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RNA‐based therapeutics have gained traction for the prevention and treatment of a variety of diseases. However, their fragility and immunogenicity necessitate a drug carrier. Lipid nanoparticles (LNPs) have emerged as the predominant delivery vehicle for RNA therapeutics. An important component of LNPs is the ionizable lipid (IL), which is protonated in the acidic environment of the endosome, prompting cargo release into the cytosol. Currently, there is growing evidence that the structure of IL lipid tails significantly impacts the efficacy of LNP‐mediated mRNA translation. Here, we optimized IL tail length for LNP‐mediated delivery of three different mRNA cargos. Using C12‐200, a gold standard IL, as a model, we designed a library of ILs with varying tail lengths and evaluated their potency in vivo. We demonstrated that small changes in lipophilicity can drastically increase or decrease mRNA translation. We identified that LNPs formulated with firefly luciferase mRNA (1929 base pairs) and C10‐200, an IL with shorter tail lengths than C12‐200, enhance liver transfection by over 10‐fold. Furthermore, different IL tail lengths were found to be ideal for transfection of LNPs encapsulating mRNA cargos of varying sizes. LNPs formulated with erythropoietin (EPO), responsible for stimulating red blood cell production, mRNA (858 base pairs), and the C13‐200 IL led to EPO translation at levels similar to the C12‐200 LNP. The LNPs formulated with Cas9 mRNA (4521 base pairs) and the C9‐200 IL induced over three times the quantity of indels compared with the C12‐200 LNP. Our findings suggest that shorter IL tails may lead to higher transfection of LNPs encapsulating larger mRNAs, and that longer IL tails may be more efficacious for delivering smaller mRNA cargos. We envision that the results of this project can be utilized as future design criteria for the next generation of LNP delivery systems for RNA therapeutics. [ABSTRACT FROM AUTHOR]

mRNA-based gene editing platforms have tremendous promise in the treatment of genetic diseases. However, for this potential to be realized in vivo, these nucleic acid cargos must be delivered safely and effectively to cells of interest. Ionizable lipid nanoparticles (LNPs), the most clinically advanced non-viral RNA delivery system, have been well-studied for the delivery of mRNA but have not been systematically optimized for the delivery of mRNA-based CRISPR-Cas9 platforms. In this study, we investigated the effect of microfluidic and lipid excipient parameters on LNP gene editing efficacy. Through in vitro screening in liver cells, we discovered distinct trends in delivery based on phospholipid, cholesterol, and lipid-PEG structure in LNP formulations. Combination of top-performing lipid excipients produced an LNP formulation that resulted in 3-fold greater gene editing in vitro and facilitated 3-fold greater reduction of a therapeutically-relevant protein in vivo relative to the unoptimized LNP formulation. Thus, systematic optimization of LNP formulation parameters revealed a novel LNP formulation that has strong potential for delivery of gene editors to the liver to treat metabolic disease. [ABSTRACT FROM AUTHOR]

