Breastfeeding Duration Reduces the Risk of Childhood Leukemia and Modifies the Risk of Developing Functional Gastrointestinal Disorders.

Objective: The aim of this study was to test the hypothesis that the duration of breastfeeding in infancy reduces the risk of childhood leukemia or lymphoma, and modifies the risk of developing functional gastrointestinal disorders (FGIDs). Subjects and Methods: This case-control study involved the recruitment of children with lymphoid malignancy and functional gastrointestinal symptoms with healthy children as controls. Focused questionnaires were used to collect data on breastfeeding history and other key risk factors. Univariate and multivariate analyses were undertaken. Results: Of the 334 children with lymphoid malignancy, 65% were male. The control group included 334 age- and sex-matched participants. Most (n = 189; 56.6%) of the children with leukemia were <10 years of age. Differences between cases and controls included the duration of breastfeeding (p < 0.0001), mean birthweight (p < 0.001), maternal age (p < 0.001), paternal age (p < 0.001), birth order (p < 0.001), mean number of children (p < 0.001), BMI percentile (p = 0.042), and maternal smoking (p = 0.012). Breastfeeding duration of up to 6 months' duration, when compared with feeding of longer than 6 months, was associated with increased odds ratios (OR) for acute lymphoblastic leukemia (OR = 3.43, 95% confidence interval [CI] 2.37-4.98; p < 0.001), Hodgkin's lymphoma (OR = 1.58, 95% CI: 0.88-2.84, p = 0.120), Non-Hodgkin's lymphoma (OR = 2.14, 95% CI: 1.25-3.65, p = 0.005), and overall (OR = 1.95, 95% CI: 1.40-2.71, p < 0.001). Cases also differed from controls with regard to FGIDs, such as stomach ache (p < 0.001), dyspepsia (p < 0.001), early satiety (p = 0.017), bowel satisfaction (p < 0.001), bloating (p < 0.001), nausea (p = 0.005), vomiting (p = 0.039), constipation (p = 0.003), diarrhea (p = 0.010), gastrointestinal canal congestion (p =0.039), muscle aches pains (p = 0.008), fecal incontinence (p = 0.021), and indigestion (p = 0.003). A multivariate stepwise regression analysis revealed that maternal smoking (p < 0.001), formula feeding (p < 0.001), duration of breastfeeding (p < 0.001), birth order (p = 0.002), mother's age (p = 0.004) and the child's birthweight (p = 0.009) were predictors for leukemia. Further analysis showed that dyspepsia (p < 0.001), gastrointestinal tract canal congestion (p < 0.001), constipation (p = 0.009), diarrhea (p = 0.013), bowel satisfaction (p = 0.021), bloating (p = 0.022), duration of breastfeeding (p < 0.001), and stomach ache (p = 0.025) were significant predictors for developing FGID symptoms after adjusting for age, gender, and other confounding variables. Conclusion: This study confirmed that breastfeeding has some effect on reducing possible risk of childhood lymphoma and leukemia and FGID symptoms compared with healthy control children.

A Systematic Review of Tools to Assess Coeliac Disease-Related Knowledge.

Background: Coeliac disease (CD) is an immune-mediated disorder, with dietary exclusion of gluten the only current treatment. A good knowledge of CD and gluten-free diet (GFD) is essential for those with CD to support effective self-management. Knowledge assessment with a validated tool helps evaluate understanding and knowledge gaps to better tailor educational resources. This study's aim was to perform a systematic review to identify validated CD knowledge assessment tools. Methods: PRISMA guidelines were followed, and searches were carried out in five literature databases. Papers were reviewed for tool development and testing process and assessed against pre-defined criteria for feasibility, validity, and reliability. Results: Twenty-five papers were included in the final analysis. Studies were from 16 countries, with a range of target populations, study designs, and development processes. Eleven reported pilot testing, and five assessed readability. Content validity was assessed in ten papers and formal content validity testing in one. Many tools contained items affecting generalisability outside the region developed. Conclusions: For a CD knowledge assessment tool to be suitable for use, it needs to be well designed, tested, and generalisable. No papers identified satisfied all requirements, thus highlighting a need to develop an appropriate tool.

Development and investigation of a non-invasive disease severity index for inflammatory bowel disease.

