ROBot-assisted physical training of older patients during acUte hospitaliSaTion-study protocol for a randomised controlled trial (ROBUST).

BACKGROUND: During hospitalisation, older patients spend most of their time passive in bed, which increases the risk of functional decline and negative adverse outcomes. Our aim is to examine the impact of robot-assisted physical training on functional status in older geriatric patients during acute hospitalisation. METHODS: This is a single-centre investigator-blinded placebo-controlled randomised controlled trial including geriatric patients aged ≥ 65 years, able to ambulate before hospitalisation, and with expected length of stay ≥ 2 days. In addition to standard physiotherapy treatment, the intervention group receive active robot-assisted resistance training and the control group passive robot-assisted sham training. Exclusion criteria are as follows: ambulation without assistance at the time of inclusion, known severe dementia, delirium, patients who have received less than three training sessions at discharge, terminal illness, recent major surgery/lower extremity fracture, conditions contradicting the use of training robot, lower extremity metastases, deemed unsuitable for robot-assisted training by a healthcare professional, or weight > 165 kg. The primary outcome is functional status assessed by change in Barthel Index-100 and 30-s chair stand test between inclusion and day of discharge. Secondary outcomes include functional status at 1- and 3-month follow-up, quality of life, depression, concern about falling, falls, cognition, qualitative interviews, need of homecare, discharge destination, readmissions, healthcare costs, sarcopenia, muscle quantity (bioimpedance), and mortality. Clinical meaningful change of the Barthel Index is 5 points. A recent study in geriatric patients reported a 6.9-point change following exercise. With a significance level of 5%, 80% power, and a drop-out rate of 20%, 244 participants per group (n = 488) are needed to detect the same mean difference. With a significance level of 5%, 80% power, and a drop-out rate of 20%, 74 participants per group (n = 148) are needed to detect a minimum clinical change of 2.6 repetitions for 30-s chair stand test. Recruitment started in January 2023 and is expected to continue for 19 months including follow-up. DISCUSSION: If our study shows that in-hospital robot-assisted training prevents functional decline in older patients, this may have a major impact on the individual patient due to increased wellbeing and a higher level of independency. In addition, society will benefit due to potential decrease in the need of municipality-delivered homecare following discharge. TRIAL REGISTRATION: ClinicalTrials.gov NCT05782855. Registration date: March 24, 2023.

New Enhancing MRI Lesions Associate with IL-17, Neutrophil Degranulation and Integrin Microparticles: Multi-Omics Combined with Frequent MRI in Multiple Sclerosis.

BACKGROUND: Blood-barrier (BBB) breakdown and active inflammation are hallmarks of relapsing multiple sclerosis (RMS), but the molecular events contributing to the development of new lesions are not well explored. Leaky endothelial junctions are associated with increased production of endothelial-derived extracellular microvesicles (EVs) and result in the entry of circulating immune cells into the brain. MRI with intravenous gadolinium (Gd) can visualize acute blood-barrier disruption as the initial event of the evolution of new lesions. METHODS: Here, weekly MRI with Gd was combined with proteomics, multiplex immunoassay, and endothelial stress-optimized EV array to identify early markers related to BBB disruption. Five patients with RMS with no disease-modifying treatment were monitored weekly using high-resolution 3T MRI scanning with intravenous gadolinium (Gd) for 8 weeks. Patients were then divided into three groups (low, medium, or high MRI activity) defined by the number of new, total, and maximally enhancing Gd-enhancing lesions and the number of new FLAIR lesions. Plasma samples taken at each MRI were analyzed for protein biomarkers of inflammation by quantitative proteomics, and cytokines using multiplex immunoassays. EVs were characterized with an optimized endothelial stress EV array based on exosome surface protein markers for the detection of soluble secreted EVs. RESULTS: Proteomics analysis of plasma yielded quantitative information on 208 proteins at each patient time point (n = 40). We observed the highest number of unique dysregulated proteins (DEPs) and the highest functional enrichment in the low vs. high MRI activity comparison. Complement activation and complement/coagulation cascade were also strongly overrepresented in the low vs. high MRI activity comparison. Activation of the alternative complement pathway, pathways of blood coagulation, extracellular matrix organization, and the regulation of TLR and IGF transport were unique for the low vs. high MRI activity comparison as well, with these pathways being overrepresented in the patient with high MRI activity. Principal component analysis indicated the individuality of plasma profiles in patients. IL-17 was upregulated at all time points during 8 weeks in patients with high vs. low MRI activity. Hierarchical clustering of soluble markers in the plasma indicated that all four MRI outcomes clustered together with IL-17, IL-12p70, and IL-1ß. MRI outcomes also showed clustering with EV markers CD62E/P, MIC A/B, ICAM-1, and CD42A. The combined cluster of these cytokines, EV markers, and MRI outcomes clustered also with IL-12p40 and IL-7. All four MRI outcomes correlated positively with levels of IL-17 (p < 0.001, respectively), and EV-ICAM-1 (p < 0.0003, respectively). IL-1ß levels positively correlated with the number of new Gd-enhancing lesions (p < 0.01), new FLAIR lesions (p < 0.001), and total number of Gd-enhancing lesions (p < 0.05). IL-6 levels positively correlated with the number of new FLAIR lesions (p < 0.05). Random Forests and linear mixed models identified IL-17, CCL17/TARC, CCL3/MIP-1α, and TNF-α as composite biomarkers predicting new lesion evolution. CONCLUSIONS: Combination of serial frequent MRI with proteome, neuroinflammation markers, and protein array data of EVs enabled assessment of temporal changes in inflammation and endothelial dysfunction in RMS related to the evolution of new and enhancing lesions. Particularly, the Th17 pathway and IL-1ß clustered and correlated with new lesions and Gd enhancement, indicating their importance in BBB disruption and initiating acute brain inflammation in MS. In addition to the Th17 pathway, abundant protein changes between MRI activity groups suggested the role of EVs and the coagulation system along with innate immune responses including acute phase proteins, complement components, and neutrophil degranulation.

