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Objective The objectives of this study were to 1) assess the content validity of generic preference-based measures (GPBMs), and (2) examine the convergent validity of the EuroQol 5 Dimension 5 Level (EQ-5D-5L), against the Patient Generated Index (PGI) in Amyotrophic Lateral Sclerosis (ALS). Methods Participants were recruited from 3 clinical sites across Canada. The PGI, EQ-5D-5L and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) were administered through an online or hardcopy survey and scores compared for convergent validation. Domains nominated by participants as important to their health-related quality of life were generated using the PGI, classified using the International Classification of Functioning, Disability and Health (ICF) and mapped onto GPBMs to determine content coverage. Results Fifty-two participants (N=28 female; 61.3 ± 11.6 mean age ± standard deviation (SD); 3.5 ± 2.9 mean ± SD years since diagnosis) completed this study. The top three ICF domains identified by participants were recreation and leisure, lower limb mobility, and interpersonal relationships. The Quality of Well-Being Self-Administered (QWB-SA) scale had the highest content coverage (87%) and the Health Utilities Index 3 (HUI3) had the lowest (33%). Two domains were covered by all GPBMs and no GPBM included all domains identified as important by participants. A moderate correlation coefficient of 0.52 between the PGI and EQ-5D-5L was found. Conclusion The majority of GPBMs covered only approximately half of the domains important to individuals with ALS suggesting the need for an ALS specific preference-based measure to better reflect the health-related quality of life of this population.

Patients with non-small cell lung cancer (NSCLC) who have distant metastases have a poor prognosis. To determine which genomic factors of the primary tumor are associated with metastasis, we analyzed data from 759 patients originally diagnosed with stage I–III NSCLC as part of the AACR Project GENIE Biopharma Collaborative consortium. We found that TP53 mutations were significantly associated with the development of new distant metastases. TP53 mutations were also more prevalent in patients with a history of smoking, suggesting that these patients may be at increased risk for distant metastasis. Our results suggest that additional investigation of the optimal management of patients with early-stage NSCLC harboring TP53 mutations at diagnosis is warranted in light of their higher likelihood of developing new distant metastases.

Although earlier studies on pregnancies derived through intracytoplasmic sperm injection (ICSI) reported increased non-mosaic aneuploidy among ICSI children, undetected mosaicism, such as confined placental mosaicism (CPM) has not been evaluated. We investigated the incidence of CPM in post-delivery placentas derived from ICSI, evaluated whether CPM was increased and whether it was a contributing factor to negative pregnancy outcome. [Fifty-one post-delivery placentas were collected from patients who underwent ICSI with a normal or negative pregnancy outcome]. Trophoblast and chorionic stroma from three sites were analyzed by comparative genomic hybridization (CGH) and flow cytometry. Detected abnormalities were confirmed by fluorescence in situ hybridization (FISH). The incidence of CPM in the ICSI population was compared to the general population from published data. We detected three cases of CPM in our study. One abnormality was found by CGH analysis; partial trisomy 7q and a partial monosomy Xp limited to the trophoblast at two sites. The abnormality was associated with a child affected by spina bifida. Two cases of mosaic tetraploidy were observed by flow cytometry in pregnancies with a normal outcome. All three abnormalities were confirmed by FISH analysis. The incidence of CPM in the ICSI study population was 5.88% (3/51), which was not statistically different from published reports in the general population (5.88% (42/714), Chi square, P > 0.05). The post-ICSI population was not at risk for CPM in this study.

Objective. The aim of this review was to synthesize the psychometric properties of generic preference-based measures (PBMs) of health-related quality of life (HRQL) in Amyotrophic Lateral Sclerosis (ALS). Methods. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four databases were searched from inception to April 2019: OVID Medline, Embase, PsycINFO, and CINAHL. Studies were included if (1) the sample represented individuals with ALS, (2) a generic PBM was utilized and reported on, and (3) information on the psychometric property of a generic PBM was provided. Results. Ninety-one articles were screened, and 39 full-text articles were reviewed. Seven full-text articles were included in this review. The mean age of participants ranged from 58.1 to 63.8 years, and mean time since diagnosis ranged from 20.5 to 44.6 months. Two generic PBMs were found, the EQ-5D-3L (n = 6) and the Quality of Well-Being Self-Administered (QWB-SA) scale (n = 1). Convergent validity of the EQ-5D-3L was large against a global scale of self-perceived health (r = 0.60) and small to large against ALS specific HRQL measures (r = 0.19 to 0.75). For the QWB-SA scale, correlations were small against a generic measure (r = 0.21) and large against ALS specific measures (r = 0.55). The EQ-5D-3L discriminated across different disease severity; however, floor effects were reported. Conclusion. This review highlights the need for more rigorously designed studies to assess the psychometric properties of generic PBMs in ALS and the development of an ALS specific PBM that adequately reflects the health concerns of individuals with ALS.