INTRODUCTION: The disease severity index (DSI) encapsulates the inflammatory bowel disease (IBD) burden but requires endoscopic investigations. This study developed a non-invasive DSI using faecal calprotectin (DSI-fCal) and faecal myeloperoxidase (DSI-fMPO) instead of colonoscopy. METHODS: Adults with IBD were recruited prospectively. Baseline biomarker concentrations were used to develop DSI-fCal and DSI-fMPO, and these were correlated with the original DSI, IBD-symptoms, endoscopic activity, and quality-of-life (QoL). Area under the receiver-operating-characteristics curves (AUROC) assessed DSI-fCal/DSI-fMPO as predictors of clinical and biochemical remission at six months (symptom remission and fCal <150 µg/g, respectively), and a complicated IBD-course at 24 months (disease relapse needing escalation of biologicals/immunomodulators/recurrent corticosteroids, IBD-hospitalisations/surgeries). Multivariable logistic regression assessed the utility of DSI-fCal/DSI-fMPO in predicting a complicated IBD-course at 24 months. RESULTS: In total, 171 patients were included (Crohn's disease=99, female=90, median age=46y (IQR 36-59)). DSI-fCal and DSI-fMPO correlated with the original DSI (r>0.9, p<0.001), endoscopic indices (r=0.45-0.49, p<0.001), IBD-symptoms (r=0.53-0.58, p<0.001) and QoL (r=-0.57-0.58, p<0.001). Baseline DSI-fCal (AUROC=0.79, 95% CI 0.65-0.92) and DSI-fMPO (AUROC=0.80, 95% CI 0.67-0.93) were associated with 6-month clinical and biochemical remission. DSI-fCal (AUROC=0.83, 95% CI 0.77-0.89) and DSI-fMPO (AUROC=0.80, 95% CI 0.73-0.87) performed similarly in predicting a complicated IBD-course to the original DSI (pdifference>0.05). The non-invasive DSI was independently associated with a complicated IBD-course on multivariable analyses (DSI-fCal28, aOR=6.04, 95% CI 2.42-15.08; DSI-fMPO25, aOR=7.84, 95% CI 2.96-20.73). CONCLUSIONS: The DSI-fCal and DSI-fMPO perform similarly in prognosticating the longitudinal disease course as the original DSI, whilst avoiding a need for an endoscopic assessment.

The role of fecal biomarkers in individuals with inflammatory bowel disease.

INTRODUCTION: Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and Ulcerative Colitis (UC), is a relapsing and remitting condition. Noninvasive biomarkers have an increasingly important role in the diagnosis of IBD and in the prediction of future disease course in individuals with IBD. Strategies for the management of IBD increasingly rely upon close monitoring of gastrointestinal inflammation. AREAS COVERED: This review provides an update on the current understanding of established and novel stool-based biomarkers in the diagnosis and management of IBD. It also highlights key gaps, identifies limitations, and advantages of current markers, and examines aspects that require further study and analysis. EXPERT OPINION: Current noninvasive inflammatory markers play an important role in the diagnosis and management of IBD; however, limitations exist. Future work is required to further characterize and validate current and novel markers of inflammation. In addition, it is essential to better understand the roles and characteristics of noninvasive markers to enable the appropriate selection to accurately determine the condition of the intestinal mucosa.

Meta-analysis: High pooled positive predictive value of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition no-biopsy approach for coeliac disease testing in children.

BACKGROUND: The European Society of Paediatric Gastroenterology, Hepatology and Nutrition established guidelines in 2012 for a no-biopsy approach to diagnose coeliac disease in children. This guideline required symptoms suggestive of coeliac disease, positive human leukocyte antigen (HLA) DQ2/DQ8 haplotypes, tissue transglutaminase type-2 immunoglobulin A antibody titre at levels greater than 10 times the upper limit of normal, and positive endomysial immune-globulin A antibody test. An updated 2020 guideline excluded the need for symptoms and positive HLA. AIMS: To assess the pooled positive predictive value (PPV) of the no-biopsy approach with small bowel biopsy (SBB) data as the reference standard for comparison. METHODS: Database searches (October 2023) provided data that we combined using a random-effects meta-analysis to provide a pooled PPV, representing the probability that a positive test result means that an individual truly has the condition. RESULTS: We included 23 studies. Study sample sizes totalled 23,769 but only 3007 children had comparative SBB. The proportion of coeliac disease confirmed by the no-biopsy approach and SBB ranged from 79.2% to 100%, with an overall pooled PPV of 97.4% (95% confidence interval 96.0, 98.6). Sensitivity analysis showed higher PPV for the criteria that included HLA (98.5% vs. 96.8%; p = 0.017). CONCLUSION: Both no-biopsy criteria exhibit high PPV when compared to the reference standard. These results provide a consistent message of accuracy and feasibility to inform change and improve outcomes.

