린복용 2 1. 임상류마티스학, 임상류마티스학편찬위원회, 한국의학사, p Michael Pignone et al. Am J Prev Med 2007;32(5):
24 KFDA 는 2008 년 3 월 11 일자로아스피린의 NSAIDs 와의병용을금기 아스피린, NSAIDs 와병용금기 - 3/11 일자허가사항변경내용 아스피린허가사항변경전 아스피린허가사항변경후 일반적주의 : 상호작용 : 다른소염진통제와병용은피하는것다른비스테로이드성소염진통제이바람직하다 (NSAIDs) 및살리실산과병용투여할경우출혈을증가시키거나신기능을감소시킬수있으므로병용투여하지않는다.
25 아스피린과의병용투여허가사항 : Celecoxib vs. other NSAIDs Celecoxib 저용량아스피린 (1일 325mg 이하 ) 이외에다른비스테로이드성소염진통제 (NSAIDs) 와병용투여할경우이상반응의위험이증가할수있으므로병용투여하지않아야합니다. meloxicam, acelofenac, diclofenac, zaltoprofen 등의 nonselective NSAIDs 다른비스테로이드성소염진통제 (NSAIDs) 와병용투여할경우이상반응의위험이증가할수있으므로병용투여하지않는다. Celecoxib can be used with low-dose aspirin
26 Risk of NSAID-associated ulcer complications over time is constant MUCOSA Trial 1 VIGOR Trial 2 of upper GI ication Probability compli NSAIDs (n=4439) incidence (%) Cumulative Naproxen (n=4029) Month Month 1. Silverstein FE et al. Ann Intern Med. 1995;123: FDA Arthritis Advisory Committee; February 8, 2001; Gaithersburg, Md
27 Risk of GI hemorrhage: ns-nsaids vs. Coxibs vs. Meloxicam Reference: Nonselective NSAIDs RR = 1.0 RR = 0.36 (95% CI: ) P=.043 RR = 0.84 (95% CI: ) P= Nonselective NSAIDs (ASA monotherapy excluded) Coxibs Meloxicam (56% at 7.5 mg/day, 38% at 15 mg/day) MacDonald TM, et al. 2003;52:
28 NSAID-induced GU bleeding (Meloxicam) Exposed vessel with spurting Hemoclipping
29 NSAIDs, Coxibs & H. pylori
30 NSAIDs and H. pylori infection : Injurious effects on the gastric mucosa Pleura DA. Am J Med 2004;117(5):63s-71s
31 H. pylori and low-dose aspirin Body Antrum Bulb 2.5 * 2.0 Injury scor re PL ASA PL ASA PL ASA PL ASA PL ASA PL ASA HP+ HP+ HP- HP- HP- HP+ Am J Gastroenterol 2001;96:
32 GI complications and H. pylori Peura DA. Am J Med 2004;117(5):63s-71s
33 Celecoxib vs Naproxen in H. pylori Patients with ulcer (%) H.pylori-positive H.pylori-negative 5 Celecoxib 200 mg b.i.d Naproxen 500 mg b.i.d * Significantly different from HP-positive celecoxib group : p<0.05 Am J Gastroenterol 2001;96:
34 Effect of H. pylori eradication in the prevention of NSAIDs ulcers Study Eradication n/n No eradication n/n OR (random) 95% CI OR (random) 95% CI CHAN /50 12/ (0.05, 0.77) HAWKEY /127 21/ (0.51, 1.95) CHAN /51 15/ (0.08, 0.74) LABENZ /161 10/ (0.04, 0.94) LAI /70 6/ (0.24, 2.82) Total (95% CI) (0.20, 0.93) Favours eradication Favours no eradication Total event: 34 (Eradicatio), 64 (No eradication) Test for heterogeneity: X 2 =9.29, df=4 (P=0.05) Test for overall effect: Z=2.15 (P<0.03) Vergara M. Aliment Pharmacol Ther 2005;21:
35 NSAIDs and Lower GI Safety
36 NSAID Toxicity Extends to the Lower GI Tract (Distal to Ligament of Treitz) Importance and clinical relevance of lower GI events are becoming increasingly recognized Lower GI is defined as events that occur distal to the ligament of Treitz, or distal to the fourth segment of the duodenum Wilcox et al. Dig Dis Sci. 1997;42: ; Lanas et al. Gastroenterology. 1997;112: Allison et al. N Engl J Med. 1992;327: Laine et al. Gastroenterology. 2003;124:
37 NSAID Toxicity Extends to the Lower* GI Tract Studies suggest that patients who take NSAIDs have an increased risk for lower GI clinical events 1,2 *Lower GI here refers to any event that occur distal to the ligament of treitz or fourth segment of the duodenum. 1 Laine et al. Gastroenterology. 2003;124: ; 2 Allison et al. N Engl J Med. 1992;327:
38 Ratio of lower GI risk in total GI risk Chan FK, Hung LC, Seun BY, et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis, N Engl J Med
