The C terminus of the mycobacterium ESX-1 secretion system substrate ESAT-6 is required for phagosomal membrane damage and virulence.

SignificanceTuberculosis (TB), an ancient disease of humanity, continues to be a major cause of worldwide death. The causative agent of TB, Mycobacterium tuberculosis, and its close pathogenic relative Mycobacterium marinum, initially infect, evade, and exploit macrophages, a major host defense against invading pathogens. Within macrophages, mycobacteria reside within host membrane-bound compartments called phagosomes. Mycobacterium-induced damage of the phagosomal membranes is integral to pathogenesis, and this activity has been attributed to the specialized mycobacterial secretion system ESX-1, and particularly to ESAT-6, its major secreted protein. Here, we show that the integrity of the unstructured ESAT-6 C terminus is required for macrophage phagosomal damage, granuloma formation, and virulence.

Behavioral Change Factors and Retention in Web-Based Interventions for Informal Caregivers of People Living With Dementia: Scoping Review.

BACKGROUND: Web-based interventions aimed at supporting informal caregivers of people living with dementia have the potential to improve caregivers' well-being and psychological health. However, few interventions are widely implemented for this population, and none of the prior reviews have systematically examined the use of behavior change techniques (BCTs), theories, and agents in web-based interventions for informal caregivers of people living with dementia. To better understand this implementation gap, we reviewed the literature to map behavioral factors (BCTs, theories, and agents) deployed in the studies. Furthermore, because there is an emerging consensus that retention could be shaped by participant characteristics and behavioral factors, we explored relationships between these features and retention rates across studies. OBJECTIVE: We pursued 3 objectives: to map behavioral factors involved in the web-based interventions for informal caregivers of people living with dementia; to examine the relationship between behavioral change elements and retention in the studies; and to examine the relationship between participant characteristics (gender, age, and spouse or adult children caregiver proportion) and study retention. METHODS: We conducted a literature review using the following keywords and their corresponding Medical Subject Headings terms: dementia, caregivers, and web-based intervention. The time limits were January 1998 to March 2022. Using the BCTv1 taxonomy, which specifies active behavioral components in interventions, 2 coders collected, summarized, and analyzed the frequency distributions of BCTs. Similarly, they abstracted and analyzed participant characteristics, behavior change theories, behavior change agents, and retention rates in the studies. RESULTS: The average age was 61.5 (SD 7.4) years, and the average proportion of spousal informal caregivers, adult children informal caregivers, and retention rates were 51.2% (SD 24.8%), 44.8% (SD 22%), and 70.4% (SD 17%), respectively. Only 53% (17/32) of the studies used behavior change theories, but 81% (26/32) included behavior change agents. The most common BCTv1 clusters were shaping knowledge and social support. The median number of BCTv1 clusters was 5 (IQR 3). We observed a negative correlation between the proportion of spousal informal caregivers and the retention rate (r=-0.45; P=.02) and between the number of BCTv1 clusters and retention rates (r=-0.47; P=.01). We also found that the proportion of adult children informal caregivers in the study was significantly and positively correlated with the retention rate (r=0.5; P=.03). No other participant characteristics or behavioral factors were associated with retention rates. CONCLUSIONS: We found that almost half of the studies were not informed by behavior change theories. In addition, spousal involvement and a higher number of BCTs were each associated with lower retention rates, while the involvement of adult children caregivers in the study was associated with higher retention. In planning future studies, researchers should consider matching participant characteristics with their intended intervention as the alignment might improve their retention rates.

Outcomes After Tracheostomy in Patients with Severe Acute Brain Injury: A Systematic Review and Meta-Analysis.

