Recognition, prevention and management of 'digital harm'.

The digital world continues to evolve and is apparent in all aspects of daily life. For children and young people, their online life is as real to them as their in-person life. Health professionals urgently need to update their knowledge and awareness of the positive and negative impacts of the myriad of online content and how this is viewed and used by children and young people. Digital harm can contribute to multiple clinical presentations and paediatricians must ask about online life in consultations and be able to provide holistic digital safety advice, while recognising serious digital harm requiring safeguarding input.This article will introduce the main areas of harm and how to include assessment in routine clinical practice. It will equip paediatricians to offer advice and safeguard children and young people and offer resources and links to further learning.

Infant massage as a stress management technique for parents of hospitalized extremely preterm infants.

Mothers of infants born extremely preterm requiring prolonged medical intervention in the Neonatal Intensive Care Unit (NICU) are at high risk of developing stress. Parent-administered infant massage is a well-established, safe intervention for preterm infants with many developmental benefits, but the published literature has mostly examined its impact on infants and parents through self-reported or observational measures of stress. The aim of this study was to measure salivary cortisol, a biomarker for stress, in extremely preterm infants and their mothers immediately pre and post parent-administered infant massage in order to detect potential changes in physiologic stress. Twenty-two mother-infant dyads completed massage education with a physical or occupational therapist. All dyads provided salivary cortisol samples via buccal swab immediately pre- and post-massage at the second session. Of mothers determined to be "cortisol responders" (15/22), salivary cortisol levels were lower after massage (pre-minus post-level: -26.47 ng/dL, [CI = -4.40, -48.53], p = .016, paired t-test). Our primary findings include a clinically significant decrease (as measured by percent change) in maternal cortisol levels immediately post parent-administered massage, indicating decreased physiological stress. Integration of infant massage into NICU clinical practice may support maternal mental health, but further powered studies are necessary to confirm findings.

Las madres de infantes nacidos extremadamente prematuros en la Unidad de Cuidado Intensivo Neonatal (NICU) se encentran bajo alto riesgo de desarrollar estrés. El masaje que una madre le da al infante es una intervención segura, bien establecida, para infantes prematuros, con muchos beneficios de desarrollo, aunque la información publicada disponible ha examinado por la mayor parte el impacto del masaje en los infantes y progenitores por medio de medidas de estrés auto reportadas o de observación. El propósito de este estudio fue medir el cortisol salival, un biomarcador de estrés, en infantes extremadamente prematuros y sus madres inmediatamente antes y después del masaje que la madre le da, para detectar posibles cambios en el estrés fisiológico. Veintidós díadas madre-infante completaron 2 sesiones educativas de masaje con un terapeuta físico u ocupacional. Todas las díadas aportaron muestras de cortisol salival por medio de hisopado bucal inmediatamente antes y después del masaje en la segunda sesión. Los niveles de cortisol en infantes no fueron suficientes para el análisis. De las madres a quienes se les determinó haber dado "respuesta de cortisol" (15/22), los niveles de cortisol salival fueron más bajos después del masaje (nivel antes menos nivel después: −26.47 ng/dL, [CI = −4.40, −48.53]. p = .016, prueba-t pareada). Entre nuestros resultados primarios se incluye una baja clínicamente significativa (tal como fue medida por el cambio porcentual) en los niveles de cortisol materno inmediatamente después del masaje. Estos resultados sugieren que el masaje dado por la madre a infantes prematuros pudiera reducir el cortisol materno, un marcador fisiológico de estrés.

A pilot exploratory study examining the potential influence of continuous positive airway pressure devices on cranial molding trajectories in preterm infants.

OBJECTIVE: The objective of this exploratory study was to assess the potential impacts of two different continuous positive airway pressure (CPAP) devices on preterm infant head shape and circumference. STUDY DESIGN: Twenty infants born at <32 weeks gestational age requiring CPAP support were enrolled. Ten infants used the Hudson RCI Nasal Prong CPAP device and 10 infants used the Fisher-Paykel CPAP device. Infant Cranial Index (CI) and head circumference (HC) were collected weekly as well as infant gestational age at birth, and total number of days on CPAP. RESULTS: At baseline, average total birthweight of infants was 1021 grams (SD = 227 grams), average gestational age was 26.9 weeks (SD = 1.80), mean CI was 79.7 cm (SD = 5.95), and HC was 10.2 cm (SD = 0.92). Days on CPAP ranged from 16 to 63 days, with an average of 40.7 (SD = 13.6) days. Neither CI nor HC differed by device type; however, the Fisher-Paykel device was associated with slightly greater HC growth rate. CONCLUSION: CPAP devices and the pressures they apply plausibly contribute to preterm infant cranial molding over time, with the greatest potential impact on infants who require CPAP support for longer periods; however, these findings must be validated in larger cohorts. Additionally, positioning practices should be further examined to determine how they may contribute to or prevent the development of cranial molding deformity.

