Objective: To evaluate a change in tumour characteristics and applied treatments over time in the control arm of all centres of the European Randomized study of Screening for Prostate Cancer (ERSPC) and to compare this with similar data of the screening arm.
Methods: Between 1993 and 2003, 182,160 men, aged 50-74 years, were randomised to the screening arm (N=82,816) and the control arm (N=99,184). Men in the screening arm were offered Prostate Specific Antigen (PSA) testing every 4 years whilst men in the control arm received usual care. Tumour characteristics and treatment were evaluated in all men diagnosed with prostate cancer up to December 2006 or the third screening round. Data on the control arm were divided into 3 periods: 1994-1998, 1999-2002 and 2003-2006.
Results: Tumour characteristics were more favourable over time in both the control and the screening arm, with especially increasing proportions of T1C tumours with 29% in 1994-1998 versus 50% in 2003-2006 and 48% at the initial screening round versus 75% at the third screening round, respectively. Tumour characteristics observed in the last period of the control arm were comparable to tumour characteristics in the initial screening round. In the control arm, treatment changed over time with surgery as the most common treatment in the entire observed period, but almost doubling of expectant management and the combination of hormone therapy and radiotherapy over time. In the initial screening round, surgery was the most common treatment (42%), changing over time to expectant management as the most frequently applied treatment in the third screening round (33%).
Conclusion: Tumour characteristics in the control arm became more favourable over time and show similarity with prostate cancer cases detected at the initial screening round. The most prominent change in treatment over time was an increase of application of expectant management in both arms of the ERSPC. These observations reflect an increasing rate of opportunistic testing over time in men randomised to the control arm.
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http://dx.doi.org/10.1016/j.ejca.2010.09.033 | DOI Listing |
Alzheimers Dement
December 2024
School of Pharmacy, Chapman University, Irvine, CA, USA.
Background: Although novel treatments for Alzheimer's disease (AD) have begun to show modest therapeutic effects, agents that target hallmark AD pathology and offer neuroprotection are desired. Erythropoietin (EPO) is a glycoprotein hormone with neuroprotective effects but is faced with challenges including limited brain uptake and increased hematopoietic side effects with long-term dosing. Therefore, EPO has been modified and bound to a chimeric transferrin receptor monoclonal antibody (cTfRMAb); the latter shuttles EPO past the blood-brain barrier (BBB) into brain parenchyma and reduces its plasma exposure and potential for side effects.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Karolinska Institute, Stockholm, Södermanland and Uppland, Sweden.
Background: Novel anti-amyloid therapies (AAT) for Alzheimer's Disease (AD) have recently been approved in the United States, Japan and China, and are under regulatory review in Europe. Questions remain regarding the long-term effectiveness and value of these drugs when used in routine clinical practice. Data from follow-up studies will be important to inform their optimal use, including criteria for treatment initiation, monitoring strategies, stopping rules, pricing and reimbursement considerations.
View Article and Find Full Text PDFBackground: Pivotal Alzheimer's Disease (AD) trials typically require thousands of participants, resulting in long enrollment timelines and substantial costs. We leverage deep learning predictive models to create prognostic scores (forecasted control outcome) of trial participants and in combination with a linear statistical model to increase statistical power in randomized clinical trials (RCT). This is a straightforward extension of the traditional RCT analysis, allowing for ease of use in any clinical program.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Background: Recruiting and retaining older adults for clinical trials is challenging, especially in low-resource settings. Such challenges led to a systematic exclusion of such participants from clinical trials, compromising the generalizability of the results obtained in high income countries.
Objective: Here we describe the strategies we used in the PROAME study for recruiting and retaining illiterate older adults from low socioeconomical levels in a non-pharmacological trial.
Alzheimers Dement
December 2024
NYU Grossman School of Medicine, New York, NY, USA.
Background: Apolipoprotein E4 (apoE4) has been identified as the major genetic risk factor for late onset Alzheimer's disease (AD). Our lab has demonstrated that chronic administration of Aβ12-28P, a synthetic peptide that blocks apoE4/Aβ binding, in middle-aged transgenic AD mice significantly ameliorates pathology progression, resulting in reduced Aβ plaques deposition and cerebral amyloid angiopathy (CAA) along with improved memory and cognition. However, whether blocking apoE4/Aβ interaction by Aβ12-28P also has an ameliorating effect on the neuronal and cognitive function of old AD mice where Aβ pathology has been extensively developed remains unknown.
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