An evaluation of psychosocial sleep interventions for children with chronic health conditions: A systematic review.

Chronic health conditions (CHC; e.g., cystic fibrosis, type 1 diabetes) in children are associated with disease-specific physical symptoms that contribute to a high prevalence of sleep problems. Sleep problems exacerbate other health-related sequelae and can impede therapeutic response to health treatments, increasing the overall complexity of symptom management. Psychosocial sleep interventions (PSI) improve sleep in children with typical development and neurodevelopmental conditions. Yet, the effectiveness of PSI for children with CHC has scarcely been investigated. This systematic review appraises the literature examining the effectiveness and acceptability of PSI for children with CHC. A search identified 20 studies that met inclusion criteria. Data related to participant characteristics, sleep targets, research design and methods, measures, sleep outcomes and collateral effects were extracted. Study rigor was then evaluated. Most studies evaluated youth-directed Cognitive Behavioral Therapy for Insomnia or parent-implemented behavioral sleep interventions. Twelve studies demonstrated positive sleep treatment effects and four demonstrated mixed effects. Collateral improvements were reported in child mental health and parental health and well-being, though physical health benefits for children were not consistently reported. One, five and 14 studies were rated as having strong, adequate, and weak methodological rigor respectively. Recommendations for clinical practice and future research are made.

Assessment of endpoint definitions in curative-intent trials for mucosal head and neck squamous cell carcinomas: Head and Neck Cancer International Group consensus recommendations.

Robust time-to-event endpoint definitions are crucial for the assessment of treatment effect and the clinical value of trial interventions. Here, the Head and Neck Cancer International Group investigated endpoint use in phase 3 trials and trials considered potentially practice-changing published between 2008 and 2021 in the curative-intent setting for patients with mucosal head and neck squamous cell carcinoma. Of the 92 trials reviewed, we show that all core components of endpoint reporting were heterogeneous, including definitions of common terms, such as overall survival and progression-free survival. Our report highlights the urgent need for harmonisation of fundamental components of clinical trial endpoints and the engagement of all stakeholders to ensure the transparent reporting of endpoint details.

Assessment of endpoint definitions in recurrent and metastatic mucosal head and neck squamous cell carcinoma trials: Head and Neck Cancer International Group consensus recommendations.

Transparent and precise endpoint definitions are a crucial aspect of clinical trial conduct and reporting, and are used to communicate the benefit of an intervention. Previous studies have identified inconsistencies in endpoint definitions across oncological clinical trials. Here, the Head and Neck Cancer International Group assessed endpoint definitions from phase 3 trials or trials considered practice-changing for patients with recurrent or metastatic mucosal head and neck squamous cell carcinoma, published between 2008 and 2021. We identify considerable and global heterogeneity in endpoint definitions, which undermines the interpretation of results and development of future studies. We show how fundamental components of even incontrovertible endpoints such as overall survival vary widely, highlighting an urgent need for increased rigour in reporting and harmonisation of endpoints.

HEART + score: integrating carotid ultrasound to chest pain assessment in the emergency department.

OBJECTIVES: The HEART score is a clinical decision tool that stratifies patients into categories of low, moderate, and high-risk of major adverse cardiac events in the emergency department (ED) but cannot identify underlying cardiovascular disease in patients without prior history. The presence of atherosclerosis can easily be detected at the bedside using carotid ultrasound. Plaque quantification is well established, and plaque composition can be assessed using ultrasound grayscale pixel distribution analysis. This study aimed to determine whether carotid plaque burden and/or composition correlated with risk of events and could improve the sensitivity of the HEART score in risk stratifying ED patients with chest pain. METHODS: The HEART score was calculated based on history, electrocardiogram, age, risk factors, and initial troponin in patients presenting to the ED with chest pain (n = 321). Focused carotid ultrasound was performed, and maximum plaque height and total plaque area were used to determine plaque burden (quantity). Plaque composition (% blood, fat, muscle, fibrous, calcium-like tissue) was assessed by pixel distribution analysis. RESULTS: Carotid plaque height and area increased with HEART score (p < 0.0001). Carotid plaque % fibrous and % calcium also increased with HEART score. The HEART score had a higher area under the curve (AUC = 0.84) in predicting 30-day events compared to the plaque variables alone (AUCs < 0.70). Integrating plaque quantity into the HEART score slightly increased test sensitivity (62-69%) for 30-day events and reclassified 11 moderate-risk participants to high-risk (score 7-10). CONCLUSION: Plaque burden with advanced composition features (fibrous and calcium) was associated with increased HEART score. Integrating plaque assessment into the HEART score identified subclinical atherosclerosis in moderate-risk patients.

