En systematisk översiktsartikel

Sahlgrenska Akademin vid Göteborgs universitet Avdelningen för invärtes medicin och klinisk nutrition Sammanfattning Titel: Kan total enteral nutrition ersätta steroidbehandling vid pediatrisk Morbus Crohn? Författare: Hanna Rymark Lehnér och Josephine Pettersson Handledare: Mette Axelsen Examinator: Anna Winkvist Linje: Dietistprogrammet, 180/240 hp Typ av arbete: Examensarbete, 15 hp Datum: 2012-05-23 Bakgrund: Morbus Crohn är en kronisk inflammatorisk tarmsjukdom som periodvis innebär mycket lidande för patienten. Det finns gediget vetenskapligt underlag för att behandling med steroider effektivt inducerar och bevarar remission. Biverkningarna är dock många och risken stor för hämmad tillväxt och påverkan på skelettutvecklingen hos barn. En allmänt utbredd uppfattning är att total enteral nutrition är lika effektiv som steroidbehandling vid pediatrisk Crohn´s. Detta skulle medföra en minskad risk för allvarliga biverkningar, samtidigt som barnets näringsintag säkerställs och chanserna för en normal tillväxt och kroppsutveckling förbättras. Syfte: Att ta reda på om nutritionsbehandling i form av total enteral nutrition kan leda till remission i samma utsträckning som steroidbehandling hos barn med Crohn´s sjukdom. Frågeställningar som sattes upp var om total enteral nutrition är ett likvärdigt val av primär behandling jämfört med steroider, med avseende på remission/reduktion av sjukdomsaktivitet, tillväxt samt biverkningar. Sökväg: Systematiska sökningar gjordes under februari 2012 i de vetenskapliga databaserna Pubmed och Scopus. Sökord som användes var Crohn disease, enteral nutrition, remission, children och diet. Urvalskriterier: Orginalartiklar på svenska och engelska som jämfört behandlingseffekten mellan total enteral nutrition och steroider hos barn mellan 0-18 år med aktiv Crohn´s. Endast randomiserade kontrollerade humanstudier med steroider som kontrollbehandling inkluderades. Studier som även innefattat Ulcerös colit och/eller parenteral nutrition exkluderades. Datainsamling och analys: Det inkluderades fyra artiklar som granskades enligt SBU´s ”granskningsmall för randomiserad kontrollerad prövning”. Den sammanlagda evidensstyrkan bedömdes utifrån ”sammanfattande evidensformulär”, som är baserat på GRADE. Resultat: Total enteral nutrition är lika effektivt som steroider för att inducera remission vid pediatrisk Crohn´s (Måttlig evidensstyrka +++). Total enteral nutrition som primär behandling leder till en bättre tillväxt jämfört med steroidbehandling. (Begränsad evidensstyrka ++). Total enteral nutrition verkar också ge mindre biverkningar jämfört med steroider(Måttlig evidensstyrka +++). Slutsats: Baserat på denna litteraturgenomgång tyder det vetenskapliga underlaget på att total enteral nutrition är ett bra alternativ till steroider som primär behandling vid pediatrisk Crohn´s.Sahlgrenska Academy at University of Gothenburg Department of internal medicine and clinical nutrition Abstract Title: Can exclusive enteral nutrition replace steroid treatment in pediatric Morbus Crohn? Author: Hanna Rymark Lehnér and Josephine Pettersson Supervisor: Mette Axelsen Examiner: Anna Winkvist Programme: Dietician study programme, 180/240 ECTS Type of paper: Examination paper, 15 hp Date: May 23, 2012 Background: Morbus Crohn is a chronic inflammatory bowel disease which periodically causes great suffering for the patient. There is solid scientific evidence that treatment with steroids effectively induces and preserves remission. However, side effects are many and a great risk for stunted growth and skeletal development exists in children. A widespread view is that exclusive enteral nutrition is as effective as steroids in pediatric Crohn´s. This would mean a reduced risk for serious side effects. At the same time, the child’s nutritional intake is ensured and chances for a normal growth and body development improves. Objective: To determine if nutrition therapy in the form of exclusive enteral nutrition can lead to remission in the same extent as steroids in the treatment of pediatric Crohn´s disease. The issues were to determine if exclusive enteral nutrition is an equal choice of primary treatment compared to steroids, with regards to remission/reduction of disease-activity, growth and side effects. Search strategy: Systematic searches were conducted during February 2012 in the scientific databases Pubmed and Scopus. Keywords used were Crohn disease, enteral nutrition, remission, children and diet. Selection criteria: Original articles in Swedish and English which compared the effect of treatment between exclusive enteral nutrition and steroids for children between 0-18 years with active Crohn´s. Only randomised controlled human studies with steroids as a control were included. Studies which also covered Ulcerous colitis and/or parenteral nutrition were excluded. Data collection and analysis: There were four articles included and audited according to SBU´s template ”granskningsmall för randomiserad kontrollerad prövning”. The total strength of evidence were assessed according to ”sammanfattande evidensformulär”, which is based on GRADE. Main results: Total enteral nutrition is as effective as steroids for inducing remission in pediatric crohn´s (moderate evidence +++). Total enteral nutrition as primary treatment leads to a better growth compared to steroid treatment (limited evidence ++). Exclusive enteral nutrition also seems to cause less side effects compared to steroids (moderate evidence +++). Conclusions: Based on this review the scientific evidence suggests that exclusive enteral nutrition is a good alternative to steroids as a primary method of treatment in pediatric Crohn´s