General population screening for paediatric type 1 diabetes-A qualitative study of UK professional stakeholders.

AIMS: Identifying children at risk of type 1 diabetes allows education for symptom recognition and monitoring to reduce the risk of diabetic ketoacidosis at presentation. We aimed to explore stakeholder views towards paediatric general population screening for type 1 diabetes in the United Kingdom (UK). METHODS: Qualitative interviews were undertaken with 25 stakeholders, including diabetes specialists, policymakers and community stakeholders who could be involved in a future type 1 diabetes screening programme in the UK. A thematic framework analysis was performed using the National Screening Committee's evaluative criteria as the overarching framework. RESULTS: Diabetic ketoacidosis prevention was felt to be a priority and proposed benefits of screening included education, monitoring and helping the family to better prepare for a future with type 1 diabetes. However, diabetes specialists were cautious about general population screening because of lack of evidence for public acceptability. Concerns were raised about the harms of living with risk, provoking health anxiety and threatening the child's right to an 'open future'. Support systems that met the clinical and psychological needs of the family living with risk were considered essential. Stakeholders were supportive of research into general population screening and acknowledged this would be a priority if an immunoprevention agent were licensed in the UK. CONCLUSIONS: Although stakeholders suggested the harms of UK paediatric general population screening currently outweigh the benefits, this view would potentially be altered if prevention therapies were licensed. In this case, an evidence-based screening strategy would need to be formulated and public acceptability explored.

Vascular adhesion protein-1 (VAP-1) in vascular inflammatory diseases.

Vascular adhesion protein-1 (VAP-1) also known as amino oxidase copper containing 3 (AOC3) is a pro-inflammatory and versatile molecule with adhesive and enzymatic properties. VAP-1 is a primary amine oxidase belonging to the semicarbazide-sensitive amine oxidase (SSAO) family, which catalyzes the oxidation of primary amines leading to the production of ammonium, formaldehyde, methylglyoxal, and hydrogen peroxide. VAP-1 is mainly expressed by endothelial cells, smooth muscle cells, adipocytes and pericytes. It is involved in a repertoire of biological functions, e.g., immune cell extravasation, angiogenesis, and vascularization. Research into VAP-1 has intensified within the last decade on its role as a novel clinical biomarker and as a potential therapeutic target of vascular inflammatory disorders such as atherosclerosis, stroke, diabetes, neurovascular disorders (e.g., Alzheimer's Disease), hepatic disease (e.g., non-alcoholic steatohepatitis), and skin conditions (e.g., psoriasis). This is the most up-to-date and comprehensive review on VAP-1 focusing on the translational aspects of VAP-1. Compared to recent reviews, our review provides novel insights on VAP-1 and heart failure, stroke and frailty, diabetes, endometriosis, osteoarthritis, COVID-19, conjunctivitis associated systemic lupus erythematosus, hematopoietic stem cells, gliomas, treatment of colorectal cancer with a novel VAP-1 inhibitor (U-V269), promoting recovery of motor functions and habit learning with a novel VAP-1 inhibitor (PXS-4681A), and 68Ga-DOTA-Siglec-9, a labelled peptide of Siglec-9 (a VAP-1 ligand), which appears to be a safe PET tracer for inflammation in rheumatoid arthritis. Finally, we present the emerging role of VAP-1 in pregnancy as a gatekeeper of immune cells, which are critical for spiral arterial remodeling, the deficiency of which could lead to vascular disorders of pregnancy such as preeclampsia. Future research should prioritize clinical trials on VAP-1 small-molecule inhibitors and monoclonal antibodies, thus, maximizing the potential of VAP-1 targeted therapy as well as research into sVAP-1 as a clinical biomarker of diseases and its prognosis.

Outcomes of a High-Volume Organ Procurement Organization in the Era of Increasing Donation After Circulatory Death.

