Are topical nitrates safe and effective for upper extremity tendinopathies?

Q. Are topical nitrates safe and effective for upper extremity tendinopathies? A. Topical nitrates provide short-term relief with some side effects, especially headache. Topical nitroglycerin (NTG) patches improve subjective pain scores by about 30% and range of motion over 3 days in patients with acute shoulder tendinopathy (strength of recommendation [SOR]: C, small randomized controlled trial [RCT] with no methodologic flaws). NTG patches, when combined with tendon rehabilitation, improve subjective pain ratings by about 30% and shoulder strength by about 10% in patients with chronic shoulder tendinopathy over 3 to 6 months, but not in the long term (SOR: C, RCTs with methodologic flaws). They improve pain and strength 15% to 50% for chronic extensor tendinosis of the elbow over a 6-month period (SOR: C, small RCT with methodologic flaws). NTG patches used without tendon rehabilitation don't improve pain or strength in chronic lateral epicondylitis over 8 weeks (SOR: C, RCT). Topical NTG patches commonly produce headaches and rashes (SOR: B, multiple RCTs)

Long‐term outcomes after paediatric sepsis (LOTUS)–A protocol for an Australian cohort study

Background: Globally, sepsis has been identified as one of the leading causes of preventable childhood mortality and morbidity. Previous studies on intensive care patients estimated that approximately 30% of children with sepsis experience some form of disability at discharge. Development of care has seen growing numbers of children treated for sepsis not requiring a PICU admission; however, outcomes in this population are yet to be understood. Further focus is required to understand sepsis survivorship across the wider population to address knowledge gaps and morbidity burden in the broader surviving population. Aims: To assess the cognitive, physical, emotional and social health of children surviving sepsis 2 years after hospital discharge. Study design: A prospective, observational cohort study. Results: Two hundred and thirty-two children will be screened, 2 years after their hospital admission, and approached for participation in this study. Children who are <18 years of age at follow-up, treated for sepsis-related organ dysfunction or septic shock in Queensland between October 2018 and December 2019, will be included. Children who are deceased at follow-up, under care of the state, or require English interpreters will be excluded from participation. Data will be collected through an online follow-up survey comprising validated caregiver-reported questionnaires covering the four Post Intensive Care Syndrome-paediatrics (PICS-p) domains (cognitive, physical, emotional and social health; Manning et al. Pediatr Crit Care Med, 2018, 19, 298-300). The primary outcome is an adaptive behaviour of the participants assessed using the Vinelands-3 tool. Secondary outcomes will include neurodevelopment, quality of life, child distress, overall function, executive function, caregiver's distress and caregiver's stress. Analysis of variance (ANOVA), Kruskal-Wallis and Fisher's exact test/chi-squared tests will be used for statistical analyses. No adjustments will be made for multiple comparisons but it is acknowledged that comparisons made in this study are exploratory. Relevance to clinical practice: With more children surviving sepsis, there is a need for a more comprehensive assessment of patient and family outcomes to allow support structures for families leaving the hospital after sepsis. This study is expected to inform clinicians and stakeholders of patient and family well-being after sepsis survivorship

Career Advancement Academies: Insights into Contextualized Teaching and Learning

This brief explores our work with the Career Ladders Project (CLP) to improve educational outcomes for underserved Californians.Launched in 2007, the Career Advancement Academies are designed to enable underserved Californians – typically first in their families to attend college, low-income, or from communities of color – to enroll in higher education and adjust to emerging and evolving workforce and industry needs. Specifically, CAAs aim to increase the supply of middle skill workers by targeting under-prepared young adults (ages 18-30) whose low basic skills in reading, writing, and mathematics shut them out of post-secondary education and high-wage jobs. CAAs support students through a holistic set of interventions to build the foundational skills needed to complete postsecondary education and enter careers

Machine learning to predict poor school performance in paediatric survivors of intensive care: a population-based cohort study