RéSUMé: OBJECTIFS: Le score HEART est un outil de décision clinique qui stratifie les patients en catégories de risque faible, modéré et élevé d'événements cardiaques indésirables majeurs à l'urgence (ED), mais ne peut pas identifier les maladies cardiovasculaires sous-jacentes chez les patients sans antécédents. La présence d'athérosclérose peut facilement être détectée au chevet du patient à l'aide de l'échographie carotide. La quantification de la plaque est bien établie et la composition de la plaque peut être évaluée à l'aide d'une analyse échographique de la distribution des pixels en niveaux de gris. Cette étude visait à déterminer si la charge et/ou la composition de la plaque carotidienne étaient corrélées avec le risque d'événements et pouvaient améliorer la sensibilité du score HEART chez les patients souffrant de douleurs thoraciques stratifiés. MéTHODES: Le score HEART a été calculé sur la base des antécédents, de l'électrocardiogramme, de l'âge, des facteurs de risque et de la troponine initiale chez les patients présentant une douleur thoracique à l'urgence (n = 321). L'échographie carotidienne focalisée a été effectuée, et la hauteur maximale de la plaque et la surface totale de la plaque ont été utilisées pour déterminer la charge de plaque (quantité). La composition de la plaque (% de sang, de graisse, de muscle, de tissu fibreux, de type calcique) a été évaluée par analyse de la distribution des pixels. RéSULTATS: La hauteur et la surface de la plaque carotide ont augmenté avec le score HEART (p<0,0001). Le pourcentage de plaque carotide fibreuse et le pourcentage de calcium ont également augmenté avec le score HEART. Le score HEART avait une zone plus élevée sous la courbe (ASC = 0,84) pour prédire les événements de 30 jours par rapport aux seules variables de la plaque (CCU < 0,70). L'intégration de la quantité de plaque dans le score HEART a légèrement augmenté la sensibilité au test (62 % à 69 %) pour les événements de 30 jours et a reclassé 11 participants à risque modéré à risque élevé (score de 7 à 10). CONCLUSION: La charge de plaque avec des caractéristiques de composition avancées (fibreuse et calcique) était associée à une augmentation du score HEART. Intégrer l'évaluation de la plaque dans le score HEART a identifié l'athérosclérose subclinique chez les patients à risque modéré.

Frailty, Outcomes, Recovery and Care Steps of Critically Ill Patients (FORECAST): a prospective, multi-centre, cohort study.

PURPOSE: Frailty is common in critically ill patients but the timing and optimal method of frailty ascertainment, trajectory and relationship with care processes remain uncertain. We sought to elucidate the trajectory and care processes of frailty in critically ill patients as measured by the Clinical Frailty Scale (CFS) and Frailty Index (FI). METHODS: This is a multi-centre prospective cohort study enrolling patients ≥ 50 years old receiving life support > 24 h. Frailty severity was assessed with a CFS, and a FI based on the elements of a comprehensive geriatric assessment (CGA) at intensive care unit (ICU) admission, hospital discharge and 6 months. For the primary outcome of frailty prevalence, it was a priori dichotomously defined as a CFS ≥ 5 or FI ≥ 0.2. Processes of care, adverse events were collected during ICU and ward stays while outcomes were determined for ICU, hospital, and 6 months. RESULTS: In 687 patients, whose age (mean ± standard deviation) was 68.8 ± 9.2 years, frailty prevalence was higher when measured with the FI (CFS, FI %): ICU admission (29.8, 44.8), hospital discharge (54.6, 67.9), 6 months (34.1, 42.6). Compared to ICU admission, aggregate frailty severity increased to hospital discharge but improved by 6 months; individually, CFS and FI were higher in 45.3% and 50.6% patients, respectively at 6 months. Compared to hospital discharge, 18.7% (CFS) and 20% (FI) were higher at 6 months. Mortality was higher in frail patients. Processes of care and adverse events were similar except for worse ICU/ward mobility and more frequent delirium in frail patients. CONCLUSIONS: Frailty severity was dynamic, can be measured during recovery from critical illness using the CFS and FI which were both associated with worse outcomes. Although the CFS is a global measure, a CGA FI based may have advantages of being able to measure frailty levels, identify deficits, and potential targets for intervention.

