Patient Confidence and Information Preferences During the Treatment Decision-making Process: Results From a Large Multiple Myeloma Patient Survey Across 12 Countries in Europe and Israel.

BACKGROUND: The relapsing nature of multiple myeloma (MM) means that patients typically receive different and multiple lines of therapy, requiring many treatment decisions over the disease course. The aim of this study was to explore patient confidence and information preferences during the treatment decision-making process. PATIENTS AND METHODS: A multinational, cross-sectional survey enrolled patients with MM. It was co-developed and distributed by Myeloma Patients Europe across 12 countries in Europe and Israel from May 2019 to March 2020. Eligibility criteria included a self-reported diagnosis of MM and being able to recall the decision-making process at the start of their latest treatment line. RESULTS: A total of 1559 patients were included, with complete responses received from 1081 (69%) patients. The median age range was 54 to 64 years; there was an equal gender split and 57% had their latest treatment decision made within the past year. Overall, 54% of patients felt "very confident" in the latest treatment decision. Patients deemed the most important information to be safety/tolerability and treatment effectiveness, but the latter was among the least frequently received. Most patients reported that their primary physician treating MM was their main source for all types of information (range, 62%-94%), with 87% of patients reporting a "very good" or "good" relationship with them. CONCLUSION: Over half of patients felt very confident in their latest treatment decision; however, patients reported not routinely receiving important treatment effectiveness information. Addressing the discrepancies between information that patients receive and consider important may enhance confidence in decision-making.

Management of Patients with Relapsed and/or Refractory Multiple Myeloma Treated with Novel Combination Therapies in Routine Clinical Practice in Germany.

INTRODUCTION: Multiple myeloma remains an incurable plasma cell malignancy which, despite improvements in overall survival over the last decade, is characterized by recurrent relapse and is associated with a poor prognosis. This study investigates the use of novel agents in current real-world clinical practice in the management of relapsed and/or refractory multiple myeloma (RRMM) in Germany over different lines of therapy. METHODS: A retrospective chart review was conducted for patients with RRMM treated at multiple centers across Germany between May 2017 and June 2018. Variables included patient demographics and clinical characteristics, current and prior treatment regimens, treatment response, cytogenetic abnormalities, testing methodology, and resource utilization. RESULTS: Data were analyzed from 484 patients from 47 centers across Germany (60% male; average age over 70 years; majority at International Staging System stage 2 or 3). Bone pain and anemia were the most common symptoms at diagnosis, with 63% of patients receiving osteoprotective drugs. Approximately one-third (32%) of patients had received autologous stem cell transplantation and approximately 70% underwent cytogenetic testing. After failure to respond to first-line treatment, most patients received regimens containing second-generation proteasome inhibitors and monoclonal antibodies, with overall response rates greater than 90% in second line (95% and 90% for daratumumab-based and carfilzomib-based therapies, respectively). The incidence of unplanned hospitalization ranged from 11% to 16% across all treatment lines, with longer hospital stays required for treatment administration than for treatment-related toxicity. CONCLUSION: Although treatment patterns for RRMM in Germany differ by line of therapy and are adapted as disease progresses, patients mostly receive combination regimens with carfilzomib or daratumumab in second and third lines, with high overall response rates achieved in all lines.

[Interdisciplinary neurovascular networks: state of the art]. / Interdisziplinäre neurovaskuläre Netzwerke: eine Standortbestimmung.

BACKGROUND: In order to treat the complete spectrum of neurovascular diseases at a high level of quality, which goes beyond the purely acute treatment of stroke, the German Stroke Society (DSG) together with the German Societies for Neurosurgery and Neuroradiology developed a certification procedure for neurovascular networks (NVN). Structurally, a NVN consists of a coordinating center with at least three neurovascular network partners with a certified stroke unit. From 2018 to 2020 a total of 15 NVN have so far been audited and certified according to this new standard. OBJECTIVE: How efficient are the NVN? Are high standards maintained? MATERIAL AND METHODS: The reports of the audits were analyzed. The data were taken from the period 2017-2019. RESULTS: The 15 NVN treated a total of 86,510 stroke patients in the years examined and were networked with a total of 107 partner clinics, which were situated an average of 25 km from the coordinating center and transferred a total of 2726 patients. The coordinating centers performed 2463 thrombectomies and treated 2383 patients with nontraumatic intracerebral bleeding. In 712 patients with acute aneurysmatic subarachnoid hemorrhages endovascular treatment was carried out and clipping in 401. The audit was successful in the majority of the NVN. CONCLUSION: The certification process of NVN has been successfully established and the audits proved to be a useful instrument for quality control and improvement. The 15 NVN are highly efficient and treat more than one quarter of stroke patients in German stroke units.

