Heparin Dose Intensity and Organ Support-Free Days in Patients Hospitalized for COVID-19.

Background: Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation. Objectives: The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin. Methods: Patients who received initial anticoagulation dosed consistently with randomization were included. The primary outcome was organ support-free days (OSFDs), a combination of in-hospital death and days free of organ support through day 21. Results: Among 2,860 participants, 1,761 (92.8%) noncritically ill and 857 (89.1%) critically ill patients were treated per-protocol. Among noncritically ill per-protocol patients, the posterior probability that therapeutic-dose heparin improved OSFDs as compared with usual care was 99.3% (median adjusted OR: 1.36; 95% credible interval [CrI]: 1.07-1.74). Therapeutic heparin had a high posterior probability of efficacy relative to both low- (94.6%; adjusted OR: 1.26; 95% CrI: 0.95-1.64) and intermediate- (99.8%; adjusted OR: 1.80; 95% CrI: 1.22-2.62) dose thromboprophylaxis. Among critically ill per-protocol patients, the posterior probability that therapeutic heparin improved outcomes was low. Conclusions: Among noncritically ill patients hospitalized for COVID-19 who were randomized to and initially received therapeutic-dose anticoagulation, heparin, compared with usual care, was associated with improved OSFDs, a combination of in-hospital death and days free of organ support. Therapeutic heparin appeared superior to both low- and intermediate-dose thromboprophylaxis.

Adaptive multi-interventional trial platform to improve patient care for fibrotic interstitial lung diseases.

BACKGROUND: Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of lung diseases associated with significant morbidity and mortality. Despite a large increase in the number of clinical trials in the last 10 years, current regulatory-approved management approaches are limited to two therapies that prevent the progression of fibrosis. The drug development pipeline is long and there is an urgent need to accelerate this process. This manuscript introduces the concept and design of an innovative research approach to drug development in fILD: a global Randomised Embedded Multifactorial Adaptive Platform in fILD (REMAP-ILD). METHODS: Description of the REMAP-ILD concept and design: the specific terminology, design characteristics (multifactorial, adaptive features, statistical approach), target population, interventions, outcomes, mission and values, and organisational structure. RESULTS: The target population will be adult patients with fILD, and the primary outcome will be a disease progression model incorporating forced vital capacity and mortality over 12 months. Responsive adaptive randomisation, prespecified thresholds for success and futility will be used to assess the effectiveness and safety of interventions. REMAP-ILD embraces the core values of diversity, equity, and inclusion for patients and researchers, and prioritises an open-science approach to data sharing and dissemination of results. CONCLUSION: By using an innovative and efficient adaptive multi-interventional trial platform design, we aim to accelerate and improve care for patients with fILD. Through worldwide collaboration, novel analytical methodology and pragmatic trial delivery, REMAP-ILD aims to overcome major limitations associated with conventional randomised controlled trial approaches to rapidly improve the care of people living with fILD.

What Do Primary and Secondary School Teachers Know About ADHD in Children? Findings From a Systematic Review and a Representative, Nationwide Sample of Danish Teachers.

OBJECTIVE: To identify what primary and secondary school teachers know about ADHD in children and, furthermore, to identify which factors predict their knowledge. METHOD: A 29-item questionnaire about ADHD was distributed to a random, nationwide, and representative sample of Danish primary and secondary school teachers. Data were analyzed descriptively and by hierarchical regression analysis. RESULTS: A total of 528 teachers were included. Most teachers identified the symptoms of ADHD (79%-96%) and effective classroom intervention strategies (75%-98%). However, knowledge about other characteristics, etiology, prognosis, and treatment was inconsistent, for example, only 56% and 17% correctly rejected diet as a cause and effective treatment for ADHD. Among the strongest predictors for correct knowledge was having been provided postgraduate education about ADHD. CONCLUSION: Teachers require knowledge about ADHD to successfully include and manage children with ADHD and, additionally, to ensure positive working environments for teachers and support constructive school-home working collaborations.

Early goal-directed nutrition versus standard of care in adult intensive care patients: the single-centre, randomised, outcome assessor-blinded EAT-ICU trial.