Structured decision support to prevent hospitalisations of community-dwelling older adults in Denmark (PATINA): an open-label, stepped-wedge, cluster-randomised controlled trial.

BACKGROUND: Ageing populations and health-care staff shortages encourage efforts in primary care to recognise and prevent health deterioration and acute hospitalisation in community-dwelling older adults. The PATINA algorithm and decision-support tool alerts home-based-care nurses to older adults at risk of hospitalisation. The study aim was to test whether use of the PATINA tool was associated with changes in health-care use. METHODS: An open-label, stepped-wedge, cluster-randomised controlled trial was done in three Danish municipalities, covering 20 area teams providing home-based care to around 7000 recipients. During a period of 12 months, area teams were randomly assigned to an intervention crossover for older adults (aged 65 years or older) who received care at home. The primary outcome was hospitalisation within 30 days of identification by the algorithm as being at risk of hospitalisation. Secondary outcomes were hospital readmission and other hospital contacts, outpatient contacts, contact with primary care physicians (PCPs), temporary care, and death, within 30 days of identification. This study was registered at ClinicalTrials.gov (NTC04398797). FINDINGS: In total, 2464 older adults participated in the study: 1216 (49·4%) in the control phase and 1248 (50·6%) in the intervention phase. In the control phase, 102 individuals were hospitalised within 30 days during 33 943 days of risk (incidence 0·09 per 30 days), compared with 118 individuals within 34 843 days of risk (0·10 per 30 days) during the intervention phase. The intervention was not associated with a reduction in the number of first hospitalisations within 30 days (incidence rate ratio [IRR] 1·10 [90% CI 0·90-1·40]; p=0·28). Furthermore it was not associated with reduced rates of other hospital contacts (IRR 1·10 [95% CI 0·90-1·40]; p=0·28), outpatient contacts (1·10 [0·88-1·40]; p=0·42), or mortality (0·82 [0·58-1·20]; p=0·25). The intervention was associated with a 59% reduction in readmissions within 30 days of hospital discharge (IRR 0·41 [95% CI 0·24-0·68]; p=0·0007), a 140% increase in contacts with PCPs (2·40 [1·18-3·20]; p<0·0001), and a 150% increase in use of temporary care (2·50 [1·40-4·70]; p=0·0027). INTERPRETATION: Despite having no effect on the primary outcome, the PATINA tool showed other benefits for older adults receiving home-based care. Such algorithms have the potential to shift health-care use from secondary to primary care but need to be tested in other home-based care settings. Implementation of algorithms in clinical practice should be informed by analysis of cost-effectiveness and potential harms as well as the benefits. FUNDING: Innovation Fund Denmark and Region of Southern Denmark. TRANSLATIONS: For the Danish, French and German translations of the abstract see Supplementary Materials section.

Conceptual framework for acute community health care services - Illustrated by assessing the development of services in Denmark.

Acute community health care services can support continuity of care by acting as a bridge between the primary and secondary health care sectors in the early detection of acute disease and provision of treatment and care. Although acute community health care services are a political priority in many countries, the literature on their organization and effect is limited. We present a conceptual framework for describing acute community health care services that can be used to support the policies and guidelines for such services. For illustrative purposes, we apply the framework to the Danish acute community health care services using implementation data from 2020 and identify gaps and opportunities for learning. The framework identifies two key pairs of dimensions: (1) capacity & capability, and (2) coordination & collaboration. These dimensions, together with the governance structure and quality assurance initiatives, are of key importance to the effect of acute community health care services. While all Danish municipalities have implemented acute community health care services, application of the framework indicates considerable variation in their approaches. The conceptual framework provides a systematic approach supporting the development, implementation, evaluation, and monitoring of acute community health care services and can assist policymakers at both national and local levels in this work.

