Advantages and disadvantages of cohort and case-control studies

Liječnici vrlo često svojim bolesnicima trebaju dati savjet o stilu života kako bi se na najmanju moguću mjeru svela vjerojatnost od oboljenja od neke bolesti. Također, potrebno je odabrati i ispravan lijek za liječenje određenih bolesti. Podatke koji im mogu olakšati ove odluke moguće je pronaći i u kohortnim i case-control studijama. Ove studije su relativno jeftine, jednostavne za provođenje, a rezultati su dostupni u relativno kratkom vremenu. Međutim, potrebno je biti svjestan prednosti i nedostataka ovakvih studija kako bi se rezultati mogli interpretirati sa sigurnošću i kako bi se mogle donositi ispravne kliničke odluke.Physicians are very often called on by their patients to give lifestyle advice to reduce the odds of contracting a certain disease. Also, it is necessary for physicians to adequately choose among different therapeutic modalities for any given disease. The data that may make these choices easier come in part from cohort and case-control studies. These studies are of relatively low cost and simple to undertake and the results are available in a relatively short time. However, one must be aware of advantages and disadvantages of these types of studies so that the results can be interpreted with certainty in order to make correct clinical decisions

Cochrane group from Rijeka – review of activities and results

Dugogodišnja suradnja riječkih gastroenterologa sa specifičnim grupama u sklopu Cochrane kolaboracije rezultirala je značajnim napretkom na polju znanstveno-istraživačke djelatnosti i brojnim publikacijama. Spoznaje i zaključci dosegnuti u Cochrane sustavnim pregledima predstavljaju pouzdane stručne dokaze u raznim područjima gastroenterologije, posebno kronične hepatitis C infekcije, kolestatskih bolesti jetre i akutnog pankreatitisa. Navedene publikacije visoko su citirani radovi, koji su implementirani i u nekim međunarodnim smjernicama, odnosno preporukama liječenja. Doprinosom riječke Cochrane grupe otvorena su vrata suradnje s brojnim inozemnim stručnjacima i suradnicima, pokrenuto je organiziranje tečajeva medicine temeljene na dokazima i unaprijeđena je suradnja s Hrvatskim Cochrane centrom te drugim domaćim znanstvenicima. Ovaj pregledni članak predstavlja pregled dosadašnjih postignuća riječkih autora u sklopu Cochrane kolaboracije uz sažeti prikaz najznačajnijih rezultata i zaključaka u objavljenim Cochrane sustavnim pregledima s ciljem upoznavanja javnosti s mogućnostima rada u Cochrane kolaboraciji i vrstom znanstveno-istraživačke djelatnosti koja se u sklopu iste provodi te promocije i popularizacije medicine temeljene na dokazima u široj znanstvenoj i stručnoj zajednici.The long-term cooperation of gastroenterologists from Rijeka with specific groups within the Cochrane Collaboration has resulted in significant progress in the field of scientific research and numerous publications. The findings and conclusions reached in the published Cochrane systematic reviews represent reliable evidence in various gastroenterology fields, particularly chronic hepatitis C infection, cholestatic liver disease and acute pancreatitis. The aforementioned publications are highly quoted papers, which are cited in different international guidelines and treatment recommendations. With the contribution of authors from Rijeka, a door to cooperation with several foreign experts and associates has been opened, courses in evidence-based medicine have been organized, and the collaboration with the Croatian Cochrane Center and other domestic scientists has been enhanced. This review article presents an overiew of the achievements of authors from Rijeka within the Cochrane Collaboration with a summary of the most important results and conclusions from the systematic reviews aiming to inform the public of the opportunities given by the Cochrane Collaboration and the type of scientific research implemented by it, as well as, to promote and popularize evidence-based medicine in a broad scientific and professional community