OBJECTIVE: To synthesize reported long-term outcomes in patients undergoing tracheostomy after severe acute brain injury (SABI). METHODS: We systematically searched PubMed, EMBASE, and Cochrane Library for studies in English, German, and Spanish between 1990 and 2019, reporting outcomes in patients with SABI who underwent tracheostomy. We adhered to the preferred reporting items for systematic reviews and meta-analyses guidelines and the meta-analyses of observational studies in epidemiology guidelines. We excluded studies reporting on less than 10 patients, mixed populations with other neurological diseases, or studies assessing highly select subgroups defined by age or procedures. Data were extracted independently by two investigators. Results were pooled using random effects modeling. The primary outcome was long-term functional outcome (mRS or GOS) at 6-12 months. Secondary outcomes included hospital and long-term mortality, decannulation rates, and discharge home rates. RESULTS: Of 1405 studies identified, 61 underwent full manuscript review and 19 studies comprising 35,362 patients from 10 countries were included in the meta-analysis. The primary outcome was available from five studies with 451 patients. At 6-12 months, about one-third of patients (30%; 95% confidence interval [CI] 17-48) achieved independence, and about one-third survived in a dependent state (36%, 95% CI 28-46%). The pooled short-term mortality for 19,048 patients was 12%, (95% CI 9-17%) with no significant difference between stroke (10%) and TBI patients (13%), and the pooled long-term mortality was 21% (95% CI 11-36). Decannulation occurred in 79% (95% CI 51-93%) of survivors. Heterogeneity was high for most outcome assessments (I2 > 75%). CONCLUSIONS: Our findings suggest that about one in three patients with SABI who undergo tracheostomy may eventually achieve independence. Future research is needed to understand the reasons for the heterogeneity between studies and to identify those patients with promising outcomes as well as factors influencing outcome.

A scoping review of new implementations of interprofessional bedside rounding models to improve teamwork, care, and outcomes in hospitals.

Poor communication within healthcare teams occurs commonly, contributing to inefficiency, medical errors, conflict, and other adverse outcomes. Interprofessional bedside rounds (IBR) are a promising model that brings two or more health professions together with patients and families as part of a consistent, team-based routine to share information and collaboratively arrive at a daily plan of care. The purpose of this systematic scoping review was to investigate the breadth and quality of IBR literature to identify and describe gaps and opportunities for future research. We followed an adapted Arksey and O'Malley Framework and PRISMA scoping review guidelines. PubMed, CINAHL, PsycINFO, and Embase were systematically searched for key IBR words and concepts through June 2020. Seventy-nine articles met inclusion criteria and underwent data abstraction. Study quality was assessed using the Mixed Methods Assessment Tool. Publications in this field have increased since 2014, and the majority of studies reported positive impacts of IBR implementation across an array of team, patient, and care quality/delivery outcomes. Despite the preponderance of positive findings, great heterogeneity, and a reliance on quantitative non-randomized study designs remain in the extant research. A growing number of interventions to improve safety, quality, and care experiences in hospital settings focus on redesigning daily inpatient rounds. Limited information on IBR characteristics and implementation strategies coupled with widespread variation in terminology, study quality, and design create challenges in assessing the effectiveness of models of rounds and optimal implementation strategies. This scoping review highlights the need for additional studies of rounding models, implementation strategies, and outcomes that facilitate comparative research.

Reactions to COVID-19, information and technology use, and social connectedness among older adults with pre-frailty and frailty.

The emergence of Coronavirus Disease 2019 (COVID-19) and social distancing measures has serious implications, particularly those age 65 and older. We performed a qualitative analysis of online discussion data generated by older adults with pre-frailty and frailty while subject to a state stay-at-home order. We provided participants with prompts relating to the public health emergency, collected 60 posts, and analyzed them using a general inductive analytic method. We report on: (1) the impact of the pandemic on daily life; (2) preparedness, perceptions, and behavior; (3) information and technology use; and (4) social impacts. Participants' lives of changed in many ways, including the adoption of precautionary measures and altered daily routines. Participants experienced negative emotional consequences including stress, worry, and anxiety. Information and technology use kept participants informed and connected. Participants reported varying degrees of preparedness. Our study findings provide insight into ways to support vulnerable older adults in pandemic circumstances.

Mycobacterial ESX-1 secretion system mediates host cell lysis through bacterium contact-dependent gross membrane disruptions.

