Long-term cognitive and pulmonary functions following a lower versus a higher oxygenation target in the HOT-ICU and HOT-COVID trials: A protocol update.

BACKGROUND: The Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial was a multicentre, randomised, parallel-group trial of a lower oxygenation target (arterial partial pressure of oxygen [PaO2 ] = 8 kPa) versus a higher oxygenation target (PaO2 = 12 kPa) in adult ICU patients with acute hypoxaemic respiratory failure; the Handling Oxygenation Targets in coronavirus disease 2019 (HOT-COVID) tested the same oxygenation targets in patients with confirmed COVID-19. In this study, we aim to evaluate the long-term effects of these oxygenation targets on cognitive and pulmonary function. We hypothesise that a lower oxygenation target throughout the ICU stay may result in cognitive impairment, whereas a higher oxygenation target may result in impaired pulmonary function. METHODS: This is the updated protocol and statistical analysis plan of two pre-planned secondary outcomes, the long-term cognitive function, and long-term pulmonary function, in the HOT-ICU and HOT-COVID trials. Patients enrolled in both trials at selected Danish sites and surviving to 1 year after randomisation are eligible to participate. A Repeatable Battery for the Assessment of Neuropsychological Status score and a full-body plethysmography, including diffusion capacity for carbon monoxide, will be obtained. The last patient is expected to be included in the spring of 2024. CONCLUSION: This study will provide important information on the long-term effects of a lower versus a higher oxygenation target on long-term cognitive and pulmonary functions in adult ICU patients with acute hypoxaemic respiratory failure.

Long-term cognitive and pulmonary functions following a lower versus a higher oxygenation target in the HOT-ICU trial: protocol and statistical analysis plan.

BACKGROUND: Although supplemental oxygen can be lifesaving, liberal oxygen administration causing hyperoxaemia may be harmful. The targets for oxygenation in patients with acute hypoxaemic respiratory failure acutely admitted to the intensive care unit (ICU) are strongly debated, and consensus on which targets to recommend has not been reached. The Handling Oxygenation Targets in the ICU (HOT-ICU) trial is a multicentre, randomised, parallel-group trial of a lower oxygenation target (arterial partial pressure of oxygen [PaO2 ] = 8 kPa) versus a higher oxygenation target (PaO2  = 12 kPa) in adult ICU patients with acute hypoxaemic respiratory failure. In this study, we aim to evaluate the effects of these targets on long-term cognitive and pulmonary function in Danish patients, enrolled in the HOT-ICU trial and surviving to 1-year follow-up. We hypothesise that a lower oxygenation target throughout the ICU stay may result in cognitive impairment, whereas a higher oxygenation target may result in impaired pulmonary function. METHODS: All patients enrolled in the HOT-ICU trial at Danish sites and surviving to 1 year after randomisation are eligible to participate. The last patient is expected to be included by November 2021. A Repeatable Battery for the Assessment of Neuropsychological Status and a body plethysmography, including diffusion capacity for carbon monoxide, both pre-planned secondary long-term outcomes of the HOT-ICU trial, will be obtained. CONCLUSION: This study will provide important information on the long-term effects of a lower versus a higher oxygenation target on cognitive and pulmonary function in adult ICU patients with acute hypoxaemic respiratory failure.

Prevalence of depression after moderate to severe traumatic brain injury among adolescents and young adults: A systematic review.

To review the prevalence of depression among adolescents and young adults after moderate to severe TBI. A systematic literature search was conducted on literature published up to December 2018 in PubMed, EMBASE, Cochrane and PsychInfo. A systematic review of the identified literature was based on PRISMA guidelines. Risk of Bias was evaluated based on the aspects of Risk of Bias assessment described by the Agency of Health Research and Quality. Seven studies were deemed eligible and information on the prevalence of depression among adolescents and young adults (age 13-35) after moderate to severe TBI was extracted. Depression was assessed at 12 months (n = 2), >12 months (n = 2) or at varying times (n = 3) after TBI. The identified studies reported a prevalence proportion of depression from 1.6% to 60%. The Risk of Bias assessment showed a range of study quality with the selection of subjects and analysis of attrition being problematic. Although literature is sparse and of varying quality, depression was found to be common among adolescents and young adults with moderate to severe TBI which implies a need to focus on depression in the rehabilitation process and calls for further research.

