What Are They Worth? Six 30-Day Readmission Risk Scores for Medical Inpatients Externally Validated in a Swiss Cohort.

BACKGROUND: Several clinical risk scores for unplanned 30-day readmission have been published, but there is a lack of external validation and head-to-head comparison. OBJECTIVE: Retrospective replication of six clinical risk scores (LACE, HOSPITAL, SEMI, RRS, PARA, Tsui et al.)f DESIGN: Models were fitted with the original intercept and beta coefficients as reported. Otherwise, a logistic model was refitted (SEMI and Tsui et al). We performed subgroup analyses on main admission specialty. This report adheres to the TRIPOD statement for reporting of prediction models. PARTICIPANTS: We used our prospective cohort of 15,639 medical patients from a Swiss tertiary care institution from 2016 through 2018. MAIN MEASURES: Thirty-day readmission rate and area under the curve (AUC < 0.50 worse than chance, > 0.70 acceptable, > 0.80 excellent) CONCLUSIONS: Among several readmission risk scores, HOSPITAL, PARA, and the score from Tsui et al. showed the best predictive abilities and have high potential to improve patient care. Interventional research is now needed to understand the effects of these scores when used in clinical routine. KEY RESULTS: Among the six risk scores externally validated, calibration of the models was overall poor with overprediction of events, except for the HOSPITAL and the PARA scores. Discriminative abilities (AUC) were as follows: LACE 0.53 (95% CI 0.50-0.56), HOSPITAL 0.73 (95% CI 0.72-0.74), SEMI 0.47 (95% CI 0.46-0.49), RRS 0.64 (95% CI 0.62-0.66), PARA 0.72 (95% CI 0.72-0.74), and the score from Tsui et al. 0.73 (95% CI 0.72-0.75). Performance in subgroups did not differ from the overall performance, except for oncology patients in the PARA score (0.57, 95% CI 0.54-0.60), and nephrology patients in the SEMI index (0.25, 95% CI 0.18-0.31), respectively.

Metabolomics and Their Ability to Distinguish Thyroid Disorders: A Retrospective Pilot Study.

Early diagnosis of thyroid disorders is key to further treatment. We assessed the ability of a high-throughput proton NMR metabolomic profile to distinguish disease type amongst of Graves' disease (n=87), Hashimoto's thyroiditis (n=17), toxic goiter (n=11), and autoimmune thyroiditis [i. e., subacute thyroiditis (n=4), postpartum thyroiditis (n=1)]. This observational study was conducted investigating patients presenting with a thyroid disorder at a Swiss hospital endocrine referral center and an associated endocrine outpatient clinic. The main outcome was diagnosis of thyroid disorder based on classical parameters. Blood draws took place as close as possible to treatment initiation. We performed one-way ANOVA and partial least squares discriminant analysis (PLS-DA) as multivariate classification and feature ranking method. One-way ANOVA analysis yielded following significantly different metabolites, triglycerides in small VLDL, triglycerides in very small VLDL, and triglycerides in large LDL (FDR=0.04). There was no distinct separation of any of the 4 diagnoses by PLS-DA. We did not find a metabolomic biomarker combination capable of predicting diagnosis. Preanalytical issues might have influenced our results. We strongly suggest replicating our work in another cohort.

Octopamine in male aggression of Drosophila.

BACKGROUND: In mammals and humans, noradrenaline is a key modulator of aggression. Octopamine, a closely related biogenic amine, has been proposed to have a similar function in arthropods. However, the effect of octopamine on aggressive behavior is little understood. RESULTS: An automated video analysis of aggression in male Drosophila has been developed, rendering aggression accessible to high-throughput studies. The software detects the lunge, a conspicuous behavioral act unique to aggression. In lunging, the aggressor rears up on his hind legs and snaps down on his opponent. By using the software to eliminate confounding effects, we now show that aggression is almost abolished in mutant males lacking octopamine. This suppression is independent of whether tyramine, the precursor of octopamine, is increased or also depleted. Restoring octopamine synthesis in the brain either throughout life or in adulthood leads to a partial rescue of aggression. Finally, neuronal silencing of octopaminergic and tyraminergic neurons almost completely abolishes lunges. CONCLUSIONS: Octopamine modulates Drosophila aggression. Genetically depleting the animal of octopamine downregulates lunge frequency without a sizable effect on the lunge motor program. This study provides access to the neuronal circuitry mediating this modulation.

Estimated glomerular filtration rate predicts 30-day mortality in medical emergency departments: Results of a prospective multi-national observational study.