Association between Paediatric Complementary and Alternative Medicine Use and Parental Health Literacy, Child Health, and Socio-Economic Variables: A Prospective Study.

Complementary and Alternative Medicines (CAMs) constitute products and practices not considered allopathic medicine. CAM use is high in children, but little is known about factors that may influence parents using CAM with their child. This study aimed to determine the variables associated with CAM use in children with a prospective study among children and their parents attending a tertiary care hospital in New Zealand (NZ). Outcomes included current CAM use, parental opinions on CAM, parental health literacy and child well-being. This study was completed by 130 parents (85% female), and the mean child age was 6.7 years. CAM use was reported for 59 (45%) children, the most common being oral supplements and body manipulation. Children were more likely to use CAM if their parent had higher health literacy (p = 0.001), and if they had previously attended the emergency department within 12 months (p = 0.03). There was no association between child well-being and CAM use. Parental opinion of using CAM only if a doctor recommended it was associated with CAM use for their child (p = 0.01). Only 40% of parents disclosed their child's CAM use to the medical team. This study highlights that parental health literacy influences the use of CAM for children in NZ, providing insight for translational research to improve CAM safety and disclosure rates in NZ.

A review of minimal access surgery provision and training within the United Kingdom.

When combined with healthcare pressures, the exponential growth of robotic-assisted surgery (RAS) has impacted UK-based training outcomes, including the learning curve to competency. Aim: To ascertain the current provision of RAS and investigate differences in access to minimal access surgical (MAS) facilities and training across the UK. A two-armed electronic survey was conducted. The first arm questioned clinical leads regarding robotic practice and future training provisions. The second investigated trainee and trainers' perceptions of MAS training and facilities. 64% (52/81) of responding trusts utilise a robotic system. The majority (68% [55/81]) have plans to expand or acquire a system within 3 years. 171 responses from 112 UK and Republic of Ireland hospitals were collected for Arm 2. Laparoscopic categories queried whether trainees had access to a formal curriculum, training days and sim-boxes. Most consultants (51.9%) and trainees (51.6%) reported that there was no formal local training curriculum for robotic surgery. Combined responses demonstrated 42.1% (n = 195/463) said "yes", 39.5% (n = 183) "no" and 18.4% (n = 85) "don't know". For combined robotic categories (simulation, training days and operative lists) 28.3% (n = 134/473) responded "yes", 51.6% (n = 244) said "no" and 20.1% (n = 95) said "don't know". This study provides insight into the current provision of robotic-assisted surgery at UK trusts and highlights the need to facilitate regular clinical training and equitable access to MAS simulation within a formal curriculum. This may aid regulation of training in parallel with the expansion of robotic practice and avoid a significant skill acquisition gap and risks to patient safety.

Administration and effects of beta blockers and oxandrolone in severely burned adults: a post hoc analysis of the RE-ENERGIZE trial.