Presentation and development of Cochrane systematic review of interventions

Sustavni pregledni radovi se danas smatraju dijelom relevantne znanstvene i stručne literature koja postaje neizostavni dio svakodnevne medicinske prakse i važan element u donošenju odluka. Radi se o znanstvenom istraživanju koje temeljem sustavne i strogo definirane metodologije pretrage, odabira i analize dostupnih znanstvenih dokaza daje odgovor na točno definirano znanstveno pitanje. Cochrane kolaboracija je svjetska neprofitna organizacija čiji je cilj stvaranje kvalitetnih sustavnih preglednih radova kroz detaljnu, razrađenu i rigoroznu metodologiju. Kroz različite znanstvene grupe, autori publiciraju Cochrane sustavne preglede intervencija i dijagnostičkih testova koji se objavljuju u Cochrane bazi sustavnih preglednih članaka. Cochrane sustavni pregledni rad se razvija u nekoliko koraka: formulacija pitanja, odabir Cochrane skupine, registracija naslova, izrada i objava protokola, te izrada, objava i održavanje sustavnog preglednog rada. Ovim radom želimo prikazati metodologiju razvoja sustavnog pregleda u sklopu Cochrane kolaboracije kao općeniti uvid u kompleksnost njegove izrade.Systematic review articles are considered today as part of relevant scientific and professional literature which is becoming an infallible part of everyday medical practice and a vital part in decision making. This scientific work is based on systematic and strictly defined methodology of search, selection and analysis of available medical evidence which provides and answer to a specific scientific question. The Cochrane Collaboration is a world non-profit organizaton whose goal is to publish high qualitiy systematic reviews through detailed and rigorous methodology. Through different scientific groups, authors publish Cochrane systematic reviews of interventions and diagnostic tests which are published in the Cochrane Database of Systematic Reviews. These reviews are developed through several steps: question formulation, Cochrane group selection, title registration, writing and publishing a protocol and writing, publishing and updating a systematic review. In this article we wish to present the methodology of Cochrane systematic review development as a general insight into its complexity

Udruženost celijakije s autoimunim hepatitisom i autoimunom bolesti štitnjače

Although celiac disease (CD) may occur in patients with other immune-mediated disorders, its coexistence with multiple autoimmune diseases is not frequently described. We report the case of a 23-year-old woman referred to our centre because of jaundice and diarrhoea, who was diagnosed with CD in childhood. She complied with a gluten-free diet until puberty. Laboratory tests and liver biopsy were performed to establish the diagnosis of autoimmune hepatitis. Her thyroid- specific peroxides levels and thyroid gland function tests were altered as well, indicating the presence of an autoimmune disorder of the thyroid gland. Immunosuppressive treatment led to normalization of transaminases levels and bilirubin. In conclusion, other autoimmune diseases should be ruled out in patients with CD.Iako celijakija ili glutenska enteropatija može biti udružena s drugim imunološkim bolestima, udruženost celijakije s više autoimunih bolesti nije česta. U ovom radu prikazujemo slučaj 23- godišnje bolesnice, liječene u našem Centru zbog ikterusa i proljeva, a kojoj je dijagnoza celijakije postavljena još u djetinjstvu. Do početka puberteta pacijentica se pridržavala bezglutenske dijete. Tijekom boravka u našem Centru, učinjenom dijagnostičkom obradom (laboratorijski pokazatelji i patohistološki nalaz bioptata jetre), dokazan je autoimuni hepatitis. Nadalje, funkcionalni testovi štitnjače, kao i pozitivan nalaz antitijela na tkivnu peroksidazu, ukazivali su na autoimunu bolest štitnjače. Primjenom imunosupresivne terapije došlo je do normalizacije vrijednosti aminotransferaza, kao i regresije ikterusa. Slijedom navedenog, u bolesnika s celijakijom nužno je razmišljati i o drugim imunološkim bolestima

Udruženost celijakije s autoimunim hepatitisom i autoimunom bolesti štitnjače

Although celiac disease (CD) may occur in patients with other immune-mediated disorders, its coexistence with multiple autoimmune diseases is not frequently described. We report the case of a 23-year-old woman referred to our centre because of jaundice and diarrhoea, who was diagnosed with CD in childhood. She complied with a gluten-free diet until puberty. Laboratory tests and liver biopsy were performed to establish the diagnosis of autoimmune hepatitis. Her thyroid- specific peroxides levels and thyroid gland function tests were altered as well, indicating the presence of an autoimmune disorder of the thyroid gland. Immunosuppressive treatment led to normalization of transaminases levels and bilirubin. In conclusion, other autoimmune diseases should be ruled out in patients with CD.Iako celijakija ili glutenska enteropatija može biti udružena s drugim imunološkim bolestima, udruženost celijakije s više autoimunih bolesti nije česta. U ovom radu prikazujemo slučaj 23- godišnje bolesnice, liječene u našem Centru zbog ikterusa i proljeva, a kojoj je dijagnoza celijakije postavljena još u djetinjstvu. Do početka puberteta pacijentica se pridržavala bezglutenske dijete. Tijekom boravka u našem Centru, učinjenom dijagnostičkom obradom (laboratorijski pokazatelji i patohistološki nalaz bioptata jetre), dokazan je autoimuni hepatitis. Nadalje, funkcionalni testovi štitnjače, kao i pozitivan nalaz antitijela na tkivnu peroksidazu, ukazivali su na autoimunu bolest štitnjače. Primjenom imunosupresivne terapije došlo je do normalizacije vrijednosti aminotransferaza, kao i regresije ikterusa. Slijedom navedenog, u bolesnika s celijakijom nužno je razmišljati i o drugim imunološkim bolestima

