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The poor translational success rate of preclinical stroke research may partly be due to inaccurate modelling of the disease. We provide data on transient middle cerebral artery occlusion (tMCAO) experiments, including detailed intraoperative monitoring to elaborate predictors indicating experimental success (ischemia without occurrence of confounding pathologies). The tMCAO monitoring data (bilateral cerebral blood flow, CBF; heart rate, HR; and mean arterial pressure, MAP) of 16 animals with an ‘ideal’ outcome (MCA-ischemia), and 48 animals with additional or other pathologies (subdural haematoma or subarachnoid haemorrhage), were checked for their prognostic performance (receiver operating characteristic curve and area under the curve, AUC). Animals showing a decrease in the contralateral CBF at the time of MCA occlusion suffered from unintended pathologies. Implementation of baseline MAP, in addition to baseline HR (AUC, 0.83, 95% c.i. 0.68 to 0.97), increased prognostic relevance (AUC, 0.89, 95% c.i. 0.79 to 0.98). Prediction performance improved when two additional predictors referring to differences in left and right CBF were considered (AUC, 1.00, 95% c.i. 1.0 to 1.0). Our data underline the importance of peri-interventional monitoring to verify a successful experimental performance in order to ensure a disease model as homogeneous as possible., Summary: An assessment of the importance of peri-interventional monitoring to verify a successful experimental performance in order to ensure a disease model that is as homogeneous as possible.

Background/Aims: IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and still constitutes one of the most important causes of end-stage renal disease. Abnormal T cell responses may play a role in IgAN pathogenesis. Co-stimulatory molecules such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are important for naive T cells to initiate and terminate immune responses. Single nucleotide polymorphisms (SNPs) in the CTLA4 gene locus are associated with several autoimmune diseases. Methods: We aimed to investigate the occurrence of the SNPs -318C/T, +49A/G and CT60 G/A within the CTLA4 locus in healthy blood donors (n=455) and IgAN patients (n=252) recruited from the recently published STOP-IgAN trial. The presence of these SNPs was then associated with baseline proteinuria in IgAN patients. Results: We observed a significantly increased frequency of the CTLA4 -318C/T genotype in IgAN patients as compared to controls (CC vs. CT+TT: OR 1.65, 95%-CI 1.03-2.65, p=0.035). No significant associations, neither with the +49A/G nor for the CT60 G/A SNP, were detected. However, when we stratified for proteinuria at time of inclusion into the STOP-IgAN trial (1 g/day), we observed significant differences in the frequencies of the CT60 G/A genotype, i.e. a significantly increased risk for higher proteinuria in patients carrying the G allele (OR 2.81, 95%-CI 1.03-7.64, p=0.042). Conclusion: The CTLA4 -318/C/T SNP was associated with an increased risk to develop IgAN, while the CT60 G/A genotype significantly associated with the risk for higher proteinuria suggesting a possible role for CTLA-4 in IgAN.

The role of immunosuppression in IgA nephropathy (IgAN) is controversial. In the Supportive Versus Immunosuppressive Therapy for the Treatment of Progressive IgA Nephropathy (STOP-IgAN) Trial, 162 patients with IgAN and proteinuria >0.75 g/d after 6 months of optimized supportive care were randomized into two groups: continued supportive care or additional immunosuppression (GFR≥60 ml/min per 1.73 m2: 6-month corticosteroid monotherapy; GFR=30–59 ml/min per 1.73 m2: cyclophosphamide for 3 months followed by azathioprine plus oral prednisolone). Coprimary end points were full clinical remission and GFR loss ≥15 ml/min per 1.73 m2 during the 3-year trial phase. In this secondary intention to treat analysis, we separately analyzed data from each immunosuppression subgroup and the corresponding patients on supportive care. Full clinical remission occurred in 11 (20%) patients receiving corticosteroid monotherapy and three (6%) patients on supportive care (odds ratio, 5.31; 95% confidence interval, 1.07 to 26.36; P=0.02), but the rate did not differ between patients receiving immunosuppressive combination and controls on supportive care (11% versus 4%, respectively; P=0.30). The end point of GFR loss ≥15 ml/min per 1.73 m2 did not differ between groups. Only corticosteroid monotherapy transiently reduced proteinuria at 12 months. Severe infections, impaired glucose tolerance, and/or weight gain in the first year were more frequent with either immunosuppressive regimen than with supportive care. In conclusion, only corticosteroid monotherapy induced disease remission in a minority of patients who had IgAN with relatively well preserved GFR and persistent proteinuria. Neither immunosuppressive regimen prevented GFR loss, and both associated with substantial adverse events.

