Evaluation of the Safer Use of Antipsychotics in Youth Study on Population Level Antipsychotic Initiation: An Interrupted Time Series Analysis.

Background: Antipsychotics carry a higher-risk profile than other psychotropic medications and may be prescribed for youth with conditions in which other first-line treatments are more appropriate. This study aimed to evaluate the population-level effect of the Safer Use of Antipsychotics in Youth (SUAY) trial, which aimed to reduce person-days of antipsychotic use among participants. Methods: We conducted an interrupted time series analysis using segmented regression to measure changes in prescribing trends of antipsychotic initiation rates pre-SUAY and post-SUAY trial at four U.S. health systems between 2013 and 2020. Results: In our overall model, adjusted for age and insurance type, antipsychotic initiation rates decreased by 0.73 (95% confidence interval [CI]: 0.30, 1.16, p = 0.002) prescriptions per 10,000 person-months before the SUAY trial. In the first quarter following the start of the trial, there was an immediate decrease in the rate of antipsychotic initiations of 6.57 (95% CI: 0.99, 12.15) prescriptions per 10,000 person-months. When comparing the posttrial period to the pretrial period, there was an increase of 1.09 (95% CI: 0.32, 1.85) prescriptions per 10,000 person-months, but the increasing rate in the posttrial period alone was not statistically significant (0.36 prescriptions per 10,000 person-months, 95% CI: -0.27, 0.99). Conclusion: The declining trend of antipsychotic initiation seen between 2013 and 2018 (pre-SUAY trial) may have naturally reached a level at which prescribing was clinically warranted and appropriate, resulting in a floor effect. The COVID-19 pandemic, which began in the final three quarters of the posttrial period, may also be related to increased antipsychotic medication initiation.

Cost of Implementing an Evidence-Based Intervention to Support Safer Use of Antipsychotics in Youth.

To estimate the cost of implementing a clinical program designed to support safer use of antipsychotics in children and adolescents (youth) age 3-17 years at the time of initiating an antipsychotic medication. We calculate the costs of implementing a psychiatric consultation and navigation program for youth prescribed antipsychotic medications across 4 health systems, which included an electronic health record (EHR) decision support tool, consultation with a child and adolescent psychiatrist, and up to 6 months of behavioral health care navigation, as well as telemental health for patients (n = 348). Cost data were collected for both start-up and ongoing intervention phases and are estimated over a 1-year period. Data sources included study records and time-in-motion reports, analyzed from a health system perspective. Costs included both labor and nonlabor costs (2019 US dollars). The average total start-up and ongoing costs per health system were $34,007 and $185,174, respectively. The average total cost per patient was $2,128. The highest average ongoing labor cost components were telemental health ($901 per patient), followed by child and adolescent psychiatrist consultation ($659), and the lowest cost component was primary care/behavioral health provider time to review/respond to the EHR decision support tool and case consultation ($24). For health systems considering programs to promote safer and targeted use of antipsychotics among youth, this study provides estimates of the full start-up and ongoing costs of an EHR decision support tool, psychiatric consultation service, and psychotherapeutic services for patients and families.Trial registration: Clinicaltrials.gov, NCT03448575.

Reducing Sitting Time in Obese Older Adults: The I-STAND Randomized Controlled Trial.

BACKGROUND: The authors tested the efficacy of the "I-STAND" intervention for reducing sitting time, a novel and potentially health-promoting approach, in older adults with obesity. METHODS: The authors recruited 60 people (mean age = 68 ± 4.9 years, 68% female, 86% White; mean body mass index = 35.4). The participants were randomized to receive the I-STAND sitting reduction intervention (n = 29) or healthy living control group (n = 31) for 12 weeks. At baseline and at 12 weeks, the participants wore activPAL devices to assess sitting time (primary outcome). Secondary outcomes included fasting glucose, blood pressure, and weight. Linear regression models assessed between-group differences in the outcomes. RESULTS: The I-STAND participants significantly reduced their sitting time compared with the controls (-58 min per day; 95% confidence interval [-100.3, -15.6]; p = .007). There were no statistically significant changes in the secondary outcomes. CONCLUSION: I-STAND was efficacious in reducing sitting time, but not in changing health outcomes in older adults with obesity.

Changes in Self-Reported Health and Psychosocial Outcomes in Older Adults Enrolled in Sedentary Behavior Intervention Study.