39 Upper vs Lower* GI Complication Trends by Source ( , Spain) N=30,498 Over the last 10 years, there has been a decreasing trend in the rates of hospitalisations due to upper GI complications in contrast with an increasing trend of lower GI complications. The clinical impact and severity of hospitalisations due to lower GI events were greater than those of upper GI events. *Lower GI refers to the small intestine (beyond the duodenum) and the colon (distal to the ligament of treitz). Lanas et al. DDW 2008 Abstract
40 Pathogenesis of damage 1. Local NSAID toxicity increases intestinal permeability 2. Mucosal response to insults from luminal contents: local inflammatory reaction 3. Intestinal ulcers 4. Intestinal complications perforation Diaphragm-like Sleisenger and Fordtrans Gastrointestinal and Liver disease, 8 th ed
41 Subclinical and clinical damage to lower GI tract associated with NSAIDs Sub-clinical damage Increased in mucosal permeablility Mucosal inflammation Fecal occult blood loss Ileal dysfunction Malabsorption Clinical damage Anemia Bleeding/ Perforation Execerbation of underlying disease Diverticultitis Strictures Small bowel, colonic and rectal ulceration Colitis Chronic inflammatory bowel disease Angiodysplsatic lesions Lanas A et al. Digestion. 2006:136
42 Mechanism of damage 1. COX inhibition with reduced prostaglandin bicarbonate and mucous secretion, as well as reduced mucosal blood flow impairing mucosal defense and repair. Inhibition of cell proliferation & angiogenesis. Increased apoptosis. 2. Direct topical effect that cause cellular damage with a breach in intestinal integrity, thus allowing the luminal contents to cause further damage. 3. Bacteria and their degradation products are neutrophil chemoattractants initiating and exacerbating the inflammatory response in the small bowel.
43 Spectrum of NSAID-induced pathology 1. Acidic NSAIDs increase intestinal permeability with 12 h of administration and that leads to small bowel inflammation within 10 days. 2. Increased permeability 2. Increased permeability Protein loss (protein losing enteropathy), bleeding from inflammated mucosa, mucosal breaks, petechial hemorrhage Perforation of an ulcer or obstruction Surgery
44 Diagnosis of NSAID enteropathy 1. NSAID-induced enteropathy is largely based on measurement of small intestinal permeability. Use of chromium -51-labeled ethylenediaminetetraacetic acid 51 Cr-EDTA 2. Assay of surrogate markers of inflammation in stool Qualitative indium 111 labeled neutrophil scintigraphy( 111 IN) 3. Enteroscopy Japanese study group for Double-balloon endoscopy database detected 51% of patients taking NSAIDs had mucosal breaks. 4. Capsule endoscopic assessment of NSAIDs enteropathy recently.
45 Double balloon enteroscopy Oral approach Anal approach
46 Capsule endoscopy
47 Capsule Endoscopy view 1
48 Capsule Endoscopy view 2
49 Result : J gastroenterology 2009;44:64-71 Table 2. Capsule endoscopy findings Group Any adenoma No/total no.(%) Relative Risk (95% CI) Adjusted Odds ratio (95% CI) Subjects with 47/199(23.6) 1.62( (1.45- hyperplastic polyps on baseline colonoscopy 2.15) 2.71) Subjects with no polyps on baseline colonoscopy 154/1057(14.6 ) Men 143/712(20.1) 1.88( ) Women 58/544(10.7) 1.92( )
50 Result : J gastroenterology 2009;44: Short term diclofenac study: New pathology in 27 (68%) of 40 pts. The most common lesion is mucosal break in 16(40%) pts. 2. Long term NSAIDs study: 82(68%) of the 120 pts on long term NSAIDs had small intestinal pathology that differed significantly from that of controls.(p<0.001) 41(34%)pts have more than on type of lesion. The main pathology was related to mucosal breaks (29%). 3. Twenty (50%) of the 40 pts on long-term selective COX-inhibitors had abnormal capsule endoscopies. No difference significantly (P>0.3) from results from NSAIDs.
