(Microsoft PowerPoint - PGYVEDMWALGD [\310\243\310\257 \270\360\265\345])
|
|
|
- 혜리 승
- 5 years ago
- Views:
Transcription
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
슬라이드 1
Resolving pain medicationrelated GI trouble 성균관대학교내과이준행 What is NSAID? N on S teroidal A nti I nflammatory D rug N umerous S ide effects A nd I ndispensable D rug Number of deaths US mortality data in
00약제부봄호c03逞풚
경희대학교 동서신의학병원 약품 정보지 2 0 0 7. S P R I N G. V O L. 0 1 신약 소개 02 Journal Review 03 Special Subject 04 복약 지도 06 의약품 안전성 정보 07 약제부 알림 07 약제부 업무 소개 08 E A S T - W E S T N E O M E D I C A L C E N T E R 본 약품
Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ
Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee University College of Medicine & Hospital E mail : ycell2@yahoo.co.kr Abstract
- i - - ii - - iii - - iv - - v - - vi - - 1 - - 2 - - 3 - 1) 통계청고시제 2010-150 호 (2010.7.6 개정, 2011.1.1 시행 ) - 4 - 요양급여의적용기준및방법에관한세부사항에따른골밀도검사기준 (2007 년 11 월 1 일시행 ) - 5 - - 6 - - 7 - - 8 - - 9 - - 10 -
Treatment and Role of Hormaonal Replaement Therapy
Treatment and Role of Hormone Replacement Therapy Chung-Ang University Hospital Chee Jeong Kim 7.2 5.3 6.4 5.6 7.3 5.5 1 1 2 3 4 10 11 7 34 49 122 123 1.0 - - 10. 2001 1998 1998 Improvement of postmenopausal
기관고유연구사업결과보고
기관고유연구사업결과보고 작성요령 2001 ~ 2004 2005 ~ 2007 2008 ~ 2010 2001 ~ 2004 2005 ~ 2007 2008 ~ 2010 1 2/3 2 1 0 2 3 52 0 31 83 12 6 3 21 593 404 304 1,301 4 3 1 8 159 191 116 466 6 11 (`1: (1: 16 33 44 106
노영남
Purpose: Delayed massive hemorrhages from pseudoaneurysm rupture of the peripancreatic large arteries, after pancreaticoduodenectomy, are fatal. We reviewed the clinical course and outcome of bleeding
한국성인에서초기황반변성질환과 연관된위험요인연구
한국성인에서초기황반변성질환과 연관된위험요인연구 한국성인에서초기황반변성질환과 연관된위험요인연구 - - i - - i - - ii - - iii - - iv - χ - v - - vi - - 1 - - 2 - - 3 - - 4 - 그림 1. 연구대상자선정도표 - 5 - - 6 - - 7 - - 8 - 그림 2. 연구의틀 χ - 9 - - 10 - - 11 -
A 617
Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R
Journal of Educational Innovation Research 2017, Vol. 27, No. 2, pp DOI: : Researc
Journal of Educational Innovation Research 2017, Vol. 27, No. 2, pp.251-273 DOI: http://dx.doi.org/10.21024/pnuedi.27.2.201706.251 : 1997 2005 Research Trend Analysis on the Korean Alternative Education
황지웅
Comparison of Laparoscopy and Exploration in the Distal Pancreatectomy BACKGROUND: To determine the benefits of laparoscopic surgery compared with exploration, the clinical outcomes of open and laparoscopic
김범수
Analysis of Outcomes after Resection of Sarcomatous Hepatocellular Carcinoma Purpose: Sarcomatous hepatocellular carcinoma (HCC) is rare. Therefore, the clinicopathologic characteristics and prognosis
1..
