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Purpose:Glucocorticoid (GC)-induced hyperglycemia is a frequent issue, however there are no specific guidelines for this diabetes subtype. Although treat-to-target insulin is recommended in general to correct hyperglycemia, it remains unclear which treatment strategy has a positive effect on outcomes. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess whether treating GC-induced hyperglycemia improves clinical outcomes. Methods: MEDLINE and EMBASE were systematically searched for RCTs on adults reporting treatment and outcomes of GC-induced hyperglycemia since the beginning of the data bases until August 2020. Glucose-lowering strategies as compared to usual care were investigated. Results: We found 14 RCTs with 595 patients and included seven trials in the quantitative analysis. Patients with an intensive glucose-lowering strategy had lower standardized mean glucose levels of – 0.42 mmol/l (95%CI -0.65 to -0.19) compared to usual care group patients. There was no increase in hypoglycemic events in the intensively treated groups (RR 0.87, 95%CI 0.48-1.56). Overall, we did not have enough trials reporting clinical outcomes for a quantitative analysis with only one trial reporting mortality. Conclusion: In GC-induced hyperglycemia, tight glucose control has a moderate effect on mean glucose levels with no apparent harmful effect regarding hypoglycemia, but there is insufficient data whether an intensive glucose-lowering strategy improves clinical outcomes. Systematic review registration Registered as CRD42020147409 at PROSPERO (https://www.crd.york.ac.uk/prospero/) on April 28, 2020

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. 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. 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). 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.

Zusammenfassung. Ein 50-jähriger Patient wurde zur weiteren Abklärung einer progredienten, chronischen Diarrhö mit Gewichtsverlust und therapierefraktärer Hypokaliämie zugewiesen. Nach den Abklärungen konnte als Ursache der Diarrhö ein neuroendokriner Tumor des Pankreas (VIPom) festgestellt und mittels erfolgreicher Pankreaslinksresektion und vorübergehender medikamentöser Behandlung mit Octreotid behandelt werden. Wichtig bei der Abklärung einer chronischen Diarrhö ist ein strukturiertes Vorgehen, insbesondere mit ausführlicher Anamnese sowie klinischen Untersuchungen, Labordiagnostik und Bildgebung.

Estimating the probability of readmission following hospitalization using prediction scores can be complex. Quality of life (QoL) may provide an easy and effective alternative. Secondary analysis of the prospective “TRIAGE” cohort. All medical in-patients admitted to a Swiss tertiary care institution (2016–2019) ≥18 years with a length of stay of ≥2 days (23,309 patients) were included. EQ-5D VAS, EQ-5D index, and Barthel index were assessed at a single telephone interview 30-day after admission. Patients lost to follow-up were excluded. Readmission was defined as a non-elective hospital stay at our institution >24 h within 1 year after discharge and assessed using area under the curve (AUC) analysis with adjustment for confounders. 12,842 patients (43% females, median age 68, IQR 55–78) were included. Unadjusted discrimination was modest at 0.59 (95% CI 0.56–0.62) for EQ-5D VAS. Partially adjusted discrimination (for gender) was identical. Additional adjustment for insurance, Charlson comorbidity index, length of stay, and native language increased the AUC to 0.66 (95% CI 0.63–0.69). Results were robust irrespective of time to event (12, 6 or 3 months). A cut-off in the unadjusted model of EQ-5D VAS of 55 could separate cases with a specificity of 80% and a sensitivity of 30%. QoL at day 30 after admission can predict one-year readmission risk with similar precision as more intricate tools. It might help for identification of high-risk patients and the design of tailored prevention strategies.

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 0.70 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-020-05638-z) contains supplementary material, which is available to authorized users.

