Occurrence of sensitive topics during ward round: an ancillary analysis of the BEDSIDE-OUTSIDE trial.

OBJECTIVE: Discussing sensitive topics (eg, medical uncertainty, social issues, non-adherence) during ward rounds is challenging and may negatively impact patient satisfaction with the healthcare they are receiving. In the previous multicentre randomised BEDSIDE-OUTSIDE trial focusing on communication during ward rounds, we investigated the interplay between sensitive topics and low reported satisfaction with care. DESIGN: Pre-planned secondary analysis of a randomised controlled trial. For this analysis data of the original trial was pooled across intervention groups. SETTING: Three Swiss teaching hospitals. PARTICIPANTS: Adult patients hospitalised for medical care. INTERVENTIONS: We analysed predefined sensitive health topics and specific elements of communication from audiotapes recorded during ward rounds, for both patients dealing with and without sensitive topics. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was overall patient satisfaction with care; measured on a Visual Analogue Scale from 0 to 100. Secondary endpoints included duration of ward rounds and further satisfaction outcomes. RESULTS: Of the 919 included patients, 474 had at least one sensitive topic including medical uncertainty (n=251), psychiatric comorbidities (n=161), tumour diagnosis (n=137) and social issues (n=125). Compared with patients without sensitive topics, patients with sensitive topics reported lower satisfaction with care (mean (SD), 87.7 (±14.6) vs 90.2 (±12.1), adjusted difference -2.5 (95% CI -4.28 to -0.72), p=0.006. Among patients with sensitive topics, risk factors for low satisfaction included several parameters concerning patient-physician interaction such as disagreements during ward rounds (mean (SD), 14/212 (6.6%) vs 41/254 (16.1%), adjusted OR 2.78 (95% CI 1.47 to 5.27), p=0.002). CONCLUSIONS: A large proportion of medical inpatients must deal with sensitive health topics. This is associated with lower satisfaction with care, particularly if the patient perceives the interaction with doctors during ward rounds as unsatisfactory. Educating physicians on specific communication techniques may help improve care for these patients. TRIAL REGISTRATION NUMBER: NCT03210987.

Canakinumab in patients with COVID-19 and type 2 diabetes - A multicentre, randomised, double-blind, placebo-controlled trial.

Background: Patients with type 2 diabetes and obesity have chronic activation of the innate immune system possibly contributing to the higher risk of hyperinflammatory response to SARS-CoV2 and severe COVID-19 observed in this population. We tested whether interleukin-1ß (IL-1ß) blockade using canakinumab improves clinical outcome. Methods: CanCovDia was a multicenter, randomised, double-blind, placebo-controlled trial to assess the efficacy of canakinumab plus standard-of-care compared with placebo plus standard-of-care in patients with type 2 diabetes and a BMI > 25 kg/m2 hospitalised with SARS-CoV2 infection in seven tertiary-hospitals in Switzerland. Patients were randomly assigned 1:1 to a single intravenous dose of canakinumab (body weight adapted dose of 450-750 mg) or placebo. Canakinumab and placebo were compared based on an unmatched win-ratio approach based on length of survival, ventilation, ICU stay and hospitalization at day 29. This study is registered with ClinicalTrials.gov, NCT04510493. Findings: Between October 17, 2020, and May 12, 2021, 116 patients were randomly assigned with 58 in each group. One participant dropped out in each group for the primary analysis. At the time of randomization, 85 patients (74·6 %) were treated with dexamethasone. The win-ratio of canakinumab vs placebo was 1·08 (95 % CI 0·69-1·69; p = 0·72). During four weeks, in the canakinumab vs placebo group 4 (7·0%) vs 7 (12·3%) participants died, 11 (20·0 %) vs 16 (28·1%) patients were on ICU, 12 (23·5 %) vs 11 (21·6%) were hospitalised for more than 3 weeks, respectively. Median ventilation time at four weeks in the canakinumab vs placebo group was 10 [IQR 6.0, 16.5] and 16 days [IQR 14.0, 23.0], respectively. There was no statistically significant difference in HbA1c after four weeks despite a lower number of anti-diabetes drug administered in patients treated with canakinumab. Finally, high-sensitive CRP and IL-6 was lowered by canakinumab. Serious adverse events were reported in 13 patients (11·4%) in each group. Interpretation: In patients with type 2 diabetes who were hospitalised with COVID-19, treatment with canakinumab in addition to standard-of-care did not result in a statistically significant improvement of the primary composite outcome. Patients treated with canakinumab required significantly less anti-diabetes drugs to achieve similar glycaemic control. Canakinumab was associated with a prolonged reduction of systemic inflammation. Funding: Swiss National Science Foundation grant #198415 and University of Basel. Novartis supplied study medication.