PURPOSE: We assessed the effects of early goal-directed nutrition (EGDN) vs. standard nutritional care in adult intensive care unit (ICU) patients. METHODS: We randomised acutely admitted, mechanically ventilated ICU patients expected to stay longer than 3 days in the ICU. In the EGDN group we estimated nutritional requirements by indirect calorimetry and 24-h urinary urea aiming at covering 100% of requirements from the first full trial day using enteral and parenteral nutrition. In the standard of care group we aimed at providing 25 kcal/kg/day by enteral nutrition. If this was not met by day 7, patients were supplemented with parenteral nutrition. The primary outcome was physical component summary (PCS) score of SF-36 at 6 months. We performed multiple imputation for data of the non-responders. RESULTS: We randomised 203 patients and included 199 in the intention-to-treat analyses; baseline variables were reasonably balanced between the two groups. The EGDN group had less negative energy (p < 0.001) and protein (p < 0.001) balances in the ICU as compared to the standard of care group. The PCS score at 6 months did not differ between the two groups (mean difference 0.0, 95% CI -5.9 to 5.8, p = 0.99); neither did mortality, rates of organ failures, serious adverse reactions or infections in the ICU, length of ICU or hospital stay, or days alive without life support at 90 days. CONCLUSIONS: EGDN did not appear to affect physical quality of life at 6 months or other important outcomes as compared to standard nutrition care in acutely admitted, mechanically ventilated, adult ICU patients. Clinicaltrials.gov identifier no. NCT01372176.

Indirect Calorimetry in Mechanically Ventilated Patients: A Prospective, Randomized, Clinical Validation of 2 Devices Against a Gold Standard.

BACKGROUND AND AIMS: The 2 currently available indirect calorimeters, CCM Express Indirect Calorimeter (MedGraphics, St Paul, MN) and Quark RMR ICU Indirect Calorimeter (COSMED, Rome, Italy), have not been validated against a gold standard in mechanically ventilated patients. Our aim was to do so using a gold-standard, modified Tissot bell-spirometer method in mechanically ventilated patients who were hemodynamically, respiratory, and metabolically stable. METHODS: We studied 30 patients undergoing general anesthesia and major gynecological surgery. We measured oxygen consumption ([Formula: see text]O2) and resting energy expenditure (REE) in a randomized, sequential, crossover design with double determination of each device. RESULTS: Compared with the modified Tissot bell-spirometer, the CCM Express Indirect Calorimeter demonstrated a mean Δ-REE of +361 kcal/d, corresponding to a 31% overestimation of energy requirements. Bland-Altman analysis for REE showed a mean (SD) bias of 384 (124) with limits of agreement 142-627 kcal/d. QUARK RMR ICU demonstrated a mean Δ-REE of 81 kcal/d, corresponding to a 7% overestimation of energy requirements. Bland-Altman plot analysis showed a mean (SD) bias of 77 (167) with limits of agreement -249 to 404 kcal/d. CONCLUSIONS: The QUARK RMR ICU Indirect Calorimeter compared better with the gold standard for values of [Formula: see text]O2 and REE than did the CCM Express Indirect Calorimeter in mechanically ventilated patients who were circulatory and respiratory stable. Both indirect calorimeters had low precision.

Early goal-directed nutrition in ICU patients (EAT-ICU): protocol for a randomised trial.

INTRODUCTION: Extensive weight loss has been docu-mented in intensive care unit (ICU) survivors, primarily as the result of muscle loss, leading to impaired physical function and reduced quality of life. The aim of the EAT-ICU trial is to test the effect of early goal-directed protein-energy nutrition based on measured requirements on short-term clinical outcomes and long-term physical quality of life in ICU patients. METHODS: The EAT-ICU trial is a single-centre, randomised, parallel-group trial with concealed allocation and blinded outcome assessment. A total of 200 consecutive, acutely admitted, mechanically ventilated intensive care patients will be randomised 1:1 to early goal-directed nutrition versus standard of care to show a potential 15% relative risk reduction in the primary outcome measure (physical function) at six months (two-sided significance level α = 0.05; power ß = 80%). Secondary outcomes include energy- and protein balances, metabolic control, new organ failure, use of life support, nosocomial infections, ICU- and hospital length of stay, mortality and cost analyses. CONCLUSION: The optimal nutrition strategy for ICU patients remains unsettled. The EAT-ICU trial will provide important data on the effects of early goal-directed protein-energy nutrition based on measured requirements in these patients. FUNDING: The EAT-ICU trial is funded by Copenhagen University Hospital, Rigshospitalet and Fresenius Kabi A/S and supported by The European Society for Clinical Nutrition and Metabolism (ESPEN). TRIAL REGISTRATION: Clinicaltrials.gov identifier no. NCT01372176.