Postupnici za periproceduralno zbrinjavanje i zbrinjavanje krvarenja u bolesnika liječenih novim oralnim antikoagulantnim lijekovima [Algorithms for periprocedural management and management of bleeding in patients treated with non-vitamin K oral anticoagulants]

The goal of therapy with vitamin K antagonists (warfarin), and new direct oral anticoagulant drugs (NOAC or DOAC) is the prevention of stroke and embolic events in patients with non-valvular atrial fibrillation and treatment and prevention of venous thromboembolism. In all cases it is necessary to determine renal function with creatinine clearance because it determines the choice and dosage of NOAC’s. It is extremely important to pay attention to older patients with a number of associated conditions and drug interactions, with a high incidence of neurological symptoms and worse outcomes. Oral anticoagulation can represent a challenge, especially in cases of drug overdose or emergencies such as bleeding and need for urgent surgery. The need for the guidelines has emerged during the last years because of new classes of oral anticoagulants being prescribed more frequently. The expert working group of emergency specialists was formed and gathered on Consensus Conference in October 2015 in Zagreb, to design guidelines for the patients with NOAC therapy and provides details of preoperative management and managements in emergency conditions

ALGORITHMS FOR PERIPROCEDURAL MANAGEMENT AND MANAGEMENT OF BLEEDING IN PATIENTS TREATED WITH NON-VITAMIN K ORAL ANTICOAGULANTS

Cilj terapije antagonistima vitamina K (varfarin) i novim oralnim antikoagulantnim lijekovima (NOAK-ima) jesu prevencija moždanog udara i drugih embolija kod bolesnika s nevalvularnom fibrilacijom atrija te liječenje i prevencija venske tromboembolije. Kod svih bolesnika potrebno je odrediti bubrežnu funkciju klirensom kreatina jer o tome ovise izbor i doziranje NOAK-a. Izuzetno je važno obratiti pozornost na starije bolesnike s brojnim pridruženim stanjima i interakcijama lijekova zbog velike učestalosti neuroloških simptoma i lošijeg ishoda. Oralno antikoagulantno liječenje izazov je, posebno u stanjima nenamjernog predoziranja lijeka, u krvarenjima ili u stanjima hitnoga prijeoperacijskog zbrinjavanja. Zbog sve većeg broja bolesnika koji uzimaju NOAK-e osnovana je 2015. godine ekspertna grupa specijalista hitne medicine koja je u listopadu 2015. održala u Zagrebu Konsenzusnu konferenciju radi donošenja postupnika za prijeoperacijsko zbrinjavanje i zbrinjavanje bolesnika u hitnim stanjima koji uzimaju NOAK-e u Hrvatskoj.The goal of therapy with vitamin K antagonists (warfarin), and new direct oral anticoagulant drugs (NOAC or DOAC) is the prevention of stroke and embolic events in patients with non-valvular atrial fibrillation and treatment and prevention of venous thromboembolism. In all cases it is necessary to determine renal function with creatinine clearance because it determines the choice and dosage of NOAC’s. It is extremely important to pay attention to older patients with a number of associated conditions and drug interactions, with a high incidence of neurological symptoms and worse outcomes. Oral anticoagulation can represent a challenge, especially in cases of drug overdose or emergencies such as bleeding and need for urgent surgery. The need for the guidelines has emerged during the last years because of new classes of oral anticoagulants being prescribed more frequently. The expert working group of emergency specialists was formed and gathered on Consensus Conference in October 2015 in Zagreb, to design guidelines for the patients with NOAC therapy and provides details of preoperative management and managements in emergency conditions