BACKGROUND: The outcomes of immunosuppressive therapy, when added to supportive care, in patients with IgA nephropathy are uncertain. METHODS: We conducted a multicenter, open-label, randomized, controlled trial with a two-group, parallel, group-sequential design. During a 6-month run-in phase, supportive care (in particular, blockade of the renin-angiotensin system) was adjusted on the basis of proteinuria. Patients who had persistent proteinuria with urinary protein excretion of at least 0.75 g per day were randomly assigned to receive supportive care alone (supportive-care group) or supportive care plus immunosuppressive therapy (immunosuppression group) for 3 years. The primary end points in hierarchical order were full clinical remission at the end of the trial (protein-to-creatinine ratio

Background Elderly patients are vulnerable to adverse drug reactions (ADRs). Drug-related readmissions (DRRs) can be a major consequence of ADR. Therefore, this study aimed to investigate the effects of a ward-based, comprehensive pharmaceutical care service on the occurrence of DRRs as the endpoint in dependent-living elderly patients. Methods A randomized, controlled trial was performed at a German University Hospital. Patients fulfilling the following criteria were eligible: admission to a cooperating ward, existing drug therapy at admission, 65 years of age and older, home-care or nursing home residents in ambulatory care, and a minimum hospital stay of three days. Patients received either standard care (control group) or pharmaceutical care (intervention group). Follow-up consultations were conducted for each patient at 1, 8, 26, and 52 weeks after discharge. The time to DRR was defined as the primary outcome measure and was analysed using the log-rank test. The Cox-proportional hazard model was used for risk factor analysis. Results Sixty patients (n = 31 intervention group, n = 29 control group) participated in the study. For patients in the intervention group, the median time to DRR was prolonged; however, the level of statistical significance was not reached (log-rank test P = 0.068; HR = 3.28, P = 0.086). When the risk factors ‘age’ or ‘length of stay on the ward’ were added to the Cox proportional hazard model, patients in the control group exhibited a significantly higher risk of experiencing a DRR than patients of the intervention group (HR = 4.62; P = 0.028 including age and HR = 5.76; P = 0.033 including length of stay on the ward). Conclusions Our findings demonstrate the successful implementation of ward-based, comprehensive pharmaceutical care for dependent-living elderly. Despite a low participation rate, which led to an underpowered study, the results provide a preliminary efficacy signal and effect size estimates to power a definitive trial. Trial registration Clinicaltrials.gov identifier: NCT01578525, prospectively registered April 13, 2012.

BACKGROUND Sepsis is a major health care problem with high morbidity and mortality rates and affects millions of patients. Telemedicine, defined as the exchange of medical information via electronic communication, improves the outcome of patients with sepsis and decreases the mortality rate and length of stay in the intensive care unit (ICU). Additional telemedicine rounds could be an effective component of performance-improvement programs for sepsis, especially in underserved rural areas and hospitals without ready access to critical care physicians. OBJECTIVE Our aim was to evaluate the impact of additional daily telemedicine rounds on adherence to sepsis bundles. We hypothesized that additional telemedicine support may increase adherence to sepsis guidelines and improve the detection rates of sepsis and septic shock. METHODS We conducted a retrospective, observational, multicenter study between January 2014 and July 2015 with one tele-ICU center and three ICUs in Germany. We implemented telemedicine as part of standard care and collected data continuously during the study. During the daily telemedicine rounds, routine screening for sepsis was conducted and adherence to the Surviving Sepsis Campaign’s 3-hour and 6-hour sepsis bundles were evaluated. RESULTS In total, 1168 patients were included in this study, of which 196 were positive for severe sepsis and septic shock. We found that additional telemedicine rounds improved adherence to the 3-hour (Quarter 1, 35% vs Quarter 6, 76.2%; P=.01) and 6-hour (Quarter 1, 50% vs Quarter 6, 95.2%; P=.001) sepsis bundles. In addition, we noted an increase in adherence to the item “Administration of fluids when hypotension” (Quarter 1, 80% vs Quarter 6, 100%; P=.049) of the 3-hour bundle and the item “Remeasurement of lactate” (Quarter 1, 65% vs Quarter 6, 100%, P=.003) of the 6-hour bundle. The ICU length of stay after diagnosis of severe sepsis and septic shock remained unchanged over the observation period. Due to a higher number of patients with sepsis in Quarter 5 (N=60) than in other quarters, we observed stronger effects of the additional rounds on mortality in this quarter (Quarter 1, 50% vs Quarter 5, 23.33%, P=.046). CONCLUSIONS Additional telemedicine rounds are an effective component of and should be included in performance-improvement programs for sepsis management.

