Neurotensin and other hypophyseotrophic factors

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Adenovirus-mediated gene therapy with sitimagene ceradenovec followed by intravenous ganciclovir for patients with operable high-grade glioma (ASPECT): a randomised, open-label, phase 3 trial.

BACKGROUND: Besides the use of temozolomide and radiotherapy for patients with favourable methylation status, little progress has been made in the treatment of adult glioblastoma. Local control of the disease by complete removal increases time to progression and survival. We assessed the efficacy and safety of a locally applied adenovirus-mediated gene therapy with a prodrug converting enzyme (herpes-simplex-virus thymidine kinase; sitimagene ceradenovec) followed by intravenous ganciclovir in patients with newly diagnosed resectable glioblastoma. METHODS: For this international, open-label, randomised, parallel group multicentre phase 3 clinical trial, we recruited patients from 38 sites in Europe. Patients were eligible if they were aged 18-70 years, had newly diagnosed supratentorial glioblastoma multiforme amenable to complete resection, and had a Karnofsky score of 70 or more at screening. We used a computer-generated randomisation sequence to allocate patients in a one-to-one ratio (with block sizes of four) to receive either surgical resection of the tumour and intraoperative perilesional injection of sitimagene ceradenovec (1 x 10(12) viral particles) followed by ganciclovir (postoperatively, 5 mg/kg intravenously twice a day) in addition to standard care or resection and standard care alone. Temozolomide, not being standard in all participating countries at the time of the study, was allowed at the discretion of the treating physician. The primary endpoint was a composite of time to death or re-intervention, adjusted for temozolamide use, assessed by intention-to-treat (ITT) analysis. This trial is registered with EudraCT, number 2004-000464-28. FINDINGS: Between Nov 3, 2005, and April 16, 2007, 250 patients were recruited and randomly allocated: 124 to the experimental group and 126 to the standard care group, of whom 119 and 117 patients, respectively, were included in the ITT analyses. Median time to death or re-intervention was longer in the experimental group (308 days, 95% CI 283-373) than in the control group (268 days, 210-313; hazard ratio [HR] 1.53, 95% CI 1.13-2.07; p=0.006). In a subgroup of patients with non-methylated MGMT, the HR was 1.72 (95% CI 1.15-2.56; p=0.008). However, there was no difference between groups in terms of overall survival (median 497 days, 95% CI 369-574 for the experimental group vs 452 days, 95% CI 437-558 for the control group; HR 1.18, 95% CI 0.86-1.61, p=0.31). More patients in the experimental group had one or more treatment-related adverse events those in the control group (88 [71%] vs 51 [43%]). The most common grade 3-4 adverse events were hemiparesis (eight in the experimental group vs three in the control group) and aphasia (six vs two). INTERPRETATION: Our findings suggest that use of sitimagene ceradenovec and ganciclovir after resection can increase time to death or re-intervention in patients with newly diagnosed supratentorial glioblastoma multiforme, although the intervention did not improve overall survival. Locally delivered gene therapy for glioblastoma should be further developed, especially for patients who are unlikely to respond to standard chemotherapy. FUNDING: Ark Therapeutics Ltd

Mate selection preferences in Germany and the United States

Two studies examined expressed mate selection preferences in German and American samples. In the first study (German N=343; American N=313), subjects ranked 13 characteristics on their desirability in a potential mate. Large and consistent sex differences were predicted and found within each country on valuation of good earning capacity (females more) and physical attractiveness (males more). The largest cultural differences were found for valuation of the characteristics Good Housekeeper (Germans more) and Physical Attractiveness (Americans more). A second study (German N=751; American N=1137) was conducted to replicate and extend these results using two separate testing instruments and larger more diverse samples within each country. The basic sex differences within countries and cultural differences across sexes were robustly replicated. None the less, the two countries showed remarkable similarity in patterns of mating preferences across characteristics. Discussion emphasizes the theoretical significance of these findings and identifies important directions for future research in human mating systems.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28242/1/0000695.pd

Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial

Background Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial infarction and stroke. There is indirect evidence that agonists of peroxisome proliferator-activated receptor gamma (PPAR gamma) could reduce macrovascular complications. Our aim, therefore, was to ascertain whether pioglitazone reduces macrovascular morbidity and mortality in high-risk patients with type 2 diabetes. Methods We did a prospective, randomised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease. We recruited patients from primary-care practices and hospitals. We assigned patients to oral pioglitazone titrated from 15 mg to 45 mg (n=2605) or matching placebo (n=2633), to be taken in addition to their glucose-lowering drugs and other medications. Our primary endpoint was the composite of all-cause mortality, non-fatal myocardial infarction (including silent myocardial infarction), stroke, acute coronary syndrome, endovascular or surgical intervention in the coronary or leg arteries, and amputation above the ankle. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN NCT00174993. Findings Two patients were lost to follow-up, but were included in analyses. The average time of observation was 34.5 months. 514 of 2605 patients in the pioglitazone group and 572 of 2633 patients in the placebo group had at least one event in the primary composite endpoint (HR 0.90, 95% CI 0.80-1.02, p=0.095). The main secondary endpoint was the composite of all-cause mortality, non-fatal myocardial infarction, and stroke. 301 patients in the pioglitazone group and 358 in the placebo group reached this endpoint (0.84, 0.72-0.98, p=0.027). Overall safety and tolerability was good with no change in the safety profile of pioglitazone identified. 6% (149 of 2065) and 4% (108 of 2633) of those in the pioglitazone and placebo groups, respectively, were admitted to hospital with heart failure; mortality rates from heart failure did not differ between groups. Interpretation Pioglitazone reduces the composite of all-cause mortality, non-fatal myocardial infarction, and stroke in patients with type 2 diabetes who have a high risk of macrovascular events

Do Certified Mail Third-Wave Follow-ups Really Boost Response Rates and Quality?

The Total Design Method (TDM) of designing and implementing mail surveys has been shown to achieve high response rates. One key step in the TDM is sending a third-wave of surveys by certified mail. However, little research exists to verify the effectiveness of this step in improving response rates and quality relative to its increased expense, although this is the 50th anniversary of certified mail in the U.S. Perhaps as a result, scholars rarely use certified mail third-waves or omit third-wave mailings altogether. This article presents the results of two experiments that we embedded in two large-scale organizational mail surveys. Both studies reveal that sending a third-wave of questionnaires significantly increases the rate of response over the first two waves of mailings. Also, the results of Study 1 show that sending a certified mail third-wave has no appreciable effect on response quality. Study 2 shows that a certified mail third-wave does not significantly increase response rate or quality compared to sending the third-wave by regular, 1st-class mail. Copyright Springer Science + Business Media, Inc. 2005response rate, response quality, questionnaire design, Total Design Method (TDM), Tailored Design Method, certified mail, third-wave surveys,