Long-term weight loss in a 24-month primary care-anchored telehealth lifestyle coaching program: Randomized controlled trial.

Long-term weight loss can reduce the risk of type 2 diabetes for people living with obesity and reduce complications for patients diagnosed with type 2 diabetes. We investigated whether a telehealth lifestyle-coaching program (Liva) leads to long-term (24 months) weight loss compared to usual care. In a randomized controlled trial, n = 340 participants living with obesity with or without type 2 diabetes were enrolled and randomized via an automated computer algorithm to an intervention group (n = 200) or to a control group (n = 140). The telehealth lifestyle-coaching program comprised of an initial one-hour face-to-face motivational interview followed by asynchronous telehealth coaching. The behavioural change techniques used were enabled by individual live monitoring. The primary outcome was a change in body weight from baseline to 24 months. Data were assessed for n = 136 participants (40%), n = 81 from the intervention group and n = 55 from the control group, who completed the 24-month follow-up. After 24 months mean body weight and body mass index were reduced significantly for completers in both groups, but almost twice as much was registered for those in the intervention group which was not significant between groups -4.4 (CI -6.1; -2.8) kg versus -2.5 (CI -3.9; -1.1) kg, P = 0.101. Haemoglobin A1c was significantly reduced in the intervention group -3.1 (CI -5.0; -1.2) mmol/mol, but not in the control group -0.2 (CI -2.4; -2.0) mmol/mol without a significant between group difference (P = 0.223). Low completion was partly due to coronavirus disease 2019. Telehealth lifestyle coaching improve long-term weight loss (> 24 months) for obese people with and without type 2 diabetes compared to usual care.

Kidney function, future health costs, and quality-adjusted life-years in kidney transplant recipients transplanted during the SARS-Cov-2 lockdown in Denmark - An observational study.

BACKGROUND: It is unknown whether lockdown due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect both clinical outcome in kidney transplant recipients and health care economics in Denmark. METHODS: We compared kidney transplant data at a tertiary university hospital before and during the lockdown period from March 13, 2020 until March 31, 2021, as well as kidney transplant data from Scandiatransplant for entire Denmark. Outcome variables included fall of plasma creatinine during the first postoperative day, and graft function three months posttransplant. We calculated the quality-adjusted life-years (QALYs) and costs which were caused by the lockdown recommendations. FINDINGS: The portion of living donation kidney transplantation was largely reduced during the lockdown period compared to before the lockdown: AB0-incompatible living donation declined from 14% to 7% (P < 0.01), and AB0-compatible living donation declined from 34% to 20% (p < 0.01).In entire Denmark during the lockdown period 78 living donor kidney transplants out of 268 kidney transplants (29%) were performed, whereas there were 878 living donor kidney transplants out of 2218 kidney transplants (39%) before the lockdown (P = 0.01).The observed reduction of living donor kidney transplants and consecutive reduction of graft survival will cause a loss of 5.04 QALYs.The additional costs in kidney transplant recipients who received a kidney transplant during the lockdown period will be 277,298 EUR. INTERPRETATION: SARS-CoV-2 lockdown period largely reduced living donation kidney transplants which will lead to reduced QALY as well as higher costs in kidney transplant recipients.

Translation of the updated clinical frailty scale 2.0 into Danish and implications for cross-sectoral reliability.

The Clinical Frailty Scale, which provides a common language about frailty, was recently updated to version 2.0 to cater for its increased use in areas of medicine usually involved in the care and treatment of older patients. We have previously translated the Clinical Frailty Scale 1.2 into Danish and found inter-rater-reliability to be excellent for primary care physicians, community nurses, and hospital doctors often involved in cross-sectoral collaborations. In this correspondence we present the Danish translation and cultural adaption of the Clinical Frailty Scale 2.0. Our recent findings on cross-sectoral inter-rater reliability for the Clinical Frailty Scale 1.2 are likely also applicable for the Clinical Frailty Scale 2.0.

The effect of pre-analytical handling on the stability of fractalkine, monocyte chemoattractant protein 1 (MCP1), interleukin 6 and interleukin 8 in samples of human cerebrospinal fluid.

