Development of Inhalable ATRA-Loaded PLGA Nanoparticles as Host-Directed Immunotherapy against Tuberculosis.

Developing new effective treatment strategies to overcome the rise in multi-drug resistant tuberculosis cases (MDR-TB) represents a global challenge. A host-directed therapy (HDT), acting on the host immune response rather than Mtb directly, could address these resistance issues. We developed an HDT for targeted TB treatment, using All Trans Retinoic Acid (ATRA)-loaded nanoparticles (NPs) that are suitable for nebulization. Efficacy studies conducted on THP-1 differentiated cells infected with the H37Ra avirulent Mycobacterium tuberculosis (Mtb) strain, have shown a dose-dependent reduction in H37Ra growth as determined by the BACT/ALERT® system. Confocal microscopy images showed efficient and extensive cellular delivery of ATRA-PLGA NPs into THP-1-derived macrophages. A commercially available vibrating mesh nebulizer was used to generate nanoparticle-loaded droplets with a mass median aerodynamic diameter of 2.13 µm as measured by cascade impaction, and a volumetric median diameter of 4.09 µm as measured by laser diffraction. In an adult breathing simulation experiment, 65.1% of the ATRA PLGA-NP dose was inhaled. This targeted inhaled HDT could offer a new adjunctive TB treatment option that could enhance current dosage regimens leading to better patient prognosis and a decreasing incidence of MDR-TB.

A Protocol to Assess Adult Outcomes at 30 Years Following Preterm Birth.

BACKGROUND: Among the most intense adversity experiences for infants is premature birth. Early birth marks the beginning of a life course that broadly affects families, healthcare, education, social systems, and the survivors themselves. For many, the transition to adulthood is challenging and often hampered by cognitive, physical and mental health, and motor and independence difficulties. OBJECTIVES: The aim of this study was to share a comprehensive protocol of a 10th follow-up study of premature infants in their 30s. The protocol accounts for stress during the neonatal period, the cumulative context (risk and protection) of development, biological and epigenetic mechanisms, and individual resilience. METHODS: The prospective, five-group longitudinal design includes 215 term-born and preterm-born individuals with various neonatal morbidities at ages 30-35 years. Adult outcomes include health, adaptive, executive function, work, and social competence. Novel measures are four system indicators of allostatic load (AL) and epigenetics. Contextual measures include socioeconomic risk and individual resilience. All measures were selected based on coherence with constructs of the scientific aims, strong psychometrics, continuity for repeated measures, and minimal subject burden. Objective assessments include body composition imaging, exercise testing, blood and saliva collection, and actigraphy. The two-phase protocol takes approximately 8 hours. DISCUSSION: After an 11-month COVID-19 pause, participant response has been strong. As of May 2022, 75 participants have completed the full protocol, and 99 have consented to participate. When socioeconomic risk is controlled, we hypothesize that life course trajectories in physical and psychological health, adaptive function, and executive function will differ between term and preterm neonatal morbidity groups. AL will vary across groups and contribute to outcomes. We expect proximal protection and resilience to mediate the cumulative medical and socioeconomic risk and AL. Epigenome-wide DNA methylation, with estimates of age acceleration, will be examined across groups and explored in longitudinal associations with medical risk, socioeconomic status, and protection. To our knowledge, this is the only U.S. study of premature infants aged 30-35 years. With millions of preterm-born individuals reaching adulthood, the protocol incorporates molecular and genetic biomarkers in a life course developmental examination to inform the timing and content of interventions.

The Development of Videoconference-Based Support for People Living With Rare Dementias and Their Carers: Protocol for a 3-Phase Support Group Evaluation.