Background: Cognitive behavioral therapy for insomnia (CBT‐I) is the gold‐standard treatment for insomnia disorder in adults. Compared to young adults, older adults have increased risk for the development of conditions associated with chronic pain, which may impact the efficacy of CBT‐I in improving insomnia symptoms in older adults. This study evaluated the effect of participant‐rated pain on sleep‐related outcomes of a supervised, non‐clinician administered CBT‐I program in older adult patients with chronic insomnia disorder. Methods: Secondary analysis was conducted using data from a randomized controlled trial among 106 community‐dwelling older adult veterans (N = 106; mean age 72.1 years, 96% male, 78.3% White, 6.6% Hispanic, 5.7% African American) with chronic (≥3 months) insomnia disorder. Participants engaged in five sessions of manual‐based CBT‐I in individual or group format within one Department of Veterans Affairs healthcare system, provided by non‐clinician "sleep coaches" who had weekly telephone supervision by behavioral sleep medicine specialists. Insomnia symptoms (Insomnia Severity Index), perceived sleep quality (Pittsburgh Sleep Quality Index), fatigue (Flinder's Fatigue Scale), daytime sleepiness (Epworth Sleepiness Scale), and perceived pain severity (items from the Geriatric Pain Measure) were assessed at 4 time points: baseline, one‐week posttreatment, 6‐month follow‐up, and 12‐month follow‐up. Mixed effects models with time invariant and time varying predictors were employed for analyses. Results: CBT‐I improved insomnia symptoms, perceived sleep quality, fatigue, and daytime sleepiness among older veterans with chronic insomnia. Participant‐reported pain was associated with greater improvements in insomnia symptoms following CBT‐I. Pain did not affect improvements in other sleep‐related outcomes (−0.38 ≤ b ≤ 0.07, p > 0.05). Between‐subjects differences in pain, but not within‐subject changes in pain over time, appeared to play a central role in insomnia symptom improvement at posttreatment, with individuals with higher‐than‐average pain showing greater insomnia symptom improvement (ISI score reduction; −0.32 ≤ b ≤ −0.28, p ≤ 0.005). Conclusions: Pain did not meaningfully hinder the effects of CBT‐I on sleep outcomes. Among older veterans with chronic insomnia disorder, individuals with higher pain exhibited slightly greater improvement in insomnia than those with lower levels of pain. These findings suggest that experiencing pain does not impair treatment response and should not preclude older adults with insomnia from being offered CBT‐I. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) monocyte and macrophage therapies are promising solid tumor immunotherapies that can overcome the challenges facing conventional CAR T cell therapy. mRNA lipid nanoparticles (mRNA‐LNPs) offer a viable platform for in situ engineering of CAR monocytes with transient and tunable CAR expression to reduce off‐tumor toxicity and streamline cell manufacturing. However, identifying LNPs with monocyte tropism and intracellular delivery potency is difficult using traditional screening techniques. Here, ionizable lipid design and high‐throughput in vivo screening are utilized to identify a new class of oxidized LNPs with innate tropism and mRNA delivery to monocytes. A library of oxidized (oLNPs) and unoxidized LNPs (uLNPs) is synthesized to evaluate mRNA delivery to immune cells. oLNPs demonstrate notable differences in morphology, ionization energy, and pKa, thereby enhancing delivery to human macrophages, but not T cells. Subsequently, in vivo library screening with DNA barcodes identifies an oLNP formulation, C14‐O2, with innate tropism to monocytes. In a proof‐of‐concept study, the C14‐O2 LNP is used to engineer functional CD19‐CAR monocytes in situ for robust B cell aplasia (45%) in healthy mice. This work highlights the utility of oxidized LNPs as a promising platform for engineering CAR macrophages/monocytes for solid tumor CAR monocyte therapy. [ABSTRACT FROM AUTHOR]

Objective/backgroundTo identify caregiving-related sleep problems and their relationship to mental health and daytime function in female Veterans.ParticipantsFemale Veterans (N = 1,477) from cross-sectional, nationwide, postal survey data.MethodsThe survey respondent characteristics included demographics, comorbidity, physical activity, health, use of sleep medications, and history of sleep apnea. They self-identified caregiving- related sleep problems (i.e., those who had trouble sleeping because of caring for a sick adult, an infant/child, or other respondents). Patient Health Questionnaire (PHQ-4) was used to assess mental health, and daytime function was measured using 11 items of International Classification of Sleep Disorders-2 (ICSD-2).ResultsFemale Veterans with self-identified sleep problems due to caring for a sick adult (n = 59) experienced significantly more symptoms of depression and anxiety (p < 0.001) and impairment in daytime function (e.g., fatigue, daytime sleepiness, loss of concentration, p < 0.001) than those with self-identified sleep problems due to caring for an infant or child (n = 95) or all other respondents (n = 1,323) after controlling for the respondent characteristics.ConclusionsHealthcare providers should pay attention to assessing sleep characteristics of female Veterans with caregiving responsibilities, particularly those caregiving for a sick adult.