Introduction: Donation after circulatory death (DCD) is rapidly increasing in the United States. Detailed data outlining the process from referral to organ transplantation is lacking. Project Aims: We sought to quantify differences at each stage along the referral to donation pathway by donor type. Additionally, we examined factors associated with successful DCD organ utilization. Design: This program evaluation analyzed data from a single organ procurement organization in 2018 to assess demographic and clinical predictors of progression through the donation process, including the role of first-person authorization in DCD. Descriptive statistics were examined by donation stage for demographic characteristics using chi-square; univariate and multivariate logistic regression was used to model predictors of utilization and authorization by organ type, respectively. Results: There were 2466 organ donation referrals during 2018, including 575 donations after brainstem death (DBD), 1890 controlled DCD referrals, and 1 uncontrolled DCD referral. Univariate and multivariate logistic regression models highlighted differences in authorization rates by donor type (DCD vs DBD) and by age, race, and ethnicity. Next-of-kin authorization was declined in 23% of first-person authorized potential DCD, highlighting issues related to the role of donor registration in DCD. Pre-mortem heparin administration was predictive of DCD organ utilization; donor age and warm ischemia time of less than 30 min was statistically significantly associated with DCD extra-renal organ utilization. Conclusion: These results provided insight into strategies for increasing authorization and transplantation of organs from DCD donors and identified areas of improvement for process standardization and policy development.

Educational preferences in individuals with cardiometabolic disease differs with age, ethnicity and educational status.

OBJECTIVES: To evaluate how sociodemographic factors influence educational modality preferences in people with cardiometabolic disease. METHODS: This was a cross-sectional study performed in people with diabetes and cardiovascular disease, who completed a questionnaire to denote their previous experience and ranked preferences for different educational modalities. RESULTS: The questionnaire was completed by 3751 people, of whom 59% were men, median (interquartile range) age was 68 (59-76) years, and 78% were White European. In total, 73% had diabetes, 35% had heart disease, and 10% had history of stroke; the majority (83.4%) had one of these conditions. Overall preference was for one-to-one education (77% ranked first choice), and telephone education ranked the lowest. People tended to prefer modalities they had previously experienced. CONCLUSIONS: We highlight the importance of considering factors that could influence selection of educational modalities including age, ethnicity, gender and educational level. We anticipate this approach will aid in the design, delivery and tailoring of educational programmes that are accessible to the diverse cohort of people living with chronic diseases, including diabetes and cardiovascular disease. PRACTICE IMPLICATIONS: Given the influence of multiple demographic factors and previous experiences on expressed preferences, providers should support individuals to make informed decisions about educational interventions to maximise engagement.

EarLy Surveillance for Autoimmune diabetes: protocol for a qualitative study of general population and stakeholder perspectives on screening for type 1 diabetes in the UK (ELSA 1).

OBJECTIVE: Type 1 diabetes (T1D) is the most common form of diabetes in children, accounting for 96% of cases, with 29 000 children affected in the UK. Studies have recently identified immunotherapies that safely delay the development of T1D for at least 3 years, and further therapies are in development. General population screening programs in other countries can now accurately identify children with presymptomatic T1D who can be entered into prevention studies. The UK does not have such a system in place. We aim to explore whether parents and children in the UK would want to be part of such a program of testing for T1D in the general population, how they would want to be informed and participate in such a program, and how any barriers to recruitment and participation can be addressed. Additionally, the views of stakeholders who would be involved in the testing program will be collected and analyzed. RESEARCH DESIGN AND METHODS: We will interview parents/guardians and children aged 3-13 years about their views on screening for T1D. We will recruit purposefully to ensure representation across ethnicities and socioeconomic groups. Interviews will be transcribed, analyzed and used to inform iterative co-design work with additional families to address any issues raised. Similar qualitative work will be undertaken with professional stakeholders who would be involved in implementing any future screening program. Where possible, all aspects of this study will be performed remotely by phone or online to minimize infection risk. CONCLUSIONS: This qualitative study will provide the first insights into acceptability of testing and monitoring for T1D in the general population from the perspective of families and stakeholders in the UK. Co-design work will help establish the barriers and identify strategies to mitigate and overcome these issues, as an important step towards consideration of national testing for T1D.

Chronotype and well-being in adults with established type 2 diabetes: A cross-sectional study.

