Evaluation of soluble suppression of tumorigenicity 2 (sST2) as serum marker for liver fibrosis.

BACKGROUND & AIMS: With the increase in patients at risk of advanced liver disease due to the obesity epidemic, there will be a need for simple screening tools for advanced liver fibrosis. Soluble suppression of tumorigenicity 2 (sST2) is a serum biomarker for fibrotic processes. The aim of this study was to evaluate sST2 as marker for liver fibrosis in patients successfully treated for chronic hepatitis C. METHODS: 424 patients from the Swiss Hepatitis C Cohort Study were screened for inclusion in this post-hoc cohort study. Inclusion criteria were sustained virological response (SVR), available elastography (VCTE) and serum samples for biomarker analysis before and after treatment. For the validation of sST2, values were compared to VCTE, FIB-4 and APRI using Spearman's correlation and AUROC analyses. RESULTS: Data of 164 subjects were finally analyzed. Median sST2 values slightly increased with VCTE-derived fibrosis stages and remained stable after reaching SVR within the respective fibrosis stage, suggesting that sST2 is not influenced by liver inflammation. However, correlation of sST2 pre- and post-treatment with VCTE was fair (Spearman's rho = 0.39 and rho = 0.36). The area under the curve (AUROC) for sST2 in detecting VCTE-defined F4 fibrosis (vs. F0-F3) before therapy was 0.74 (95%CI 0.65-0.83), and 0.67(95%CI 0.56-0.78) for the discrimination of F3/F4 fibrosis vs. F0-F2. Adding sST2 to either APRI or FIB-4, respectively, increased diagnostic performance of both tests. CONCLUSIONS: sST2 can potentially identify patients with advanced fibrosis as a single serum marker and in combination with APRI and FIB-4.

Lead and generator dysfunction in children and adolescents with epicardial pacemaker and implantable cardioverter defibrillator systems: The challenge of early recognition.

BACKGROUND: A major issue of cardiac implantable electronic device therapy in pediatric patients is the high incidence of lead dysfunctions and associated reinterventions. This study aims to analyze the timing and mode of generator and lead dysfunction. METHODS: Retrospective single-center analysis of 283 children and young adults with an epicardial pacemaker or implantable cardioverter defibrillator therapy from 1998 to 2018. RESULTS: Mean age at implant was 6.1 years (SD ± 5.8 years) and median follow-up 6.4 years (IQR, 3.4-10.4 years) with a total of 1998.1 patient-years of cardiac device therapy. A total of 120 lead-related complications were observed in 82 patients (29.0%). They were detected by device interrogation (n = 86), symptoms (n = 13), intraoperative findings (n = 7), routine chest radiography (n = 5), routine ECG (n = 4), patient alert sound by device (n = 3), and physical examination (n = 2). It was possible to find the date of the event on the device memory in 21 out of 120 lead dysfunctions (18%) with a median time interval between occurrence and detection of 1.3 months (IQR, 0.2-5.0 months). Moreover, 20 generator-related complications were found in 13 patients. CONCLUSIONS: Early recognition of lead and generator dysfunction remains challenging in pediatric patients. As symptoms are relatively rare conditions in the context of PM and ICD dysfunction, close patient monitoring is mandatory, even in asymptomatic patients with a good clinical course. To further improve the safety of pediatric pacing systems, more durable epicardial electrodes are desirable.

Prevalence, risk factors and impact of delirium in adult inpatients in a tertiary care hospital: A point prevalence study.