Volume 12, Number 1, 6~16, Factors influencing consultation time and waiting time of ambulatory patients in a tertiary teaching hospital Jee-In Hwang College of Nursing Science, Kyung Hee University :
May 10~ Hotel Inter-Burgo Exco, Daegu Plenary lectures From metabolic syndrome to diabetes Meta-inflammation responsible for the progression fr
May 10~12 2012 Hotel Inter-Burgo Exco, Daegu Plenary lectures From metabolic syndrome to diabetes Meta-inflammation responsible for the progression from obesity to metabolic syndrome originates in the
- 2 -
- 1 - - 2 - - 3 - - 4 - - 5 - - 6 - - 7 - - 8 - - 9 - - 10 - - 11 - - 12 - - 13 - - 14 - - 15 - - 16 - - 17 - - 18 - - 19 - - 20 - - 21 - - 22 - - 23 - - 24 - - 25 - - 26 - - 27 - - 28 - - 29 - - 30 -
歯1.PDF
200176 .,.,.,. 5... 1/2. /. / 2. . 293.33 (54.32%), 65.54(12.13%), / 53.80(9.96%), 25.60(4.74%), 5.22(0.97%). / 3 S (1997)14.59% (1971) 10%, (1977).5%~11.5%, (1986)
DBPIA-NURIMEDIA
27(2), 2007, 96-121 S ij k i POP j a i SEXR j i AGER j i BEDDAT j ij i j S ij S ij POP j SEXR j AGER j BEDDAT j k i a i i i L ij = S ij - S ij ---------- S ij S ij = k i POP j a i SEXR j i AGER j i BEDDAT
( )Jkstro011.hwp
비인강암의방사선치료결과및생존율에관한예후인자분석 2005 2 1 2005 3 28. :, Tel: 053)250-7665, Fax: 053)250-7984 E-mail: jhkim@dsmc.or.kr 정영연외 2 인 : 비인강암의예후인자분석 정영연외 2 인 : 비인강암의예후인자분석 Carcinoma of the nasopharynx treated by radiotherapy
ÀÇÇа�ÁÂc00Ì»óÀÏ˘
Common Allergic Diseases in Children Sang - Il Lee, M.D. Department of pediatrics Sungkyunkwan University School of Medicine, Samsung Medical Center E - mail : silee@smc.samsung.co.kr Abstract Allergy
슬라이드 1
소화성궤양, Peptic Ulcer 성균관대학교의과대학내과이준행 소화 소화성궤양 궤양 보통분들에게물어보았습니다. 소화성궤양 이라면어떤증상이생각나십니까? 소화불량 더부룩 가스 소화제는소화에도움이되지않는약입니다. 소화제는만성췌장염환자에서부족한소화효소를보충하는약입니다. 보통사람이소화불량증세로소화제를먹는다고소화가촉진되는것은아닙니다. 위궤양, 십이지장궤양이라부릅시다.
페링야간뇨소책자-내지-16
야간뇨의진단과치료 - 실제적접근 - Reference 1. Choo MS, Ku JH, Park CH et al. Prevalence of Nocturia in a Korean Population Aged 40 to 89 Years. Neurourol Urodyn 2008; 27:60-64. 2. Weiss JP. Prevalence
012임수진
Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar
Sheu HM, et al., British J Dermatol 1997; 136: Kao JS, et al., J Invest Dermatol 2003; 120:
Sheu HM, et al., British J Dermatol 1997; 136:884-890 Kao JS, et al., J Invest Dermatol 03; 1:446-464 1 10 0 3 Day Normal MLE Lotion Lotion MLE Cream Cream 80 7 70 6 3 Day Normal MLE Lotion Lotion MLE
대한한의학원전학회지26권4호-교정본(1125).hwp
http://www.wonjeon.org http://dx.doi.org/10.14369/skmc.2013.26.4.267 熱入血室證에 대한 小考 1 2 慶熙大學校大學校 韓醫學科大學 原典學敎室 韓醫學古典硏究所 白裕相1, 2 *117) A Study on the Pattern of 'Heat Entering The Blood Chamber' 1, Baik 1
#Ȳ¿ë¼®
http://www.kbc.go.kr/ A B yk u δ = 2u k 1 = yk u = 0. 659 2nu k = 1 k k 1 n yk k Abstract Web Repertoire and Concentration Rate : Analysing Web Traffic Data Yong - Suk Hwang (Research
한국 출산력의 저하 요인에 관한 연구