Patient Characteristics and Outcomes of Relapsed/Refractory Multiple Myeloma in Patients Treated with Proteasome Inhibitors in Germany.

INTRODUCTION: Real-world data reflects treatments and outcomes in clinical practice in contrast with controlled clinical trials. This study evaluates real-life multiple myeloma (MM) patients receiving proteasome inhibitor (PI)-based treatments in the second or third therapy line in 2017 in Germany. METHODS: This is a retrospective chart review on adult relapsed/refractory MM patients treated with ≥1 dose of a PI-based regimen in either the second or the third line of therapy. Participating physicians had ≥3 years of clinical experience in treating symptomatic MM patients and used PI according to the label. RESULTS: Distinct patient profiles for each PI-based regimen emerged. Younger, fitter, transplant-eligible patients received novel PI triplets such as carfilzomib in combination with lenalidomide and dexamethasone (KRd) or IRd. Patients receiving lenalidomide in first-line therapy mostly received lenalidomide-free regimens in second-line therapy. In high-risk patients, no clear treatment patterns could be ascertained. The complete response rates were highest with KRd (13.0%), followed by carfilzomib in combination with dexamethasone (Kd) (5.7%) and bortezomib (4.8%). The very good partial response rates were highest with IRd (76.9%), followed by KRd (53.7%), Kd (25.7%), and bortezomib (20.5%). None of the KRd- or IRd-treated patients responded below a partial response. DISCUSSION/CONCLUSION: Clear patient profiles for each PI type were observed. In second-line therapy, younger, fitter, transplant-eligible patients received novel-PI-based triplets, e.g., KRd or IRd. Patients treated with lenalidomide in first-line therapy mostly received lenalidomide-sparing regimens in second-line therapy. In high-risk patients no clear treatment patterns could be ascertained due to the limited sample size.

Historical review: a short history of German neurology - from its origins to the 1940s.

This paper aims at reconstructing the development and role of German neurology between 1840 and 1940. Therefore a couple of original sources as well as selected material form the scattered secondary literature were assessed and reviewed. Since the middle of the nineteenth century, an intricate process of separation from internal medicine and psychiatry gradually led to forming a self-conscious community of German neurologists. While Moritz Heinrich Romberg had constructed a cognitive basis for neurology, scientific founders such as Wilhelm Erb, Carl Wernicke, Alois Alzheimer, Hermann Oppenheim, Max Nonne, and many others established the new discipline within modern medicine. In 1891, the first generation of "pure" neurologists succeeded in founding the German Journal for Neurology (Deutsche Zeitschrift für Nervenheilkunde) followed by an autonomous professional organisation, the Society of German Neurologists (Gesellschaft Deutscher Nervenärzte) in 1907. A variety of external factors, however, hampered the institutional evolution and thus the implementation of chairs and departments remained quite modest. In 1935, only 2 years after the National Socialists had seized power, the regulatory merger with the psychiatrists' society caused the cautious attempts of German neurologists for autonomy to end in complete failure. The imprisonment, murder and expulsion of neuroscientists declared as Jewish or non-Aryan caused profound changes in neurology, medicine, academic life, and health care in general. Further historical research is needed to reconstruct in detail the involvement of German neurologists in racial-hygienic and eugenic research as well as the institutional and scientific development of German neurology after World War II.