AIMS: To describe the point prevalence, risk factors and possible outcomes of delirium in inpatients. DESIGN: A cross-sectional point prevalence study. BACKGROUND: Delirium is an acute brain syndrome that negatively affects patients, healthcare professionals and institutions alike; it is common in inpatient settings and is preventable in about one third of cases. Although guidelines recommend systematic screening and assessment, delirium is often unrecognised, undiagnosed and uncoded. There is a lack of valid data on this patient safety indicator in German-speaking countries. METHODS: The study was conducted in a tertiary care hospital in Switzerland on 5 July 2022. Specially trained registered nurses collected data from all patients meeting the inclusion criteria using CAM, ICDSC or mCAM-ED. Data were analysed descriptively with stratification by delirium status, setting and surgery. RESULTS: The point prevalence across all settings was 6.9% (27/390), with large variation between settings: ICU 28.6% (4/14), IMC 28.0% (7/25), wards 4.6% (15/326) and ED 4% (1/25). Surgical patients were almost twice as likely to be affected as medical patients (8.9% vs. 4.8%). Patients with delirium differed most clearly from those without by having a larger number of ICD-10 F-diagnoses, a larger number of medications and higher age, which are known risk factors. Moreover, those with delirium had more missed diagnoses, increased mortality, more adverse events and higher costs. CONCLUSIONS: A significant number of patients experienced delirium and adverse clinical outcomes. Missed delirium diagnoses may further jeopardise patient safety and result in lost revenue. It remains unclear to what extent the risk factors and effects of delirium are causal and what determinants underlie missed diagnoses. RELEVANCE TO CLINICAL PRACTICE: Consistent identification of high-risk patients and treatment settings with elevated risk, accompanied by the implementation of effective preventive and management strategies, is critical to addressing delirium.

A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation.

BACKGROUND & AIMS: Machine perfusion is a novel method intended to optimize livers before transplantation. However, its effect on morbidity within a 1-year period after transplantation has remained unclear. METHODS: In this multicenter controlled trial, we randomly assigned livers donated after brain death (DBD) for liver transplantation (LT). Livers were either conventionally cold stored (control group), or cold stored and subsequently treated by 1-2 h hypothermic oxygenated perfusion (HOPE) before implantation (HOPE group). The primary endpoint was the occurrence of at least one post-transplant complication per patient, graded by the Clavien score of ≥III, within 1-year after LT. The comprehensive complication index (CCI), laboratory parameters, as well as duration of hospital and intensive care unit stay, graft survival, patient survival, and biliary complications served as secondary endpoints. RESULTS: Between April 2015 and August 2019, we randomized 177 livers, resulting in 170 liver transplantations (85 in the HOPE group and 85 in the control group). The number of patients with at least one Clavien ≥III complication was 46/85 (54.1%) in the control group and 44/85 (51.8%) in the HOPE group (odds ratio 0.91; 95% CI 0.50-1.66; p = 0.76). Secondary endpoints were also not significantly different between groups. A post hoc analysis revealed that liver-related Clavien ≥IIIb complications occurred less frequently in the HOPE group compared to the control group (risk ratio 0.26; 95% CI 0.07-0.77; p = 0.027). Likewise, graft failure due to liver-related complications did not occur in the HOPE group, but occurred in 7% (6 of 85) of the control group (log-rank test, p = 0.004, Gray test, p = 0.015). CONCLUSIONS: HOPE after cold storage of DBD livers resulted in similar proportions of patients with at least one Clavien ≥III complication compared to controls. Exploratory findings suggest that HOPE decreases the risk of severe liver graft-related events. IMPACT AND IMPLICATIONS: This randomized controlled phase III trial is the first to investigate the impact of hypothermic oxygenated perfusion (HOPE) on cumulative complications within a 12-month period after liver transplantation. Compared to conventional cold storage, HOPE did not have a significant effect on the number of patients with at least one Clavien ≥III complication. However, we believe that HOPE may have a beneficial effect on the quantity of complications per patient, based on its application leading to fewer severe liver graft-related complications, and to a lower risk of liver-related graft loss. The HOPE approach can be applied easily after organ transport during recipient hepatectomy. This appears fundamental for wide acceptance since concurring perfusion technologies need either perfusion at donor sites or continuous perfusion during organ transport, which are much costlier and more laborious. We conclude therefore that the post hoc findings of this trial should be further validated in future studies.

Did the first wave of the COVID-19 pandemic impact the cesarean delivery rate? A retrospective cohort study at a primary care center in Switzerland.