가족계획실천율 가족계획실천자 세 유배우부인 조출생률 년간 총출생아수 연앙인구수 일반출산율 년간 총출생아수 가임연령 여자연앙인구수 합계출산율 세 연령층 여성이 출산한 출생아수 세 연령층 여성의 연앙인구수 즉 합계출산율 합 6 계 출 산 율 5 4 3 2 1 1960 1973 1977 1981 1985 1989 1993 1997 2001
Abstract Background : Most hospitalized children will experience physical pain as well as psychological distress. Painful procedure can increase anxie
Volume 12, Number 1, 92~102, An Intervention Study of Pain Reduction during IV Therapy in Hospitalized Children Myo-Jin Kim 1), Joung-Hae Bak 1), Won-Seok Seo 2) Mi-Young Kim 3), Sun-Kyoung Park 3), Jai-Soung
2011´ëÇпø2µµ 24p_0628
2011 Guide for U.S. Graduate School Admissions Table of Contents 02 03 04 05 06 08 09 10 11 13 15 21 LEADERS UHAK INTERNATIONAL STUDENTS SERVICE www.leadersuhak.com Leaders Uhak International Students
11¹Ú´ö±Ô
A Review on Promotion of Storytelling Local Cultures - 265 - 2-266 - 3-267 - 4-268 - 5-269 - 6 7-270 - 7-271 - 8-272 - 9-273 - 10-274 - 11-275 - 12-276 - 13-277 - 14-278 - 15-279 - 16 7-280 - 17-281 -
- iii - - i - - ii - - iii - 국문요약 종합병원남자간호사가지각하는조직공정성 사회정체성과 조직시민행동과의관계 - iv - - v - - 1 - - 2 - - 3 - - 4 - - 5 - - 6 - - 7 - - 8 - - 9 - - 10 - - 11 - - 12 - - 13 - - 14 - α α α α - 15 - α α α α α α
Lumbar spine
Lumbar spine CT 32 111 DOI : 10.3831/KPI.2010.13.2.111 Lumbar Spine CT 32 Received : 10. 05. 23 Revised : 10. 06. 04 Accepted : 10. 06. 11 Key Words: Disc herniation, CT scan, Clinical analysis The Clinical
석사논문.PDF
ABO Rh A study on the importance of ABO and Rh blood groups information in Public Health 2000 2 1 ABO Rh A study on the importance of ABO and Rh blood groups information in Public Health 2000 2 2 ABO Rh
386-390.hwp
386 HANYANG MEDICAL REVIEWS Vol. 29 No. 4, 2009 우리나라 미숙아의 통계와 의료비용 Statistics and Medical Cost of Preterm in Korea 윤혜선 을지대학교 노원을지병원 소아청소년과학교실 Hye Sun Yoon, M.D., Ph.D., Department of Pediatrics, Nowon
원위부요척골관절질환에서의초음파 유도하스테로이드주사치료의효과 - 후향적 1 년경과관찰연구 - 연세대학교대학원 의학과 남상현
원위부요척골관절질환에서의초음파 유도하스테로이드주사치료의효과 - 후향적 1 년경과관찰연구 - 연세대학교대학원 의학과 남상현 원위부요척골관절질환에서의초음파 유도하스테로이드주사치료의효과 - 후향적 1 년경과관찰연구 - 연세대학교대학원 의학과 남상현 원위부요척골관절질환에서의초음파 유도하스테로이드주사치료의효과 - 후향적 1 년경과관찰연구 - 지도김석원교수 이논문을석사학위논문으로제출함
γ
경락경혈학회지 Vol.27, No.1, pp.87 106, 2010 Journal of Meridian & Acupoint Dept. of 1 Meridian & Acupoint, 3 Acupuncture & Moxibustion, College of Oriental Medicine, Daejeon University 2 Division of Clinical
Vol.257 C O N T E N T S M O N T H L Y P U B L I C F I N A N C E F O R U M
2017.11 Vol.257 C O N T E N T S 02 06 38 52 69 82 141 146 154 M O N T H L Y P U B L I C F I N A N C E F O R U M 2 2017.11 3 4 2017.11 6 2017.11 1) 7 2) 22.7 19.7 87 193.2 160.6 83 22.2 18.4 83 189.6 156.2
<BFA9BAD02DB0A1BBF3B1A4B0ED28C0CCBCF6B9FC2920B3BBC1F62E706466>
001 002 003 004 005 006 008 009 010 011 2010 013 I II III 014 IV V 2010 015 016 017 018 I. 019 020 021 022 023 024 025 026 027 028 029 030 031 032 033 034 035 036 037 038 039 040 III. 041 042 III. 043
