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Existing barriers to care were exacerbated by the development and implementation of necessary public health restrictions during the COVID-19 pandemic. Children with complex care needs and their families represent a small portion of the paediatric population, and yet they require disproportionately high access to services. Little is known about the impact of COVID-19 public health measures on this population. This study will generate evidence to uncover the wider impact of COVID-19 measures on the lives of children with complex care needs and their families in relation to policy and service changes. This multi-site sequential mixed methods study will take place across the Canadian Maritime provinces and use an integrated knowledge translation approach. There are two phases to this study: 1) map COVID-19 public health restrictions and service changes impacting children with complex care needs by conducting an environmental scan of public health restrictions and service changes between March 2020 and March 2022 and interviewing key informants involved in the development or implementation of restrictions and service changes, and 2) explore how children with complex care needs and their families experienced public health restrictions and service changes to understand how their health and well-being were impacted., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Curran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Asymptomatic SARS-CoV-2 infections were widely reported during the COVID-19 pandemic, acting as a hidden source of infection. Many existing studies investigating asymptomatic immunity failed to recruit true asymptomatic individuals. Thus, we conducted a longitudinal cohort study to evaluate humoral- and cell-mediated responses to infection and vaccination in well-defined asymptomatic young adults (the Asymptomatic COVID-19 in Education [ACE] cohort)., Methods: Asymptomatic testing services located at three UK universities identified asymptomatic young adults who were subsequently recruited with age- and sex-matched symptomatic and uninfected controls. Blood and saliva samples were collected after SARS-CoV-2 Wuhan infection, and again after vaccination. 51 participant's anti-spike antibody titres, neutralizing antibodies, and spike-specific T-cell responses were measured, against both Wuhan and Omicron B.1.1.529.1., Results: Asymptomatic participants exhibited reduced Wuhan-specific neutralization antibodies pre- and post-vaccination, as well as fewer Omicron-specific neutralization antibodies post-vaccination, compared to symptomatic participants. Lower Wuhan and Omicron-specific IgG titres in asymptomatic individuals were also observed pre- and post-vaccination, compared to symptomatic participants. There were no differences in salivary IgA levels. Conventional flow cytometry analysis and multi-dimensional clustering analysis indicated unvaccinated asymptomatic participants had significantly fewer Wuhan-specific IL-2 secreting CD4 + CD45RA + T cells and activated CD8 + T cells than symptomatic participants, though these differences dissipated after vaccination., Conclusions: Asymptomatic infection results in decreased antibody and T cell responses to further exposure to SARS-CoV-2 variants, compared to symptomatic infection. Post-vaccination, antibody responses are still inferior, but T cell immunity increases to match symptomatic subjects, emphasising the importance of vaccination to help protect asymptomatic individuals against future variants., (© 2024. The Author(s).)

Lay Abstract: Research has suggested that autistic people enjoy spending time with other autistic people and find them easier to talk to. We wanted to find out what autistic people say about spending time with other autistic people and whether this makes their life better. We found 52 papers which described this and reviewed what they found. We found that many autistic people had positive experiences of spending time with other autistic people and these experiences had positive impact on their lives in a range of different ways. The papers did not tell us whether this also happens for autistic people with a learning disability. More research is needed to find out more about why spending time with other autistic people helps some autistic people., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To identify the prevalence and type of central venous access device-associated skin complications for adult cancer patients, describe central venous access device management practices, and identify clinical and demographic characteristics associated with risk of central venous access device-associated skin complications., Methods: A prospective cohort study of 369 patients (626 central venous access devices; 7,682 catheter days) was undertaken between March 2017 and March 2018 across two cancer care in-patient units in a large teaching hospital., Results: Twenty-seven percent (n = 168) of participants had a central venous access device-associated skin complication. In the final multivariable analysis, significant (P < .05) risk factors for skin complications were cutaneous graft versus host disease (2.1 times greater risk) and female sex (1.4 times greater risk), whereas totally implanted vascular access device reduced risk for skin complications by two-thirds (incidence risk ratio 0.37)., Conclusion: Central venous access device-associated skin complications are a significant, potentially avoidable injury, requiring cancer nurses to be aware of high-risk groups and use evidence-based preventative and treatment strategies., Implications for Practice: This study has confirmed how common these potentially preventable injuries are. Therefore, the prevalence of these complications could be reduced by focusing on improvements in skin assessment, reductions in central venous access device dressing variation and improving clinician knowledge of this injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported here., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Camouflaging is frequently reported in autistic people and entails the disguising of autistic traits in social situations. Camouflaging is associated with poor mental health in autistic people. This study examined the manifestation of camouflaging in a nonautistic sample, examining the relationship between autistic traits, self-reported camouflaging, gender, and mental health., Method: In total 110 nonautistic adults completed standardized self-report questionnaires that measured autistic traits, mental health symptoms, and camouflaging behaviors. Hierarchical multiple linear regression models were used to analyze data and examine the unique contributions of autistic traits and camouflaging to mental health., Results: Self-reported autistic traits were associated with increased symptoms of poor mental health. However, autistic traits were not associated with mental health symptoms when controlling for self-reported camouflaging, and self-reported camouflaging predicted increased mental health symptoms over and above the effects of autistic traits. Women had poorer mental health than men in our sample, and in women there was a stronger relationship between camouflaging and mental health than in men., Conclusions: Camouflaging may contribute to poor mental health outcomes in the general population, just as it does for autistic people, to the extent that camouflaging more clearly relates to mental health profile than self-reported autism traits. This suggests camouflaging is an important construct for understanding mental health in general, and for exploring the complex relationship between autism and autistic traits., Competing Interests: No competing financial interests exist., (Copyright 2024, Mary Ann Liebert, Inc., publishers.)

Background: People who use alcohol and/or drugs (PWUAD) are at higher risk of infectious disease, experiencing stigma, and recurrent hospitalization. Further, they have a higher likelihood of death once hospitalized when compared to people who do not use drugs and/or alcohol. The use of harm reduction strategies within acute care settings has shown promise in alleviating some of the harms experienced by PWUAD. This review aimed to identify and synthesize evidence related to the implementation of harm reduction strategies in acute care settings., Methods: A scoping review investigating harm reduction strategies implemented in acute care settings for PWUAD was conducted. A search strategy developed by a JBI-trained specialist was used to search five databases (Medline, Embase, CINAHL, PsychInfo and Scopus). Screening of titles, abstracts and full texts, and data extraction was done in duplicate by two independent reviewers. Discrepancies were resolved by consensus or with a third reviewer. Results were reported narratively and in tables. Both patients and healthcare decision makers contributing to the development of the protocol, article screening, synthesis and feedback of results, and the identification of gaps in the literature., Findings: The database search identified 14,580 titles, with 59 studies included in this review. A variety of intervention modalities including pharmacological, decision support, safer consumption, early overdose detection and turning a blind eye were identified. Reported outcome measures related to safer use, managed use, and conditions of use. Reported barriers and enablers to implementation related to system and organizational factors, patient-provider communication, and patient and provider perspectives., Conclusion: This review outlines the types of alcohol and/or drug harm reduction strategies, which have been evaluated and/or implemented in acute care settings, the type of outcome measures used in these evaluations and summarizes key barriers and enablers to implementation. This review has the potential to serve as a resource for future harm reduction evaluation and implementation efforts in the context of acute care settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Crowther et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In Australia, Indigenous children have rates of overweight and obesity 1.5 times those of non-Indigenous children. Culturally safe and effective nutrition interventions are needed for this group. This paper aims to describe a Community-based Participatory Action Research (CPAR) approach to designing formative nutrition intervention research with First Australian children and their families and to reflect on the challenges arising from this process. After obtaining ethical approvals, a Steering Committee (SC), including nine Aboriginal and Torres Strait Islander people experienced in delivering or receiving health care, was established as a project governance body to develop culturally safe project materials and methods. The Indigenous research method of yarning circles was chosen by the SC for the community consultation, and the First Australian SC members were trained to collect the data. They liaised with community organizations to recruit yarning circle participants. Individual interviews conducted by an Aboriginal research assistant replaced yarning circles due to the COVID-19 pandemic lockdowns. While the CPAR approach to formative research was successful, the pandemic and other factors tripled the study duration. To authentically, ethically and safely engage First Australians in research, researchers need to decolonize their methodological approach, and funding bodies need to allow adequate time and resources for the process.