BACKGROUND: People living with rarer dementias face considerable difficulty accessing tailored information, advice, and peer and professional support. Web-based meeting platforms offer a critical opportunity to connect with others through shared lived experiences, even if they are geographically dispersed, particularly during the COVID-19 pandemic. OBJECTIVE: We aim to develop facilitated videoconferencing support groups (VSGs) tailored to people living with or caring for someone with familial or sporadic frontotemporal dementia or young-onset Alzheimer disease, primary progressive aphasia, posterior cortical atrophy, or Lewy body dementia. This paper describes the development, coproduction, field testing, and evaluation plan for these groups. METHODS: We describe a 3-phase approach to development. First, information and knowledge were gathered as part of a coproduction process with members of the Rare Dementia Support service. This information, together with literature searches and consultation with experts by experience, clinicians, and academics, shaped the design of the VSGs and session themes. Second, field testing involved 154 Rare Dementia Support members (people living with dementia and carers) participating in 2 rounds of facilitated sessions across 7 themes (health and social care professionals, advance care planning, independence and identity, grief and loss, empowering your identity, couples, and hope and dementia). Third, a detailed evaluation plan for future rounds of VSGs was developed. RESULTS: The development of the small groups program yielded content and structure for 9 themed VSGs (the 7 piloted themes plus a later stages program and creativity club for implementation in rounds 3 and beyond) to be delivered over 4 to 8 sessions. The evaluation plan incorporated a range of quantitative (attendance, demographics, and geography; pre-post well-being ratings and surveys; psycholinguistic analysis of conversation; facial emotion recognition; facilitator ratings; and economic analysis of program delivery) and qualitative (content and thematic analysis) approaches. Pilot data from round 2 groups on the pre-post 3-word surveys indicated an increase in the emotional valence of words selected after the sessions. CONCLUSIONS: The involvement of people with lived experience of a rare dementia was critical to the design, development, and delivery of the small virtual support group program, and evaluation of this program will yield convergent data about the impact of tailored support delivered to geographically dispersed communities. This is the first study to design and plan an evaluation of VSGs specifically for people affected by rare dementias, including both people living with a rare dementia and their carers, and the outcome of the evaluation will be hugely beneficial in shaping specific and targeted support, which is often lacking in this population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35376.

Rethinking primary prevention of child trafficking: Recommendations from the Human Trafficking Task Force of the Global Alliance for Behavioral Health and Social Justice.

Child trafficking is one of the most egregious violations of children's rights and well-being. In 2014, the Global Alliance for Behavioral Health and Social Justice formed a task force to focus on the issue. After completing two comprehensive reviews and consultations with experts in the field, the task force identified the need for a coherent framework, which conceptualized the primary prevention of child trafficking, which includes children vulnerable to being trafficked and becoming traffickers. This article describes the process undertaken to develop the primary prevention framework, an innovative, aspirational plan for communities to be absent of trafficking. It describes the framework in detail, including the theories that underlie it and the principles that guide it. The framework's flexibility is evident in its application to such worldwide challenges as racism, inequities, and a pandemic. Although the full consequences of the impact of the COVID-19 pandemic on children are not yet known, this article describes certain trends, which have been identified and discusses critical lessons for applying a dynamic framework, as global disruptors will continue. The article ends with examples of how the framework could be implemented by all stakeholders in the community, to address the primary prevention of child trafficking in both the physical and the virtual world. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Impact of the COVID-19 Pandemic on Loneliness and Social Isolation: A Multi-Country Study.

The COVID-19 global pandemic and subsequent public health social measures have challenged our social and economic life, with increasing concerns around potentially rising levels of social isolation and loneliness. This paper is based on cross-sectional online survey data (available in 10 languages, from 2 June to 16 November 2020) with 20,398 respondents from 101 different countries. It aims to help increase our understanding of the global risk factors that are associated with social isolation and loneliness, irrespective of culture or country, to support evidence-based policy, services and public health interventions. We found the prevalence of severe loneliness was 21% during COVID-19 with 6% retrospectively reporting severe loneliness prior to the pandemic. A fifth were defined as isolated based on their usual connections, with 13% reporting a substantial increase in isolation during COVID-19. Personal finances and mental health were overarching and consistently cross-cutting predictors of loneliness and social isolation, both before and during the pandemic. With the likelihood of future waves of COVID-19 and related restrictions, it must be a public health priority to address the root causes of loneliness and social isolation and, in particular, address the needs of specific groups such as carers or those living alone.