K O R E A C E N T E R S F O R D I S E A S E C O N T R O L & P R E V E N T I O N PHWR Vol. 5 No. 41 www.cdc.go.kr/phwr 2012 10 12 5 41 ISSN:2005-811X Comparison of drug-susceptibility test to the anti-tuberculosis
( )Kju269.hwp
만성세균성전립선염모델흰쥐에서 의항염효과 Anti-inflammatory Effect of Lycopene on Chronic Bacterial Prostatitis Rat Model Cho Hwan Yang, Dong Wan Sohn, Yong-Hyun Cho From the Department of Urology, The Catholic University
Á¶´öÈñ_0304_final.hwp
제조 중소기업의 고용창출 성과 및 과제 조덕희 양현봉 우리 경제에서 일자리 창출은 가장 중요한 정책과제입니다. 근래 들어 우리 사회에서 점차 심각성을 더해 가고 있는 청년 실업 문제에 대처하고, 사회적 소득 양극화 문제에 대응하기 위해서도 일자리 창 출은 무엇보다도 중요한 정책과제일 것입니다. 고용창출에서는 중소기업의 역할이 대기업보다 크다는 것이 일반적
` Companies need to play various roles as the network of supply chain gradually expands. Companies are required to form a supply chain with outsourcing or partnerships since a company can not
<B0E6C8F1B4EBB3BBB0FAC0D3BBF3B0ADC1C E687770>
개원의와함께하는임상강좌 2011 역류성식도질환제대로이해하기 Division of Gastroenterology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea Jae-Young Jang, M.D., PhD. 개원의와함께하는임상강좌 2011 109 최신치료
05-08 087ÀÌÁÖÈñ.hwp
산별교섭에 대한 평가 및 만족도의 영향요인 분석(이주희) ꌙ 87 노 동 정 책 연 구 2005. 제5권 제2호 pp. 87118 c 한 국 노 동 연 구 원 산별교섭에 대한 평가 및 만족도의 영향요인 분석: 보건의료노조의 사례 이주희 * 2004,,,.. 1990. : 2005 4 7, :4 7, :6 10 * (jlee@ewha.ac.kr) 88 ꌙ 노동정책연구
272 石 堂 論 叢 49집 기꾼이 많이 확인된 결과라 할 수 있다. 그리고 이야기의 유형이 가족 담, 도깨비담, 동물담, 지명유래담 등으로 한정되어 있음도 확인하였 다. 전국적인 광포성을 보이는 이인담이나 저승담, 지혜담 등이 많이 조사되지 않은 점도 특징이다. 아울
271 부산지역 구비설화 이야기꾼의 현황과 특징 정 규 식* 1) - 목 차 - Ⅰ. 서론 Ⅱ. 부산지역 구비설화 이야기꾼의 전반적 현황 1. 이야기꾼의 여성 편중성 2. 구연 자료의 민요 편중성 3. 이야기꾼의 가변적 구연력 4. 이야기 유형의 제한성 5. 이야기꾼 출생지의 비부산권 강세 Ⅲ. 부산지역 구비설화 이야기꾼의 특징 Ⅳ. 결론 개 요 본고의 목적은
Microsoft PowerPoint - Freebairn, John_ppt
Tax Mix Change John Freebairn Outline General idea of a tax mix change Some detailed policy options Importance of casting assessment in the context of a small open economy Economic effects of a tax mix
(Microsoft PowerPoint - CXBTUEOAPVQY.ppt [\310\243\310\257 \270\360\265\345])
![(Microsoft PowerPoint - CXBTUEOAPVQY.ppt [\310\243\310\257 \270\360\265\345])](/thumbs/102/154983535.jpg "(Microsoft PowerPoint - CXBTUEOAPVQY.ppt [\310\243\310\257 \270\360\265\345])")
당뇨병환자에서항혈소판제사용 - 아스피린일차예방을중심으로 - 경희대학교강동경희대병원 황유철 말씀드릴내용 당뇨병및심혈관질환의역학 아스피린의심혈관질환 1차, 2차예방효과 아스피린부작용및용량에따른효과차이 당뇨병환자에서아스피린사용의적응증 사망원인순위, 2010 년 25.6% 통계청 심혈관질환에의한의료비추세 6 조 1400 억 국민건강보험공단, 2002-2009 Multidisciplinary
내시경 conference
부울경소화기내시경학회 6월집담회 고신대학교복음병원소화기내과전임의서광일 F/63 CASE C.C) epigastric pain for 2 wks P. I) 2014.04.16 EGD at LMC adm via OPD for further evaluation. P. Hx) CASE HTN/DM/Hepatitis/Tbc (+/+/-/-) S. Hx) N-S ROS)
<BFACBCBCC0C7BBE7C7D02831302031203139292E687770>
延 世 醫 史 學 제12권 제2호: 29-40, 2009년 12월 Yonsei J Med Hist 12(2): 29-40, 2009 특집논문 3 한국사회의 낙태에 대한 인식변화 이 현 숙 이화여대 한국문화연구원 1. 들어가며 1998년 내가 나이 마흔에 예기치 않은 임신을 하게 되었을 때, 내 주변 사람들은 모두 들 너무나도 쉽게 나에게 임신중절을 권하였다.
