Cardiovascular risk in patients with acromegaly vs. non-functioning pituitary adenoma following pituitary surgery: an active-comparator cohort study.

PURPOSE: Given the increased cardio-metabolic risk in patients with acromegaly, this study compared cardiovascular outcomes, mortality, and in-hospital outcomes between patients with acromegaly and non-functioning pituitary adenoma (NFPA) following pituitary surgery. METHODS: This was a nationwide cohort study using data from hospitalized patients with acromegaly or NFPA undergoing pituitary surgery in Switzerland between January 2012 and December 2021. Using 1:3 propensity score matching, eligible acromegaly patients were paired with NFPA patients who underwent pituitary surgery, respectively. The primary outcome comprised a composite of cardiovascular events (myocardial infarction, cardiac arrest, ischemic stroke, hospitalization for heart failure, unstable angina pectoris, cardiac arrhythmias, intracranial hemorrhage, hospitalization for hypertensive crisis) and all-cause mortality. Secondary outcomes included individual components of the primary outcome, surgical re-operation, and various hospital-associated outcomes. RESULTS: Among 231 propensity score-matched patients with acromegaly and 491 with NFPA, the incidence rate of the primary outcome was 8.18 versus 12.73 per 1,000 person-years (hazard ratio [HR], 0.64; [95% confidence interval [CI], 0.31-1.32]). Mortality rates were numerically lower in acromegaly patients (2.43 vs. 7.05 deaths per 1,000 person-years; HR, 0.34; [95% CI, 0.10-1.17]). Individual components of the primary outcome and in-hospital outcomes showed no significant differences between the groups. CONCLUSION: This cohort study did not find an increased risk of cardiovascular outcomes and mortality in patients with acromegaly undergoing pituitary surgery compared to surgically treated NFPA patients. These findings suggest that there is no legacy effect regarding higher cardio-metabolic risk in individuals with acromegaly once they receive surgical treatment.

BackWards - Unveiling the brain's topographic organization of paraspinal sensory input.

Cortical reorganization and its potential pathological significance are being increasingly studied in musculoskeletal disorders such as chronic low back pain (CLBP) patients. However, detailed sensory-topographic maps of the human back are lacking, and a baseline characterization of such representations, reflecting the somatosensory organization of the healthy back, is needed before exploring potential sensory map reorganization. To this end, a novel pneumatic vibrotactile stimulation method was used to stimulate paraspinal sensory afferents, while studying their cortical representations in unprecedented detail. In 41 young healthy participants, vibrotactile stimulations at 20 Hz and 80 Hz were applied bilaterally at nine locations along the thoracolumbar axis while functional magnetic resonance imaging (fMRI) was performed. Model-based whole-brain searchlight representational similarity analysis (RSA) was used to investigate the organizational structure of brain activity patterns evoked by thoracolumbar sensory inputs. A model based on segmental distances best explained the similarity structure of brain activity patterns that were located in different areas of sensorimotor cortices, including the primary somatosensory and motor cortices and parts of the superior parietal cortex, suggesting that these brain areas process sensory input from the back in a "dermatomal" manner. The current findings provide a sound basis for testing the "cortical map reorganization theory" and its pathological relevance in CLBP.

Nutritional issues concerning general medical ward patients: feeding patients recovering from critical illness.

PURPOSE OF REVIEW: ICU survivors often spend long periods of time in general wards following transfer from ICU in which they are still nutritionally compromised. This brief review will focus on the feeding of patients recovering from critical illness, as no formal recommendations or guidelines on nutrition management are available for this specific situation. RECENT FINDINGS: While feeding should start in the ICU, it is important to continue and adapt nutritional plans on the ward to support individuals recovering from critical illness. This process is highly complex - suboptimal feeding may contribute significantly to higher morbidity and mortality, and seriously hinder recovery from illness. Recently, consensus diagnostic criteria for malnutrition have been defined and large-scale trials have advanced our understanding of the pathophysiological pathways underlying malnutrition. They have also helped further develop treatment algorithms. However, we must continue to identify specific clinical parameters and blood biomarkers to further personalize therapy for malnourished patients. Better understanding of such factors may help us adapt nutritional plans more efficiently. SUMMARY: Adequate nutrition is a vigorous component of treatment in the post-ICU period and can enhance recovery and improve clinical outcome. To better personalize nutritional treatment because not every patient benefits from support in the same manner, it is important to further investigate biomarkers with a possible prognostic value.