OBJECTIVES: During the first 3 months of the coronavirus disease 2019 (COVID-19) pandemic, our hospital's quality management team determined a decline in the rate of cesarean deliveries (CD). Thus, in this study we examined both the factors associated with this decrease as well as neonatal outcomes. METHODS: This was a retrospective observational cohort study comparing deliveries (n=597) between March and May 2020 (first nationwide "lockdown" in Switzerland) with those during the same period in 2018 and 2019 (n=1,063). A multivariable logistic regression analysis was used to examine the association between CD and the pandemic, adjusting for relevant risk factors for CD. RESULTS: The overall rate of CD during the pandemic period was lower (30.0%), than during the pre-pandemic period (38.7%, unadjusted odds ratio 0.68, 95% confidence interval [95%CI]: 0.55 to 0.84, p=0.0004) a result that was supported by the adjusted odds ratio (0.73, 95%CI: 0.54 to 0.99, p=0.04). CONCLUSIONS: The results of this study confirmed a significant reduction in the rate of CD in early 2020, during the first lockdown period due to COVID-19, but without major differences in maternal and infant health indicators or in obstetric risk factors than before the pandemic. These results may have been due to a difference in the composition of the obstetric team as well as the behavior of the obstetrics team and in the patients during the pandemic, given the burden it placed on healthcare systems. However, this hypothesis remains to be tested in further research.

Clinical parameters associated with gastric portal hypertensive polyps.

OBJECTIVES: Portal hypertensive polyps (PHPs) are incompletely characterized lesions that can be found in the distal stomach of patients with portal hypertension. We aimed to delineate clinical factors associated with the appearance of these rare polyps. MATERIAL AND METHODS: We conducted a cross-sectional study of a cohort with 513 cirrhotic patients comparing patients with and without PHP using descriptive analyses and multivariable logistic regression. To address the problem of missing values, in particular for HVPG and liver stiffness, we used multiple imputation of missing values. RESULTS: The prevalence of macroscopically diagnosed PHP was 3.3% (95% confidence interval 2.0 - 5.4%). In 53% of cases, the correct classification was missed on index gastroscopy. Patients with PHP were older at gastroscopy (65 years vs. 59), had higher hepatic venous pressure gradients (HVPG, 28 mmHg vs. 19 mmHg), higher transient elastography (TE) measurements (50.7 kPa vs. 21.8 kPa) and more often had previous rubber band ligations (RBL, 64.7% vs. 25.8%). The multivariable logistic regression on the outcome macroscopically diagnosed PHP estimated an odds ratio (OR) for HPVG of 1.13 (CI 0.95-1.34), increased liver stiffness of 1.03 (1.00 - 1.07) and previous RBL of 3.84 (1.24 - 11.88), respectively. CONCLUSION: The prevalence of PHPs in the stomach was higher than assumed in previous studies and misclassification was commonly observed. The appearance of these rare polyps is associated with previous RBL and may correlate with severity of PH. Thus, PHPs may be regarded as marker for relevant PH, but clinical significance of these polyps is still uncertain.

Specialised Paediatric PAlliativE CaRe: Assessing family, healthcare professionals and health system outcomes in a multi-site context of various care settings: SPhAERA study protocol.

BACKGROUND: The number of children and adolescents living with life-limiting conditions and potentially in need for specialised paediatric palliative care (SPPC) is rising. Ideally, a specialised multiprofessional team responds to the complex healthcare needs of children and their families. The questions of, how SPPC is beneficial, for whom, and under what circumstances, remain largely unanswered in the current literature. This study's overall target is to evaluate the effectiveness of a SPPC programme in Switzerland with respect to its potential to improve patient-, family-, health professional-, and healthcare-related outcomes. METHODS: This comparative effectiveness study applies a quasi-experimental design exploring the effectiveness of SPPC as a complex intervention at one treatment site in comparison with routine care provided in a generalised PPC environment at three comparison sites. As the key goal of palliative care, quality of life - assessed at the level of the patient-, the family- and the healthcare professional - will be the main outcome of this comparative effectiveness research. Other clinical, service, and economic outcomes will include patient symptom severity and distress, parental grief processes, healthcare resource utilisation and costs, direct and indirect health-related expenditure, place of death, and introduction of SPPC. Data will be mainly collected through questionnaire surveys and chart analysis. DISCUSSION: The need for SPPC has been demonstrated through numerous epidemiological and observational studies. However, in a healthcare environment focused on curative treatment and struggling with limited resources, the lack of evidence contributes to a lack of acceptance and financing of SPPC which is a major barrier against its sustainability. This study will contribute to current knowledge by reporting individual and child level outcomes at the family level and by collecting detailed contextual information on healthcare provision. We hope that the results of this study can help guiding the expansion and sustainability of SPPC and improve the quality of care for children with life-limiting conditions and their families internationally. TRIAL REGISTRATION: Registered prospectively on ClinicalTrials.gov on January 22, 2020. NCT04236180 PROTOCOL VERSION: Amendment 2, March 01, 2021.

