The development and validation of a digital biomarker for remote assessment of Alzheimer's diseases risk.

Background: Digital cognitive assessment is becoming increasingly widespread in ageing research and care, especially since the COVID-19 pandemic. Remote online collection provides opportunities for ageing and dementia professionals to collect larger datasets, increase the diversity of research participants and patients and offer cost-effective screening and monitoring methods for clinical practice and trials. However, the reliability of self-administered at-home tests compared to their lab-based counterparts often goes unexamined, compromising the validity of adopting such measures. Objective: Our aim is to validate a self-administered web-based version of the visual short-term memory binding task (VSTMBT), a potential digital biomarker sensitive to Alzheimer's disease processes, suitable for use on personal devices. Methods: A final cross-sectional sample of 37 older-adult (51-77 years) participants without dementia completed our novel self-administered version of the VSTMBT, both at home on a personal device and in the lab, under researcher-controlled conditions. Results: ANOVA and Bayesian t-test found no significant differences between the task when it was remotely self-administered by participants at home compared to when it was taken under controlled lab conditions. Conclusions: These results indicate the VSTMBT can provide reliable data when self-administered at-home using an online version of the task and on a personal device. This finding has important implications for remote screening and monitoring practices of older adults, as well as supporting clinical practices serving diverse patient communities. Future work will assess remote administration in older adults with cognitive impairment and diverse socio-economic and ethno-cultural backgrounds as well as a bench-to-bedside application.

Early tracheostomy in patients undergoing mechanical thrombectomy for acute ischemic stroke.

PURPOSE: Respiratory failure following mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a known complication, and requirement of tracheostomy is associated with worse outcomes. Our objective is to evaluate characteristics associated with tracheostomy timing in AIS patients treated with MT. METHODS: The National Inpatient Sample was queried for adult patients treated with MT for AIS from 2016 to 2019. Baseline demographic characteristics, comorbidities, and inpatient outcomes were analyzed for associations in patients who received tracheostomy. Timing of early tracheostomy (ETR) was defined as placement before day 8 of hospital stay. RESULTS: Of 3505 AIS-MT patients who received tracheostomy, 915 (26.1%) underwent ETR. Patients who underwent ETR had shorter length of stay (LOS) (25.39 days vs 32.43 days, p < 0.001) and lower total hospital charges ($483,472.07 vs $612,362.86, p < 0.001). ETR did not confer a mortality benefit but was associated with less acute kidney injury (OR, 0.697; p = 0.013), pneumonia (OR, 0.449; p < 0.001), and sepsis (OR, 0.536; p = 0.002). CONCLUSION: An expected increase in complications and healthcare resource utilization is seen in AIS-MT patients receiving tracheostomy, likely reflecting the severity of patients' post-stroke neurologic injury. Among these high-risk patients, ETR was predictive of shorter LOS and fewer complications.

Treatment time and circadian genotype interact to influence radiotherapy side-effects. A prospective European validation study using the REQUITE cohort.

BACKGROUND: Circadian rhythm impacts broad biological processes, including response to cancer treatment. Evidence conflicts on whether treatment time affects risk of radiotherapy side-effects, likely because of differing time analyses and target tissues. We previously showed interactive effects of time and genotypes of circadian genes on late toxicity after breast radiotherapy and aimed to validate those results in a multi-centre cohort. METHODS: Clinical and genotype data from 1690 REQUITE breast cancer patients were used with erythema (acute; n=340) and breast atrophy (two years post-radiotherapy; n=514) as primary endpoints. Local datetimes per fraction were converted into solar times as predictors. Genetic chronotype markers were included in logistic regressions to identify primary endpoint predictors. FINDINGS: Significant predictors for erythema included BMI, radiation dose and PER3 genotype (OR 1.27(95%CI 1.03-1.56); P < 0.03). Effect of treatment time effect on acute toxicity was inconclusive, with no interaction between time and genotype. For late toxicity (breast atrophy), predictors included BMI, radiation dose, surgery type, treatment time and SNPs in CLOCK (OR 0.62 (95%CI 0.4-0.9); P < 0.01), PER3 (OR 0.65 (95%CI 0.44-0.97); P < 0.04) and RASD1 (OR 0.56 (95%CI 0.35-0.89); P < 0.02). There was a statistically significant interaction between time and genotypes of circadian rhythm genes (CLOCK OR 1.13 (95%CI 1.03-1.23), P < 0.01; PER3 OR 1.1 (95%CI 1.01-1.2), P < 0.04; RASD1 OR 1.15 (95%CI 1.04-1.28), P < 0.008), with peak time for toxicity determined by genotype. INTERPRETATION: Late atrophy can be mitigated by selecting optimal treatment time according to circadian genotypes (e.g. treat PER3 rs2087947C/C genotypes in mornings; T/T in afternoons). We predict triple-homozygous patients (14%) reduce chance of atrophy from 70% to 33% by treating in mornings as opposed to mid-afternoon. Future clinical trials could stratify patients treated at optimal times compared to those scheduled normally. FUNDING: EU-FP7.