Patients' Preference for Participation in Medical Decision-Making: Secondary Analysis of the BEDSIDE-OUTSIDE Trial.

BACKGROUND: Patients may prefer different levels of involvement in decision-making regarding their medical care which may influence their medical knowledge. OBJECTIVE: We investigated associations of patients' decisional control preference (DCP) with their medical knowledge, ward round performance measures (e.g., duration, occurrence of sensitive topics), and perceived quality of care measures (e.g., trust in the healthcare team, satisfaction with hospital stay). DESIGN: This is a secondary analysis of a randomized controlled multicenter trial conducted between 2017 and 2019 at 3 Swiss teaching hospitals. PARTICIPANTS: Adult patients that were hospitalized for inpatient care. MAIN MEASURES: The primary outcome was patients' subjective average knowledge of their medical care (rated on a visual analog scale from 0 to 100). We classified patients as active, collaborative, and passive according to the Control Preference Scale. Data collection was performed before, during, and after the ward round. KEY RESULTS: Among the 761 included patients, those with a passive DCP had a similar subjective average (mean ± SD) knowledge (81.3 ± 19.4 points) compared to patients with a collaborative DCP (78.7 ± 20.3 points) and active DCP (81.3 ± 21.5 points), p = 0.25. Regarding patients' trust in physicians and nurses, we found that patients with an active vs. passive DCP reported significantly less trust in physicians (adjusted difference, - 5.08 [95% CI, - 8.69 to - 1.48 points], p = 0.006) and in nurses (adjusted difference, - 3.41 [95% CI, - 6.51 to - 0.31 points], p = 0.031). Also, patients with an active vs. passive DCP were significantly less satisfied with their hospital stay (adjusted difference, - 7.17 [95% CI, - 11.01 to - 3.34 points], p < 0.001). CONCLUSION: Patients with active DCP have lower trust in the healthcare team and lower overall satisfaction despite similar perceived medical knowledge. The knowledge of a patient's DCP may help to individualize patient-centered care. A personalized approach may improve the patient-physician relationship and increase patients' satisfaction with medical care. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03210987).

How to best use procalcitonin to diagnose infections and manage antibiotic treatment.

OBJECTIVES: Procalcitonin (PCT) is a host-response biomarker that has shown clinical value for assessing the likelihood of bacterial infections and guiding antibiotic treatment. Identifying situations where PCT can improve clinical care is therefore highly important. METHODS: The aim of this narrative review is to discuss strategies for the usage and integration of PCT into clinical routine, based on the most recent clinical evidence. RESULTS: Although PCT should not be viewed as a traditional diagnostic marker, it can help differentiate bacterial from non-bacterial infections and inflammation states - particularly in respiratory illness. Several trials have found that PCT-guided antibiotic stewardship reduces antibiotic exposure and associated side-effects among patients with respiratory infection and sepsis. Studies have demonstrated that patient-specific decisions regarding antibiotic usage is highly complex. Factors to consider include: the clinical situation (with a focus on the pretest probability for bacterial infection), the acuity and severity of presentation, as well as PCT test results. Low PCT levels help rule out bacterial infection in patients with both low pretest probability for bacterial infection and low-risk general condition. In high-risk individuals and/or high pretest probability for infection, empiric antibiotic treatment is mandatory. Subsequent monitoring of PCT helps track the resolution of infection and guide decisions regarding early termination of antibiotic treatment. CONCLUSIONS: PCT possesses high potential to improve decision-making regarding antibiotic treatment - when combined with careful patient assessment, evidence-based clinical algorithms, and continuous notification and regular feedback from all antibiotic stewardship stakeholders. Medical Journals such as Clinical Chemistry and Laboratory Medicine (CCLM) have played a critical role in reviewing and dissemination the high-quality evidence about assays for PCT measurement, observational research regarding association with outcomes among different populations, and interventional research proofing its effectiveness for patient care.

An algorithm for PCT-guided antimicrobial therapy: a consensus statement by Japanese experts.