Editor's Choice - Risk of Stroke before Revascularisation in Patients with Symptomatic Carotid Stenosis: A Pooled Analysis of Randomised Controlled Trials.

OBJECTIVE: Current guidelines recommending rapid revascularisation of symptomatic carotid stenosis are largely based on data from clinical trials performed at a time when best medical therapy was potentially less effective than today. The risk of stroke and its predictors among patients with symptomatic carotid stenosis awaiting revascularisation in recent randomised controlled trials (RCTs) and in medical arms of earlier RCTs was assessed. METHODS: The pooled data of individual patients with symptomatic carotid stenosis randomised to stenting (CAS) or endarterectomy (CEA) in four recent RCTs, and of patients randomised to medical therapy in three earlier RCTs comparing CEA vs. medical therapy, were compared. The primary outcome event was any stroke occurring between randomisation and treatment by CAS or CEA, or within 120 days after randomisation. RESULTS: A total of 4 754 patients from recent trials and 1 227 from earlier trials were included. In recent trials, patients were randomised a median of 18 (IQR 7, 50) days after the qualifying event (QE). Twenty-three suffered a stroke while waiting for revascularisation (cumulative 120 day risk 1.97%, 95% confidence interval [CI] 0.75 - 3.17). Shorter time from QE until randomisation increased stroke risk after randomisation (χ2 = 6.58, p = .011). Sixty-one patients had a stroke within 120 days of randomisation in the medical arms of earlier trials (cumulative risk 5%, 95% CI 3.8 - 6.2). Stroke risk was lower in recent than earlier trials when adjusted for time between QE and randomisation, age, severity of QE, and degree of carotid stenosis (HR 0.47, 95% CI 0.25 - 0.88, p = .019). CONCLUSION: Patients with symptomatic carotid stenosis enrolled in recent large RCTs had a lower risk of stroke after randomisation than historical controls. The added benefit of carotid revascularisation to modern medical care needs to be revisited in future studies. Until then, adhering to current recommendations for early revascularisation of patients with symptomatic carotid stenosis considered to require invasive treatment is advisable.

Comparison of the resonance sonorheometry based Quantra® system with rotational thromboelastometry ROTEM® sigma in cardiac surgery - a prospective observational study.

BACKGROUND: Measures of the sonorheometry based Quantra® viscoelastic hemostatic analyzer (HemoSonics, LCC, Charlottesville, VA, USA) were compared with corresponding results of the ROTEM® sigma device (Instrumentation Laboratory, Bedford, MA, USA). METHODS: In thirty-eight patients scheduled for elective cardiac surgery between December 2018 and October 2019, blood samples were taken after induction of anesthesia (sample 1) and after heparin neutralization (sample 2) and measured on Quantra (QPlus® Cartridge) and ROTEM sigma (ROTEM® sigma complete + hep Cartridge). Clot times and clot stiffness values were recorded. Clot stiffness values of ROTEM amplitudes (A in mm) were converted to shear modulus (G) in hectoPascal (hPa): G (hPa) = (5 x A)/(100-A). Additionally, time-to-results was recorded. Spearman rank test correlation and Bland Altman analysis were performed. RESULTS: Clot stiffness parameters of the Quantra correlated strongly with corresponding measurements of the ROTEM with r = 0.93 and 0.94 for EXTEM A10 vs CS and r = 0.94 and 0.96 for FIBTEM A10 vs FCS for sample 1 and 2, respectively. Quantra clot time correlated strongly with ROTEM INTEM CT with r = 0.71 for sample 1 and r = 0.75 for sample 2. However, Bland Altman analysis showed no agreement in all compared assays of both methods. The median time to delivery of first and complete results was significantly shorter for Quantra (412 and 658 s) compared to ROTEM sigma (839 and 1290 s). CONCLUSIONS: The Quantra showed a strong correlation with the ROTEM sigma for determining clot times and clot stiffness and the parameters assess similar aspects of clot development. However, these parameters are not directly interchangeable and implicate that separate cut-off values need to be established for users of the Quantra device. Word count: 278. TRIAL REGISTRATION: The study was retrospectively registered with ClinicalTrials.gov (ID: NCT04210830 ) at December 20th 2019.