Trends in overweight and obesity by socioeconomic status in Year 6 school children, Australian Capital Territory, 2006-2018.

BACKGROUND: Due to the high prevalence and adverse consequences, overweight and obesity in children continues to be a major public health concern worldwide. Socioeconomic background and health-related behaviours (such as diet, physical activity and sedentary behaviors) are important factors associated with weight status in children. Using a series of height and weight assessments from the Australian Capital Territory Physical Activity and Nutrition Survey (ACTPANS), trends in prevalence of overweight and obesity by socioeconomic status were examined in ACT Year 6 school children between 2006 and 2018. METHODS: The ACTPANS has been conducted every 3 years since 2006. A total of 6729 children were surveyed. Complete data on height and weight were available for 6384 (94.9%) participants. Trends in the prevalence of overweight and obesity and associations between weight status and risk factors (such as socioeconomic status, physical activity, screen time and consumption of sugar-sweetened soft drinks (SSD)) were examined using logistic regression. RESULTS: The prevalence of overweight and obesity remained stable in girls (from 22.5% in 2006 to 21.6% in 2018) but declined in boys (from 27.8 to 17.9%). During the same period, levels of physical activity increased slightly, while screen time and the consumption of fast food and SSD decreased. Socioeconomic gradient, based on the school-level Index of Community Socio-Educational Advantage (ICSEA), was highly associated with prevalence of overweight and obesity. Since 2006, the estimated prevalence of overweight and obesity has remained high in the lowest SES groups, but a concurrent downward trend was observed in the highest SES group, leading to increasing disparity between SES groups. Children in the lowest ICSEA quintile were more likely to be overweight or obese compared to those in the moderate and highest ICSEA quintiles. Children in lower ICSEA quintiles also reported lower levels of physical activity, higher levels of screen time, and higher levels of fast food and SSD consumption compared to those in higher ICSEA quintiles. CONCLUSIONS: While recent trends in overweight and obesity in ACT children are encouraging, the prevalence remains unacceptably high, especially in those from low socioeconomic backgrounds. Additional prevention efforts are required to address the socioeconomic disparity.

Brief report: Correlates of inpatient psychiatric admission in children and adolescents with eating disorders.

OBJECTIVE: To examine the prevalence and importance of psychological, behavioural, and situational correlates of impending psychiatric inpatient admissions in children and adolescents with eating disorders. METHOD: The sample consisted of 285 patients (8-17 years, M = 14.4, SD = 1.49) with DSM-5 eating disorders assessed between 2006 and 2013 from the Helping to Outline Pediatric Eating Disorders (HOPE) Project. The sample was split into two groups, those with (n = 38) and without (n = 247) impending psychiatric admission; Discriminant function analysis was used to examine correlates. RESULTS: The prevalence of impending psychiatric admission was 13.3%. Suicidal ideation provided the greatest discriminating power, followed by eating pathology, depressive symptoms, anxiety, multiple methods of weight control, binge eating, and family functioning. CONCLUSIONS: Earlier recognition of comorbid symptoms in eating disorders in the community may reduce the number of young people with eating disorders who present needing critical psychiatric care.

Psychotropic drug prescribing in an Australian specialist child and adolescent eating disorder service: a retrospective study.