In Japan, a national antimicrobial resistance (AMR) action plan was adopted in 2016, advocating a 20% reduction in antibiotic consumption by 2020. However, there is still room for improvement to accomplish this goal. Many randomized controlled trials have reported that procalcitonin (PCT)-guided antimicrobial therapy could help to reduce antibiotic consumption without negative health effects, specifically in acute respiratory infections. In September 2018, some experts in Europe and the USA proposed algorithms for PCT-guided antimicrobial therapy in mild to moderate infection cases outside the ICU and severe cases in the ICU (the international experts consensus). Thereafter, a group of Japanese experts, including specialists in intensive care medicine, emergency medicine, respiratory medicine and infectious diseases, created a modified version of a PCT-guided algorithm (Japanese experts consensus). This modified algorithm was adapted to better fit Japanese medical circumstances, since PCT-guided therapy is not widely used in daily clinical practice in Japan. The Japanese algorithm has three specific characteristics. First, the target patients are limited to only hospitalized ICU or non-ICU patients. Second, pneumonia due to Pseudomonas aeruginosa, Staphylococcus aureus and Legionella species are excluded. Finally, a different timing of PCT follow-up measurement was proposed to meet restrictions of the Japanese medical insurance system. The adapted algorithms has high potential to further improve the safe reduction in antibiotic consumption in Japan, while reducing the spread of AMR pathogens.

Association of admission cortisol levels with outcomes and treatment response in patients at nutritional risk : A secondary analysis of a randomized clinical trial.

INTRODUCTION: Cortisol is a metabolically active stress hormone that may play a role in the pathogenesis of malnutrition. We studied the association between admission cortisol levels and nutritional parameters, disease severity, and response to nutritional support among medical inpatients at nutritional risk. METHODS: Admission cortisol was measured in a subset of 764 patients participating in the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a multicentre, randomized-controlled trial that compared individualized nutritional support with usual nutritional care. RESULTS: Overall, mean cortisol levels were 570 (± 293) nmol/L and significantly higher in patients with high nutritional risk (NRS ≥ 5) and in patients reporting loss of appetite. Cortisol levels in the highest quartile (> 723 nmol/l) were associated with adverse outcomes including mortality at 30 days and 5 years (adjusted HR 2.31, [95%CI 1.47 to 3.62], p = 0.001 and 1.51, [95%CI 1.23 to 1.87], p < 0.001). Nutritional treatment tended to be more effective regarding mortality reduction in patients with high vs. low cortisol levels (adjusted OR of nutritional support 0.54, [95%CI 0.24 to 1.24] vs. OR 1.11, [95%CI 0.6 to 2.04], p for interaction = 0.134). This effect was most pronounced in the subgroup of patients with severe malnutrition (NRS 2002 ≥ 5, p for interaction = 0.047). CONCLUSION: This secondary analysis of a randomized nutritional trial suggests that cortisol levels are linked to nutritional and clinical outcome among multimorbid medical patients at nutritional risk and may help to improve risk assessment, as well as response to nutritional treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02517476.

Adjunct prednisone in community-acquired pneumonia: 180-day outcome of a multicentre, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Several trials and meta-analyses found a benefit of adjunct corticosteroids for community-acquired pneumonia with respect to short-term outcome, but there is uncertainty about longer-term health effects. Herein, we evaluated clinical outcomes at long term in patients participating in the STEP trial (Corticosteroid Treatment for Community-Acquired Pneumonia). METHODS: This predefined secondary analysis investigated 180-day outcomes in 785 adult patients hospitalized with community-acquired pneumonia included in STEP, a randomised, placebo-controlled, double-blind trial. The primary endpoint was time to death from any cause at 180 days verified by telephone interview. Additional secondary endpoints included pneumonia-related death, readmission, recurrent pneumonia, secondary infections, new hypertension, and new insulin dependence. RESULTS: From the originally included 785 patients, 727 were available for intention-to-treat analysis at day 180. There was no difference between groups with respect to time to death from any cause (HR for corticosteroid use 1.15, 95% CI 0.68 to 1.95, p = 0.601). Compared to placebo, corticosteroid-treated patients had significantly higher risks for recurrent pneumonia (OR 2.57, 95% CI 1.29 to 5.12, p = 0.007), secondary infections (OR 1.94, 95% CI 1.25 to 3.03, p = 0.003) and new insulin dependence (OR 8.73, 95% CI 1.10 to 69.62, p = 0.041). There was no difference regarding pneumonia-related death, readmission and new hypertension. CONCLUSIONS: In patients with community-acquired pneumonia, corticosteroid use was associated with an increased risk for recurrent pneumonia, secondary infections and new insulin dependence at 180 days. Currently, it is uncertain whether these long-term adverse effects outweigh the short-term effects of corticosteroids in moderate CAP. TRIAL REGISTRATION: This trial was registered with ClinicalTrials. gov, number NCT00973154 before the recruitment of the first patient. First posted: September 9, 2009. Last update posted: April 21, 2015.