Co-modality - A forgotten concept?

Co-modality was first introduced in 2006 by the European Commission, the definition was stated as “the efficient use of different transport modes on their own or in combination will result in an optimal and sustainable utilisation of resources”. The authors decided to dig deeper into the true meaning of this vaguely defined concept. Stakeholders within the transport industry were asked upon their view of co-modality. A few of these knew the true definition as stated by the European Commission, while the majority interpreted it as equal to intermodality or were not even aware about the concept. These results lead the authors to try to find out if the co-modality actually is a viable and useful concept for future development within the freight transport industry. In order to do this, the authors hypothetically suggested the inclusion of a triple bottom line model, to by some means assess and measure transport solutions. Furthermore, the authors investigated the possibility to draw parallels to philosophies of improvements, found in other industry sectors. The results out of this hypothesis was that out of economic, environmental and social aspects included in a triple bottom line model, the economic and environmental aspects linked to freight transport were extensively covered in research and business agendas, while the social aspects showed to be less considered. This made the authors obliged to put extra attention towards social aspects, with respect to freight transport. The suggested parallel to other philosophies of improvements, proved to reach consensus by stakeholders of the transport industry. By viewing co-modality as a philosophy of improvements, applicable to the transport industry rather than as a vaguely defined concept, the possibility of co-modality to reach further coherence as a useful way to develop transports in the future should increase.MSc in Logistics and Transport Managemen

Comparison between the Hybrid Capture II Test and a PCR-Based Human Papillomavirus Detection Method for Diagnosis and Posttreatment Follow-Up of Cervical Intraepithelial Neoplasia

Human papillomavirus (HPV) infection is the major cause of cervical cancer and its precursor, cervical intraepithelial neoplasia (CIN), and HPV testing has therefore been proposed for improved triaging and follow-up of women treated for CIN. We compared two common HPV DNA detection tests (Hybrid Capture II [HCII] and PCR-enzyme immunosorbent assay (EIA) using the primers GP5+/GP6+ followed by HPV typing with reverse dot blot hybridization) for sensitivity and specificity for detection of CIN and of CIN recurrence after treatment. Two hundred and thirty-nine women referred to the Department of Obstetrics and Gynaecology in Västerås, Sweden, were enrolled because of atypical Pap smears; 177 of these were later treated for dysplasia by conization or loop diathermy. Samples for HPV DNA testing were taken before and 4 to 6 months after treatment. There was substantial agreement between the HCII and PCR-EIA (kappa, 0.70 before treatment and 0.72 after treatment). The sensitivity for histopathologically confirmed CIN III was 100.0% for PCR-EIA and 95.6% for HCII. For patients with CIN II or worse (CIN II+), the sensitivities were 92.9% (PCR-EIA) and 91.8% (HCII). The specificities for CIN II+ in the pretreatment setting were 30.4% for PCR-EIA and 24.1% for HCII. After treatment, the sensitivities for CIN III in cytology were 100.0% by both methods, and for CIN II+, sensitivities were 80.0% by both methods. The specificities for CIN II+ in the posttreatment setting were 83.5% for PCR and 85.4% for HCII. In conclusion, the sensitivities of both PCR-EIA and HCII are high and almost equal, suggesting that both methods are suitable as tools for detection and posttreatment follow-up of CIN II-III