Depression and cognitive sequelae registered within the first year among young Danish TBI survivors.

The aim of the study was to determine the proportion of depression and cognitive sequelae among young (15-30 years) Danish TBI survivors referred to interdisciplinary evaluation through a nationwide government-initiated health initiative. The cross-sectional study is based on data from the "Danish register for young adults with acquired brain injury" on TBI survivors included from October 2013 to December 2016. The main measures were Major depression inventory, Trail making test A and B, Fluency, Word learning with selective reminding, Matrix reasoning, Coding and Glasgow outcome scale - extended (GOS-E). During the study period, 131 young TBI survivors were referred to one of five national outpatient clinics. Ninety-six had complete data and of these 14.6% fulfilled the ICD-10 diagnostic criteria for depression and 34.4% had cognitive sequelae. An association was found between depression and cognitive sequelae (p = 0.004). Patients with both depression and cognitive sequelae (n = 10) had a significantly lower mean score on GOS-E (p = 0.0001). Depression and cognitive sequelae were frequent and associated with a poorer global functional outcome among young TBI survivors referred within a year after trauma. This finding and the notion that only 20% of the expected TBI population was referred to this nationwide health initiative indicate an unacknowledged need for interdisciplinary follow-up.

Spontaneous Extradural Hematoma in a Sickle Cell Anemia Patient with Hyperinflammation and Thrombotic Microangiopathy Successfully Treated with Eculizumab: A Case Report and Review of the Literature.

BACKGROUND: The event of extradural hematoma in the absence of head trauma is a rare central nervous system complication of sickle cell disease. We report here a case of spontaneous extradural hematoma in a patient being treated for sickle cell vasoocclusive crisis complicated by hyperinflammation and thrombotic microangiopathy. The significance of inflammation as an integral component of the pathomechanism of vasoocclusive crisis in patients with sickle cell disease and the role of heme in activating the complement system's alternative pathway are highlighted in this case report. CASE PRESENTATION: A teenage patient with sickle cell disease developed a spontaneous right parietal extradural hematoma while receiving treatment for sickle cell vasoocclusive crisis. The concurrent events of hyperinflammation, disseminated intravascular coagulation, hyperhemolysis syndrome, thrombotic microangiopathy, and refractory postoperative bleeding complicated this patient's clinical course after surgical evacuation of extradural hematoma. This patient was subsequently treated with eculizumab and improved in the days following. CONCLUSION: Treatment with the anti-C5 monoclonal antibody eculizumab, which targets and inhibits terminal complement system activation, reversed the deleterious cascade of events in this patient with sickle cell disease.

Implementation of the S100 Calcium-Binding Protein B Biomarker in a Clinical Setting: A Retrospective Study of Benefits, Safety, and Effectiveness.

Recent years have seen the emergence of the S100 calcium-binding protein B (S100B) biomarker used in the initial management of minor traumatic brain injury (TBI) patients. S100B has been found to reduce cerebral computed tomography (CT-C) scans and was recently implemented in the Scandinavian Neurotrauma Committee (SNC) guidelines. In a clinical setup, we retrospectively investigated the use of the S100B biomarker in relation to the SNC guidelines in the respective year before and after implementation. Accordingly, minor TBI patients with the International Classification of Diseases, Tenth Revision diagnostic code of S06.0 commotio cerebri were included in 2018 (n = 786) and 2019 (n = 709) for comparison of emergency department time (EDT) and CT-Cs. In 2019, we included all patients with an S100B sample (n = 547; 348/199 male:female; median age, 52 years). We found an S100B sensitivity of 92% and negative predictive value (NPV) of 99% (cutoff, 0.10 µg/L) regardless of SNC guideline compliance. With strict SNC guideline management, sensitivity and NPV increased to 100%, even at a 0.20-µg/L cutoff that increased the specificity from 49% to 76%. After S100B implementation, we found the median EDT to significantly increase from 196 min (interquartile range [IQR] = 127-289) in 2018 to 216 min (IQR = 134.0-309.5) in 2019 (p = 0.0148), which may have resulted from poor guideline compliance (53.9%). Contrarily, the proportion of CT-C scanned patients decreased from 70% to 56.3% equal to a relative 27.5% decrease of scanned patients (p < 0.0001). Conclusively, our study supported the safe and efficient clinical use of the S100B biomarker, albeit with a minor EDT increase. S100B combination with the SNC guidelines improved clinical potential.