Evaluation of a caries prevention programme for preschool children in Switzerland: is the target group being reached?

BACKGROUND: With the goal of reducing the prevalence of early childhood caries, the city of Zurich, Switzerland, started a specific prevention programme in 2010. All 2-year-olds are invited to a free dental check-up at a local public dental health service before the first legally mandated yearly dental check-up for school children between 4 and 5 years of age (at kindergarten). However, for the success of this prevention programme, it is of particular importance that children at high risk of caries are reached. The objective of our study was to assess the effectiveness of the prevention programme in (1) reaching the children who needed it the most and (2) improving subsequent oral health. METHODS: This retrospective cohort study included all children born between July 1, 2013 and July 15, 2014 who had lived in Zurich between the ages of 23 and 36 months. Socio-economic data were extracted from official school records, and dental health data from public dental clinic records. Binomial and quasi-binomial generalised linear models were used to identify the socio-economic factors associated with toddler check-up attendance and to assess the associations between attendance and caries experience (dmft [Formula: see text] 1) as well as degree of treatment (proportion m+f out of dmft) at the kindergarten check-up, adjusting for socio-economic factors. RESULTS: From a total of 4376 children, 2360 (54%) attended the toddler check-up (mean age 2.4 years) and 3452 (79%) had a dental examination at kindergarten (mean age 5.3 years). Non-Swiss origin of the primary caretaker, presence of older siblings, low amount of savings and allocation to certain public dental clinics were associated with a lower odds of attendance. Factors associated with a higher odds of caries experience were similar to those associated with a lower odds of attendance at the toddler check-up, but additionally included low income. Attendance at the toddler check-up was non-significantly associated with a lower odds of caries experience at kindergarten (adjusted OR 0.84, 95% CI from 0.70 to 1.01), but was significantly associated with a higher degree of treatment at this stage (adjusted OR 2.41, 95% CI from 1.79 to 3.24). CONCLUSIONS: Our study suggests that children with a high caries risk are less likely to attend the toddler check-up. Greater effort should be put into reaching these children.

Impact of a nurse-led family support intervention on family members' satisfaction with intensive care and psychological wellbeing: A mixed-methods evaluation.

BACKGROUND: Families of critically ill persons face uncertainty and experience distress during and after their close other's stay in an intensive care unit (ICU). Proactive nurse engagement and support is recommended to meet families' needs in the ICU, but little is known about its impact on quality of family care. We introduced a family support intervention that consisted of an interprofessional family support pathway and a new role of an advanced practice family nurse. OBJECTIVES: The aim of the study was to examine the effect of an advanced practice nurse-led family support intervention on family members' satisfaction, wellbeing, and psychological distress. METHODS: We conducted a quasi-experimental before-and-after study with embedded qualitative interviews in a Swiss University Hospital from March 2018 to July 2019 using a questionnaire (Family Satisfaction in the ICU-24 Survey, Hospital Anxiety and Depression Scale, and Impact of Event Scale-Revised-6) and qualitative interviews (n = 19) after patient discharge. RESULTS: Families in the intervention group (n = 75) showed a trend for increased overall satisfaction (difference of 5.544, 95% confidence interval [CI]: -0.11 to 11.20), a statistically significant increase in satisfaction with decision-making (7.258, 95% CI: 0.89 to 13.63), and a nonsignificant increase in satisfaction with care (4.178, 95% CI: -1.53 to 9.89). Psychological distress was higher in the intervention group, with depression reaching statistical significance (difference of 1.706, 95% CI: 0.16 to 3.25), which may be explained by longer ICU stays and higher proportion of deaths in the intervention group. Families receiving the intervention reported to be feeling cared for, well informed, and better able to cope. Data integration suggests that early onset, fit to need, and quality of intervention were the most important intervention characteristics impacting family wellbeing. CONCLUSIONS: Our study found that family members experience a nurse-led support intervention as beneficial for their wellbeing. It increased their satisfaction, but was unable to demonstrate a favourable impact on psychological distress.

