Arginine or Hypertonic Saline-Stimulated Copeptin to Diagnose AVP Deficiency.

BACKGROUND: Distinguishing between arginine vasopressin (AVP) deficiency and primary polydipsia is challenging. Hypertonic saline-stimulated copeptin has been used to diagnose AVP deficiency with high accuracy but requires close sodium monitoring. Arginine-stimulated copeptin has shown similar diagnostic accuracy but with a simpler test protocol. However, data are lacking from a head-to-head comparison between arginine-stimulated copeptin and hypertonic saline-stimulated copeptin in the diagnosis of AVP deficiency. METHODS: In this international, noninferiority trial, we assigned adult patients with polydipsia and hypotonic polyuria or a known diagnosis of AVP deficiency to undergo diagnostic evaluation with hypertonic-saline stimulation on one day and with arginine stimulation on another day. Two endocrinologists independently made the final diagnosis of AVP deficiency or primary polydipsia with use of clinical information, treatment response, and the hypertonic-saline test results. The primary outcome was the overall diagnostic accuracy according to prespecified copeptin cutoff values of 3.8 pmol per liter after 60 minutes for arginine and 4.9 pmol per liter once the sodium level was more than 149 mmol per liter for hypertonic saline. RESULTS: Of the 158 patients who underwent the two tests, 69 (44%) received the diagnosis of AVP deficiency and 89 (56%) received the diagnosis of primary polydipsia. The diagnostic accuracy was 74.4% (95% confidence interval [CI], 67.0 to 80.6) for arginine-stimulated copeptin and 95.6% (95% CI, 91.1 to 97.8) for hypertonic saline-stimulated copeptin (estimated difference, -21.2 percentage points; 95% CI, -28.7 to -14.3). Adverse events were generally mild with the two tests. A total of 72% of the patients preferred testing with arginine as compared with hypertonic saline. Arginine-stimulated copeptin at a value of 3.0 pmol per liter or less led to a diagnosis of AVP deficiency with a specificity of 90.9% (95% CI, 81.7 to 95.7), whereas levels of more than 5.2 pmol per liter led to a diagnosis of primary polydipsia with a specificity of 91.4% (95% CI, 83.7 to 95.6). CONCLUSIONS: Among adult patients with polyuria polydipsia syndrome, AVP deficiency was more accurately diagnosed with hypertonic saline-stimulated copeptin than with arginine-stimulated copeptin. (Funded by the Swiss National Science Foundation; CARGOx ClinicalTrials.gov number, NCT03572166.).

Refeeding syndrome is associated with increased mortality in malnourished medical inpatients: Secondary analysis of a randomized trial.

BACKGROUND: Whether the occurrence of refeeding syndrome (RFS), a metabolic condition characterized by electrolyte shifts after initiation of nutritional therapy, has a negative impact on clinical outcomes remains ill-defined. We prospectively investigated a subgroup of patients included in a multicentre, nutritional trial (EFFORT) for the occurrence of RFS. METHODS: In this secondary analysis of a randomized-controlled trial investigating the effects of nutritional support in malnourished medical inpatients, we prospectively screened patients for RFS and classified them as "RFS confirmed" and "RFS not confirmed" based on predefined criteria (i.e. electrolyte shifts, clinical symptoms, clinical context, and patient history). We assessed associations of RFS and mortality within 180 days (primary endpoint) and other secondary endpoints using multivariable regression analysis. RESULTS: Among 967 included patients, RFS was confirmed in 141 (14.6%) patients. Compared to patients with no evidence for RFS, patients with confirmed RFS had significantly increased 180-days mortality rates (42/141 (29.8%) vs 181/826 (21.9%), adjusted odds ratio (OR) 1.53 (95% CI 1.02 to 2.29), P < .05). Patients with RFS also had an increased risk for ICU admission (6/141 (4.3%) vs 13/826 (1.6%), adjusted OR 2.71 (95% CI 1.01 to 7.27), P < .05) and longer mean length of hospital stays (10.5 ±â€Š6.9 vs 9.0 ±â€Š6.6 days, adjusted difference 1.57 days (95% CI 0.38-2.75), P = .01). CONCLUSION: A relevant proportion of medical inpatients with malnutrition develop features of RFS upon hospital admission, which is associated with long-term mortality and other adverse clinical outcomes. Further studies are needed to develop preventive strategies for RFS in this patient population.