Mycobacterium tuberculosis and Mycobacterium marinum are thought to exert virulence, in part, through their ability to lyse host cell membranes. The type VII secretion system ESX-1 [6-kDa early secretory antigenic target (ESAT-6) secretion system 1] is required for both virulence and host cell membrane lysis. Both activities are attributed to the pore-forming activity of the ESX-1-secreted substrate ESAT-6 because multiple studies have reported that recombinant ESAT-6 lyses eukaryotic membranes. We too find ESX-1 of M. tuberculosis and M. marinum lyses host cell membranes. However, we find that recombinant ESAT-6 does not lyse cell membranes. The lytic activity previously attributed to ESAT-6 is due to residual detergent in the preparations. We report here that ESX-1-dependent cell membrane lysis is contact dependent and accompanied by gross membrane disruptions rather than discrete pores. ESX-1-mediated lysis is also morphologically distinct from the contact-dependent lysis of other bacterial secretion systems. Our findings suggest redirection of research to understand the mechanism of ESX-1-mediated lysis.

An Integrative Review of Nurse-to-Nurse Incivility, Hostility, and Workplace Violence: A GPS for Nurse Leaders.

Bullying, lateral violence, and incivility are real phenomena in the nursing workplace and remain widespread across all care settings. The American Nurses Association recommends zero tolerance for any form of violence from any source and adopting evidence-based strategies to mitigate incivility and bullying. This integrative review examined the evidence regarding nurse-to-nurse incivility, bullying, and workplace violence for 4 nurse populations-student, new graduate, experienced, and academic faculty. Ganong and Cooper's review methodology structured the evidence synthesis. Twenty-one articles pertained to the clinical inquiry. The evidence consistently described the incidents, instigators, and targets of incivility/bullying, which contributes to 84 negative academic, organizational, work unit, and personal outcomes. A safe and just organizational culture demands a comprehensive systems-level approach to create civil environments. The evidence-based structures, processes, and recommendations serve as a Global Positioning System for practice and academic leaders to use in creating a healthy work environment where nurses are encouraged and empowered. The critical choices by nurse leaders will determine not only the future of 21st century professional nursing practice but how the public views the nursing profession for many years to come.

XoxF Acts as the Predominant Methanol Dehydrogenase in the Type I Methanotroph Methylomicrobium buryatense.

UNLABELLED: Many methylotrophic taxa harbor two distinct methanol dehydrogenase (MDH) systems for oxidizing methanol to formaldehyde: the well-studied calcium-dependent MxaFI type and the more recently discovered lanthanide-containing XoxF type. MxaFI has traditionally been accepted as the major functional MDH in bacteria that contain both enzymes. However, in this study, we present evidence that, in a type I methanotroph, Methylomicrobium buryatense, XoxF is likely the primary functional MDH in the environment. The addition of lanthanides increases xoxF expression and greatly reduces mxa expression, even under conditions in which calcium concentrations are almost 100-fold higher than lanthanide concentrations. Mutations in genes encoding the MDH enzymes validate our finding that XoxF is the major functional MDH, as XoxF mutants grow more poorly than MxaFI mutants under unfavorable culturing conditions. In addition, mutant and transcriptional analyses demonstrate that the lanthanide-dependent MDH switch operating in methanotrophs is mediated in part by the orphan response regulator MxaB, whose gene transcription is itself lanthanide responsive. IMPORTANCE: Aerobic methanotrophs, bacteria that oxidize methane for carbon and energy, require a methanol dehydrogenase enzyme to convert methanol into formaldehyde. The calcium-dependent enzyme MxaFI has been thought to primarily carry out methanol oxidation in methanotrophs. Recently, it was discovered that XoxF, a lanthanide-containing enzyme present in most methanotrophs, can also oxidize methanol. In a methanotroph with both MxaFI and XoxF, we demonstrate that lanthanides transcriptionally control genes encoding the two methanol dehydrogenases, in part by controlling expression of the response regulator MxaB. Lanthanides are abundant in the Earth's crust, and we demonstrate that micromolar amounts of lanthanides are sufficient to suppress MxaFI expression. Thus, we present evidence that XoxF acts as the predominant methanol dehydrogenase in a methanotroph.

Electroporation-Based Genetic Manipulation in Type I Methanotrophs.

