Naslov Pronalaženje dokaza o djelotvornosti i sigurnosti antioksidansa u prevenciji karcinoma probavnog trakta : "sustavni" pregled literature : diplomski rad Naslov (engleski) Finding evidence of efficacy and safety of antioxidant supplements for preventing gastrointestinal cancers : systematic review approach : master thesis Autor Kristina Matas Mentor Darko Modun (mentor)Član povjerenstva Livia Puljak (predsjednik povjerenstva)Član povjerenstva Matko Marušić (član povjerenstva)Član povjerenstva Darko Modun (član povjerenstva)Ustanova koja je dodijelila Sveučilište u Splitu Ustanova koja je dodijelila Sveučilište u Splitu Datum i država obrane 2015-10-30, Hrvatska Znanstveno / umjetničko BIOMEDICINA I ZDRAVSTVO Sažetak Cilj istraţivanja: Pronaći najbolje dostupne dokaze o djelotvornosti i sigurnosti antioksidansa u prevenciji karcinoma probavnog trakta.
Materijal i metode: Na stranici Cochrane knjiţnice pronaĎen je sustavni pregled „Antioxidant supplements for preventing gastrointestinal cancers“ na kojem se temeljilo daljnje istraţivanje. Potom su pretraţene baze podataka MEDLINE (PubMed), DARE i CENTRAL s ciljem pronalaska novih randomiziranih kontroliranih pokusa i sustavnih pregleda, a prema ulaznim i
... Više izlaznim kriterijima navedenima u Cochrane sustavnom pregledu.
Nakon pretraţivanja literature Cochrane sustavni pregled i novi pronaĎeni sustavni pregledi su ocijenjeni koristeći R-AMSTAR obrazac.
Rezultati: Prema Cochrane sustavnom pregledu, antioksidansi nisu imali značajne učinke na smrtnost u modelu meta-analize slučajnih učinaka (RR 1,02, 95% CI 0,97-1,07, I2 = 53,5%), ali su znatno povećali smrtnost u modelu meta-analize fiksnih učinaka (RR 1,04, 95% CI 1,02-1,07). Beta-karoten u kombinaciji s vitaminom A(RR 1,16, 95% CI 1,09-1,23) i vitaminom E (RR 1.06, 95% CI 1,02-1,11) znatno povećava smrtnost. Povećano ţutilo koţe i podrigivanje su bezopasne nuspojave beta-karotena. U pet studija (četiri s visokim rizikom od pristranosti), selen je pokazao značajan blagotvoran učinak na pojavu gastrointestinalnog raka (RR 0,59, 95% CI 0,46-0,75, I2 = 0%). Pronašli smo još dva RCT. U jednoj studiji nije bilo statistički značajne redukcije raka debelog crijeva (HR, 0.89; 95% CI 0.68-1.17, p = 0,39) niti raka gušterače (HR, 1,19; 95% CI, 0.76- 1,85; P = 0,45). Ukupna smrtnost nije značajno smanjena (HR, 0,94; 95% CI, 0,88-1,02; P = 0,13). Ispitanici koji su uzimali aktivnu tvar u odnosu na placebo multivitamina bili su skloniji osipu na koţi (2,111 i 1,973 muškaraca u odgovarajućim aktivnim i placebo skupinama; HR, 1,08; 95% CI, 1.01-1.15, p = 0,016). U drugoj studiji je izvješteno o povećanom riziku od dijabetesa tipa 2 u kraku sa selenom, koji nije bio značajan (P = 0,16; 1,07; RR = 99% CI, 0,94-1,22) te je umanjen u drugom izvještaju od ove studije (HR: 1.04; 99% CI: 0.93–1.17). Nije bilo značajne razlike meĎu skupinama tretmana za rak debelog crijeva za selen, vitamina E ili njihovu kombinaciju. Cochrane sustavni pregled je prema R-AMSTAR procjeni ocijenjen s 40 bodova. PronaĎena su još dva sustavna pregleda, koja su ocijenjena s 29 i 24 boda. Ova dva sustavna pregleda su dala iste zaključke kao i Cochrane sustavni pregled iako su se razlikovali u kvaliteti. Sustavni pregled ocijenjen s 29 bodova pokazao je da dodaci antioksidansa nemaju učinka u prevenciji raka jednjaka. Sustavni pregled ocijenjen s 24 boda pokazao je da dodaci antioksidansa nisu imali značajan učinak na pojavnost kolorektalnog karcinoma niti na ukupnu smrtnost.
Zaključak: Na temelju pregledanih sustavnih pregleda i randomiziranih kontroliranih pokusa nisu se uspjeli naći uvjerljivi dokazi o upotrebi dodataka antioksidansa u prevenciji karcinoma gastrointestinalnog trakta. Upravo suprotno, čini se da dodaci antioksidansa povećavaju ukupnu smrtnost. Potencijalni preventivni učinak selena bi se trebao podrobnije ispitati na odgovarajućoj populaciji i u odgovarajuće provedenim randomiziranim pokusima. Sakrij dio sažetka Sažetak (engleski) Diploma Thesis Title: Finding evidence of efficacy and safety of antioxidant supplements for preventing gastrointestinal cancers: systematic review approach
Objectives: Finding the best available evidence of efficacy and safety of antioxidant supplements for preventing gastrointestinal cancers.