Clinical nutrition 38(6), 2756-2762 (2019). doi:10.1016/j.clnu.2018.11.033, Published by Elsevier, Amsterdam [u.a.]

Background The Oxford classification of IgA nephropathy (IgAN) defines histologic criteria (MEST-C) that provide prognostic information based on the kidney biopsy. There are few data on the predictive impact of this classification in randomized clinical trial settings. Methods We performed an exploratory analysis of MEST-C scores in 70 available renal biopsies from 162 randomized STOP-IgAN trial participants and correlated the results with clinical outcomes. Analyses were performed by researchers blinded to the clinical outcome of the patients. Biopsies had been obtained 6.5 to 95 (median 9.4) months prior to randomization. Results Mesangial hypercellularity (M1) associated with higher annual eGFR-loss during the 3-year trial (M1: − 5.06 ± 5.17 ml/min/1.73 m2, M0: − 0.79 ± 4.50 ml/min/1.73 m2, p = 0.002). An M0-score additionally showed a weak association with full clinical remission, whereas the percentage of patients losing ≥15 ml/min/1.73 m2 over the 3-year trial phase was higher among those scored as M1. Among patients with additional immunosuppression, ESRD occurred more frequently in patients when tubulointerstitial fibrosis (T1/2) was present (T1/2 = 33%, T0 = 0%, p = 0.008). In patients receiving supportive care only, ESRD frequencies were similar (T1/2 = 18%, T0 = 7%, p = 0.603). At randomization, eGFR was significantly lower when tubulointerstitial fibrosis was present (T1/2: 45.2 ± 15.7 ml/min/1.73 m2, T0: 74.6 ± 28.2 ml/min/1.73 m2, p

During the last decades, pharmaceutical care services have been developed and implemented to optimize drug therapies and ensure medication safety. To investigate the need for pharmaceutical care services, drug-related problems can be measured.Thus, the aim of this study was to analyse number, type and occurrence of drug-related problems in different clinical departments.A pharmaceutical care service was established on general wards in Urology, Neurology and Gastroenterology at the University Hospital RWTH Aachen, Germany.For each of a total of 306 patients, a pharmacist conducted an extended medication history, performed medication reconciliation, conducted medication safety checks and if drug-related problems were discovered, gave valid recommendations to the attending healthcare team. Drug-related problems were classified using the APS-Doc system. For statistical analyses, SAS(®) 9.1.3, SAS Institute, Cary NC, USA was applied. The project was approved by the local ethics committee.Type, occurrence and frequency of DRP in different medical departments.On average, 2.3 drug-related problems per patient were documented for all three departments. Drug-related problems were found in each category of the APS-Doc system. The most pronounced drug-related problems found were drug-drug interactions (34.6 %). 37 % of the identified drug-related problems occurred before hospital admission, 27 % during transitional care, and 36 % on the ward. Subgroup analysis revealed specific drug-related problem patterns for each clinical department. The number of drug-related problems was found to be associated with the number of drugs and age.Drug-related problems frequently occur in all investigated clinical departments. A holistic pharmaceutical care service could be an option to address this issue. In case of limited resources, individual drug-related problem patterns can be used as a basis for a tailored pharmaceutical care service. As number of drugs and age have been shown to be significant risk factors, it is crucial that the healthcare team including the pharmacist pays special attention to elderly patients and those with polymedication.