BACKGROUND: Renal failure is common in patients seeking help in medical emergency departments. Decreased renal function is associated with increased mortality in patients with heart failure or sepsis. In this study, the association between renal function (reflected by estimated glomerular filtration rate (eGFR) at the time of admission) and clinical outcome was evaluated. METHODS/OBJECTIVES: Data was used from a prospective, multi-national, observational cohort of patients treated in three medical emergency departments of tertiary care centers. The eGFR was calculated from the creatinine at the time of admission (using the Chronic Kidney Disease-Epidemiology Collaboration equation,CKD-EPI). Uni- and multivariate regression models were used for eGFR and 30-day mortality, in hospital mortality, length of stay and intensive care unit admission rate. RESULTS: 6983 patients were included. The 30-day mortality was 1.8%, 3.5%, 6.9%, 11.1%, 13.6%, and 14.2% in patients with eGFR of above 90, 60-89, 45-59, 30-44, 15-29, and <15 ml/min/1.73m2, respectively. Using multivariate regression, the adjusted odds ratio (OR) was 2.31 (for 15-29 ml/min/1.73m2, 95% confidence interval 1.36 to 3.90, p = 0.002) and 3.73 (for eGFR <15ml/min/1.73m2 as compared to >90 ml/min/1.73m2, 95% CI 2.04 to 6.84, p<0.001). For 10 ml/min/1.73m2 decrease in eGFR the OR for the 30-day mortality was 1.15 (95% CI1.09 to 1.22, p<0.001).The eGFR was also significantly associated with in-hospital mortality, the percentage of ICU-admissions, and with a longer hospital stay. No association was found with hospital readmission within 30 days. As limitations, only eGFR at admission was available and the number of patients on hemodialysis was unknown. CONCLUSION: Reduced eGFR at the time of admission is a strong and independent predictor for adverse outcome in this large population of patients admitted to medical emergency departments.

Relationship of Nutritional Status, Inflammation, and Serum Albumin Levels During Acute Illness: A Prospective Study.

BACKGROUND: Low serum albumin levels resulting from inflammation-induced capillary leakage or disease-related anorexia during acute illness are associated with poor outcomes. We investigated the relationship of nutritional status and inflammation with low serum albumin levels and 30-day mortality in a large cohort. METHODS: We prospectively enrolled adult patients in the medical emergency department of a Swiss tertiary care center and investigated associations of C-reactive protein (CRP) and Nutritional Risk Screening 2002 as markers of inflammation and poor nutritional status, respectively, with low serum albumin levels and mortality using multivariate regression analyses. RESULTS: Among the 2465 patients, 1019 (41%) had low serum albumin levels (<34 g/L), 619 (25.1%) had increased nutritional risk (Nutritional Risk Screening 2002 ≥3), and 1086 (44.1%) had CRP values >20 mg/L. Multivariate analyses adjusted for age, gender, diagnosis, and comorbidities revealed elevated CRP values (adjusted odds ratio [OR] 10.51, 95% confidence interval, 7.51-14.72, P <.001) and increased malnutrition risk (adjusted OR 2.87, 95% confidence interval, 1.98-4.15, P <.001) to be associated with low serum albumin levels, even adjusting for both parameters. Low serum albumin levels, elevated CRP values, and increased nutritional risk independently predicted 30-day mortality, with areas under the curve of 0.77, 0.70, and 0.75, respectively. Combination of these 3 parameters showed an area under the curve of 0.82 to predict mortality. CONCLUSIONS: Elevated parameters of inflammation and high nutritional risk were independently associated with hypoalbuminemia. All 3 parameters independently predicted mortality. Combining them during initial evaluation of patients in emergency departments facilitates mortality risk stratification.

Combination of the National Early Warning Score (NEWS) and inflammatory biomarkers for early risk stratification in emergency department patients: results of a multinational, observational study.

