jurnal hepato
TRANSCRIPT
DRUG INDUCED ACUTE PANCREATITIS : RESULT FROM THE HOSPITAL-BASED
BERLIN CASE CONTROL SURVEILLANCE STUDY OF 102 CASE
A.Douros, E.Bronder, F.Andersohn, et all
Alimentary Pharmacology and Therapeutics
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DRUG TOXICITY common cause of non alcoholic ACUTE PANCREATITIS
> 500 drugs, Various classes
Spontaneous reporting reports and published case control
Valuable source to provide signal of drug risk
INTRODUCTION
METHODS
The hospital-based Berlin case control survellance study FAKOS
Initiated in 2000 serious toxic of drugs
Comprised > 180 department of Internal Medicine,Neurology,Psychiatri, and Anaesthesiology
Of all 51 Berlin Hospital
October 2002 – December 2011
CASE IDENTIFICATION AND RECRUITMENT
Case identified study centre
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reported
Trained member of
FAKOS
• obtained informed consent• Face to face interview • Collecting on all previous drug intakes• Co-morbidity• Other possible risk factor e.g chemicals,solvent or smoking
METHODS
the standardised questionnaire first asked the control and case for previous and current
Disease and for the drugs taken for the disease
The study region was in Berlin, with 2.8 million adult inhabitants as source population
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METHODS
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METHODS
INCLUDED CRITERIA • minimum age of 18 years • a new diagnosis of IAP within the last 6 months • at least 2 of the following 3 criteria ; elevation of lipase or amylase at least threefold above ULN, characteristic upper abdominal pain or signs of pancreatitis in imaging
EXCLUDED CRITERIA
• Chronic pancreatitis• Biliary etiology icl. Choledocholitiasis • Prior history of biliary colic• Dilated biliary tract or concomitant rise of transminase and bilirubin • Other obstruction-related etiology of AP such as pancreatic tumor or pancreatic malformations• Alcoholic • Ischaemic trauma induced AP• Hyperparathyroid• Massive hypertriglyceridaemia ( > 11.2 mmol/L)• ERCP in the last 48 hours
IAP was validated as certain, propable,possible, or unlikely based on clinical information about laboratory and other diagnostic test
The grading of pancreatitis was based on imaging findings
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METHODS
Case validation and characterisaton
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METHODS
Control selection •Conducted from january 2002 – december 2011 at the same hospital where case were recruited
• the aim to raise a multiple of controls compared with cases to increase study power
•The control/case ratio was approximately 7:1
•Informed consent was obtain and control patients were subsequently interviewed in the same standarised way as the IAP patients
• the index date was defined as the date of hospitalitation or date of the onset of the control disease if this preceded hospitalitation
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A drug reaction was evaluated as “certain”
A clinically reasonable response on drug withdrawal (“possitive dechallenge”) was observed
AP was observed on re-exposure to the same drug (“positive rechallenge”)
The causality “was propable” when AP occured with a reasonable time sequence to the drug administration and not attributed to other causes
the drug reaction was possible when there was a plausible time sequence to drug intake
Standardised assessment of drug causality in individual cases
METHODS
Included all cases validated as certain or probable irrespective of the result of causality assessment
out patient case & control were considered as exposed to drug if the drug had taken in last 7 days before the index time
Odds ratio (OR) and 95% confidence interval (CI) of IAP associated with exposure to spesific drug , calculated by logistic regression analysis
all risk calculatioon were performed by SAS statistical software
a two tailed P value < 0.05 was considered significant
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METHODS
Case control analysis
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RESULTS
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RESULTS
Drug causality assessment in
individual casesAP
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RESULTS
Case Controlanalysis
Show the characteristic of out-patient
cases,including grading of AP, associated
laboratory findings and clinical symptom,
complication,imaging findings and outcome
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RESULTS
associated?Lancashire et al using GRPD :
“ a few drug commonly reported as suspected to cause AP either did’nt have an increased at all ( statin) or did’nt have an increased risk compared with other, more seldom reported drugs of the same class ( valproic acid )
risk
azathioprine, mesalazine, mercaptopurin , ACE Inhibitor, fenofibrat and leflunomide ( RARE )
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DISCUSSION
500 drugs AP
Case control analysis
This study corroborate previous findings that suggest an absence of fixed duration of drug use in DIAP
The thiopurines azathioprine and mercaptopurin as well as dervative of salysilic acid mesalazine, have been repeatedly reported AP
a positive rechallenge was doumented, and therefore a certain causality was indicated
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DISCUSSION
Potentialpancreatotoxic
herbal Harpagophytum and valerian radix as well as for tocilizumab
probable
relation
not significant
However, as biliary sludge depicts as idiopathic, this remains a potential limitation to this study
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DISCUSSION
Cefouraxim, cefotaxime, and cefixime AP ceftriaxone
DM,Smokers AP
not narowing it’s focus to spesific drugs
able to assess a wide range of drug
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DISCUSSION
FAKOS
Participated by
Hospital and medical
department
In case of characteristic abdominal pain or an elevation of the respective laboratory parameters, drugs should be part of the differential diagnosis, especially when alcohol
intake or gallstone can be ruled out as posible causes
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