Biomarkers for risk stratification and antibiotic stewardship in elderly patients.

PURPOSE: Optimal treatment of infections in the elderly patients population is challenging because clinical symptoms and signs may be less specific potentially resulting in both, over- and undertreatment. Elderly patients also have a less pronounced immune response to infection, which may influence kinetics of biomarkers of infection. METHODS: Within a group of experts, we critically reviewed the current literature regarding biomarkers for risk stratification and antibiotic stewardship in elderly patients with emphasis on procalcitonin (PCT). RESULTS: The expert group agreed that there is strong evidence that the elderly patient population is particularly vulnerable for infections and due to ambiguity of clinical signs and parameters in the elderly, there is considerable risk for undertreatment. At the same time, however, this group of patients is particularly vulnerable for off-target effects from antibiotic treatment and limiting the use of antibiotics is therefore important. The use of infection markers including PCT to guide individual treatment decisions has thus particular appeal in geriatric patients. For the elderly, there is evidence that PCT is a valuable biomarker for assessing the risk of septic complications and adverse outcomes, and helpful for guiding individual decisions for or against antibiotic treatment. There is need for additional educational efforts regarding the concept of "biomarker-guided antibiotic stewardship" for health care providers caring for elderly patients. CONCLUSION: Use of biomarkers, most notably PCT, has high potential to improve the antibiotic management of elderly patients with possible infection for improving both, undertreatment and overtreatment. Within this narrative review, we aim to provide evidence-based concepts for the safe and efficient use of PCT in elderly patients.

Low-Cost Sensor Node for Air Quality Monitoring: Field Tests and Validation of Particulate Matter Measurements.

Air pollution is still a major public health issue, which makes monitoring air quality a necessity. Mobile, low-cost air quality measurement devices can potentially deliver more coherent data for a region or municipality than stationary measurement stations are capable of due to their improved spatial coverage. In this study, air quality measurements obtained during field tests of our low-cost air quality sensor node (sensor-box) are presented and compared to measurements from the regional air quality monitoring network. The sensor-box can acquire geo-tagged measurements of several important pollutants, as well as other environmental quantities such as light and sound. The field test consists of sensor-boxes mounted on utility vehicles operated by municipalities located in Central Switzerland. Validation is performed against a measurement station that is part of the air quality monitoring network of Central Switzerland. Often not discussed in similar studies, this study tests and discusses several data filtering methods for the removal of outliers and unfeasible values prior to further analysis. The results show a coherent measurement pattern during the field tests and good agreement to the reference station during the side-by-side validation test.

Procalcitonin for individualizing antibiotic treatment: an update with a focus on COVID-19.

Procalcitonin (PCT) is useful for differentiating between viral and bacterial infections and for reducing the unnecessary use of antibiotics. As the rise of antimicrobial resistance reaches "alarming" levels according to the World Health Organization, the importance of using biomarkers, such as PCT to limit unnecessary antibiotic exposure has further increased. Randomized trials in patients with respiratory tract infections have shown that PCT has prognostic implications and its use, embedded in stewardship protocols, leads to reductions in the use of antibiotics in different clinical settings without compromising clinical outcomes. However, available data are heterogeneous and recent trials found no significant benefit. Still, from these trials, we have learned several key considerations for the optimal use of PCT, which depend on the clinical setting, severity of presentation, and pretest probability for bacterial infection. For patients with respiratory infections and sepsis, PCT can be used to determine whether to initiate antimicrobial therapy in low-risk settings and, together with clinical data, whether to discontinue antimicrobial therapy in certain high-risk settings. There is also increasing evidence regarding PCT-guided therapy in patients with coronavirus disease 2019 (COVID-19). This review provides an up-to-date overview of the use of PCT in different clinical settings and diseases, including a discussion about its potential to improve the care of patients with COVID-19.