Methane is becoming a major candidate for a prominent carbon feedstock in the future, and the bioconversion of methane into valuable products has drawn increasing attention. To facilitate the use of methanotrophic organisms as industrial strains and accelerate our ability to metabolically engineer methanotrophs, simple and rapid genetic tools are needed. Electroporation is one such enabling tool, but to date it has not been successful in a group of methanotrophs of interest for the production of chemicals and fuels, the gammaproteobacterial (type I) methanotrophs. In this study, we developed electroporation techniques with a high transformation efficiency for three different type I methanotrophs: Methylomicrobium buryatense 5GB1C, Methylomonas sp. strain LW13, and Methylobacter tundripaludum 21/22. We further developed this technique in M. buryatense, a haloalkaliphilic aerobic methanotroph that demonstrates robust growth with a high carbon conversion efficiency and is well suited for industrial use for the bioconversion of methane. On the basis of the high transformation efficiency of M. buryatense, gene knockouts or integration of a foreign fragment into the chromosome can be easily achieved by direct electroporation of PCR-generated deletion or integration constructs. Moreover, site-specific recombination (FLP-FRT [FLP recombination target] recombination) and sacB counterselection systems were employed to perform marker-free manipulation, and two new antibiotics, zeocin and hygromycin, were validated to be antibiotic markers in this strain. Together, these tools facilitate the rapid genetic manipulation of M. buryatense and other type I methanotrophs, promoting the ability to perform fundamental research and industrial process development with these strains.

Genetic tools for the industrially promising methanotroph Methylomicrobium buryatense.

Aerobic methanotrophs oxidize methane at ambient temperatures and pressures and are therefore attractive systems for methane-based bioconversions. In this work, we developed and validated genetic tools for Methylomicrobium buryatense, a haloalkaliphilic gammaproteobacterial (type I) methanotroph. M. buryatense was isolated directly on natural gas and grows robustly in pure culture with a 3-h doubling time, enabling rapid genetic manipulation compared to many other methanotrophic species. As a proof of concept, we used a sucrose counterselection system to eliminate glycogen production in M. buryatense by constructing unmarked deletions in two redundant glycogen synthase genes. We also selected for a more genetically tractable variant strain that can be conjugated with small incompatibility group P (IncP)-based broad-host-range vectors and determined that this capability is due to loss of the native plasmid. These tools make M. buryatense a promising model system for studying aerobic methanotroph physiology and enable metabolic engineering in this bacterium for industrial biocatalysis of methane.

Bioreactor performance parameters for an industrially-promising methanotroph Methylomicrobium buryatense 5GB1.

BACKGROUND: Methane is a feedstock of interest for the future, both from natural gas and from renewable biogas sources. Methanotrophic bacteria have the potential to enable commercial methane bioconversion to value-added products such as fuels and chemicals. A strain of interest for such applications is Methylomicrobium buryatense 5GB1, due to its robust growth characteristics. However, to take advantage of the potential of this methanotroph, it is important to generate comprehensive bioreactor-based datasets for different growth conditions to compare bioprocess parameters. RESULTS: Datasets of growth parameters, gas utilization rates, and products (total biomass, extracted fatty acids, glycogen, excreted acids) were obtained for cultures of M. buryatense 5GB1 grown in continuous culture under methane limitation and O2 limitation conditions. Additionally, experiments were performed involving unrestricted batch growth conditions with both methane and methanol as substrate. All four growth conditions show significant differences. The most notable changes are the high glycogen content and high formate excretion for cells grown on methanol (batch), and high O2:CH4 utilization ratio for cells grown under methane limitation. CONCLUSIONS: The results presented here represent the most comprehensive published bioreactor datasets for a gamma-proteobacterial methanotroph. This information shows that metabolism by M. buryatense 5GB1 differs significantly for each of the four conditions tested. O2 limitation resulted in the lowest relative O2 demand and fed-batch growth on methane the highest. Future studies are needed to understand the metabolic basis of these differences. However, these results suggest that both batch and continuous culture conditions have specific advantages, depending on the product of interest.

