Dyspepsia - An Evidence Based Approach
-
Upload
jarrod-lee -
Category
Health & Medicine
-
view
246 -
download
0
Transcript of Dyspepsia - An Evidence Based Approach
Dyspepsia
An Evidence Based Approach Asian Consensus 2012, NICE 2014, Rome III 2006, AGA 2005, ACG 2005
Dr Jarrod Lee gutCARE @ Mount Elizabeth Novena Hospital
Scope
• Case Scenarios
• Overview & Definitions
• Diagnostic Approach
– Symptoms
– OGD
• Management Approach
– Medical treatments
– Dietary & lifestyle
– Alternative treatments
2
Case Scenarios
3
Overview
4
Overview
• Dyspepsia affects 20-40% of adults annually
• 7-40% prevalence based on population studies
• 50% self medicate
• 10-25% will seek medical attention
• Quality of life impaired; more absent work days
• Symptoms often short duration & self limited, but may be chronic
5
Definitions
• Dyspepsia:
– Symptom or set of symptoms considered to originate from gastroduodenal region
• Symptoms:
– Epigastric pain, epigastric bloating, postprandial fullness, early satiety, nausea, vomiting, belching
• Functional Dyspepsia:
– Characterized by chronic dyspepsia in absence organic, systemic or metabolic conditions
– Definition evolved considerably over last 20 yrs
6
7
Pathophysiology
8
9
ROME Criteria
10
ROME II
Rome III Criteria
11
Duration: 3 vs 6 mths; can be continuous, intermittent or recurrent
Rome II III: Paradigm Shift
• From “pain or discomfort in upper abdomen” to accommodate variations in symptoms & patterns
• Recognizes “meal related” (PDS) & “pain related‟ (EPS) symptoms associated with distinct pathophysiological mechanisms
• Syndromes may overlap:
– FD can co-exist with GERD & IBS
– Overlap of EPS & PDS: 15%
– Up to 40% may switch FGID subgroups over 10 yrs
12
Differential Diagnosis
13
Differential Diagnosis
Diagnosis Prevalence
Functional dyspepsia Up to 70%
Peptic ulcer disease 15-25%
Reflux oesophagitis 5-15%
Gastric or oesophageal cancer < 2%
Others: abdominal cancer, biliary tract
disease, malabsorption, infilitrative
disease, parasites, gastroparesis,
hepatoma, systemic disease, etc
Rare
14
Based on studies in patients with dyspepsia evaluated with endoscopy
Asian Populations
• Different diet, lifestyle, HP prevalence
• Majority of dyspepsia without alarm symptoms have FD: mainly from single studies
– China (2005): 69%
– Korea (2004): 70%
– Malaysia (2008): 62%
– Singapore (2002): 80%
• Significant overlap with IBS: up to 25%
• May have significant overlap with GERD
15
Drug Induced Dyspepsia
• Acarbose
• Antibiotics
• Bisphosphonates
• Corticosteroids
• Iron
• Metformin
• NSAIDs
• Opiates
• Orlistat
• Potassium chloride
• Theophylline
• Herbs, e.g. garlic, gingko
16
17
Value of Symptoms
• Systemic review to compare primary care physicians, gastroenterologists & computer models in diagnosing organic dyspepsia (as determined by endoscopy)
• 15 studies with 11 366 patients
18 JAMA 2006; 295: 1566-76
Sensitivity Specificity Positive
LR
Negative
LR
Primary Care Physicians
4 studies; n=1459
67-95% 25-52% 1.3 0.66
Gastroenterologists
5 studies; n=3707
59-86% 63-71% 1.9 0.4
Computer Models
9 studies; n=7148
60-99% 17-80% 1.6 0.45
19
Conclusions
• Diagnosis based on clinical history of limited use in distinguishing organic & functional dyspepsia
• Clinical opinion & computer models better than chance
• Differences between groups not statistically significant
• Patients with dyspepsia > 2 wks (n=347)
• Provisional diagnosis by GPs & gastreonterologists (GAs)
• OGD within 5 days
20
• 45% agreement by GPs & GAs
• Unaided clinical diagnosis by both groups unreliable
• 50% PUD & reflux oesophagitis classified as FD
21
Alarm Symptoms
• Low PPV for diagnosis of organic causes
• Consensus is to investigate further
• Alarm symptoms:
– Unintended LOW, progressive dysphagia, recurrent or persistent vomiting, BGIT, anemia, fever, positive FH
• OGD is diagnostic modality of choice
• Selected cases if OGD negative:
– US or CT
– FBC, RP, TFT, LFT, stool for parasites
22
Value of Endoscopy 23
• 9 studies with dyspepsia & OGD; N=5,389