Pharmacogenetic Studies of Paclitaxel in the Treatment of Ovarian Cancer

The purpose of this study was to evaluate the role of sequence variants in the CYP2C8, ABCB1 and CYP3A4 genes and the CYP3A4 phenotype for the pharmacokinetics and toxicity of paclitaxel in ovarian cancer patients. Thirty-eight patients were treated with paclitaxel and carboplatin. The genotypes of CYP2C8*1B, *1C, *2, *3, *4, *5, *6, *7, *8 and P404A, ABCB1 G2677T/A and C3435T, as well as CYP3A4*1B, were determined by pyrosequencing. Phenotyping of CYP3A4 was performed in vivo with quinine as a probe. The patients were monitored for toxicity and 23 patients underwent a more extensive neurotoxicity evaluation. Patients heterozygous for G/A in position 2677 in ABCB1 had a significantly higher clearance of paclitaxel than most other ABCB1 variants. A lower clearance of paclitaxel was found for patients heterozygous for CYP2C8*3 when stratified according to the ABCB1 G2677T/A genotype. In addition, the CYP3A4 enzyme activity in vivo affected which metabolic pathway was dominant in each patient, but not the total clearance of paclitaxel. The exposure to paclitaxel correlated to the degree of neurotoxicity. Our findings suggest that interindividual variability in paclitaxel pharmacokinetics might be predicted by ABCB1 and CYP2C8 genotypes and provide useful information for individualized chemotherapy.This is the authors’ version of the following article: Henrik Green, Peter Söderkvist, Per Rosenberg, Rajaa A Mirghani, Per Rymark, Elisabeth Avall Lundqvist and Curt Peterson, Pharmacogenetic Studies of Paclitaxel in the Treatment of Ovarian Cancer, 2009, Basic and clinical pharmacology and toxicology, (104), 2, 130-137. which has been published in final form at: http://dx.doi.org/10.1111/j.1742-7843.2008.00351.x Copyright: Blackwell Publishing http://eu.wiley.com/WileyCDA/Brand/id-35.html</p

http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-16525 Paclitaxel pharmacogenetics in ovarian cancer Pharmacogenetic Studies of Paclitaxel in the Treatment of Ovarian Cancer

N.B.: When citing this work, cite the original article. This is the authors ’ version of the following article: Henrik Green, Peter Söderkvist, Per Rosenberg, Rajaa A Mirghani, Per Rymark, Elisabeth Avall Lundqvist and Curt Peterson, Pharmacogenetic Studies of Paclitaxel in the Treatment of Ovarian Cancer, 2009, Basic and clinical pharmacology and toxicology, (104), 2, 130-137

Break

The purpose of this study was to evaluate the role of sequence variants in the CYP2C8, ABCB1 and CYP3A4 genes and the CYP3A4 phenotype for the pharmacokinetics and toxicity of paclitaxel in ovarian cancer patients. Thirty-eight patients were treated with paclitaxel and carboplatin. The genotypes of CYP2C8*1B, *1C, *2, *3, *4, *5, *6, *7, *8 and P404A, ABCB1 G2677T/A and C3435T, as well as CYP3A4*1B, were determined by pyrosequencing. Phenotyping of CYP3A4 was performed in vivo with quinine as a probe. The patients were monitored for toxicity and 23 patients underwent a more extensive neurotoxicity evaluation. Patients heterozygous for G/A in position 2677 in ABCB1 had a significantly higher clearance of paclitaxel than most other ABCB1 variants. A lower clearance of paclitaxel was found for patients heterozygous for CYP2C8*3 when stratified according to the ABCB1 G2677T/A genotype. In addition, the CYP3A4 enzyme activity in vivo affected which metabolic pathway was dominant in each patient, but not the total clearance of paclitaxel. The exposure to paclitaxel correlated to the degree of neurotoxicity. Our findings suggest that interindividual variability in paclitaxel pharmacokinetics might be predicted by ABCB1 and CYP2C8 genotypes and provide useful information for individualized chemotherapy.This is the authors’ version of the following article: Henrik Green, Peter Söderkvist, Per Rosenberg, Rajaa A Mirghani, Per Rymark, Elisabeth Avall Lundqvist and Curt Peterson, Pharmacogenetic Studies of Paclitaxel in the Treatment of Ovarian Cancer, 2009, Basic and clinical pharmacology and toxicology, (104), 2, 130-137. which has been published in final form at: http://dx.doi.org/10.1111/j.1742-7843.2008.00351.x Copyright: Blackwell Publishing http://eu.wiley.com/WileyCDA/Brand/id-35.html</p