Purpose: Whilst survival in paediatric critical care has improved, clinicians lack tools capable of predicting long-term outcomes. We developed a machine learning model to predict poor school outcomes in children surviving intensive care unit (ICU). Methods: Population-based study of children < 16 years requiring ICU admission in Queensland, Australia, between 1997 and 2019. Failure to meet the National Minimum Standard (NMS) in the National Assessment Program-Literacy and Numeracy (NAPLAN) assessment during primary and secondary school was the primary outcome. Routine ICU information was used to train machine learning classifiers. Models were trained, validated and tested using stratified nested cross-validation. Results: 13,957 childhood ICU survivors with 37,200 corresponding NAPLAN tests after a median follow-up duration of 6 years were included. 14.7%, 17%, 15.6% and 16.6% failed to meet NMS in school grades 3, 5, 7 and 9. The model demonstrated an Area Under the Receiver Operating Characteristic curve (AUROC) of 0.8 (standard deviation SD, 0.01), with 51% specificity to reach 85% sensitivity [relative Area Under the Precision Recall Curve (rel-AUPRC) 3.42, SD 0.06]. Socio-economic status, illness severity, and neurological, congenital, and genetic disorders contributed most to the predictions. In children with no comorbidities admitted between 2009 and 2019, the model achieved a AUROC of 0.77 (SD 0.03) and a rel-AUPRC of 3.31 (SD 0.42). Conclusion: A machine learning model using data available at time of ICU discharge predicted failure to meet minimum educational requirements at school age. Implementation of this prediction tool could assist in prioritizing patients for follow-up and targeting of rehabilitative measures. Keywords: Child, Intensive care, Machine learning, Neurodevelopment, Schoo

Study protocol: NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC trial): a randomised controlled trial

Introduction Congenital heart disease (CHD) is a major cause of infant mortality. Many infants with CHD require corrective surgery with most operations requiring cardiopulmonary bypass (CPB). CPB triggers a systemic inflammatory response which is associated with low cardiac output syndrome (LCOS), postoperative morbidity and mortality. Delivery of nitric oxide (NO) into CPB circuits can provide myocardial protection and reduce bypass-induced inflammation, leading to less LCOS and improved recovery. We hypothesised that using NO during CPB increases ventilator-free days (VFD) (the number of days patients spend alive and free from invasive mechanical ventilation up until day 28) compared with standard care. Here, we describe the NITRIC trial protocol. Methods and analysis The NITRIC trial is a randomised, double-blind, controlled, parallel-group, two-sided superiority trial to be conducted in six paediatric cardiac surgical centres. One thousand three-hundred and twenty infants <2 years of age undergoing cardiac surgery with CPB will be randomly assigned to NO at 20 ppm administered into the CPB oxygenator for the duration of CPB or standard care (no NO) in a 1:1 ratio with stratification by age (<6 and ≥6 weeks), single ventricle physiology (Y/N) and study centre. The primary outcome will be VFD to day 28. Secondary outcomes include a composite of LCOS, need for extracorporeal membrane oxygenation or death within 28 days of surgery; length of stay in intensive care and in hospital; and, healthcare costs. Analyses will be conducted on an intention-to-treat basis. Preplanned secondary analyses will investigate the impact of NO on host inflammatory profiles postsurgery. Ethics and dissemination The study has ethical approval (HREC/17/QRCH/43, dated 26 April 2017), is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617000821392) and commenced recruitment in July 2017. The primary manuscript will be submitted for publication in a peer-reviewed journal. Trial registration number ACTRN12617000821392.</p

Nitric Oxide on Extracorporeal Membrane Oxygenation in Neonates and Children (NECTAR Trial): Protocol for a Randomized Controlled Trial

