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Background: Hyperinsulinism (HI) due to dysregulation of pancreatic beta-cell insulin secretion is the most common and most severe cause of persistent hypoglycemia in infants and children. In the 65 years since HI in children was first described, there has been a dramatic advancement in the diagnostic tools available, including new genetic techniques and novel radiologic imaging for focal HI; however, there have been almost no new therapeutic modalities since the development of diazoxide., Summary: Recent advances in neonatal research and genetics have improved our understanding of the pathophysiology of both transient and persistent forms of neonatal hyperinsulinism. Rapid turnaround of genetic test results combined with advanced radiologic imaging can permit identification and localization of surgically-curable focal lesions in a large proportion of children with congenital forms of HI, but are only available in certain centers in "developed" countries. Diazoxide, the only drug currently approved for treating HI, was recently designated as an "essential medicine" by the World Health Organization but has been approved in only 16% of Latin American countries and remains unavailable in many under-developed areas of the world. Novel treatments for HI are emerging, but they await completion of safety and efficacy trials before being considered for clinical use., Key Messages: This international consensus statement on diagnosis and management of HI was developed in order to assist specialists, general pediatricians, and neonatologists in early recognition and treatment of HI with the ultimate aim of reducing the prevalence of brain injury caused by hypoglycemia. A previous statement on diagnosis and management of HI in Japan was published in 2017. The current document provides an updated guideline for management of infants and children with HI and includes potential accommodations for less-developed regions of the world where resources may be limited., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Breastfeeding is internationally recognized as the optimal form of infant nutrition. The Baby-Friendly Initiative (BFI) is an evidence-informed program that leads to improved breastfeeding outcomes. Despite the benefits of breastfeeding, Nova Scotia has one of the lowest breastfeeding rates in Canada. Additionally, only two birthing hospitals in the province have BFI designation. We aim to address this gap using a sequential qualitative descriptive design across three phases. In Phase 1, we will identify barriers and facilitators to BFI implementation through individual, semi-structured interviews with 40 health care professionals and 20 parents. An analysis of relevant policy and practice documents will complement these data. In Phase 2, we will develop implementation interventions aimed at addressing the barriers and facilitators identified in Phase 1. An advisory committee of 10-12 administrative, clinical, and parent partners will review these interventions. In Phase 3, the interventions will be reviewed by a panel of 10 experts in BFI implementation through an online survey. Feedback on the revised implementation interventions will then be sought from 20 health system and parent partners through interviews. This work will use implementation science methods to support integrated and sustained implementation of the BFI across hospital/community and rural/urban settings in Nova Scotia. This study was not registered.

Context: Lower levels of free T3 (FT3) occur during acute illness, as part of "euthyroid sick syndrome." A chronic form of this syndrome also exists., Objective: To determine whether thyroid hormone levels predict long-term survival., Design and Setting: This was a "big-data" study of thyroid function tests from samples taken between 2008 and 2014. Data were crossed with electronic health records for morbidity and mortality. Test results were converted to age- and gender-adjusted percentiles (AGAPs). The hazard ratio for death was crossed with ranges of initial AGAPs and change in AGAPs for 2 subgroups: "not healthy" (subjects with at least 1 of 5 chronic conditions registered in their electronic health chart) and "healthy" (all others)., Participants: 2 453 091 sets of thyroid function tests from 365 965 distinct patients were evaluated. 