Purpose and background Emergency medical services (EMSs) vary considerably. While some are physician staffed, most systems are run by paramedics. The objective of this randomized, controlled simulation study was to compare the emergency care between physician staffed EMS teams (control group) and paramedic teams that were supported telemedically by an EMS physician (telemedicine group). Methods Overall 16 teams (1 EMS physician, 2 paramedics) were randomized to the control group or the telemedicine group. Telemedical functionalities included two-way audio communication, transmission of vital data (numerical values and curves) and video streaming from the scenario room to the remotely located EMS physician. After a run-in scenario all teams completed four standardized scenarios, in which no highly invasive procedures (e.g. thoracic drain) were required, two using high-fidelity simulation (burn trauma, intoxication) and two using standardized patients (renal colic, barotrauma). All scenarios were videotaped and analyzed by two investigators using predefined scoring items. Results Non case-specific items (31 vs. 31 scenarios): obtaining of ‘symptoms', ‘past medical history' and ‘events' were carried out comparably, but in the telemedicine group ‘allergies' (17 vs. 28, OR 7.69, CI 2.1–27.9, p =0.002) and ‘medications' (17 vs. 27, OR 5.55, CI 1.7–18.0, p =0.004) were inquired more frequently. No significant differences were found regarding the case-specific items and in both groups no potentially dangerous mistreatments were observed. Conclusion Telemedically assisted paramedic care was feasible and at least not inferior compared to standard EMS teams with a physician on-scene in these scenarios.

Prehospital hypertensive emergencies and urgencies are common, but evidence is lacking. Telemedically supported hypertensive emergencies and urgencies were prospectively collected (April 2014-March 2015) and compared retrospectively with a historical control group of on-scene physician care in the emergency medical service of Aachen, Germany. Blood pressure management and guideline adherence were evaluated. Telemedical (n=159) vs conventional (n=172) cases: blood pressure reductions of 35±24 mm Hg vs 44±23 mm Hg revealed a group effect adjusted for baseline differences (P=.0006). Blood pressure management in categories: no reduction 6 vs 0 (P=.0121); reduction ≤25% (recommended range) 113 vs 110 patients (P=.2356); reduction >25% to 30% 13 vs 29 (0.020); reduction >30% 12 vs 16 patients (P=.5608). The telemedical approach led to less pronounced blood pressure reductions and a tendency to improved guideline adherence. Telemedically guided antihypertensive care may be an alternative to conventional care especially for potentially underserved areas.

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest a 6-month course of corticosteroids (CS) for IgA nephropathy (IgAN) patients with persistent proteinuria ≥1 g/day despite 3-6 months of renin-angiotensin system (RAS) blockers and glomerular filtration rate (GFR) >50 mL/min/1.73 m2 In December 2015, Rauen et al. (N Engl J Med 2015; 373: 2225-2236) published an article entitled 'Intensive supportive care plus immunosuppression in IgA nephropathy' (STOP-IgAN), which presented results from 379 IgAN patients from 32 nephrology centres in Germany. During a run-in phase of 6 months, patients received supportive care therapy including RAS blockers, dietary counselling, advice to stop smoking and avoid nephrotoxic drugs, and statins if required. After 6 months, 177 patients with proteinuria >0.75 g/day (non-responder patients) were randomized to either receive continued supportive care or supportive care plus immunosuppression (monotherapy with CS or combined therapy with three immunosuppressants). The authors reported that, after 36 months of observation, the addition of immunosuppressants to ongoing comprehensive supportive care was not beneficial in IgAN patients with moderate proteinuria and chronic kidney disease stages 1-3. These conclusions are questionable for several reasons: (i) studies on time-average proteinuria have shown that beneficial effects on renal survival, not evident after 36 months, emerge over the course of longer observation periods; (ii) supportive care in the STOP-IgAN study resulted in a small loss of renal function during the 36 months of observation (annual decrease in the estimated GFR of 1.6 mL/min/1.73 m2), but was unable to reduce proteinuria below 1 g/day; in contrast, 6 months of steroid therapy lowered proteinuria below 1 g/day; and (iii) the lack of any assessment of the histological data does not allow the importance of the morphological lesions on renal survival and therapy effects to be monitored. Further evaluation with a longer follow-up period is needed to obtain more reliable answers than the weak evidence of this study.

