New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Assessing Preferences in Patients with Head and Neck Squamous Cell Carcinoma: Phase I and II of Questionnaire Development.

Shared-decision making for head and neck squamous cell carcinoma (HNSCC) is challenged by the difficulty to integrate the patient perception of value within the framework of a multidisciplinary team approach. The aim of this study was to develop a questionnaire to assess the preferences of HNSCC patients with respect to the disease trajectory, expected treatment, and toxicities. In accordance with the standardized EORTC Quality of Life Group's methodology for the development of quality of life modules, a phase 1-2 study was envisaged. Following a systematic review of the literature, a consolidated list of 28 issues was administered through a semi-structured interview to 111 patients from 7 institutions in 5 countries. Overall, "cure of disease", "survival", and "trusting in health care professionals" were the 3 most common priorities, being chosen by 87.3%, 73.6% and 59.1% of patients, respectively. When assessing the correlation with the treatment subgroup, the issue of "being thoroughly and sincerely informed about treatments' efficacy and survival expectation" was highly prevalent in an independent manner (71.4%, 75% and 90% of patients in the follow-up, palliative and curative subgroups, respectively). Based on prespecified scoring criteria, a 24-item list was generated. Pending clinical applicability, further testing and validation of the questionnaire are warranted

Assessing preferences in patients with head and neck squamous cell carcinoma: Phase i and ii of questionnaire development

Shared-decision making for head and neck squamous cell carcinoma (HNSCC) is challenged by the difficulty to integrate the patient perception of value within the framework of a multidisciplinary team approach. The aim of this study was to develop a questionnaire to assess the preferences of HNSCC patients with respect to the disease trajectory, expected treatment, and toxicities. In accordance with the standardized EORTC Quality of Life Group’s methodology for the development of quality of life modules, a phase 1–2 study was envisaged. Following a systematic review of the literature, a consolidated list of 28 issues was administered through a semi-structured interview to 111 patients from 7 institutions in 5 countries. Overall, “cure of disease”, “survival”, and “trusting in health care professionals” were the 3 most common priorities, being chosen by 87.3%, 73.6% and 59.1% of patients, respectively. When assessing the correlation with the treatment subgroup, the issue of “being thoroughly and sincerely informed about treatments’ efficacy and survival expectation” was highly prevalent in an independent manner (71.4%, 75% and 90% of patients in the follow-up, palliative and curative subgroups, respectively). Based on prespecified scoring criteria, a 24-item list was generated. Pending clinical applicability, further testing and validation of the questionnaire are warranted. © 2020 by the authors. Licensee MDPI, Basel, Switzerland