Management of disease-related malnutrition for patients being treated in hospital.

Disease-related malnutrition in adult patients who have been admitted to hospital is a syndrome associated with substantially increased morbidity, disability, short-term and long-term mortality, impaired recovery from illness, and cost of care. There is uncertainty regarding optimal diagnostic criteria, definitions for malnutrition, and how to identify patients who would benefit from nutritional intervention. Malnutrition has become the focus of research aimed at translating current knowledge of its pathophysiology into improved diagnosis and treatment. Researchers are particularly interested in developing nutritional interventions that reverse the negative effects of disease-related malnutrition in the hospital setting. High-quality randomised trials have provided evidence that nutritional therapy can reduce morbidity and other complications associated with malnutrition in some patients. Screening of patients for risk of malnutrition at hospital admission, followed by nutritional assessment and individualised nutritional interventions for malnourished patients, should become part of routine clinical care and multimodal treatment in hospitals worldwide.

In the back of your mind: Cortical mapping of paraspinal afferent inputs.

Topographic organisation is a hallmark of vertebrate cortex architecture, characterised by ordered projections of the body's sensory surfaces onto brain systems. High-resolution functional magnetic resonance imaging (fMRI) has proven itself as a valuable tool to investigate the cortical landscape and its (mal-)adaptive plasticity with respect to various body part representations, in particular extremities such as the hand and fingers. Less is known, however, about the cortical representation of the human back. We therefore validated a novel, MRI-compatible method of mapping cortical representations of sensory afferents of the back, using vibrotactile stimulation at varying frequencies and paraspinal locations, in conjunction with fMRI. We expected high-frequency stimulation to be associated with differential neuronal activity in the primary somatosensory cortex (S1) compared with low-frequency stimulation and that somatosensory representations would differ across the thoracolumbar axis. We found significant differences between neural representations of high-frequency and low-frequency stimulation and between representations of thoracic and lumbar paraspinal locations, in several bilateral S1 sub-regions, and in regions of the primary motor cortex (M1). High-frequency stimulation preferentially activated Brodmann Area (BA) regions BA3a and BA4p, whereas low-frequency stimulation was more encoded in BA3b and BA4a. Moreover, we found clear topographic differences in S1 for representations of the upper and lower back during high-frequency stimulation. We present the first neurobiological validation of a method for establishing detailed cortical maps of the human back, which might serve as a novel tool to evaluate the pathological significance of neuroplastic changes in clinical conditions such as chronic low back pain.

Identification of COVID-19 patients at risk of hospital admission and mortality: a European multicentre retrospective analysis of mid-regional pro-adrenomedullin.

BACKGROUND: Mid-Regional pro-Adrenomedullin (MR-proADM) is an inflammatory biomarker that improves the prognostic assessment of patients with sepsis, septic shock and organ failure. Previous studies of MR-proADM have primarily focussed on bacterial infections. A limited number of small and monocentric studies have examined MR-proADM as a prognostic factor in patients infected with SARS-CoV-2, however there is need for multicenter validation. An evaluation of its utility in predicting need for hospitalisation in viral infections was also performed. METHODS: An observational retrospective analysis of 1861 patients, with SARS-CoV-2 confirmed by RT-qPCR, from 10 hospitals across Europe was performed. Biomarkers, taken upon presentation to Emergency Departments (ED), clinical scores, patient demographics and outcomes were collected. Multiclass random forest classifier models were generated as well as calculation of area under the curve analysis. The primary endpoint was hospital admission with and without death. RESULTS: Patients suitable for safe discharge from Emergency Departments could be identified through an MR-proADM value of ≤ 1.02 nmol/L in combination with a CRP (C-Reactive Protein) of ≤ 20.2 mg/L and age ≤ 64, or in combination with a SOFA (Sequential Organ Failure Assessment) score < 2 if MR-proADM was ≤ 0.83 nmol/L regardless of age. Those at an increased risk of mortality could be identified upon presentation to secondary care with an MR-proADM value of > 0.85 nmol/L, in combination with a SOFA score ≥ 2 and LDH > 720 U/L, or in combination with a CRP > 29.26 mg/L and age ≤ 64, when MR-proADM was > 1.02 nmol/L. CONCLUSIONS: This international study suggests that for patients presenting to the ED with confirmed SARS-CoV-2 infection, MR-proADM in combination with age and CRP or with the patient's SOFA score could identify patients at low risk where outpatient treatment may be safe.