Endoscopic diagnostic and therapeutical methods in oncology patients

Već dulji niz godina endoskopija je nezaobilazna u dijagnostici gastrointestinalnih, uroloških i plućnih malignih oboljenja. Novije endoskopske metode, zahvaljujući tehnikama poboljšanja slike, pružaju sve više mogućnosti za točnu dijagnozu već tijekom endoskopskog pregleda. U posljednje vrijeme unaprjeđenjem endoskopskih tehnika moguće je odstraniti sve veći broj već razvijenih malignih lezija ili učiniti neki od palijativnih zahvata u svrhu održanja prohodnosti probavne cijevi.Endoscopy is corner stone in diagnostics of gastrointestinal, urological and pumological malignancies. Some newer imaging enhancement techniques improve diagnostics accuracy during endoscopy. Endoscopy now offers a greater possibility of removing malignant lesions or performing palliative procedure sin order to maintain patency of gastrointestinal tract

Diagnostic accuracy of different tests for diagnosis of common bile duct stones : doctoral thesis

Cilj istraživanja: zasebno odrediti dijagnostičku točnost kolestatskih biljega, ultrazvuka abdomena, endoskopskog ultrazvuka, kolangkopankreatografije magnetskom rezonancom (MRCP), endoskopske retrogradne kolangiopankreatografije (ERCP) i intraoperativne kolangiografije koristeci metode Cochrane sustavnog pregleda i meta-analize. Nadalje, cilj rada je usporediti dijagnostičku točnost parova dijagnostičkih postupaka prema njihovom mjestu u postupku dijagnostike koledokolitijaze. Treći cilj je na osnovu dokaza dobivenih meta-analizom razviti postupnik dijagnostike kod bolesnika koji se prezentiraju simptomima i znakovima suspektnim za koledokolitijazu, a koji je temeljen na dokazima. Materijal i metode: u rad su uključeni ispitanici u studijama dijagnostičke točnosti analiziranih postupaka koje zadovoljavaju kriterije uključenja. Iz uključcnih studija izvadeni su podaci o indeksnom postupku i referentnom standardu na način koji omogućuje izračunavanje ukupnog broja stvarno pozitivnih, stvarno negativnih, lažno pozitivnih i lažno negativnih bolesnika koji su dijagnosticirani indeksnim postupkom, a u ovisnosti o rezultalu referentnog standarda. Kao referentni standard uzeta je potvrda prisutnosti iIi odsutnosti koledokolitijaze endoskopskom ili kirurškom eksploracijom zajedničkog žučnog voda. U slučaju negativnog rezultata indeksnog postupka, kada je neetično raditi invazivnu eksploraciju, kao potvrda odsutnosti koledokolitijaze prihvaćeno je asimplomatsko praćenje u trajanju najmanje šest mjeseci. Za meta-analizu korišten je bivarijatni model statističke analize i METADAS makro za SAS statistički program. Također su izračunate post-testne vjerojatnosti postojanja koledokolitijaze nakon pozitivnog i negativnog rezultata svakog od istraživanih dijagnostičkih postupaka s pripadajućim 95%-tnim intervalima pouzdanosti (CI od engl. confidence interval. Za konstrukciju forest plotova bivarijatnih ROC krivulja korišten je računalni program Review Manager (Rev Man) 5.2 razvijen od strane Cochrane kolaboracije. Rezultati: pretraživanjem literature zadanom strategijom pretraživanja dobiveno je 22790 studija. Nakon eliminacije dvostrukih rezultata preostale su 16923 studije. Nadalje je isključeno 16405 studija zbog nepovezanosti s tematikom dijagnostičke točnosti koledokolitijaze. Prema kriterijima uključenja ocijenjeno je 518 studija, od kojih je 36 studija uključeno u sustavni pregled i meta-analizu. Za analizu dijagnostičke točnosti kolestatskih biljega nema dovoljno studija u literaturi; pronađena je samo jedna studija koja zadovoljava kriterije uključenja. Ultrazvuk abdomena pokazao je post-testnu vjerojatnost nakon pozitivnog rezultata od 84,5% (95% Cl 75,0% do 90, I %), dok je post-testna vjerojatnost nakon negativnog rezultata 17,2% (95% CI 8,0% do 33,2%). Ukupno 