Implementation and evaluation of a care bundle for prevention of non-ventilator-associated hospital-acquired pneumonia (nvHAP) - a mixed-methods study protocol for a hybrid type 2 effectiveness-implementation trial.

BACKGROUND: Hospital acquired pneumonia (HAP) is divided in two distinct groups, ventilator-associated pneumonia (VAP) and non-ventilator-associated HAP (nvHAP). Although nvHAP occurs more frequently than VAP and results in similar mortality and costs, prevention guidelines and prevention focus almost exclusively on VAP. Scientific evidence about nvHAP prevention and its implementation is scarce. Therefore, we designed a mixed-methods hybrid type 2 effectiveness-implementation study to investigate both the effectiveness and implementation of a newly developed nvHAP prevention bundle. METHODS: This single-centre project at the 950-bed University Hospital Zurich (UHZ) will engage the wards of nine departments with substantial nvHAP rates. The nvHAP bundle consists of five primary prevention measures: 1) oral care, 2) prevention of dysphagia-related aspiration, 3) mobilization, 4) stopping unnecessary proton pump inhibitors, and, 5) respiratory therapy. Implementation includes the engagement of department-level implementation teams, who sustain the 'core' intervention components of education, training, and environmental restructuring and tailor the implementation strategy to local needs. Both effectiveness and implementation outcomes will be assessed using mixed-methods. As a primary outcome, nvHAP incidence rates will be analysed by Poisson regression models to compare incidence rates before, during, and after the implementation phases (on the hospital and department level). Additionally, the association between process indicators and nvHAP incidence rates will be analysed using longitudinal Poisson regression models. A longitudinal, qualitative study and formative evaluation based on interviews, focus groups, and observations identifies supporting or hindering factors for implementation success in participating departments dynamically over time. This accumulating implementation experience will be constantly fed back to the implementation teams and thus, represents an active implementation element. DISCUSSION: This comprehensive hybrid mixed-methods study is designed to both, measure the effectiveness of a new nvHAP prevention bundle and multifaceted implementation strategy, while also providing insights into how and why it worked or failed. The results of this study may contribute substantially to advancing knowledge and patient safety in the area of a rediscovered healthcare-associated infection - nvHAP. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03361085 . Registered December 2017.

Immediate and Delayed Procedural Stroke or Death in Stenting Versus Endarterectomy for Symptomatic Carotid Stenosis.

Background and Purpose- Stenting for symptomatic carotid stenosis (carotid artery stenting [CAS]) carries a higher risk of procedural stroke or death than carotid endarterectomy (CEA). It is unclear whether this extra risk is present both on the day of procedure and within 1 to 30 days thereafter and whether clinical risk factors differ between these periods. Methods- We analyzed the risk of stroke or death occurring on the day of procedure (immediate procedural events) and within 1 to 30 days thereafter (delayed procedural events) in 4597 individual patients with symptomatic carotid stenosis who underwent CAS (n=2326) or CEA (n=2271) in 4 randomized trials. Results- Compared with CEA, patients treated with CAS were at greater risk for immediate procedural events (110 versus 42; 4.7% versus 1.9%; odds ratio, 2.6; 95% CI, 1.9-3.8) but not for delayed procedural events (59 versus 46; 2.5% versus 2.0%; odds ratio, 1.3; 95% CI, 0.9-1.9; interaction P=0.006). In patients treated with CAS, age increased the risk for both immediate and delayed events while qualifying event severity only increased the risk of delayed events. In patients treated with CEA, we found no risk factors for immediate events while a higher level of disability at baseline and known history of hypertension were associated with delayed procedural events. Conclusions- The increased procedural stroke or death risk associated with CAS compared with CEA was caused by an excess of events occurring on the day of procedure. This finding demonstrates the need to enhance the procedural safety of CAS by technical improvements of the procedure and increased operator skill. Higher age increased the risk for both immediate and delayed procedural events in CAS, mechanisms of which remain to be elucidated. Clinical Trial Registration- URL: https://clinicaltrials.gov . Unique identifier: NCT00190398. URL: http://www.isrctn.com . Unique identifier: ISRCTN57874028. URL: http://www.isrctn.com . Unique identifier: ISRCTN25337470. URL: https://clinicaltrials.gov . Unique identifier: NCT00004732.

