A substantial portion of the older adult population suffers from frequent feelings of loneliness, but a large proportion remains relatively unscathed by loneliness. To date, research examining both protective and risk factors for loneliness has not included data from the United States. The present study used the first two waves of data from the National Social Life, Health, and Aging Project to examine sociodemographic, structural, and functional factors thought to be associated with loneliness in older adults. Functional limitations and low family support were associated with an increase in loneliness frequency (as were more strained friendships) and with transitioning from nonlonely to lonely status. Better self-rated health, higher levels of socializing frequency, and lower family strain were associated with transitioning from lonely to nonlonely status. Interventions that target these factors may be effective in preventing and reducing loneliness and its effects on health and well-being in older adults.

Glucocorticoid receptor (GR) overexpression is associated with poor prognosis ER-negative breast cancer. GR antagonism with mifepristone increases chemotherapy-induced breast cancer cell death, therefore we conducted a phase I clinical trial of mifepristone and nab-paclitaxel in advanced breast cancer. A novel randomized phase I design was used to assess the effect of mifepristone on nab-paclitaxel pharmacokinetics and toxicity. Patients were randomized to placebo or mifepristone for the first cycle; mifepristone was given to all for subsequent cycles. Nine patients were enrolled. All were found to have a twofold or greater increase in serum cortisol after mifepristone administration, reflecting effective GR inhibition. Neutropenia occurred at both nab-paclitaxel dose levels studied (100 and 80 mg/m2), and was easily managed with dose reduction and/or growth factor administration. Pharmacokinetic data suggest an interaction between nab-paclitaxel and mifepristone in some patients. Two patients had complete responses (CR), three partial responses (PR), one stable disease (SD), and three progressive disease (PD). Immunohistochemical staining for GR found six of nine tumors were GR-positive. All six GR-positive tumors were triple-negative at the time of recurrence. Of these six patients, two had CRs, two PRs, one SD, and one PD. GR appears to be a promising target in TNBC, and GR inhibition plus chemotherapy produces manageable toxicity. While neutropenia was observed in some, a nab-paclitaxel dose of 100 mg/m2 plus mifepristone 300 mg was found to be tolerable, and a randomized phase II trial of nab-paclitaxel with/without mifepristone is planned in GR-positive advanced TNBC.

Studies suggest that individuals with aphasia present with impairments in attention. However, most research has been conducted with small sample sizes using experimental protocols that lack established psychometric properties. We examined the attention performance of 114 individuals with chronic post-stroke aphasia using a standardised, norm-referenced assessment of attention, the Conners’ Continuous Performance Test-II (CPT-II; Conners, C. K. (2000). Conner s’ Continuous Performance Test II. Toronto: Multi-Health Systems Inc). Participants completed the CPT-II and the Western Aphasia Battery-Revised (WAB-R; Kertesz, A. (2007). Western Aphasia Battery-Revised. San Antonio, TX: PsychCorp). As a group, variable performance on selected CPT-II measures was observed. Participants demonstrated impairments on omissions (48.2%) and hit reaction time (67.5%), with 11.4% demonstrating atypically slow performance and over half of the sample (56.1%) performing atypically fast. The Confidence Index, a summary score, was also within the impaired range for the majority of participants. However, there were also measures in which a greater percentage of participants demonstrated performance within normal limits. Using the WAB-R Aphasia Quotient (AQ) as a measure of severity, there was significantly worse performance in participants with more severe (AQ < 50) compared to less severe (AQ ≥ 50) aphasia. No significant differences in attention were identified between participants with fluent versus non-fluent aphasia. The CPT-II is a feasible measure for persons with aphasia, which may assist in identifying attention performance deficits that potentially affect language.

High-grade serous ovarian cancer (HGSOC) is characterized by a complex genomic landscape, with both genetic and epigenetic diversity contributing to its pathogenesis, disease course, and response to treatment. To better understand the association between genomic features and response to treatment among 370 patients with newly diagnosed HGSOC, we utilized multi-omic data and semi-biased clustering of HGSOC specimens profiled by TCGA. A Cox regression model was deployed to select model input features based on the influence on disease recurrence. Among the features most significantly correlated with recurrence were the promotor-associated probes for the NFRKB and DPT genes and the TREML1 gene. Using 1467 transcriptomic and methylomic features as input to consensus clustering, we identified four distinct tumor clusters—three of which had noteworthy differences in treatment response and time to disease recurrence. Each cluster had unique divergence in differential analyses and distinctly enriched pathways therein. Differences in predicted stromal and immune cell-type composition were also observed, with an immune-suppressive phenotype specific to one cluster, which associated with short time to disease recurrence. Our model features were additionally used as a neural network input layer to validate the previously defined clusters with high prediction accuracy (91.3%). Overall, our approach highlights an integrated data utilization workflow from tumor-derived samples, which can be used to uncover novel drivers of clinical outcomes.

Patients with solid tumor brain metastases that progress after whole-brain radiation have limited options. This prospective trial investigated the efficacy, safety, and tolerability of bevacizumab as salvage therapy in this population. Eligible patients received bevacizumab 10 mg/kg intravenously every 2 weeks until progression. The primary endpoint was radiologic response using Response Assessment in Neuro-Oncology (RANO) criteria. The secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response, and safety. Quality of life (QOL) was studied using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) scale. Twenty-seven patients were enrolled, with twenty-four having evaluable data for response. The majority of histologies (n = 21, 78%) were breast cancer. The remaining histologies were non-small-cell lung cancer (n = 4, 15%), neuroendocrine cancer (n = 1, 3%), and papillary fallopian serous adenocarcinoma (n = 1, 3%). Eighteen patients had radiologic response, with two patients demonstrating partial response (8.33%) and sixteen patients demonstrating stable disease (66.7%). The median duration of response was 203 days. PFS at 6 months was 46%, median PFS was 5.3 m, and median OS was 9.5 m. Treatment was well tolerated, with six patients experiencing grade 3 lymphopenia and hypertension. There was one grade 3 thromboembolism. QOL was not negatively impacted. Bevacizumab is a safe and feasible salvage treatment with durable response and favorable overall survival for patients with progressive brain metastases after whole-brain radiation.