Impact of Adrenal Function on Hemostasis/Endothelial Function in Patients Undergoing Surgery.

CONTEXT: Glucocorticoids regulate hemostatic and endothelial function, and they are critical for adaptive functions during surgery. No data regarding the impact of adrenal function on hemostasis and endothelial function in the perioperative setting are available. OBJECTIVE: We assessed the association of adrenal response to adrenocorticotropic hormone (ACTH) and markers of endothelial/hemostatic function in surgical patients. METHODS: This prospective observational study, conducted at a tertiary care hospital, included 60 patients (35 male/25 female) undergoing abdominal surgery. Adrenal function was evaluated by low-dose ACTH stimulation test on the day before, during, and the day after surgery. According to their stimulated cortisol level (cutoff ≥ 500 nmol/L), patients were classified as having normal hypothalamic-pituitary-adrenal (HPA)-axis function (nHPA) or deficient HPA-axis function (dHPA). Parameters of endothelial function (soluble vascular cell adhesion molecule-1, thrombomodulin) and hemostasis (fibrinogen, von Willebrand factor antigen, factor VIII [FVIII]) were measured during surgery. RESULTS: Twenty-one patients had dHPA and 39 had nHPA. Compared with nHPA, patients with dHPA had significantly lower peak cortisol before (median 568 vs 425 nmol/L, P < 0.001) and during (693 vs 544 nmol/L, P < 0.001) surgery and lower postoperative hemoglobin levels (116 g/L vs 105 g/L, P = 0.049). FVIII was significantly reduced in patients with dHPA in uni- and multivariable analyses; other factors displayed no significant differences. Coagulation factors/endothelial markers changed progressively in relation to stimulated cortisol levels and showed a turning point at cortisol levels between 500 and 600 nmol/L. CONCLUSIONS: Patients with dHPA undergoing abdominal surgery demonstrate impaired hemostasis which can translate into excessive blood loss.

10 Years' Experience of Using Low-Field Intraoperative MRI in Transsphenoidal Surgery for Pituitary Adenoma: Results of the Swiss Pituitary Registry (SwissPit).

BACKGROUND: For 20 years, several studies have reported intraoperative magnetic resonance imaging (iMRI) utility to achieve gross total resections in transsphenoidal pituitary adenoma surgery. Although few studies on low-field iMRI included >100 patients, data on hormonally active tumors remain scarce and follow-up times are <3 years. This is not sufficient to judge the long-term efficiency of the use of low-field iMRI. The aim of this retrospective study is to report the detailed outcome of iMRI-controlled transsphenoidal surgery in >200 patients during a follow-up exceeding 5 years. METHODS: Patients undergoing surgery for pituitary adenoma by iMRI-controlled, endoscopically assisted transsphenoidal surgery at the authors' institution between 2006 and 2016 were eligible for inclusion. Data were collected in the Swiss Pituitary Registry. A Polestar 0.15T-scanner was used. RESULTS: A total of 231 patients had surgery for 160 nonfunctioning adenomas; 28 hGH-, 27 PRL-, 10 ACTH-secreting and 6 mixed adenomas and were followed for 62 months (9-178). Additional iMRI-guided resections were possible in 54% and increased the gross total resection rate by 4% (P = 0.004). Remission rates were as follows: nonfunctioning adenoma, 53%; acromegaly, 61%; prolactinoma, 50%; Cushing disease, 90%. Tumor regrowth and recurrence was detected at a mean time of 24 and 63 months, respectively. Recovery of deficient hormone axes was detected in 22% to 27%. The risk for new postoperative hormonal deficiencies was 15%. Postoperative relieve of visual field and visual acuity deficiencies was seen in 94 (86%) and 73 (81%) patients, respectively. CONCLUSION: Judged by long-term follow-ups of >200 nonfunctioning/functioning pituitary adenomas, the use of low-field iMRI in transsphenoidal surgery increases resection rates and sustainably influences outcomes.

