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BackgroundPeople with advanced cancer frequently use the GP out-of-hours (GPOOH) service. Considerable amounts of routine GPOOH data are uncoded. Therefore, these data are omitted from existing healthcare datasets.AimTo conduct a free-text analysis of a GPOOH dataset, to identify reasons for attendance and care delivered through GPOOH to people with advanced cancer.Design and settingAn analysis of a GPOOH healthcare dataset was undertaken. It contained all coded and free- text information for 5749 attendances from a cohort of 2443 people who died from cancer in Tayside, Scotland, from 2013–2015.MethodRandom sampling methods selected 575 consultations for free-text analysis. Each consultation was analysed by two independent reviewers to determine the following: assigned presenting complaints; key and additional palliative care symptoms recorded in free text; evidence of anticipatory care planning; and free-text recording of dispensed medications. Inter-rater reliability concordance was established through Kappa testing.ResultsMore than half of all coded reasons for attendance (n= 293; 51.0%) were ‘other’ or ‘missing’. Free-text analysis demonstrated that nearly half (n= 284; 49.4%) of GPOOH attendances by people with advanced cancer were for pain or palliative care. More than half of GPOOH attendances (n= 325; 56.5%) recorded at least one key or additional palliative care symptom in free text, with the commonest being breathlessness, vomiting, cough, and nausea. Anticipatory care planning was poorly recorded in both coded and uncoded records. Uncoded medications were dispensed in more than one- quarter of GPOOH consultations.ConclusionGPOOH delivers a substantial amount of pain management and palliative care, much of which is uncoded. Therefore, it is unrecognised and under-reported in existing large healthcare data analyses.

ObjectiveChronic liver disease continues to be a significant cause of morbidity and mortality yet remains challenging to prognosticate. This has been one of the barriers to implementing palliative care, particularly at an early stage. The Bristol Prognostic Score (BPS) was developed to identify patients with life expectancy less than 12 months and to act as a trigger for referral to palliative care services. This study retrospectively evaluated the BPS in a cohort of patients admitted to three Scottish hospitals.MethodRoutinely collated healthcare data were used to obtain demographics, BPS and analyse 1-year mortality for patients with decompensated liver disease admitted to three gastroenterology units over two 90-day periods. Statistical analysis was undertaken to assess performance of BPS in predicting mortality.Results276 patients were included in the final analysis. Participants tended to be late middle-aged men, socioeconomically deprived and have alcohol-related liver disease. A similar proportion was BPS+ve (>3) in this study compared with the original Bristol cohort though had more hospital admissions, higher ongoing alcohol use and poorer performance status. BPS performed poorer in this non-Bristol group with sensitivity 54.9% (72.2% in original study), specificity 58% (83.8%) and positive predictive value (PPV) 43.4% (81.3%).ConclusionBPS was unable to accurately predict mortality in this Scottish cohort. This highlights the ongoing challenge of prognostication in patients with chronic liver disease, furthering the call for more work in this field.

Sex and Gender Science seeks to better acknowledge that the body cannot be removed from the world it inhabits. We believe that to best answer any neuroscience question, the biological and the social need to be addressed through both objective means to learn, "how it is like" and subjective means to learn, "what it is like." We call bringing the biological and social together, "Situated Neuroscience" and the mixing of approaches to do so, Very Mixed Methods. Taken together, they constitute an approach to Sex and Gender Science. In this chapter, we describe neural phenomena for which considering sex and gender together produces a fuller knowledge base: sleep, pain, memory, and concussion. For these brain phenomena examples, studying only quantitative measures does not reveal the full impact of these lived experiences on the brain but studying only the qualitative would not reveal how the brain responds. We discuss how Sex and Gender Science allows us to begin to bring together biology and its social context and acknowledge where context can contribute to resolving ignorance to offer more expansive, complementary, and interrelating pictures of an intricate neuro-landscape.

The present study explored whether early midlife bilateral salpingo-oophorectomy (BSO), a female-specific risk factor for dementia, is associated with reduced medial temporal lobe structure and function. Younger middle-aged women with the BRCA1/2 mutation and a BSO prior to spontaneous menopause (SM) were recruited. We determined the performance of women with BSO not taking estradiol-based hormone therapy (n = 18) on a task measuring object and scene recognition and quantified medial temporal lobe subregion volumes using manually segmented high-resolution T2-weighted MRI scans. Comparisons were made to those with BSO taking estradiol-based hormone therapy (n = 20), age-matched premenopausal controls (n = 28), and older women in SM not taking hormone therapy matched for duration of hormone deprivation (n = 17). Reduced hippocampal integrity specific to the BSO group not taking hormone therapy was observed, reflected by significantly smaller dentate gyrus/CA2/CA3 volumes and lower scene recognition memory performance. These findings show that hippocampal subfield volume may be useful for identifying early midlife changes in women at elevated risk for dementia.