An Automated Culture System for Use in Preclinical Testing of Host-Directed Therapies for Tuberculosis.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), was the most significant infectious disease killer globally until the advent of COVID-19. Mtb has evolved to persist in its intracellular environment, evade host defenses, and has developed resistance to many anti-tubercular drugs. One approach to solving resistance is identifying existing approved drugs that will boost the host immune response to Mtb. These drugs could then be repurposed as adjunctive host-directed therapies (HDT) to shorten treatment time and help overcome antibiotic resistance. Quantification of intracellular Mtb growth in macrophages is a crucial aspect of assessing potential HDT. The gold standard for measuring Mtb growth is counting colony-forming units (CFU) on agar plates. This is a slow, labor-intensive assay that does not lend itself to rapid screening of drugs. In this protocol, an automated, broth-based culture system, which is more commonly used to detect Mtb in clinical specimens, has been adapted for preclinical screening of host-directed therapies. The capacity of the liquid culture assay system to investigate intracellular Mtb growth in macrophages treated with HDT was evaluated. The HDTs tested for their ability to inhibit Mtb growth were all-trans Retinoic acid (AtRA), both in solution and encapsulated in poly(lactic-co-glycolic acid) (PLGA) microparticles and the combination of interferon-gamma and linezolid. The advantages of this automated liquid culture-based technique over the CFU method include simplicity of setup, less labor-intensive preparation, and faster time to results (5-12 days compared to 21 days or more for agar plates).

The Resilience of Cardiac Care Through Virtualized Services During the COVID-19 Pandemic: Case Study of a Heart Function Clinic.

BACKGROUND: Virtual care has historically faced barriers to widespread adoption. However, the COVID-19 pandemic has necessitated the rapid adoption and expansion of virtual care technologies. Although the intense and prolonged nature of the COVID-19 pandemic has renewed people's interest in health systems resilience, which includes how services adapt or transform in response to shocks, evidence regarding the role of virtual care technologies in health systems resilience is scarce. OBJECTIVE: At Toronto General Hospital in Ontario, Canada, the rapid virtualization of cardiac care began on March 9, 2020, as a response to the pandemic. The objective of this study was to understand people's experiences with and the barriers and facilitators of the rapid virtualization and expansion of cardiac care resulting from the pandemic. METHODS: A single-case study was conducted with 3 embedded units of analysis. Patients, clinicians, and staff were recruited purposively from an existing mobile, phone-based telemonitoring program at a heart function clinic in Toronto, Canada. Individual, semistructured phone interviews were conducted by two researchers and transcribed verbatim. An inductive thematic analysis at the semantic level was used to analyze transcripts and develop themes. RESULTS: A total of 29 participants were interviewed, including patients (n=16), clinicians (n=9), and staff (n=4). The following five themes were identified: (1) patient safety as a catalyst for virtual care adoption; (2) piecemeal virtual care solutions; (3) confronting new roles and workloads; (4) missing pieces in virtual care; and (5) the inequity paradox. The motivation to protect patient safety and a piecemeal approach to virtual care adoption facilitated the absorptive and adaptive resilience of cardiac care during the COVID-19 pandemic. However, ad hoc changes to clinic roles and workflows, challenges in building relationships through remote methods, and widened inequities were barriers that threatened virtual care sustainment. CONCLUSIONS: We contend that sustaining virtual care hinges upon transformative actions (rather than adaptive actions) that strengthen health systems so that they can face the dynamic and emergent challenges associated with COVID-19 and other shocks. Based on the barriers and facilitators we identified, we present the lessons we learned and recommend transformations for sustaining virtual care during and beyond the COVID-19 pandemic.

Developing an Outpatient Pediatric Pre-Procedure COVID-19 Testing Model.

PURPOSE: The purpose of this project was to design, develop, implement, and manage a sustainable process for pediatric preoperative COVD-19 testing and use the test results to determine the level of personal protective equipment and infection control required for each patient for optimal surgical scheduling and preservation of resources. DESIGN: This quality improvement project used the Plan-Do-Study-Act methodology. Multiple cycles of re-evaluation refined this process which was standardized across the enterprise. METHODS: A process for preoperative testing for all patients undergoing procedures requiring anesthesia was developed and implemented. FINDINGS: A safe, feasible, timely process was developed and piloted to obtain COVID-19 test results to guide individualized interventions. During the pilot, 1,707 patients were screened, and five tested positive for COVID-19, eliminating the need to manage 1702 patients as COVID-19 positive. CONCLUSION: To continue to safely re-open, knowledge of the patient's COVID-19 status is imperative to ensure a safe journey through the perioperative area.