PURPOSE: To estimate changes in self-reported health and psychosocial factors associated with a 12-week sedentary behavior intervention for older adults. DESIGN: Exploratory secondary analysis of pilot randomized controlled trial. SETTING: Kaiser Permanente Washington. SUBJECTS: Sixty adults aged 60 to 89 with body mass index ≥30 kg/m2. INTERVENTION: Participants were randomized to the I-STAND intervention or control group. I-STAND involved 6 coaching sessions, a study workbook, Jawbone UP activity tracker to prompt breaks from sitting, and activPAL feedback on objective sitting time. MEASURES: At baseline and 12-week follow-up, participants completed a survey with validated measures of self-reported health outcomes (depression, stress, memory/concentration, sleep, pain, ability to do daily activities, energy, and quality of life) and modified scales measuring psychosocial factors (perceived benefits/barriers, social support, self-efficacy, and sedentary habit strength) regarding sedentary behavior. ANALYSIS: Generalized linear models assessed associations between group assignment and change in each self-reported health and psychosocial score, adjusting for baseline scores. RESULTS: I-STAND participants demonstrated improvements in self-efficacy (ß = 0.35, 95% confidence interval [CI]: 0.10 to 0.60) and reduced habit strength (ß= -0.23, 95% CI: -0.42 to -0.04) compared to control participants. There were no significant differences in self-reported health outcomes, although power was limited in this exploratory analysis. CONCLUSION: A sedentary behavior reduction intervention for older adults resulted in improvements for some psychosocial factors. Health outcomes may require longer than 12 weeks to observe improvements.

Systematic Multi-Domain Alzheimer's Risk Reduction Trial (SMARRT): Study Protocol.

This article describes the protocol for the Systematic Multi-domain Alzheimer's Risk Reduction Trial (SMARRT), a single-blind randomized pilot trial to test a personalized, pragmatic, multi-domain Alzheimer's disease (AD) risk reduction intervention in a US integrated healthcare delivery system. Study participants will be 200 higher-risk older adults (age 70-89 years with subjective cognitive complaints, low normal performance on cognitive screen, and ≥ two modifiable risk factors targeted by our intervention) who will be recruited from selected primary care clinics of Kaiser Permanente Washington, oversampling people with non-white race or Hispanic ethnicity. Study participants will be randomly assigned to a two-year Alzheimer's risk reduction intervention (SMARRT) or a Health Education (HE) control. Randomization will be stratified by clinic, race/ethnicity (non-Hispanic white versus non-white or Hispanic), and age (70-79, 80-89). Participants randomized to the SMARRT group will work with a behavioral coach and nurse to develop a personalized plan related to their risk factors (poorly controlled hypertension, diabetes with evidence of hyper or hypoglycemia, depressive symptoms, poor sleep quality, contraindicated medications, physical inactivity, low cognitive stimulation, social isolation, poor diet, smoking). Participants in the HE control group will be mailed general health education information about these risk factors for AD. The primary outcome is two-year cognitive change on a cognitive test composite score. Secondary outcomes include: 1) improvement in targeted risk factors, 2) individual cognitive domain composite scores, 3) physical performance, 4) functional ability, 5) quality of life, and 6) incidence of mild cognitive impairment, AD, and dementia. Primary and secondary outcomes will be assessed in both groups at baseline and 6, 12, 18, and 24 months.

Acceptability of a sitting reduction intervention for older adults with obesity.