Ovarian hormones, including 17β-estradiol, are implicated in numerous physiological processes, including sleep. Beginning at puberty, girls report more sleep complaints than boys, which is maintained throughout the reproductive life stage. Sleep problems are exacerbated during the menopausal transition, evidenced by greater risk for sleep disorders. There is emerging evidence that menopause-associated hormone loss contributes to this elevated risk, but age is also an important factor. The extent to which menopause-associated sleep disturbance persists into postmenopause above and beyond the effects of age remains unknown. Untreated sleep disturbances have important implications for cognitive health, as they are emerging as risk factors for dementia. Given that sleep loss impairs memory, an important knowledge gap concerns the role played by menopause-associated hormone loss in exacerbating sleep disturbance and, ultimately, cognitive function in aging women. In this review, we take a translational approach to illustrate the contribution of ovarian hormones in maintaining the sleep–wake cycle in younger and middle-aged females, with evidence implicating 17β-estradiol in supporting the memory-promoting effects of sleep. Sleep physiology is briefly reviewed before turning to behavioral and neural evidence from young females linking 17β-estradiol to sleep–wake cycle maintenance. Implications of menopause-associated 17β-estradiol loss is also reviewed before discussing how ovarian hormones may support the memory-promoting effects of sleep, and why menopause may exacerbate pathological aging via effects on sleep. While still in its infancy, this research area offers a new sex-based perspective on aging research, with a focus on a modifiable risk factor for pathological aging.

Introduction 17β-estradiol loss is related to Alzheimer’s disease (AD) risk factors, including disordered sleep and associative memory decrements. Women have higher risk for AD than men, and those with mid-life 17β-estradiol loss due to surgical menopause, including bilateral salpingo-oophorectomy (BSO) before age 48, have even higher risk. We wondered whether sleep and associative memory in women with BSO (mean age 44–46) would be comparable to those with spontaneous/natural menopause (SM; mean age 57), and whether 17β-estradiol-based hormone therapy (ET) might mitigate these effects. Methods We assessed sleep using the average of three nights of portable polysomnography (Temec) in women with BSO either taking ET (BSO+ET; n=16), or not (BSO; n=18), and in older spontaneously menopausal women (SM; n=14). Using EEG (Fp1-Fp2), we obtained sleep staging automatically (Neurobit Technologies). Participants also completed a face-name associative memory task during functional magnetic resonance imaging. Recognition accuracy and brain activation during encoding were measured. Results BSO exhibited reduced sleep efficiency compared to BSO+ET. For BSO, there was no relationship between percent of total sleep time in N3 and hippocampal activation during associative encoding, even though percent of total sleep time in N3 was negatively associated with hippocampal activation during associative encoding in BSO+ET. For all groups, including BSO, lower latency to consolidated N3 correlated with better associative memory accuracy. There were no group differences in associative memory accuracy. In contrast to BSO, SM showed significantly longer latency to consolidated N3 than BSO+ET. Conclusion Younger women with BSO have comparable sleep to older women in SM. In younger women with BSO, ET improves sleep efficiency. Further, while associative memory may be disrupted by increased latency to consolidated N3 in all women, BSO and BSO+ET showed similar associative memory accuracy and latency to consolidated N3. Only BSO+ET exhibited a significant correlation between hippocampal activity during associative encoding and time spent in N3, indicating that ET may support the negative relationship between N3 and hippocampal function. Overall, ET in younger women with BSO potentially ameliorates poor sleep and associative memory decrements. Support (if any) Alzheimer’s Association/Brain Canada Foundation: AARF-17-504715; Wilfred and Joyce Posluns Chair in Women’s Brain Health and Aging