AIMS: 'Chronotype' describes an individual's sleep-wake schedule, and can be classified into morning, intermediate or evening types. Evening chronotype has been widely associated with increased cardiometabolic risk and mortality in people with type 2 diabetes. We explored associations between chronotype and markers of well-being in people with type 2 diabetes. METHODS: Participants of the 'Chronotype of Patients with Type 2 Diabetes and Effect on Glycaemic Control' (CODEC) observational study completed questionnaires to determine chronotype (Morningness-Eveningness Questionnaire, MEQ) and concurrent measures of well-being (Diabetes-related Distress scale, Patient Health Questionnaire-9 to measure depression, and Self-Compassion Scale), as a secondary endpoint of the study. Adjusted generalised linear models were used to compare well-being between chronotype subgroups in this cohort. RESULTS: Of the 808 individuals included in the CODEC study, from convenience sampling, 476 individuals completed the psychosocial questionnaire substudy. Of these, 67% (n = 321) were male, and 86% (n = 408) were white European. From the MEQ, 24% (n = 114) were morning chronotype, 24% (n = 113) were evening and 52% (n = 249) were intermediate chronotype. Diabetes-related distress was significantly higher in evening chronotypes (exponentiated adjusted coefficient = 1.18 (CI: 1.05-1.32)), compared to morning (padjusted  = 0.005) and intermediate chronotypes (padjusted  = 0.039). Similarly, depression was significantly higher in evening chronotypes (exponentiated adjusted coefficient = 1.84 (CI: 1.28-2.65)) compared to morning (padjusted  = 0.001) and intermediate chronotypes (padjusted  = 0.016). DISCUSSION: Evening chronotype in people with type 2 diabetes may be associated with higher levels of diabetes-related distress and depression. These findings warrant further investigation to establish causality and evidence-based interventions that negate the effects of evening chronotype in people with type 2 diabetes.

Low Branched Chain Amino Acids and Tyrosine in Thai Patients with Type 2 Diabetes Mellitus Treated with Metformin and Metformin-Sulfonylurea Combination Therapies.

Type 2 diabetes mellitus (T2DM) is a growing public health challenge for Thailand (current prevalence ~10.0%). Amino acids offer novel biomarkers to predict risk of T2DM and indicate sub-optimal disease management, which could facilitate earlier treatment. We studied amino acid profiles in a Thai cohort comprising of individuals with T2DM (n = 65 single-drug-treated; n = 38 multi-drug-treated) compared to healthy controls (n = 104) using liquid chromatography-mass spectrometry. Age and BMI were significantly lower in the healthy controls compared to the single or multi-treated T2DM groups. The BCAA (leucine and valine) were significantly lower in the single and multi-treated T2DM groups compared to healthy controls (p < 0.001 and p < 0.001) and isoleucine was significantly lower in the single-treated compared to the healthy controls (p = 0.014). These findings beg the question whether BCAAs supplementation be beneficial in T2DM patients treated with single or multi-drug therapy? Tyrosine was significantly lower in the single and multi-treated T2DM groups compared to healthy controls (p < 0.001 and p = 0.002), whereas phenylalanine was significantly higher in the multi-treated T2DM group compared to the single treated T2DM group (p = 0.045). We provide novel insights into the effects of diabetes treatments on these amino acids in insulin resistant states such as T2DM in a unique but understudied Thai population.

Environmental Determinants of Type 1 Diabetes: From Association to Proving Causality.

The rising incidence of type 1 diabetes (T1D) cannot be ascribed to genetics alone, and causative environmental triggers and drivers must also be contributing. The prospective TEDDY study has provided the greatest contributions in modern time, by addressing misconceptions and refining the search strategy for the future. This review outlines the evidence to date to support the pathways from association to causality, across all stages of T1D (seroconversion to beta cell failure). We focus on infections and vaccinations; infant growth and childhood obesity; the gut microbiome and the lifestyle factors which cultivate it. Of these, the environmental determinants which have the most supporting evidence are enterovirus infection, rapid weight gain in early life, and the microbiome. We provide an infographic illustrating the key environmental determinants in T1D and their likelihood of effect. The next steps are to investigate these environmental triggers, ideally though gold-standard randomised controlled trials and further prospective studies, to help explore public health prevention strategies.

Patient and Professional Experiences With Virtual Antenatal Clinics During the COVID-19 Pandemic in a UK Tertiary Obstetric Hospital: Questionnaire Study.

BACKGROUND: The COVID-19 pandemic required rapid implementation of virtual antenatal care to keep pregnant women safe. This transition from face-to-face usual care had to be embraced by patients and professionals alike. OBJECTIVE: We evaluated patients' and professionals' experiences with virtual antenatal clinic appointments during the COVID-19 pandemic to determine satisfaction and inquire into the safety and quality of care received. METHODS: A total of 148 women who attended a virtual antenatal clinic appointment at our UK tertiary obstetric care center over a 2-week period provided feedback (n=92, 62% response rate). A further 37 health care professionals (HCPs) delivering care in the virtual antenatal clinics participated in another questionnaire study (37/45, 82% response rate). RESULTS: We showed that women were highly satisfied with the virtual clinics, with 86% (127/148) rating their experience as good or very good, and this was not associated with any statistically significant differences in age (P=.23), ethnicity (P=.95), number of previous births (P=.65), or pregnancy losses (P=.94). Even though 56% (83/148) preferred face-to-face appointments, 44% (65/148) either expressed no preference or preferred virtual, and these preferences were not associated with significant differences in patient demographics. For HCPs, 67% (18/27) rated their experience of virtual clinics as good or very good, 78% (21/27) described their experience as the same or better than face-to-face clinics, 15% (4/27) preferred virtual clinics, and 44% (12/27) had no preference. Importantly, 67% (18/27) found it easy or very easy to adapt to virtual clinics. Over 90% of HCPs agreed virtual clinics should be implemented long-term. CONCLUSIONS: Our study demonstrates high satisfaction with telephone antenatal clinics during the pandemic, which supports the transition toward widespread digitalization of antenatal care suited to 21st-century patients and professionals.