ImportanceSwitzerland’s mandatory health insurance provides universal coverage, but residents can opt for supplementary private insurance for nonessential, nonvital amenities. It is debated whether people with supplementary private insurance receive overtreatment due to financial incentives.ObjectiveTo assess whether incidence rates of cardiovascular procedures in people with supplementary private insurance are higher than in those with basic insurance only.Design, Setting, and ParticipantsA population-based weighted cohort comparative effectiveness study, using administrative claims data from Switzerland assessing incidence rates (IRs), was conducted in adults undergoing a nonemergency cardiovascular inpatient procedure from January 1, 2012, to December 31, 2020. Analysis included primary or secondary discharge procedure codes for 1 of the following: percutaneous transluminal coronary angioplasty (PTCA), left atrial appendage (LAA) occlusion, patent foramen ovale (PFO) closure, transcatheter aortic valve replacement (TAVR), mitral valve clip implantation, cardiac pacemaker implantation, and atrial fibrillation/atrial flutter ablation.ExposuresSupplementary private health insurance.Main Outcomes and MeasuresIncidence rates of cardiovascular procedures between insurance groups calculated by negative binomial regression adjusted by inverse probability weights.ResultsOf 590 919 admissions (median age, 68 years; IQR, 57-77 years), 55.5% male, 15.7% non-Swiss nationality), 70.1% had basic insurance only. Independent of insurance status, IR for all cardiovascular procedures steadily increased over the study years. In general, people with supplementary private insurance received cardiovascular procedures more frequently (IR ratio [IRR], 1.11; 99% CI, 1.10-1.11) than people with basic insurance only. There was also an increase for every procedure: PTCA (IRR, 1.12; 99% CI, 1.12-1.13), LAA closure (IRR, 1.15; 99% CI, 1.13-1.16), mitral valve clip implantation (IRR, 1.08; 99% CI, 1.07-1.09), TAVR (IRR, 1.04; 99% CI, 1.03-1.06), PFO closure (IRR, 1.01; 99% CI, 1.00-1.02), pacemaker implantation (IRR, 1.08; 99% CI, 1.07-1.09), and atrial fibrillation/atrial flutter ablation (IRR, 1.12; 99% CI, 1.11-1.12). Sensitivity analyses, including side procedures, stratification by length of stay, and propensity score matching, suggested robustness of the results.Conclusions and RelevanceThis study found an association between supplementary private insurance and a higher likelihood of receiving nonemergency cardiovascular procedures. Whether this higher rate of procedures in people with supplementary private insurance is based on clinical reasoning or due to financial incentives warrants further exploration.

VIPoma of the Pancreas

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. Supplementary Information The online version contains supplementary material available at 10.1007/s15010-021-01728-0.

Survival after allogeneic stem cell transplantation (allo-HSCT) has improved, but so have long-term sequelae. We studied risk factors for fractures and impaired bone health in allo-HSCT patients in the Basel HSCT registry from 01/2003 to 12/2014 using cox proportional models adjusted for age, gender and Karnofsky Index. Our primary endpoint was the incidence of fractures. Out of 652 patients, 32 (5.0%) had a new fracture after transplantation (yearly incidence rate of 1.6%, 95% Confidence Interval [95%CI] 1.1-2.3%) and 325 (49.8%) had low bone mineral density (yearly incidence rate of 13.1%, 95%CI 11.6-14.8%), including 36.0% with osteopenia and 13.8% with osteoporosis. We found vitamin D deficiency during follow-up (Hazard Ratio [HR] 1.25, 95%CI 1.11-1.41, p

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.

A 60-year-old man presented to our hospital because of febrile neutropenia due to chemotherapy for his metastasized colon cancer. During hospital stay, polyuria and polydipsia were noted. He reported that his thirst had become increasingly intolerable over the last weeks. Diabetes mellitus was diagnosed. Polyuria and polydipsia persisted despite euglycemia under insulin treatment. Because of thirst and high urine volumes during the night, diabetes insipidus was suspected. Endocrinological work up revealed complete panhypopituitarism with impairment of all anterior and posterior axes. After substitution with hydrocortisone, levothyroxine and desmopressin symptoms resolved. MRI of the brain revealed one round, contrast enhancing lesion in the pituitary stalk and one in the pineal gland. Because of extensive extracerebral metastasis and poor performance status, the patient opted for radiation therapy only. He died 2.5 months later due to non-cerebral manifestations of his cancer before cerebral radiotherapy could be initiated.