BACKGROUND: Older adults spend more time sitting than any other age group, contributing to poor health outcomes. Effective behavioral interventions are needed to encourage less sitting among older adults, specifically those with obesity, but these programs must be acceptable to the target population. We explored participant acceptance of a theory-based and technology-enhanced sitting reduction intervention designed for older adults (I-STAND). METHODS: The 12-week I-STAND intervention consisted of 6 health coaching contacts, a study workbook, a Jawbone UP band to remind participants to take breaks from sitting, and feedback on sitting behaviors (generated from wearing an activPAL device for 7 days at the beginning and mid-point of the study). Semi-structured interviews were conducted with 22 participants after they completed the intervention. Interview transcripts were iteratively coded by a team, and thematic analysis was used to identify and refine emerging themes. RESULTS: Overall, participants were satisfied with the I-STAND intervention, thought the sedentary behavior goals of the intervention were easy to incorporate, and found the technologies to be helpful additions to (but not substitutes for) health coaching. Barriers to standing more included poor health, ingrained sedentary habits, lack of motivation to change sedentary behavior, and social norms that dictate when it is appropriate to sit/stand. Facilitators to standing more included increased awareness of sitting, a sense of accountability, daily activities that involved standing, social support, and changing ways of interacting in the home environment. Participants reported that the intervention improved physical health, increased energy, increased readiness to engage in physical activity, improved mood, and reduced stress. CONCLUSIONS: The technology-enhanced sedentary behavior reduction intervention was acceptable, easy to incorporate, and had a positive perceived health impact on older adults with obesity. TRIAL REGISTRATION: The I-STAND study was registered at clinicaltrials.gov (ID: NCT02692560 ) February 2016.

Reducing Sedentary Time for Obese Older Adults: Protocol for a Randomized Controlled Trial.

BACKGROUND: Older adults have high rates of obesity and are prone to chronic health conditions. These conditions are in part due to high rates of sedentary time (ST). As such, reducing ST could be an innovative strategy for improving health outcomes among obese older adults. To test this theory, we developed a novel, technology-enhanced intervention to reduce sitting time (I-STAND) and pilot tested it to assess the feasibility, acceptability, and preliminary effects of the intervention on ST and biometric outcomes. OBJECTIVE: The current paper aims to describe the rationale, design, and methods of the I-STAND sitting reduction pilot trial. METHODS: Older adults with obesity (n=60) were recruited from a large health care system and randomized to receive I-STAND or a healthy living intervention. I-STAND combined personal coaching with a technology-enhanced intervention (Jawbone UP band) to cue breaks from sitting. Participants completed self-report and biometric assessments at baseline and 3 months. Additional qualitative results were collected from a subset of I-STAND participants (n=22) to further inform the feasibility and acceptability of the interventions. The primary outcome was total hours of daily sitting time measured by the activPAL device. Secondary outcomes included sit-to-stand transitions, bouts of sitting longer than 30 minutes, physical function, blood pressure, fasting glucose, cholesterol, and depressive symptoms. RESULTS: Study enrollment has ended and data processing is underway. CONCLUSIONS: Data from randomized trials on sitting reduction are needed to inform novel approaches to health promotion among older adults with obesity. Our trial will help fill this gap. The methods used in our study can guide future research on using technology-based devices to assess or prompt sedentary behavior reduction, or those interested in behavioral interventions targeting obese older adults with novel approaches. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02692560; https://clinicaltrials.gov/ct2/show/NCT02692560 (Archived by WebCite at http://www.webcitation.org/6wppLTWAl).

Multimodal Characterization of the Late Effects of Traumatic Brain Injury: A Methodological Overview of the Late Effects of Traumatic Brain Injury Project.

Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer's disease (AD) and Parkinson's disease (PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here, we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional magnetic resonance imaging (MRI), and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole-mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study.

Neuropathological and transcriptomic characteristics of the aged brain.

As more people live longer, age-related neurodegenerative diseases are an increasingly important societal health issue. Treatments targeting specific pathologies such as amyloid beta in Alzheimer's disease (AD) have not led to effective treatments, and there is increasing evidence of a disconnect between traditional pathology and cognitive abilities with advancing age, indicative of individual variation in resilience to pathology. Here, we generated a comprehensive neuropathological, molecular, and transcriptomic characterization of hippocampus and two regions cortex in 107 aged donors (median = 90) from the Adult Changes in Thought (ACT) study as a freely-available resource (http://aging.brain-map.org/). We confirm established associations between AD pathology and dementia, albeit with increased, presumably aging-related variability, and identify sets of co-expressed genes correlated with pathological tau and inflammation markers. Finally, we demonstrate a relationship between dementia and RNA quality, and find common gene signatures, highlighting the importance of properly controlling for RNA quality when studying dementia.

Application of N-of-1 Experiments to Test the Efficacy of Inactivity Alert Features in Fitness Trackers to Increase Breaks from Sitting in Older Adults.