Palivizumab immunoprophylaxis for infants with BPD has medium- and long-term benefits: myth or maxim?

It is uncertain whether immunoprophylaxis against RSV protects preterm babies with BPD against future respiratory problems. It is biologically plausible that it does, at least in some infants. https://bit.ly/3ikzwZD.

Respiratory syncytial virus prophylaxis for prevention of recurrent childhood wheeze and asthma: a systematic review.

BACKGROUND: Acute bronchiolitis caused by respiratory syncytial virus (RSV) has been associated with greater risk of recurrent wheezing and asthma. However, it is unclear whether this association is causal. RSV-specific monoclonal antibodies have been shown to reduce RSV-related hospitalisations in high-risk infants, but the longer-term follow-up has given conflicting evidence for prevention of recurrent wheeze or asthma. OBJECTIVE: We performed a systematic review and meta-analysis to determine whether monoclonal antibody prophylaxis against RSV bronchiolitis reduces the risk of subsequent recurrent wheeze or asthma. If so, this may support the hypothesis of causality. METHODS: Studies were identified via an online database search using Embase, MEDLINE, PubMed, Web of Science and the Cochrane Library. Manufacturers of monoclonal antibodies were contacted directly for unpublished data. The intervention of interest was RSV monoclonal antibody prophylaxis, and the primary outcome measure was recurrent wheeze and/or asthma. Studies were screened according to inclusion/exclusion criteria. Included studies were evaluated for quality and assessed for bias independently by 3 reviewers using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) approach. Results were extracted into 2 × 2 outcome tables and a meta-analysis carried out producing forest plots based on relative risk. Heterogeneity was assessed using the I2 statistic. RESULTS: The search identified 141 articles, which, after screening, resulted in eight studies (2 randomised controlled trials), thus including 11,195 infants in the meta-analysis. The overall result demonstrated a non-statistically significant reduction in relative risk of developing recurrent wheeze or asthma (RR 0.60; 95% CI 0.31 to 1.16). Study quality was generally low with evidence of publication bias and statistical heterogeneity. However, sub-group analysis excluding studies deemed to be 'very low' quality showed a relative risk of 0.42 (95% CI 0.22 to 0.80, p = 0.008). A further sub-group analysis for infants aged 32 to < 36 weeks showed a statistically significant relative risk of 0.35 (95% CI 0.14 to 0.86, p = 0.02). DISCUSSION: We did not identify an overall statistically significant benefit. However, our two sub-group analyses did find statistically significant benefits of monoclonal antibody therapy on the risk of recurrent wheeze and asthma. The main limitation of this study is the lack of high-quality randomised controlled trials, highlighting the need for more research in this field.

Virtual Consultations and the Role of Technology During the COVID-19 Pandemic for People With Type 2 Diabetes: The UK Perspective.

The coronavirus disease (COVID-19) pandemic has presented unique challenges for people with diabetes, in addition to their high-risk stratification for infection. Supporting people with diabetes to self-care has been critical to reduce their risk of severe infection. This global pandemic has presented an opportunity to digitalize diabetes care and rapidly implement virtual diabetes clinics, with the aim of optimizing diabetes management and well-being, while keeping patients safe. We performed a rapid review of the literature to evaluate the feasibility and effectiveness of virtual clinics in diabetes care before and during the COVID-19 pandemic and have combined these findings with our own reflections in practice. We identified examples demonstrating safety and feasibility of virtual diabetes clinics, which aligns with our own clinical experience during the pandemic. The advantages of virtual clinics include reduced treatment burden, improved therapeutic alliances, societal and psychological benefits, and in our experience, innovative solutions to overcome the challenges presented by the transition from in-person to virtual care. We have provided three infographics to illustrate lessons learned and key recommendations, including steps to establish a virtual diabetes clinic, a checklist guide for health care professionals conducting virtual clinics, and a patient guide for making the most out of the virtual clinic. It is important to continue adapting to this pandemic and to make technology a sustainable option for the future of diabetes care.