Genome-scale metabolic reconstructions and theoretical investigation of methane conversion in Methylomicrobium buryatense strain 5G(B1).

BACKGROUND: Methane-utilizing bacteria (methanotrophs) are capable of growth on methane and are attractive systems for bio-catalysis. However, the application of natural methanotrophic strains to large-scale production of value-added chemicals/biofuels requires a number of physiological and genetic alterations. An accurate metabolic model coupled with flux balance analysis can provide a solid interpretative framework for experimental data analyses and integration. RESULTS: A stoichiometric flux balance model of Methylomicrobium buryatense strain 5G(B1) was constructed and used for evaluating metabolic engineering strategies for biofuels and chemical production with a methanotrophic bacterium as the catalytic platform. The initial metabolic reconstruction was based on whole-genome predictions. Each metabolic step was manually verified, gapfilled, and modified in accordance with genome-wide expression data. The final model incorporates a total of 841 reactions (in 167 metabolic pathways). Of these, up to 400 reactions were recruited to produce 118 intracellular metabolites. The flux balance simulations suggest that only the transfer of electrons from methanol oxidation to methane oxidation steps can support measured growth and methane/oxygen consumption parameters, while the scenario employing NADH as a possible source of electrons for particulate methane monooxygenase cannot. Direct coupling between methane oxidation and methanol oxidation accounts for most of the membrane-associated methane monooxygenase activity. However the best fit to experimental results is achieved only after assuming that the efficiency of direct coupling depends on growth conditions and additional NADH input (about 0.1-0.2 mol of incremental NADH per one mol of methane oxidized). The additional input is proposed to cover loss of electrons through inefficiency and to sustain methane oxidation at perturbations or support uphill electron transfer. Finally, the model was used for testing the carbon conversion efficiency of different pathways for C1-utilization, including different variants of the ribulose monophosphate pathway and the serine cycle. CONCLUSION: We demonstrate that the metabolic model can provide an effective tool for predicting metabolic parameters for different nutrients and genetic perturbations, and as such, should be valuable for metabolic engineering of the central metabolism of M. buryatense strains.

Do mycobacteria produce endospores?

The genus Mycobacterium, which is a member of the high G+C group of Gram-positive bacteria, includes important pathogens, such as M. tuberculosis and M. leprae. A recent publication in PNAS reported that M. marinum and M. bovis bacillus Calmette-Guérin produce a type of spore known as an endospore, which had been observed only in the low G+C group of Gram-positive bacteria. Evidence was presented that the spores were similar to endospores in ultrastructure, in heat resistance and in the presence of dipicolinic acid. Here, we report that the genomes of Mycobacterium species and those of other high G+C Gram-positive bacteria lack orthologs of many, if not all, highly conserved genes diagnostic of endospore formation in the genomes of low G+C Gram-positive bacteria. We also failed to detect the presence of endospores by light microscopy or by testing for heat-resistant colony-forming units in aged cultures of M. marinum. Finally, we failed to recover heat-resistant colony-forming units from frogs chronically infected with M. marinum. We conclude that it is unlikely that Mycobacterium is capable of endospore formation.

Digital health interventions to support family caregivers: An updated systematic review.

Objective: Chronic diseases are the leading causes of death and disability in the U.S., and disease management largely falls onto patients' family caregivers. The long-term burden and stress of caregiving negatively impact caregivers' well-being and ability to provide care. Digital health interventions have the potential to support caregivers. This article aims to provide an updated review of interventions using digital health tools to support family caregivers and the scope of the Human-Centered Design (HCD) approaches. Methods: We conducted a systematic search on July 2019 and January 2021 in PubMed, CINAHL, Embase, Cochrane Library, PsycINFO, ERIC, and ACM Digital Library, limiting to 2014-2021 to identify family caregiver interventions assisted by modern technologies. The Mixed Methods Appraisal Tool and the Grading of Recommendations Assessment, Development and Evaluation were used to evaluate the articles. Data were abstracted and evaluated using Rayyan and Research Electronic Data Capture. Results: We identified and reviewed 40 studies from 34 journals, 10 fields, and 19 countries. Findings included patients' conditions and relationships with family caregivers, how the technology is used to deliver the intervention, HCD methods, theoretical frameworks, components of the interventions, and family caregiver health outcomes. Conclusion: This updated and expanded review revealed that digitally enhanced health interventions were robust at providing high-quality assistance and support to caregivers by improving caregiver psychological health, self-efficacy, caregiving skills, quality of life, social support, and problem-coping abilities. Health professionals need to include informal caregivers as an essential component when providing care to patients. Future research should include more marginalized caregivers from diverse backgrounds, improve the accessibility and usability of the technology tools, and tailor the intervention to be more culturally and linguistically sensitive.

