Metastatic breast cancer is a major cause of cancer-related deaths in woman. Brain metastasis is a common and devastating site of relapse for several breast cancer molecular subtypes, including ...oestrogen receptor-positive disease, with life expectancy of less than a year. While efforts have been devoted to developing therapeutics for extra-cranial metastasis, drug penetration of blood-brain barrier (BBB) remains a major clinical challenge. Defining molecular alterations in breast cancer brain metastasis enables the identification of novel actionable targets.
Global transcriptomic analysis of matched primary and metastatic patient tumours (n = 35 patients, 70 tumour samples) identified a putative new actionable target for advanced breast cancer which was further validated in vivo and in breast cancer patient tumour tissue (n = 843 patients). A peptide mimetic of the target's natural ligand was designed in silico and its efficacy assessed in in vitro, ex vivo and in vivo models of breast cancer metastasis.
Bioinformatic analysis of over-represented pathways in metastatic breast cancer identified ADAM22 as a top ranked member of the ECM-related druggable genome specific to brain metastases. ADAM22 was validated as an actionable target in in vitro, ex vivo and in patient tumour tissue (n = 843 patients). A peptide mimetic of the ADAM22 ligand LGI1, LGI1MIM, was designed in silico. The efficacy of LGI1MIM and its ability to penetrate the BBB were assessed in vitro, ex vivo and in brain metastasis BBB 3D biometric biohybrid models, respectively. Treatment with LGI1MIM in vivo inhibited disease progression, in particular the development of brain metastasis.
ADAM22 expression in advanced breast cancer supports development of breast cancer brain metastasis. Targeting ADAM22 with a peptide mimetic LGI1MIM represents a new therapeutic option to treat metastatic brain disease.
OBJECTIVE
This study assessed the distribution and correlates of objective sleep duration in the older population in Ireland.
DESIGN
Cross‐sectional study using population‐derived data from wave 3 of ...The Irish Longitudinal Study on Ageing.
SETTING
Community‐dwelling adults.
PARTICIPANTS
Adults, aged 50 years and older, who wore an accelerometer for at least 4 days (N = 1533).
MEASUREMENTS
Sleep was measured for at least 4 days in 1533 participants using a GENEActiv wrist‐worn accelerometer device. Sleep parameters included total sleep time (TST) and self‐reported sleep problems. TST was categorized as short and long sleep duration using US National Sleep Foundation guidelines. Linear and multinomial logistic regression models assessed sociodemographic, health, and behavioral correlates of sleep duration.
RESULTS
Mean TST for the sample was 463 minutes (SD = 72.6 minutes). Of participants, 13.9% and 16.5% measured short and long sleep duration, respectively. TST decreased as sleep problems increased, as did durations recorded in summer compared to winter recordings. Advancing age was associated with longer sleep, as was antidepressant use. Retired/unemployed participants recorded longer TST and were more likely to record long sleep compared to employed participants. Fair/poor self‐rated health and separated/divorced participants were more likely to record short sleep. Those reporting moderate or high physical activity were less likely to record short or long sleep, respectively, compared to those reporting low physical activity. Participants reporting a limiting disability were less likely to record long sleep.
CONCLUSION
Average TST was within recommended guidelines; however, a significant subset of older adults recorded sleep duration outside of the guidelines. Independent demographic and health correlates of suboptimal sleep were identified, many of which are modifiable. Patients and clinicians should be aware of factors potentially influencing sleep patterns. Longitudinal analyses to confirm directionality of relationships with potential risk factors are warranted. J Am Geriatr Soc 68:120–128, 2019
Using digital technologies to provide services and supports remotely may improve efficiency and accessibility of healthcare, and support people with disabilities to live independently. This study ...aimed to explore the experience of using digital technologies to access and provide disability services and supports during the Covid-19 pandemic, from the perspective of people with disabilities, families and service providers.
Using a multiple case study design, we purposively sampled three cases based on service user characteristics and geographical reach of the service. We conducted semi-structured interviews with 40 service users and service providers. Topic guides and analysis were informed by the Consolidated Framework for Implementation Research (CFIR). Analysis followed a largely deductive approach, using the CFIR constructs as a coding framework. A summary memo was developed for each case. Influence and strength of each construct was rated to identify constructs that influenced implementation of digital technologies. Ratings were compared across services to identify facilitators and barriers to implementation.
Service users and providers were positive about using digital technologies to access and provide disability services and supports remotely. Advantages over in-person delivery included reduced travel time, increased opportunity for peer support and peer learning, more choice and opportunity to participate in activities, and an enhanced sense of self while accessing services from the secure environment of their home. The urgency to identify new modes of service delivery to meet the needs of service users during Covid-19 was a strong facilitator but did not necessarily result in successful implementation. Other factors that were strong facilitators were the use of adaptations to enable service users to access the online service, service users' willingness to try the online service, service users' persistence when they encountered challenges, and the significant time and effort that service providers made to support service users to participate in the online service. Barriers to implementation included the complexity of accessing online platforms, poor design quality of online platforms, and organisations prioritising in-person delivery over online services.