[Nutritional Therapy in the Elderly - What Do We Know Today?] / Nutzen der Ernährungstherapie beim älteren medizinischen Patienten ­ was wissen wir heute?

Nutritional Therapy in the Elderly - What Do We Know Today? Abstract. Malnutrition in the elderly has a high prevalence and is a strong and independent risk factor for complications and high mortality. Early diagnosis and therapeutic intervention have demonstrated positive effects on the risk for complications and morbidity/mortality. The nutritional therapy should be individually tailored to meet patients' needs and nutritional goals. Associated factors and diseases need to be taken into account while deciding on the nutritional therapy and nutritional targets. A big interprofessional effort is needed to address this specific problem. However, the latest EFFORT study showed: The expenditure is worthwhile!

[Fasting - Effects on the Human Body and Psyche]. / Fasten ­ Auswirkungen auf Körper und Psyche.

Fasting - Effects on the Human Body and Psyche Abstract. Fasting has become a trend: to lose weight, to increase well-being, or to heal acute and chronic diseases. The positive and negative effects of fasting are controversially discussed. The aim of this pilot study was to investigate the possible effects of fasting on body and well-being/psychic features. A group of twelve healthy volunteers (ten women and two men) was fasting for one week. Several clinical (body weight, blood pressure) and mental (feeling hungry, feeling cold, mood, power, and sleep quality) parameters were measured during this period. Side effects were recorded as well. This pilot study showed a wide range of effects and remarkable interindividual variation.

Estimation of treatment allocation in a randomised, double-blinded, placebo-controlled trial.

  AIM OF THE STUDY: The internal validity of double blinding in randomised placebo-controlled trials (RCTs) has become a target of criticism. The goal of this study was to investigate (a) how accurately the patients and their treating physicians were able to guess their assigned treatment, and (b) predictors for an accurate guess. METHODS: Data on treatment estimation from patients (n = 382) and their physicians (n = 358 guesses) in an RCT investigating the role of adjunct prednisone for community-acquired pneumonia in a tertiary care setting were analysed. At discharge, patients and their physicians had to guess whether they had been assigned to the prednisone or to the placebo group. The alternative possibility was “uncertain”. Percentages and confidence intervals (CIs) were calculated for the proportion of patients guessing correctly. Chance finding was defined as having 50% or less correct guesses. To test for predictors for prednisone treatment guess, a mixed effects logistic regression model was performed. RESULTS: In the prednisone group, 28.9% (55/190; 95% CI 22.6–36.0%) of the patients made a correct guess and the majority (61.6%, 117/190) was uncertain. In the placebo group, 13.0% (25/192; 95% CI 8.8–18.8%) guessed correctly, with the majority being uncertain (69.8%, 134/192). Physicians guessed correctly in 48.3% (87/180, 95% CI 40.8–55.9%) of cases in the prednisone group and in 66.3% (118/178, 95% CI 58.8–73.2%) of cases in the placebo group, which was above chance for the placebo group. The physicians were uncertain in 21.7% (39/180) of cases in the prednisone group, and in 15.2% (27/178) of cases in the placebo group. Significant predictors for guessing prednisone were the occurrence of hyperglycaemia (odds ratio [OR] 3.77, 95% CI 2.39–5.95; p<0.001) and a shorter time to clinical stability (OR 0.95, 95% CI 0.91–0.99; p = 0.02). CONCLUSIONS: We confirmed that patient blinding was achieved in this study. Physicians made correct guesses more often than patients. Treatment estimation by both patients and physicians was led not only by the expectations of treatment effects of the study drug but also by known side effects of prednisone. Trial registration no.: NCT00973154  .