Background: Learning health systems strive to continuously integrate data and evidence into practice to improve patient outcomes and ensure value-based healthcare. While the LHS concept is gaining traction, the operationalization of LHSs is underexplored., Objective: To identify and synthesize the existing evidence on the implementation and evaluation of advancing learning health systems across international health care settings., Methods: A mixed methods systematic review was conducted. Six databases (CINAHL, Embase, Medline, PAIS, Scopus and Nursing at Allied Health Database) were searched up to July 2022 for terms related to learning health systems, implementation, and evaluation measures. Any study design, health care setting and population were considered for inclusion. No limitations were placed on language or date of publication. Two reviewers independently screened the titles, abstracts, and full texts of identified articles. Data were extracted and synthesized using a convergent integrated approach. Studies were critically appraised using relevant JBI critical appraisal checklists., Results: Thirty-five studies were included in the review. Most studies were conducted in the United States (n = 21) and published between 2019 and 2022 (n = 24). Digital data capture was the most common LHS characteristic reported across studies, while patient engagement, aligned governance and a culture of rapid learning and improvement were reported least often. We identified 33 unique strategies for implementing LHSs including: change record systems, conduct local consensus discussions and audit & provide feedback. A triangulation of quantitative and qualitative data revealed three integrated findings related to the implementation of LHSs: (1) The digital infrastructure of LHSs optimizes health service delivery; (2) LHSs have a positive impact on patient care and health outcomes; and (3) LHSs can influence health care providers and the health system., Conclusion: This paper provides a comprehensive overview of the implementation of LHSs in various healthcare settings. While this review identified key implementation strategies, potential outcome measures, and components of functioning LHSs, further research is needed to better understand the impact of LHSs on patient, provider and population outcomes, and health system costs. Health systems researchers should continue to apply the LHS concept in practice, with a stronger focus on evaluation., (© 2023. The Author(s).)

Background: Pediatric emergency departments (ED) in many countries are implementing electronic tools such as kiosks, mobile apps, and electronic patient portals, to improve the effectiveness of discharge communication., Objective: This study aimed to survey nurse and physician readiness to adopt these tools., Methods: An electronic, cross-sectional survey was distributed to a convenience sample of currently practicing ED nurses and physicians affiliated with national pediatric research organizations in Canada, Australia, and New Zealand. Survey development was informed by the nonadoption, abandonment, scale-up, spread, sustainability framework. Measures of central tendency, and parametric and nonparametric tests were used to describe and compare nurse and physician responses., Results: Out of the 270 participants, the majority were physicians (61%, 164/270), female (65%, 176/270), and had 5 or more years of ED experience (76%, 205/270). There were high levels of consensus related to the value proposition of electronic discharge communication tools (EDCTs) with 82% (221/270) of them agreeing that they help parents and patients with comprehension and recall. Lower levels of consensus were observed for organizational factors with only 37% (100/270) agreeing that their staff is equipped to handle challenges with communication technologies. Nurses and physicians showed significant differences on 3 out of 21 readiness factors. Compared to physicians, nurses were significantly more likely to report that EDs have a responsibility to integrate EDCTs as part of a modern system (P<.001) and that policies are in place to guide safe and secure electronic communication (P=.02). Physicians were more likely to agree that using an EDCT would change their routine tasks (P=.04). One third (33%, 89/270) of participants indicated that they use or have used EDCT., Conclusions: Despite low levels of uptake, both nurses and physicians in multiple countries view EDCTs as a valuable support to families visiting pediatric ED. Leadership for technology change, unclear impact on workflow, and disparities in digital literacy skills require focused research effort., (©Janet Curran, Lori Wozney, Emma Tavender, Catherine Wilson, Krista C Ritchie, Helen Wong, Allyson Gallant, Mari Somerville, Patrick M Archambault, Christine Cassidy, Mona Jabbour, Rebecca Mackay, Amy C Plint. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 11.10.2023.)

Molnupiravir, an oral antiviral shown to reduce COVID-19 severity, is available in Australia via the Pharmaceutical Benefits Scheme (PBS) for treatment of mild-moderate COVID-19. For people less than 70 years of age it is only available with risk factors for severe disease, hence the majority of healthcare workers do not qualify. Currently, Australian health services are under considerable strain due to COVID-related staff shortages. Thirty staff members of a tertiary hospital, not eligible under the PBS, were offered molnupiravir within the first five days of COVID-19 illness. Their median age was 43 years, and 73% were female. All completed treatment with rates of adverse events that were low and comparable with clinical trial data. The reported duration of illness ranged from 1-16 days with a median of four days. A negative rapid antigen test on the final day of treatment was reported in 81% of people, and 73% reported being well enough to return to work at the completion of mandatory isolation. Only 22% of people reported transmission in their household after they commenced treatment. The implementation of a policy allowing access to molnupiravir outside of PBS recommendations for healthcare workers with mild-moderate COVID-19 may have important individual benefits to workers health and wellbeing and help alleviate the acute staff shortages experienced currently by the Australian healthcare workforce., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 O’Keeffe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

High endothelial venules (HEV) are specialized post capillary venules that recruit naïve T cells and B cells into secondary lymphoid organs (SLO) such as lymph nodes (LN). Expansion of HEV networks in SLOs occurs following immune activation to support development of an effective immune response. In this study, we used a carcinogen-induced model of fibrosarcoma to examine HEV remodeling after depletion of regulatory T cells (Treg). We used light sheet fluorescence microscopy imaging to visualize entire HEV networks, subsequently applying computational tools to enable topological mapping and extraction of numerical descriptors of the networks. While these analyses revealed profound cancer- and immune-driven alterations to HEV networks within LNs, these changes did not identify successful responses to treatment. The presence of HEV networks within tumors did however clearly distinguish responders from nonresponders. Finally, we show that a successful treatment response is dependent on coupling tumor-associated HEV (TA-HEV) development to T-cell activation implying that T-cell activation acts as the trigger for development of TA-HEVs which subsequently serve to amplify the immune response by facilitating extravasation of T cells into the tumor mass.

Objective: While eating disorders (EDs) are more commonly diagnosed in females, there is growing awareness that men also experience EDs and may do so in a different way. Difficulties with emotion processing and emotion regulation are believed to be important in EDs, but as studies have involved predominantly female samples, it is unclear whether this is also true for males., Methods: In a sample of 1604 participants (n = 631 males), we assessed emotion processing and emotion regulation in males with EDs (n = 109) and compared results to both females with EDs (n = 220) and males from the general population (n = 522). We also looked at whether emotion processing and emotion regulation difficulties predicted various aspects of eating psychopathology and whether this was moderated by sex. We assessed emotion processing with the Toronto Alexithymia Scale, emotion regulation with the Difficulties in Emotion Regulation Scale and the Emotion Regulation Questionnaire, and eating psychopathology with the Eating Disorder Examination Questionnaire., Results: We found that males with ED, like their female counterparts, suffered from emotion processing and emotion regulation deficits. We did find some sex differences, in that males with EDs tended to report more difficulties with their emotions as well as a more externally oriented thinking style compared to females with EDs. Difficulties with emotion processing and emotion regulation were strongly predictive of various aspects of eating psychopathology in both sexes. Importantly, we found that sex moderated the relationship between cognitive reappraisal and eating restraint. As such, low use of reappraisal was found to be associated with higher levels of restraint in females but not in males., Discussion: Difficulties with emotion processing and emotion regulation are associated with eating psychopathology in both males and females. Reappraisal was not found to be associated with reduced eating psychopathology in males, suggesting a cautious approach to interventions targeting this strategy. Research around explanatory mechanisms and interventions must adopt a broader viewpoint including those that are traditionally overlooked in EDs., (© 2022. The Author(s).)