These findings may allow service providers to leverage facilitators that support implementation of online disability services and supports.
To establish agreement between self-reported and actigraphy-based total sleep time (TST). To determine the impact of self-reported sleep problems on these measurements.
Cross-sectional study using ...data from Wave 3 of The Irish Longitudinal Study on Ageing (2014–2015).
Community-dwelling older adults, aged ≥50 years, with self-reported sleep information and ≥4 days of actigraphy-based TST (n = 1520).
Self-reported total sleep time, daytime sleepiness, insomnia symptoms (trouble falling asleep, trouble waking too early) measured during a structured self-interview. Actigraphy-based total TST was collected using GENEactiv wrist-worn accelerometers. Demographic characteristics and health information were controlled for. Analyses included descriptive statistics, reliability and agreement analysis using paired t-tests, intra-class correlations and Bland-Altman analysis. Linear regression was used to model associations with measurement discrepancies.
Participants reported that they slept 7.0 hours (SD: 1.4, Range: 2.0–13.0 hours) on average, compared to 7.7 hours (SD: 1.2 hours, Range: 3.0–13.0 hours) recorded by accelerometry. Trouble falling asleep or waking too early “most of the time” were associated with under-reporting of sleep by 2.3, and 2.2 hours respectively. Agreement between measurements had an intra-class correlation of 0.18 and wide 95% limits of agreement (-3.90 to 2.55 hours). Under-reporting of sleep was independently associated with insomnia symptoms.
The agreement between self-reported and actigraphy-based TST in community dwelling older adults was low. Self-reported insomnia symptoms were independently associated with under-reporting of sleep. Studies seeking to measure sleep duration should consider inclusion of questions measuring experience of insomnia symptoms to account for potential influence on measurements.
Background
Patients with anogenital symptoms may delay before seeking medical attention. Attempted self‐treatment with multiple topical preparations and excessive hygiene measures offer ideal ...conditions for sensitization. The aim of this study was to identify the common allergens detected on cutaneous allergy testing in patients presenting with anogenital symptoms.
Methods
A retrospective chart review of patients who underwent cutaneous allergy testing for perianal and/or genital symptoms over a 3‐year period, January 2013 to December 2015, n = 99. Information was gathered from medical records, pretesting questionnaires, and cutaneous allergy testing records.
Results
At least one relevant allergen(s) was identified in 44/99 (45%) in our cohort, with allergic reactions to fragrances, Myroxylon pereirae, caine mix, sodium metabisulfite, and methylisothiazolinone most frequently observed.
Conclusions
Cutaneous allergy testing is a useful investigation in patients presenting with anogenital symptoms, but advice regarding general skin care measures should not be omitted. The most commonly identified relevant allergens in our study were those present in over‐the‐counter cleansing and hemorrhoid preparations.
Minutes matter for trauma patients in hemorrhagic shock. How trauma team function impacts time to the next phase of care has not been rigorously evaluated. We hypothesized better team performance ...scores to be associated with decreased time to the next phase of trauma care.
This retrospective secondary analysis of a prospective multicenter observational study included hypotensive trauma patients at 19 centers. Using trauma video review, we analyzed team performance with the validated Non-Technical Skills for Trauma scale: leadership, cooperation and resource management, communication, assessment/decision making, and situational awareness. The primary outcome was minutes from patient arrival to next phase of care; deaths in the bay were excluded. Secondary outcomes included time to initiation and completion of first unit of blood and inpatient mortality. Associations between team dynamics and outcomes were assessed with a linear mixed-effects model adjusting for Injury Severity Score, mechanism, initial blood pressure and heart rate, number of team members, and trauma team lead training level and sex.
A total of 441 patients were included. The median Injury Severity Score was 22 (interquartile range, 10-34), and most (61%) sustained blunt trauma. The median time to next phase of care was 23.5 minutes (interquartile range, 17-35 minutes). Better leadership, communication, assessment/decision making, and situational awareness scores were associated with faster times to next phase of care (all p < 0.05). Each 1-point worsening in the Non-Technical Skills for Trauma scale score (scale, 5-15) was associated with 1.6 minutes more in the bay. The median resuscitation team size was 12 (interquartile range, 10-15), and larger teams were slower ( p < 0.05). Better situational awareness was associated with faster completion of first unit of blood by 4 to 5 minutes ( p < 0.05).
Better team performance is associated with faster transitions to next phase of care in hypotensive trauma patients, and larger teams are slower. Trauma team training should focus on optimizing team performance to facilitate faster hemorrhage control.
Therapeutic/Care Management; Level III.
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