STUDY OBJECTIVES: Sleep quality is poor among patients with chronic obstructive pulmonary disease (COPD), and studies show that sleep disturbance is associated with low overall quality of life in this population. We evaluated the impact of patient-reported sleep quality and sleep apnea risk on disease-specific and overall quality of life within patients with COPD enrolled in the SPIROMICS study, after accounting for demographics and COPD disease severity. METHODS: Baseline data from 1341 participants [892 mild/moderate COPD (FEV1 ≥ 50% predicted); 449 severe COPD (FEV1 < 50%)] were used to perform three nested (blocks) regression models to predict quality of life (Short Form-12 mental and physical components and St. Georges Respiratory Questionnaire). Dependent measures used for the nested regressions included the following: Block1: demographics and smoking history; Block 2: disease severity (forced expiratory volume 1 s; 6 min walk test); Block 3: risk for obstructive sleep apnea (OSA; Berlin questionnaire); and Block 4: sleep quality (Pittsburgh Sleep Quality Index [PSQI]). RESULTS: Over half of participants with COPD reported poor sleep quality (Mean PSQI 6.4 ± 3.9; 50% with high risk score on the Berlin questionnaire). In all three nested regression models, sleep quality (Block 4) was a significant predictor of poor quality of life, over and above variables included in blocks 1-3. CONCLUSIONS: Poor sleep quality represents a potentially modifiable risk factor for poor quality of life in patients with COPD, over and above demographics and smoking history, disease severity, and risk for OSA. Improving sleep quality may be an important target for clinical interventions. CLINICAL TRIAL: SPIROMICS. CLINICAL TRIAL URL: http://www2.cscc.unc.edu/spiromics/. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01969344.

OBJECTIVES:This study compared subjective (questionnaire) and objective (actigraphy) sleep assessments, and examined agreement between these methods, in vulnerable older adults participating in a Veterans Administration Adult Day Health Care (ADHC) program. METHODS:59 ADHC participants (95% male, mean age = 78 years) completed sleep questionnaires and 72 continuous hours of wrist actigraphy. Linear regression was used to examine agreement between methods and explore discrepancies in subjective/objective measures. RESULTS:Disturbed sleep was common, yet there was no agreement between subjective and objective sleep assessment methods. Compared with objective measures, one-half of participants reported worse sleep efficiency (SE) on questionnaires while one-quarter over-estimated SE. Participants reporting worse pain had a greater discrepancy between subjective and objective SE. CONCLUSIONS:Vulnerable older adults demonstrated unique patterns of reporting sleep quality when comparing subjective and objective methods. Additional research is needed to better understand how vulnerable older adults evaluate sleep problems. CLINICAL IMPLICATIONS:Objective and subjective sleep measures may represent unique and equally important constructs in this population. Clinicians should consider utilizing both objective and subjective sleep measures to identify individuals who may benefit from behavioral sleep treatments, and future research is needed to develop and validate appropriate sleep assessments for vulnerable older adults.

ObjectivesTo examine relationships between cognitive expectancies about sleep and hypnotics and use of medications commonly used for insomnia (hypnotics).MethodsWe analyzed baseline data from older veterans who met diagnostic criteria for insomnia and were enrolled in a trial comparing CBTI delivered by a supervised, sleep educator to an attention control condition (N = 159; 97% male, mean age 72 years). We classified individuals as hypnotic users (N = 23) vs. non-users (N = 135) based upon medication diaries. Associations between hypnotic status and Dysfunctional Beliefs and Attitudes about Sleep-16 (DBAS) total score (0-10, higher = worse) and two DBAS medication item scores (Item 1: "…better off taking a sleeping pill rather than having a poor night's sleep;" Item 2: "Medication… probably the only solution to sleeplessness"; 0-10, higher = worse) were examined in logistic regression models.ResultsHigher scores on the DBAS medication items (both odds ratios = 1.3; p-values < .001) were significantly associated with hypnotic use. DBAS-16 total score was not associated with hypnotic use.ConclusionCognitive expectancy (dysfunctional beliefs) about hypnotics was associated with hypnotic use in older adults with chronic insomnia disorder.Clinical implicationsStrategies that specifically target dysfunctional beliefs about hypnotics are needed and may impact hypnotic use in older adults.

We examined whether baseline self-reported physical activity is associated with the efficacy of cognitive behavioral therapy for insomnia (CBT-I) in older veterans. Community-dwelling veterans aged 60 years and older with insomnia received CBT-I in a randomized controlled trial. Participants who received active treatment were divided into low and high physical activity based on self-report. Sleep outcomes were measured by sleep diary, questionnaire and wrist actigraphy; collected at baseline, post-treatment, 6-month and 12-month follow-up. Mixed-effects models compared differences between physical activity groups in change in sleep outcome from baseline to each follow-up, and equivalence tests examined if physical activity groups were clinically equal. There were no significant differences in sleep outcomes between physical activity groups. Equivalence tests suggested possible equality in physical activity groups for five of seven sleep outcomes. Efficacy of CBT-I in older veterans was not associated with self-reported physical activity at baseline. Older adults with insomnia who report low levels of physical activity can benefit from CBT-I.