OBJECTIVES: The National Early Warning Score (NEWS) helps to estimate mortality risk in emergency department (ED) patients. This study aimed to investigate whether the prognostic value of the NEWS at ED admission could be further improved by adding inflammatory blood markers (ie, white cell count (WCC), procalcitonin (PCT) and midregional-proadrenomedullin (MR-proADM). DESIGN: Secondary analysis of a multinational, observational study (TRIAGE study, March 2013-October 2014). SETTING: Three tertiary care centres in France, Switzerland and the USA. PARTICIPANTS: A total of 1303 adult medical patients with complete NEWS data seeking ED care were included in the final analysis. NEWS was calculated retrospectively based on admission data. MAIN OUTCOME MEASURES: The primary outcome was all-cause 30-day mortality. Secondary outcome was intensive care unit (ICU) admission. We used multivariate regression analyses to investigate associations of NEWS and blood markers with outcomes and area under the receiver operating curve (AUC) as a measure of discrimination. RESULTS: Of the 1303 included patients, 54 (4.1%) died within 30 days. The NEWS alone showed fair prognostic accuracy for all-cause 30-day mortality (AUC 0.73), with a multivariate adjusted OR of 1.26 (95% CI 1.13 to 1.40, p<0.001). The AUCs for the prediction of mortality using the inflammatory markers WCC, PCT and MR-proADM were 0.64, 0.71 and 0.78, respectively. Combining NEWS with all three blood markers or only with MR-proADM clearly improved discrimination with an AUC of 0.82 (p=0.002). Combining the three inflammatory markers with NEWS improved prediction of ICU admission (AUC 0.70vs0.65 when using NEWS alone, p=0.006). CONCLUSION: NEWS is helpful in risk stratification of ED patients and can be further improved by the addition of inflammatory blood markers. Future studies should investigate whether risk stratification by NEWS in addition to biomarkers improve site-of-care decision in this patient population. TRIAL REGISTRATION NUMBER: NCT01768494; Post-results.

Validation of the hospital frailty risk score in a tertiary care hospital in Switzerland: results of a prospective, observational study.

OBJECTIVES: Recently, the Hospital Frailty Risk Score based on a derivation and validation study in the UK has been proposed as a low-cost, systematic screening tool to identify older, frail patients who are at a greater risk of adverse outcomes and for whom a frailty-attuned approach might be useful. We aimed to validate this Score in an independent cohort in Switzerland. DESIGN: Secondary analysis of a prospective, observational study (TRIAGE study). SETTING: One 600-bed tertiary care hospital in Aarau, Switzerland. PARTICIPANTS: Consecutive medical inpatients aged ≥75 years that presented to the emergency department or were electively admitted between October 2015 and April 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was all-cause 30-day mortality. Secondary endpoints were length of hospital stay, hospital readmission, functional impairment and quality of life measures. We used multivariate regression analyses. RESULTS: Of 4957 included patients, 3150 (63.5%) were classified as low risk, 1663 (33.5%) intermediate risk, and 144 (2.9%) high risk for frailty. Compared with the low-risk group, patients in the moderate risk and high-risk groups had increased risk for 30-day mortality (OR (OR) 2.53, 95% CI 2.09 to 3.06, p<0.001 and OR 4.40, 95% CI 2.94 to 6.57, p<0.001) with overall moderate discrimination (area under the ROC curve 0.66). The results remained robust after adjustment for important confounders. Similarly, we found longer length of hospital stay, more severe functional impairment and a lower quality of life in higher risk group patients. CONCLUSION: Our data confirm the prognostic value of the Hospital Frailty Risk Score to identify older, frail people at risk for mortality and adverse outcomes in an independent patient population. TRIAL REGISTRATION NUMBER: NCT01768494; Post-results.

Metabolomics for Prediction of Relapse in Graves' Disease: Observational Pilot Study.

Background: There is a lack of biochemical markers for early prediction of relapse in patients with Graves' disease [GD], which may help to direct treatment decisions. We assessed the prognostic ability of a high-throughput proton NMR metabolomic profile to predict relapse in a well characterized cohort of GD patients. Methods: Observational study investigating patients presenting with GD at a Swiss hospital endocrine referral center and an associated endocrine outpatient clinic. We measured 227 metabolic markers in the blood of patients before treatment initiation. Main outcome was relapse of hyperthyroidism within 18 months of stopping anti-thyroid drugs. We used ROC analysis with AUC to assess discrimination. Results: Of 69 included patients 18 (26%) patients had a relapse of disease. The clinical GREAT score had an AUC of 0.68 (95% CI 0.63-0.70) to predict relapse. When looking at the metabolomic markers, univariate analysis revealed pyruvate and triglycerides in medium VLDL as predictors with AUCs of 0.73 (95% CI 0.58-0.84) and 0.67 (95% CI 0.53-0.80), respectively. All other metabolomic markers had lower AUCs. Conclusion: Overall, metabolomic markers in our pilot study had low to moderate prognostic potential for prediction of relapse of GD, with pyruvate and triglycerides being candidates with acceptable discriminatory abilities. Our data need validation in future larger trials.