The German trial on Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE): a multicenter, randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Comprehensive treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major clinical challenge. The current therapy gold standard is aciclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains around 20% and a majority of survivors suffer from severe disability. Experimental research and recent retrospective clinical observations suggest a favourable therapy response to adjuvant dexamethasone. Currently there is no randomized clinical trial evidence, however, to support the routine use of adjuvant corticosteroid treatment in HSVE. METHODS: The German trial of Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE) studied the effect of adjuvant dexamethasone versus placebo on top of standard aciclovir treatment in adult patients aged 18 up to 85 years with proven HSVE in German academic centers of Neurology in a randomized and double blind fashion. The trial was open from November 2007 to December 2012. The initially planned sample size was 372 patients with the option to increase to up to 450 patients after the second interim analysis. The primary endpoint was a binary functional outcome after 6 months assessed using the modified Rankin scale (mRS 0-2 vs. 3-6). Secondary endpoints included mortality after 6 and 12 months, functional outcome after 6 months measured with the Glasgow outcome scale (GOS), functional outcome after 12 months measured with mRS and GOS, quality of life as measured with the EuroQol 5D instrument after 6 and 12 months, neuropsychological testing after 6 months, cranial magnetic resonance imaging findings after 6 months, seizures up to day of discharge or at the latest at day 30, and after 6 and 12 months. RESULTS: The trial was stopped prematurely for slow recruitment after 41 patients had been randomized, 21 of them treated with dexamethasone and 20 with placebo. No difference was observed in the primary endpoint. In the full analysis set (n = 19 in each group), 12 patients in each treatment arm achieved a mRS of 0-2. Similarly, we did not observe significant differences in the secondary endpoints (GOS, mRS, quality of life, neuropsychological testing). CONCLUSION: GACHE being prematurely terminated demonstrated challenges encountered performing randomized, placebo-controlled trials in rare life threatening neurological diseases. Based upon our trial results the use of adjuvant steroids in addition to antiviral treatment remains experimental and is at the decision of the individual treating physician. Unfortunately, the small number of study participants does not allow firm conclusions. TRIAL REGISTRATION: EudraCT-Nr. 2005-003201-81.

[Crew resource management and simulator training in acute stroke therapy]. / Crew-Ressource-Management und Simulatortraining in der akuten Schlaganfalltherapie.

BACKGROUND: Time is of critical importance in acute stroke management. The establishment of thrombectomy now adds to the complexity and interdisciplinarity of the initial phase. In non-medical high-fidelity situations, such as aviation, crew resource management (CRM) has proven to be highly efficient. It has therefore also been implemented in professional cardiovascular life support training. In a setting where every minute counts, CRM and regular training of the high-fidelity stroke team could offer ways to improve treatment of acute stroke patients. OBJECTIVES: We evaluated the effects of a CRM-based stroke team with regular simulation training on the quality of care (e.g. door to needle time and thrombolysis rate) as well as on staff satisfaction and perceived patient safety in the emergency department of a tertiary care neurocenter. MATERIAL AND METHODS: We implemented a dedicated stroke team consisting of 7 persons who are notified by a collective call via speed dial and conceived a simulator-based team training for all new stroke team members which we conduct at monthly intervals. We recorded door to needle times of all consecutive patients, staff satisfaction in the emergency room and the acceptance of this new learning format. RESULTS: This approach led to a relevant and sustained reduction of the mean door to needle time to less than 30 min. It improved perceived patient safety in residents with professional experience of less than 2 years. There was a very high acceptance within the stroke team training and staff and its usefulness was judged to be very high. CONCLUSION: Even though our data do not allow positive effects on patient outcomes to be inferred, the implementation of a CRM-based stroke team and simulator training has had multiple positive effects on the workflow and work satisfaction in the treatment of acute stroke patients.

Potential for polyhydroxyalkanoate production on German or European municipal waste water treatment plants.