51 Discussion(1) J gastroenterology 2009;44: Regardless of duration of use NSAIDs, the spectrum of pathology & lesions is also similar. (Mucosal breaks of the most prevalent clinically significant lesion) 2. Overall proportion of mucosal breaks is smaller in the longterm group, as strictures are prevalent in this group. 3.COX-2 selective agents were intended to reduce gastrointestinal toxicity by sparing COX1-relativly toxicity. However our results show that long term treatment with COX- 2 selective agents is associated with a high prevalence of small bowel damage.
52 Disscussion(2) J gastroenterology 2009;44: COX-2 selective inhibitors are selective & not exclusive and thus have some COX-1 inhibitory activity also. 2COX-2 is also found constitutively in some organs & may have a regulatory role in some tissues, such as altering mucosal blood flow. 3 Despite the roles of COX-1 in housekeeping & GI mucosal integrity and of COX-2 in inflammation, respectively, COX-1 knockout mice do not develop GI ulceration.
53 Disscussion(3) J gastroenterology 2009;44: In if patients are naturally low or even deficient in COX-1, then COX-2 selective inhibition will effectively be nonselective. 5 COX-2 may have an anti-inflammatory role in the vasculature (cell proliferation, adhesion molecule receptor expression, and cytokine release) and so its inhibition may have proinflammation.
54 Conclusions : J gastroenterology 2009;44: Capsule endoscopy demonstrates evidence of macroscopic injury to the small intestine, in upto 68%of volunteers, resulting form 2 weeks ingestion of slow release diclofenac. 2. Long term use of NSAIDs and COX-2 inhibitors causes comparable small bowel damage(50%~68%).
55 Small intestinal ulcers and Stricture Erosions and ulcers in the small intestine have been directly imaged at colonoscopy, enteroscopy, and recently during capsule endoscopy.
56 Small intestinal ulcers and Stricture Diaphragm stricture Believe to be pathognomonic of NSAID use. multiple,2 to 4-mm thick septae in mid small bowel. Can reduce the lumen to a pinhole.
57 Functional aspects of NSAID induced enteropathy Characterized by increased intestinal permeability and mild mucosal inflammation. About 70% of NSAID users demonstrate intestinal inflammation by indirect methods of 111 In-labeled leukocyte scintigraphy and 111 In fecal excretion. Intestinal protein loss can occur, up to the equivalent of more than 300 ml serum per day. This can be sufficient to be produce hypoalbuminemia.
58 NSAIDs and exacerbation of IBD NSAIDs exacerbate disease activity in both ulcerative colitis and CD. Comparing disease activity in 60 patients with inflammatory bowel disease (IBD) and 62 with irritable bowel syndrome (IBS), NSAIDs provoked disease activity in 31% of IBD patients compared with 2% of the IBS patients. COX-2 inhibitors appear to exacerbate symptoms of IBD in the same way that nonselective NSAIDs do. Consistent with other studies, 39% of the 33 IBD patients experienced exacerbation of their disease.
59 Mechanism(1) The etiology of NSAID damage to the small bowel is probably mediated by COX-independent mechanisms. The protective effects of misoprostol suggest that COX mechanisms play at least some part.
60 Mechanism(2) 1.First step The initiation of mucosal damage is the result of acidic moieties directly damaging surface membrane phospholipids. NSAIDs then damage enterocyte mitochondria during their absorption by uncoupling oxidative phosphorylation. 2.Second step Mitochondrial damage leads to intracellular energy depletion, efflux of calcium, and secondary generation of free Radicals 3.Third step Loss of the mucosal barrier leaves the enterocyte vulnerable to damage by intraluminal contents: bile, food, bacteria, and enzymes.
61 NSAIDs toxicity in major outcome studies 1.The rate of serious lower GI events per 100 patient years was 0.41 for rofecoxib and 0.89 for naproxen. Rec) Serious lower gastrointestinal clinical events with nonselective NSAID or Coxib use. Gastroenterology 2003; 124: Celecoxib is Significantly lower incidence of clinically significant decreases in hemoglobin and/or hematocrit compared with NSAIDtreated patients. Rec) Silverstein FE, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib cs NSAIDs for OA and RA in the CLASS study. JAMA 2000; 284:
62 Diagnosis 1.suspicion: pts taking NSAIDs who have occult GI blood loss hypoalbuminemia, or even obstructive symptom. 2.Research tool: (1) Scintigraphy (2) 51 Cr-EDTA measure (3) Enteroscopy Lesions attributed to NSAID use have been found in 40% of NSAID users at enteroscopy but the procedure is technically difficult, time-consuming and requires sedation. (4) Capsule endoscopy
63 Management 1.Cessation of nonsteroidal anti-inflammatory drugs Removal of the causative drug is the first priority. 2.Misoprostol High-dose (1200-mg) misoprostol has been shown in some trials to moderate the increased intestinal permeability caused by indomethacin. 3.Metronidazole Given the putative role of enteric bacteria in accentuating NSAID enteropathy. Protective effect by a direct effect on mitochondrial oxidative phosphorylation rather than its antibacterial reaction. 4.Sulfasalazine Reduce intestinal permeability to pts with RA on NSAIDs.