Tailoring Materials for Mottronics: Excess Oxygen Doping of a Prototypical Mott Insulator.

The Mott transistor is a paradigm for a new class of electronic devices-often referred to by the term Mottronics-which are based on charge correlations between the electrons. Since correlation-induced insulating phases of most oxide compounds are usually very robust, new methods have to be developed to push such materials right to the boundary to the metallic phase in order to enable the metal-insulator transition to be switched by electric gating. Here, it is demonstrated that thin films of the prototypical Mott insulator LaTiO3 grown by pulsed laser deposition under oxygen atmosphere are readily tuned by excess oxygen doping across the line of the band-filling controlled Mott transition in the electronic phase diagram. The detected insulator to metal transition is characterized by a strong change in resistivity of several orders of magnitude. The use of suitable substrates and capping layers to inhibit oxygen diffusion facilitates full control of the oxygen content and renders the films stable against exposure to ambient conditions. These achievements represent a significant advancement in control and tuning of the electronic properties of LaTiO3+x thin films making it a promising channel material in future Mottronic devices.

Personalised immunomodulating treatments for Graves' disease: fact or fiction?

Although Graves' disease has been recognised for more than 100 years, its physiopathological mechanisms are incompletely understood. Treatment strategies today mainly focus on suppression of thyroid hormone production by use of antithyroid drugs or radio-iodine, but neglect the underlying immunological mechanisms. Although Graves' disease is often seen as a prototype for an autoimmune mechanism, it is more likely to be a heterogeneous syndrome showing characteristics of both autoimmunity and immunodeficiency. The interplay of these two mechanisms may well characterise the physiopathology of this disease and its complications. Immunodeficiency may be either genetically determined or secondarily acquired. Various triggering events lead to autoimmunity with stimulation of the thyroid gland resulting in the clinical syndrome of hyperthyroidism. Also, relapse risk differs from patient to patient and can be estimated from clinical parameters incorporated into the Graves' Recurrent Events After Therapy (GREAT) score. Accurate risk stratification may help to distinguish high-risk patients for whom a more definitive treatment approach should be used from others where there is a high probability that the disease will recover with medical treatment alone. Several smaller trials having found positive effects of immunosuppressive drugs on recurrence risk in Graves' disease; therefoore, there is great potential in the use of novel immunomodulating drugs in addition to the currently used antithyroid drugs for the successful treatment of this condition. Further in-depth exploration of susceptibility, triggering factors and immunological mechanisms has the potential to improve treatment of Graves' disease, with more personalised, risk-adapted treatment strategies based on the different physiopathological concepts of this heterogeneous condition.

In Situ Control of Separate Electronic Phases on SrTiO3 Surfaces by Oxygen Dosing.

Insulating SrTiO3 (STO) can host 2D electron systems (2DESs) on its surfaces, caused by oxygen defects. This study shows that the STO surface exhibits phase separation once the 2DES is formed and relates this inhomogeneity to recently reported magnetic order at STO surfaces and interfaces. The results open pathways to exploit oxygen defects for engineering the electronic and magnetic properties of oxides.

Simultaneous determination of phosphatidylcholine-derived quaternary ammonium compounds by a LC-MS/MS method in human blood plasma, serum and urine samples.