Estimating the probability of readmission following hospitalization using prediction scores can be complex. Quality of life (QoL) may provide an easy and effective alternative.Secondary analysis of the prospective "TRIAGE" cohort. All medical in-patients admitted to a Swiss tertiary care institution (2016-2019) ≥18 years with a length of stay of ≥2 days (23,309 patients) were included. EQ-5D VAS, EQ-5D index, and Barthel index were assessed at a single telephone interview 30-day after admission. Patients lost to follow-up were excluded. Readmission was defined as a non-elective hospital stay at our institution 24 h within 1 year after discharge and assessed using area under the curve (AUC) analysis with adjustment for confounders.12,842 patients (43% females, median age 68, IQR 55-78) were included. Unadjusted discrimination was modest at 0.59 (95% CI 0.56-0.62) for EQ-5D VAS. Partially adjusted discrimination (for gender) was identical. Additional adjustment for insurance, Charlson comorbidity index, length of stay, and native language increased the AUC to 0.66 (95% CI 0.63-0.69). Results were robust irrespective of time to event (12, 6 or 3 months). A cut-off in the unadjusted model of EQ-5D VAS of 55 could separate cases with a specificity of 80% and a sensitivity of 30%.QoL at day 30 after admission can predict one-year readmission risk with similar precision as more intricate tools. It might help for identification of high-risk patients and the design of tailored prevention strategies.

Background & aims The EFFORT trial reported a substantial risk reduction for adverse events and mortality in medical in-patients receiving a nutritional support intervention. With the use of an untargeted metabolomics approach, we investigated the prognostic and therapeutic potential of metabolomic markers to understand, whether there are distinct metabolic patterns associated with malnutrition risk as assessed by the Nutritional Risk screening (NRS 2002) score, the risk of 30-day mortality and the response to nutritional support, respectively. Methods Out of the 2088 samples we randomly selected 120 blood samples drawn on day 1 after hospital admission and before treatment initiation. Samples were stratified by NRS 2002, treatment allocation (intervention vs. control), and mortality at 30 days, but not on the type of medical illness. We performed untargeted analysis by liquid chromatography mass spectrometry (LC-MS/MS). Results We measured 1389 metabolites in 120 patients of which 81 (67.5%) survived until day 30. After filtering, 371 metabolites remained, and 200 were matched to one or more Human Metabolome Data Base (HMDB) entries. Between group analysis showed a slight distinction between the treatment groups for patients with a NRS 3, but not for those with NRS 4 and ≥ 5. C-statistic between those who died and survived at day 30 ranged from 0.49 (95% confidence interval 0.35–0.68) for a combination of 5 metabolites/predictors to 0.66 (95% confidence interval 0.53–0.79) for a combination of 100 metabolites. Pathway analysis found significant enrichment in the pathways for nitrogen, vitamin B3 (nicotinate and nicotinamide), leukotriene, and arachidonic acid metabolisms in nutritional support responders compared to non-responders. Conclusion In our heterogenous population of medical inpatients with different illnesses and comorbidities, metabolomic markers showed little prognostic and therapeutic potential for better phenotyping malnutrition and response to nutritional therapy. Future studies should focus on more selected patient populations to understand whether a metabolomic approach can advance the nutritional care of patients., Clinical Nutrition, 40 (9), ISSN:0261-5614

Un homme âge de 64 ans s’est presente dans le service des urgences, atteint d’un sepsis. Les analyses de sang ont revele, en tant qu’anomalies concomitantes, un TSH de 0,03 mU/l, un fT3 de

Ein 64-jahriger Mann stellte sich mit einer Sepsis auf der Notfallstation vor. In der Blutentnahme zeigten sich als Nebenbefund ein TSH von 0,03 mU/l, ein fT3 von

AIM OF THE STUDY To compare admission characteristics, predictors and outcomes of patients with confirmed coronavirus disease 2019 (COVID-19) hospitalised in a tertiary care hospital in Switzerland during the first and second waves of the pandemic. METHODS This retrospective observational analysis included adult patients with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection confirmed by a real-time reverse transcriptase polymerase chain reaction (RT-PCR) or rapid antigen test and hospitalised at the Cantonal Hospital Aarau from 26 February to 30 April 2020 (first wave) and from 1 October to 31 December 2020 (second wave). The primary endpoint was all-cause in-hospital mortality. The secondary endpoints were transfer to the intensive care unit (ICU) and length of hospital stay (LOS). RESULTS Overall, 486 patients (mean age 65.9 years ± 14.7 SD, 65% male) were included. Ninety-two patients (19%) died during the hospital stay and 92 patients (19%) were transferred to the ICU. Admission characteristics, including comorbidities and frailty, were similar for patients of the first (n = 100) and second wave (n = 386). However, during the second wave the median time from symptom onset to presentation to the emergency department (ED) was shorter (7 days, interquartile range [IQR] 4–9 vs 8 days, IQR 4–11; p = 0.02). In the second wave, most patients received high-dose glucocorticoid treatment (0% vs 76%, p