To compare a novel, pressure-limited, flow adaptive ventilator that enables manual triggering of ventilations (MEDUMAT Easy CPR, Weinmann, Germany) with a bag-valve-mask (BVM) device during simulated cardiac arrest.Overall 74 third-year medical students received brief video instructions (BVM: 57s, ventilator: 126s), standardised theoretical instructions and practical training for both devices. Four days later, the students were randomised into 37 two-rescuer teams and were asked to perform 8min of cardiopulmonary resuscitation (CPR) on a manikin using either the ventilator or the BVM (randomisation list). Applied tidal volumes (V(T)), inspiratory times and hands-off times were recorded. Maximum airway pressures (P(max)) were measured with a sensor connected to the artificial lung. Questionnaires concerning levels of fatigue, stress and handling were evaluated. V(T), pressures and hands-off times were compared using t-tests, questionnaire data were analysed using the Wilcoxon test.BVM vs. ventilator (mean±SD): the mean V(T) (408±164ml vs. 315±165ml, p=0.10) and the maximum V(T) did not differ, but the number of recorded V(T)200ml differed (8.1±11.3 vs. 17.0±14.4 ventilations, p=0.04). P(max) did not differ, but inspiratory times (0.80±0.23s vs. 1.39±0.31s, p0.001) and total hands-off times (133.5±17.8s vs. 162.0±11.1s, p0.001) did. The estimated levels of fatigue and stress were comparable; however, the BVM was rated to be easier to use (p=0.03).For the user group investigated here, this ventilator exhibits no advantages in the setting of simulated CPR and carries a risk of prolonged no-flow time.

Background: Medical emergencies in dental practice are generally perceived as being rare. Nonetheless, recent studies have shown that incidents occur on a regular basis. Therefore, patients have the right to expect necessary skills to manage life-threatening situations from every dentist. Objective: To observe students’ attitude and self-assessment towards emergency medical care (EMC) and its practical appliance. Material and methods: Students of dentistry took part in small group sessions for adult and paediatric basic life support. Participants filled out pre–post questionnaires regarding knowledge and attitude towards EMC (6, respectively, 10-point Likert scale). Additionally, feedback was asked for the quality of course and tutors. Results: Forty dental students in their last 2 years of study registered for the EMC courses. The majority had never attended any first-aid course; the mean age was 25% and 75% were women. A comparison between pre- and post-evaluation showed that the participation in practical training easily enhances the students’ awareness of EMC importance as well as self-confidence in managing emergencies. After the course, 71% shared the opinion that retraining should be obligatory for all medical personnel. At the same time, students’ self-assessment of confidence for specific tasks got significant upgrades in every aspect. Conclusion: The evaluation data clearly show the participants’ needs to deal with topics of EMC within the curriculum of dentistry. The proposed course is able to change participants’ attitudes towards EMC and its importance for their daily practice. The considerable enhancement of self-confidence in performing EMC-techniques might also lead to more willingness to manage emergency situations.

quartile range, and Receiver Operator Characteristic (ROC) curves. Results: Median PlGF concentrations in cases and controls were [Triage; 12 (IQR 12–15) v 256 (IQR 130–781) pg/ml, and Delfia; 38 (IQR 28–43) v 236 (IQR 161–419) pg/ml], respectively. The area under the ROC curve (AUC) for the diagnosis of early onset preeclampsia was 1.0 (95% CI, 1.0–1.0) for Triage and 0.97 (95% CI, 0.94–1.0) for Delfia. Conclusions: The Triage PlGF assay achieves greater separation of cases from controls. Further studies are needed to understand whether differences in analytical specificity (PlGF isoforms or complexed vs non-complexed PlGF) explain the lower levels of PlGF in preeclampsia for the Triage immunoassay.