Call, chosen, HA2T2, ANDC: validation of four severity scores in COVID-19 patients.

PURPOSE: To externally validate four previously developed severity scores (i.e., CALL, CHOSEN, HA2T2 and ANDC) in patients with COVID-19 hospitalised in a tertiary care centre in Switzerland. METHODS: This observational analysis included adult patients with a real-time reverse-transcription polymerase chain reaction or rapid-antigen test confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection hospitalised consecutively at the Cantonal Hospital Aarau from February to December 2020. The primary endpoint was all-cause in-hospital mortality. The secondary endpoint was disease progression, defined as needing invasive ventilation, ICU admission or death. RESULTS: From 399 patients (mean age 66.6 years ± 13.4 SD, 68% males), we had complete data for calculating the CALL, CHOSEN, HA2T2 and ANDC scores in 297, 380, 151 and 124 cases, respectively. Odds ratios for all four scores showed significant associations with mortality. The discriminative power of the HA2T2 score was higher compared to CALL, CHOSEN and ANDC scores [area under the curve (AUC) 0.78 vs. 0.65, 0.69 and 0.66, respectively]. Negative predictive values (NPV) for mortality were high, particularly for the CALL score (≥ 6 points: 100%, ≥ 9 points: 95%). For disease progression, discriminative power was lower, with the CHOSEN score showing the best performance (AUC 0.66). CONCLUSION: In this external validation study, the four analysed scores had a lower performance compared to the original cohorts regarding prediction of mortality and disease progression. However, all scores were significantly associated with mortality and the NPV of the CALL and CHOSEN scores in particular allowed reliable identification of patients at low risk, making them suitable for outpatient management.

Glucose control after glucocorticoid administration in hospitalized patients - a retrospective analysis.

BACKGROUND: Glucocorticoid (GC)-induced hyperglycemia is a frequent adverse effect in hospitalized patients. Guidelines recommend insulin treatment to a target range of 6-10 mmol/L (108-180 mg/dl), but efficacies of particular regimes have not been well-studied. METHODS: In this retrospective cohort study, hospitalized patients receiving GCs at the medical ward were analyzed by treatment (basal-bolus vs. bolus-only vs. pre-mixed insulin) and compared to a non-insulin-therapy reference group. Coefficients of glucose variation (CV), percentage of glucose readings in range (4-10 mmol/L (72-180 mg/dl)) and hypoglycemia (< 4 mmol/L (< 72 mg/dl)) were evaluated. RESULTS: Of 2424 hospitalized patients receiving systemic GCs, 875 (36%) developed GC-induced hyperglycemia. 427 patients (17%) had a previous diagnosis of diabetes. Adjusted relative risk ratios (RRR) for the top tertile of CV (> 29%) were 1.47 (95% Cl 1.01-2.15) for bolus-only insulin, 4.77 (95% CI 2.67-8.51) for basal-bolus insulin, and 4.98 (95% CI 2.02-12.31) for premixed insulin, respectively. Adjusted RRR for percentages of glucose readings in range were 0.98 (95% Cl 0.97-0.99) for basal-bolus insulin, 0.99 (95% Cl 0.98-1.00) for premixed insulin, and 1.01 (95% Cl 1.00-1.01) for bolus-only insulin, respectively. Adjusted RRR for hypoglycemia was 13.17 (95% Cl 4.35-39.90) for basal-bolus insulin, 8.92 (95% Cl 2.60-30.63) for premixed insulin, and 2.99 (95% Cl 1.01-8.87) for bolus-only insulin, respectively. CONCLUSIONS: Current guidelines recommend a basal-bolus regimen for treatment of GC-induced hyperglycemia, but we found similar outcomes with pre-mixed and bolus-only insulin regimens. As GC-induced hyperglycemia is a frequent issue in hospitalized patients, it might be reasonable to prospectively study the ideal regimen.