Background Uncertainty about factors influencing the susceptibility and triggers for Graves’ disease persists, along with a wide variation in the response to anti-thyroid drugs, currently at approximately 50% of non-responders. The aim of this narrative review is to summarize immunological concepts, with a combined endocrine and immunological perspective, to highlight potential new areas of research. Main text Relevant studies were identified through a systematic literature search using the PubMed and EMBASE databases in March 2016. No cut-offs regarding dates were imposed. We used the terms “Graves’ Disease” or “Basedow” or “thyrotoxicosis” together with the terms “etiology”, “pathophysiology”, “immunodeficiency”, “causality”, and “autoimmunity”. The terms “orbitopathy”, “ophthalmopathy”, and “amiodarone” were excluded. Articles in English, French, German, Croatian, Spanish, and Italian were eligible for inclusion. Conclusions While concepts such as the impact of iodine, smoking, human leucocyte antigen, infections, and ethnicity are established, new ideas have emerged. Pertaining evidence suggests the involvement of autoimmunity and immunodeficiency in the pathophysiology of Graves’ disease. Recent studies point to specific immunological mechanisms triggering the onset of disease, which may also serve as targets for more specific therapies.

Background: Metabolic syndrome is a major risk factor for cardiovascular diseases, which are still the major cause of death in developed countries. Methods: We cross-sectionally studied the association between urinary phytoestrogen excretion and metabolic cardiovascular risk factors. Hence, we used data from the National Health and Nutrition Examination Survey from 1999 to 2004 with 1,748 participants, who had urine levels of isoflavones and lignans measured. Geometric means of waist circumference, blood pressure, fasting glucose, HDL cholesterol, and triglyceride levels were computed by quartiles of isoflavone or lignan urinary excretion. Outcome was assessed as the presence of metabolic syndrome according to NCEP-ATP III criteria. The association between phytoestrogen concentration and the metabolic syndrome was calculated using logistic regression analyses. Results: Plasma triglyceride and HDL cholesterol levels were lower in participants in the highest quartile of lignan excretion compared with the lowest (both P

Background Early diagnosis and relapse prediction in Graves’ disease influences treatment. We assessed the abilities of four TSH-receptor antibody tests [TRAb] and one cyclic adenosine monophosphate bioassay to predict relapse of Graves’ disease. Methods Observational study investigating patients presenting with Graves’ disease at a Swiss hospital endocrine referral center or an endocrine outpatient clinic. Main outcomes were diagnosis and relapse of Graves’ disease after stop of anti-thyroid drugs. We used Cox regression to study associations of TRAb levels with relapse risk and calculated c-statistics [AUC] to assess discrimination. Blood draws took place as close as possible to treatment initiation. Results AUCs ranged from 0.90 (TSAb Biossay by RSR) to 0.97 (IMMULITE TSI by Siemens). Highest sensitivity (94.0%) was observed for IMMULITE TSI and RSR TRAb Fast, while the greatest specificity (97.9%) was found with the EliA anti-TSH-R (by Thermo Fisher). In Cox regression analysis comparing the highest versus the lower quartiles, the highest hazard ratio [HR] for relapse was found for BRAHMS TRAK (by Thermo Fisher) (2.98, 95% CI 1.13–7.84), IMMULITE TSI (2.40, 95% CI 0.91–6.35), EliA anti-TSH-R (2.05, 95% CI 0.82–5.10), RSR Fast TRAb (1.80, 95% CI 0.73–4.43), followed by RSR STIMULATION (1.18, 95% CI 0.46–2.99). Discrimination analyses showed respective AUCs of 0.68, 0.65, 0.64, 0.64, and 0.59. Conclusion The assays tested had good diagnostic power and relapse risk prediction with few differences among the new assays. Due to the small sample size and retrospective design with possible selection bias, our data need prospective validation. Electronic supplementary material The online version of this article (10.1186/s12902-019-0363-6) contains supplementary material, which is available to authorized users.