BACKGROUND: Frequent breaks from sitting could improve health. Many commercially available fitness trackers deliver vibration alerts that could be used to cue sitting breaks. As a potentially pragmatic approach to promote frequent breaks from sitting, we tested the efficacy of inactivity alerts among obese older adults, a highly sedentary population. METHODS: We conducted 10 sequential N-of-1 (single-case) experimental ABA trials. Participants (mean age = 68, mean BMI = 35) were monitored for a baseline phase ("A1") followed by an intervention phase ("B"). The intervention was then removed and participants were monitored to test an experimental effect (reversal "A2" phase). Total time in the study was limited to 25 days. During the intervention phase ("B"), participants used fitness trackers to stand up or move every time they received an alert (every 15 or 20 minutes of inactivity). Participants wore activPAL devices to measure breaks from sitting each day. Randomization tests were used to determine whether the number of breaks was significantly higher during the "B" phase than the two "A" phases. RESULTS: Breaks were higher by 7.2 breaks per day during the "B" phase compared to the mean of the "A" phases. Seven out of 10 participants had more sitting breaks during the intervention phase which subsequently decreased during the reversal "A2" phase (combined p-value < .05). CONCLUSION: Inactivity alert features within commercially available devices are efficacious for promoting modest improvements in breaks from sitting among older adults with obesity and could be a simple health-promoting strategy in this population.

Decision-to-Implement Worksheet for Evidence-based Interventions: From the WWAMI Region Practice and Research Network.

BACKGROUND: Health-related scientific discoveries are often not applied in clinical settings after publication, even when recommended by a trusted journal or professional association. This article describes an assessment tool we developed for use by primary care clinicians and practice administrators to evaluate whether to implement recommended evidence-based interventions in their practices. METHODS: We used dissemination and implementation theory to develop a worksheet to guide decision making about whether interventions are suitable for implementation in primary care practice settings. We tested the tool by analyzing how members of a primary care practice-based research network rated 4 evidence-based interventions. RESULTS: The median likelihood of implementation ranged from 2 to 3.5 on a scale of 1 (low) to 5 (high). Raters' level of agreement with statements about 3 intervention characteristics was associated (P < .05) with a higher likelihood of implementation using Spearman rank-order correlation: simple to implement, testable before fully implementing, and modifiable to meet the needs of the practice. Raters found the worksheet helpful in thinking through potential implementation, especially the prompts about modifiability and relevance to the practice's patients and priorities. CONCLUSIONS: The Decision-to-Implement Worksheet provides a new resource for primary care practices that want to assess whether evidence-based interventions are suitable to adopt or adapt to meet their needs.

Participant views on consent in cancer genetics research: preparing for the precision medicine era.

The Precision Medicine Initiative (PMI) has created considerable discussions about research participant issues including re-consent and how and when to incorporate the patient experience into clinical trials. Within the changing landscape of genetic and genomic research, the preferences of participants are lacking yet are needed to inform policy. With the growing use of biobanks intended to support studies, including the national research cohort proposed under the PMI, understanding participant preferences, including re-consent, is a pressing concern. The Participant Issues Project (PIP) addresses this gap, and here we present data on participant attitudes regarding re-consent and broad consent in research studies. PIP study participants came from the Northwest Cancer Genetics Registry and included cancer patients, relatives, and controls. Thirty telephone interviews were conducted and analyzed using content and thematic analysis. Results indicate that in some scenarios, re-consent is needed. Most participants agreed that re-consent was necessary when the study direction changed significantly or a child participant became an adult, but not if the genetic variant changed. Most participants' willingness to participate in research would not be affected if the researcher or institution profited or if a broad consent form were used. Participants emphasized re-consent to provide information and control of the use of their data, now relevant for tailored treatment, while also prioritizing research as important. In the era of precision medicine, it is essential that policy makers consider participant preferences with regard to use of their materials and that participants understand genetic and genomic research and its harms and benefits as well as what broad consent entails, including privacy and re-identification risks.

Motivators and Barriers to Reducing Sedentary Behavior Among Overweight and Obese Older Adults.