Expanding Telemonitoring in a Virtual World: A Case Study of the Expansion of a Heart Failure Telemonitoring Program During the COVID-19 Pandemic.

BACKGROUND: To minimize the spread and risk of a COVID-19 outbreak, societal norms have been challenged with respect to how essential services are delivered. With pressures to reduce the number of in-person ambulatory visits, innovative models of telemonitoring have been used during the pandemic as a necessary alternative to support access to care for patients with chronic conditions. The pandemic has led health care organizations to consider the adoption of telemonitoring interventions for the first time, while others have seen existing programs rapidly expand. OBJECTIVE: At the Toronto General Hospital in Ontario, Canada, the rapid expansion of a telemonitoring program began on March 9, 2020, in response to COVID-19. The objective of this study was to understand the experiences related to the expanded role of a telemonitoring program under the changing conditions of the pandemic. METHODS: A single-case qualitative study was conducted with 3 embedded units of analysis. Semistructured interviews probed the experiences of patients, clinicians, and program staff from the Medly telemonitoring program at a heart function clinic in Toronto, Canada. Data were analyzed using inductive thematic analysis as well as Eakin and Gladstone's value-adding approach to enhance the analytic interpretation of the study findings. RESULTS: A total of 29 participants were interviewed, including patients (n=16), clinicians (n=9), and operational staff (n=4). Four themes were identified: (1) providing care continuity through telemonitoring; (2) adapting telemonitoring operations for a more virtual health care system; (3) confronting virtual workflow challenges; and (4) fostering a meaningful patient-provider relationship. Beyond supporting virtual visits, the program's ability to provide a more comprehensive picture of the patient's health was valued. However, issues relating to the lack of system integration and alert-driven interactions jeopardized the perceived sustainability of the program. CONCLUSIONS: With the reduction of in-person visits during the pandemic, virtual services such as telemonitoring have demonstrated significant value. Based on our study findings, we offer recommendations to proactively adapt and scale telemonitoring programs under the changing conditions of an increasingly virtual health care system. These include revisiting the scope and expectations of telemedicine interventions, streamlining virtual patient onboarding processes, and personalizing the collection of patient information to build a stronger virtual relationship and a more holistic assessment of patient well-being.

The Use of Storytelling With Grief Reactions in Children During the COVID-19 Pandemic.

Children are living through the COVID-19 pandemic and the traumatic changes the virus has had on the structure and schedule of their daily existence. They are struggling to cope with the loss of the normalcy of their lives and the resulting sense of grief. As the loneliness and isolation required by social distancing can worsen grief, it is important to increase communication with children and include strategies to reduce stress and increase resilience. Storytelling is the oldest form of teaching and has multiple benefits, including identifying emotional states, developing a vocabulary to allow self-advocacy, encouraging the use of strategy, and promoting a sense of hope. In addition, models of positive psychological attitude can diminish anxiety and divert attention to a more productive and positive outlook. Stories are powerful tools and convey thoughts, ideas, and values while encouraging purposeful discussion. For children, hearing stories is a rich avenue to gain insight, resources, and approaches to cope with these unprecedented times. It would be helpful to explore the long-term effects on children of COVID-19-related confinement and loss. [Journal of Psychosocial Nursing and Mental Health Services, 59(2), 13-15.].

Consider storytelling to help children cope during COVID-19

This is a frightening time for all of us, but especially for children. Children are living through COVID-19 and the traumatic changes the virus has had on the routine and schedule of their daily lives. School is a primary source of structure and socialization for most youngsters. As the pandemic continues to unfold, children are experiencing unprecedented shifts in school openings, learning models, extracurricular activities, and even access to play dates and other socialization venues. Without teachers, friends, coaches, or even time outside of the home, children are experiencing tremendous loss and are struggling to understand their new reality.