Cytokine networks in cerebrospinal fluid (CSF) are important to our understanding of several neuroinflammatory diseases. Knowledge about optimal handling of samples is limited but important to minimize bias and reduce costs in CSF biomarker studies. The aim of this study was to examine the effect of storage temperature and time delay from CSF sample collection until freezing on the concentration of 11 different cytokines thought to be associated with chronic pain. CSF samples from 21 individuals undergoing hip or knee arthroplasty under spinal anesthesia were divided between two tubes. One tube was stored and centrifuged (within 30 min) at room temperature, and one tube was stored in ice water and centrifuged (within 30 min) at 4 °C. Each tube was split into six vials that were frozen at -80 °C, 0.5, 1, 2, 3, 4, or 5 h after collection. Cytokines were analyzed using a multiplex panel. A random effect panel data regression was conducted for each biomarker including the variables of storage temperature until freezing and time delay. Four cytokines had detectable levels: Fractalkine, monocyte chemoattractant protein 1(MCP-1), interleukine 6 (IL-6), and interleukine 8 (IL-8). There was no significant effect of storage temperature and time delay on MCP-1, IL-6, or IL-8 concentrations. Fractalkine concentration showed no clear trend. No concentration differences were observed between samples kept in ice water and those at room temperature except at the 3-h time point, and there was no overall significant effect of time delay on fractalkine concentration. We found no clear effect of storage temperature and time delay up to five hours from sample collection until freezing on the CSF concentrations of fractalkine, MCP-1, IL-6, or IL-8.

Serum melatonin concentration in critically ill patients randomized to sedation or non-sedation.

BACKGROUND: Abolished circadian rhythm is associated with altered cognitive function, delirium, and as a result increased mortality in critically ill patients, especially in those who are mechanically ventilated. The causes are multifactorial, of which changes in circadian rhythmicity may play a role. Melatonin plays a crucial role as part of the circadian and sleep/wake cycle. Whether sedation effects circadian regulation is unknown. Hence, the objective of this study was to evaluate the melatonin concentration in critically ill patients randomized to sedation or non-sedation and to investigate the correlation with delirium. METHODS: All patients were included and randomized at the intensive care unit at the hospital of southwest Jutland, Denmark. Seventy-nine patients completed the study (41 sedated and 38 non-sedated). S-melatonin was measured 3 times per day, (03.00, 14.00, and 22.00), for 4 consecutive days in total, starting on the second day upon randomization/intubation. The study was conducted as a sub-study to the NON-SEDA study in which one hundred consecutive patients were randomized to sedation or non-sedation with a daily wake-up call (50 in each arm). PRIMARY OUTCOME: melatonin concentration in sedated vs. non-sedated patients (analyzed using linear regression). Secondary outcome: risk of developing delirium or non-medically induced (NMI) coma in sedated vs. non-sedated patients, assessed by CAM-ICU (Confusion Assessment Method for the Intensive Care Unit) analyzed using logistic regression. RESULTS: Melatonin concentration was suppressed in sedated patients compared to the non-sedated. All patients experienced an elevated peak melatonin level early on in the course of their critical illness (p = 0.01). The risk of delirium or coma (NMI) was significantly lower in the non-sedated group (OR 0.42 CI 0.27; 0.66 p < 0.0001). No significant relationship between delirium development and suppressed melatonin concentration was established in this study (OR 1.004 p = 0.29 95% CI 0.997; 1.010). CONCLUSION: Melatonin concentration was suppressed in sedated, critically ill patients, when compared to non-sedated controls and the frequency of delirium was elevated in sedated patients. Trail registration Clinicaltrials.gov (NCT01967680) on October 23, 2013.

Prevention of AcuTe admIssioN algorithm (PATINA): study protocol of a stepped wedge randomized controlled trial.

BACKGROUND: The challenges imposed by ageing populations will confront health care systems in the years to come. Hospital owners are concerned about the increasing number of acute admissions of older citizens and preventive measures such as integrated care models have been introduced in primary care. Yet, acute admission can be appropriate and lifesaving, but may also in itself lead to adverse health outcome, such as patient anxiety, functional loss and hospital-acquired infections. Timely identification of older citizens at increased risk of acute admission is therefore needed. We present the protocol for the PATINA study, which aims at assessing the effect of the 'PATINA algorithm and decision support tool', designed to alert community nurses of older citizens showing subtle signs of declining health and at increased risk of acute admission. This paper describes the methods, design and intervention of the study. METHODS: We use a stepped-wedge cluster randomized controlled trial (SW-RCT). The PATINA algorithm and decision support tool will be implemented in 20 individual area home care teams across three Danish municipalities (Kerteminde, Odense and Svendborg). The study population includes all home care receiving community-dwelling citizens aged 65 years and above (around 6500 citizens). An algorithm based on home care use triggers an alert based on relative increase in home care use. Community nurses will use the decision support tool to systematically assess health related changes for citizens with increased risk of acute hospital admission. The primary outcome is acute admission. Secondary outcomes are readmissions, preventable admissions, death, and costs of health care utilization. Barriers and facilitators for community nurse's acceptance and use of the algorithm will be explored too. DISCUSSION: This 'PATINA algorithm and decision support tool' is expected to positively influence the care for older community-dwelling citizens, by improving nurses' awareness of citizens at increased risk, and by supporting their clinical decision-making. This may increase preventive measures in primary care and reduce use of secondary health care. Further, the study will increase our knowledge of barriers and facilitators to implementing algorithms and decision support in a community care setup. TRIAL REGISTRATION: ClinicalTrials.gov , identifier: NCT04398797 . Registered 13 May 2020.