Structurally diverse natural products that cause potassium leakage trigger multicellularity in Bacillus subtilis.

We report a previously undescribed quorum-sensing mechanism for triggering multicellularity in Bacillus subtilis. B. subtilis forms communities of cells known as biofilms in response to an unknown signal. We discovered that biofilm formation is stimulated by a variety of small molecules produced by bacteria--including the B. subtilis nonribosomal peptide surfactin--that share the ability to induce potassium leakage. Natural products that do not cause potassium leakage failed to induce multicellularity. Small-molecule-induced multicellularity was prevented by the addition of potassium, but not sodium or lithium. Evidence is presented that potassium leakage stimulates the activity of a membrane protein kinase, KinC, which governs the expression of genes involved in biofilm formation. We propose that KinC responds to lowered intracellular potassium concentration and that this is a quorum-sensing mechanism that enables B. subtilis to respond to related and unrelated bacteria.

Patient Digital Health Technologies to Support Primary Care Across Clinical Contexts: Survey of Primary Care Providers, Behavioral Health Consultants, and Nurses.

BACKGROUND: The acceptance of digital health technologies to support patient care for various clinical conditions among primary care providers and staff has not been explored. OBJECTIVE: The purpose of this study was to explore the extent of potential differences between major groups of providers and staff in primary care, including behavioral health consultants (BHCs; eg, psychologists, social workers, and counselors), primary care providers (PCPs; eg, physicians and nurse practitioners), and nurses (registered nurses and licensed practical nurses) in the acceptance of various health technologies (ie, mobile apps, wearables, live video, phone, email, instant chats, text messages, social media, and patient portals) to support patient care across a variety of clinical situations. METHODS: We surveyed 151 providers (51 BHCs, 52 PCPs, and 48 nurses) embedded in primary care clinics across the United States who volunteered to respond to a web-based survey distributed in December 2020 by a large health care market research company. Respondents indicated the technologies they consider appropriate to support patients' health care needs across the following clinical contexts: acute and chronic disease, medication management, health-promoting behaviors, sleep, substance use, and common and serious mental health conditions. We used descriptive statistics to summarize the distribution of demographic characteristics by provider type. We used contingency tables to compile summaries of the proportion of provider types endorsing each technology within and across clinical contexts. This study was exploratory in nature, with the intent to inform future research. RESULTS: Most of the respondents were from urban and suburban settings (125/151, 82.8%), with 12.6% (n=19) practicing in rural or frontier settings and 4.6% (n=7) practicing in rural-serving clinics. Respondents were dispersed across the United States, including the Northeast (31/151, 20.5%), Midwest (n=32, 21.2%), South (n=49, 32.5%), and West (n=39, 25.8%). The highest acceptance for technologies across clinical contexts was among BHCs (32/51, 63%) and PCPs (30/52, 58%) for live video and among nurses for mobile apps (30/48, 63%). A higher percentage of nurses accepted all other technologies relative to BHCs and PCPs. Similarly, relative to other groups, PCPs indicated lower levels of acceptance. Within clinical contexts, the highest acceptance rates were reported among 80% (41/51) of BHCs and 69% (36/52) of PCPs endorsing live video for common mental health conditions and 75% (36/48) of nurses endorsing mobile apps for health-promoting behaviors. The lowest acceptance across providers was for social media in the context of medication management (9.3% [14/151] endorsement across provider type). CONCLUSIONS: The survey suggests potential differences in the way primary care clinicians and staff envision using technologies to support patient care. Future work must attend to reasons for differences in the acceptance of various technologies across providers and clinical contexts. Such an understanding will help inform appropriate implementation strategies to increase acceptability and gain greater adoption of appropriate technologies across conditions and patient populations.