Background: Prospective randomized trials in severely burned children have shown the positive effects of oxandrolone (OX), beta blockers (BB) and a combination of the two (BBOX) on hypermetabolism, catabolism and hyperinflammation short- and long-term post-burn. Although data on severely burned adults are lacking in comparison, BB, OX and BBOX appear to be commonly employed in this patient population. In this study, we perform a secondary analysis of an international prospective randomized trial dataset to provide descriptive evidence regarding the current utilization patterns and potential treatment effects of OX, BB and BBOX. Methods: The RE-ENERGIZE (RandomizEd Trial of ENtERal Glutamine to minimIZE Thermal Injury, NCT00985205) trial included 1200 adult patients with severe burns. We stratified patients according to their receipt of OX, BB, BBOX or none of these drugs (None) during acute hospitalization. Descriptive statistics describe the details of drug therapy and unadjusted analyses identify predisposing factors for drug use per group. Association between OX, BB and BBOX and clinical outcomes such as time to discharge alive and 6-month mortality were modeled using adjusted multivariable Cox regressions. Results: More than half of all patients in the trial received either OX (n = 138), BB (n = 293) or BBOX (n = 282), as opposed to None (n = 487, 40.6%). Per study site and geographical region, use of OX, BB and BBOX was highly variable. Predisposing factors for the use of OX, BB and BBOX included larger total body surface area (TBSA) burned, higher acute physiology and chronic health evaluation (APACHE) II scores on admission and younger patient age. After adjustment for multiple covariates, the use of OX was associated with a longer time to discharge alive [hazard ratio (HR) 0.62, confidence interval (CI) (0.47-0.82) per 100% increase, p = 0.001]. A higher proportion of days on BB was associated with lower in-hospital-mortality (HR: 0.5, CI 0.28-0.87, p = 0.015) and 6-month mortality (HR: 0.44, CI 0.24-0.82, p = 0.01). Conclusions: The use of OX, BB and BBOX is common within the adult burn patient population, with its use varying considerably across sites worldwide. Our findings found mixed associations between outcomes and the use of BB and OX in adult burn patients, with lower acute and 6-month-mortality with BB and longer times to discharge with OX. Further research into these pharmacological modulators of the pathophysiological response to severe burn injury is indicated.

Exploring the Diagnostic Spectrum of Children with Raised Faecal Calprotectin Levels.

Faecal calprotectin (FC) is a marker of gut inflammation. The cause and relevance of raised FC in children outside the context of established inflammatory bowel disease (IBD) have had minimal attention. This study aimed to address this by carrying out a retrospective study on children with abnormal FC tests aged 4-17 years without established IBD in the South Island, New Zealand. Abnormal FC results were stratified: 51-249 µg/g, 250-499 µg/g, and 500+ µg/g, and participants were categorised into diagnostic groups. Data were collected on symptoms and diagnostic tests. Three-hundred and ten children had abnormal index FC results, with a mean age of 12.9 years, and a 55% proportion of females. The median FC was 125 µg/g; 71% had levels 51-249 µg/g and 21% had levels 500+ µg/g. Of those with FC 500+ µg/g, 89% either had infectious diarrhoea or were diagnosed with IBD at the time of, or subsequent to, the index FC. Alarm symptoms did not delineate between groups with FC 500+ µg/g. Abnormalities in platelet levels, abdominal ultrasound, and colonoscopy were more frequent for children diagnosed with IBD. Repeat FC test levels were significantly reduced except for those subsequently diagnosed with IBD. Abnormal FC levels for the majority were below the level indicative of mucosal inflammation. Repeat FC testing could play an important role in distinguishing between diagnoses.

Association between serum 25-hydroxyvitamin D level and myopia in children and adolescents: a cross-sectional study.

Background: Prior reports have indicated an inconsistent relationship between vitamin D levels and myopia in children and adolescents with limited sample size. This study was undertaken to further clarify this relationship with a repeated cross-section study. Methods: The National Health and Nutrition Examination Survey (NHANES) database with samples <19 years old was utilized. Data on rates of myopia (spherical equivalent less than or equal to -1.0 D), serum 25-hydroxyvitamin D [25(OH)D] level (high performance liquid chromatography), and other key variables were extracted and analyzed. Three models were utilized to evaluate the dose response of vitamin D levels using stepwise logistic regression. Logistic regressions for sex subgroups and other covariates were also performed, and Forest plots were drawn. Results: Data were available from 6,814 children (49.5% girls; mean age: 14.9±1.85 years). The myopia and non-myopia differed in serum 25(OH)D level, gender, race, poverty income ratio (PIR), and body mass index (BMI). Serum 25(OH)D levels were negatively correlated with myopia [odds ratio (OR) =0.98, 95% confidence interval (CI): 0.77-0.99, P<0.05] regardless of sex. Although the relationship did not appear to be linear, there was a dose effect with higher serum 25(OH)D levels linked with lower rates of myopia. In addition, rates of myopia were increased in females compared with males (OR =1.12, 95% CI: 1.01-1.24, P=0.03), those with a high PIR (OR =1.08, 95% CI: 1.04-1.11, P<0.001), and those with high BMI (OR =1.19, 95% CI: 1.11-1.27, P<0.001). White ethnicity (OR =0.78, 95% CI: 0.68-0.90, P<0.001) and leisure-time exercise (OR =0.94, 95% CI: 0.92-0.97, P=0.02) were associated with lower rates of myopia. Conclusions: These findings indicate that higher serum 25(OH)D levels and increased amounts of leisure-time exercise are associated with lower rates of myopia in this group of children and adolescents. Meanwhile, female gender, high PIR level, and high BMI were associated with greater rates of myopia. The findings indicated that children and adolescents needed leisure-time exercise to lower the risk of myopia.

