Understanding the assistive technology needs of people over 55: The future of mobility aids.

OBJECTIVE: To understand mobility issues not adequately serviced by assistive technology (AT). METHODS: A two-stage mixed-methods research project that forms the basis of future AT design and manufacture. Stage 1: a focus group comprising 46 participants (people aged 55 years or older with mobility issue/s) and their support networks. Stage 2: a sample of 413 people over 55 completed a purpose-designed survey informed by stage 1, regarding mobility issues and perceived desirability of suggested AT mobility aids. RESULTS: Two core themes emerged: (a) functionality issues relating to existing AT designs and (b) identified mobility issues encountered during activities of daily living that could potentially be resolved by developing new AT. Importance was placed on certain features of AT mobility aids with cost, transportability and aesthetics being primary issues. CONCLUSION: Consulting end-users and their networks ensures valuable insight into how future AT can better address and target mobility needs.

Survey of Maternal, Child and Family Health Nurses' attitudes and practice relating to preconception health promotion.

Environmental factors including poor nutrition, obesity, smoking, exposure to toxins and drug and alcohol use at the time of conception can adversely affect the future health of the offspring. As primary health care (PHC) professionals who interact with women of reproductive age, Maternal, Child and Family Health Nurses (MCaFHNs) are ideally placed to promote preconception health to women who want another child. The aim of this study was to assess MCaFHNs attitudes towards preconception health promotion, whether and under what circumstances they talk to their families about this, and what might help them start a conversation about preconception health. Of the 192 respondents, most (65%) agreed it is part of the MCaFHNs role to promote preconception health but only one in eight (13%) felt very confident that they knew as much as they needed and less than half (46%) 'routinely' or 'sometimes' promoted preconception health in their clinical practice. Almost all agreed that more information and education on the topic would increase their confidence to discuss preconception health. The findings suggest that, with adequate educational and structural support, most MCaFHNs are willing to deliver preconception health promotion in their clinical practice. As most new mothers access MCaFHNs, the potential health benefits of this are considerable.

A Phase Ib Dose-Escalation and Expansion Study of the BCL2 Inhibitor Venetoclax Combined with Tamoxifen in ER and BCL2-Positive Metastatic Breast Cancer.

Venetoclax, a potent and selective BCL2 inhibitor, synergizes with endocrine therapy in preclinical models of ER-positive breast cancer. Using a phase Ib 3 + 3 dose-escalation and expansion study design, 33 patients with ER and BCL2-positive metastatic disease (mean prior regimens, 2; range, 0-8) were treated with daily tamoxifen (20 mg) and venetoclax (200-800 mg). Apart from uncomplicated "on-target" lymphopenia, no dose-limiting toxicities or high-grade adverse events were observed in the escalation phase (15 patients), and 800 mg was selected as the recommended phase II dose (RP2D). In the expansion phase (18 patients), few high-grade treatment-related adverse events were observed. For 24 patients treated at the RP2D, the confirmed radiologic response rate was 54% and the clinical benefit rate was 75%. Treatment responses were preempted by metabolic responses (FDG-PET) at 4 weeks and correlated with serial changes in circulating tumor DNA. Radiologic responses (40%) and clinical benefit (70%) were observed in 10 patients with plasma-detected ESR1 mutations. SIGNIFICANCE: In the first clinical study to evaluate venetoclax in a solid tumor, we demonstrate that combining venetoclax with endocrine therapy has a tolerable safety profile and elicits notable activity in ER and BCL2-positive metastatic breast cancer. These findings support further investigation of combination therapy for patients with BCL2-positive tumors.See related commentary by Drago et al., p. 323.This article is highlighted in the In This Issue feature, p. 305.

Assessing THK523 selectivity for tau deposits in Alzheimer's disease and non-Alzheimer's disease tauopathies.

INTRODUCTION: The introduction of tau imaging agents such as (18)F-THK523 offers new hope for the in vivo assessment of tau deposition in tauopathies such as Alzheimer's disease (AD), where preliminary (18)F-THK523-PET studies have demonstrated significantly higher cortical retention of (18)F-THK523 in AD compared to age-matched healthy individuals. In addition to AD, tau imaging with PET may also be of value in assessing non-AD tauopathies, such as corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and Pick's disease (PiD). METHODS: To further investigate the ability of THK523 to recognize tau lesions, we undertook immunohistochemical and fluorescence studies in serial brain sections taken from individuals with AD (n = 3), CBD (n = 2), PSP (n = 1), PiD (n = 2) and Parkinson's disease (PD; n = 2). In addition to the neuropathological analysis, one PSP patient had undergone a (18)F-THK523 PET scan 5 months before death. RESULTS: Although THK523 labelled tau-containing lesions such as neurofibrillary tangles and neuropil threads in the hippocampus and frontal regions of AD brains, it failed to label tau-containing lesions in non-AD tauopathies. Furthermore, though THK523 faintly labelled dense-cored amyloid-ß plaques in the AD frontal cortex, it failed to label α-synuclein-containing Lewy bodies in PD brain sections. CONCLUSION: The results of this study suggest that (18)F-THK523 selectively binds to paired helical filament tau in AD brains but does not bind to tau lesions in non-AD tauopathies, or to α-synuclein in PD brains.