Background: Tapinarof (VTAMA&reg;; Dermavant Sciences, Inc.) is a novel, non-steroidal, topical, aryl hydrocarbon receptor agonist, FDA approved for psoriasis treatment and under investigation for atopic dermatitis treatment as a 1% cream formulation for once-daily (QD) application., Objective: Evaluate cumulative skin irritation, sensitization, and photoallergic and phototoxic potential of tapinarof cream 1% across a range of dosing frequencies and conditions., Methods: We conducted 4 randomized, controlled, phase 1 trials of topical tapinarof cream 1% vs vehicle or other appropriate controls in healthy adults. Cumulative skin irritation was assessed following QD application for 21 days under fully occlusive patch conditions. Contact sensitization, photoallergenicity, and phototoxicity were assessed under semi-occlusive patch conditions. The contact sensitization and photoallergenicity trials used an induction phase of repeated applications followed by a 2-week rest period and a 1-time challenge, with rechallenge if responses indicated sensitization/photosensitization; the phototoxicity trial comprised a single application. Ultraviolet A and B irradiation was used to assess photoallergenicity/toxicity., Results: 376 participants were randomized across the 4 trials. In the cumulative irritation trial, tapinarof cream 1% QD was classified as having a slight potential for very mild cumulative irritation under the exaggerated test conditions of repeated dosing for 21 days. There was no evidence of sensitization, photosensitization, or phototoxicity. Tapinarof was well tolerated and there was a low discontinuation rate across all trials., Conclusions: Tapinarof cream 1% was well tolerated, non-sensitizing, non-phototoxic, and non-photoallergic, with no evidence of clinically meaningful cumulative skin irritation in 4 dermal safety trials in healthy adults., Trial Registration: IND 104601 J Drugs Dermatol. 2022;21(10):1084-1090. doi:10.36849/JDD.6627R1.

Background: The COVID-19 pandemic has presented a unique opportunity to explore how health systems adapt under rapid and constant change and develop a better understanding of health system transformation. Learning health systems (LHS) have been proposed as an ideal structure to inform a data-driven response to a public health emergency like COVID-19. The aim of this study was to use a LHS framework to identify assets and gaps in health system pandemic planning and response during the initial stages of the COVID-19 pandemic at a single Canadian Health Centre., Methods: This paper reports the data triangulation stage of a concurrent triangulation mixed methods study which aims to map study findings onto the LHS framework. We used a triangulation matrix to map quantitative (textual and administrative sources) and qualitative (semi-structured interviews) data onto the seven characteristics of a LHS and identify assets and gaps related to health-system receptors and research-system supports., Results: We identified several health system assets within the LHS characteristics, including appropriate decision supports and aligned governance. Gaps were identified in the LHS characteristics of engaged patients and timely production and use of research evidence., Conclusion: The LHS provided a useful framework to examine COVID-19 pandemic response measures. We highlighted opportunities to strengthen the LHS infrastructure for rapid integration of evidence and patient experience data into future practice and policy changes., Competing Interests: The authors have declared that no competing interests exist.

Background: A learning health system (LHS) framework provides an opportunity for health system restructuring to provide value-based healthcare. However, there is little evidence showing how to effectively implement a LHS in practice., Objective: A mixed-methods review is proposed to identify and synthesize the existing evidence on effective implementation strategies and outcomes of LHS in an international context., Methods: A mixed-methods systematic review will be conducted following methodological guidance from Joanna Briggs Institute (JBI) and PRISMA reporting guidelines. Six databases (CINAHL, Embase, MEDLINE, PAIS, Scopus and Nursing & Allied Health Database) will be searched for terms related to LHS, implementation and evaluation measures. Three reviewers will independently screen the titles, abstracts and full texts of retrieved articles. Studies will be included if they report on the implementation of a LHS in any healthcare setting. Qualitative, quantitative or mixed-methods study designs will be considered for inclusion. No restrictions will be placed on language or date of publication. Grey literature will be considered for inclusion but reviews and protocol papers will be excluded. Data will be extracted from included studies using a standardized extraction form. One reviewer will extract all data and a second will verify. Critical appraisal of all included studies will be conducted by two reviewers. A convergent integration approach to data synthesis will be used, where qualitative and quantitative data will be synthesized separately and then integrated to present overarching findings. Data will be presented in tables and narratively., Conclusion: This review will address a gap in the literature related to implementation of LHS. The findings from this review will provide researchers with a better understanding of how to design and implement LHS interventions. This systematic review was registered in PROSPERO (CRD42022293348)., (© 2022. The Author(s).)

Objective: This systematic review will evaluate the effectiveness of nutrition care interventions delivered by general practitioners versus usual care or no care on dietary and health outcomes in adults with diet-related chronic conditions or risk states., Introduction: General practitioners are usually the first contacts in the health care system for patients with diet-related chronic conditions. While there is some evidence that general practitioners can be effective in delivering nutrition care for a number of outcomes, to inform future care, an update of the evidence is required as well as an examination of which components are associated with positive outcomes., Inclusion Criteria: Published studies will be included if they report on adults with or at risk of diet-related chronic conditions; one-on-one nutrition care interventions individually delivered by general practitioners during primary care consultations; usual or no care as comparators; dietary and/or health outcomes with a minimum three-month follow-up; and randomized controlled trials. Included studies will be available in, or able to be translated into, English and will have no date restrictions., Methods: The databases to be searched will include CINAHL, Embase, MEDLINE, and ProQuest Nursing and Allied Health. Following deduplication, two reviewers will independently screen the titles and abstracts in Covidence, followed by the full texts of potentially relevant studies. Disagreements will be resolved through discussion or with a third reviewer. Included studies will be critically appraised and data will be extracted using a modified JBI tool. Findings will be reported in tables and narrative synthesis, and pooled with statistical meta-analysis, where possible., Systematic Review Registration Number: PROSPERO CRD42021289011., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 JBI.)

Background: Electronic discharge communication tools (EDCTs) are increasingly common in pediatric emergency departments (EDs). These tools have been shown to improve patient-centered communication, support postdischarge care at home, and reduce unnecessary return visits to the ED., Objective: This study aimed to map and assess the evidence base for EDCTs used in pediatric EDs according to their functionalities, intended purpose, implementation context features, and outcomes., Methods: A systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) procedures for identification, screening, and eligibility. A total of 7 databases (EBSCO, MEDLINE, CINAHL, PsycINFO, EMBASE Scopus, and Web of Science) were searched for studies published between 1989 and 2021. Studies evaluating discharge communication-related outcomes using electronic tools (eg, text messages, videos, and kiosks) in pediatric EDs were included. In all, 2 researchers independently assessed the eligibility. Extracted data related to study identification, methodology, settings and demographics, intervention features, outcome implementation features, and practice, policy, and research implications. The Mixed Method Appraisal Tool was used to assess methodological quality. The synthesis of results involved structured tabulation, vote counting, recoding into common metrics, inductive thematic analysis, descriptive statistics, and heat mapping., Results: In total, 231 full-text articles and abstracts were screened for review inclusion with 49 reports (representing 55 unique tools) included. In all, 70% (26/37) of the studies met at least three of five Mixed Method Appraisal Tool criteria. The most common EDCTs were videos, text messages, kiosks, and phone calls. The time required to use the tools ranged from 120 seconds to 80 minutes. The EDCTs were evaluated for numerous presenting conditions (eg, asthma, fracture, head injury, fever, and otitis media) that required a range of at-home care needs after the ED visit. The most frequently measured outcomes were knowledge acquisition, caregiver and patient beliefs and attitudes, and health service use. Unvalidated self-report measures were typically used for measurement. Health care provider satisfaction or system-level impacts were infrequently measured in studies. The directionality of primary outcomes pointed to positive effects for the primary measure (44/55, 80%) or no significant difference (10/55, 18%). Only one study reported negative findings, with an increase in return visits to the ED after receiving the intervention compared with the control group., Conclusions: This review is the first to map the broad literature of EDCTs used in pediatric EDs. The findings suggest a promising evidence base, demonstrating that EDCTs have been successfully integrated across clinical contexts and deployed via diverse technological modalities. Although caregiver and patient satisfaction with EDCTs is high, future research should use robust trials using consistent measures of communication quality, clinician experience, cost-effectiveness, and health service use to accumulate evidence regarding these outcomes., Trial Registration: PROSPERO CRD42020157500; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=157500., (©Lori Wozney, Janet Curran, Patrick Archambault, Christine Cassidy, Mona Jabbour, Rebecca Mackay, Amanda Newton, Amy C Plint, Mari Somerville. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org), 24.06.2022.)