Virtual Intervention for Caregivers of Persons With Lewy Body Dementia: Pilot Quasi-Experimental Single-Arm Study.

BACKGROUND: Compared to other types of dementia, family caregivers of people with Lewy body dementia (LBD) report higher stress levels and more severe depressive symptoms. Although several digital support interventions for caregivers of persons with dementia exist, few target LBD specifically or leverage a fully remote and asynchronous approach suitable for pandemic circumstances. OBJECTIVE: We performed a pilot evaluation of a digital intervention designed to help caregivers of people with LBD address challenges they have experienced, with the end goal of reducing psychological distress in this population. METHODS: We recruited 15 family caregivers of people with LBD to participate in the quasi-experimental, single-arm, mixed methods study titled Virtual Online Communities for Aging Life Experience-Lewy Body Dementia (VOCALE-LBD). The study offers an 8-week web-based intervention that uses a digital discussion platform and involves moderation, peer-to-peer support, didactic training, and problem-solving skill enactment. RESULTS: Participants' baseline characteristics were the following: mean age 66 (SD 8) years; 14 of 15 (93%) of them were female; all (15/15, 100%) were White; and 8 (53%) of them had at least a postgraduate degree. Throughout the intervention, participants engaged in weekly web-based discussions, generating a total of 434 posts (average 4 posts per week). Attrition was 20% (3/15). Upon study exit, participants showed the following average improvements: 3.0 (SD 6.0) in depression, 8.3 (SD 16.7) in burden, 2.9 (SD 6.8) in stress, and 0.3 (SD 0.8) in loneliness. When looking at the proportion of participants with clinically significant improvement versus those with a worsening of ≥0.5 SD for each outcome, we observed net improvements of 50% (6/12), 33% (4/12), 25% (3/12), and 25% (3/12) in depression, loneliness, burden, and stress, respectively. In terms of the benefits of participation, participants reported that participation helped them "a great deal" to (1) improve their understanding of LBD (9/12, 75%), (2) gain confidence in dealing with difficult behaviors of the care recipient (6/12, 50%), and (3) improve in one's abilities to provide care to the care recipient (4/12, 33%). CONCLUSIONS: The study generated promising feasibility and preliminary efficacy data for a low-cost, web-based intervention designed for caregivers of persons with LBD. Though the study was not powered for significance, we observed nominal average and net improvements in important psychological outcomes. Moreover, many caregivers reported that study participation helped them better understand the disease, feel more confident in dealing with difficult behaviors of the care recipient, and improve their ability to care for the care recipient. If validated in future studies, the intervention could be an accessible, on-demand resource for caregivers, enabling them to engage in moderated remote discussions with peers at their own convenience in terms of location, time of the day, and frequency.

PICO: What it is and what it is not.

AIM: To assess the role and effectiveness of the mnemonic PICO (Population, Intervention, Comparator and Outcome) in evidence-based practice (EBP) pedagogy. BACKGROUND: The mnemonic "PICO" is a well-established tool in nursing EBP pedagogy. Nevertheless, application of this tool in nursing curricula is not currently supported by evidence of its effectiveness. Further, there are reports that PICO as a tool is unhelpful in the classroom. DESIGN/METHODS: We reviewed the literature on PICO; specifically, the mnemonic's origin, purpose, and effectiveness in practice. RESULTS: Our analysis reveals that PICO is limited in terms of its effectiveness and scope of inquiry. CONCLUSION: A reevaluation of PICO's role in nursing pedagogy is essential. To start, we propose a de-emphasis on PICO as an exclusive or preferred tool, and an emphasis on critical evaluation of the literature, and the whole of the EBP process. We propose a search for more effective methods to improve matching native clinical questions to the retrieval of data that informs patient care.

Promoting Problem Solving About Health Management: A Mixed-Methods Pilot Evaluation of a Digital Health Intervention for Older Adults With Pre-Frailty and Frailty.