Background Extracorporeal membrane oxygenation (ECMO) provides support for the pulmonary or cardiovascular function of children in whom the predicted mortality risk remains very high. The inevitable host inflammatory response and activation of the coagulation cascade due to the extracorporeal circuit contribute to additional morbidity and mortality in these patients. Mixing nitric oxide (NO) into the sweep gas of ECMO circuits may reduce the inflammatory and coagulation cascade activation during ECMO support. Objective The purpose of this study is to test the feasibility and safety of mixing NO into the sweep gas of ECMO systems and assess its effect on inflammation and coagulation system activation through a pilot randomized controlled trial. Methods The Nitric Oxide on Extracorporeal Membrane Oxygenation in Neonates and Children (NECTAR) trial is an open-label, parallel-group, pilot randomized controlled trial to be conducted at a single center. Fifty patients who require ECMO support will be randomly assigned to receive either NO mixed into the sweep gas of the ECMO system at 20 ppm for the duration of ECMO or standard care (no NO) in a 1:1 ratio, with stratification by support type (veno-venous vs veno-arterial ECMO). Results Outcome measures will focus on feasibility (recruitment rate and consent rate, and successful inflammatory marker measurements), the safety of the intervention (oxygenation and carbon dioxide control within defined parameters and methemoglobin levels), and proxy markers of efficacy (assessment of cytokines, chemokines, and coagulation factors to assess the impact of NO on host inflammation and coagulation cascade activation, clotting of ECMO components, including computer tomography scanning of oxygenators for clot assessments), bleeding complications, as well as total blood product use. Survival without ECMO and the length of stay in the pediatric intensive care unit (PICU) are clinically relevant efficacy outcomes. Long-term outcomes include neurodevelopmental assessments (Ages and Stages Questionnaire, Strength and Difficulties Questionnaire, and others) and quality of life (Pediatric Quality of Life Inventory and others) measured at 6 and 12 months post ECMO cannulation. Analyses will be conducted on an intention-to-treat basis. Conclusions The NECTAR study investigates the safety and feasibility of NO as a drug intervention during extracorporeal life support and explores its efficacy. The study will investigate whether morbidity and mortality in patients treated with ECMO can be improved with NO. The intervention targets adverse outcomes in patients who are supported by ECMO and who have high expected mortality and morbidity. The study will be one of the largest randomized controlled trials performed among pediatric patients supported by ECMO. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12619001518156; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376869 International Registered Report Identifier (IRRID) DERR1-10.2196/4376

Resuscitation With Early Adrenaline Infusion for Children With Septic Shock: A Randomized Pilot Trial

OBJECTIVES: In children with septic shock, guidelines recommend resuscitation with 40–60 mL/kg of fluid boluses, yet there is a lack of evidence to support this practice. We aimed to determine the feasibility of a randomized trial comparing early adrenaline infusion with standard fluid resuscitation in children with septic shock. DESIGN: Open-label parallel randomized controlled, multicenter pilot study. The primary end point was feasibility; the exploratory clinical endpoint was survival free of organ dysfunction by 28 days. SETTING: Four pediatric Emergency Departments in Queensland, Australia. PATIENTS: Children between 28 days and 18 years old with septic shock. INTERVENTIONS: Patients were assigned 1:1 to receive a continuous adrenaline infusion after 20 mL/kg fluid bolus resuscitation (n = 17), or standard care fluid resuscitation defined as delivery of 40 to 60 mL/kg fluid bolus resuscitation prior to inotrope commencement (n = 23). MEASUREMENTS AND MAIN RESULTS: Forty of 58 eligible patients (69%) were consented with a median age of 3.7 years (interquartile range [IQR], 0.9–12.1 yr). The median time from randomization to inotropes was 16 minutes (IQR, 12–26 min) in the intervention group, and 49 minutes (IQR, 29–63 min) in the standard care group. The median amount of fluid delivered during the first 24 hours was 0 mL/kg (IQR, 0–10.0 mL/kg) in the intervention group, and 20.0 mL/kg (14.6–28.6 mL/kg) in the standard group (difference, –20.0; 95% CI, –28.0 to –12.0). The number of days alive and free of organ dysfunction did not differ between the intervention and standard care groups, with a median of 27 days (IQR, 26–27 d) versus 26 days (IQR, 25–27 d). There were no adverse events reported associated with the intervention. CONCLUSIONS: In children with septic shock, a protocol comparing early administration of adrenaline versus standard care achieved separation between the study arms in relation to inotrope and fluid bolus use

Mental Well-Being in UK Higher Education During Covid-19: Do Students Trust Universities and the Government?