Vitamin D Deficiency Strongly Predicts Adverse Medical Outcome Across Different Medical Inpatient Populations: Results From a Prospective Study.

Vitamin D deficiency has been associated with several adverse outcomes mainly in the outpatient setting. The objective of this study was to examine the prevalence of vitamin D deficiency and its association with risk of adverse clinical outcomes in a large prospective cohort of medical inpatients.We collected clinical data and measured 25(OH)D levels in adult medical patients upon hospital admission and followed them for 30 days. Regression analyses adjusted for age, gender, comorbidities, and main medical diagnosis were performed to study the effect of vitamin D deficiency on several hospital outcomes.Of 4257 included patients, 1510 (35.47%) had 25(OH)D levels of 25 to 50 nmol/L (vitamin D insufficiency) and 797 (18.72%) had levels of <25nmol/L (severe deficiency). Vitamin D insufficiency and severe deficiency were associated (OR/HR, 95%CI) with an increased risk of 30-day mortality (OR 1.70, 1.22-2.36 and 2.70, 1.22-2.36) and increased length of stay (HR 0.88, 0.81-0.97 and 0.72, 0.65-0.81). Severe deficiency was associated with risk of falls (OR 1.77, 1.18-2.63), impaired Barthel index (OR 1.80, 1.42-2.28), and impairment in quality of life. Most associations remained robust after multivariate adjustment and in subgroups stratified by gender, age, comorbidities, and main diagnoses (P for interaction >0.05).In this comprehensive and large medical inpatient cohort, vitamin D deficiency was highly prevalent and strongly associated with adverse clinical outcome. Interventional research is urgently needed to prove the effect of vitamin D supplementation on these outcomes.

Unraveling the Link between Malnutrition and Adverse Clinical Outcomes: Association of Acute and Chronic Malnutrition Measures with Blood Biomarkers from Different Pathophysiological States.

BACKGROUND AND AIMS: Malnutrition is associated with poor clinical outcomes. Whether there is a causal relationship or it merely mirrors a severe patient condition remains unclear. We examined the association of malnutrition with biomarkers characteristic of different pathophysiological states to better understand the underlying etiological mechanisms. METHODS: We prospectively followed consecutive adult medical inpatients. Multivariable regression models were used to investigate the associations between malnutrition - as assessed using the Nutritional Risk Screening (NRS 2002) - and biomarkers linked to inflammation, stress, renal dysfunction, nutritional status and hematologic function. RESULTS: A total of 529 patients were included. In a fully adjusted model, malnutrition was significantly associated with the inflammatory markers procalcitonin (0.20, 95% CI 0.03-0.37), proadrenomedullin (0.28, 95% CI 0.12-0.43) and albumin (-0.39, 95% CI -0.57 to -0.21), the stress marker copeptin (0.34, 95% CI 0.17-0.51), the renal function marker urea (0.23, 95% CI 0.07-0.38), the nutritional markers vitamin D25 (-0.22, 95% CI -0.41 to -0.02) and corrected calcium (0.29, 95% CI 0.10-0.49) and the hematological markers hemoglobin (-0.27, 95% CI -0.43 to -0.10) and red blood cell distribution width (0.26, 95% CI 0.07-0.44). Subgroup analysis suggested that acute malnutrition rather than chronic malnutrition was associated with elevated biomarker levels. CONCLUSION: Acute malnutrition was associated with a pronounced inflammatory response and an alteration in biomarkers associated with different pathophysiological states. Interventional trials are needed to prove causality.

Performance of the Manchester Triage System in Adult Medical Emergency Patients: A Prospective Cohort Study.