Patterns of vitamin D testing and supplementation for children with inflammatory bowel disease in Australasia.

Background and Aim: For children with inflammatory bowel disease (IBD), optimal levels of vitamin D are ascribed anti-inflammatory and essential immune system roles that are associated with reduced disease activity, lower postoperative recurrence, and higher quality of life. International guidelines for vitamin D testing and supplementation provide inconsistent recommendations. The aim of this study was to survey Australasian pediatric gastroenterologists to ascertain current practices of vitamin D testing and supplementation for children with IBD. Methods: Members of the Australian Society of Pediatric Gastroenterology, Hepatology and Nutrition were invited to complete an online survey. Respondents were asked to provide information on frequency of vitamin D testing and supplementation, adherence, and benefits of vitamin D to children with IBD. Results: Thirty-two (54%) pediatric gastroenterologists completed the survey: 27 (84%) from Australia and 5 (16%) from New Zealand. The majority (90%) tested vitamin D levels at diagnosis and follow up, although testing frequency varied (1-3 times/year) and only 8 (28%) tested seasonally. While 28 (88%) recommended supplementation based on serum levels, inconsistent cutoff values were used. Most respondents (n = 27) recommended Stoss (single dose) or vitamin D3 (daily for 8-12 weeks). The majority (84%) rated the overall benefit of optimal vitamin D levels at ≥6/10, although fewer (54%) rated the benefit to disease activity at ≥6/10. Conclusions: The results indicate that standardized guidelines for vitamin D testing and supplementation for clinicians caring for children with IBD throughout Australasia are required. Consensus statements may optimize the care of children with IBD in this diverse geographical region.

Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19: A Phase 2 Randomized Controlled Double-Blind Study.

OBJECTIVES: Respiratory failure secondary to COVID-19 is associated with morbidity and mortality. Current anti-inflammatory therapies are effective but are given systemically and have significant side effects. Furosemide has anti-inflammatory properties, can be administered by inhalation, and is inexpensive. We investigated the efficacy of nebulized furosemide as an adjunctive therapy for COVID-19 respiratory failure. DESIGN: A double-blind, randomized, placebo-controlled trial. SETTING: Multicenter ICU study. PATIENTS: Adults requiring invasive mechanical ventilation secondary to COVID-19. INTERVENTION: Patients were randomized within 48 hours of intubation to receive inhaled furosemide or placebo until day 28, death, or liberation from mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: The study was stopped early due to waning incidence of COVID-19; 39 patients were available for analysis with mean ± sd age of 70.5 (10.8) years, Acute Physiology and Chronic Health Evaluation II 26.1 (7.8) and Fio2 60.0% (21.9). Baseline characteristics were similar between the groups. For the primary outcome of change in Pao2/Fio2 ratio between day 1 and day 6, it was +31.4 (83.5) in the furosemide arm versus +20.1 (92.8) in the control (p = 0.58). For secondary outcomes, furosemide versus control: 60-day mortality was 48% versus 71% (p = 0.20), hospital stay was 25.6 (21.9) versus 27.4 (25.0) days, p = 0.94 and VFD was 6.0 (9.1) versus 3.1 (7.1), p value of equals to 0.28. A post hoc analysis of the hierarchical composite outcome, alive and ventilator-free favored furosemide. There were no adverse events. CONCLUSIONS: In this trial of inhaled furosemide for COVID-19 respiratory failure, differences in Pao2/Fio2 ratio to day 6 and other clinical outcomes were not significantly different, although the trial was underpowered due to early termination. Given the favorable profile of inhaled furosemide, further study is warranted in disease states where acute pulmonary inflammation contributes to the underlying pathophysiology.