DBPIA-NURIMEDIA
The e-business Studies Volume 17, Number 4, August, 30, 2016:319~332 Received: 2016/07/28, Accepted: 2016/08/28 Revised: 2016/08/27, Published: 2016/08/30 [ABSTRACT] This paper examined what determina
04-다시_고속철도61~80p
Approach for Value Improvement to Increase High-speed Railway Speed An effective way to develop a highly competitive system is to create a new market place that can create new values. Creating tools and
YI Ggodme : The Lives and Diseases of Females during the Latter Half of the Joseon Dynasty as Reconstructed with Cases in Yeoksi Manpil (Stray Notes w
497 의사학 제24권 제2호(통권 제50호) 2015년 8월 Korean J Med Hist 24 ː497-532 Aug 2015 c대한의사학회 http://dx.doi.org/10.13081/kjmh.2015.24.497 pissn 1225-505X, eissn 2093-5609 역시만필( 歷 試 漫 筆 ) 의 사례로 재구성한 조선후기 여성의 삶과 질병
大学４年生の正社員内定要因に関する実証分析
190 2016 JEL Classification Number J24, I21, J20 Key Words JILPT 2011 1 190 Empirical Evidence on the Determinants of Success in Full-Time Job-Search for Japanese University Students By Hiroko ARAKI and
Journal of Educational Innovation Research 2017, Vol. 27, No. 1, pp DOI: * The
Journal of Educational Innovation Research 2017, Vol. 27, No. 1, pp.243-268 DOI: http://dx.doi.org/10.21024/pnuedi.27.1.201703.243 * - 2001 2015 - The Research Trends on Peer Counseling in Elementary and
서론
- i - - ii - - iii - - iv - - v - - vi - - 1 - - 2 - - 3 - - 4 - - 5 - - 6 - - 7 - - 8 - - 9 - - 10 - - 11 - - 12 - - 13 - - 14 - - 15 - - 16 - - 17 - - 18 - - 19 - - 20 - - 21 - - 22 - - 23 - - 24 - -
(Microsoft PowerPoint - S13-3_\261\350\273\363\307\366 [\310\243\310\257 \270\360\265\345])
![(Microsoft PowerPoint - S13-3_\261\350\273\363\307\366 [\310\243\310\257 \270\360\265\345])](/thumbs/100/144769741.jpg "(Microsoft PowerPoint - S13-3_\261\350\273\363\307\366 [\310\243\310\257 \270\360\265\345])")
Cardiovascular Disease in Metabolic Syndrome 김상현 보라매병원내과 서울대학교의과대학내과학교실 Contents Metabolic syndrome and Cardiovascular system CVD Mortality Coronary artery disease Heart failure Atrial fibrillation Management
..........5-45..
K O R E A C E N T E R S F O R D I S E A S E C O N T R O L & P R E V E N T I O N PHWR Vol. 5 No. 45 www.cdc.go.kr 2012 11 9 5 45 ISSN:2005-811X Monitoring of antimicrobial resistance on non-tertiary hospitals
<B0E6C8F1B4EBB3BBB0FA20C0D3BBF3B0ADC1C E687770>
심전도연수강좌 : 처음시작하는사람들을위한심전도 연세대학교원주의과대학순환기내과학교실 안민수 Cardiac Electrophysiology I : Automaticity : 60-100 회 /min, His bundle : 40-60 회 /min Bundle branch : 20-40 회 /min Purkinje fiber : 20 회 /min Cardiac Electrophysiology
139~144 ¿À°ø¾àħ
2 139 DOI : 10.3831/KPI.2010.13.2.139 2 Received : 10. 04. 08 Revised : 10. 04. 26 Two Case Report on Wrist Ganglion Treated with Scolopendrid Pharmacopuncture Accepted : 10. 05. 04 Key Words: Wrist Ganglion,
Rheu-suppl hwp
Objective: This paper reviews the existing Korean medical and public health, and nursing academy articles on disease-specific and domain-specific quality of life, and provides recommendations for the universally
DBPIA-NURIMEDIA
