Symptoms and diagnostic delays in bladder cancer with high risk of recurrence : results from a prospective FinnBladder 9 trial

Purpose To investigate the symptoms and delays in the clinical pathway of bladder cancer (BC). Methods This is a substudy of a prospective, randomized, multicenter phase III study (FinnBladder 9, NCT01675219) where the efficacy of photodynamic diagnosis and 6 weekly optimized mitomycin C instillations are studied in pTa bladder cancer with high risk for recurrence. The data of presenting symptoms and critical time points were prospectively collected, and the effect of factors on delays was analyzed. Results At the time of analysis, 245 patients were randomized. Analysis included 131 patients with primary bladder cancer and their complete data. Sixty-nine percent had smoking history and 67% presented with macroscopic hematuria. Median patient delay (from symptoms to health-care contact) was 7 days. The median general practice delay (from health-care contact to urology referral) was 8 days. Median time from urology referral to cystoscopy was 23 days and from cystoscopy to TUR-BT 21 days. Total time used in the clinical pathway (from symptom to TUR-BT) was 78 days. Current and former smokers had non-significantly shorter patient-related and general practice delays compared to never smokers. TUR-BT delay was significantly shorter in patients with malignant cytology (16 days) compared to patients with benign cytology (21 days, p = 0.03). Conclusions Patient-derived delay was short and most of the delay occurred in the referral centers. The majority had macroscopic hematuria as the initial symptom. Surprisingly, current and past smokers were more prone to contact the health-care system compared to never smokers.Peer reviewe

Etyleenioksidisteriloinnin vaikutus luun morfogeenisen proteiinin luuta tuottavaan omainaisuuteen.

Syventävä työ ei kirjastoss

Etyleenioksidisteriloinnin vaikutus luun morfogeenisen proteiinin luuta tuottavaan omainaisuuteen.

Syventävä työ ei kirjastoss

Effect of sterilization and delivery systems on the osteoinductivity of reindeer bone morphogenetic protein extract

Abstract Bone morphogenetic proteins (BMPs) constitute a large family of osteoinductive proteins. Different BMPs are widely used in animal experiments and increasingly in the field of bone surgery. However, the sterilization of BMPs and the choice of a suitable mode of delivery, which binds and slowly releases BMP molecules, are still under intensive investigation. The aims of this study were to evaluate the effects of ethylene oxide and gamma sterilizations and different delivery systems on the osteoinductivity of reindeer BMP extract by using heterotopic and orthopic animal models. Ethylene oxide gas (Steri-Vac 4XL, temperature 29 °C, exposure time 4 h, concentration 860 mg/l) and gamma (doses of 3.15 or 4.15 Mrad) sterilizations were used. The tested delivery systems for reindeer BMP were collagen (Lyostypt®), gelatine capsule (no.1) and composites containing collagen combined with tricalcium phosphate (TCP) or hydroxyapatite (HA) or biphasic tricalcium phosphate-hydroxyapatite (TCP/HA) or biocoral (NC) frames. The injectability of reindeer BMP was tested by using injections containing a saline or gelatine vehicle. Osteoinductivity was evaluated as ectopic bone formation in the thigh muscle pouches of mouse hind legs. The induced new bone was evaluated based on the incorporation of 45Ca or calcium yield, radiographs and histological examination three weeks after the operations. The effect of gamma sterilization on the bone healing capacity of reindeer BMP extract was evaluated in a rabbit radial bone defect model in comparison with non-sterilized reindeer BMP extract and recombinant BMP-2. Bone healing was evaluated after eight weeks based on radiographs, mechanical tests and peripheral computerized tomography (pQCT). All BMP implants induced new bone in vivo visible in radiographs, but no bone formation was seen in the control implants without reindeer BMP. Gamma sterilization did not decrease significantly the osteoinductivity of reindeer BMP extract, except when administered as an injection containing gelatine vehicle. Ethylene oxide sterilization decreased significantly the osteoinductivity of reindeer BMP extract and was significantly inferior compared to gamma sterilization. Reindeer BMP combined with collagen or composite containing collagen and TCP/HA frame induced new bone significantly better than reindeer BMP combined with composite containing collagen and TCP frame. BMP injections with gelatine or saline vehicles induced new bone effectively. Injections were easy to handle and well tolerated by the mice. Reindeer BMP extract administered with collagen carrier healed the bone defect of the rabbit radius significantly better than control implants without reindeer BMP or no treatment and its effect was comparable with rhBMP-2 treatment

Uusia näkökulmia ympäröivään maailmaan

Taloustieteen taju tarjoaa uusia näkökulmia ympäröivän maailman tarkastelemiseen ja yhteiskunnallisia kysymyksiä taloustieteen keinoin.nonPeerReviewe