Background: There is a need for interventions to promote health management of older adults with pre-frailty and frailty. Technology poses promising solutions, but questions exist about effective delivery. Objectives: We present the results of a mixed-methods pilot evaluation of Virtual Online Communities for Older Adults (VOCALE), an 8-week intervention conducted in the northwestern United States, in which participants shared health-related experiences and applied problem solving skills in a Facebook group. Methods: We performed a mixed-methods process evaluation, integrating quantitative and qualitative data, to characterize the intervention and its effects. We focus on four areas: health-related measures (health literacy and self-efficacy), participation, problem solving skills enacted, and subjective feedback. Results: Eight older adults with pre-frailty and frailty (age = 82.7 ± 6.6 years) completed the study. There was an upward trend in health literacy and health self-efficacy post-intervention. Participants posted at least two times per week. Content analysis of 210 posts showed participants were able to apply the problem solving skills taught, and exit interviews showed participants' increased awareness of the need to manage health, and enjoyment in learning about others. Conclusion: This mixed-methods evaluation provides insight into feasibility and design considerations for online interventions to promote health management among vulnerable older adults.

Association of Alternative Payment and Delivery Models With Outcomes for Mental Health and Substance Use Disorders: A Systematic Review.

Importance: Health care spending in the United States continues to grow. Mental health and substance use disorders (MH/SUDs) are prevalent and associated with worse health outcomes and higher health care spending; alternative payment and delivery models (APMs) have the potential to facilitate higher quality, integrated, and more cost-effective MH/SUD care. Objective: To systematically review and summarize the published literature on populations and MH/SUD conditions examined by APM evaluations and the associations of APMs with MH/SUD outcomes. Evidence Review: A literature search of MEDLINE, PsychInfo, Scopus, and Business Source was conducted from January 1, 1997, to May 17, 2019, for publications examining APMs for MH/SUD services, assessing at least 1 MH/SUD outcome, and having a comparison group. A total of 27 articles met these criteria, and each was classified according to the Health Care Payment Learning and Action Network's APM framework. Strength of evidence was graded using a modified Oxford Centre for Evidence-Based Medicine framework. Findings: The 27 included articles evaluated 17 APM implementations that spanned 3 Health Care Payment Learning and Action Network categories and 6 subcategories, with no single category predominating the literature. APMs varied with regard to their assessed outcomes, funding sources, target populations, and diagnostic focuses. The APMs were primarily evaluated on their associations with process-of-care measures (15 [88.2%]), followed by utilization (11 [64.7%]), spending (9 [52.9%]), and clinical outcomes (5 [29.4%]). Medicaid and publicly funded SUD programs were most common, with each representing 7 APMs (41.2%). Most APMs focused on adults (11 [64.7%]), while fewer (2 [11.8%]) targeted children or adolescents. More than half of the APMs (9 [52.9%]) targeted populations with SUD, while 4 (23.5%) targeted MH populations, and the rest targeted MH/SUD broadly defined. APMs were most commonly associated with improvements in MH/SUD process-of-care outcomes (12 of 15 [80.0%]), although they were also associated with lower spending (4 of 8 [50.0%]) and utilization (5 of 11 [45.5%]) outcomes, suggesting gains in value from APMs. However, clinical outcomes were rarely measured (5 APMs [29.4%]). A total of 8 APMs (47.1%) assessed for gaming (ie, falsification of outcomes because of APM incentives) and adverse selection, with 1 (12.5%) showing evidence of gaming and 3 (37.5%) showing evidence of adverse selection. Other than those assessing accountable care organizations, few studies included qualitative evaluations. Conclusions and Relevance: In this study, APMs were associated with improvements in process-of-care outcomes, reductions in MH/SUD utilization, and decreases in spending. However, these findings cannot fully substitute for assessments of clinical outcomes, which have rarely been evaluated in this context. Additionally, this systematic review identified some noteworthy evidence for gaming and adverse selection, although these outcomes have not always been duly measured or analyzed. Future research is needed to better understand the varied qualitative experiences across APMs, their successful components, and their associations with clinical outcomes among diverse populations and settings.