10 tips on how to use dynamic risk assessment and alerts for AKI

Acute kidney injury (AKI) is a common syndrome in hospitalized patients and is associated with increased morbidity and mortality. The focus of AKI care requires a shift away from strictly supportive management of established injury to the early identification and timely prevention of worsening renal injury. Identifying patients at risk for developing or progression of severe AKI is crucial for improving patient outcomes, reducing the length of hospitalization and minimizing resource utilization. Implementation of dynamic risk scores and incorporation of novel biomarkers show promise for early detection and minimizing progression of AKI. Like any risk assessment tools, these require further external validation in a variety of clinical settings prior to widespread implementation. Additionally, alerts that may minimize exposure to a variety of nephrotoxic medications or prompt early nephrology consultation are shown to reduce the incidence and progression of AKI severity and enhance renal recovery. While dynamic risk scores and alerts are valuable, implementation requires thoughtfulness and should be used in conjunction with the overall clinical picture in certain situations, particularly when considering the initiation of fluid and diuretic administration or renal replacement therapy. Despite the contemporary challenges encountered with alert fatigue, implementing an alert-based bundle to improve AKI care is associated with improved outcomes, even when implementation is incomplete. Lastly, all alert-based interventions should be validated at an institutional level and assessed for their ability to improve institutionally relevant and clinically meaningful outcomes, reduce resource utilization and provide cost-effective interventions

The impact of substance use on brain structure in people at high risk of developing schizophrenia

Ventricular enlargement and reduced prefrontal volume are consistent findings in schizophrenia. Both are present in first episode subjects and may be detectable before the onset of clinical disorder. Substance misuse is more common in people with schizophrenia and is associated with similar brain abnormalities. We employ a prospective cohort study with nested case control comparison design to investigate the association between substance misuse, brain abnormality, and subsequent schizophrenia. Substance misuse history, imaging data, and clinical information were collected on 147 subjects at high risk of schizophrenia and 36 controls. Regions exhibiting a significant relationship between level of use of alcohol, cannabis or tobacco, and structure volume were identified. Multivariate regression then elucidated the relationship between level of substance use and structure volumes while accounting for correlations between these variables and correcting for potential confounders. Finally, we established whether substance misuse was associated with later risk of schizophrenia. Increased ventricular volume was associated with alcohol and cannabis use in a dose-dependent manner. Alcohol consumption was associated with reduced frontal lobe volume. Multiple regression analyses found both alcohol and cannabis were significant predictors of these abnormalities when simultaneously entered into the statistical model. Alcohol and cannabis misuse were associated with an increased subsequent risk of schizophrenia. We provide prospective evidence that use of cannabis or alcohol by people at high genetic risk of schizophrenia is associated with brain abnormalities and later risk of psychosis. A family history of schizophrenia may render the brain particularly sensitive to the risk-modifying effects of these substances

EXTOD-Immune: a randomised controlled trial to investigate whether a remotely monitored, home-based exercise intervention can reduce disease activity in people with type 1 diabetes

Type 1 diabetes (T1D) is a chronic autoimmune disease in which the adaptive immune system targets insulin-producing β-cells of pancreatic islets, leading to dependence on exogenous insulin therapy. Cytotoxic (CD8+) T-cells specific for islet antigens are major players in T1D autoimmunity. Data indicate that regular exercise may preserve β-cell function in people recently diagnosed with T1D, but the role of islet-reactive CD8+ T-cells is unclear. In a randomised crossover design, this study will determine the impact of a 12-week exercise programme on the frequency and proliferative state of islet-reactive CD8+ T-cells in the peripheral blood of 20 adults diagnosed with T1D within the past 3 years. The exercise intervention will consist of three high-intensity interval training sessions per week (6–10 1 min intervals >80% maximum heart rate, with 1 min rest), the duration of which will incrementally increase from 14 to 22 min. Habitual physical activity and diet will be maintained during control and washout periods. At weeks 0, 12, 24 and 36, a fasting blood sample will be collected to quantify the frequency, phenotype and proliferative activity of islet-reactive CD8+ T-cells (primary outcome) and various clinical parameters. Glycaemic control will also be evaluated using 14-day continuous glucose monitoring at the start and end of each study arm. Findings may provide a rationale for conducting large-scale trials to evaluate the implementation of exercise into routine clinical care, particularly for people recently diagnosed with T1D when maintenance of β-cell function is critical to counteract disease progression. Trial registration number: ISRCTN79006041