The e-business Studies Volume 17, Number 6, December, 30, 2016:275~289 Received: 2016/12/02, Accepted: 2016/12/22 Revised: 2016/12/20, Published: 2016/12/30 [ABSTRACT] SNS is used in various fields. Although
975_983 특집-한규철, 정원호
Focused Issue of This Month Gyu Cheol an, MD Department of Otolaryngology ead & Neck Surgery, Gachon University of College Medicine E - mail : han@gilhospital.com Won-o Jung, MD Department of Otolaryngology
°Ç°�°úÁúº´6-2È£
K O R E A C E N T E R S F O R D I S E A S E C O N T R O L & P R E V E N T I O N PHWR Vol. 6 No. 2 www.cdc.go.kr 2013 1 11 6 2 ISSN:2005-811X Flavivirus surveillance in mosquitoes collected from the quarantine
<C7D1B1B9B1A4B0EDC8ABBAB8C7D0BAB85F31302D31C8A35F32C2F75F303132392E687770>
버스 외부 광고의 효과에 관한 탐색적 연구 : 매체 접촉률과 인지적 반응을 중심으로 1) 고한준 국민대학교 언론정보학부 조교수 노봉조 벅스컴애드 대표 이사 최근 몇 년 사이 옥외 광고나 인터넷 광고 등 BTL(Below the Line) 매체가 광고 시장에서 차지하 는 비중이 점점 높아지고 있다. 버스 외부 광고는 2004년 7월 서울시 교통체계개편 이후 이용자
http://www.kbc.go.kr/pds/2.html Abstract Exploring the Relationship Between the Traditional Media Use and the Internet Use Mee-Eun Kang This study examines the relationship between
Vol.259 C O N T E N T S M O N T H L Y P U B L I C F I N A N C E F O R U M
2018.01 Vol.259 C O N T E N T S 02 06 28 61 69 99 104 120 M O N T H L Y P U B L I C F I N A N C E F O R U M 2 2018.1 3 4 2018.1 1) 2) 6 2018.1 3) 4) 7 5) 6) 7) 8) 8 2018.1 9 10 2018.1 11 2003.08 2005.08
노인정신의학회보14-1호
제14권 1호 통권 제23호 www.kagp.or.kr 발행인 : 정인과 / 편집인 : 이동우 / 발행처 : 정인과 (152-703) 서울특별시 구로구 구로동 80번지 고려대학교 구로병원 정신과 / TEL : 02-818-6608 / FAX : 02-852-1937 발행일 : 2008년 4월 30일 / 제 작 : (주)엠엘커뮤니케이션 140-846 서울특별시
ECG & EP CASES Young-Keun On, MD, PhD Division of Cardiology, Department of Medicine Cardiac & Vascular Center, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea A case of
달생산이 초산모 분만시간에 미치는 영향 Ⅰ. 서 론 Ⅱ. 연구대상 및 방법 達 은 23) 의 丹 溪 에 최초로 기 재된 처방으로, 에 복용하면 한 다하여 난산의 예방과 및, 등에 널리 활용되어 왔다. 達 은 이 毒 하고 는 甘 苦 하여 氣, 氣 寬,, 結 의 효능이 있
대한한방부인과학회지 THE JOURNAL OF ORIENTAL OBSTETRICS & GYNECOLOGY VOL.17, NO.2 : 115-122 (2004) 달생산이 초산모 분만시간에 미치는 영향 * 북경한의원, ** 윤산부인과의원, *** 최은림산부인과의원, 상지대학교 한의과대학 부인과학교실 ****, 경희대학교 동서의학대학원 김성준 *****, 윤왕준
Can032.hwp
Chromosomal Alterations in Hepatocellular Carcinoma Cell Lines Detected by Comparative Genomic Hybridization Sang Jin Park 1, Mahn Joon Ha, Ph.D. 1, Hugh Chul Kim, M.D. 2 and Hyon Ju Kim, M.D. 1 1 Laboratory
2017.09 Vol.255 C O N T E N T S 02 06 26 58 63 78 99 104 116 120 122 M O N T H L Y P U B L I C F I N A N C E F O R U M 2 2017.9 3 4 2017.9 6 2017.9 7 8 2017.9 13 0 13 1,007 3 1,004 (100.0) (0.0) (100.0)
<31382D322D3420BDC5B1D4C8AF5FB3EDB9AE28C3D6C1BEBABB292E687770>
醫 史 學 제18권 제2호(통권 제35호) 2009년 12월 Korean J Med Hist 18ː57 72 18ː173-188 Dec. Dec. 2009 2009 C 大 韓 醫 史 學 會 ISSN ISSN 1225 505X 1225-505X 지방병 연구와 식민지배 : 1927년 영흥 및 해남지역 에메틴 중독사건을 중심으로 신 규 환* 1. 머리말 2. 일제의
l l l l l l l l l Lee, Geon Kook None This project was designed to establish the Tumor Bank of National Cancer Center in 2000. From the first tumor sample in 2000, the total of tumor and tumor-related
untitled
Case Report : Asan Medical Center Cardiac Rehabilitation AACVPR (http://www.aacvpr.org/) KACVPR (http://www.kacvpr.com/) Backgrounds PCI 2,395 consecutive patients in Minnesota (Mayo Clinic) Between1994