BACKGROUND: To describe the rates, indications, and adverse effects of psychotropic drug prescription in a specialist tertiary hospital child and adolescent eating disorder service. METHODS: Retrospective case note study of all active eating disorder patients (N = 115) over the period of treatment from referral to time of study (M = 2 years), covering patient demographics, clinical characteristics, drug prescriptions, indications, and adverse effects. RESULTS: Psychotropic drugs were prescribed in 45% of cases, most commonly antidepressants (41%), followed by anxiolytics (29%) and antipsychotics (22%), with 8% initiated before referral to the specialist eating disorder program. Common indications were depressed mood, agitation, anxiety, and insomnia. Patient clinical severity and complexity was associated with prescribing. Adverse effects, mostly minor, were recorded in 23% of antidepressant prescriptions, 39% of antipsychotic prescriptions, and 13% of anxiolytic prescriptions. Second generation antipsychotic prescription was associated with subsequent new onset binge eating, in this preliminary observational study. Self-harm by overdose of psychotropics occurred in 11% of patients prescribed medication. CONCLUSIONS: Psychotropic medications were frequently prescribed to adolescent eating disorder patients to treat distressing symptoms. Prospective randomised controlled trials to clarify efficacy and safety are needed. Given the difficulties of conducting clinical trials in this population, services are encouraged to monitor and audit medication safety and efficacy in everyday practice, and to report their findings.

Resveratrol enhances anti-proliferative effect of VACM-1/cul5 in T47D cancer cells.

Vasopressin-activated calcium-mobilizing (VACM-1) protein is a cul-5 gene product that forms complexes with a subclass of ubiquitin E3 ligases involved in proteasomal protein degradation. The expression of VACM-1 cDNA in the T47D breast cancer cell line inhibits growth and decreases phosphorylation of mitogen activated protein kinase. Factors that regulate expression or stability of VACM-1 protein have not been identified, however. In our search to identify drugs/substances that may control VACM-1 protein expression, we examined the effects of resveratrol (trans-3,5,4'-trihydroxystilbene), a natural component in the human diet which inhibits tumor initiation and promotion. CMV vector and VACM-1 cDNA stably transfected T47D breast cancer-derived cells were treated with resveratrol and cell growth and VACM-1 protein concentrations were measured. Since the cellular mechanism of resveratrol-dependent inhibition of cell growth also involves the regulation of estrogen receptors, the effect of 17-ß-estradiol and resveratrol on ERα levels and on cell growth was examined in control and in VACM-1 cDNA transfected cells. Our results demonstrate that antiproliferative effect of resveratrol observed in the control T47D cancer cells was significantly enhanced in VACM-1 cDNA transfected T47D cells. Western blot results indicated that resveratrol increased VACM-1 protein concentration. Finally, treatment with resveratrol for 24 and 48 h attenuated 17-ß-estradiol induced increase in cell growth both in control and in VACM-1 cDNA transfected cells. The effect was significantly higher in the VACM-1 cDNA transfected cells when compared to controls. These results indicate that the antiproliferative effect of resveratrol may involve induction of VACM-1/cul5.

Impact of more intensive written information in patients having radical radiation therapy: results of a prospective randomized phase III trial.

BACKGROUND AND PURPOSE: A diagnosis of malignancy and its treatment is a very stressful time for patients and their families. This study was conducted to determine the impact of more intensive written information on patients' anxiety levels. The secondary aim was to determine the impact of this information on patients' satisfaction levels. MATERIALS AND METHODS: This prospective randomized trial consisted of patients with a pathological diagnosis of cancer having radical radiotherapy (RT). Patients were randomized to receive the more intensive information (including written information and a telephone call from the research nurse) or not to receive the more intensive information at the time of their initial consultation with the radiation oncologist. Study questionnaires measuring anxiety (STAI form) were completed prior to their first consultation (baseline) at the time of simulation (pre-RT) and at the completion of radiotherapy. A second questionnaire assessing satisfaction with the information given (ISQ) was completed at the time of simulation prior to commencing RT. RESULTS: One hundred and ninety-four patients were enrolled in the study. The mean age of the patients was 58.5 years and 70% of patients were female. Breast cancer (67%) was the commonest cancer. One hundred and two patients were randomized to receive the intensive information package and 92 patients received the standard consultation. There was no significant difference in mean State or Trait anxiety scores between any of the time intervals and no difference between the two information groups. There was no significant difference between the groups with regard to mean satisfaction scores with the overall information given, nor with any individual question. The satisfaction scores with lifestyle information given were lower than those for any other type of information in both randomization arms. CONCLUSION: More intensive information did not significantly change patients' anxiety scores or satisfaction levels. The patients were generally very satisfied with the information they received but less satisfied with the information on lifestyle issues.