Introduction Early loss of 17β-estradiol (E2), as experienced by women with bilateral salpingo-oophorectomy (BSO; removal of ovaries and fallopian tubes), is associated with increased prevalence of sleep disorders and greater Alzheimer’s disease (AD) risk. In older adults, poor sleep heightens AD risk; hypoxia increases markers for incipient AD, including circulating Aβ, and is linked to prefrontal cortical thinning. Thus, we wondered: 1) if this at-risk population of middle-aged women with BSO had sleep hypoxia, measured by oxygen desaturation, and 2) whether this related to decreased prefrontal cortical thickness in women taking and not taking estradiol therapy (ET). Methods Sleep and percent oxygen desaturation (SPO2%) were measured via at-home polysomnography (TEMEC). Prefrontal cortical thickness was obtained from T1-weighted structural scans using the CIVET pipeline. We recruited middle-age women with BSO, some of whom were taking ET (BSO+ET; n=15), and some not (BSO; n=15). We compared their sleep and cortical thickness with that of age and education-matched premenopausal controls (AMC; n=18). Results Women with BSO (BSO, BSO+ET) had lower minimum SPO2% values than AMC, and thinner right medial orbitofrontal (rmOF) cortices. There was a trend for women with BSO to have lower average SPO2% than AMC. Analyses separating groups based on ET therapy status (BSO vs BSO+ET vs AMC) revealed only trending differences between groups, such that women with BSO tended to have lower minimum SPO2% and thinner rmOF cortices than AMC. Conclusion These preliminary results suggest early loss of E2 due to BSO may drive greater drops in SPO2% in middle-age women, and may be related to reduced prefrontal cortical thickness. This study is the first to show hypoxia in women with BSO. Support (if any) Ontario Graduate Scholarship Award (to LG), Alzheimer’s Association Research Fellowship (co-sponsored by Brain Canada Foundation; AARF-17-504715 to NJG), Alzheimer’s Society Canada Postdoctoral Fellowship (to AA), Canadian Institutes of Health Research (CIHR) Masters Award (to LG, AB, and RR), Wilfred and Joyce Posluns Chair in Women’s Brain Health and Aging (from the Posluns Family Foundation, CIHR, Ontario Brain Institute, and Alzheimer Society of Canada; WJP-150643 to GE)

Oophorectomy prior to menopause is associated with late-life dementia. Memory decline may start within 6 months after oophorectomy in middle-aged women, suggested by lower verbal and working memory performance. Unknown is whether such changes persist beyond 6 months, and whether they are reversed by estradiol. Short-term benefits of estradiol on verbal memory following oophorectomy were observed in one study, but longer term effects remain unknown. In the present study, middle-aged BRCA1/2 mutation carriers with early oophorectomy at least 1 year prior to study onset were tested on verbal and working memory with results stratified by (1) current estradiol use (n = 22) or (2) no history of estradiol use (n = 24), and compared to age-matched premenopausal controls (n = 25). Both memory abilities were adversely affected by oophorectomy, but only working memory was maintained by estradiol. Estrogen metabolite levels correlated with working memory, suggesting a role for estradiol in preserving this ability. Memory decline appears to persist after early oophorectomy, particularly for women who do not take estradiol.

Sex differences in visuospatial cognition have long been reported, with men being advantaged on the Mental Rotations Test (MRT). The data, however, are variable, and sensitive to design parameters. When men and women are compared directly, with women in different hormonal milieus combined, there seem to be sex differences. When women alone are studied, taking into account different ovarian steroid concentrations and treatments, MRT performance varies with these changes. Indeed, several reports describe better performance among women with reduced estrogens. To better understand whether the sex difference in MRT persists once hormonal status is considered, we recruited reproductive age adults designated male and female at birth (MAB, FAB), and administered the Vandenberg-Kuse (V/K) MRT—comparing performance among MAB (n = 169) and FAB (n = 219). For FAB combined, we found a sex difference with MAB performing better than FAB. However, when FAB were analyzed by current menstrual cycle phase (Early Follicular (EF), Periovulatory (PO), Midluteal (ML)) or by hormone therapy (transmasculine testosterone administration (TM+), oral contraceptive (OC) ingestion prior to (OC+) or after cognitive testing (OC-)), low-estradiol groups (EF, OC-, TM+) performed as strongly as MAB, and had better MRT than cycling FAB in high-estradiol menstrual cycle phases (PO, ML). On a verbal memory control task, neither a sex difference nor a low estrogen advantage was detected, although performance varied with hormonal milieu. Our findings support a dynamic model of spatial performance and suggest that both MAB and FAB perform strongly on MRT, contingent on hormonal status.

The patient denied any headaches, vertigo, weakness, confusion, bowel or bladder dysfunction and the unsteadiness was independent of position. Bowel movements were normal and he reported no other symptoms of abdominal pathology. The patient drank on average 10 units of alcohol a week and reported no recent increase in consumption. He was a life-long non-smoker, and denied any recent symptoms of respiratory pathology. On further questioning it emerged that he had noticed weight loss of approx 10kg over the last 2 months. He had no past medical history of note and was currently taking no medications. His father had been diagnosed at 84 with a glioblastoma and a first-cousin, 63 years old, had recently been diagnosed with Parkinson’s disease. There was no other family history of neurological or neoplastic disorders.