Provision of protein and energy in relation to measured requirements in intensive care patients.

BACKGROUND & AIMS: Adequacy of nutritional support in intensive care patients is still a matter of investigation. This study aimed to relate mortality to provision, measured requirements and balances for energy and protein in ICU patients. DESIGN: Prospective observational cohort study of 113 ICU patients in a tertiary referral hospital. RESULTS: Death occurred earlier in the tertile of patients with the lowest provision of protein and amino acids. The results were confirmed in Cox regression analyses which showed a significantly decreased hazard ratio of death with increased protein provision, also when adjusted for baseline prognostic variables (APACHE II, SOFA scores and age). Provision of energy, measured resting energy expenditure or energy and nitrogen balance was not related to mortality. The possible cause-effect relationship is discussed after a more detailed analysis of the initial part of the admission. CONCLUSION: In these severely ill ICU patients, a higher provision of protein and amino acids was associated with a lower mortality. This was not the case for provision of energy or measured resting energy expenditure or energy or nitrogen balances. The hypothesis that higher provision of protein improves outcome should be tested in a randomised trial.

[Heat stroke and burns resulting from use of sauna]. / Hedeslag og brandsår i forbindelse med saunaophold.

We describe a case of severe heat stroke resulting from exposure to extreme heat in a sauna for an unknown period of time. The patient sustained 20% 2nd degree burns. On arrival at the emergency department, the patient's temperature was 40.5 degrees C. At the critical care unit, the patient developed severe multi-organ failure and critical polyneuropathy. Severe heat stroke is a rare diagnosis in Denmark. The treatment is symptomatic and the prognosis is grave, especially in combination with severe burns.

[What is intensive care medicine? Multidisciplinary intensive care units]. / Hvad er intensiv medicinsk terapi? Multidisciplinaer intensivafdeling.

Intensive care medicine is described from a multidisciplinary point of view. The term "multidisciplinary" is used, although "multispeciality" may be more appropriate. Intensive care medicine is defined as an observational, diagnostical and therapeutical approach to the critically-ill patient, requiring specialized medical and nursing skills that cannot be met in a general ward. Critical illness is considered as overt or threatening, potentially reversible severe organ dysfunction. Intensive care medicine is conducted in the high-technology environment of intensive care units. These are further classified according to their own competency base as well as the level of the hospital in which they are situated.

Procalcitonin increase in early identification of critically ill patients at high risk of mortality.

OBJECTIVE: To investigate day-by-day changes in procalcitonin and maximum obtained levels as predictors of mortality in critically ill patients. DESIGN: Prospective observational cohort study. SETTING: : Multidisciplinary intensive care unit at Rigshospitalet, Copenhagen University Hospital, a tertiary reference hospital in Denmark. PATIENTS: Four hundred seventy-two patients with diverse comorbidity and age admitted to this intensive care unit. INTERVENTIONS: Equal in all patient groups: antimicrobial treatment adjusted according to the procalcitonin level. MEASUREMENTS AND MAIN RESULTS: Daily procalcitonin measurements were carried out during the study period as well as measurements of white blood cell count and C-reactive protein and registration of comorbidity. The primary end point was all-cause mortality in a 90-day follow-up period. Secondary end points were mortality during the stay in the intensive care unit and in a 30-day follow-up period. A total of 3,642 procalcitonin measurements were evaluated in 472 critically ill patients. We found that a high maximum procalcitonin level and a procalcitonin increase for 1 day were independent predictors of 90-day all-cause mortality in the multivariate Cox regression analysis model. C-reactive protein and leukocyte increases did not show these qualities. The adjusted hazard ratio for procalcitonin increase for 1 day was 1.8 (95% confidence interval 1.3-2.7). The relative risk for mortality in the intensive care unit for patients with an increasing procalcitonin was as follows: after 1 day increase, 1.8 (95% confidence interval 1.4-2.4); after 2 days increase, 2.2 (95% confidence interval 1.6-3.0); and after 3 days increase: 2.8 (95% confidence interval 2.0-3.8). CONCLUSIONS: A high maximum procalcitonin level and a procalcitonin increase for 1 day are early independent predictors of all-cause mortality in a 90-day follow-up period after intensive care unit admission. Mortality risk increases for every day that procalcitonin increases. Levels or increases of C-reactive protein and white blood cell count do not seem to predict mortality.