PURPOSE OF THE STUDY: To explore individual, social, environmental, and program-related motivators, barriers, and impacts of sedentary behavior (SB) reduction among a group of overweight and obese older adults aged 60 and older. DESIGN AND METHODS: Semistructured interviews were conducted with 24 participants following a SB reduction intervention. Transcripts from these interviews were iteratively coded by a team, and key themes were defined and refined guided by the social-ecological framework. RESULTS: Motivators included the desire to improve health, newly acquired awareness of SB, the ease of incorporating SB reduction into current lifestyle, an adaptable environment, and the use of reminders. Barriers included existing health conditions, enjoyment of sedentary activities, unadaptable environments, fatigue, and difficulty understanding SB reduction as distinct from physical activity (PA). Participants reported impacts on physical and mental health and changes in awareness, exercise, and daily activity. IMPLICATIONS: Although in many ways motivators and barriers to reducing SB are similar to those of PA, SB interventions have special considerations and may ultimately be easier for some individuals to incorporate into their lifestyle.

The Feasibility of Reducing Sitting Time in Overweight and Obese Older Adults.

BACKGROUND: Overweight and obese older adults have high sedentary time. We tested the feasibility and preliminary effects of a sedentary time reduction intervention among adults over age 60 with a body mass index over 27 kg/m2 using a nonrandomized one-arm design. METHODS: Participants (N = 25, mean age = 71.4, mean body mass index = 34) completed an 8-week theory-based intervention targeting reduced total sitting time and increased sit-to-stand transitions. An inclinometer (activPAL) measured the primary outcomes, change in total sitting time and sit-to-stand transitions. Secondary outcomes included physical activity (ActiGraph GT3X+ accelerometer), self-reported sedentary behaviors, physical function (Short Physical Performance Battery), depressive symptoms (8-item Patient Health Questionnaire), quality of life (PROMIS), and study satisfaction. Paired t tests examined pre-post test changes in sitting time, sit-to-stand transitions, and secondary outcomes. RESULTS: Inclinometer measured sitting time decreased by 27 min/day (p < .05) and sit-to-stand transitions increased by 2 per day (p > .05), while standing time increased by 25 min/day (p < .05). Accelerometer measured sedentary time, light-intensity, and moderate-to-vigorous physical activity improved (all p values ≤ .05). Self-reported sitting time, gait speed, and depressive symptoms also improved (all p values < .05). Effect sizes were small. Study satisfaction was high. CONCLUSIONS: Reducing sitting time is feasible, and the intervention shows preliminary evidence of effectiveness among older adults with overweight and obesity. Randomized trials of sedentary behavior reduction in overweight and obese older adults, most of whom have multiple chronic conditions, may be promising.

A report on eight early-stage state and regional projects testing value-based payment.

To help contain health care spending and improve the quality of care, practitioners and policy makers are trying to move away from fee-for-service toward value-based payment, which links providers' reimbursement to the value, rather than the volume, of services delivered. With funding from the Robert Wood Johnson Foundation, eight grantees across the country are designing and implementing value-based payment reform projects. For example, in Salem, Oregon, the Physicians Choice Foundation is testing "Program Oriented Payments," which include incentives for providers who follow a condition-specific program of care designed to meet goals set jointly by patient and provider. In this article we describe the funding rationale and the specific objectives, strategies, progress, and early stages of implementation of the eight projects. We also share some early lessons and identify prerequisites for success, such as ensuring that providers have broad and timely access to data so they can meet patients' needs in cost-effective ways.

Awareness and uptake of direct-to-consumer genetic testing among cancer cases, their relatives, and controls: the Northwest Cancer Genetics Network.

AIMS: To determine if awareness of, interest in, and use of direct-to-consumer (DTC) genetic testing is greater in a sample of high-risk individuals (cancer cases and their relatives), compared to controls. METHODS: Participants were recruited from the Northwest Cancer Genetics Network. A follow-up survey was mailed to participants to assess DTC genetic testing awareness, interest, and use. RESULTS: One thousand two hundred sixty-seven participants responded to the survey. Forty-nine percent of respondents were aware of DTC genetic testing. Of those aware, 19% indicated interest in obtaining and <1% reported having used DTC genetic testing. Additional information supplied by respondents who reported use of DTC genetic tests indicated that 55% of these respondents likely engaged in clinical genetic testing, rather than DTC genetic testing. CONCLUSION: Awareness of DTC genetic testing was greater in our sample of high-risk individuals than in controls and population-based studies. Although interest in and use of these tests among cases in our sample were equivalent to other population-based studies, interest in testing was higher among relatives and people who self-referred for a registry focused on cancer than among cases and controls. Additionally, our results suggest that there may be some confusion about what constitutes DTC genetic testing.