BACKGROUND: Accurate initial patient triage in the emergency department (ED) is pivotal in reducing time to effective treatment by the medical team and in expediting patient flow. The Manchester Triage System (MTS) is widely implemented for this purpose. Yet the overall effectiveness of its performance remains unclear. OBJECTIVES: We investigated the ability of MTS to accurately assess high treatment priority and to predict adverse clinical outcomes in a large unselected population of medical ED patients. METHODS: We prospectively followed consecutive medical patients seeking ED care for 30 days. Triage nurses implemented MTS upon arrival of patients admitted to the ED. The primary endpoint was high initial treatment priority adjudicated by two independent physicians. Secondary endpoints were 30-day all-cause mortality, admission to the intensive care unit (ICU), and length of stay. We used regression models with area under the receiver operating characteristic curve (AUC) as a measure of discrimination. RESULTS: Of the 2407 patients, 524 (21.8%) included patients (60.5 years, 55.7% males) who were classified as high treatment priority; 3.9% (n = 93) were transferred to the ICU; and 5.7% (n = 136) died. The initial MTS showed fair prognostic accuracy in predicting treatment priority (AUC 0.71) and ICU admission (AUC 0.68), but not in predicting mortality (AUC 0.55). Results were robust across most predefined subgroups, including patients diagnosed with infections, or cardiovascular or gastrointestinal diseases. In the subgroup of neurological symptoms and disorders, the MTS showed the best performance. CONCLUSION: The MTS showed fair performance in predicting high treatment priority and adverse clinical outcomes across different medical ED patient populations. Future research should focus on further refinement of the MTS so that its performance can be improved. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01768494.

Can We Reduce Negative Blood Cultures With Clinical Scores and Blood Markers? Results From an Observational Cohort Study.

Only a small proportion of blood cultures routinely performed in emergency department (ED) patients is positive. Multiple clinical scores and biomarkers have previously been examined for their ability to predict bacteremia. Conclusive clinical validation of these scores and biomarkers is essential.This observational cohort study included patients with suspected infection who had blood culture sampling at ED admission. We assessed 5 clinical scores and admission concentrations of procalcitonin (PCT), C-reactive protein (CRP), lymphocyte and white blood cell counts, the neutrophil-lymphocyte count ratio (NLCR), and the red blood cell distribution width (RDW). Two independent physicians assessed true blood culture positivity. We used logistic regression models with area under the curve (AUC) analysis.Of 1083 patients, 104 (9.6%) had positive blood cultures. Of the clinical scores, the Shapiro score performed best (AUC 0.729). The best biomarkers were PCT (AUC 0.803) and NLCR (AUC 0.700). Combining the Shapiro score with PCT levels significantly increased the AUC to 0.827. Limiting blood cultures only to patients with either a Shapiro score of ≥4 or PCT > 0.1 µg/L would reduce negative sampling by 20.2% while still identifying 100% of positive cultures. Similarly, a Shapiro score ≥3 or PCT >0.25 µg/L would reduce cultures by 41.7% and still identify 96.1% of positive blood cultures.Combination of the Shapiro score with admission levels of PCT can help reduce unnecessary blood cultures with minimal false negative rates.The study was registered on January 9, 2013 at the 'ClinicalTrials.gov' registration web site (NCT01768494).

Association of nutritional risk and adverse medical outcomes across different medical inpatient populations.