Depression and cognitive sequelae after a traumatic brain lesion.

INTRODUCTION: To improve rehabilitation in young people with an acquired brain injury, the Danish Ministry of Health initiated the "National study on young brain injury survivors" in 2012. Using data from this initiative, we examined the changes in depression, cognition, global functional outcome and return to work/school among young traumatic brain injury (TBI) survivors. METHOD: This was an observational one-year follow-up study based on data from "Danish registry for young adults with acquired brain injury". The main measures were Major Depression Inventory, neuropsychological examination, and Glasgow Outcome Scale - extended (GOS-E). RESULTS: A total of 76 young TBI survivors attended two interdisciplinary examinations and had complete data. Sixty-six (86.8%) had rehabilitation between the two visits, and the global functional outcome was vastly higher at the second visit (z = -3.373, p = 0.0007). At the first versus the second visit, the prevalence proportion of depression was 14.5% (95% confidence interval (CI): 7.5-24.4) versus 10.5% (95% CI: 4.7-19.7), and for cognitive sequelae it was 31.6% (95% CI: 21.4-43.3) versus 19.7% (95% CI: 11.5-30.5). Patients with depression and/or cognitive sequelae had a lower GOS-E score (p = 0.0016) than patients without depression/cognitive sequelae and a negative association was found between depression, cognitive sequelae and return to work/school (p = 0.045). CONCLUSION: Emotional and cognitive rehabilitation for young TBI survivors seems essential as depression and cognitive sequelae are associated with a lower global functional outcome and return to work/school. FUNDING: none. TRIAL REGISTRATION: not relevant.

Patient costs and patient flow after implementation of S100B in Scandinavian head trauma guidelines.

INTRODUCTION: The serum biomarker S100B has been implemented in the Scandinavian Neurotrauma Committee (SNC) 2013 Head Injury Guidelines for patients classified with mild head injury (MHI). Patients with a serum S100B level less-than 0.10 µg/l sampled within six hours after trauma can be discharged without further observation or investigation. The aim of this study was to examine the influence of S100B implementation on patient costs and patient flow in an emergency department. METHODS: In this retrospective study, we included MHI patients (≥ 18 years) admitted to Rigshospitalet, Copenhagen, Denmark, between 1 February 2013 and 31 January 2014. Medical records were examined for the time of trauma, time of S100B sampling, serum S100B level, the severity of the head injury, clinical symptoms, radiological examinations, hospitalisation, discharge, surgical intervention, readmission and mortality. RESULTS: Among 2,033 patients screened for potential study candidates, 227 patients met the inclusion criteria and were enrolled in the study. Among these patients, 119 (52%) were not treated according to SNC 2013 Head Injury Guidelines, leaving 108 (48%) with full guideline adherence. Compared with MHI management without S100B, implementation of S100B produced an additional cost of €1.26 per patient. Overall, the addition of S100B did not affect the waiting time for examination with S100B sampling or CT. CONCLUSION: The use of S100B in the SNC 2013 Head Injury Guidelines did not reduce patient costs, nor did it cause substantial additional patient costs or delayed patient flow. FUNDING: none. TRIAL REGISTRATION: The Danish Data Protection Agency (journal number 2012-58-0004 and I-suite number RH-2017-164).

Cognitive function after adjuvant treatment for early breast cancer: a population-based longitudinal study.