OBJECTIVES:(1) To examine relationships between frequency of nocturia and self-reported sleep quality and objective sleep measures in older women, and (2) to estimate the amount of variation in sleep measures that is specifically attributable to frequency of nocturia. DESIGN AND SETTING:Secondary, cross sectional analysis of the multicenter prospective cohort Study of Osteoporotic Fractures (SOF). PARTICIPANTS:Community-dwelling women aged ≥80 years. MEASUREMENTS:Frequency of nocturia in the previous 12 months, Pittsburgh Sleep Quality Index sleep quality subscale, and actigraphy-measured wake after sleep onset (WASO) and total sleep time (TST). RESULTS:Of 1,520 participants, 25% (n = 392) reported their nocturia frequency was 3-4 times/night and an additional 60% (n = 917) reported their nocturia frequency was 1-2 times/night. More frequent nocturia was associated with poor sleep quality (3-4/night: 26.8% reported fairly bad or very bad sleep quality; 1-2/night: 14.7%; 0/night: 7.7%; P < .001) and longer WASO (3-4/night: 89.8 minutes; 1-2/night: 70.6; 0/night: 55.5; P < .001). In nested regression models, a nocturia frequency of 3-4/night quadrupled the odds of poor sleep quality (odds ratio: 4.26 [95% CI 1.65, 11.01]; P = .003) and was associated with a 37-minute worsening in WASO (95% CI 26.0, 49.0; P < .001). Frequency of nocturia explained an additional 6% variation in WASO, above and beyond demographic, medical/psychiatric conditions, and medication factors (∆R2 = 0.06). CONCLUSIONS:Nocturia is common among octogenarian and nonagenarian women and is independently associated with poor sleep quality and longer wake time at night. Interventions that improve nocturia may be useful in improving sleep quality and wake time at night.

Nanoparticles have been used for engineering composite materials to improve the intrinsic properties and/or add functionalities to pristine polymers. The majority of the studies have focused on the incorporation of spherical nanoparticles within the composite fibers. Herein, we incorporate anisotropic branched-shaped zinc oxide (ZnO) nanoparticles into fibrous scaffolds fabricated by electrospinning. The addition of the branched particles resulted in their protrusion from fibers, mimicking the architecture of a rose stem. We demonstrated that the encapsulation of different-shape particles significantly influences the physicochemical and biological activities of the resultant composite scaffolds. In particular, the branched nanoparticles induced heterogeneous crystallization of the polymeric matrix and enhance the ultimate mechanical strain and strength. Moreover, the three-dimensional (3D) nature of the branched ZnO nanoparticles enhanced adhesion properties of the composite scaffolds to the tissues. In addition, the rose stem-like constructs offered excellent antibacterial activity, while supporting the growth of eukaryote cells.

The 22q11.2 deletion syndrome (22q11.2DS; DiGeorge syndrome/velocardiofacial syndrome) occurs in 1 of 4000 live births, and 60% to 70% of affected individuals have congenital heart disease, ranging from mild to severe. In our cohort of 1472 subjects with 22q11.2DS, a total of 62% (n=906) have congenital heart disease and 36% (n=326) of these have tetralogy of Fallot (TOF), comprising the largest subset of severe congenital heart disease in the cohort. To identify common genetic variants associated with TOF in individuals with 22q11.2DS, we performed a genome-wide association study using Affymetrix 6.0 array and imputed genotype data. In our cohort, TOF was significantly associated with a genotyped single-nucleotide polymorphism (rs12519770, P=2.98×10-8) in an intron of the adhesion GPR98 (G-protein-coupled receptor V1) gene on chromosome 5q14.3. There was also suggestive evidence of association between TOF and several additional single-nucleotide polymorphisms in this region. Some genome-wide significant loci in introns or noncoding regions could affect regulation of genes nearby or at a distance. On the basis of this possibility, we examined existing Hi-C chromatin conformation data to identify genes that might be under shared transcriptional regulation within the region on 5q14.3. There are 6 genes in a topologically associated domain of chromatin with GPR98, including MEF2C (Myocyte-specific enhancer factor 2C). MEF2C is the only gene that is known to affect heart development in mammals and might be of interest with respect to 22q11.2DS. In conclusion, common variants may contribute to TOF in 22q11.2DS and may function in cardiac outflow tract development.