The determination of circulating trimethylamine-N-oxide (TMAO), choline, betaine, l-carnitine and O-acetyl-l-carnitine concentration in different human matrices is of great clinical interest. Recent results highlighted the prognostic value of TMAO and quaternary ammonium containing metabolites in the field of cardiovascular and kidney diseases. Herein, we report a method for the rapid and simultaneous measurement of closely related phosphatidylcholine-derived metabolites in three different biological matrices by stable isotope dilution assay. Plasma, serum and urine samples were simply deproteinized and separated by HILIC-chromatography. Detection and quantification were performed using LC-MS/MS with electrospray ionization in positive mode. For accuracy and precision, full calibration was performed covering more than the full reference range. Assay performance metrics include intra- and interday imprecision were below 10% for all analytes. To exclude matrix effects standard addition methods were applied for all matrices. It was shown that calibration standards and quality control prepared in water can be used instead of matrix-matched calibration and controls. The LC/MS/MS-based assay described in this article may improve future clinical studies evaluating TMAO and related substances as prognostic markers for cardiovascular risk and all-cause mortality in different patient populations.

Early safety outcome following transcatheter aortic valve implantation: is the amount of contrast media used a matter of concern?

QUESTIONS UNDER STUDY: The study objective was to evaluate the impact of the amount of contrast medium used for transcatheter aortic valve implantation (TAVI) on short-term outcome. Patients undergoing TAVI are exposed to repeat contrast medium application both for preprocedural screening and during the TAVI procedure itself. Whether the amount of contrast media is associated with worse outcome is unclear. METHODS: A total of 257 patients were included (median age 82.7 years) and divided into two groups with preserved and reduced kidney function (glomerular filtration rate <60 ml/min/1.73 m2), respectively. Total volume of contrast media administered during and within 5 days prior to TAVI was analysed. A combined early safety endpoint at 30 days was evaluated. RESULTS: The early safety endpoint was reached by 31 patients and acute kidney injury occurred in 22 patients. The median total volume of contrast media administered was 144 ml (interquartile range 81-225 ml). The amount of contrast did not independently predict the early safety endpoint in the overall population (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.56 to 1.53, p = 0.774) and in subgroups with preserved and reduced kidney function. Change in creatinine was an independent strong predictor of the early safety endpoint in the overall population (OR 18.13, 95% CI 4.70 to 69.99, p <0.001), as well as in subgroups with preserved and reduced kidney function. The amount of contrast did not predict a change in creatinine within 72 hours following TAVI (r = 0.02, 95% CI -0.02 to 0.07, p = 0.368). CONCLUSION: Decreased kidney function after TAVI influences outcome. When rather small amounts of contrast media are used for screening and the TAVI procedure itself, the amount of contrast media seems not to be an independent predictor of outcome, further suggesting that decreased kidney function after TAVI is multifactorial.

"The obesity paradox" in disease--is the protective effect of obesity true?

Although obesity and the associated metabolic syndrome negatively impact on health outcomes, a paradoxical relationship between obesity and mortality has been reported for specific patient populations - the "obesity paradox". However, underlying mechanisms remain unclear and several possible explanations are being discussed. First, a true protective effect of obesity is possible, mediated through differences in the immune response and more metabolic reserves. Although there is a growing body of evidence supporting this hypothesis, the influence of obesity on immune function is complex and not completely understood. Second, a statistical bias is possible, owing to confounding, selection bias, performance bias and measurement bias of most observational studies reporting the obesity paradox. Within this article, we summarise current concepts regarding the underlying pathophysiology and possible explanation for the obesity paradox, and discuss open questions such as whether age is an effect modifier on the relationship of obesity and mortality.

Management of patients with respiratory infections in primary care: procalcitonin, C-reactive protein or both?

Use of inflammatory biomarkers to guide antibiotic decisions has shown promising results in the risk-adapted management of respiratory tract infections, mainly in the inpatient setting. Several observational and interventional trials have investigated the benefits of procalcitonin (PCT) and C-reactive protein (CRP) testing in primary care. Both markers have shown promising results, although CRP is an inflammatory biomarker while PCT is more specific for bacterial infections. For CRP, point-of-care testing is widely established. Recently, sensitive point-of-care testing for PCT has also become available. A high-quality trial comparing these two markers for the management of patients in primary care is currently lacking. The aim of this paper is to review the existing literature investigating the use of PCT and CRP in primary care. The authors compare their performance for guiding antibiotic stewardship and analyze the cut-off values and endpoints to put these parameters into context in a low-acuity environment.