Biopolymers, which are made of renewable raw materials and/or biodegradable residual materials present a possible alternative to common plastic. A potential analysis, based on experimental results in laboratory scale and detailed data from German waste water treatment plants, showed that the theoretically possible production of biopolymers in Germany amounts to more than 20% of the 2015 worldwide biopolymer production. In addition a profound estimation regarding all European Union member states showed that theoretically about 115% of the actual worldwide biopolymer production could be produced on European waste water treatment plants. With an upgraded biopolymer production and a theoretically reachable biopolymer proportion of around 60% of the cell dry weight a total of 1,794,656tPHAa or approximately 236% of today's biopolymer production could be produced on waste water treatment plants in the European Union, using primary sludge as raw material only.

The effect of long or chopped straw on pig behaviour.

In the EU, pigs must have permanent access to manipulable materials such as straw, rope, wood, etc. Long straw can fulfil this function, but can increase labour requirements for cleaning pens, and result in problems with blocked slatted floors and slurry systems. Chopped straw might be more practical, but what is the effect on pigs' behaviour of using chopped straw instead of long straw? Commercial pigs in 1/3 slatted, 2/3 solid pens of 15 pigs were provided with either 100 g/pig per day of long straw (20 pens) or of chopped straw (19 pens). Behavioural observations were made of three focal pigs per pen (one from each of small, medium and large weight tertiles) for one full day between 0600 and 2300 h at each of ~40 and ~80 kg. The time spent rooting/investigating overall (709 s/pig per hour at 40 kg to 533 s/pig per hour at 80 kg), or directed to the straw/solid floor (497 s/pig per hour at 40 kg to 343 s/pig per hour at 80 kg), was not affected by straw length but reduced with age. Time spent investigating other pigs (83 s/pig per hour at 40 kg), the slatted floor (57 s/pig per hour) or pen fixtures (21 s/pig per hour) was not affected by age or straw length. Aggressive behaviour was infrequent, but lasted about twice as long in pens with chopped straw (2.3 s/pig per hour at 40 kg) compared with pens with long straw (1.0 s/pig per hour at 40 kg, P=0.060). There were no significant effects of straw length on tail or ear lesions, but shoulders were significantly more likely to have minor scratches with chopped straw (P=0.031), which may reflect the higher levels of aggression. Smaller pigs showed more rooting/investigatory behaviour, and in particular directed towards the straw/solid floor and the slatted floor than their larger pen-mates. Females exhibited more straw and pen fixture-directed behaviour than males. There were no effects of pig size or sex on behaviour directed towards other pigs. In summary, pigs spent similar amounts of time interacting with straw/solid floor when long and chopped straw were provided, and most aspects of pig-directed behaviour and injuries were not affected by straw length. There was an increase in pigs with minor shoulder lesions with chopped straw, perhaps because of increased aggression. The use of chopped straw as an enrichment material for pigs warrants further investigation in larger and more detailed studies.

Behaviour of liquid-fed growing pigs provided with straw in various amounts and frequencies.

Straw possesses many characteristics that make it attractive to pigs and can therefore be effective in preventing negative penmate-directed behaviours. However, straw is difficult to handle in current vacuum slurry systems under most commercial conditions and can therefore only be used in limited amounts. To occupy pigs effectively, straw must remain attractive to pigs throughout the whole day; hence, have a certain degree of novelty. We investigated the penmate-directed behaviour of liquid-fed growing pigs in a production herd, assigned to five experimental treatments: 1×25, 1×50, 1×100, 2×50 and 4×25 g of chopped straw/pig per day, with 20 replicates of each treatment (pen was regarded as experimental unit). Behaviour was observed at two different growth stages; ~40 and 80 kg live weight of the pigs. Activity and exploratory behaviour directed at penmates, straw, pen components and the slatted floor were registered continuously for 15 min of each hour during day time (0600 to 2200 h) by use of video observation of three focal pigs per pen. The pigs were active for about one-third of the day corresponding to ~5 h/day. Of the active time, an average of 7% (35 min) was spent on penmate-directed behaviour. The pigs were more active and increased their straw-directed behaviour when provided with 100 g straw/pig per day compared with 25 and 50 g (P<0.001). However, penmate-directed behaviour was not reduced with an increased amount of straw (P>0.05), and there was no effect on pigs' behaviour when straw provision was increased per day (P>0.05). Pigs became less active and reduced their straw-directed activities when their weight increased from 40 to 80 kg live weight (P<0.001), but the amount of penmate-directed behaviour was similar (P>0.05). Further, the residual straw results indicated that perhaps a more frequent straw provision could help establish a more even level of fresh available straw during the day. However, the frequent straw provision did not occupy pigs more than one daily allocation did. In conclusion, there was no difference in penmate-directed behaviour of the pigs when given 25 or 50 g of straw/pig per day compared with 100 g of straw/pig per day, nor were there any difference when 100 g of straw/pig per day was provided more frequently.