EXTOD-Immune: A randomised controlled trial to investigate whether a remotely monitored, home-based exercise intervention can reduce disease activity in people with type 1 diabetes

Type 1 diabetes (T1D) is a chronic autoimmune disease in which the adaptive immune system targets insulin-producing β-cells of pancreatic islets, leading to dependence on exogenous insulin therapy. Cytotoxic (CD8 +) T-cells specific for islet antigens are major players in T1D autoimmunity. Data indicate that regular exercise may preserve β-cell function in people recently diagnosed with T1D, but the role of islet-reactive CD8 + T-cells is unclear. In a randomised crossover design, this study will determine the impact of a 12-week exercise programme on the frequency and proliferative state of islet-reactive CD8 + T-cells in the peripheral blood of 20 adults diagnosed with T1D within the past 3 years. The exercise intervention will consist of three high-intensity interval training sessions per week (6-10 1 min intervals >80% maximum heart rate, with 1 min rest), the duration of which will incrementally increase from 14 to 22 min. Habitual physical activity and diet will be maintained during control and washout periods. At weeks 0, 12, 24 and 36, a fasting blood sample will be collected to quantify the frequency, phenotype and proliferative activity of islet-reactive CD8 + T-cells (primary outcome) and various clinical parameters. Glycaemic control will also be evaluated using 14-day continuous glucose monitoring at the start and end of each study arm. Findings may provide a rationale for conducting large-scale trials to evaluate the implementation of exercise into routine clinical care, particularly for people recently diagnosed with T1D when maintenance of β-cell function is critical to counteract disease progression

Political stringency, infection rates, and higher education students' adherence to government measures in the Nordic countries and the UK during the first wave of the COVID-19 outbreak

Understanding predictors of adherence to governmental measures to prevent the spread of the COVID-19 is fundamental to guide health communication. This study examined whether political stringency and infection rates during the first wave of the pandemic were associated with higher education students' adherence to COVID-19 government measures in the Nordic countries (Denmark, Finland, Norway, Iceland, and Sweden) and the United Kingdom. Both individual- and country-level data were used in present study. An international cross-sectionalsubsample (n = 10,345) of higher-education students was conducted in May–June 2020 to collect individual-level information on socio-demographics, study information, living arrangements, health behaviors, stress, and COVID-19-related concerns, including adherence to government measures. Country-level data on political stringency from the Oxford COVID-19 Government Response Tracker and national infection rates were added to individual-level data. Multiple linear regression analyses stratified by country were conducted. Around 66% of students reported adhering to government measures, with the highest adherence in the UK (73%) followed by Iceland (72%), Denmark (69%), Norway (67%), Finland (64%) and Sweden (49%). Main predictors for higher adherence were older age, being femaleand being worried about getting infected with COVID-19 (individual-level), an increase in number of days since lockdown, political stringency, and information about COVID-19 mortality rates (country-level). However, incidence rate was an inconsistent predictor, which may be explained by imperfect data quality during the onset of the pandemic. We conclude that shorter lockdown periods and political stringency are associated with adherence to government measures among higher education students at the outset of the COVID-19 pandemic.Peer reviewe

EXamining the feasibility of exerCisE to manage symptoms of Lupus (EXCEL): A protocol for a randomised controlled pilot study

Introduction SLE is a chronic autoimmune disease that results in sustained hyperactivation of innate and adaptive immune cells and widespread inflammatory damage. Regular exercise reduces SLE symptoms including fatigue and joint pain and improves patient quality of life. However, most individuals with SLE are not sufficiently active to achieve these benefits, and guidance on the optimal approach to exercise is limited. EXCEL will examine the feasibility of conducting a large-scale randomised controlled trial comparing the effects of a remotely monitored, home-based, exercise programme with standard of care for individuals with SLE. Methods and analysis 30 females with SLE will be recruited, and those randomised into Exercise (SLE-Ex) will codesign a progressive training plan with support from the research team. The aim of each 12-week plan will be to complete 150 min of moderate (60-70% heart rate max, HR max) or 90 min of vigorous exercise (>70% HR max) per week. SLE-Ex will be encouraged to exercise independently (without support) from weeks 13-18. Participants with SLE that are randomised into Control (SLE-Con) will maintain habitual activity without support for 18 weeks. Measures of feasibility and acceptability will be reported, and peripheral blood will be collected at weeks 0, 12 and 18 to explore whether the frequency, phenotype and metabolic profile of lymphocyte subsets has changed. Biomarkers of SLE activity, and self-reported measures of fatigue, sleep quality and health-related quality of life will also be monitored at these timepoints. Blood and self-reported measures will be compared with a healthy control (HC) group (n=15, age and body mass index matched) at baseline only. Ethics and dissemination A favourable ethical opinion was given by South East Scotland Research Ethics Committee (22/SS/0082). Findings will be disseminated at conferences and published in peer-reviewed journals