258 695 sets remained after excluding patients registered as taking thyroid preparations or anti-thyroid drugs., Main Outcome Measure: Hazard ratio for death, planned before data collection., Results: The cohort included 151 868 not healthy and 106 827 healthy people. After a median of 6.8 years, 5865/151 868 (10.4%) of the not healthy had died and 2504/106 827 (2.3%) of healthy participants. Low initial FT3 AGAPs were predictive of poor survival. The hazard ratio for survival compared between the lowest 5 and highest 50 percentiles of initial FT3 AGAPs for not healthy participants was 5.71 [confidence interval (CI) 5.23-6.26, P < .001] and for healthy was 3.92 (CI 3.06-5.02, P < .001)., Conclusion: Low FT3 AGAPs predicted poor survival, most strongly among not healthy people., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To assess the long-term efficacy of burosumab for pediatric patients with X-linked hypophosphatemia, focusing on linear growth. This multi-center retrospective study included 35 pediatric patients who began treatment with burosumab between January 2018 and January 2021. We collected clinical data, anthropometric measurements, laboratory results, and Rickets Severity Score (RSS), from 2 years prior to treatment initiation and up to 4 years after. Burosumab was initiated at a mean age of 7.5 ± 4.4 years (range 0.6-15.9), with a mean initial dose of 0.8 ± 0.3 mg/kg, which was subsequently increased to 1.1 ± 0.4 mg/kg. The patients were followed for 2.9 ± 1.4 years (range 1-4) after initiating burosumab. Serum phosphorus levels increased from 2.7 ± 0.8 mg/dl at burosumab initiation to 3.4 ± 0.6 mg/dl after 3 months and remained stable (p < 0.001). Total reabsorption of phosphorus increased from 82.0 ± 6.8 to 90.1 ± 5.3% after 12 months of treatment (p = 0.041). The RSS improved from 1.7 ± 1.0 at burosumab initiation to 0.5 ± 0.6 and 0.3 ± 0.6 after 12 and 24 months, respectively (p < 0.001). Both height z-score and weight z-score improved from burosumab initiation to the end of the study: from - 2.07 ± 1.05 to - 1.72 ± 1.04 (p < 0.001) and from - 0.51 ± 1.12 to - 0.11 ± 1.29 (p < 0.001), respectively. Eight children received growth hormone combined with burosumab treatment. Height z-score improved among those who received growth hormone (from - 2.33 ± 1.12 to - 1.94 ± 1.24, p = 0.042) and among those who did not (from - 2.01 ± 1.01 to - 1.66 ± 1.01, p = 0.001)., Conclusion:  Burosumab treatment in a real-life setting improved phosphate homeostasis and rickets severity and enhanced linear growth., What Is Known: • Compared to conventional therapy, burosumab treatment has been shown to increase serum phosphate levels and reduce the severity of rickets. • The effect of burosumab on growth is still being study., What Is New: • Height z-score improved between the start of burosumab treatment and the end of the study (-2.07 ± 1.05 vs. -1.72 ± 1.04, p < 0.001). • Eight children received burosumab combined with growth hormone treatment without side effects during the concomitant treatments., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Idiopathic Anaphylaxis (IA) is the most common anaphylactic syndrome in adults. Mental health problems associated with IA are not well recognised. We aimed to assess if patients diagnosed with IA were more likely to experience mental health problems compared to a normative Australian population. We additionally hypothesised that the number of anaphylactic episodes would correlate with symptoms of anxiety., Methods: A total of 34 patients with at least one episode of IA were recruited from an adult immunology clinic. Patients were recruited as part of a separate study evaluating alternative aetiologies in IA. Mental health problems were measured using the Depression, Anxiety and Stress Scale (DASS-21). An extension of the survey included questions specifically focused on the psychological impact of IA., Results: Compared to population norms, those with IA had significantly higher levels of mental health problems. Statistically significant DASS-21 scores were identified for depression 4.24 vs. 2.57 (p < 0.001), anxiety 4.76 vs. 1.74 (p < 0.012), stress 7.35 vs. 3.95 (p < 0.001) and total score 16.35 vs. 8.00 (p < 0.001). There was no association between two or more episodes of anaphylaxis and increased anxiety levels (β = 0.52, CI -2.59-3.62, p = 0.74)., Conclusions: This is the first paper to demonstrate that patients living with idiopathic anaphylaxis are more symptomatic for mental illness than those in the community. Screening for mental illness and referral for psychological support should be undertaken in people with IA., (© 2023. Canadian Society of Allergy & Clinical Immunology.)