Effect of non-sedation on physical function in survivors of critical illness - A substudy of the NONSEDA randomized trial.

PURPOSE: Critical illness impairs physical function. The NONSEDA trial was a multicenter randomized trial, assessing non-sedation versus sedation during mechanical ventilation. The aim of this sub-study was to assess the effect of non-sedation on physical function. METHODS: All patients from one NONSEDA trial site were included. At ICU discharge and three months thereafter, survivors were assessed for physical function. RESULTS: 205 patients were included, 118 survived to follow-up, 116 participated (98%). PRIMARY OUTCOME: Three months after ICU-discharge, health-related quality of life (SF-36, physical component score) was similar (non-sedated 38.3 vs sedated 36.6, mean difference 1.7, 95% CI -1.7 to 5.1), as was function in activities of daily living (Barthel Index, non-sedated 19.5 vs sedated 18, median difference 1.5, 95% CI -0.2 to 3.2). SECONDARY OUTCOMES: Non-sedated patients had a better Barthel Index at ICU-discharge (median 9 vs 4, median difference 5, 95% CI 2.5 to 7.5). At three months post-ICU discharge, the two groups did not differ regarding handgrip strength, walking distance, muscle size or biomechanical data. CONCLUSION: Non-sedation did not lead to improved quality of life regarding physical function or better function in activities of everyday living. Non-sedated patients had a better physical recovery at ICU discharge. TRIAL REGISTRATION: Clinicaltrials.govNCT02034942, registered January 14., 2014.

Cross-sectoral inter-rater reliability of the clinical frailty scale - a Danish translation and validation study.

BACKGROUND: Focus on frailty status has become increasingly important when determining care plans within and across health care sectors. A standardized frailty measure applicable for both primary and secondary health care sectors is needed to provide a common reference point. The aim of this study was to translate the Clinical Frailty Scale (CFS) into Danish (CFS-DK) and test inter-rater reliability for key health care professionals in the primary and secondary sectors using the CFS-DK. METHODS: The Clinical Frailty Scale was translated into Danish using the ISPOR principles for translation and cultural adaptation that included forward and back translation, review by the original developer, and cognitive debriefing. For the validation exercise, 40 participants were asked to rate 15 clinical case vignettes using the CFS-DK. The raters were distributed across several health care professions: primary care physicians (n = 10), community nurses (n = 10), hospital doctors from internal medicine (n = 10) and intensive care (n = 10). Inter-rater reliability was assessed using intraclass correlation coefficients (ICC), and sensitivity analysis was performed using multilevel random effects linear regression. RESULTS: The Clinical Frailty Scale was translated and culturally adapted into Danish and is presented in this paper in its final form. Inter-rater reliability in the four professional groups ranged from ICC 0.81 to 0.90. Sensitivity analysis showed no significant impact of professional group or length of clinical experience. The health care professionals considered the CFS-DK to be relevant for their own area of work and for cross-sectoral collaboration. CONCLUSION: The Clinical Frailty Scale was translated and culturally adapted into Danish. The inter-rater reliability was high in all four groups of health care professionals involved in cross-sectoral collaborations. However, the use of case vignettes may reduce the generalizability of the reliability findings to real-life settings. The CFS has the potential to serve as a common reference tool when treating and rehabilitating older patients.

Evaluation of the Clinical and Economic Effects of a Primary Care Anchored, Collaborative, Electronic Health Lifestyle Coaching Program in Denmark: Protocol for a Two-Year Randomized Controlled Trial.