에너지경제연구 제13권 제1호
에너지경제연구 Korean Energy Economic Review Volume 13, Number 1, March 2014 : pp. 83~119 거시계량모형을이용한유가변동및 유류세변화의파급효과분석 * 83 84 85 86 [ 그림 1] 모형의해결정과정 87 [ 그림 2] 거시계량모형의흐름도 (flow chart) 88 89 < 표 1> 유류세현황 (2013
레이아웃 1
대한위장관기질종양연구회 01 GIST 06 02 11 03 Imatinib 14 04 05 06 07 Sunitinib 32 40 44 48 GIST 6 01 7 GIST Guide book GIST 8 01 9 GIST Guide book GIST (CT) MRI FDG-PET 10 02 11 GIST Guide book 12 02 (Imatinib)
step 1-1
Written by Dr. In Ku Kim-Marshall STEP BY STEP Korean 1 through 15 Action Verbs Table of Contents Unit 1 The Korean Alphabet, hangeul Unit 2 Korean Sentences with 15 Action Verbs Introduction Review Exercises
03±èÀçÈÖ¾ÈÁ¤ÅÂ
x x x x Abstract The Advertising Effects of PPL in TV Dramas - Identificaiton by Implicit Memory-based Measures Kim, Jae - hwi(associate professor, Dept. of psychology, Chung-Ang University) Ahn,
Y 1 Y β α β Independence p qp pq q if X and Y are independent then E(XY)=E(X)*E(Y) so Cov(X,Y) = 0 Covariance can be a measure of departure from independence q Conditional Probability if A and B are
대한한의학원전학회지24권6호-전체최종.hwp
小兒藥證直訣 의 五臟辨證에 대한 小考 - 病證과 處方을 중심으로 1 2 慶熙大學校大學校 韓醫學科大學 原典學敎室 ㆍ 韓醫學古典硏究所 白裕相1,2*1)2) A study on The Diagnosis and Treatment Using The Theory of Five Organs in Soayakjeungjikgyeol(小兒藥證直訣) 1 Dept. of Oriental
°Ç°�°úÁúº´5-44È£ÃÖÁ¾
K O R E A C E N T E R S F O R D I S E A S E C O N T R O L & P R E V E N T I O N PHWR Vol. 5 No. 44 www.cdc.go.kr/phwr 2012 11 2 5 44 ISSN:2005-811X Vector surveillance after elimination of lymphatic filariasis
<30322D28C6AF29C0CCB1E2B4EB35362D312E687770>
한국학연구 56(2016.3.30), pp.33-63. 고려대학교 한국학연구소 세종시의 지역 정체성과 세종의 인문정신 * 1)이기대 ** 국문초록 세종시의 상황은 세종이 왕이 되면서 겪어야 했던 과정과 닮아 있다. 왕이 되리라 예상할 수 없었던 상황에서 세종은 왕이 되었고 어려움을 극복해 갔다. 세종시도 갑작스럽게 행정도시로 계획되었고 준비의 시간 또한 짧았지만,
590호(01-11)
T H E K O R E A N D O C T O R S W E E K L Y www.docdocdoc.co.kr I N S I D E 38 3 5 6 7 10 13 28 29 30 31 38 41 42 2 Advertisement Government & Medicine 3 Government & Medicine 4 Government & Medicine Government
저작자표시 - 비영리 - 변경금지 2.0 대한민국 이용자는아래의조건을따르는경우에한하여자유롭게 이저작물을복제, 배포, 전송, 전시, 공연및방송할수있습니다. 다음과같은조건을따라야합니다 : 저작자표시. 귀하는원저작자를표시하여야합니다. 비영리. 귀하는이저작물을영리목적으로이용할
저작자표시 - 비영리 - 변경금지 2.0 대한민국 이용자는아래의조건을따르는경우에한하여자유롭게 이저작물을복제, 배포, 전송, 전시, 공연및방송할수있습니다. 다음과같은조건을따라야합니다 : 저작자표시. 귀하는원저작자를표시하여야합니다. 비영리. 귀하는이저작물을영리목적으로이용할수없습니다. 변경금지. 귀하는이저작물을개작, 변형또는가공할수없습니다. 귀하는, 이저작물의재이용이나배포의경우,
274 한국문화 73
- 273 - 274 한국문화 73 17~18 세기통제영의방어체제와병력운영 275 276 한국문화 73 17~18 세기통제영의방어체제와병력운영 277 278 한국문화 73 17~18 세기통제영의방어체제와병력운영 279 280 한국문화 73 17~18 세기통제영의방어체제와병력운영 281 282 한국문화 73 17~18 세기통제영의방어체제와병력운영 283 284
Trd022.hwp
김신태, 이선녕, 이석정, 정필문, 박홍준, 신명상, 김종환, 이부길, 김상하, 리원연, 신계철, 용석중 Shin-Tae Kim, M.D., Shun Nyung Lee, M.D., Seok Jeong Lee, M.D., Pil Moon Jung, M.D., Hong Jun Park, M.D., Myung Sang Shin, M.D., Chong Whan Kim,
DBPIA-NURIMEDIA
방송통신연구 2011년 봄호 연구논문 64 98 PD수첩 관련 판례에서 보이는 사법부의 사실성에 대한 인식의 차이 연구* 1)2) 이승선 충남대학교 언론정보학과 부교수** Contents 1. 문제제기와 연구문제 2. 공적인물에 대한 명예훼손 보도의 면책 법리 3. 분석결과의 논의 4. 마무리 본 이른바 PD수첩 광우병 편 에 대해 다양한 법적 대응이 이뤄졌다.