Since the early 1990s, porcine reproductive and respiratory syndrome (PRRS) virus outbreaks have been reported across various parts of North America, Europe, and Asia. The incursion of PRRS virus (PRRSV) in swine herds could result in various clinical manifestations, resulting in a substantial impact on the incidence of respiratory morbidity, reproductive loss, and mortality. Veterinary experts, among others, regularly analyze the PRRSV open reading frame-5 (ORF-5) for prognostic purposes to assess the risk of severe clinical outcomes. In this study, we explored if predictive modeling techniques could be used to identify the severity of typical clinical signs observed during PRRS outbreaks in sow herds. Our study aimed to evaluate four baseline machine learning (ML) algorithms: logistic regression (LR) with ridge and lasso regularization techniques, random forest (RF), k-nearest neighbor (KNN), and support vector machine (SVM), for the clinical impact classification of ORF-5 sequences and demographic data into high impact and low impact categories. First, baseline classifiers were evaluated using different input representations of ORF-5 nucleotides, amino acid sequences, and demographic data using a 10-fold cross-validation technique. Then, we designed a consensus voting ensemble approach to aggregate the different types of input representations for genetic and demographic data for classifying clinical impact. In this study, we observed that: (a) for abortion and pre-weaning mortality (PWM), different classifiers gained improvement over baseline accuracy, which showed the plausible presence of both genotypic-phenotypic and demographic-phenotypic relationships, (b) for sow mortality (SM), no baseline classifier successfully established such linkages using either genetic or demographic input data, (c) baseline classifiers showed good performance with a moderate variance of the performance metrics, due to high-class overlap and the small dataset size used for training, and (d) the use of consensus voting ensemble techniques helped to make the predictions more robust and stabilized the performance evaluation metrics, but overall accuracy did not substantially improve the diagnostic metrics over baseline classifiers., 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 © 2023 Chadha, Dara, Pearl, Gillis, Rosendal and Poljak.)

Objective: The Royal Australian and New Zealand College of Psychiatrists recommends screening for a range of antibodies in first-episode psychosis, including anti-glutamic acid decarboxylase antibodies. Glutamic acid decarboxylase antibody-associated encephalitis occurs with high antibody titres and may cause cognitive dysfunction, seizures and psychiatric symptoms. However, glutamic acid decarboxylase antibodies are more frequently found in lower titre in association with other autoimmune disorders (such as diabetes mellitus type 1) and in healthy individuals. The utility of testing unselected populations of consumers with psychosis is unclear. The psychiatric manifestations of this disorder are also poorly described., Methods: First, systematic review of cohort and case-control studies that tested for IgG glutamic acid decarboxylase antibodies in psychiatric populations was conducted. Random-effects meta-analysis of odds ratio for antibody positivity in cases with psychosis and controls assessed prevalence. Second, literature review of all published cases and case series of glutamic acid decarboxylase antibody-associated limbic encephalitis was assessed for frequency and description of psychotic symptoms., Results: There were 17 studies, in which 2754 individuals with psychotic disorders were tested for glutamic acid decarboxylase IgG antibodies. Thirty-one consumers with psychosis (0.7%) had positive glutamic acid decarboxylase antibodies compared to 24 controls (1.0%), all at low titre and not fulfilling diagnostic criteria for autoimmune encephalitis. Meta-analysis found no significant difference in rates of glutamic acid decarboxylase antibody positivity (odds ratio = 1.8, 95% confidence interval: [0.90, 3.63]). Literature review found 321 cases of glutamic acid decarboxylase antibody-associated limbic encephalitis, with psychosis in 15 (4.3%) cases. Clinical screening would have identified all cases that presented to psychiatric services., Conclusion: Glutamic acid decarboxylase antibodies were uncommon in consumers with psychosis, with no significant difference in prevalence from controls and no cases of encephalitis identified. In cases with established glutamic acid decarboxylase antibody-associated limbic encephalitis, psychotic symptoms were uncommon and identifiable by clinical assessment. Targeted antibody testing guidelines should be further considered.