Background: A rapid, accurate, non-invasive diagnostic screen is needed to identify people with SARS-CoV-2 infection. We investigated whether organic semi-conducting (OSC) sensors and trained dogs could distinguish between people infected with asymptomatic or mild symptoms, and uninfected individuals, and the impact of screening at ports-of-entry., Methods: Odour samples were collected from adults, and SARS-CoV-2 infection status confirmed using RT-PCR. OSC sensors captured the volatile organic compound (VOC) profile of odour samples. Trained dogs were tested in a double-blind trial to determine their ability to detect differences in VOCs between infected and uninfected individuals, with sensitivity and specificity as the primary outcome. Mathematical modelling was used to investigate the impact of bio-detection dogs for screening., Results: About, 3921 adults were enrolled in the study and odour samples collected from 1097 SARS-CoV-2 infected and 2031 uninfected individuals. OSC sensors were able to distinguish between SARS-CoV-2 infected individuals and uninfected, with sensitivity from 98% (95% CI 95-100) to 100% and specificity from 99% (95% CI 97-100) to 100%. Six dogs were able to distinguish between samples with sensitivity ranging from 82% (95% CI 76-87) to 94% (95% CI 89-98) and specificity ranging from 76% (95% CI 70-82) to 92% (95% CI 88-96). Mathematical modelling suggests that dog screening plus a confirmatory PCR test could detect up to 89% of SARS-CoV-2 infections, averting up to 2.2 times as much transmission compared to isolation of symptomatic individuals only., Conclusions: People infected with SARS-CoV-2, with asymptomatic or mild symptoms, have a distinct odour that can be identified by sensors and trained dogs with a high degree of accuracy. Odour-based diagnostics using sensors and/or dogs may prove a rapid and effective tool for screening large numbers of people.Trial Registration NCT04509713 (clinicaltrials.gov)., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society of Travel Medicine.)

Background: As of November 25th 2021, four SARS-CoV - 2 variants of concern (VOC: Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2)) have been detected. Variable degrees of increased transmissibility of the VOC have been documented, with potential implications for hospital and health system capacity and control measures. This rapid review aimed to provide a synthesis of evidence related to health system responses to the emergence of VOC worldwide., Methods: Seven databases were searched up to September 27, 2021, for terms related to VOC. Titles, abstracts, and full-text documents were screened independently by two reviewers. Data were extracted independently by two reviewers using a standardized form. Studies were included if they reported on at least one of the VOC and health system outcomes., Results: Of the 4877 articles retrieved, 59 studies were included, which used a wide range of designs and methods. Most of the studies reported on Alpha, and all except two reported on impacts for capacity planning related to hospitalization, intensive care admissions, and mortality. Most studies (73.4%) observed an increase in hospitalization, but findings on increased admission to intensive care units were mixed (50%). Most studies (63.4%) that reported mortality data found an increased risk of death due to VOC, although health system capacity may influence this. No studies reported on screening staff and visitors or cohorting patients based on VOC., Conclusion: While the findings should be interpreted with caution as most of the sources identified were preprints, evidence is trending towards an increased risk of hospitalization and, potentially, mortality due to VOC compared to wild-type SARS-CoV - 2. There is little evidence on the need for, and the effect of, changes to health system arrangements in response to VOC transmission., (© 2022. The Author(s).)

Introduction: Children with medical complexity and their families are an important population of interest within the Canadian healthcare system. Despite representing less than 1% of the paediatric population, children with medical complexity require extensive care and account for one third of paediatric healthcare expenditures. Opportunities to conduct research to assess disparities in care and appropriate allocation of health resources relies on the ability to accurately identify this heterogeneous group of children. This study aims to better understand the population of children with medical complexity in the Canadian Maritimes, including Nova Scotia (NS), New Brunswick (NB) and Prince Edward Island (PEI). This will be achieved through three objectives: (1) Evaluate the performance of three algorithms to identify children with medical complexity in the Canadian Maritimes in administrative data; then using the 'best fit' algorithm (2) Estimate the prevalence of children with medical complexity in the Canadian Maritimes from 2003 to 2017 and (3) Describe patterns of healthcare utilisation for this cohort of children across the Canadian Maritimes., Methods and Analysis: The research will be conducted in three phases. In Phase 1, an expert panel will codevelop a gold-standard definition of paediatric medical complexity relevant to the Canadian Maritime population. A two-gate validation process will then be conducted using NS data and the gold-standard definition to determine the 'best fit' algorithm. During phase 2 the 'best fit' algorithm will be applied to estimate the prevalence of children with medical complexity in NS, NB and PEI. Finally, in phase 3 will describe patterns of healthcare utilisation across the Canadian Maritimes., Ethics and Dissemination: Ethics approval for this protocol was granted by the institutional research ethics board at the IWK Health Centre (REB # 1026245). A waiver of consent was approved. This study will use an integrated knowledge translation approach, where end users are involved in each stage of the project, which could increase uptake of the research into policy and practice. The findings of this research study will be submitted for publication and dissemination through conference presentations and with our end users., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The United Kingdom Warnock Committee (1984) was a landmark contributor to the ethics and law governing human embryo experimentation. It recommended a time limit up to 14 days of development after fertilisation within which such experimentation may take place, which mirrors the late 1970s' proposal of the United States Department of Health, Education, and Welfare Ethics Advisory Board (EAB). This study analyses the EAB's and the Warnock Committee's reasoning and conclusions regarding what constitutes ethical behaviour towards the human embryo. Current embryology and recently created embryo-like structures are considered. After the Warnock Report, several Australian Federal and State committees in Australia investigated the ethics which should guide experimentation on human embryos. The reports of these Australian committees are reviewed and the potential influence of both earlier committees on their deliberations is discussed. The rationale informing current Australian law governing human embryo experimentation is examined. Considering current more advanced knowledge of embryology, it is concluded that this legislation should be reassessed., Competing Interests: None.

Accurate assessment of SARS-CoV-2 immunity is critical in evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS-CoV-2-specific T-cell responses are a critical feature that will likely form a key correlate of protection against COVID-19. Here, we developed and optimized a high-throughput whole blood-based assay to determine the T-cell response associated with prior SARS-CoV-2 infection and/or vaccination amongst 231 healthy donors and 68 cancer patients. Following overnight in vitro stimulation with SARS-CoV-2-specific peptides, blood plasma samples were analysed for T H 1-type cytokines. Highly significant differential IFN-γ + /IL-2 + SARS-CoV-2-specific T-cell responses were seen amongst previously infected COVID-19-positive healthy donors in comparison with unknown / naïve individuals (p < 0·0001). IFN-γ production was more effective at identifying asymptomatic donors, demonstrating higher sensitivity (96·0% vs. 83·3%) but lower specificity (84·4% vs. 92·5%) than measurement of IL-2. A single COVID-19 vaccine dose induced IFN-γ and/or IL-2 SARS-CoV-2-specific T-cell responses in 116 of 128 (90·6%) healthy donors, reducing significantly to 27 of 56 (48·2%) when measured in cancer patients (p < 0·0001). A second dose was sufficient to boost T-cell responses in the majority (90·6%) of cancer patients, albeit IFN-γ + responses were still significantly lower overall than those induced in healthy donors (p = 0·034). Three-month post-vaccination T-cell responses also declined at a faster rate in cancer patients. Overall, this cost-effective standardizable test ensures accurate and comparable assessments of SARS-CoV-2-specific T-cell responses amenable to widespread population immunity testing, and identifies individuals at greater need of booster vaccinations., (© 2021 The Authors. Immunology published by John Wiley & Sons Ltd.)