64 ns-nsaids significantly increase lower GI tract clinical outcome - bleeding Pts with hematoc chesia or LGIB, % % % 25 % 19 % 60 % 34 % Ns-NSAIDs NSAIDs Controls Holt et al. 1 (n=98/95) Lanas et al. 2 (n=21/138) Wilcox et al. 3 (n=105/1895) 1. Holt et al. Dig Dis Sci 1993: Lanas et al. Gastroenterol 1992: Wilcox et al. Dig Dis Sci 1997:990
65 ns-nsaids significantly increase lower GI tract clinical outcome - perforation Pts with hemato ochesia or LGIB, % % 10 % 75 % 27 % Ns-NSAIDs NSAIDs Controls Langman et al. 1 (n=107/107) Lanas et al. 2 (n=16/152) 1. Langman et al. Br Med J 1985: Lanas et al. Gastroenterol 1997:683
66 Capsule endoscopy study % of subjects with small bowel mucosal breaks 60 P<.001 P< Incidence of SB 1 Mucosal Br reaks, % P = 0.04 for celecoxib vs. placebo. 7 0 Celecoxib Naproxene plus PPI Placebo Goldstein JL et al. Clini Gastroenterol Hepatol. 2005:133
67 Lower GI toxicity of ns-nsaids: Summary Nonselective NSAIDs (ns-nsaids) are associated with increased risk of lower GI damages Small and large bowel mucosal break or ulcers Increase fecal blood loss Hypoalbuminemia Lower GI damage may occur rapidly, within the first 2 weeks of treatment Gastroprotective agents, such as omeprazole, do not adequately protect against ns-nsaid-related lower GI damage
68 Case 1: Multiple small bowel ulcers
69 Case 2: Web & web with ulcer in small bowel
70 Case 3: Stricture in small bowel
71 Diagnosis and Management for GI Complications of NSAIDs
72 NSAID Induced Bleeding (Ibuprofen) Active bleeding Injection
73 Fig. 1 Initial EGD findings There was a giant duodenal ulcer encircling the lumen from the pylorus to the postbulbar portion.
74 Fig. 2 Follow-up EGD findings: 17 days later The previous duodenal ulcer was healed and the luminal stenosis was noted at the Bulb.
75 Fig. 3 Follow-up EGD Finding: 24 days later The Luminal Obstruction was noted at the Duodenal Bulb.
76 Healing of NSAID-induced ulcer NSAID-induced ulcer is slow to heal Rate of relapse/ rebleeding is high Differential diagnosis with gastric cancer is sometimes difficult
77 Methods of endoscopic hemostasis Electrocauterization - Bipolar catheter, Heat probe, Hot biopsy forcep Epinephrine injection treatment Endoscopic cliping APC (argon plasma coagulation) Thrombin Surgery Angiography with embolization
78 Hemostasis with APC Hemostasis with APC
79 Hemo-clipping GU (A1) with oozing s/p clip
80 90 세 / 여, femor nect Fx with op: 1 주일후 bleeding- Hemoclipping
81 Treatment & Prevention
82 Treatment of NSAID-related GI symptoms Dyspepsia : Empirical Treatment with H 2 RA or PPI; Individualize Therapy, PPI favored H. pylori infection : Eradication Treatment only in Patients with a History of Peptic Ulcer Peptic Ulcer (NSAID discontinued) : H 2 RA or PPI Peptic Ulcer (NSAID continued) : PPI Wolfe. NEJM 1999;340:
83 Utilization of protective strategies by presence of GI risk factors Risk Factor More Risk Factors 2.5% 10.8% 0.1% 4.0% 14.7% 0.2% 86.6% 81.2% Coxib alone Protective strategy (PS) PS + Coxib No gastroprotection Sturkenboom MC. et al. Rheumatology 2003;42(S3):22-31
84 Prevention of NSAID-induced ulcers H 2 RA (H 2 Receptor Antagonists) : Usual healing dose does not prevent complications. Prostaglandins E Analogs (ex. Misoprostol) : Side Effects (nausea, pain, diarrhea) Seldom recommended Proton Pump Inhibitors COX-2 Selective Agents Sleisenger and Fordtrans Gastrointestinal and Liver disease, 8 th ed
85 Antacids/ H2RA relieves dyspepsia but not ulcer risk Singh et al. Arch Intern Med ;156:
86 Using antacids/ H2 blocker in patients with NSAID-related dyspepsia may increase ulcer complications by... Masking dyspeptic symptoms, thereby Creating a false sense of security in patients with underlying high GI risk Sleisenger and Fordtrans Gastrointestinal and Liver disease, 8 th ed
87 Is acid suppression the answer to dyspepsia? Patients with sympto om relief (%) Cumulative proportion of patients with symptom relief on esomeprazole (E) 20 mg and 40 mg vs placebo Cox-2 selective E40 (n = 134) E20 (n = 118) Placebo (n = 133) Days Log-rank test: E40 vs placebo, P < 0.001; E20 vs placebo, P = Nonselective E40 (n = 240) E20 (n = 257) Placebo (n = 257) Days Log-rank test: E40 vs placebo, P = 0.002; E20 vs placebo, P = Hawkey C, et al. Am J Gastroenterol. 2005;100:
88 Dyspeptic symptoms are less common with celecoxib compared to diclofenac Findings at 1 year 25 Celecoxib ients * Diclofenac % pati 0 * P < 0.05 Self-reported dyspepsia Goldstein et al. Aliment Pharmacol Ther. 2002;16:819.
89 ns-nsaid + PPI vs. Celecoxib : Overall upper GI complications Less complications More complications ns-nsaids alone (reference category) 1 ns-nsaids + PPI 0.67 ( )* Celecoxib alone ns-nsaid + low-dose misoprostol 0.39 ( )** 0.74 ( )** Adjusted OR (95%CI) *p<0.05 **p<0.01 ET Laura et al. Gastroenterology 2008 Apr; 134(4):937-44
90 Increase in Serious Upper Ulcer Complications Following COX-2 Decline Year COX-2 Users (%) PPIs Users (%) Misoprostol (%) Gastroprotection Gap* (%) Serious Ulcer GI Complications (per 100,000 NSAID prescriptions) *Defined as patients not receiving gastroprotection. COX-2, cyclooxygenase-2 selective NSAID; PPI, proton pump inhibitor. Singh et al. Ann Rheum Dis. 2007;66(suppl II):509.
91 Increasing Rates of Serious GI Complications Despite Increase in PPI Use Serious ulcer complications have increased despite an increase in PPI prescriptions following COX-2 selective NSAID use decline Year COX-2 Users (%) PPIs Users (%) Misoprostol (%) Gastroprotection Gap* (%) Serious Ulcer GI Complications (per 100,000 NSAID prescriptions) *Defined as patients not receiving gastroprotection. Singh et al. Ann Rheum Dis. 2007;66(suppl II):509.
92 Take home messages NSAIDs-induced GI complications are very prevalent and their mortality is high NSAIDS-related GI complications are problematic even more because most of the patients are asymptomatic
93 Take home messages Aspirin use, anticoagulant therapy, age, steroids use, and etc. should be considered seriously as GI risk factors As H. pylori eradication itself cannot eliminate ulcer induced by NSAIDs, gastroprotective strategies are needed
94 Take home messages (Cont d) Ns-NSAIDs are associated with increased risk of lower GI damages that may occur rapidly within the fist 2 weeks of treatment and PPI do not adequately protect Among conventional gastroprotective strategies, H 2 RA and 2 misoprostol are not recommended to use
95 Prevention & Management of NSAID induced Gastropathy PPI PG High Dose of H2RA COX-2 Selective Agent
96 Prevention & Management of NSAID induced Enteropathy PG Metronidazole Sulfasalazine COX-2 Selective Agent
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connect educational content with entertainment content and that production of various contents inducing educational motivation is important. Key words: edutainment, virtual world, fostering simulation
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대한수혈학회지:제권 제호, 0 한 대학병원의 혈액 폐기 분석 김병철ㆍ서영익ㆍ채금란ㆍ신정원ㆍ최태윤 = Abstract = 순천향대학교 의과대학 서울병원 진단검사의학교실 Analysis of Discarded Blood Components at a University Hospital in Korea Byung Chul Kim, Young Ik Seo, Gum Ran
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