Background: Glucocorticoid (GC)-induced hyperglycemia is a frequent side effect in hospitalized patients. Guidelines recommend treat-to-target treatment between 6&ndash, 10 mmol/L (108&ndash, 180 mg/dL) with insulin, but data on outcome is scarce. We investigated the 30-day outcome in hospitalized patients receiving GCs. Methods: All patient records of hospitalized patients between January 2014 and April 2018 were screened for GC administration and consecutive hyperglycemia. The primary combined endpoint consisted of death, cardiovascular events, and infections until 30 days after admission. Hypoglycemia was a secondary outcome. Results: Of the 2424 hospitalized patients (9.6% of all hospitalized patients) who received systemic GCs and met inclusion criteria, the overall incidence for GC-induced hyperglycemia was 812 (33.5%), and 89 (3.7%) had at least one documented hypoglycemia during their hospital stay. Compared to patients with normoglycemia, GC-induced hyperglycemia had an adjusted-odds ratio of 1.68 (95% CI 1.25&ndash, 2.26) for the combined primary endpoint. Hypoglycemia even had an odds ratio of 1.95 (95% CI 1.2&ndash, 3.17). Conclusions: Mortality, cardiovascular events, and rate of infections were markedly higher in patients with GC-induced hyperglycemia as compared to patients with normoglycemia. Importantly, hypoglycemia was associated with a doubled risk for adverse outcome. Future studies should evaluate whether optimized glucose control by minimizing the risk for hypoglycemia has a beneficial effect on clinical outcomes in patients with GC-induced hyperglycemia.

Whether the addition of immunosuppressive drugs to standard antithyroid drugs reduces the relapse risk in Graves' disease remains uncertain.The aim of this study was to investigate the effects of immunosuppressive drugs on the relapse rate after a first episode of hyperthyroidism due to Graves' disease.Based on a pre-specified protocol, PubMed (1946-July 2015), EMBASE (1947-July 2015), and Cochrane (1992-July 2015) databases were searched. The search was for (randomized) controlled trials comparing immunosuppressive drugs with a control group. PRISMA and SIGN statements were used for assessing data quality. Two reviewers extracted data, with any disagreement being resolved by consensus. Data were pooled using a random-effects model.The primary endpoint was relapse of disease until follow-up. Secondary endpoints included reduction of thyroid volume and decrease in thyrotropin-receptor antibody (TRAb) levels. Seven trials with 862 participants were included. Most trials were small with a moderate to high risk of bias. There were 113 relapses in 481 (23.5%) patients receiving immunosuppressive drugs compared with 225 relapses in 381 (59.1%) control patients (risk ratio for recurrence 0.55; [confidence interval (CI) 0.41-0.75]). Subgroup analyses showed similar effects for randomized trials and controlled trials (I(2) 0%), and for trials using corticosteroid and non-corticosteroid immunosuppressive drugs (I(2) 0%). Use of immunosuppressive drugs also resulted in significant reductions in thyroid volume (-10.72 mL [CI -15.59 to -5.85]) and TRAb levels (-17.01 IU/L [CI -33.31 to -0.72]). Immunosuppressive drug-related adverse effects were not systematically reported, and thus were not included in the quantitative analysis.Current evidence suggests a possible relevant reduction in relapse risk when immunosuppressive drugs are added to standard treatment of Graves' disease. The small number of trials with high heterogeneity in regard to treatment modalities and the lack of systematic reporting of adverse effects calls for larger, conclusive trials.

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 (NRS 2002) as markers of inflammation and poor nutritional status, respectively, with low serum albumin levels and mortality using multivariate regression analyses. RESULTS Of 2,465 patients, 1,019 (41%) had low serum albumin levels (20mg/L. Multivariate analyses adjusted for age, gender, diagnosis, and comorbidities revealed elevated CRP values (adjusted odds ratio [OR] 10.51, 95% confidence intervals [CI] 7.51 to 14.72, P

Le traitement de la maladie de Basedow a peu evolue au cours des dernieres annees. Une nouvelle approche «personnalisee» fait appel a l’evaluation initiale du risque de recidive.