This qualitative descriptive study explored health consumers' preferences for receiving nutrition care in Australian primary care. The study was underpinned by a constructivist research paradigm. Semistructured telephone interviews were conducted with 25 health consumers (age 19-78 years; 19 female) from across Australia between May and August 2020. Content analysis, using an inductive approach revealed emergent themes. was used to reveal emergent themes. Five themes were identified in the data: (1) health consumers want to receive nutrition care from a qualified person; (2) nutrition care is viewed as important, and health consumers want to receive it in a format that meets their needs; (3) nutrition care should be low cost and available to everyone; (4) nutrition care services should be conveniently located; and (5) health consumers want nutrition care to be offered frequently, across their lifespan. Health consumers have a clear idea of how they would like to receive nutrition care in the primary care setting, but reported challenges to receiving this care within the current system. New models of service delivery are needed to meet the needs of health consumers.

Objectives: The four SARS-CoV-2 variants of concern (VOC; Alpha, Beta, Gamma and Delta) identified by May 2021 are highly transmissible, yet little is known about their impact on public health measures. We aimed to synthesise evidence related to public health measures and VOC., Design: A rapid scoping review., Data Sources: On 11 May 2021, seven databases (MEDLINE, Embase, the Cochrane Database of Systematic Reviews, Central Register of Controlled Trials, Epistemonikos' L-OVE on COVID-19, medRxiv, bioRxiv) were searched for terms related to VOC, public health measures, transmission and health systems. No limit was placed on date of publication., Eligibility Criteria: Studies were included if they reported on any of the four VOCs and public health measures, and were available in English. Only studies reporting on data collected after October 2020, when the first VOC was reported, were included., Data Extraction and Synthesis: Titles, abstracts and full-text articles were screened by two independent reviewers. Data extraction was completed by two independent reviewers using a standardised form. Data synthesis and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines., Results: Of the 37 included studies, the majority assessed the impact of Alpha (n=32) and were conducted in Europe (n=12) or the UK (n=9). Most were modelling studies (n=28) and preprints (n=28). The majority of studies reported on infection control measures (n=17), followed by modifying approaches to vaccines (n=13), physical distancing (n=6) and either mask wearing, testing or hand washing (n=2). Findings suggest an accelerated vaccine rollout is needed to mitigate the spread of VOC., Conclusions: The increased severity of VOC requires proactive public health measures to control their spread. Further research is needed to strengthen the evidence for continued implementation of public health measures in conjunction with vaccine rollout. With no studies reporting on Delta, there is a need for further research on this and other emerging VOC on public health measures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: People who use alcohol and/or drugs (PWUAD) are at high risk of medical complications, frequent hospitalisation and drug-related death following discharge from inpatient settings and emergency departments (EDs). Harm reduction strategies implemented in these settings may mitigate negative health outcomes for PWUAD. However, the scope of harm reduction strategies used globally within inpatient settings and EDs is unknown. The objective of this review is to identify and synthesise reported harm reduction strategies that have been implemented across inpatient settings and EDs for PWUAD., Methods and Analysis: This review will include studies from any country and health service reporting on harm reduction strategies implemented in inpatient settings or EDs. The population of interest includes people of any race, gender and age identifying as PWUAD, or individuals who provided care to PWUAD. Studies which describe implementation strategies and barriers and enablers to implementation will be included. Studies published in English, or those available for English translation will be included. The following databases will be searched: MEDLINE All (Ovid), Embase (Elsevier Embase.com), CINAHL with Full Text (EBSCOhost), PsycINFO (EBSCOhost) and SCOPUS (Elsevier Scopus.com). A grey literature search will be conducted. There will be no date restrictions on the search. Titles, abstracts and full texts will be screened in duplicate. Data will be extracted using a standardised form. The results will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews., Ethics and Dissemination: Scoping reviews do not require ethical approval. Patient partners with lived experience and relevant knowledge users will be engaged as research team members throughout all phases of the research process. A report detailing context, methodology and findings from this review will be disseminated to knowledge users and relevant community stakeholders. This review will be submitted for publication to a relevant peer-reviewed journal., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Infectious illness, including lower respiratory tract infection (LRTI), is a leading cause of childhood morbidity and infant mortality in Inuit children in Nunavut Canada. The carnitine palmitoyltransferase 1A (CPT1A) p.P479L variant is common in arctic Indigenous populations of Alaska, Canada, and Greenland. CPT1A is a fatty acid oxidation enzyme expressed in the liver, immunocytes and other tissues, and is needed to use fats for energy during fasting. Previous association of the variant with early childhood infectious illness and infant death has been challenged because of sample size and limited adjustment for confounders. We evaluated whether the p.P479L variant is associated with infectious illness in Inuit children of Nunavut, Canada. Methods: We conducted a retrospective clinical chart review of 2,225 Inuit children (0-5 years) for infectious illness (including otitis media, gastroenteritis, and hospital admission for LRTI), prenatal, perinatal, and socioeconomic indicators, subsequently linking to CPT1A genotype. Multivariable logistic regression adjusted for birth characteristics, breastfeeding, maternal smoking, food insecurity, and socioeconomic indicators. Results: Overall, 27% of children were hospitalized for LRTI, 86% had otitis media and 50% had gastroenteritis. The p.P479L allele frequency was 0.82. In multivariable analysis, p.P479L homozygosity was associated with LRTI admission (aOR:2.88 95%CI:1.46-5.64), otitis media (aOR:1.83, 95%CI:1.05-3.21), and gastroenteritis (aOR:1.74, 95%CI:1.09-2.77), compared to non-carriers. Conclusion: Children homozygous for the p.P479L variant were more likely to experience infectious illness than non-carriers, including hospitalization for respiratory tract infections. Given the role of CPT1A in immunocytes, our findings indicate that more study is needed to determine if there is a role of the variant in immune response. Continued Inuit involvement is essential when considering next steps., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Collins, Edmunds, Akearok, Thompson, Erickson, Hildes-Ripstein, Miners, Somerville, Goldfarb, Rockman-Greenberg and Arbour.)

Background and Objectives: Guidelines recommend people with prediabetes receive diet and lifestyle support to avoid type 2 diabetes, yet it is unclear whether this care is provided in practice. The aim of this article is to explore the perspectives and nutrition care practices of healthcare providers (HCPs) for patients with prediabetes., Method: This was a mixed-methods case study of an urban practice comprising a retrospective chart review and semi-structured interviews. Charts of adult patients with prediabetes were reviewed and informed a protocol used to interview HCPs. Interviews were thematically analysed., Results: Charts of 47 patients, representing 1096 consultations, were reviewed. The majority (74.5%) of patients had 'diet' noted in their chart, yet this accounted for only 8.1% of consultations. Only 19.1% of patients were referred to a dietitian. Interviews provided HCP explanations of the quantitative findings., Discussion: HCPs value nutrition care, yet are limited by the healthcare system to provide comprehensive care to people with prediabetes.

Background: Indigenous populations throughout the world experience poorer health outcomes than non-indigenous people. The reasons for the health disparities are complex and due in part to historical treatment of Indigenous groups through colonisation. Evidence-based interventions aimed at improving health in this population need to be culturally safe. However, the extent to which cultural adaptation strategies are incorporated into the design and implementation of nutrition interventions designed for Indigenous peoples is unknown. The aim of this scoping review was to explore the cultural adaptation strategies used in the delivery of nutrition interventions for Indigenous populations worldwide., Methods: Five health and medical databases were searched to January 2020. Interventions that included a nutrition component aimed at improving health outcomes among Indigenous populations that described strategies to enhance cultural relevance were included. The level of each cultural adaptation was categorised as evidential, visual, linguistic, constituent involving and/or socio-cultural with further classification related to cultural sensitivity (surface or deep)., Results: Of the 1745 unique records screened, 98 articles describing 66 unique interventions met the inclusion criteria, and were included in the synthesis. The majority of articles reported on interventions conducted in the USA, Canada and Australia, were conducted in the previous 10 years (n = 36) and focused on type 2 diabetes prevention (n = 19) or management (n = 7). Of the 66 interventions, the majority included more than one strategy to culturally tailor the intervention, combining surface and deep level adaptation approaches (n = 51), however, less than half involved Indigenous constituents at a deep level (n = 31). Visual adaptation strategies were the most commonly reported (n = 57)., Conclusion: This paper is the first to characterise cultural adaptation strategies used in health interventions with a nutrition component for Indigenous peoples. While the majority used multiple cultural adaptation strategies, few focused on involving Indigenous constituents at a deep level. Future research should evaluate the effectiveness of cultural adaptation strategies for specific health outcomes. This could be used to inform co-design planning and implementation, ensuring more culturally appropriate methods are employed.