327% bolesnika koji se podvrgnu ultrazvuku abdomena s ciljem procjene prisutnosti ili odsutnosti koledokolitijaze bit će pogrešno dijagnosticirani. Endoskopski ultrazvuk pokazuje post-testnu vjerojatnost za pozitivan rezultat od 96,0% (95% CI 91 ,8% do 98,1 %) , dok je vjerojatnost za negativan rezultat 3,6% (95% C1 2,2% do 5,8%). Endoskopskim ultrazvukom 7,6% bolesnika dobit ce pogrešnu dijagnozu. MRCP pokazuje post-testnu vjerojatnost za pozitivan rezultat od 93,9% (95% CI 86,7% do 97,3%), dok je vjerojatnost za negativan rezultat 4,9% (95% Cl 2,6% do 8,9%). Ukupno 11 % bolesnika imat ce pogrešno postavljenu dijagnozu nakon učinjenog MRCP-a. Nema statistički značajne razlike između dijagnostičke točnosti endoskopskog ultrazvuka i MRCP-a, medutim MRCP pokazuje nesto bolje rezultate kod prethodno kolecistektomiranih bolesnika. ERCP je pokazao post-testnu vjerojatnost za pozitivan rezultat od 99,0% (95% CI 91 ,0% do 99,9%), dok je vjerojatnost za negativan rezultat 7 4% (95% C1 3 2% do 16 3%). Nakon dijagnostike ERCP-om 8,4% bolesnika bit ce pogrešno dijagnosticirano. Intraoperativna kolangiografija pokazuje post-testnu vjerojatnost za pozitivan rezultat od 98,0% (95% Cl 94,6% do 99,3%), dok je vjerojatnost za negativan rezultat 1,1% (95% CI 0,0% do 31 ,0%). Ovom metodom 3,1% bolesnika imat će pogrešnu dijagnozu. Nema statistički značajne razlike između dijagnostičke točnosti ERCP-a i intraoperativne kolangiografije, međutim kako su ovo vrlo invazivni postupci ne preporučuju se u rutinskoj dijagnostici koledokolitijaze. U bolesnika koji nisu kolecistektomirani preporučuje se učiniti intraoperativnu kolangiografiju u slučaju da bolesnik ima simptome i znakove a rezultati prethodnih dijagnostičkih postupaka su negativni, u centrima koji imaju ovakvu mogućnost. Na osnovi rezultata ovog rada razvijen je dijagnostički postupnik temeljen na dokazima kod bolesnika sa suspektnom koledokolitijazom. Zaključak: ovim radom dobiveni su podaci o dijagnostičkoj točnosti različitih postupaka u dijagnostici koledokolitijaze koji su temeljeni na dokazima dobivenima Cochrane sustavnim pregledom i meta-analizom. Uspoređeni su parovi postupaka koji se primijenjuju na svakom od tri stupnja dijagnostičke obrade bolesnika. Također je predložen i dijagnostički postupnik koji se temelji na rezultatima ovog rada. Daljnja istraživanja trebaju biti provedena u prikladno odabranim populacijama bolesnika uz primjenu najboljih mogućih referentnih postupaka.DIAGNOSTIC ACCURACY OF DIFFERENT TESTS FOR DIAGNOSIS OF COMMON BILE DUCT STONES Objectives: this thesis aimed to determine diagnostic test accuracy of liver funcion tests, abdominal ultrasound, endoscopic ultrasound, megnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP) and intraoperative cholangiography by using the methods of Cochrane systematic review and meta-analysis. Further, the aim was to compare diagnostic accuracy of pairs of tests according to their position in the diagnostic pathway. Third aim was to develop a diagnostic algorithm for evaluation of patients suspected of common bile duct stones which is based on evidence aquired by this research. Material and methods: subjects from diagnostic accuracy studies that fulfilled the inclusion criteria were included. Data on the index test and the reference standard were extracted from included studies in the manner so that number of true positive, true negative, false positive and false negative could be calculated based on the results of the reference standard. Results of positive or negative endoscopic or surgical exploration of the common bile duct were accepted as reference standard. In the case of negative index test result, when it would be unethical to explore the common bile duct, the confirmation of absence of stones by asymptomatic follow-up of at