Comorbid substance abuse and brain morphology in recent-onset psychosis

The aim of the presented study was to compare schizophrenia and schizoaffective patients early in the course of the disease with and without comorbid substance abuse disorder (SUD vs. NSUD) with regard to brain morphology. In a prospective design 41 patients (20 SUD vs. 21 NSUD) diagnosed as recent-onset schizophrenia or schizoaffective disorder consecutively admitted to hospital received standardized psychopathological evaluation (BPRS, SANS, MADRS, CGI, GAF) and MRI scanning with volumetric measurement of superior temporal gyrus (STG), amygdala-hippocampal complex, and cingulum. Patients with SUD (primarily cannabis) were significantly younger, predominantly male and had a lower socioeconomic status. Despite less attentional impairment (SANS subscore) and elevated anxiety/depression (BPRS subscore) in patients with SUD compared to NSUD, no other psychopathological differences could be detected. There were no differences in the assessed temporolimbic brain morphology between the two subgroups. In conclusion, in this study substance abuse in recent-onset psychosis had no effect on brain morphology and the earlier onset of psychosis in patients with comorbid SUD could not be explained by supposed accentuated brain abnormalities in temporolimbic regions

Adolescent Brain Development and the Risk for Alcohol and Other Drug Problems

Dynamic changes in neurochemistry, fiber architecture, and tissue composition occur in the adolescent brain. The course of these maturational processes is being charted with greater specificity, owing to advances in neuroimaging and indicate grey matter volume reductions and protracted development of white matter in regions known to support complex cognition and behavior. Though fronto-subcortical circuitry development is notable during adolescence, asynchronous maturation of prefrontal and limbic systems may render youth more vulnerable to risky behaviors such as substance use. Indeed, binge-pattern alcohol consumption and comorbid marijuana use are common among adolescents, and are associated with neural consequences. This review summarizes the unique characteristics of adolescent brain development, particularly aspects that predispose individuals to reward seeking and risky choices during this phase of life, and discusses the influence of substance use on neuromaturation. Together, findings in this arena underscore the importance of refined research and programming efforts in adolescent health and interventional needs

EXTOD-Immune: a randomised controlled trial to investigate whether a remotely monitored, home-based exercise intervention can reduce disease activity in people with type 1 diabetes.

Type 1 diabetes (T1D) is a chronic autoimmune disease in which the adaptive immune system targets insulin-producing β-cells of pancreatic islets, leading to dependence on exogenous insulin therapy. Cytotoxic (CD8+) T-cells specific for islet antigens are major players in T1D autoimmunity. Data indicate that regular exercise may preserve β-cell function in people recently diagnosed with T1D, but the role of islet-reactive CD8+ T-cells is unclear. In a randomised crossover design, this study will determine the impact of a 12-week exercise programme on the frequency and proliferative state of islet-reactive CD8+ T-cells in the peripheral blood of 20 adults diagnosed with T1D within the past 3 years. The exercise intervention will consist of three high-intensity interval training sessions per week (6-10 1 min intervals >80% maximum heart rate, with 1 min rest), the duration of which will incrementally increase from 14 to 22 min. Habitual physical activity and diet will be maintained during control and washout periods. At weeks 0, 12, 24 and 36, a fasting blood sample will be collected to quantify the frequency, phenotype and proliferative activity of islet-reactive CD8+ T-cells (primary outcome) and various clinical parameters. Glycaemic control will also be evaluated using 14-day continuous glucose monitoring at the start and end of each study arm. Findings may provide a rationale for conducting large-scale trials to evaluate the implementation of exercise into routine clinical care, particularly for people recently diagnosed with T1D when maintenance of β-cell function is critical to counteract disease progression. Trial registration number: ISRCTN79006041.</p