Purpose: Primary care is the ideal setting to promote weight management, warranting innovative ways to support patients. This systematic review aimed to determine whether providing food to patients in primary care can help to reduce body weight., Methods: Four databases were searched for studies that aimed to elicit weight loss by directly providing foodstuffs and/or supplements to patients in primary care settings. Interventions with adults of any gender or race were included. Interventions that involved other components such as exercise classes or education sessions were excluded. The methodological quality of each study was appraised using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies., Results: Four heterogeneous studies met the eligibility criteria, representing 476 adults. Two studies used meal-replacement products but differed in length and intensity, another study provided green tea and vitamin E supplementation, and the final study provided vouchers for use at a farmers' market hosted at a primary care clinic. Interventions ranged in length from 4 to 13 weeks. Three of the four studies observed weight loss in some form and all studies observed at least one other improvement in a health outcome such as waist circumference, blood pressure or fasting insulin levels., Conclusions: A small yet notable body of literature supports the concept of providing food to patients in primary care settings to support weight loss. Further, high-quality research is needed on the efficacy and cost-effectiveness of this approach to ultimately inform policy initiatives for primary care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The nature of the tumor microenvironment (TME) influences the ability of tumor-specific T cells to control tumor growth. In this study, we performed an unbiased comparison of the TME of regulatory T-cell (Treg)-replete and Treg-depleted carcinogen-induced tumors, including Treg-depleted responding (regressing) and non-responding (growing) tumors. This analysis revealed an inverse relationship between extracellular matrix (ECM) and T-cell infiltrates where responding tumors were T-cell rich and ECM poor, whereas the converse was observed in non-responder tumors. For this reason, we hypothesized that the ECM acted as a barrier to successful T-cell infiltration and tumor rejection. However, further experiments revealed that this was not the case but instead showed that an effective T-cell response dramatically altered the density of ECM in the TME. Along with loss of ECM and high numbers of infiltrating T cells, responder tumors were distinguished by the development of lymphatic and blood vessel networks with specialized immune function. ECM-rich tumors exhibited a stem cell-like gene expression profile and superior tumor-initiating capacity, whereas such features were absent in responder tumors. Overall, these findings define an extended role for an effective immune response, not just in direct killing of tumor cells but in widescale remodeling of the TME to favor loss of ECM, elimination of cancer stem cells, and propagation of adaptive immunity., (©2020 American Association for Cancer Research.)

Although metastatic disease is responsible for the majority of cancer deaths, tests of novel immunotherapies in mouse tumour models often focus on primary tumours without determining whether these therapies also target metastatic disease. This study examined the impact of depleting Foxp3 + regulatory T cells (Treg), on lung metastases, using a mouse model of breast cancer. After Treg-depletion, generation of an immune response to the primary tumour was a critical determinant for limiting development of metastasis. Indeed, resection of the primary tumour abrogated any effect of Treg-depletion on metastases. In addition, whilst the immune response, generated by the primary tumour, prevented metastases development, it had little impact on controlling established disease. Collectively, the data indicate that metastatic cells in the lung are not controlled by immune responses induced by the primary tumour. These findings indicate that targeting Tregs alone will not suffice for treating lung metastases.

Background: Despite striking successes, immunotherapies aimed at increasing cancer-specific T cell responses are unsuccessful in most patients with cancer. Inactivating regulatory T cells (Treg) by inhibiting the PI3Kδ signaling enzyme has shown promise in preclinical models of tumor immunity and is currently being tested in early phase clinical trials in solid tumors., Methods: Mice bearing 4T1 mammary tumors were orally administered a PI3Kδ inhibitor (PI-3065) daily and tumor growth, survival and T cell infiltrate were analyzed in the tumor microenvironment. A second treatment schedule comprised PI3Kδ inhibitor with anti-LAG3 antibodies administered sequentially 10 days later., Results: As observed in human immunotherapy trials with other agents, immunomodulation by PI3Kδ-blockade led to 4T1 tumor regressor and non-regressor mice. Tumor infiltrating T cells in regressors were metabolically fitter than those in non-regressors, with significant enrichments of antigen-specific CD8 + T cells, T cell factor 1 (TCF1) + T cells and CD69 - T cells, compatible with induction of a sustained tumor-specific T cell response. Treg numbers were significantly reduced in both regressor and non-regressor tumors compared with untreated tumors. The remaining Treg in non-regressor tumors were however significantly enriched with cells expressing the coinhibitory receptor LAG3, compared with Treg in regressor and untreated tumors. This striking difference prompted us to sequentially block PI3Kδ and LAG3. This combination enabled successful therapy of all mice, demonstrating the functional importance of LAG3 in non-regression of tumors on PI3Kδ inhibition therapy. Follow-up studies, performed using additional cancer cell lines, namely MC38 and CT26, indicated that a partial initial response to PI3Kδ inhibition is an essential prerequisite to a sequential therapeutic benefit of anti-LAG3 antibodies., Conclusions: These data indicate that LAG3 is a key bottleneck to successful PI3Kδ-targeted immunotherapy and provide a rationale for combining PI3Kδ/LAG3 blockade in future clinical studies., Competing Interests: Competing interests: BV is a consultant for Karus Therapeutics (Oxford, UK), iOnctura (Geneva, Switzerland) and Venthera (Palo Alto, USA) and has received speaker fees from Gilead., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

The first signs of diabetic neuropathy typically result from small-diameter nerve fiber dysfunction. This review synthesized the evidence for small-diameter nerve fiber neuropathy measured via quantitative sensory testing (QST) in patients with diabetes with and without painful and non-painful neuropathies. Electronic databases were searched to identify studies in patients with diabetes with at least one QST measure reflecting small-diameter nerve fiber function (thermal or electrical pain detection threshold, contact heat-evoked potentials, temporal summation or conditioned pain modulation). Four groups were compared: patients with diabetes (1) without neuropathy, (2) with non-painful diabetic neuropathy, (3) with painful diabetic neuropathy and (4) healthy individuals. Recommended methods were used for article identification, selection, risk of bias assessment, data extraction and analysis. For the meta-analyses, data were pooled using random-effect models. Twenty-seven studies with 2422 participants met selection criteria; 18 studies were included in the meta-analysis. Patients with diabetes without symptoms of neuropathy already showed loss of nerve function for heat (standardized mean difference (SMD): 0.52, p<0.001), cold (SMD: -0.71, p=0.01) and electrical pain thresholds (SMD: 1.26, p=0.01). Patients with non-painful neuropathy had greater loss of function in heat pain threshold (SMD: 0.75, p=0.01) and electrical stimuli (SMD: 0.55, p=0.03) compared with patients with diabetes without neuropathy. Patients with painful diabetic neuropathy exhibited a greater loss of function in heat pain threshold (SMD: 0.55, p=0.005) compared with patients with non-painful diabetic neuropathy. Small-diameter nerve fiber function deteriorates progressively in patients with diabetes. Because the dysfunction is already present before symptoms occur, early detection is possible, which may assist in prevention and effective management of diabetic neuropathy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Prediabetes increases the risk of developing type 2 diabetes (T2D). Improving diet quality is key in preventing this progression, yet little is known about the characteristics of individuals with prediabetes or the nutrition care they receive., Objectives: This study aims to identify characteristics and experiences associated with receiving a prediabetes diagnosis prior to developing T2D., Methods: A mixed methods study encompassed a quantitative subanalysis of participants with newly diagnosed T2D from The 3D Study, and semi-structured telephone interviews with a subsample of participants who were previously diagnosed with prediabetes. Interviews were thematically analysed and survey data synthesized using SPSS statistical software., Results: Of the 225 study participants, 100 individuals were previously diagnosed with prediabetes and 120 participants were not. Those with prediabetes were less likely to be smokers (P = 0.022) and more likely to be satisfied with seeing a dietitian (P = 0.031) than those without a previous prediabetes diagnosis. A total of 20 participants completed semi-structured interviews. Thematic analysis revealed three themes: (i) experiencing a prediabetes diagnosis; (ii) receiving nutrition care during prediabetes and (iii) reflecting on the experience of receiving care for prediabetes versus T2D., Conclusions: There are gaps in the current management of prediabetes in Australia. Low rates of prediabetes diagnosis and an ambiguous experience of receiving this diagnosis suggest an area of health service improvement. With no difference in diet quality between individuals with and without a previous prediabetes diagnosis, the nutrition care during prediabetes may be more important than the diagnosis itself in delaying the onset of T2D., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Galectin-3 (formerly known as Mac-2), encoded by the LGALS3 gene, is proposed to regulate macrophage adhesion, chemotaxis, and apoptosis. We investigated the role of galectin-3 in determining the inflammatory profile of macrophages and composition of atherosclerotic plaques. Approach and Results: We observed increased accumulation of galectin-3-negative macrophages within advanced human, rabbit, and mouse plaques compared with early lesions. Interestingly, statin treatment reduced galectin-3-negative macrophage accrual in advanced plaques within hypercholesterolemic (apolipoprotein E deficient) Apoe -/- mice. Accordingly, compared with Lgals3 +/+ : Apoe -/- mice, Lgals3 -/- : Apoe -/- mice displayed altered plaque composition through increased macrophage:smooth muscle cell ratio, reduced collagen content, and increased necrotic core area, characteristics of advanced plaques in humans. Additionally, macrophages from Lgals3 -/- mice exhibited increased invasive capacity in vitro and in vivo. Furthermore, loss of galectin-3 in vitro and in vivo was associated with increased expression of proinflammatory genes including MMP (matrix metalloproteinase)-12, CCL2 (chemokine [C-C motif] ligand 2), PTGS2 (prostaglandin-endoperoxide synthase 2), and IL (interleukin)-6, alongside reduced TGF (transforming growth factor)-β1 expression and consequent SMAD signaling. Moreover, we found that MMP12 cleaves macrophage cell-surface galectin-3 resulting in the appearance of a 22-kDa fragment, whereas plasma levels of galectin-3 were reduced in Mmp12 -/- : Apoe -/- mice, highlighting a novel mechanism where MMP12-dependent cleavage of galectin-3 promotes proinflammatory macrophage polarization. Moreover, galectin-3-positive macrophages were more abundant within plaques of Mmp12 -/- : Apoe -/- mice compared with Mmp12 +/+ : Apoe -/- animals., Conclusions: This study reveals a prominent protective role for galectin-3 in regulating macrophage polarization and invasive capacity and, therefore, delaying plaque progression.