Analytical modeling, finite-difference simulation and experimental validation of air-coupled ultrasound beam refraction and damping through timber laminates, with application to non-destructive testing.

Reliable non-destructive testing (NDT) ultrasound systems for timber composite structures require quantitative understanding of the propagation of ultrasound beams in wood. A finite-difference time-domain (FDTD) model is described, which incorporates local anisotropy variations of stiffness, damping and density in timber elements. The propagation of pulsed air-coupled ultrasound (ACU) beams in normal and slanted incidence configurations is reproduced by direct definition of material properties (gas, solid) at each model pixel. First, the model was quantitatively validated against analytical derivations. Time-varying wavefronts in unbounded timber with curved growth rings were accurately reproduced, as well as the acoustic properties (velocity, attenuation, beam skewing) of ACU beams transmitted through timber lamellas. An experimental sound field imaging (SFI) setup was implemented at NDT frequencies (120 kHz), which for specific beam incidence positions allows spatially resolved ACU field characterization at the receiver side. The good agreement of experimental and modeled beam shifts across timber laminates allowed extrapolation of the inner propagation paths. The modeling base is an orthotropic stiffness dataset for the desired wood species. In cross-grain planes, beam skewing leads to position-dependent wave paths. They are well-described in terms of the growth ring curvature, which is obtained by visual observation of the laminate. Extraordinary refraction phenomena were observed, which lead to well-collimated quasi-shear wave coupling at grazing beam incidence angles. The anisotropic damping in cross-grain planes is satisfactorily explained in terms of the known anisotropic stiffness dataset and a constant loss tangent. The incorporation of high-resolution density maps (X-ray computed tomography) provided insight into ultrasound scattering effects in the layered growth ring structure. Finally, the combined potential of the FDTD model and the SFI setup for material property and defect inversion in anisotropic materials was demonstrated. A portable SFI demonstrator was implemented with a multi-sensor MEMs receiver array that captures and compensates for variable wave propagation paths in glued laminated timber, and improves the imaging of lamination defects.

[Daily routine of informal caregivers-needs and concerns with regard to the discharge of their elderly family members from the hospital setting-a qualitative study]. / Der Alltag pflegender Angehöriger - Was sie während des Spitalaufenthalts ihres Familienmitglieds beschäftigt im Hinblick auf den Austritt und was sie diesbezüglich für sich benötigen: eine qualitative Studie.

BACKGROUND: The care of an elderly frail and ill family member places a great responsibility on informal caregivers. Following discharge of the older person from the hospital setting it can be observed that caregivers are often inadequately informed about aspects such as health status, prognosis, complications, and care interventions. Concerns and needs of caregivers regarding their daily living and routine following hospital discharge has not been investigated and is considered important for an optimized discharge management. AIM: To explore personal needs and concerns of informal caregivers with regard to daily living prior to discharge of their family member. METHOD: Eight narrative interviews were conducted with caregivers and were analysed using Mayring's content analysing method. RESULTS: All caregivers had concerns regarding the maintenance of a functional daily routine. As well as caring and household duties, this functional daily routine included negotiating one's own personal time off duties, the reality of the deteriorating health status of the family member and the associated sense of hope. The intensity of family ties affected the functional daily routine. Caregivers had different expectations with regard to their integration during the hospital period. CONCLUSIONS: To support caregivers in their situation it is advisable to assess the functional daily routine of caregivers. Their need for time off their household and caring duties and their informational and educational needs to pertaining to disease progression, possible sources of support and symptom management should be recognised. Further inquiries into caregiver's involvement and responsibilities in the discharge process are needed.

Bisphosphonate induced hypocalcaemia - report of six cases and review of the literature.