Trotz Fortschritten bei anderen Autoimmunerkrankungen hat sich die Therapie des Morbus Basedow in den letzten Jahren wenig verandert. Ein neuer «personalisierter» Ansatz nutzt die initiale Abschatzung des Rezidivrisikos.

BACKGROUND Hyponatremia is a common feature of acute illness and associated with increased mortality. This may be explained by a stress-mediated activation of the vasopressin system with an increase in free-water reabsorption. OBJECTIVES To investigate whether the association between hyponatremia and mortality could be explained by activation of the vasopressin system. METHODS We prospectively enrolled adult, medical patients seeking emergency care in three centres in Switzerland, France and the United States. We investigated associations between admission plasma sodium and copeptin, a stable portion of the vasopressin-precursor peptide, with 30-day mortality. We performed uni- and multivariate regression analysis. RESULTS Of 6962 included patients, 18% had hyponatremia (sodium ≤135 mmol L-1 ), which doubled their risk for mortality compared to patients with normonatremia (8.3% vs. 3.8%). This association was confirmed in a multivariate-adjusted logistic regression analysis [adjusted odds ratio (OR) 1.47, 95% CI 1.12-1.93, P = 0.005]. Vasopressin levels, mirrored by copeptin, were also increased in nonsurvivors and strongly associated with mortality (adjusted OR 3.42, 95% CI 2.76-4.25, P < 0.001). The association between hyponatremia and mortality remained unchanged when adding copeptin levels to the regression model (fully adjusted OR 1.53, 95% CI 1.16-2.00, P = 0.002). CONCLUSION This prospective study including medical patients upon emergency room admission found hyponatremia as well as an activation of the vasopressin system to be independently associated with mortality. This suggests that stress- and vasopressin-independent mechanisms are responsible for the association of low sodium levels with mortality.

Understanding how best to manage the complex healthcare needs of hospitalised, mostly multimorbid medical patients is an international priority. Healthcare should be effective, safe and provide high quality at a reasonable cost. However, basic logistic and organisational issues of medical ward-based care have received less attention than the medical treatment of specific pathologies. Consequently, we still use old-fashioned care and transition procedures for medical inpatients. This contrasts with dynamic developments in other, non-healthcare industries, where process optimisation is a major part of innovation. Promising new approaches to better align healthcare needs of hospitalised medical patients from clinical trials will help to advance the field significantly. Healthcare costs attributable to the aging, multimorbid population are rising worldwide. One cost driver is the high resource use of in-hospital treatment. In view of the expected demographic evolution of an aging population, better resource allocation is important. As in other countries, the Swiss healthcare system is in the midst of transformation aiming to improve health outcomes of patients at an affordable cost. One important area of redesign is identifying the best setting for diagnosis, treatment and management of acute medical conditions with a shift of in-hospital to outpatient care. Also, safely reducing in-hospital length of stay of inpatient treatment is important, because inpatient care accounts for the largest share of total Swiss healthcare costs. Integration of new technology into these processes holds promises for optimisation. Use of electronic health record-based tools has resulted in improved patient care and patient transitions. But evidence from clinical studies regarding the effect of inter-professional team care interventions on patient relevant outcomes, including activity of daily living, mortality and length of hospital stay, are inconsistent. Thus, there is room for improvement and a need for high quality trials providing evidence on how best to combine technology with innovative transition models for an ameliorated care of medical inpatients. We review in narrative form different transition interventions that have been evaluated for improved medical inpatient care and highlight important patient-centred outcome measures that were investigated. Further, we discuss a novel patient-management tool (In-HospiTOOL), which is currently being evaluated in an ongoing large Swiss multicentre study.

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.