Study objectiveTo test the effectiveness of a 4-week behavioral Sleep Intervention Program (SIP: sleep compression, modified stimulus control, and sleep hygiene) compared to a 4-week information-only control (IC) among older adults attending a VA Adult Day Health Care (ADHC) program in a double-blind, randomized, clinical trial.MethodsForty-two individuals (mean age: 77 years, 93% male) enrolled in a VA ADHC program were randomized to receive SIP or IC. All completed in-person sleep and health assessments at baseline, post-treatment and 4-months follow-up that included 3 days/nights of wrist actigraphy, the Pittsburgh Sleep Quality Index (PSQI), and the Insomnia Severity Index (ISI). Mixed repeated measures analysis was used to compare sleep outcomes at post-treatment and 4-months follow-up, with baseline values as covariates.ResultsSIP participants (n = 21) showed significant improvement on actigraphy sleep efficiency (p = .007), number of nighttime awakenings (p = .016), and minutes awake at night (p = .001) at post-treatment, compared to IC participants (n = 21). Benefits were slightly attenuated but remained significant at 4-month follow-up (all p's < .05). There were no differences in total sleep time between groups. There was significant improvement on PSQI factor 3 (daily disturbances) at 4-month follow-up (p = .016), but no differences were observed between SIP and IC on other PSQI components or ISI scores at post-treatment or 4-month follow-up.ConclusionsA short behavioral sleep intervention may have important benefits in improving objectively measured sleep in older adults participating in ADHC. Future studies are needed to study implementation of this intervention into routine clinical care within ADHC.

ObjectivesInsomnia is a significant public health concern known to particularly impact women and the veteran population; however, rates of insomnia disorder among women veterans are not known.MethodWomen veterans who had received health care at VA Greater Los Angeles Healthcare System between 2008 and 2010 and resided within 25 miles of the facility were sent a postal survey assessing sleep, demographics, and other related patient characteristics.ResultsA total of 660 women (43.1% of potential responders) returned the postal survey and provided sufficient information for insomnia diagnosis. On average, women reported 6.2 hours of sleep per night. The prevalence of insomnia, determined according to diagnostic criteria from the International Classification of Sleep Disorders-2, was 52.3%. Women with insomnia reported more severely disturbed sleep, and more pain, menopausal symptoms, stress/worries, and nightmares compared with women without insomnia. There was a quadratic relationship between age and insomnia with women in their mid-40s, most likely to have insomnia.ConclusionsThis survey study found that insomnia symptoms were endorsed by more than one-half of the women veterans in this sample of VA users, highlighting the critical need for enhanced clinical identification and intervention. Further research is needed to establish national rates of insomnia among women veterans and to improve access to evidence-based treatment of insomnia disorder.

Study objectivesTo examine the usability of positive airway pressure (PAP) devices and its association with PAP adherence among older adults with sleep-disordered breathing.MethodsWe mailed questionnaires to patients aged ≥65 years prescribed PAP therapy during the prior 36 months from two large healthcare systems. Survey participants completed the Usability of Sleep Apnea Equipment-Positive Airway Pressure (USE-PAP) questionnaire, which assessed the usability of their PAP device. Other questionnaire items included demographics and self-rated health. We also abstracted adherence data (mean nightly hours of PAP use available from one site) and interface type from the electronic health record.ResultsFive hundred sixty-four patients completed the survey (response rate = 33%). The mean USE-PAP score (0 = best to 100 = worst) was 20 (SD ± 20). Mean duration of PAP use (available in 189 respondents) was 5.2 hours per night (SD ± 2.0). In a nested regression model predicting nightly hours of PAP use, a 10-point (0.5 SD) increase in USE-PAP score corresponded to a 0.37 hour/night reduction in PAP use. The model including the USE-PAP score explained a significant proportion (R2 = 15%) of the variation in nightly hours of PAP use above and beyond demographics, self-reported health, and interface type (∆R2 = 12%).ConclusionsOur results demonstrate that PAP usability varies among older patients and is associated with PAP adherence, above and beyond other predictors of adherence. These results support measuring and improving PAP usability to further improve PAP adherence for older patients.