BACKGROUND: Obesity is linked to a number of chronic health conditions, such as type 2 diabetes, heart disease, and cancer, and weight loss interventions are often expensive. Recent systematic reviews concluded that app and web-based interventions can improve lifestyle behaviors and weight loss at a reasonable cost, but long-term sustainability needs to be demonstrated. OBJECTIVE: This study protocol is for a 2-year randomized controlled trial that aims to evaluate the clinical and economic effects of a primary care, anchored, collaborative, electronic health (eHealth) lifestyle coaching program (long-term Lifestyle change InterVention and eHealth Application [LIVA] 2.0) in obese participants with and without type 2 diabetes. The program's primary outcome is weight loss. Its secondary outcome is the hemoglobin A1c (HbA1c) level, and its tertiary outcomes are retention rate, quality of life (QOL), and cost effectiveness. Analytically, the focus is on associations of participant characteristics with outcomes and sustainability. METHODS: We conduct a multicenter trial with a 1-year intervention and 1-year retention. LIVA 2.0 is implemented in municipalities within administrative regions in Denmark, specifically eight municipalities located within the Region of Southern Denmark and two municipalities located within the Capital Region of Denmark. The participants are assessed at baseline and at 6-, 12-, and 24-month follow-ups. Individual data from the LIVA 2.0 platform are combined with clinical measurements, questionnaires, and participants' usage of municipality and health care services. The participants have a BMI ≥30 but ≤45 kg/m2, and 50% of the participants have type 2 diabetes. The participants are randomized in an approximately 60:40 manner, and based on sample size calculations on weight loss and intention-to-treat statistics, 200 participants are randomized to an intervention group and 140 are randomized to a control group. The control group is offered the conventional preventive program of the municipality, and it is compared to the intervention group, which follows the LIVA 2.0 in addition to the conventional preventive program. RESULTS: The first baseline assessments have been carried out in March 2018, and the 2-year follow-up will be carried out between March 2020 and April 2021. The hypothesis is that the trial results will demonstrate decreased body weight and that the number of patients who show normalization of their HbA1c levels in the intervention group will be much higher than that in the control group. The participants in the intervention group are also expected to show a greater decrease in their use of glucose-lowering medication and a greater improvement in their QOL when compared with the control group. Operational costs are expected to be lower than standard care, and the intervention is expected to be cost-effective. CONCLUSIONS: This is the first time that an app and web-based eHealth lifestyle coaching program implemented in Danish municipalities will be clinically and economically evaluated. If the LIVA 2.0 eHealth lifestyle coaching program is proven to be effective, there is great potential for decreasing the rates of obesity, diabetes, and related chronic diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT03788915; https://clinicaltrials.gov/ct2/show/NCT03788915. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19172.

Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients.

BACKGROUND: In critically ill, mechanically ventilated patients, daily interruption of sedation has been shown to reduce the time on ventilation and the length of stay in the intensive care unit (ICU). Data on whether a plan of no sedation, as compared with a plan of light sedation, has an effect on mortality are lacking. METHODS: In a multicenter, randomized, controlled trial, we assigned, in a 1:1 ratio, mechanically ventilated ICU patients to a plan of no sedation (nonsedation group) or to a plan of light sedation (i.e., to a level at which the patient was arousable, defined as a score of -2 to -3 on the Richmond Agitation and Sedation Scale [RASS], on which scores range from -5 [unresponsive] to +4 [combative]) (sedation group) with daily interruption. The primary outcome was mortality at 90 days. Secondary outcomes were the number of major thromboembolic events, the number of days free from coma or delirium, acute kidney injury according to severity, the number of ICU-free days, and the number of ventilator-free days. Between-group differences were calculated as the value in the nonsedation group minus the value in the sedation group. RESULTS: A total of 710 patients underwent randomization, and 700 were included in the modified intention-to-treat analysis. The characteristics of the patients at baseline were similar in the two trial groups, except for the score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, which was 1 point higher in the nonsedation group than in the sedation group, indicating a greater chance of in-hospital death. The mean RASS score in the nonsedation group increased from -1.3 on day 1 to -0.8 on day 7 and, in the sedation group, from -2.3 on day 1 to -1.8 on day 7. Mortality at 90 days was 42.4% in the nonsedation group and 37.0% in the sedated group (difference, 5.4 percentage points; 95% confidence interval [CI], -2.2 to 12.2; P = 0.65). The number of ICU-free days and of ventilator-free days did not differ significantly between the trial groups. The patients in the nonsedation group had a median of 27 days free from coma or delirium, and those in the sedation group had a median of 26 days free from coma or delirium. A major thromboembolic event occurred in 1 patient (0.3%) in the nonsedation group and in 10 patients (2.8%) in the sedation group (difference, -2.5 percentage points; 95% CI, -4.8 to -0.7 [unadjusted for multiple comparisons]). CONCLUSIONS: Among mechanically ventilated ICU patients, mortality at 90 days did not differ significantly between those assigned to a plan of no sedation and those assigned to a plan of light sedation with daily interruption. (Funded by the Danish Medical Research Council and others; NONSEDA ClinicalTrials.gov number, NCT01967680.).

Goal-directed therapy with bolus albumin 5% is not superior to bolus ringer acetate in maintaining systemic and mesenteric oxygen delivery in major upper abdominal surgery: A randomised controlled trial.