least six months was accepted. Bivariate statistical analysis mode and METADAS macro for SAS were used to meta-analyse the data. Also, post-test probabilities for positive and negative index tests with corresponding 95% confidence intervals (CI) were calculated for each of the tests that were evaluated. For construction of forest plots and bivariate ROC curves we used Review Manager (RevMan) 5.2 developed and provided by the Cochrane Collaboration. Results: A total of 22790 studies were evaluated for inclusion in the systematic review. After deletion of duplicates 16923 studies were further evaluated. A further 16405 studies were eliminated because of evident lack of connection with diagnostic accuracy of common bile duct stones. The remaining 518 studies were evaluated for inclusion, out of which 36 studies were included in the systematic review and meta-analysis. There were not enough studies for evaluation of liver function tests, only one study met the inclusion criteria. Abdominal ultrasound showed post-test probability for positive test of 84.5% (95% CI 75.0% to 90.1%), while post-test probability for negative test is 17.2% (95% CI 8.0% to 33.2%). A total of 32.7% of patients that undergo abdominal ultrasound for evaluation of presence of absence of common bile duct stones will receive wrong diagnosis. Endoscopic ultrasound showed post-test probability for positive test of 96.0% (95% CI 91.8% to 98.1%). Post-test probability for negative test is 3.6% (95% CI 2.2% to 5.8%). Patients evaluated with endoscopic ultrasound will receive wrong diagnosis on 7.6% of cases. MRCP showed post-test probability for positive test of 93.9% (95% CI 86.7% to 97.3%), while post-test probability for negative test is 4.9% (95% CI 2.6% to 8.9%). A total of 11% of patients evaluated with MRCP will receive the wrong diagnosis. There is not statistically significant difference between diagnostic accuracy of endoscopic ultrasound and MRCP. However, MRCP showed somewhat better results in patients with previous cholecystectomy. ERCP showed post-test probability for positive test of 99.0% (95% CI 91.0% to 99.9%), while the post-test probability for negative test is 7.4% (95% CI 3.2% to 16.3%). After performing ERCP, 8.4% of patients will receive the wrong diagnosis. Intraoperative cholangiography showed post-test probability for positive test of 98.0% (95% CI 94.6% to 99.3%), while the post-test probability for a negative test is 1.1% (95% CI 0.0% to 31.0%). There is a probability that 3.1% evaluated with intraoperative cholangiography will receive the wrong diagnosis. There is no statistically significant difference between diagnostic accuracy of ERCP and intraoperative cholangiography. However, since those are highly invasive procedures they are not recommended in routine diagnostic evaluation for common bile duct stones. In patients that have not been previously cholecystectomysed it is recommended to perform intraoperative cholangiography when a patient has signs and symptoms and results of previous diagnostic test are negative, in centres with such capabilities. A diagnostic algorithm for diagnosis of patients suspected of common bile duct stones was developed. The diagnostic algorithm is based on evidence obtained in this study. Conclusion: results of diagnostic accuracy of different tests of diagnosis of common bile duct stones are presented in this thesis, based on evidence obtained with a Cochrane systematic review and meta-analysis. Pairs of diagnostic tests that are performed on each of the three steps of diagnostic pathway were compared. Also, a diagnostic algorithm was presented, based on results of this thesis. Further research should be performed in adequately selected populations of patients and best available reference standards should be applied

