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Challenges related to the implementation of a technology-enhanced intervention in existing mental health clinics are discussed, as well as implications for future research and practice. INTRODUCTION Persons living with Alzheimer's disease and related dementias (ADRD) frequently experience pain and behavioral and psychological symptoms of dementia (BPSD) which decrease quality of life (QOL) and influence caregiver burden. Home healthcare professionals however may underrecognize or lack the ability to manage BPSD. INTERVENTION This protocol describes an ADRD palliative quality assurance performance improvement program for home healthcare, Aliviado Dementia Care-Home Health Edition. It includes training, mentoring, and a toolbox containing intervention strategies. METHODS This embedded pragmatic clinical trial will utilize a multi-site, cluster randomized control design. Recruitment will occur from three home healthcare agencies located in New Jersey, Utah, and Florida. At each agency, care teams will be randomized as clusters and assigned to either the Aliviado Dementia Care program or usual care. We plan to enroll 345 persons living with ADRD and their informal caregiver dyads. The primary outcome will be to measure QOL in both the person living with ADRD and their informal caregiver, and emergency department visits and hospital admissions. Secondary outcomes in the person living with ADRD will include the examination of pain, BPSD, antipsychotic and analgesic use. Secondary outcomes in caregivers include burden, depressive symptoms, functional health and wellbeing, and healthcare utilization. CONCLUSION This study will be the first large-scale embedded pragmatic clinical trial in home healthcare focused on care quality and outcomes in addressing QOL in ADRD. If proven successful, the intervention can then be disseminated to agencies throughout the country to improve the quality of care for this vulnerable, underserved population. TRIAL REGISTRATION Clinical Trials.gov NCT03255967. BACKGROUND Pregnancy presents a teachable moment to engage male smokers whose partners are pregnant in smoking cessation. Evidence on how to approach and help these smokers quit smoking in antenatal settings has remained scarce. This paper presents the rationale and study design of a trial which aims to evaluate the effectiveness of a brief intervention model for promoting smoking cessation in expectant fathers. METHODS BANSAR is a pragmatic randomised controlled trial conducted in antenatal clinic in seven public hospitals in Hong Kong, China. An estimated 1148 fathers who smoke at least one cigarette daily and whose partners are pregnant and non-smoking will be randomised (11) to receive brief advice combined with 1-week sample of nicotine replacement therapy (NRT) and active referral to smoking cessation services, or brief advice only (usual care). Outcome will be assessed at 3 and 6 months after treatment initiation. The primary outcome is carbon monoxide-verified ( less then 4 part per million) abstinence at 6 months post-treatment initiation. Secondary outcomes include self-reported 7-day point-prevalence abstinence and 24-week continuous abstinence, use of smoking cessation service and NRT and quit attempt, and smoking reduction, change in nicotine dependence and intention to quit in continuing smokers. COMMENT This trial will provide real-world evidence on the effectiveness of a combined brief intervention model for smoking cessation in expectant fathers, an understudied population. The findings may be particularly relevant to low and middle-income countries, where male-to-female smoking ratios and birth rates tend to be higher than higher-income countries. TRIAL REGISTRATION ClinicalTrials.gov, number NCT03671707. Multiple Sclerosis (MS) is a common cause of neurological disability among young adults and has a high economic burden. Currently there are 18 disease modifying agents for relapsing MS, which were tested in clinical trials versus placebo or an active comparator in a pairwise manner. However, there is currently no consensus on the fundamental principles of treatment approach and initial therapy selection. These factors result in variable use of disease modifying therapies. Here we describe the study protocol for Determining the Effectiveness of earLy Intensive Versus Escalation approaches for the Treatment of Relapsing-remitting Multiple Sclerosis (DELIVER-MS). The main objective of the study is to determine whether an early highly effective treatment approach, defined as use of one of four monoclonal antibodies as initial therapy, is more effective than an escalation treatment approach (any other approved medication as initial therapy with subsequent escalation to higher efficacy treatments guided by radiological and clinical evaluation). The primary endpoint of the study is reduction in normalized brain volume loss from baseline visit to month 36 visit using MRI. Brain volume loss was selected as the best short-term predictor of long-term clinical disability. A total of 400 participants will be randomized 11 using minimization to account for age and sex by site, and 400 will be enrolled into a parallel observational cohort. The study results will help guide overall treatment philosophy and will have important implications for patient choice, clinical practice, and treatment access. Small molecules targeting the colchicine site of tubulin represent an attractive cancer treatment strategy. In this study, a total of 468 models derived from 1076 diverse inhibitors binding to the tubulin colchicine site were constructed based on fingerprints using three machine learning approaches 1) naive Bayesian (NB); 2) single tree (ST); and 3) random forest (RF). The overall predictive accuracy of the best models exceeded 85.12% for both the training and test sets. We designed an integrated virtual screening (VS) strategy for identifying new tubulin inhibitors by combining established models, molecular docking, and similarity-based analog searching. Hexadimethrine Bromide Through two rounds of VS, compound 23g was identified as a novel potent anticancer agent exhibiting activity against MDA-MB-231, HeLa, A549, HepG2, CNE2, and HCT116 tumor cell lines with IC50 values of 5.45, 8.61, 7.47, 2.29, 2.91, and 4.10 μM, respectively. Compared with taxol, colchicine, and adriamycin, 23g also displayed potent cytotoxicity against the drug-resistant tumor cell lines, HepG2/ADR, A549/CDDP, and A549/TAX cells, with IC50 values of 4.

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