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.

Postoperative Pain Relief After Ambulatory Laparoscopic Surgery a Nonmatched Case-Control Study.

PURPOSE: To examine whether patient involvement using a Patient Decision Aid has a positive effect on pain levels, by giving them an active role in choosing a pain schedule for postoperative pain assessment and pain management. DESIGN: A nonmatched case-control study. METHODS: 101 adults 18 years or older were included to choose between 1 of 3 possible schedules for postoperative pain management. Perioperative variables, for example, patients' assessments of pain were registered at the hospital and further variables after discharge at postoperative day 1 (POD1), POD3, and POD7, for example, patients' ability to sleep and assessment of nausea. FINDINGS: Less pain after discharge was seen among patients choosing pain schedule II at POD1 (P = .0439). A significantly higher consumption of opioids (P = 0010) on POD1 in patients who have chosen pain schedule II. CONCLUSIONS: Improved patient involvement by choosing a user-controlled pain schedule (pain schedule II) in postoperative pain management increased patient empowerment.

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.

The Danish Pain Research Biobank (DANPAIN-Biobank): a collection of blood, cerebrospinal fluid, and clinical data for the study of neuroimmune and glia-related biomarkers of chronic pain.

Background: Chronic pain is a major health problem worldwide but the limited knowledge of its underlying pathophysiology impairs the opportunities for diagnostics and treatment. Biomarkers of chronic pain are greatly needed to understand the disease and develop new targets for interventions and drug treatments, and potentially introduce more precise diagnostic procedures. Much evidence points to a neuroimmune pathology for many chronic pain conditions and that important neuroimmune biomarkers exist in the cerebrospinal fluid (CSF) of patients with chronic pain. Systematic collection of CSF in large cohorts of chronic pain patients and healthy volunteers has proven difficult, however. We established the Danish Pain Research Biobank (DANPAIN-Biobank) with the aim of studying potential neuroimmune and glia-related biomarkers of chronic pain. In this paper, we describe the methods and the study population of the DANPAIN-Biobank. Methods: In this cross-sectional study, we included (I) participants with high-impact (HI) chronic pain from a tertiary, interdisciplinary pain center; (II) participants with osteoarthritic pain scheduled for arthroplasty surgery of the hip or knee at a regional hospital; and (III) pain-free volunteers. All participants completed a questionnaire assessing pain, functional impairment, anxiety, depression, and insomnia before samples of blood and CSF were extracted. Quantitative sensory tests were performed on participants with HI chronic pain and pain-free volunteers, and postoperative outcome scores were available on participants with osteoarthritic pain. Results: Of the 352 participants included, 201 had HI chronic pain (of which 71% had chronic widespread pain), 81 had chronic osteoarthritic pain, and 70 were pain-free volunteers. Samples were handled uniformly, and CSF samples were frozen within 30 minutes. Conclusions: We describe the content of the DANPAIN-Biobank, which is unique in terms of the number of participants (including pain-free volunteers), extensive clinical data, and uniformity in sample handling. We believe it presents a promising new platform for the study of neuroimmune and glia-related biomarkers of chronic pain.

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.

Long-term Weight Loss in a Primary Care-Anchored eHealth Lifestyle Coaching Program: Randomized Controlled Trial.

BACKGROUND: Long-term weight loss in people living with obesity can reduce the risk and progression of noncommunicable diseases. Observational studies suggest that digital coaching can lead to long-term weight loss. OBJECTIVE: We investigated whether an eHealth lifestyle coaching program for people living with obesity with or without type 2 diabetes led to significant, long-term (12-month) weight loss compared to usual care. METHODS: In a randomized controlled trial that took place in 50 municipalities in Denmark, 340 people living with obesity with or without type 2 diabetes were enrolled from April 16, 2018, to April 1, 2019, and randomized via an automated computer algorithm to an intervention (n=200) or a control (n=140) group. Patients were recruited via their general practitioners, the Danish diabetes organization, and social media. The digital coaching intervention consisted of an initial 1-hour face-to-face motivational interview followed by digital coaching using behavioral change techniques enabled by individual live monitoring. The primary outcome was change in body weight from baseline to 12 months. RESULTS: Data were assessed for 200 participants, including 127 from the intervention group and 73 from the control group, who completed 12 months of follow-up. After 12 months, mean body weight and BMI were significantly reduced in both groups but significantly more so in the intervention group than the control group (-4.5 kg, 95% CI -5.6 to -3.4 vs -1.5 kg, 95% CI -2.7 to -0.2, respectively; P<.001; and -1.5 kg/m2, 95% CI -1.9 to -1.2 vs -0.5 kg/m2, 95% CI -0.9 to -0.1, respectively; P<.001). Hemoglobin A1c was significantly reduced in both the intervention (-6.0 mmol/mol, 95% CI -7.7 to -4.3) and control (-4.9 mmol/mol, 95% CI -7.4 to -2.4) groups, without a significant group difference (all P>.46). CONCLUSIONS: Compared to usual care, digital lifestyle coaching can induce significant weight loss for people living with obesity, both with and without type 2 diabetes, after 12 months. TRIAL REGISTRATION: ClinicalTrials.gov NCT03788915; https://clinicaltrials.gov/ct2/show/NCT03788915.