Diagnostic accuracy of different tests for diagnosis of common bile duct stones : doctoral thesis

Cilj istraživanja: zasebno odrediti dijagnostičku točnost kolestatskih biljega, ultrazvuka abdomena, endoskopskog ultrazvuka, kolangkopankreatografije magnetskom rezonancom (MRCP), endoskopske retrogradne kolangiopankreatografije (ERCP) i intraoperativne kolangiografije koristeci metode Cochrane sustavnog pregleda i meta-analize. Nadalje, cilj rada je usporediti dijagnostičku točnost parova dijagnostičkih postupaka prema njihovom mjestu u postupku dijagnostike koledokolitijaze. Treći cilj je na osnovu dokaza dobivenih meta-analizom razviti postupnik dijagnostike kod bolesnika koji se prezentiraju simptomima i znakovima suspektnim za koledokolitijazu, a koji je temeljen na dokazima. Materijal i metode: u rad su uključeni ispitanici u studijama dijagnostičke točnosti analiziranih postupaka koje zadovoljavaju kriterije uključenja. Iz uključcnih studija izvadeni su podaci o indeksnom postupku i referentnom standardu na način koji omogućuje izračunavanje ukupnog broja stvarno pozitivnih, stvarno negativnih, lažno pozitivnih i lažno negativnih bolesnika koji su dijagnosticirani indeksnim postupkom, a u ovisnosti o rezultalu referentnog standarda. Kao referentni standard uzeta je potvrda prisutnosti iIi odsutnosti koledokolitijaze endoskopskom ili kirurškom eksploracijom zajedničkog žučnog voda. U slučaju negativnog rezultata indeksnog postupka, kada je neetično raditi invazivnu eksploraciju, kao potvrda odsutnosti koledokolitijaze prihvaćeno je asimplomatsko praćenje u trajanju najmanje šest mjeseci. Za meta-analizu korišten je bivarijatni model statističke analize i METADAS makro za SAS statistički program. Također su izračunate post-testne vjerojatnosti postojanja koledokolitijaze nakon pozitivnog i negativnog rezultata svakog od istraživanih dijagnostičkih postupaka s pripadajućim 95%-tnim intervalima pouzdanosti (CI od engl. confidence interval. Za konstrukciju forest plotova bivarijatnih ROC krivulja korišten je računalni program Review Manager (Rev Man) 5.2 razvijen od strane Cochrane kolaboracije. Rezultati: pretraživanjem literature zadanom strategijom pretraživanja dobiveno je 22790 studija. Nakon eliminacije dvostrukih rezultata preostale su 16923 studije. Nadalje je isključeno 16405 studija zbog nepovezanosti s tematikom dijagnostičke točnosti koledokolitijaze. Prema kriterijima uključenja ocijenjeno je 518 studija, od kojih je 36 studija uključeno u sustavni pregled i meta-analizu. Za analizu dijagnostičke točnosti kolestatskih biljega nema dovoljno studija u literaturi; pronađena je samo jedna studija koja zadovoljava kriterije uključenja. Ultrazvuk abdomena pokazao je post-testnu vjerojatnost nakon pozitivnog rezultata od 84,5% (95% Cl 75,0% do 90, I %), dok je post-testna vjerojatnost nakon negativnog rezultata 17,2% (95% CI 8,0% do 33,2%). Ukupno 327% bolesnika koji se podvrgnu ultrazvuku abdomena s ciljem procjene prisutnosti ili odsutnosti koledokolitijaze bit će pogrešno dijagnosticirani. Endoskopski ultrazvuk pokazuje post-testnu vjerojatnost za pozitivan rezultat od 96,0% (95% CI 91 ,8% do 98,1 %) , dok je vjerojatnost za negativan rezultat 3,6% (95% C1 2,2% do 5,8%). Endoskopskim ultrazvukom 7,6% bolesnika dobit ce pogrešnu dijagnozu. MRCP pokazuje post-testnu vjerojatnost za pozitivan rezultat od 93,9% (95% CI 86,7% do 97,3%), dok je vjerojatnost za negativan rezultat 4,9% (95% Cl 2,6% do 8,9%). Ukupno 11 % bolesnika imat ce pogrešno postavljenu dijagnozu nakon učinjenog MRCP-a. Nema statistički značajne razlike između dijagnostičke točnosti endoskopskog ultrazvuka i MRCP-a, medutim MRCP pokazuje nesto bolje rezultate kod prethodno kolecistektomiranih bolesnika. ERCP je pokazao post-testnu vjerojatnost za pozitivan rezultat od 99,0% (95% CI 91 ,0% do 99,9%), dok je vjerojatnost za negativan rezultat 7 4% (95% C1 3 2% do 16 3%). Nakon dijagnostike ERCP-om 8,4% bolesnika bit ce pogrešno dijagnosticirano. Intraoperativna kolangiografija pokazuje post-testnu vjerojatnost za pozitivan rezultat od 98,0% (95% Cl 94,6% do 99,3%), dok je vjerojatnost za negativan rezultat 1,1% (95% CI 0,0% do 31 ,0%). Ovom metodom 3,1% bolesnika imat će pogrešnu dijagnozu. Nema statistički značajne razlike između dijagnostičke točnosti ERCP-a i intraoperativne kolangiografije, međutim kako su ovo vrlo invazivni postupci ne preporučuju se u rutinskoj dijagnostici koledokolitijaze. U bolesnika koji nisu kolecistektomirani preporučuje se učiniti intraoperativnu kolangiografiju u slučaju da bolesnik ima simptome i znakove a rezultati prethodnih dijagnostičkih postupaka su negativni, u centrima koji imaju ovakvu mogućnost. Na osnovi rezultata ovog rada razvijen je dijagnostički postupnik temeljen na dokazima kod bolesnika sa suspektnom koledokolitijazom. Zaključak: ovim radom dobiveni su podaci o dijagnostičkoj točnosti različitih postupaka u dijagnostici koledokolitijaze koji su temeljeni na dokazima dobivenima Cochrane sustavnim pregledom i meta-analizom. Uspoređeni su parovi postupaka koji se primijenjuju na svakom od tri stupnja dijagnostičke obrade bolesnika. Također je predložen i dijagnostički postupnik koji se temelji na rezultatima ovog rada. Daljnja istraživanja trebaju