Background: We evaluated a cohort of 35 children diagnosed with long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, or arrhythmogenic right ventricular cardiomyopathy with regard to physical and psychosocial well-being., Material and Methods: Patients wore an accelerometer to record their time involved in moderate- to vigorous-intensity physical activity and completed the Pediatric Quality of Life Inventory and the Pediatric Cardiac Quality of Life Inventory. Parents were also asked to describe if their child had changed their physical activity because of their diagnosis and how difficult and upsetting it was for the child to adapt to the physical activity recommendations., Results: Patients were involved in less moderate- to vigorous-intensity physical activity per day (35 min/day versus 55 min/day) and had lower Pediatric Quality of Life Inventory total health scores (79 versus 84) compared to normative data. Overall, 51% of the cohort modified their physical activity in some way because of their diagnosis and changing physical activity was associated with lower Pediatric Quality of Life Inventory and Pediatric Cardiac Quality of Life Inventory scores., Conclusion: Our cohort was involved in less moderate- to vigorous-intensity physical activity and had lower Pediatric Quality of Life Inventory total health scores compared to normative paediatric data. Modifying one's physical activity was associated with worse health-related quality of life scores, highlighting a vulnerable sub-group of children. These findings are useful for families and healthcare professionals caring for children who are adjusting to a new cardiac diagnosis of an inherited arrhythmia or cardiomyopathy.

If, in jurisdictions with legalized euthanasia, obtaining organs for transplant from euthanized people is allowed, must their organs be taken only after death or should euthanasia be allowed to be performed by removal of vital organs? Asked another way, if "Donation after Death" is practiced, why not "Death by Donation?" The article addresses two questions. First, "What issues does connecting euthanasia and organ donation raise?" They include dealing with uncertainty regarding the definition of death, defining what constitutes conscientiously objecting healthcare professionals' involvement in euthanasia, and whether connecting euthanasia and transplantation makes conflicts of interest for healthcare professionals unavoidable. Additional issues raised by death by donation include breach of the "dead-donor rule"; what would constitute informed consent to it; and what impact its acceptance would have on important foundational societal values, especially respect for human dignity and human life. The second question is "Why might some people who agree with euthanasia and even organ donation after death by euthanasia find death by donation ethically unacceptable?" Considerations again include its harmful impact on upholding respect for human dignity and human life and that the "wisdom of repugnance" could be informing these people's reaction. It is concluded that in order to avoid serious breaches of ethics, organ transplantation and euthanasia should not be linked in any way., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© Catholic Medical Association 2019.)

To synthesise the literature on nutrition care for prediabetes from both the perspective of healthcare providers and patients, six databases (CINAHL, MEDLINE, Embase, PsycINFO, Scopus and ProQuest) were searched to identify qualitative or quantitative studies that focussed on nutrition care and prediabetes in primary care practice. Studies examining the perspectives of patients with prediabetes and healthcare providers were included. Outcomes of interest included knowledge of nutrition care for prediabetes, attitudes around providing or receiving nutrition care and actual nutrition care practices for prediabetes. Overall, 12851 studies were screened and 26 were included in the final review. Inductive analysis produced five themes: (i) nutrition care is preferable to pharmacological intervention; (ii) patients report taking action for behaviour change; (iii) healthcare providers experience barriers to nutrition care; (iv) healthcare providers tend not to refer patients for nutrition care; and (v) there are contradictory findings around provision and receipt of nutrition care. This review has revealed the contradictions between patients' and healthcare providers' knowledge, attitudes and practices around nutrition care for prediabetes. Further research is needed to shed light on how to resolve these disconnects in care and to improve nutrition care practices for people with prediabetes.

Effective environmental assessment and management requires quantifiable biodiversity targets. Biodiversity benchmarks define these targets by focusing on specific biodiversity metrics, such as species richness. However, setting fixed targets can be challenging because many biodiversity metrics are highly variable, both spatially and temporally. We present a multivariate, hierarchical Bayesian method to estimate biodiversity benchmarks based on the species richness and cover of native terrestrial vegetation growth forms. This approach uses existing data to quantify the empirical distributions of species richness and cover within growth forms, and we use the upper quantiles of these distributions to estimate contemporary, "best-on-offer" biodiversity benchmarks. Importantly, we allow benchmarks to differ among vegetation types, regions, and seasons, and with changes in recent rainfall. We apply our method to data collected over 30 yr at ~35,000 floristic plots in southeastern Australia. Our estimated benchmarks were broadly consistent with existing expert-elicited benchmarks, available for a small subset of vegetation types. However, in comparison with expert-elicited benchmarks, our data-driven approach is transparent, repeatable, and updatable; accommodates important spatial and temporal variation; aligns modeled benchmarks directly with field data and the concept of best-on-offer benchmarks; and, where many benchmarks are required, is likely to be more efficient. Our approach is general and could be used broadly to estimate biodiversity targets from existing data in highly variable environments, which is especially relevant given rapid changes in global environmental conditions., (© 2019 The Authors. Ecological Applications published by Wiley Periodicals, Inc. on behalf of Ecological Society of America.)