Polyhydroxyalkanoate production as a side stream process on a municipal waste water treatment plant.

This work describes the production of polyhydroxyalkanoates (PHAs) as a side stream process on a municipal waste water treatment plant (WWTP) at different operation conditions. Therefore various tests were conducted regarding a high PHA production and stable PHA composition. Influence of substrate concentration, temperature, pH and cycle time of an installed feast/famine-regime were investigated. The results demonstrated a strong influence of the operating conditions on the PHA production. Lower substrate concentration, 20°C, neutral pH-value and a 24h cycle time are preferable for high PHA production up to 28.4% of cell dry weight (CDW). PHA composition was influenced by cycle time only and a stable PHA composition was reached.

[WINHO quality indicators for outpatient oncology care in Germany]. / WINHO-Qualitätsindikatoren für die ambulante onkologische Versorgung in Deutschland.

The aim of the WINHO indicators project is to describe and enhance the quality of outpatient oncology care in Germany with indicators. This paper deals with the development of a set of evidence- and consensus-based meaningful indicators to assess the quality of outpatient oncology care in Germany. These indicators are intended to be applied in assessments of quality of patient care in oncology practices, in quality reports and in peer-to-peer benchmarking. A set of 272 already existing indicators was identified through internet and literature searches. After redundancy reduction and addition of newly developed indicators for areas of ambulatory oncology care that were not yet covered, a preliminary set of 67 indicators was established. The further development of the indicator set was based on a modified version of the two-step RAND/UCLA expert evaluation method, which has been internationally established for developing quality indicator sets. The indicators were modified after the first round of ratings. After completing and assessing the second round of ratings, a set of 46 homogeneously positively rated quality indicators is now available for outpatient oncology care in Germany.

Hematoma expansion in experimental intracerebral hemorrhage is not altered by peracute treatment with recombinant tissue plasminogen activator.

Recombinant tissue-type plasminogen activator (rt-PA) is the mainstay of acute stroke treatment and the only approved medical therapy so far. Because of its fibrinolytic action, it is presumed to aggravate intracerebral hemorrhage (ICH). Since clinical features do not discriminate between ischemic stroke and ICH, brain imaging is strictly required before the initiation of thrombolysis. A recent study has shown that rt-PA does not worsen (primary) ICH in two different experimental mouse models. Here, we further explored this surprising finding and examined hematoma expansion and long-term outcome after rt-PA treatment in a murine model of ICH. We induced ICH by collagenase injection into the right basal ganglia of C57BL/6 mice. At 30 min, 90 min or 4h after ICH induction, respectively, mice were treated with vehicle or 10mg/kg rt-PA. In parallel, we administered the vascular tracer Evans Blue (EB) and sacrificed the mice 2h after injection to assess EB extravasation as a marker of ongoing bleeding and rt-PA induced rebleeding. Additionally, we observed mice which were treated with vehicle or rt-PA 30 min after ICH induction for 72 h and quantified functional outcome and hematoma volume. EB extravasation was highest in the groups that were treated after 30 min and decreased thereafter according to a cessation of active bleeding. At all three time points covering the early phase of ICH, treatment with rt-PA did not increase EB extravasation. In the 72 h observation, there was also no difference in functional outcome and hematoma volume. In our experimental study, we were not able to demonstrate that peracute rt-PA treatment in (primary) ICH has detrimental effects on hematoma expansion, hematoma volume or functional outcome. This finding needs careful consideration in future translational studies.

Time trends in systemic thrombolysis in a large hospital-based stroke registry.