biti provedena u prikladno odabranim populacijama bolesnika uz primjenu najboljih mogućih referentnih postupaka.DIAGNOSTIC ACCURACY OF DIFFERENT TESTS FOR DIAGNOSIS OF COMMON BILE DUCT STONES Objectives: this thesis aimed to determine diagnostic test accuracy of liver funcion tests, abdominal ultrasound, endoscopic ultrasound, megnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP) and intraoperative cholangiography by using the methods of Cochrane systematic review and meta-analysis. Further, the aim was to compare diagnostic accuracy of pairs of tests according to their position in the diagnostic pathway. Third aim was to develop a diagnostic algorithm for evaluation of patients suspected of common bile duct stones which is based on evidence aquired by this research. Material and methods: subjects from diagnostic accuracy studies that fulfilled the inclusion criteria were included. Data on the index test and the reference standard were extracted from included studies in the manner so that number of true positive, true negative, false positive and false negative could be calculated based on the results of the reference standard. Results of positive or negative endoscopic or surgical exploration of the common bile duct were accepted as reference standard. In the case of negative index test result, when it would be unethical to explore the common bile duct, the confirmation of absence of stones by asymptomatic follow-up of at least six months was accepted. Bivariate statistical analysis mode and METADAS macro for SAS were used to meta-analyse the data. Also, post-test probabilities for positive and negative index tests with corresponding 95% confidence intervals (CI) were calculated for each of the tests that were evaluated. For construction of forest plots and bivariate ROC curves we used Review Manager (RevMan) 5.2 developed and provided by the Cochrane Collaboration. Results: A total of 22790 studies were evaluated for inclusion in the systematic review. After deletion of duplicates 16923 studies were further evaluated. A further 16405 studies were eliminated because of evident lack of connection with diagnostic accuracy of common bile duct stones. The remaining 518 studies were evaluated for inclusion, out of which 36 studies were included in the systematic review and meta-analysis. There were not enough studies for evaluation of liver function tests, only one study met the inclusion criteria. Abdominal ultrasound showed post-test probability for positive test of 84.5% (95% CI 75.0% to 90.1%), while post-test probability for negative test is 17.2% (95% CI 8.0% to 33.2%). A total of 32.7% of patients that undergo abdominal ultrasound for evaluation of presence of absence of common bile duct stones will receive wrong diagnosis. Endoscopic ultrasound showed post-test probability for positive test of 96.0% (95% CI 91.8% to 98.1%). Post-test probability for negative test is 3.6% (95% CI 2.2% to 5.8%). Patients evaluated with endoscopic ultrasound will receive wrong diagnosis on 7.6% of cases. MRCP showed post-test probability for positive test of 93.9% (95% CI 86.7% to 97.3%), while post-test probability for negative test is 4.9% (95% CI 2.6% to 8.9%). A total of 11% of patients evaluated with MRCP will receive the wrong diagnosis. There is not statistically significant difference between diagnostic accuracy of endoscopic ultrasound and MRCP. However, MRCP showed somewhat better results in patients with previous cholecystectomy. ERCP showed post-test probability for positive test of 99.0% (95% CI 91.0% to 99.9%), while the post-test probability for negative test is 7.4% (95% CI 3.2% to 16.3%). After performing ERCP, 8.4% of patients will receive the wrong diagnosis. Intraoperative cholangiography showed post-test probability for positive test of 98.0% (95% CI 94.6% to 99.3%), while the post-test probability for a negative test is 1.1% (95% CI 0.0% to 31.0%). There is a probability that 3.1% evaluated with intraoperative cholangiography will receive the wrong diagnosis. There is no statistically significant difference between diagnostic accuracy of ERCP and intraoperative cholangiography. However, since those are highly invasive procedures they are not recommended in routine diagnostic evaluation for common bile duct stones. In patients that have not been previously cholecystectomysed it is recommended to perform intraoperative cholangiography when a patient has signs and symptoms and results of previous diagnostic test are negative, in centres with such capabilities. A diagnostic algorithm for diagnosis of patients suspected of common bile duct stones was developed. The diagnostic algorithm is based on evidence obtained in this study. Conclusion: results of diagnostic accuracy of different tests of diagnosis of common bile duct stones are presented in this thesis, based on evidence obtained with a Cochrane systematic review and meta-analysis. Pairs of diagnostic tests that are performed on each of the three steps of diagnostic pathway were compared. Also, a diagnostic algorithm was presented, based on results of this thesis. Further research should be performed in adequately selected populations of patients and best available reference standards should be applied