Intravenous bisphosphonates are widely used to treat osteoporosis and bone metastasis in cancer patients The risk of hypocalcaemia is a rare but underestimated side effect of anti-resorptive treatment. Clinically apparent hypocalcaemia is mostly related to high-dose treatment with zoledronate and denosumab in cancer patients Particular caution is mandatory in all malnourished patients and patients with renal failure who are treated for either bone metastases or osteoporosis. To avoid serious hypocalcaemia, pre-treatment calcium and vitamin D status should be assessed and corrected if appropriate.

Loss of appetite in acutely ill medical inpatients: physiological response or therapeutic target?

Loss of appetite and ensuing weight loss is a key feature of severe illnesses. Protein-energy malnutrition (PEM) contributes significantly to the adverse outcome of these conditions. Pharmacological interventions to target appetite stimulation have little efficacy but considerable side effects. Therefore nutritional therapy appears to be the logical step to combat inadequate nutrition. However, clinical trial data demonstrating benefits are sparse and there is no current established standard algorithm for use of nutritional support in malnourished, acutely ill medical inpatients. Recent high-quality evidence from critical care demonstrating harmful effects when parenteral nutritional support is used indiscriminately has led to speculation that loss of appetite in the acute phase of illness is indeed an adaptive, protective response that improves cell recycling (autophagy) and detoxification. Outside critical care, there is an important gap in high quality clinical trial data shedding further light on these important issues. The selection, timing, and doses of nutrition should be evaluated as carefully as with any other therapeutic intervention, with the aim of maximising efficacy and minimising adverse effects and costs. In light of the current controversy, a reappraisal of how nutritional support should be used in acutely ill medical inpatients outside critical care is urgently required. The aim of this review is to discuss current pathophysiological concepts of PEM and to review the current evidence for the efficacy of nutritional support regarding patient outcomes when used in an acutely ill medical patient population outside critical care.

The use of copeptin, the stable peptide of the vasopressin precursor, in the differential diagnosis of sodium imbalance in patients with acute diseases.

BACKGROUND: Sodium imbalance is common in-hospital electrolyte disturbance and is largely related to inequalities in water homeostasis. An important mechanism leading to dysnatraemic disorders is inadequately secreted plasma arginine vasopressin (AVP). Unfortunately, AVP measurement is cumbersome and not reliable. Copeptin is secreted in an equimolar ratio to AVP and is a promising marker in the differential diagnosis of hyponatraemia and possibly hypernatraemia in stable hospitalised patients. This study assessed copeptin concentrations in sick patients with serum sodium imbalance of different aetiology on admission to the emergency department. METHODS: This is a secondary analysis of three previous prospective studies including patients with lower respiratory tract infections (LRTI) and acute cerebrovascular events. Patients were classified into different aetiological groups of hyponatraemia and hypernatraemia based on gold standard diagnostic algorithms. Copeptin levels were compared between different volaemic states and different aetiologies, firstly within the different study populations and secondly in an overall pooled analysis using hierarchical regression analysis adjusted for age and gender. RESULTS: In LRTI, hyponatraemia was found in 10.6% (58/545) and hypernatraemia in 3.7% (20/545). For acute cerebrovascular events, the corresponding numbers were 4.3% (22/509) and 8.4% (43/509). In LRTI patients with hyponatraemia, copeptin levels were only lower in the subgroup of patients with gastrointestinal losses compared to the group of patients with renal failure (mean difference: -73.6 mmol/l, 95%CI -135.0, -12.3). For hypernatraemic patients and stoke patients with hypo- and hypernatraemia, no differences were observed. In the combined analysis, copeptin levels in the hyponatraemic population were higher in patients with a hypervolaemic volume state and in patients with heart failure and renal failure. When focusing on severity, copeptin levels increased with increasing severity of disease, as classified by the Pneumonia Severity Index (p < 0.0001) or the National Institute of Health Stroke Scale Score (p < 0.0001). CONCLUSION: Although limited by small sample size, this study found that plasma copeptin level appears to add very little information to the work up of sodium imbalance in this cohort of medical inpatients. It is likely that the non-osmotic "stress"-stimulus in acute hospitalised patients is a major confounder and overrules the osmotic stimulus.