BACKGROUND: Systemic thrombolysis for acute stroke was approved by German authorities in 2002. While recombinant tissue plasminogen activator (rtPA) use first remained low, systemic thrombolysis is nowadays an established part of common stroke care. The purpose of this study was to determine changes in systemic thrombolysis rates within an observation period of 7 years following the approval of rtPA therapy in Germany in a large state-wide stroke data set. METHODS: We analyzed a prospective hospital-based stroke registry covering the entire federal state of Hesse, Germany. All hospitals providing stroke care in Hesse (neurology hospitals and hospitals for internal medicine) are obligated to register all inpatients. All cases admitted between 2003 and 2009 with a final diagnosis of ischemic stroke (ICD-10: I63) were selected. We analyzed the relationship between thrombolysis rates, onset-to-admission time (hospital arrival ≤3 and >3 h after symptom onset), patient age (quartiles and dichotomized in ≤80 and >80 years) and disability at admission (assessed by the Rankin Scale). A one-way ANOVA with Bonferroni correction for multiple comparisons was performed to test for significant changes during the observation period. RESULTS: 88,340 patients with ischemic stroke were identified. Thrombolysis rates increased continuously from 2.5% in 2003 to 8.4% in 2009. In patients admitted within 3 h after symptom onset, the thrombolysis rate was 2.5-fold higher in 2009 (25.4%) as compared to 2003 (10.5%). The mean age (±SD) of thrombolyzed patients increased from 68.7 (±11.5) years in 2003 to 70.7 (±13.4) years in 2009 (p for trend = 0.014), but remained stable in the entire cohort. 20.1% of all systemic thrombolytic treatments were performed in patients >80 years old. Disability at admission decreased more pronouncedly in rtPA-treated patients (Rankin Scale score 0-2: 15.2% in 2003 and 24.5% in 2009; p for trend <0.001) as compared to the entire cohort (34.5% in 2003 and 41.5% in 2009; p for trend <0.001). CONCLUSIONS: Thrombolytic therapy is increasingly used in acute stroke, particularly in patients admitted within the 3-hour time window. Higher treatment rates are at least partially explained by spreading rtPA application, including older and less severely affected patients. Approximately one fifth of all rtPA treatments were given to the very old (>80 years), which is outside the age limit for rtPA approval. In the light of upcoming demographic changes, the proportion of very aged stroke patients will increase substantially, further tightening the current discussion of an upper age limit for thrombolytic therapy.

[Spontaneous subarachnoid hemorrhage]. / Spontane Subarachnoidalblutung.

The diagnosis, management and long-term implications of non-traumatic subarachnoid hemorrhage continue to be a multidisciplinary challenge. Often, the patients present to emergency or primary care physicians not particularly experienced in the differential diagnosis of headache. In most cases of a proven hemorrhage (aneurysm rupture in 85%), further treatment will require the discussion between experienced neurosurgeons and neuroradiologists whether to "clip or coil". Thus, subarachnoid hemorrhage is the first cerebrovascular disorder where a multidisciplinary approach has become the evidence-based standard of care. Patients with this condition are relatively young, and the survivors have a good life expectancy. Their neurologic, cognitive and psychiatric morbidity, risk of recurrent bleeding and elevated risk of other vascular diseases remain underestimated tasks for long-term care.

Operating experiences with a molten carbonate fuel cell at Stuttgart-Möhringen wastewater treatment plant.

Fuel cells on wastewater treatment plants are a relatively new technology to convert biogas from anaerobic digestion into thermal and electrical energy. Since the end of 2007, a type of MCFC fuel cell (>250 kW(el), 180 kW(th)) has been installed at Stuttgart-Möhringen wastewater treatment plant. The goals of this research project are to raise the power self-sufficiency in Stuttgart-Möhringen, to further optimise high temperature fuel cells using biogas and to gain practical experience. After approximately 9,000 h of operation, a mean electrical 'gross'-efficiency of 44% was achieved. To fully exploit this high electrical efficiency, it is essential to keep the energy consumption of peripheral devices (gas pressure unit, gas cleaning unit, etc.) of the fuel cell as low as possible.