K.Vita®: a feasibility study of a blend of medium chain triglycerides to manage drug-resistant epilepsy

This prospective open-label feasibility study aimed to evaluate acceptability, tolerability and compliance with dietary intervention with K.Vita, a medical food containing a unique ratio of decanoic acid to octanoic acid, in individuals with drug-resistant epilepsy. Adults and children aged 3–18 years with drug-resistant epilepsy took K.Vita daily whilst limiting high-refined sugar food and beverages. K.Vita was introduced incrementally with the aim of achieving ≤35% energy requirements for children or 240 ml for adults. Primary outcome measures were assessed by study completion, participant diary, acceptability questionnaire and K.Vita intake. Reduction in seizures or paroxysmal events was a secondary outcome. 23/35 (66%) children and 18/26 (69%) adults completed the study; completion rates were higher when K.Vita was introduced more gradually. Gastrointestinal disturbances were the primary reason for discontinuation, but symptoms were similar to those reported from ketogenic diets and incidence decreased over time. At least three-quarters of participants/caregivers reported favourably on sensory attributes of K.Vita, such as taste, texture and appearance, and ease of use. Adults achieved a median intake of 240 ml K.Vita, and children 120 ml (19% daily energy). Three children and one adult had ß-hydroxybutyrate >1 mmol/l. There was 50% (95% CI 39–61%) reduction in mean frequency of seizures/events. Reduction in seizures or paroxysmal events correlated significantly with blood concentrations of medium chain fatty acids (C10 and C8) but not ß-hydroxybutyrate. K.Vita was well accepted and tolerated. Side effects were mild and resolved with dietetic support. Individuals who completed the study complied with K.Vita and additional dietary modifications. Dietary intervention had a beneficial effect on frequency of seizures or paroxysmal events, despite absent or very low levels of ketosis. We suggest that K.Vita may be valuable to those with drug-resistant epilepsy, particularly those who cannot tolerate or do not have access to ketogenic diets, and may allow for more liberal dietary intake compared to ketogenic diets, with mechanisms of action perhaps unrelated to ketosis. Further studies of effectiveness of K.Vita are warranted

Electrocardiogram-based mortality prediction in patients with COVID-19 using machine learning

Background and purpose: The electrocardiogram (ECG) is frequently obtained in the work-up of COVID-19 patients. So far, no study has evaluated whether ECG-based machine learning models have added value to predict in-hospital mortality specifically in COVID-19 patients. / Methods: Using data from the CAPACITY-COVID registry, we studied 882 patients admitted with COVID-19 across seven hospitals in the Netherlands. Raw format 12-lead ECGs recorded within 72 h of admission were studied. With data from five hospitals (n = 634), three models were developed: (a) a logistic regression baseline model using age and sex, (b) a least absolute shrinkage and selection operator (LASSO) model using age, sex and human annotated ECG features, and (c) a pre-trained deep neural network (DNN) using age, sex and the raw ECG waveforms. Data from two hospitals (n = 248) was used for external validation. / Results: Performances for models a, b and c were comparable with an area under the receiver operating curve of 0.73 (95% confidence interval [CI] 0.65–0.79), 0.76 (95% CI 0.68–0.82) and 0.77 (95% CI 0.70–0.83) respectively. Predictors of mortality in the LASSO model were age, low QRS voltage, ST depression, premature atrial complexes, sex, increased ventricular rate, and right bundle branch block. / Conclusion: This study shows that the ECG-based prediction models could be helpful for the initial risk stratification of patients diagnosed with COVID-19, and that several ECG abnormalities are associated with in-hospital all-cause mortality of COVID-19 patients. Moreover, this proof-of-principle study shows that the use of pre-trained DNNs for ECG analysis does not underperform compared with time-consuming manual annotation of ECG features

Optimal clinical management of children receiving ketogenic parenteral nutrition: a clinical practice guide

AIM To give evidence-based recommendations on the application of ketogenic diet parenteral nutrition (KD-PN) in emergency situations. METHOD An international group of experts (n=14) researched the literature and distributed a survey among 150 expert centers. International accepted guidelines (European Society for Clinical Nutrition and Metabolism/European Society for Paediatric Gastroenterology Hepatology and Nutrition and the American Society for Parenteral and Enteral Nutrition) and handbooks for parenteral nutrition were considered general standards of care. RESULTS In the literature, we identified 35 reports of patients treated by KD-PN. International guidelines and handbooks provided some conflicting information. Twenty-four expert teams from nine countries responded to the survey, reflecting the limited clinical experience. INTERPRETATION This paper highlights 23 consensus-based recommendations for safe and effective KD-PN (e.g. diet initiation, calculation, application, monitoring, and evaluation) based on the best evidence available and expert opinions

Practice Induces Function-Specific Changes in Brain Activity

Practice can have a profound effect on performance and brain activity, especially if a task can be automated. Tasks that allow for automatization typically involve repeated encoding of information that is paired with a constant response. Much remains unknown about the effects of practice on encoding and response selection in an automated task.To investigate function-specific effects of automatization we employed a variant of a Sternberg task with optimized separation of activity associated with encoding and response selection by means of m-sequences. This optimized randomized event-related design allows for model free measurement of BOLD signals over the course of practice. Brain activity was measured at six consecutive runs of practice and compared to brain activity in a novel task.Prompt reductions were found in the entire cortical network involved in encoding after a single run of practice. Changes in the network associated with response selection were less robust and were present only after the third run of practice.This study shows that automatization causes heterogeneous decreases in brain activity across functional regions that do not strictly track performance improvement. This suggests that cognitive performance is supported by a dynamic allocation of multiple resources in a distributed network. Our findings may bear importance in understanding the role of automatization in complex cognitive performance, as increased encoding efficiency in early stages of practice possibly increases the capacity to otherwise interfering information

Passive movement therapy in patients with moderate to severe paratonia; study protocol of a randomised clinical trial (ISRCTN43069940)

Contains fulltext : 65492.pdf ( ) (Open Access

National identity predicts public health support during a global pandemic

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics

National identity predicts public health support during a global pandemic

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics

Aggressive vs. conservative phototherapy for infants with extremely low birth weight.

BACKGROUND: It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less). METHODS: We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments. RESULTS: Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P\u3c0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g. CONCLUSIONS: Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.