Objective: Adrenocorticotrophic hormone (ACTH) stimulation testing is the current standard for assessing primary and secondary adrenal insufficiency (AI). We aimed to investigate the value of basal cortisol level for prediction of AI. Methods: We retrospectively analyzed 804 consecutive patients who had high-dose (250 μg, HDT) or low-dose (1 μg, LDT) ACTH testing as part of their diagnostic work-up. Site-specific cut-off levels for AI were Results: Overall, 70/400 (17.5%) in the LDT group and 118/404 (29.2%) in the HDT group showed an insufficient increase of cortisol and were categorized as AI. The receiver operating characteristic curve analysis showed an overall area under the curve (AUC) for basal cortisol of 0.88, which was comparable in LDT (area under the curve lAUC] 0.88) and HDT (AUC 0.88). If basal cortisol levels were ≥450 nmol/L (n = 234/804, 29.1%), the negative predictive value to rule out AI was 98.7%. If cortisol was ≤100 nmol/L (n = 69/804, 8.6%) the positive predictive value was 93.2% to rule in AI. There was a minimal additional value of the 30-minute cortisol level in HDT as compared to the 60-minute result, as well as for delta values. Conclusion: Basal cortisol levels ≤100 and ≥450 nmol/L were found in almost half of patients tested for possible AI and had high diagnostic accuracy, abolishing the need for formal ACTH testing. The 30-minute cortisol value in HDT did not increase diagnostic accuracy. These data may help guide clinicians when testing can safely be omitted, thereby reducing expenses and simplifying test protocols. Abbreviations: ACTH = adrenocorticotropic hormone AI = adrenal insufficiency AUC = area under the curve CI = confidence interval HDT = high-dose test HPA axis = hypothalamus-pituitary-adrenal axis ITT = insulin tolerance test LDT = low-dose test NR = normal responders LR+/- = positive/negative likelihood ratio NPV = negative predictive value PPV = positive predictive value

Context First-line treatment in Graves’ disease is often done with antithyroid agents (ATD), but relapse rates remain high making definite treatment necessary. Predictors for relapse risk help guiding initial treatment decisions. Objective We aimed to externally validate the prognostic accuracy of the recently proposed Graves’ Recurrent Events After Therapy (GREAT) score to predict relapse risk in Graves’ disease. Design, setting and participants We retrospectively analyzed data (2004–2014) of patients with a first episode of Graves’ hyperthyroidism from four Swiss endocrine outpatient clinics. Main outcome measures Relapse of hyperthyroidism analyzed by multivariate Cox regression. Results Of the 741 included patients, 371 experienced a relapse (50.1%) after a mean follow-up of 25.6 months after ATD start. In univariate regression analysis, higher serum free T4, higher thyrotropin-binding inhibitor immunoglobulin (TBII), younger age and larger goiter were associated with higher relapse risk. We found a strong increase in relapse risk with more points in the GREAT score from 33.8% in patients with GREAT class I (0–1 points), 59.4% in class II (2–3 points) with a hazard ratio of 1.79 (95% CI: 1.42–2.27, P P Conclusions Based on this retrospective analysis within a large patient population from a multicenter study, the GREAT score shows good external validity and can be used for assessing the risk for relapse in Graves’ disease, which influence the initial treatment decisions.

ObjectivesRecently, 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.DesignSecondary analysis of a prospective, observational study (TRIAGE study).SettingOne 600-bed tertiary care hospital in Aarau, Switzerland.ParticipantsConsecutive 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 measuresThe 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.ResultsOf 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, pConclusionOur 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 numberNCT01768494; Post-results.

BackgroundIdentification of pretreatment risk factors predicting relapse in patients with hyperthyroidism of Graves’ disease after stopping anti-thyroid drugs (ATD) is decisive to guide therapeutic options.PurposeWe performed a systematic search and meta-analysis to study predictors for relapse after stopping ATD in patients with Graves’ disease.MethodsBased on a pre-specified protocol, we searched PubMed, EMBASE and Cochrane in July 2015 for case–control, controlled and randomized-controlled trials reporting risk factors for relapse after stopping ATD. The primary endpoint was relapse of disease until follow-up. PRISMA and SIGN statements were used for reviewing the data and assessing the quality of included trials.ResultsWe included 54 trials with a total of 7595 participants. Most trials were small with moderate-to-high risk for bias. Ten trials were assessed only qualitatively (2227 patients), genomic data were reported in 13 trials (2178 patients) and 31 trials (4346 patients) were assessed quantitatively. In total, there were 3696 relapses in 7595 patients (48.7%). By using random-effects meta-analysis, orbitopathy, smoking, thyroid volume measured by sonography, goiter size, fT4, tT3, TRAb and TBII were significantly associated with relapse, whereas male vs female sex, age and initial tT4 level did not show significant associations.ConclusionsThis analysis found several risk factors to predict relapse in Graves’ disease, which can be combined in a risk score. Prospective studies should evaluate the prognostic accuracy of such a score to guide treatment decisions.