The aim of the study was to evaluate the bone-optimal pediatric levels of 25-hydroxy-vitamin D (25OHD) by testing the level at which 25OHD optimally effects calcium, phosphorus, and parathyroid hormone levels in a large population-based dataset. This was an observational retrospective "big-data" study. We analyzed 49 935 25OHD tests from children sampled in Clalit Health Services, Jerusalem district between 2009 and 2019. Associated data were available in the following number of samples: corrected calcium; 18 869, phosphorus: 1241, and PTH: 449. We tested correlations between each parameter and 25OHD, adjusting phosphorus levels by age using a "phosphorus index". Pearson's and Spearman's correlation coefficients were calculated to determine the strength of the correlation between 25OHD and each parameter. There was a significant correlation between 25OHD levels and both PTH and calcium but not for the phosphorus index. The level at which increase in 25OHD continued to cause significant alteration was: for PTH up to 100 nmol/l (40 ng/ml), for corrected calcium it increased beyond 100 nmol/l. Increasing levels of 25OHD levels up to at least 100 nmol/l are associated with improvement in parameters known to be associated with increased bone mineralization. Therefore, one should aim for a 25OHD level of 100 nmo/l., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Aim: Angiotensin II type 1 receptor antibody (AT1R Ab) is a non-Human Leucocyte Antigen (HLA) antibody that is maybe associated with early severe kidney transplant rejection and worse graft outcomes. This study aimed to assess the association between AT1R Ab and kidney transplant rejection and graft outcomes., Methods: We performed a retrospective analysis of all adult kidney transplant recipients in an Australian centre who had an AT1R Ab test between 1 January 2015 to 30 June 2020. AT1R Ab positive patients were compared to AT1R Ab negative patients. Primary outcomes were rejection risk, type and histopathological severity scores. Secondary outcomes were 8-week graft function and graft loss., Results: Of 965 kidney transplants that were performed during the study period, 73 patients had AT1R Ab tested; 16 (22%) were positive and 57(78%) were negative. Positive patients were on average younger and had higher level of donor-specific HLA antibodies. Rejection occurred in 13 (81%) positive patients and 41 (72%) negative patients (P = 0.45). No significant differences in rejection type or severity were found. HLA mismatch and peak panel reactive antibody ≥80%, but not AT1R Ab, independently predicted rejection. Average (132 vs. 177 mmol/L, P = 0.302) and graft loss were not significantly different between groups., Conclusion: The study found no evidence that AT1R Ab is associated with rejection type, severity or worse graft function. Future studies should assess its relationship with graft outcomes to help complement immunological risk assessment and potentially provide therapeutic options to alter outcomes., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Although burnout is often discussed as 'present' or 'not-present', the conceptual framework of an engagement-burnout continuum is more accurate and useful. Recognition of individuals' transitional states of burnout also allows for earlier detection of issues and tailored interventions to address the full burnout spectrum., Methods: Previously reported Maslach Burnout Inventory-Human Services Scale (MBI-HSS) data from a 2017 national survey of 1272 veterinarians across Canada were re-analysed using a latent profile analysis to classify individuals along the engagement-burnout continuum., Results: Four clusters were identified: engaged (10.8%), ineffective (18.9%), overextended (29.6%) and burnout (40.7%). These results indicate that most participants (89.2%) had one, or a combination, of high exhaustion, high depersonalisation and low professional efficacy., Limitations: This cross-sectional study represents data from one point in time and may be subject to response bias., Conclusion: We discuss strategies-particularly long-term, organisational-level interventions-to promote engagement and help address workplace issues contributing to inefficacy, overextension and burnout in the veterinary profession. We also recommend MBI data be analysed via latent profiles to provide a more nuanced view of burnout, allow for earlier recognition of workplace issues and facilitate more meaningful interventions and comparisons across populations., (© 2022 British Veterinary Association.)

Background: Anti-N-methyl-D-aspartate-receptor (anti-NMDA-R) encephalitis is a complex autoimmune neuropsychiatric syndrome. Although initially associated with ovarian teratoma, subsequent studies have demonstrated that anti-NMDA-R encephalitis may occur without an identifiable cause or be triggered by viral infection of the central nervous system such as herpes simplex virus encephalitis (HSVE)., Aim: To present details from a Queensland cohort analysing triggering events in patients with anti-NMDA-R encephalitis in an Australian context., Methodology: The authors identified patients with anti-NMDA-R encephalitis diagnosed and managed through public hospitals in Queensland, Australia, between 2010 and the end of 2019. Data collected included demographics, clinical presentation, investigation results, management and outcome measurements., Results: Thirty-one cases of anti-NMDA-R encephalitis were included in the study. Three cases of anti-NMDA-R encephalitis were triggered by prior HSVE, five cases were associated with ovarian teratoma and 23 cases had no identifiable trigger. There were an additional three cases in which anti-NMDA receptor antibodies were present in the context of other disease states but where the patient did not develop anti-NMDA-R encephalitis. Cases triggered by HSVE or associated with ovarian teratoma experienced a more severe disease course compared to cases with no identifiable trigger. All groups responded to immunosuppressive or immunomodulatory therapy. Analysis of clinical characteristics revealed a complex heterogeneous syndrome with some variability between groups., Conclusion: In this cohort, the number of cases of anti-NMDA-R encephalitis triggered by HSVE is comparable to those triggered by ovarian teratoma. However, the majority of cases of anti-NMDA-R encephalitis had no identifiable trigger or associated disease process., (© 2021 Royal Australasian College of Physicians.)