PurposeFemale veterans are at high risk for sleep problems, and there is a need to provide effective treatment for this population who experience insomnia. This study's primary goal was to compare the acceptability of medication versus nonmedication treatments for insomnia among female veterans. In addition, we examined the role of patient age, severity of sleep disturbance, and psychiatric symptoms on acceptability of each treatment approach and on the differences in acceptability between these approaches.MethodsA large nationwide postal survey was sent to a random sample of 4000 female veterans who had received health care at a Veterans Administration (VA) facility in the previous 6 months (May 29, 2012-November 28, 2012). A total of 1559 completed surveys were returned. Survey items used for the current analyses included: demographic characteristics, sleep quality, psychiatric symptoms, military service experience, and acceptability of medication and nonmedication treatments for insomnia. For analysis, only ratings of "very acceptable" were used to indicate an interest in the treatment approach (vs ratings of "not at all acceptable," "a little acceptable," "somewhat acceptable," and "no opinion/don׳t know").FindingsIn the final sample of 1538 women with complete data, 57.7% rated nonmedication treatment as very acceptable while only 33.5% rated medication treatment as very acceptable. This difference was statistically significant for the group as a whole and when examining subgroups of patients based on age, sleep quality, psychiatric symptoms, and military experience. The percentage of respondents rating medication treatment as very acceptable was higher for women who were younger, had more severe sleep disturbances, had more psychiatric symptoms, who were not combat exposed, and who had experienced military sexual trauma. By contrast, the percentage of respondents rating nonmedication treatment as very acceptable differed only by age (younger women were more likely to find nonmedication treatment acceptable) and difficulty falling asleep.ImplicationsFemale veterans are more likely to find nonmedication insomnia treatment acceptable compared with medication treatment. Thus, it is important to match these patients with effective behavioral interventions such as cognitive behavioral therapy for insomnia. Efforts to educate providers about these preferences and about the efficacy of cognitive behavioral therapy for insomnia may serve to connect female veterans who have insomnia to the treatment they prefer. These findings also suggest that older female veterans may be less likely to find either approach as acceptable as their younger counterparts.

PurposeObstructive sleep apnea is a prevalent sleep disorder among older adults. Oral appliances are increasingly prescribed as therapy for obstructive sleep apnea. Adherence to oral appliance therapy is highly variable. Based on value-expectancy theory and other social-psychological theories, adherence to oral appliance therapy may be influenced by patients' perceived effectiveness of the therapy, self-efficacy, and availability of social support. We examined these perceptions among older adults with obstructive sleep apnea who were prescribed oral appliance therapy.MethodsWe mailed surveys to all patients aged ≥65 years who had been prescribed oral appliance therapy for obstructive sleep apnea over the prior 36 months at a Veterans Affairs medical center. We examined frequencies of responses to items that assessed perceived effectiveness, self-efficacy, and social support for nightly use of oral appliances from friends, family, or health care staff.FindingsThirty-nine individuals responded (response rate, 30%; mean [SD] age 71.4 [SD 6.3] years; 97% male). Thirty-six percent of the respondents perceived regular use of oral appliance therapy to be effective in managing obstructive sleep apnea; 39% agreed that they felt confident about using oral appliances regularly; 41% felt supported by people in their life in using oral appliance therapy; and 38% agreed that health care staff would help them to use their oral appliance regularly. These rates represented less than half of respondents despite the finding that 65% of patients believed that they would use their oral appliance regularly.ImplicationsAlthough oral appliance therapy is increasingly prescribed for obstructive sleep apnea, only about one third of older adults prescribed it perceived it to be an effective treatment, were confident about oral appliance use, and/or believed that they would receive needed support. Future research is needed to better understand older adults' perceptions so that interventions can be designed to improve the effectiveness of oral appliances, their self-efficacy for using oral appliances, and their social support for this therapy, which may, in turn, improve oral appliance therapy adherence.