• OGD findings in patients with dyspepsia compared to those without dyspepsia
• Only PUD more common in dyspepsia; OR 2.07
24
Findings in Dyspepsia
A. Broad Definition
B. Rome Criteria
25
Findings in Dyspepsia
A. Asian studies
B. Western studies
26
• 5 066 consecutive OGDs for dyspepsia
• 19.5% had significant disease: PUD (14.9%), oesophagitis (5.0%), cancer (0.5%)
• Cumulative frequency of cancer:
– < 35 yrs: 0.68 per 1000 OGDs
– < 45 yrs: 1.15
– > 45 yrs: 9.60
27
Diagnostic Approach
• FD is a diagnosis of exclusion
– Need to focus on excluding serious & specifically treatable diseases
– Balance against resources needed for investigations
• Consider empirical therapy
– History & physical examination alone has low sensitivity & specificity for predicting organic disease
– High incidence of normal endoscopy
– Very low incidence of cancer
– Investigations are costly & invasive
28
Diagnostic Strategies
• Initial strategies for un-investigated dyspepsia:
– Trial of acid suppression
– Test & treat (for HP)
– Early endoscopy
• Cochrane review (2005)
– In absence of warning signs, test & treat is more effective & cheaper than early endoscopy
– Initial endoscopy provides a small reduction in risk of recurrent symptoms
29
„Cut Off‟ Age
• Consider OGD in new onset dyspepsia before diagnosing FD if above „cut off‟ age
• Cut off age depends on gastric cancer prevalence
– 40 yrs: high risk population e.g. China, Korea, Japan
– 45 yrs: intermediate risk e.g. Singapore, Malaysia, Hong Khong, Taiwan, Vietnam
– 50 yrs: low risk e.g. India, Thailand, Bangladesh
30
Management Approach
31
Treatment
• Frustrating for patient & doctors
• Few proven options
• Management should be individualized
– Continued reassurance & support important
– Generally aimed at the presumed underlying aetiology
• Use „IBS approach‟ to address multiple factors:
– Biological factors e.g. post GI infection
– Psychological factors e.g. psychosocial factors
– Social factors e.g. dietary changes
32
HP Eradication
• Large population studies show increased incidence of HP infection in patient with FD
• Significance of association unclear
• HP eradication reduces risk of PUD and gastric cancer
• Most recent Cochrane meta-analysis of 17 RCTs (2006): significant symptom relief with RRR 10%, NNT 14
• HEROES trial1: large RCT, primary care setting
– HP eradication vs PPI + placebo
– 50% symptom improvement at 1yr: 49% vs 36.5%
– P=0.01, NNT 8
33 1. Arch Int Med 2011; 171: 1929-36
HP Eradication in Asians
• Meta-analysis of 7 Chinese RCTs1: OR 3.61 benefit
• Recent Chinese study using Rome III criteria2:
– Benefit for epigastric pain & epigastric burning: 60.8-65.7% vs 33.3-31.8%; P<0.05
– No difference for postprandial fullness, early satiety, nausea, belching
• 2x Singapore RCTs
– CGH (2006)3: 31% complete symptom resolution; 62% global symptom resolution
– NUH (2009)4: 39% symptom resolution if HP eradicated; 3% if HP persistent
34 1. Helicobacter 2007; 12: 542-6 2. World J Gastroenterol 2011; 17: 3242-7 3. J Gastroenterol 2006; 41: 647-53 4. Eur J Gastroenterol Hepatol 2009; 21: 417-24
Proton Pump Inhibitors (PPIs)
• Meta-analysis of all 7 trials1
– 6 in Western population, 1 from Asian population
– Modest benefit vs placebo: 40.3 vs 32.7%; NNT 14.6
– Benefit confined to „ulcer like‟ or „reflux like‟ dyspepsia
– Only 1 negative result from Asian (HK) study
• Recent HK RCT2: no benefit
• Singapore open label study3: no benefit
• Multiple studies: no benefit of high dose vs standard dose
35 1. Clin Gastroenterol Hepatol 2007; 5: 178-85 2. Am J Gastroenterol 2007; 102: 1483-8 3. J Clin Gastroenterol 2008; 42: 134-8
Prokinetics
• Simulate GI motility via different mechanisms
• Cochrane meta-analysis (2006):
– 24 RCTs; N=3,178
– Prokinetics superior to placebo: 57% vs 47%
– RRR 33%, NNT 6
– Mainly for domperidone & cisapride
– Limitations due to high degree of heterogenicity, small sample sizes, publication bias
• New prokinetics: itopride, acotiamide
36
Antidepressants & Anxiolytics
• Limited studies, inconsistent results
• Meta-analysis of 13 trials1 (n=1,717):