Impact of chronic hyponatremia on neurocognitive and neuromuscular function.

BACKGROUND: Chronic hyponatremia is common and associated with increased morbidity and mortality. However, whether treatment improves outcome in patients without significant symptoms is unclear. We here assessed the therapeutic outcome on clinical symptoms, neurocognitive and neuromuscular function in patients with chronic non profound hyponatremia. MATERIAL AND METHODS: Prospective case-control study in 19 patients from the University Hospital Würzburg with chronic non profound hyponatremia without clinically apparent symptoms. At baseline and after a 14-day treatment period of hyponatremia, patients were assessed by specific clinical symptoms questionnaire, neurocognitive and neuromuscular function was analysed by five attention tests and a gait test consisting of 3 steps "in tandem." The results were compared to a control group of healthy volunteers. RESULTS: Compared to healthy volunteers, patients with mild (n = 10, mean serum sodium 132 ± 1.2 mmol/L) and moderate hyponatremia (n = 9, mean 126 ± 3.3 mmol/L) performed significantly worse in the neurocognitive subtests alertness (P = 0.018), divided attention (P = 0.017) and go/no-go (P = 0.026). Performance in the neuromuscular subtests was also lower in the patient group without reaching significance. The extent of hyponatremia had no impact on the specific test and questionnaire results. Fourteen-day treatment of hyponatremia improved clinical symptoms in all patients (P = 0.003) and neurocognitive function in sodium-normalised patients (go/no-go test, P = 0.029). CONCLUSION: Chronic hyponatremia is symptomatic and impairs neurocognitive and neuromuscular function. Short-time therapeutic intervention led to improved clinical symptoms and neurocognitive function, but had no effect on neuromuscular function. Larger trials with long-term treatment are needed to specify the therapeutic need in chronic hyponatremia.

Long-term efficacy and safety of biodegradable-polymer biolimus-eluting stents: main results of the Basel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination II (BASKET-PROVE II), a randomized, controlled noninferiority 2-year outcome trial.

BACKGROUND: Biodegradable-polymer drug-eluting stents (BP-DES) were developed to be as effective as second-generation durable-polymer drug-eluting stents (DP-DES) and as safe >1 year as bare-metal stents (BMS). Thus, very late stent thrombosis (VLST) attributable to durable polymers should no longer appear. METHODS AND RESULTS: To address these early and late aspects, 2291 patients presenting with acute or stable coronary disease needing stents ≥3.0 mm in diameter between April 2010 and May 2012 were randomly assigned to biolimus-A9-eluting BP-DES, second-generation everolimus-eluting DP-DES, or thin-strut silicon-carbide-coated BMS in 8 European centers. All patients were treated with aspirin and risk-adjusted doses of prasugrel. The primary end point was combined cardiac death, myocardial infarction, and clinically indicated target-vessel revascularization within 2 years. The combined secondary safety end point was a composite of VLST, myocardial infarction, and cardiac death. The cumulative incidence of the primary end point was 7.6% with BP-DES, 6.8% with DP-DES, and 12.7% with BMS. By intention-to-treat BP-DES were noninferior (predefined margin, 3.80%) compared with DP-DES (absolute risk difference, 0.78%; -1.93% to 3.50%; P for noninferiority 0.042; per protocol P=0.09) and superior to BMS (absolute risk difference, -5.16; -8.32 to -2.01; P=0.0011). The 3 stent groups did not differ in the combined safety end point, with no decrease in events >1 year, particularly VLST with BP-DES. CONCLUSIONS: In large vessel stenting, BP-DES appeared barely noninferior compared with DP-DES and more effective than thin-strut BMS, but without evidence for better safety nor lower VLST rates >1 year. Findings challenge the concept that durable polymers are key in VLST formation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01166685.