Material and Methods: „Antioxidant supplements for preventing gastrointestinal cancers“ systematic review was found by searching the Cochrane Library website. Further, we searched MEDLINE (PubMed),
... Više DARE and CENTRAL databases in order to find new randomised controlled trials and systematic reviews, following the same criteria that were used in Cochrane systematic review. After the search for studies was done, we made quality assessment of all systematic reviews using R-AMSTAR tool.
Results: According to Cochrane systematic review, antioxidant supplements were without significant effects on gastrointestinal cancers (RR 0.94, 95% CI 0.83 to 1.06). However, there was significant heterogeneity (I(2) = 54.0%, P = 0.003). The heterogeneity may have been explained by bias risk (low-bias risk trials RR 1.04, 95% CI 0.96 to 1.13 compared to highbias risk trials RR 0.59, 95% CI 0.43 to 0.80; test of interaction P < 0.0005), and type of antioxidant supplement (beta-carotene potentially increasing and selenium potentially decreasing cancer risk). The antioxidant supplements had no significant effects on mortality in a random-effects model meta-analysis (RR 1.02, 95% CI 0.97 to 1.07, I(2) = 53.5%), but significantly increased mortality in a fixed-effect model meta-analysis (RR 1.04, 95% CI 1.02 to 1.07). Beta-carotene in combination with vitamin A (RR 1.16, 95% CI 1.09 to 1.23) and vitamin E (RR 1.06, 95% CI 1.02 to 1.11) significantly increased mortality. Increased yellowing of the skin and belching were non-serious adverse effects of beta-carotene. In five trials (four with high risk of bias), selenium seemed to show significant beneficial effect on gastrointestinal cancer occurrence (RR 0.59, 95% CI 0.46 to 0.75, I(2) = 0%). We found two more RCTs. In one study there were statistically non-significant reductions in colorectal (HR, 0.89; 95% CI, 0.68–1.17; P=0.39) and pancreatic cancer (HR, 1,19; 95% CI, 0.76-1.85; P=0.45). Total mortality was not significantly reduced (HR, 0.94; 95% CI, 0.88–1.02; P=0.13). Those taking the active versus placebo multivitamin use were more likely to have skin rashes (2,111 and 1,973 men in corresponding active and placebo multivitamin groups; HR, 1.08; 95% CI, 1.01–1.15; P=0.016). In the other study, there were nonsignificant increased risks of Type 2 diabetes mellitus in the selenium arm (p=0.16; RR=1.07; 99% CI,
0.94–1.22). However, this slight increase was diminished in the second report (HR: 1.04; 99% CI: 0.93–1.17) There were no significant differences among treatment groups for colorectal cancer for selenium, vitamin E or their combination. Total R-AMSTAR score for Cochrane systematic review was 40. Two more systematic reviews were found. R-AMSTAR total score for them was 29 and 24. These two systematic reviews give the same conclusions as the Cochrane systematic review, although they differ in quality. A systematic review evaluated with 29 points showed that antioxidant supplements had no effect in the prevention of esophageal cancer. A systematic review evaluated with 24 points showed that antioxidant supplements had no significant effect on the incidence of colorectal cancer or in total mortality.
Conclusion: Based on the reviewed systematic reviews and randomised controlled trials, convincing evidence that antioxidant supplements prevent gastrointestinal cancers could not be found. On the contrary, antioxidant supplements seem to increase overall mortality. The potential cancer preventive effect of selenium should be tested in adequately conducted randomised trials on appropriate type of population. Sakrij dio sažetka Ključne riječi
antioksidansi
karcinomi probavnog trakta
sustavno pretraživanje literature
R-AMSTAR procjena kvalitete
pretraživači
Science Citation Index Expanded (SCI-EXPANDED)
Chinese Biomedical Database
MEDLINE (PubMed)
Cochrane knjižnica
EMBASE(Excerpta Medica Database)
DARE (Database of Abstracts of Reviews of Effects)
CENTRAL
farmakoterapija utemeljena na dokazima
diplomski rad
Ključne riječi (engleski)
antioxidants
gastrointestinal cancers
literature retrieval
R-AMSTAR quality control
search engines
Science Citation Index Expanded (SCI-EXPANDED)
Chinese Biomedical Database
MEDLINE (PubMed)
Cochrane library
EMBASE (Excerpta Medica Database)
DARE (Database of Abstracts of Reviews of Effects)
CENTRAL
evidence base pharmacotherapy
master thesis
Jezik hrvatski URN:NBN urn:nbn:hr:167:546382 Studijski program Naziv: Farmacija Vrsta resursa Tekst Način izrade datoteke Izvorno digitalna Prava pristupa Otvoreni pristup Uvjeti korištenja Javna napomena Ključne riječi doradio knjižničar / Key words have been revised by the librarian Datum i vrijeme pohrane 2016-02-23 12:01:04