OBJECTIVE: The aim of this study was to examine the prevalence of nutritional risk and its association with multiple adverse clinical outcomes in a large cohort of acutely ill medical inpatients from a Swiss tertiary care hospital. METHODS: We prospectively followed consecutive adult medical inpatients for 30 d. Multivariate regression models were used to investigate the association of the initial Nutritional Risk Score (NRS 2002) with mortality, impairment in activities of daily living (Barthel Index <95 points), hospital length of stay, hospital readmission rates, and quality of life (QoL; adapted from EQ5 D); all parameters were measured at 30 d. RESULTS: Of 3186 patients (mean age 71 y, 44.7% women), 887 (27.8%) were at risk for malnutrition with an NRS ≥3 points. We found strong associations (odds ratio/hazard ratio [OR/HR], 95% confidence interval [CI]) between nutritional risk and mortality (OR/HR, 7.82; 95% CI, 6.04-10.12), impaired Barthel Index (OR/HR, 2.56; 95% CI, 2.12-3.09), time to hospital discharge (OR/HR, 0.48; 95% CI, 0.43-0.52), hospital readmission (OR/HR, 1.46; 95% CI, 1.08-1.97), and all five dimensions of QoL measures. Associations remained significant after adjustment for sociodemographic characteristics, comorbidities, and medical diagnoses. Results were robust in subgroup analysis with evidence of effect modification (P for interaction < 0.05) based on age and main diagnosis groups. CONCLUSION: Nutritional risk is significant in acutely ill medical inpatients and is associated with increased medical resource use, adverse clinical outcomes, and impairments in functional ability and QoL. Randomized trials are needed to evaluate evidence-based preventive and treatment strategies focusing on nutritional factors to improve outcomes in these high-risk patients.

Use of procalcitonin, C-reactive protein and white blood cell count to distinguish between lower limb erysipelas and deep vein thrombosis in the emergency department: A prospective observational study.

Early differentiation of erysipelas from deep vein thrombosis (DVT) based solely on clinical signs and symptoms is challenging. There is a lack of data regarding the usefulness of the inflammatory biomarkers procalcitonin (PCT), C-reactive protein (CRP) and white blood cell (WBC) count in the diagnosis of localized cutaneous infections. Herein, we investigated the diagnostic value of inflammatory markers in a prospective at-risk patient population. This is an observational quality control study including consecutive patients presenting with a final diagnosis of either erysipelas or DVT. The association of PCT (µg/L) and CRP (mg/L) levels and WBC counts (g/L) with the primary outcome was assessed using logistic regression models with area under the receiver-operator curve. Forty-eight patients (erysipelas, n = 31; DVT, n = 17) were included. Compared with patients with DVT, those with erysipelas had significantly higher PCT concentrations. No significant differences in CRP concentrations and WBC counts were found between the two groups. At a PCT threshold of 0.1 µg/L or more, specificity and positive predictive values (PPV) for erysipelas were 82.4% and 85.7%, respectively, and increased to 100% and 100% at a threshold of more than 0.25 µg/L. Levels of PCT also correlated with the severity of erysipelas, with a stepwise increase according to systemic inflammatory response syndrome criteria. We found a high discriminatory value of PCT for differentiation between erysipelas and DVT, in contrast to other commonly used inflammatory biomarkers. Whether the use of PCT levels for early differentiation of erysipelas from DVT reduces unnecessary antibiotic exposure needs to be assessed in an interventional trial.

Procalcitonin improves the Glasgow Prognostic Score for outcome prediction in emergency patients with cancer: a cohort study.

The Glasgow Prognostic Score (GPS) is useful for predicting long-term mortality in cancer patients. Our aim was to validate the GPS in ED patients with different cancer-related urgency and investigate whether biomarkers would improve its accuracy. We followed consecutive medical patients presenting with a cancer-related medical urgency to a tertiary care hospital in Switzerland. Upon admission, we measured procalcitonin (PCT), white blood cell count, urea, 25-hydroxyvitamin D, corrected calcium, C-reactive protein, and albumin and calculated the GPS. Of 341 included patients (median age 68 years, 61% males), 81 (23.8%) died within 30 days after admission. The GPS showed moderate prognostic accuracy (AUC 0.67) for mortality. Among the different biomarkers, PCT provided the highest prognostic accuracy (odds ratio 1.6 (95% confidence interval 1.3 to 1.9), P < 0.001, AUC 0.69) and significantly improved the GPS to a combined AUC of 0.74 (P = 0.007). Considering all investigated biomarkers, the AUC increased to 0.76 (P < 0.001). The GPS performance was significantly improved by the addition of PCT and other biomarkers for risk stratification in ED cancer patients. The benefit of early risk stratification by the GPS in combination with biomarkers from different pathways should be investigated in further interventional trials.