BACKGROUND: Goal-directed therapy (GDT) is increasingly used in abdominal surgery. Whether crystalloids can exert the same effect as colloid, and how this may affect perfusion, is still unclear. The effect of GDT on the systemic oxygen delivery index (sDO2I) and the mesenteric oxygen delivery index (mDO2I) can be quantified by measuring cardiac index and flow in the superior mesenteric artery, respectively. OBJECTIVE: The aim of this study was to test the hypothesis that intra-operative GDT with bolus human albumin 5% is superior to GDT with bolus ringer acetate in maintaining sDO2I and mDO2I in elective major upper gastrointestinal cancer surgery. DESIGN: Randomised controlled double blinded trial. SETTING: Odense University Hospital, Denmark, from May 2014 to June 2015. PATIENTS: A total of 89 adults scheduled for elective major upper gastrointestinal cancer surgery were randomised and data from 60 were analysed. EXCLUSION CRITERIA: contraindications for using the LiDCOplus system, known allergy to albumin, pre-operative renal failure, pancreatic cancer and pre-operative down staging using chemotherapy and/or radiation therapy, pregnancy. INTERVENTIONS: Patients were randomised to intra-operative GDT with either bolus human albumin or ringer acetate 250 ml, guided by pulse pressure variation and stroke volume. MAIN OUTCOME MEASURES: Changes in sDO2I and mDO2I. Secondary outcomes were changes in other haemodynamic variables, fluid balance, blood transfusions, fluid-related complications and length of stay (LOS) in ICU and hospital. RESULTS: Median [IQR] sDO2I was 522 [420 to 665] ml min m in the ringer acetate group and 490 [363 to 676] ml min m in the human albumin group, P = 0.36. Median [IQR] mDO2I was 12.1 [5.8 to 28.7] ml min m in the ringer acetate group and 17.0 [7.6 to 27.5] ml min m in the human albumin group, P = 0.17. Other haemodynamic comparisons did not differ significantly. More trial fluid was administered in the ringer acetate group. We found no significant difference in transfusions, complications or LOS. CONCLUSION: Bolus human albumin 5% was not superior to bolus ringer acetate in maintaining systemic or mesenteric oxygen delivery in elective major upper gastrointestinal cancer surgery, despite the administration of larger volumes of trial fluid in the ringer acetate group. No significant difference was seen in fluid-related complications or LOS. TRIAL REGISTRATION: https://eudract.ema.europa.eu/ Identifier: 2013-002217-36.

A randomised controlled trial of lidocaine infusion on post-operative opioid consumption in patients undergoing robotic colorectal surgery.

INTRODUCTION: Intravenous lidocaine has been shown to have analgesic effects leading to a reduced post-operative opiate need, but this effect is still debated in various surgical populations. We investigated whether this effect could be demonstrated in robot-assisted colorectal surgery. METHODS: A total of 60 adult patients undergoing robot-assisted colorectal surgery were randomly assigned to two groups in this prospective, double-blinded trial. The lidocaine group was treated with intravenous lidocaine. Treatment was initiated before induction of anaesthesia with a bolus of 1.5 mg/kg and immediately followed by infusion of 1.5 mg/kg/h continued until 2 h after end of surgery. The control group received placebo treatment with an equal volume and a dosing of 0.9% saline. The follow-up period was 72 h. RESULTS: No significant difference between groups in the median cumulated morphine consumption at 24 and 72 h was observed. Nor were there any differences in pain score, use of antiemetics, time until flatus and/or defecation or length of hospital stay. CONCLUSIONS: In this randomised, double-blinded, prospective study using intravenous lidocaine versus 0.9% saline in robot-assisted colorectal surgery, we found no significant difference in post-operative cumulated morphine consumption at 24 or at 72 h. FUNDING: The study received funding from DASAIMs Forskningsinitiativ (2016) and DASAIMs Smerteforskningspris (2016). TRIAL REGISTRATION: The trial is registered with EudraCT (2014-003466-25) and ClinicalTrials.gov (ID: NCT03044808).

Do family health conversations impact patients with glioblastoma multiforme and their family members?

AIMS AND OBJECTIVES: To assess the impact of family health conversations (FamHC) as a supplement to conventional care on health-related quality of life (HRQoL), family functioning (FFSS) and family hardiness or resilience (FHI) 4 and 14 weeks postoperatively among patients with glioblastoma multiforme and their family members. BACKGROUND: There is a lack of knowledge about the efficiency of FamHC among families experiencing glioblastoma multiforme. DESIGN: A quasi-experimental pre- and post-test design adhering to the STROBE (Strengthening the reporting of observational studies in epidemiology) guidelines for case-control studies. Patients and family members were included consecutively in the pretest period from November 2013-December 2014 for the control group (offered traditional care only), and in the post-test period from January 2015-December 2015 for the intervention group (offered traditional care and FamHC). For both groups, 4 and 14 weeks postoperative measurement were obtained. METHODS: Differences in outcomes were assessed using a difference-in-difference regression analysis approach measuring difference across pre and post groups and across 4 and 14 weeks measurements. RESULTS: The study does not reveal significant effects of FamHC (all p-values larger than 0.05) as measured by the three instruments WHOQOL-BREF, FFSS and FHI. CONCLUSIONS: The present study was not able to show significant effects of FamHC. However, it cannot be left out that the intervention might be helpful and supportive at a later state of the illness trajectory. RELEVANCE FOR CLINICAL PRACTICE: The study adds to the growing evidence-based knowledge on FamHC by questioning their potential use in different cultural contexts among families experiencing critical illness. Oncological nurses need to adapt this information to support their daily care for the patients and their close relatives. For future studies, it is recommended that the families themselves choose when the conversations should take place during the course of the illness.