IDH mutation is associated with higher risk of malignant transformation in low-grade glioma.

Acquisition of IDH1 or IDH2 mutation (IDHmut) is among the earliest genetic events that take place in the development of most low-grade glioma (LGG). IDHmut has been associated with longer overall patient survival. However, its impact on malignant transformation (MT) remains to be defined. A collection of 210 archived adult LGG previously stratified by IDHmut, MGMT methylation (MGMTmet), 1p/19q combined loss of heterozygosity (1p19qloh) and TP53 immunopositivity (TP53pos) status was analyzed. We used multistate models to assess MT-free survival, considering one initial, one transient (MT), and one absorbing state (death). Missing explanatory variables were multiply imputed. Overall, although associated with a lower risk of death (HR(DEATH) = 0.35, P = 0.0023), IDHmut had a non-significantly higher risk of MT (HR(MT) = 1.84; P = 0.1683) compared to IDH wild type (IDHwt). The double combination of IDHmut and MGMTmet and the triple combination of IDHmut, MGMTmet and 1p/19qloh, despite significantly lower hazards for death (HR(DEATH) versus IDHwt: 0.35, P = 0.0194 and 0.15, P = 0.0008, respectively), had non-significantly different hazards for MT. Conversely, the triple combination of IDHmut/MGMTmet/TP53pos, with a non-significantly different hazard for death, had a significantly higher hazard for MT than IDHwt (HR(MT) versus IDHwt: 2.83; P = 0.0452). Although IDHmut status is associated with longer overall patient survival, all IDHmut/MGMTmet subsets consistently showed higher risks of MT than of death, compared to IDHwt LGG. This supports the findings that molecular events relevant to IDH mutations impact early glioma development prior to malignant transformation.

Superiority in Quality of Life Improvement of Biologics over Conventional Systemic Drugs in a Swiss Real-Life Psoriasis Registry.

BACKGROUND: Randomized controlled trials have shown the efficacy of systemic treatments in moderate-to-severe psoriasis. Clinical outcomes in psoriasis patients under real-world conditions are less well understood. OBJECTIVE: This study compared Psoriasis Area and Severity Index (PASI) and Dermatological Life Quality Index (DLQI) improvement in all psoriasis patients registered in the Swiss Dermatology Network for Targeted Therapies. We asked whether outcomes differed between 4 treatment strategies, namely biologic monotherapy versus conventional systemic monotherapy, versus combined biologic and conventional systemic drugs, and versus therapy adaptation (switching from one type to another). METHODS: PASI and DLQI within 1 year after onset of systemic treatment, measured at 3, 6, and 12 months, were compared among the 4 groups using generalized linear mixed-effects models. RESULTS: Between March 2011 and December 2014, 334 patients were included; 151 received conventional systemic therapeutics, 145 biologics, 13 combined treatment, and 25 had a therapy adaptation. With regard to the absolute PASI, neither the biologic cohort nor the combined treatment cohort significantly differed from the conventional systemic therapeutics cohort. The odds of reaching PASI90 was significantly increased with combined therapy compared to conventional systemic therapeutics (p = 0.043) and decreased with a higher body mass index (p = 0.041). At visits 3 and 4, the PASI was generally lower than at visit 2 (visit 3 vs. visit 2, p = 0.0019; visit 4 vs. visit 2, p < 0.001). After 12 months, patients with biologic treatment had a significantly lower DLQI than those with conventional systemic therapeutics (p = 0.001). CONCLUSION: This study suggests that after 1 year of treatment, biologics are superior in improving the subjective disease burden compared to conventional systemic drugs.