44-4대지.07이영희532~
A Spatial Location Analysis of the First Shops of Foodservice Franchise in Seoul Metropolitan City Younghee Lee* 1 1 (R) 0 16 1 15 64 1 Abstract The foodservice franchise is preferred by the founders who
04_이근원_21~27.hwp
1) KIGAS Vol. 16, No. 5, pp 21~27, 2012 (Journal of the Korean Institute of Gas) http://dx.doi.org/10.7842/kigas.2012.16.5.21 실험실의 사례 분석에 관한 연구 이근원 이정석 한국산업안전보건공단 산업안전보건연구원 (2012년 9월 5일 투고, 2012년 10월 19일
<C0C7B7CAC0C720BBE7C8B8C0FB20B1E2B4C9B0FA20BAAFC8AD5FC0CCC7F6BCDB2E687770>
ꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚ ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ 儀 禮 의 社 會 的 機 能 과 變 化 李 顯 松 裵 花 玉 ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ ꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚ
<283732372D3733312920B4D9C3CAC1A120BCD2C7C1C6AEC4DCC5C3C6AEB7BBC1EEC0C720B3EBBEC8C0C720BDC3B7C2BAB8C1A4BFA120B4EBC7D120C0AFBFEBBCBA20C6F2B0A1283035292E687770>
대한안과학회지 제 49 권 제 5 호 2008 J Korean Ophthalmol Soc 49(5):727-731, 2008 DOI : 10.3341/jkos.2008.49.5.727 다초점 소프트콘택트렌즈의 노안의 시력보정에 대한 유용성 평가 김현경 1 김효명 2 정성근 1 가톨릭대학교 의과대학 성모병원 안과학교실 1, 고려대학교 의과대학 안암병원 안과학교실
Minimally invasive parathyroidectomy
2013. 2. 2 대한간암연구학회 7차 심포지움 및 학술대회 Indication and Clinical Outcomes of Metachronous HCC Metastasectomy Shin Hwang Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan
Output file
connect educational content with entertainment content and that production of various contents inducing educational motivation is important. Key words: edutainment, virtual world, fostering simulation
1. 서론 1-1 연구 배경과 목적 1-2 연구 방법과 범위 2. 클라우드 게임 서비스 2-1 클라우드 게임 서비스의 정의 2-2 클라우드 게임 서비스의 특징 2-3 클라우드 게임 서비스의 시장 현황 2-4 클라우드 게임 서비스 사례 연구 2-5 클라우드 게임 서비스에
IPTV 기반의 클라우드 게임 서비스의 사용성 평가 - C-Games와 Wiz Game 비교 중심으로 - Evaluation on the Usability of IPTV-Based Cloud Game Service - Focus on the comparison between C-Games and Wiz Game - 주 저 자 : 이용우 (Lee, Yong Woo)
2 환경법과 정책 제16권(2016.2.28.) Ⅰ. 들어가며 Ⅱ. 가습기살균제 사건의 경과 Ⅲ. 가습기살균제 사건과 제조물 책임 Ⅳ. 가습기살균제 사건과 인과관계 입증 완화 Ⅴ. 나가며 Ⅰ. 들어가며 피해유발행위(혹은 인자)가 직접적인 손해를 즉각적으로 유발하는 경우
가습기 살균제 사건의 민사적 쟁점: 제조물책임과 인과관계 입증 송 정 은* 1)정 남 순**2) 가습기살균제를 사용함으로써 손해를 입은 피해자들은 현재 가습기살균제를 제조 및 판매한 업 체를 상대로 손해배상소송을 진행하고 있다. 가습기살균제 사건은 고도의 기술이 집약되어 대량으 로 생산되는 제품의 결함으로 인하여 피해자에게 손해가 발생한 사안으로
... 수시연구 국가물류비산정및추이분석 Korean Macroeconomic Logistics Costs in 권혁구ㆍ서상범...
... 수시연구 2013-01.. 2010 국가물류비산정및추이분석 Korean Macroeconomic Logistics Costs in 2010... 권혁구ㆍ서상범... 서문 원장 김경철 목차 표목차 그림목차 xi 요약 xii xiii xiv xv xvi 1 제 1 장 서론 2 3 4 제 2 장 국가물류비산정방법 5 6 7 8 9 10 11 12 13
¹Ìµå¹Ì3Â÷Àμâ
MIDME LOGISTICS Trusted Solutions for 02 CEO MESSAGE MIDME LOGISTICS CO., LTD. 01 Ceo Message We, MIDME LOGISTICS CO., LTD. has established to create aduance logistics service. Try to give confidence to
슬라이드 1
Proposed Korean guideline for the diagnosis of BPH Hyun Woo Kim The Catholic University of Korea BPH Guideline AHCPR guideline on BPH (1994) AUA guideline on BPH (2003) EAU guideline on BPH (2004) International
04김호걸(39~50)ok
Journal of Environmental Impact Assessment, Vol. 22, No. 1(2013) pp.39~50 Prediction of Landslides Occurrence Probability under Climate Change using MaxEnt Model Kim, Hogul* Lee, Dong-Kun** Mo, Yongwon*
untitled
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
연하곤란
2015.03.04 부울경소화기내시경지회 Intramucosal gastric cancer: The rate of lymph node metastasis in signet ring cell carcinoma was as low as that in welldifferentiated adenocarcinoma 인제대부산백병원 소화기내과 지삼룡 Signet ring