Effect of Bedside Compared With Outside the Room Patient Case Presentation on Patients' Knowledge About Their Medical Care : A Randomized, Controlled, Multicenter Trial.

BACKGROUND: Although bedside case presentation contributes to patient-centered care through active patient participation in medical discussions, the complexity of medical information and jargon-induced confusion may cause misunderstandings and patient discomfort. OBJECTIVE: To compare bedside versus outside the room patient case presentation regarding patients' knowledge about their medical care. DESIGN: Randomized, controlled, parallel-group trial. (ClinicalTrials.gov: NCT03210987). SETTING: 3 Swiss teaching hospitals. PATIENTS: Adult medical patients who were hospitalized. INTERVENTION: Patients were randomly assigned to bedside or outside the room case presentation. MEASUREMENTS: The primary endpoint was patients' average knowledge of 3 dimensions of their medical care (each rated on a visual analogue scale from 0 to 100): understanding their disease, the therapeutic approach being used, and further plans for care. RESULTS: Compared with patients in the outside the room group (n = 443), those in the bedside presentation group (n = 476) reported similar knowledge about their medical care (mean, 79.5 points [SD, 21.6] vs. 79.4 points [SD, 19.8]; adjusted difference, 0.09 points [95% CI, -2.58 to 2.76 points]; P = 0.95). Also, an objective rating of patient knowledge by the study team was similar for the 2 groups, but the bedside presentation group had higher ratings of confusion about medical jargon and uncertainty caused by team discussions. Bedside ward rounds were more efficient (mean, 11.89 minutes per patient [SD, 4.92] vs. 14.14 minutes per patient [SD, 5.65]; adjusted difference, -2.31 minutes [CI, -2.98 to -1.63 minutes]; P < 0.001). LIMITATION: Only Swiss hospitals and medical patients were included. CONCLUSION: Compared with outside the room case presentation, bedside case presentation was shorter and resulted in similar patient knowledge, but sensitive topics were more often avoided and patient confusion was higher. Physicians presenting at the bedside need to be skilled in the use of medical language to avoid confusion and misunderstandings. PRIMARY FUNDING SOURCE: Swiss National Foundation (10531C_ 182422).

Association of mannose-binding lectin, ficolin-2 and immunoglobulin concentrations with future exacerbations in patients with chronic obstructive pulmonary disease: secondary analysis of the randomized controlled REDUCE trial.

BACKGROUND: The innate and adaptive immune system is involved in the airway inflammation associated with acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). We evaluated the association of mannose-binding lectin (MBL), immunoglobulin (Ig) and ficolin-2 concentrations with COPD exacerbations and according to the glucocorticoid treatment duration for an index exacerbation. METHODS: Post-hoc analysis of the randomized, double-blind, placebo-controlled REDUCE trial of 5 vs. 14 days of glucocorticoid treatment for an index exacerbation. MBL, ficolin-2 and total IgG/IgA and subclass concentrations were determined in stored samples drawn (n = 178) 30 days after the index exacerbation and associated with the risk of re-exacerbation during a 180-day follow-up period. RESULTS: IgG and subclass concentrations were significantly lower after 14 days vs. 5 days of glucocorticoid treatment. Patients with higher MBL concentrations were more likely to suffer from a future exacerbation (multivariable hazard ratio 1.03 per 200 ng/ml increase (95% confidence interval (CI) 1.00-1.06), p = 0.048), whereas ficolin-2 and IgG deficiency were not associated. The risk was most pronounced in patients with high MBL concentrations, IgG deficiency and 14 days of glucocorticoid treatment pointing towards an interactive effect of MBL and IgG deficiency in the presence of prolonged glucocorticoid treatment duration [Relative excess risk due to interaction 2.13 (95% CI - 0.41-4.66, p = 0.10)]. IgG concentrations were significantly lower in patients with frequent re-exacerbations (IgG, 7.81 g/L vs. 9.53 g/L, p = 0.03). CONCLUSIONS: MBL modified the short-term exacerbation risk after a recent acute exacerbation of COPD, particularly in the setting of concurrent IgG deficiency and recent prolonged systemic glucocorticoid treatment. Ficolin-2 did not emerge as a predictor of a future exacerbation risk.