Background: Historically, individuals diagnosed with an inherited arrhythmia or cardiomyopathy have been advised to avoid participating in competitive sports. Consequently, these individuals may be more susceptible to weight gain and obesity., Methods: A retrospective longitudinal chart review was performed for a population of children with a genetic or clinical diagnosis of the long-QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, or arrhythmogenic right ventricular cardiomyopathy. We recorded the physical activity recommendation, postdiagnosis sports participation, and body mass index (BMI) over time., Results: A total of 109 charts were reviewed. Some level of physical activity restriction was documented for the majority of phenotype-positive children (80%) but was less common for phenotype-negative children (37%) (P < 0.001). Overall, 38% ( n = 41) of the study population were reportedly participating in a moderate or high dynamic sports following their diagnosis. Nonetheless, the BMI did not differ over time based on physical activity restriction or sports participation, and the proportion of overweight and obese children at follow-up was consistent with that seen in the Canadian pediatric population., Conclusion: Physical activity restriction was recommended for the majority of phenotype-positive children with an inherited arrhythmia or cardiomyopathy. However, many children continue to participate in competitive sports. Children prescribed physical activity restriction appear to face similar concerns relating to obesity as other Canadian children. This study highlights the need to further assess the effectiveness of physical activity recommendations and its impact on the cardiovascular health., (© 2018 Wiley Periodicals, Inc.)

Background: Communication between professionals, patients and families about palliative and end-of-life care after stroke is complex and there is a need for educational resources in this area., Methods: To explore the key learning needs of healthcare professionals, a multidisciplinary, expert group developed a short electronic survey with open and closed questions, and then distributed it to six UK multiprofessional networks and two groups of local clinicians., Results: A total of 599 healthcare professionals responded. Educational topics that were either definitely or probably needed were: ensuring consistent messages to families and patients (88%); resolving conflicts among family members (83%); handling unrealistic expectations (88%); involving families in discussions without them feeling responsible for decisions (82%); discussion of prognostic uncertainties (79%); likely mode of death (72%); and oral feeding for 'comfort' in patients at risk of aspiration (71%). The free-text responses (n = 489) and 82 'memorable' cases identified similar themes., Conclusion: Key topics of unmet need for education in end-of-life care in stroke have been identified and these have influenced the content of an open access, web-based educational resource., Competing Interests: This survey and the development of the educational resource were funded by the Scottish Government Stroke Improvement Fund. FD is supported by a Garfield Weston Stroke Association Senior Clinical Lecturership. FB and MS report grants for an e-learning module from Scottish Government to Chest Heart & Stroke Scotland under the stroke improvement plan during the conduct of the study

Cascade predictive genetic testing is available for many families as a means to identify individuals at risk of long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC). The general issue of offering predictive genetic testing to minors has been an area of ethical debate among genetic counselors and other healthcare professionals for many years. An online questionnaire was circulated to four international genetic counseling associations to assess the views of cardiac genetic counselors regarding when to offer predictive genetic testing to children at risk of LQTS, CPVT, HCM, and ARVC. Analysis was both quantitative and qualitative. The study sample comprised 98 respondents. The majority reported that they offer predictive genetic testing before 5 years of age to children at risk of LQTS (83%) and CVPT (75%) and before 10 years of age to children at risk of HCM (66%) or ARVC (70%). Influencing factors included country of practice, clinical setting, and years of experience. The rationale provided for when to offer predictive genetic testing is encompassed by the ethical principles of beneficence, non-maleficence, autonomy, and informed consent. In conclusion, significant practice variation exists among cardiac genetic counselors regarding predictive genetic testing for children at risk of an inherited cardiomyopathy. These variations call for more research in the area to assist with the development of evidence-based guidelines.

Aims: To synthesize peer-reviewed literature that investigates the dietary intake by food group of individuals with type 2 diabetes mellitus (T2DM) and compare intakes to national and international dietary guidelines., Methods: Four electronic databases (MEDLINE, EMBASE, CINAHL and Web of Sciences) were searched for studies that investigated the dietary intake of adults (≥18 years) with T2DM using the five main food groups (fruit, vegetables, dairy, grains and meat/meat alternatives). Food group intake in serves was compared against national guidelines and fruit and vegetable intake in grams was compared against the World Health Organization (WHO) guidelines., Results: After screening 13,662 publications, 11 studies were included. All reported cross-sectional data. Majority of participants were consuming less than the recommended serves of fruit, vegetables, grains and dairy and were meeting or exceeding the recommended serves for meat/meat alternatives. Two of six studies reported fruit and vegetable recommendations were being met, two reported dairy recommendations were being met and two reported grain recommendations were being met. Of the five studies reporting intake in grams, four met the WHO minimum intake for fruit and vegetables., Conclusions: Individuals with T2DM do not comply with food group recommendations; particularly for fruit, vegetables, dairy and grains. Longitudinal research is required to better understand how food group intake changes over time after diagnosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Predictive genetic testing in minors should be considered when clinical intervention is available. Children who carry a pathogenic variant for an inherited arrhythmia or cardiomyopathy require regular cardiac screening and may be prescribed medication and/or be told to modify their physical activity. Medical genetics and pediatric cardiology charts were reviewed to identify factors associated with uptake of genetic testing and cardiac evaluation for children at risk for long QT syndrome, hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. The data collected included genetic diagnosis, clinical symptoms in the carrier parent, number of children under 18 years of age, age of children, family history of sudden cardiac arrest/death, uptake of cardiac evaluation and if evaluated, phenotype for each child. We identified 97 at risk children from 58 families found to carry a pathogenic variant for one of these conditions. Sixty six percent of the families pursued genetic testing and 73% underwent cardiac screening when it was recommended. Declining predictive genetic testing was significantly associated with genetic specialist recommendation (p < 0.001) and having an asymptomatic carrier father (p = 0.006). Cardiac evaluation was significantly associated with uptake of genetic testing (p = 0.007). This study provides a greater understanding of factors associated with uptake of genetic testing and cardiac evaluation in children at risk of an inherited arrhythmia or cardiomyopathy. It also identifies a need to educate families about the importance of cardiac evaluation even in the absence of genetic testing.

Deficits in behavioral activation, exertion of effort, and other psychomotor/motivational symptoms are frequently seen in people with depression and other disorders. Depressed people show a decision bias towards selection of low effort activities, and animal tests of effort-related decision making are being used as models of motivational dysfunctions seen in psychopathology. The present studies investigated the ability of drugs that block dopamine transport (DAT), norepinephrine transport (NET), and serotonin transport (SERT) to modulate work output in rats responding on a test of effort-related decision making (i.e., a progressive ratio (PROG)/chow feeding choice task). With this task, rats choose between working for a preferred food (high carbohydrate pellets) by lever pressing on a PROG schedule vs. obtaining a less preferred lab chow that is freely available in the chamber. The present studies focused on the effects of the selective DAT inhibitor GBR12909, the selective SERT inhibitor fluoxetine, and the selective NET inhibitors desipramine and atomoxetine. Acute and repeated administration of GBR12909 shifted choice behavior, increasing measures of PROG lever pressing but decreasing chow intake. In contrast, fluoxetine, desipramine and atomoxetine failed to increase lever pressing output, and actually decreased it at higher doses. In the behaviorally effective dose range, GBR12909 elevated extracellular dopamine levels in accumbens core as measured by microdialysis, but fluoxetine, desipramine and atomoxetine decreased extracellular dopamine. Thus, blockade of DAT increases selection of the high effort instrumental activity, while inhibition of SERT or NET does not. These results have implications for the use of monoamine uptake inhibitors for the treatment of effort-related psychiatric symptoms in humans., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Management of individuals with long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy may involve exercise restriction and/or β-blocker therapy., Objective: This study assessed the practices of a group of paediatric electrophysiologists regarding the management of genotype-positive/phenotype-positive and genotype-positive/phenotype-negative individuals with these conditions., Method: An online survey was circulated to members of the Pediatric and Congenital Electrophysiology Society in May, 2014. The survey included questions addressing the respondents' approach regarding exercise recommendations and prescription of β-blocker therapy., Results: A total of 45 cardiologists completed the survey. The majority of respondents restricted symptomatic patients from competitive sports; however, only approximately half restricted phenotype-negative mutation carriers from this level of activity. Recommendations were less consistent regarding other types of activities. A trend was identified regarding physician physical activity and exercise recommendations for phenotype-negative mutation carriers. Less-active physicians were more likely to restrict exercise. β-blocker therapy was discussed by the majority of respondents for symptomatic patients and a significant number of asymptomatic patients., Conclusion: Exercise restriction for patients with long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy varies based on several factors including phenotype, type of exercise, guidelines referred to, and physicians' own level of activity.