This paper draws upon the concept of recreancy to examine the mental well-being of university students during the Covid-19 pandemic. Briefly, recreancy is loss of societal trust that results when institutional actors can no longer be counted on to perform their responsibilities. Our study of mental well-being and recreancy focuses on the role of universities and government regulators within the education sector. We surveyed 600 UK students attending 161 different public higher education providers in October 2020 during a time when many UK students were isolated in their residences and engaged in online learning. We assessed student well-being using the Short Warwick-Edinburgh Mental Well-being Scale (scored 7–35) and found the mean score to be 19.9 [95% confidence interval (CI) 19.6, 20.2]. This level of well-being indicates that a significant proportion of UK students face low levels of mental well-being. Structural equation modeling (SEM) analysis indicates that high recreancy—measured as a low trust in universities and the government—is associated with low levels of mental well-being across the student sample. While these findings are suggestive, they are also important and we suggest that government and university leaders should not only work to increase food and housing security during the Covid-19 pandemic, but also consider how to combat various sector trends that might intensify recreancy

Resuscitation With Vitamin C, Hydrocortisone, and Thiamin in Children With Septic Shock: A Multicenter Randomized Pilot Study

OBJECTIVES: Adjunctive therapy with vitamin C, hydrocortisone, and thiamin has been evaluated in adults, but randomized controlled trial (RCT) data in children are lacking. We aimed to test the feasibility of vitamin C, hydrocortisone, and thiamin in PICU patients with septic shock; and to explore whether the intervention is associated with increased survival free of organ dysfunction. DESIGN: Open-label parallel, pilot RCT multicenter study. The primary endpoint was feasibility. Clinical endpoints included survival free of organ dysfunction censored at 28 days and nine secondary outcomes, shock reversal, and two proxy measures of intervention efficacy. SETTING: Six PICUs in Australia and New Zealand. PATIENTS: Children of age between 28 days and 18 years requiring vasoactive drugs for septic shock between August 2019 and March 2021. INTERVENTIONS: Patients were assigned 1:1 to receive 1 mg/kg hydrocortisone every 6 hours (q6h), 30 mg/kg ascorbic acid q6h, and 4 mg/kg thiamin every 12 hours (n = 27), or standard septic shock management (n = 33). MEASUREMENTS AND MAIN RESULTS: Sixty of 77 (78%) eligible patients consented with 91% of approached parents providing consent. The median time from randomization to intervention was 44 (interquartile range [IQR] 29–120) min. Seventy of seventy-seven (28%) patients had received IV steroids before randomization. Median survival alive and free of organ dysfunction was 20.0 (0.0–26.0) days in the intervention and 21.0 (0.0–25.0) days in the standard care group. Median PICU length of stay was 5.3 (2.5–11.3) days in the intervention group versus 6.9 (3.0–11.5) days in the control group. Shock reversal occurred at a median of 35.2 (14.6–101.2) hours in the intervention group versus 47.3 (22.4–106.8) hours in the standard care group (median difference –12 hr; 95% CI, –56.8 to 32.7 hr). CONCLUSIONS: In children requiring vasopressors for septic shock, a protocol comparing adjunctive treatment with high-dose vitamin C, hydrocortisone, and thiamin versus standard care was feasible. These findings assist in making modifications to the trial protocol to enable a better-designed larger RCT