Web-based interventions for weight loss and weight maintenance among rural midlife and older women: protocol for a randomized controlled trial

Background: Weight loss is challenging and maintenance of weight loss is problematic among midlife and older rural women. Finding effective interventions using innovative delivery methods that can reach underserved and vulnerable populations of overweight and obese rural women is a public health challenge. Methods/Design: This Women Weigh-In for Wellness (The WWW study) randomized-controlled trial is designed to compare the effectiveness of theory-based behavior-change interventions using (1) website only, (2) website with peer-led support, or (3) website with professional email-counseling to facilitate initial weight loss (baseline to 6 months), guided continuing weight loss and maintenance (7-18 months) and self-directed weight maintenance (19-30 months) among rural women ages 45-69 with a BMI of 28-45. Recruitment efforts using local media will target 306 rural women who live within driving distance of a community college site where assessments will be conducted at baseline, 3, 6, 12, 18, 24 and 30 months by research nurses blinded to group assignments. Primary outcomes include changes in body weight, % weight loss, and eating and activity behavioral and biomarkers from baseline to each subsequent assessment. Secondary outcomes will be percentage of women achieving at least 5% and 10% weight loss without regain from baseline to 6, 18, and 30 months and achieving healthy eating and activity targets. Data analysis will use generalized estimating equations to analyze average change across groups and group differences in proportion of participants achieving target weight loss levels. Discussion: The Women Weigh-In for Wellness study compares innovative web-based alternatives for providing lifestyle behavior-change interventions for promoting weight loss and weight maintenance among rural women. If effective, such interventions would offer potential for reducing overweight and obesity among a vulnerable, hard-to-reach, population of rural women

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Radical Chemistry and Cytotoxicity of Bioreductive 3-Substituted Quinoxaline Di-N-Oxides

The radical chemistry and cytotoxicity of a series of quinoxaline di-N-oxide (QDO) compounds has been investigated to explore the mechanism of action of this class of bioreductive drugs. A series of water-soluble 3-trifluoromethyl (4–10), 3-phenyl (11–19), and 3-methyl (20-21) substituted QDO compounds were designed to span a range of electron affinities consistent with bioreduction. The stoichiometry of loss of QDOs by steady-state radiolysis of anaerobic aqueous formate buffer indicated that one-electron reduction of QDOs generates radicals able to initiate chain reactions by oxidation of formate. The 3-trifluoromethyl analogues exhibited long chain reactions consistent with the release of the HO•, as identified in EPR spin trapping experiments. Several carbon-centered radical intermediates, produced by anaerobic incubation of the QDO compounds with N-terminal truncated cytochrome P450 reductase (POR), were characterized using N-tert-butyl-α-phenylnitrone (PBN) and 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide (DEPMPO) spin traps and were observed by EPR. Experimental data were well simulated for the production of strongly oxidizing radicals, capable of H atom abstraction from methyl groups. The kinetics of formation and decay of the radicals produced following one-electron reduction of the parent compounds, both in oxic and anoxic solutions, were determined using pulse radiolysis. Back oxidation of the initially formed radical anions by molecular oxygen did not compete effectively with the breakdown of the radical anions to form oxidizing radicals. The QDO compounds displayed low hypoxic selectivity when tested against oxic and hypoxic cancer cell lines in vitro. The results from this study form a kinetic description and explanation of the low hypoxia-selective cytotoxicity of QDOs against cancer cells compared to the related benzotriazine 1,4-dioxide (BTO) class of compounds

A preliminary trial examining a ‘real world’ approach for increasing physical activity among breast cancer survivors: findings from project MOVE