The purpose of this study was to examine cognitive function in patients with early breast cancer before and after adjuvant chemotherapy or 6 months of tamoxifen. We performed a population-based study in the county of North Jutland, Denmark, including 120 women aged <60 years who received adjuvant chemotherapy with seven cycles of cyclophosphamide, epirubicin and fluoruracil or adjuvant tamoxifen for 6 months for early breast cancer from 2004 to 2006. They were compared with an aged-matched group of 208 women without previous cancer selected randomly from the same population. Data were collected before start of adjuvant treatment and after 6 months by neuropsychological tests and questionnaires to evaluate cognitive function, quality of life and psychological distress. Neuropsychological tests did not reveal any differences in cognitive function between breast cancer patients after chemotherapy and healthy controls. Patients rated their own cognitive functions as improved after 6 months, and patients, who did not receive adjuvant medical treatment, reached the same level as controls within 6 months. Patients receiving chemotherapy or tamoxifen were up to three times more likely than controls to rate themselves as impaired at 6 months. Our results do not support that adjuvant chemotherapy is associated with cognitive side effects in breast cancer patients.

A Danish version of the Oxford cognitive screen: a stroke-specific screening test as an alternative to the MoCA.

Cognitive deficits are common following stroke and have many negative consequences. They must be identified to provide appropriate interventions and care. In Denmark, the Montreal Cognitive Assessment (MoCA), a dementia screening tool, is commonly used to screen for cognitive deficits following stroke, despite its limitations in this context. This study aimed to make the Oxford Cognitive Screen (OCS), a stroke-specific cognitive screening tool, available in Danish and to provide population appropriate normative data. Additionally, the study aimed to evaluate the appropriateness of the MoCA cutoff of 25/26 currently used in Denmark. A sample of healthy Danish participants aged 36-89 was assessed using the Danish OCS and MoCA. Mean performance and 5th percentile cutoffs were calculated for both tests. OCS results were similar to results from European studies. For the MoCA, 5th percentile corresponded to 22.35, suggesting that the cutoff currently used in Denmark is inappropriate.

Cognitive function and quality of life after surgery for early breast cancer in North Jutland, Denmark.

OBJECTIVE: The aim of this study was to assess cognitive function, quality of life, and psychological distress after surgery for early breast cancer but before initiation of adjuvant treatment. MATERIAL AND METHODS: We performed a population-based study in the county of North Jutland, Denmark, including 124 women aged less than 60 years who had surgery for early breast cancer from 2004 - 2006. They were compared with an aged-matched group of 224 women without previous cancer selected randomly from the same population. The cognitive function of patients and controls was tested using a revised battery from the ISPOCD study. Data were collected on quality of life (EORTC QLQ-C30) and psychological distress (POMS). RESULT: The neuropsychological tests did not reveal significant differences between patients and controls. Compared to the control group, breast cancer patients had a significantly 3 - 4 fold increased risk of experiencing cognitive impairment. Quality of life and psychological distress were also significantly poorer among patients. CONCLUSION: This study demonstrated that women diagnosed with breast cancer experience a significant deterioration of their perceived cognitive functioning, quality of life and of psychological well being.

Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial.

OBJECTIVE: To investigate the effect of a restricted intravenous fluid regimen versus a standard regimen on complications after colorectal resection. SUMMARY BACKGROUND DATA: Current fluid administration in major surgery causes a weight increase of 3-6 kg. Complications after colorectal surgery are reported in up to 68% of patients. Associations between postoperative weight gain and poor survival as well as fluid overload and complications have been shown. METHODS: We did a randomized observer-blinded multicenter trial. After informed consent was obtained, 172 patients were allocated to either a restricted or a standard intraoperative and postoperative intravenous fluid regimen. The restricted regimen aimed at maintaining preoperative body weight; the standard regimen resembled everyday practice. The primary outcome measures were complications; the secondary measures were death and adverse effects. RESULTS: The restricted intravenous fluid regimen significantly reduced postoperative complications both by intention-to-treat (33% versus 51%, P = 0.013) and per-protocol (30% versus 56%, P = 0.003) analyses. The numbers of both cardiopulmonary (7% versus 24%, P = 0.007) and tissue-healing complications (16% versus 31%, P = 0.04) were significantly reduced. No patients died in the restricted group compared with 4 deaths in the standard group (0% versus 4.7%, P = 0.12). No harmful adverse effects were observed. CONCLUSION: The restricted perioperative intravenous fluid regimen aiming at unchanged body weight reduces complications after elective colorectal resection.