Small for gestational age neonates (SGA) could be subdivided into two groups according to the underlying causes leading to low birth weight. Intrauterine growth restriction (IUGR) is a pathologic condition with diminished growth velocity and fetal compromised well-being, while non-growth restricted SGA neonates are constitutionally (genetically determined) small. Antenatal sonographic measurements are used to differentiate these two subgroups. Maternal metabolic changes contribute to the pathogenesis of IUGR. A disturbed lipid metabolism and cholesterol supply might affect the fetus, with consequences for fetal programming of cardiovascular diseases. We evaluated fetal serum lipids and hypothesized a more atherogenic lipoprotein profile in IUGR fetuses.Umbilical cord serum lipids and oxidative modified, low-density lipoprotein (oxLDL) concentrations were measured by colorimetric enzymatic measurements, or by ELISA. Values of IUGR (n=36) and constitutionally small for gestational age neonates (SGA, n=22) were compared with those of healthy, adequate for gestational age, born neonates (CN, n=97). SAS-statistic software was used and two-way ANOVA was adjusted for gestational age at delivery.Fetal high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) concentrations were found to be lower in the IUGR compared to the CN and SGA groups (HDL-C: P0.001, TC: P0.01). Atherogenic indices, including the oxLDL/LDL-C ratio, were increased in the IUGR compared to the CN group (oxLDL/LDL-C ratio: P0.001).Our results support the hypothesis of a disturbed cholesterol supply in IUGR fetuses. Born SGA has been shown to be a risk factor for developing cardiovascular disease later in life. Since HDL-C has anti-inflammatory properties, a reduced HDL-C during fetal development, and an increase in atherogenic indices, might provide a link to this observation in IUGR fetuses.

Despite increasing use of prothrombin complex concentrate (PCC) to treat hemorrhage-associated coagulopathy, few studies have investigated PCC in trauma, and there is a particular lack of safety data. This study was performed to evaluate PCC therapy in a porcine model of coagulopathy with blunt liver injury. Coagulopathy was induced in 27 anesthetized pigs by replacing approximately 70% blood volume with hydroxyethyl starch 130/0.4 and Ringer's lactate solution; erythrocytes were collected and retransfused. Ten minutes after trauma, animals randomly received PCC (35 or 50 IU/kg) or saline. Coagulation parameters including thromboelastometry, thrombin generation, and blood loss were monitored for 2 hours. Internal organs were examined macroscopically and histologically to determine the presence of emboli and assess liver injury. Total blood loss was significantly lower and survival was higher in both PCC groups versus the control group (P < .05). These outcomes appeared to be dose-independent. Thromboembolism was found in all animals treated with 50 IU/kg PCC; 44% also showed signs of disseminated intravascular coagulation. Liver injury was similar in all animals. In conclusion, 35 IU/kg PCC safely improved coagulation and attenuated blood loss. However, the higher dose of PCC (50 IU/kg) appeared to increase the risk of thromboembolism and disseminated intravascular coagulation.

Background Teleconsultation from the scene of an emergency to an experienced physician including real-time transmission of monitoring, audio and visual information seems to be feasible. In preparation for bringing such a system into practice within the research project "Med-on-@ix", a simulation study has been conducted to investigate whether telemedical assistance (TMA) in Emergency Medical Services (EMS) has an impact on compatibility to guidelines and timing. Material and methods In a controlled simulation study 29 EMS teams (one EMS physician, two paramedics) ran through standardized scenarios (STEMI: ST-elevation myocardial infarction; MT: major trauma) on high-fidelity patient simulators with defined complications (treatable clearly following guidelines). Team assignments were randomized and each team had to complete one scenario with and another without TMA. Analysis was based on videotaped scenarios using pre-defined scoring items and measured time intervals for each scenario. Results Adherence to treatment algorithms improved using TMA. STEMI: cathlab informed (9/14 vs. 15/15; p =0.0169); allergies checked prior to acetylsalicylic acid (5/14 vs. 13/15; p =0.0078); analgosedation prior to cardioversion (10/14 vs. 15/15; p =0.0421); synchronized shock (6/14 vs. 14/15; p =0.0052). MT: adequate medication for intubation (3/15 vs. 10/14; p =0.0092); mean time to inform trauma centre 547 vs. 189s ( p =0.0001). No significant impairment of performance was detected in TMA groups. Conclusions In simulated setting TMA was able to improve treatment and safety without decline in timing. Nevertheless, further research is necessary to optimize the system for medical, organizational and technical reasons prior to the evaluation of this system in routine EMS.

PLoS one 7(5), e36796 (2012). doi:10.1371/journal.pone.0036796, Published by PLoS [u.a.], Lawrence, Kan.