Reversing Type 2 Diabetes in a Primary Care-Anchored eHealth Lifestyle Coaching Programme in Denmark: A Randomised Controlled Trial.

The goal of this trial was to investigate whether an eHealth lifestyle coaching programme led to significant weight loss and decreased Haemoglobin A1c (HbA1c) in patients with type 2 diabetes. In an RCT, 170 patients were enrolled from 2018 to 2019 for intervention or control. Inclusion criteria were diagnosed with type 2 diabetes, BMI 30−45 kg/m2, and aged 18−70 years. Exclusion criteria were lacks internet access, pregnant or planning a pregnancy, or has a serious disease. Primary and secondary outcomes were a reduction in body weight and HbA1c. At six months, 75 (75%) patients in the intervention group and 53 (76%) patients in the control group remained in the trial. The mean body weight loss was 4.2 kg (95% CI, −5.49; −2.98) in the intervention group and 1.5 kg (95% CI, −2.57; −0.48) in the control group (p = 0.005). In the intervention group, 24 out of 62 patients with elevated HbA1c at baseline (39%) had a normalized HbA1c < 6.5% at six months, compared to 8 out of 40 patients with elevated HbA1c at baseline (20%) in the control group (p = 0.047). The eHealth lifestyle coaching programme can lead to significant weight loss and decreased HbA1c among patients with type 2 diabetes, compared to standard 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.

Risk of delirium and impaired neurological outcome associated with delay in neurorehabilitation after acquired brain injury.

INTRODUCTION Brain injury from haemorrhage, trauma, aneurysm and stroke is characterised by high mortality and impaired neurological outcome. In the OUTREACH study, the authors wanted to assess patient care from admission to intensive neuro rehabilitation to discharge. We hypothesised that early rehabilitation was beneficial to neurological outcome. METHODS 180-day mortality and modified Rankin Scale (mRS) were primary end points. Secondary end points included length of stay, Glasgow Coma Scale (GCS) on admission, ventilator days, Simplified Acute Physiology Score (SAPS II/III) and serious adverse events. RESULTS Sixty-seven patients were included. Mortality at 180 days was 17.91% and the median mRS score was four. Length of stay was 20.89 ± 12.33 days. GCS at admittance was 13 (3-15). The average SAPS II/III score was 55.72 ± 20.03. Twenty-eight patients suffered from serious adverse events. In all, 47 patients waited for transfer to another facility for an average of 7.77 ± 6.08 days. For mRS, the linear model indicated a negative effect of waiting time (effect = -0.056 (95% confidence interval (CI): -0.117-0.004); p = 0.07). Risk of delirium was significantly affected by waiting time; an additional day of waiting increased the risk of delirium by 13.4% (odds ratio = 1.134 (95% CI: 1.028-1.252); p = 0.01). CONCLUSIONS In this study, mortality and neurological outcome were comparable with those reported in similar studies. Waiting for transfer to another facility due to capacity significantly impairs neurological outcome and increases delirium. FUNDING none. TRIAL REGISTRATION not relevant.

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 family nursing therapeutic conversations on patients with heart failure and their family members: Secondary outcomes of a randomised multicentre trial.

AIMS AND OBJECTIVES: This study evaluates the short-term (3 months), medium-term (6 months) and long-term (12 months) effect of family nursing therapeutic conversations added to conventional care versus conventional care on social support, family health and family functioning in outpatients with heart failure and their family members. BACKGROUND: It has been emphasised that increased social support from nurses is an important resource to strengthen family health and family functioning and thus improve the psychological well-being of patients with heart failure and their close family members. DESIGN: A randomised multicentre trial. METHODS: A randomised multicentre trial adhering to the CONSORT checklist was performed in three Danish heart failure clinics. Consecutive patients (n = 468) with family members (n = 322) were randomly assigned to either the intervention or control group. Participants were asked to fill out family functioning, family health and social support questionnaires. Data were measured ahead of first consultation and again after 3, 6 and 12 months. RESULTS: Social support scores increased statistically significant both at short-term (p = 0.002) medium-term (p = 0.008) and long-term (p = 0.018) among patients and their family members (p = <0.001; 0.007 and 0.014 respectively) in the intervention group in comparison with the control group. Both patients and their family members reported increased reinforcement, feedback, decision-making capability and collaboration with the nurse. No significant differences between the intervention and control groups were seen in the family health and family functioning scales among patients and family members. CONCLUSIONS: Family nursing therapeutic conversations were superior to conventional care in providing social support from nurses. RELEVANCE TO CLINICAL PRACTICE: Family nursing therapeutic conversations are suitable to improve the support from nurses among families living with heart failure.

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.).