Association of endothelial activation assessed through endothelin-I precursor peptide measurement with mortality in COVID-19 patients: an observational analysis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has been linked to thrombotic complications and endothelial dysfunction. We assessed the prognostic implications of endothelial activation through measurement of endothelin-I precursor peptide (proET-1), the stable precursor protein of Endothelin-1, in a well-defined cohort of patients hospitalized with COVID-19. METHODS: We measured proET-1 in 74 consecutively admitted adult patients with confirmed COVID-19 and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n = 876) and viral bronchitis (n = 371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality. RESULTS: Overall, median admission proET-1 levels were lower in COVID-19 patients compared to those with pneumonia and exacerbated bronchitis, respectively (57.0 pmol/l vs. 113.0 pmol/l vs. 96.0 pmol/l, p < 0.01). Although COVID-19 non-survivors had 1.5-fold higher admission proET-1 levels compared to survivors (81.8 pmol/l [IQR: 76 to 118] vs. 53.6 [IQR: 37 to 69]), no significant association of proET-1 levels and mortality was found in a regression model adjusted for age, gender, creatinine level, diastolic blood pressure as well as cancer and coronary artery disease (adjusted OR 0.1, 95% CI 0.0009 to 14.7). In patients with pneumonia (adjusted OR 25.4, 95% CI 5.1 to 127.4) and exacerbated bronchitis (adjusted OR 120.1, 95% CI 1.9 to 7499) we found significant associations of proET-1 and mortality. CONCLUSIONS: Compared to other types of pulmonary infection, COVID-19 shows only a mild activation of the endothelium as assessed through measurement of proET-1. Therefore, the high mortality associated with COVID-19 may not be attributed to endothelial dysfunction by the surrogate marker proET-1.

Effect of different corticosteroid regimes for hospitalised patients with exacerbated COPD: pooled analysis of individual participant data from the REDUCE and CORTICO-COP trials.

BACKGROUND: Systemic corticosteroid administration for severe acute exacerbations of COPD (AECOPD) reduces the duration of hospital stays. Corticosteroid-sparing regimens have showed non-inferiority to higher accumulated dose regimens regarding re-exacerbation risk in patients with AECOPD. However, it remains unclear whether 14-day or 2-5-day regimens would result in shorter admission durations and changes in mortality risk. We explored this by analysing the number of days alive and out of hospital based on two randomised controlled trials with different corticosteroid regimens. METHODS: We pooled individual patient data from the two available multicentre randomised trials on corticosteroid-sparing regimens for AECOPD: the REDUCE (n = 314) and CORTICO-COP (n = 318) trials. In the 14-day regimen group, patients were older, fewer patients received pre-treatment with antibiotics and more patients received pre-treatment with systemic corticosteroids. Patients randomly allocated to the 14-day and 2-5-day regimens were compared, with adjustment for baseline differences. RESULTS: The number of days alive and out of hospital within 14 days from recruitment was higher for the 2-5 day regimen group (mean 8.4 days; 95% confidence interval [CI] 8.0-8.8) than the 14-day regimen patient group (4.2 days; 95% CI3.4-4.9; p < 0.001). The 14-day AECOPD group had longer hospital stays (mean difference, 5.4 days [standard error ± 0.6]; p < 0.0001) and decreased likelihood of discharge within 30 days (hazard ratio [HR] 0.5; 95% CI 0.4-0.6; p < 0.0001). Comparing the 14-day regimen and the 2-5 day regimen group showed no differences in the composite endpoint 'death or ICU admission' (odds ratio [OR] 1.4; 95% CI 0.8-2.3; p = 0.15), new or aggravated hypertension (OR 1.5; 95% CI 0.9-2.7; p = 0.15), or mortality risk (HR 0.8; 95% CI 0.4-1.5; p = 0.45) during the 6-month follow-up period. CONCLUSION: 14-day corticosteroid regimens were associated with longer hospital stays and fewer days alive and out of hospital within 14 days, with no apparent 6-month benefit regarding death or admission to ICU in COPD patients. Our results favour 2-5 day regimens for treating COPD exacerbations. However, prospective studies are needed to validate these findings.