– FD improved in 11 trials
– Pooled RRR 45%
• SSRIs & SNRIs: only 1 RCT to date showed no benefit2
• Central factors (e.g. psychological factors, sleep disturbance) may be important determinants of response
• May be useful for FD-IBS overlap
• Psychotherapy: weak & inconsistent evidence
37 1. J Gastroenterol 2005; 40: 1036-42 2. Clin Gastroenterol Hepatol 2008; 6: 746-52
Diet & Lifestyle
38
Dietary Modification
• Experimental studies suggest certain food ingredients such as chilli, spice & fats may provoke symptoms
• No well controlled study to demonstrate that dietary exclusion of specific food ingredients is effective in FD
• Trials are conflicting:
– Some show FD patients consume more fat & less carbohydrate
– Others show no difference in diets
• Eating pattern: FD patients have no difference in number of meals, eating speed, or inter meal interval
39
Spicy Food
• Capsaicin: Active ingredient in hot & spicy foods
– Activates receptors on nociceptive C fibres, inducing burning sensation & pain
• Ingestion of capsaicin capsules causes greater symptom severity in FD patients vs controls1,2
• FD patients had moderate pain at a lower dose of capsaicin vs controls: 0.5mg vs 1.0mg3
• Symptom scores in FD patients reduced by 2.5g red peppers per day x 5wks vs placebo: 60% vs < 30%4
40 1. Neurogastroenterol Motil 2008; 20: 125-33 2. Neurogastroenterol Motil 2011; 23: 918-e397 3. Neurogastroenterol Motil 2012 Nov 21 epub 4. Aliment Pharmacol Ther 2002; 16: 1075-82
• „Food intolerance‟ occur more frequently in FD patients
• Few studies evaluate role of specific foods
• Certain foods may provoke specific dyspeptic symptoms
41 14. Carvalho et al. Dig Dis Sci 2012; 55: 60-5 15. Filipovic et al. Eur J Intern Med 2011; 22: 300-4
Specific Foods
Specific Foods
• Rice
– Completely absorbed in SB, producing little gas
– Low allergenicity, low fibre
– Rice based exclusion diet improves IBS symptoms
– No trials for FD
• Fibre
– May worsen symptoms in FD patients
– Effect uncertain, may be due to IBS overlap
• Fat
– Implicated in some studies
42
Lifestyle Factors
• Stress & anxiety shown to be independent predictors
• Large survey of 18,000 FD patients meeting Rome III criteria vs healthy individuals1
– Higher daily stress & stress susceptibility; P<0.01
– Felt sleep insufficient, less exercise
• Exercise may improve intestinal gas transit in bloating2
• Large community based studies show coffee, smoking & alcohol not risk factors for FD
43 1. Miwa et al. Neurogastroenterol Motil 2012; 24: 464-71 2. Villoria et al. Am J Gastroenterol 2006; 101: 2552-7
Complementary & Alternative Medicine
44
Herbal Therapies
• RCTs showing benefit vs placebo with:
– STW 5: herbal preparation with bitter candy tuft, matricaria flower, peppermint leaves, caraway, liquorice root, lemon balm
– Artichoke leaf extract
• Limited data on:
– Peppermint + caraway oil combination
– Banana powder capsules
• Antioxidants: trials show no benefit
45
• Xiaoyao San:
– Most studied herbal medicine for FD
– Regulates liver Qi, tonifies spleen & nourishes blood
46 J Gastroenterol Hepatol 2009; 24: 1320-5
• Meta-analysis of 33 studies: significantly reduced symptoms compared to prokinetics alone (OR 3.26)
• Quality of studies generally poor
• Meta-analysis of 15 RCTs
• Symptom relief:
– LJZT vs prokinetics: OR 1.96
– XSLJZT vs prokinetics: OR 2.63
• No ADR for LJZT & XSLJZT, ADRs reported in prokinetics
• Most studies poor quality
47 Evid Based Complement Alternat Med 2012; 2012: 936459
• 72 FD patients by Rome III criteria
• Randomized to acupuncture vs sham acupuncture
– Electro acupuncture performed for 30min, 5 times per week; total duration 4 weeks
• Symptom Index of Dyspepsia (SID): FD symptoms
– SID improvement significantly better in acupuncture group: 1.912 to 0.880 vs 1.930 to 1.400; P<0.05
48 Am J Gastroenterol 2012; 107: 1236-47
Back to Scenarios
49
50
Conclusion
• Functional dyspepsia is common
• Need to tailor diagnostic & management approach for each patient
51
Diagnostic Algorithm
52
Management Algorithm
Thank You
Questions?