Thyroid screening is recommended during pregnancy with serum thyrotropin (TSH) as the primary test. However, since human chorionic gonadotropin, the serum hallmark of pregnancy, has TSH-like effects, the adequacy of TSH as a screening tool in this constellation requires further study. This study aimed to evaluate the relationship between TSH and thyroid hormones during pregnancy in order to determine if TSH is an adequate screening tool. This was a retrospective study utilizing the Clalit Health Service, Jerusalem district database between 2006-2017 in which we analyzed TSH, FT4 and FT3 measurements from 32430 pregnancies resulting in live birth. We grouped FT4 and FT3 levels by trimester and by the following TSH levels: (1) below 0.1/0.2/0.3 mIU/l, (2) 0.1-2.5/0.2-3.0/0.3-3.0 mIU/l, (3) 2.6-4.0/3.1-4.0 mIU/l, (4) 4.1-10.0 mIU/l and (5) above 10.0 mIU/l. In the first trimester, the most important for fetal brain development, FT3 was below normal, defined as below the 2.5th percentile for the population, in only 15.3% of tests with TSH over 10 mIU/l. FT4 was below normal in only 12.8% of such tests. Similar findings were noted for the second and third trimesters. As expected, there were far less abnormal tests when lower TSH cutoff levels were tested. In conclusion, TSH levels beyond the range accepted as normal do not, in most cases, reflect abnormal thyroid hormone levels during pregnancy. TSH is not a good screen for overt hypothyroidism in pregnancy. This may be due, at least in the first trimester, to thyrotropic effects of HCG., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Robust evidence of whether vitamin D deficiency is associated with COVID-19 infection and its severity is still lacking. The aim of the study was to evaluate the association between vitamin D levels and the risks of SARS-CoV-2 infection and severe disease in those infected. A retrospective study was carried out among members of Clalit Health Services (CHS), the largest healthcare organization in Israel, between March 1 and October 31, 2020. We created two matched case-control groups of individuals for which vitamin D levels and body mass index (BMI) were available before the pandemic: group (A), in which 41,757 individuals with positive SARS-CoV-2 PCR tests were matched with 417,570 control individuals without evidence of infection, and group (B), in which 2533 patients hospitalized in severe condition for COVID-19 were matched with 2533 patients who were tested positive for SARS-CoV-2, but were not hospitalized. Conditional logistic models were fitted in each of the groups to assess the association between vitamin D levels and outcome. An inverse correlation was demonstrated between the level of vitamin D and the risks of SARS-CoV-2 infection and of severe disease in those infected. Patients with very low vitamin D levels (< 30 nmol/L) had the highest risks for SARS-CoV-2 infection and also for severe COVID-19 when infected-OR 1.246 [95% CI 1.210-1.304] and 1.513 [95% CI 1.230-1.861], respectively. In this large observational population study, we show a significant association between vitamin D deficiency and the risks of SARS-CoV-2 infection and of severe disease in those infected., (© 2021. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Successful mitigation of emerging infectious disease requires that the public adopt recommended behaviours, which is directly influenced by effective crisis communication. Social media has become an important communication channel during COVID-19 where official actors, influencers, and the public are co-creating crisis messages. Our research examined COVID-19-related crisis messages across Canadian influencer accounts within news media, politicians, public health and government, science communicators, and brand influencer and celebrities, posted on Instagram between December 2019 and March 2021 for Health Belief Model and Extended Parallel Processing Model constructs and the corresponding public comment sentiment and engagement. Thirty-three influencer accounts resulted in a total of 2,642 Instagram posts collected, along with 461,436 comments, which showed overall low use of constructs in both captions and images. Further, most posts used no combinations (n = 0 or 1 construct per post) of constructs in captions and images and very infrequently used captions that combined threat (severity and susceptibility) with cues to action and efficacy. Brand influencers and celebrities, politicians, and science communicators had above average post engagement while public health and government and news media had lower. Finally, most influencers saw the largest proportion of neutral sentiment comments. Crisis messages must be designed to include combinations of constructs that increase message acceptance and influence risk perception and efficacy to increase the adoption of recommended and mandated behaviours., (© 2022. The Author(s).)