Atypical sleep in critically ill patients on mechanical ventilation is associated with increased mortality.

Sleep patterns in critically ill patients' polysomnographic sleep studies (PSG) are severely abnormal. PURPOSE: We aimed to investigate the association of atypical sleep patterns, micro-sleep phenomena (sleep spindles and K-complexes) and rapid eye movement (REM) sleep with intensive care unit (ICU), in-hospital and 90-day mortality in conscious critically ill patients on mechanical ventilation. METHOD: This was a prospective descriptive study. We analysed 52 PSGs recorded in conscious critically ill patients on mechanical ventilation. PSGs were scored according to standard classification when possible. Otherwise, modified classification proposed for scoring sleep in critically ill patients was used. The association of PSG findings with mortality was studied using logistic regression and Weibull model of survival analysis. RESULTS: The presence of atypical sleep patterns in accordance with modified sleep scoring classification was associated with higher odds for ICU mortality (odds ratio 11.63; p = 0.03). The absence of K-complexes was associated with higher odds for ICU mortality (odds ratio 11.63; p = 0.03), while the absence of sleep spindles was associated with higher odds for in-hospital (odds ratio 7.80; p = 0.02) and 90-day mortality (odds ratio 5.51; p = 0.02). Loss of sleep spindles was associated with higher mortality risk with cutoff point 90 days (hazard ratio 3.87; p = 0.03). CONCLUSIONS: The presence of atypical sleep and absence of normal PSG sleep characteristics in conscious critically ill patients on mechanical ventilation indicates involvement of sleep producing brain structures in the pathological process and is associated with poor outcome.

Translation and validation of the Danish version of the brief family assessment measure III in a sample of acutely admitted elderly medical patients.

RATIONALE AND OBJECTIVE: Family functioning plays a pivotal role in the adaptation to illness of both individuals and families, especially among elderly patients. The Brief Family Assessment Measure Third Edition (Brief FAM-III) is among the most frequently used self-report instruments that measures family functioning. However, no Danish translation or measure of its psychometric properties in a Danish population is available. The purpose of this study was to translate the Brief FAM-III into Danish and then evaluate its psychometric properties in elderly patients. METHODS: The Brief FAM-III was translated into Danish using the forward-backward translation procedure and examined its psychometric properties in 60 elderly patients (aged over 65) consecutively admitted to an acute medical ward. Internal consistency reliability was assessed by Cronbach's alpha coefficients, and confirmatory factor analysis was used to examine the construct validity of the Brief FAM-III. RESULTS: Evaluation of the Danish version of the Brief FAM-III confirmed the three-factor structure (General Scale, Self-Rating Scale and Dyadic Relationships Scale) identified in the original instrument. However, goodness-of-fit indicators showed a relatively poor model fit. Cronbach's alpha for the total scales of Brief FAM-III was 0.94 suggesting good internal consistency. CONCLUSIONS: The Danish version of the Brief FAM-III demonstrated satisfactory validity and reliability to assess family functioning among acutely admitted elderly Danish patients. We suggest that it may also be useful for monitoring family functioning over time or determining the effects of therapeutic interventions in elderly medical patients; however, further testing is recommended.

Efficacy of Prewarming With a Self-Warming Blanket for the Prevention of Unintended Perioperative Hypothermia in Patients Undergoing Hip or Knee Arthroplasty.

PURPOSE: Unintended perioperative hypothermia (UPH) is a common and serious complication for patients undergoing anesthesia. The purpose of this study was to identify the incidence of UPH and evaluate the efficacy of a self-warming blanket on the drop in core temperature and risk of UPH in patients undergoing hip or knee arthroplasty. DESIGN: A case-control study was used. METHODS: Sixty patients were included. Thirty patients received prewarming with a self-warming blanket and forced-air warming intraoperatively; thirty patients received only forced-air warming intraoperatively. FINDING: The incidence of UPH (<36°C) was identified in 13% of the patients in the prewarmed group and 43% of the patients in the control group. Mean core temperature in the prewarmed group was significantly higher and remained above 36°C in the perioperative period. CONCLUSIONS: The study suggests that preoperative warming with a self-warming blanket reduces the incidence of UPH and decreases the drop in core temperature.