Objective: Culturally safe service provision is essential to improving social and emotional wellbeing among Aboriginal and Torres Strait Islander communities, and to eliminating health inequities. Cultural safety is about ensuring that all people have a safe and healing journey through services, regardless of their cultural background. In this project, we aim to (1) understand how Aboriginal and Torres Strait Islander peoples conceptualise cultural safety, and (2) co-design a qualitative interview for the next phase of this project, where we plan to learn about experiences of cultural safety within mental health services. Methods: We conducted six focus groups (in one metro and two regional areas, Western Australia). Following an Aboriginal Participatory Action Research methodology, we yarned with Aboriginal and Torres Strait Islander mental health service users, carers, community members, mental health professionals and Cultural Healers about cultural safety. Results: Participants described a culturally safe service as one where Aboriginal cultural knowledges, life experiences, issues and protocols are understood and acknowledged, and reported that mainstream mental health services are not currently culturally safe. Participants emphasised the importance of building trust, rapport, reciprocity and following appropriate relational processes when designing a qualitative interview for the next phase. Conclusions: A lack of cultural safety in mental health services is likely to contribute to the disparity in outcomes between Aboriginal and Torres Strait Islander peoples and non-Indigenous Australians. Embedding cultural safety into research design allows for authentic community engagement and facilitates knowledge sharing around ways to improve cultural safety in mental health services. [ABSTRACT FROM AUTHOR]

Objectives: Insomnia may contribute to fewer value-consistent choices and less engagement in meaningful life activities. We sought to identify values commonly expressed by women veterans engaged in a trial testing psychological treatment of insomnia disorder. Methods: Seventy-four women veterans (mean age = 48.3 [±13] years), meeting DSM-5 diagnostic criteria for insomnia disorder received an acceptance-based behavioral treatment for insomnia. In the first session, participants responded to questions regarding personal values and the impact of insomnia on those values. Responses were categorized into values domains informed by the Bull's Eye Values survey (level 1 categories) and the Valued Living Questionnaire (level 2 categories). Results: Raters reached 100% agreement after independent coding and adjudication. Level 1 value categories in frequency order were: relationships (n = 68), personal care/health (n = 51), work/education (n = 46), pets (n = 12), and leisure (n = 5). The most frequently reported level 2 value categories were: family (other than marriage/parenting; n = 50), parenting (n = 31), work (n = 31), physical health (n = 30), and spirituality (n = 19). The level 1 value categories impacted by insomnia in frequency order were: personal care/health (n = 65), relationships (n = 58), work/education (n = 46), pets (n = 12), and leisure (n = 5). Conclusions: Women veterans undergoing insomnia treatment highly value relationships and personal care/health, which should be considered patientcentered outcomes of insomnia treatments. [ABSTRACT FROM AUTHOR]

The aim is to pilot a low-touch program for reducing benzodiazepine receptor agonist (BZRA; benzodiazepines, z-drugs) prescriptions among older veterans. Pilot randomized controlled trial consists of 2,009 veterans aged ≥ 65 years who received BZRA prescriptions from a Veterans Health Administration pharmacy (Colorado or Montana) during the prior 18 months. Active: Arm 1 was a mailed brochure about BZRA risks that also included information about a free, online cognitive behavioral therapy for the insomnia (CBTI) program. Arm 2 was a mailed brochure (same as arm 1) and telephone reinforcement call. Control: Arm 3 was a mailed brochure without insomnia treatment information. Active BZRA prescriptions at follow-up (6 and 12 months) were measured. In logistic regression analyses, the odds of BZRA prescription at 6- and 12-month follow-ups were not significantly different for arm 1 or 2 (active) versus arm 3 (control), including models adjusted for demographics and prescription characteristics (p-values >0.36). Although we observed no differences in active BZRA prescriptions, this pilot study provides guidance for conducting a future study, indicating a need for a more potent intervention. A full-scale trial testing an optimized program would provide conclusive results. Mailing information about BZRA risks and CBTI did not affect BZRA prescriptions. [ABSTRACT FROM AUTHOR]

This manuscript offers an overview of 11 disciplinary perspectives on the failed and destructive War on Drugs and the salutary prospects from decriminalizing drug use, including History, African American studies, Journalism, Sociology, Political Science, Cost Accounting, Urban Education, Counseling, Psychology, Nursing, and Public Health. This offers a roadmap for counselor social and political advocacy with drug policy and highlights community collaboration opportunities. [ABSTRACT FROM AUTHOR]