Background: Physical activity (PA) is a safe and effective strategy to help mitigate health challenges associated with breast cancer (BC) survivorship. However, the majority of BC survivors are not meeting the minimum recommended PA (≥150 min of moderate to vigorous intensity). Project MOVE was developed as a model for increasing PA that combined a) Microgrants: funds ($2000) awarded to applicant groups to develop and implement a PA initiative and b) Financial incentives: a reward ($500) for increasing group PA. The purpose of this paper was to provide an exploratory analysis of effectiveness of Project MOVE on PA behavior, PA motivation, and quality of life (QoL) in female BC survivors. The differential outcomes between women meeting and not meeting PA guidelines were also investigated. Methods: This pre-post test, preliminary trial included groups of adult (18+ years) self-identified female BC survivors, who were post-surgery and primary systemic chemo- and radiation therapy, and living in British Columbia, Canada. PA was assessed by accelerometry. PA motivation and QoL were assessed by self-report. Data were collected at baseline, 6-months, and 12-month time points. Repeated measures mixed ANOVAs were used to test changes in the main outcomes. Results: A total of 10 groups were awarded microgrants between May 2015 and January 2016. Groups comprised of 8 to 12 women with a total of 87 participants. A statistically significant increase was found between time points on weekly moderate to vigorous PA (p = .012). This was mediated by a significant interaction between those meeting PA guidelines and those not meeting guidelines at baseline by time points (p = .004), with those not meeting guidelines at baseline showing the greatest increase in MVPA. A statistically significant difference across time points was found for intrinsic motivation (p = .02), physical functioning (p < .001), physical health limitations (p = .001), emotional health limitations (p = .023), social functioning (p = .001) and general health (p = .004). Conclusion: These results provide promising support for a unique approach to increasing PA among BC survivors by empowering women and optimizing PA experiences through the use of microgrants and financial incentives. Trial registration: ClinicalTrials.gov NCT03548636 , Retrospectively registered June 7, 2018.Health and Social Development, Faculty of (Okanagan)Medicine, Faculty ofOther UBCNon UBCHealth and Exercise Sciences, School of (Okanagan)Nursing, School of (Okanagan)Physical Therapy, Department ofPopulation and Public Health (SPPH), School ofReviewedFacult

Radical Chemistry and Cytotoxicity of Bioreductive 3‑Substituted Quinoxaline Di‑<i>N</i>‑Oxides

The radical chemistry and cytotoxicity of a series of quinoxaline di-<i>N</i>-oxide (QDO) compounds has been investigated to explore the mechanism of action of this class of bioreductive drugs. A series of water-soluble 3-trifluoromethyl (<b>4</b>–<b>10</b>), 3-phenyl (<b>11</b>–<b>19</b>), and 3-methyl (<b>20</b>-<b>21</b>) substituted QDO compounds were designed to span a range of electron affinities consistent with bioreduction. The stoichiometry of loss of QDOs by steady-state radiolysis of anaerobic aqueous formate buffer indicated that one-electron reduction of QDOs generates radicals able to initiate chain reactions by oxidation of formate. The 3-trifluoromethyl analogues exhibited long chain reactions consistent with the release of the HO^•, as identified in EPR spin trapping experiments. Several carbon-centered radical intermediates, produced by anaerobic incubation of the QDO compounds with N-terminal truncated cytochrome P450 reductase (POR), were characterized using <i>N</i>-<i>tert</i>-butyl-α-phenylnitrone (PBN) and 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-<i>N</i>-oxide (DEPMPO) spin traps and were observed by EPR. Experimental data were well simulated for the production of strongly oxidizing radicals, capable of H atom abstraction from methyl groups. The kinetics of formation and decay of the radicals produced following one-electron reduction of the parent compounds, both in oxic and anoxic solutions, were determined using pulse radiolysis. Back oxidation of the initially formed radical anions by molecular oxygen did not compete effectively with the breakdown of the radical anions to form oxidizing radicals. The QDO compounds displayed low hypoxic selectivity when tested against oxic and hypoxic cancer cell lines <i>in vitro</i>. The results from this study form a kinetic description and explanation of the low hypoxia-selective cytotoxicity of QDOs against cancer cells compared to the related benzotriazine 1,4-dioxide (BTO) class of compounds