Symptom burden, psychosocial distress and palliative care needs in heart failure - A cross-sectional explorative pilot study.

BACKGROUND: Beyond guideline-directed treatments aimed at improving cardiac function and prognosis in heart failure (HF), patient-reported outcomes have gained attention. PURPOSE: Using a cross-sectional approach, we assessed symptom burden, psychosocial distress, and potential palliative care (PC) needs in patients with advanced stages of HF. METHODS: At a large tertiary care center, we enrolled HF patients in an exploratory pilot study. Symptom burden and psychosocial distress were assessed using the MIDOS (Minimal Documentation System for Patients in PC) questionnaire and the Distress Thermometer (DT), respectively. The 4-item Patient Health Questionnaire (PHQ-4) was used to screen for anxiety and depression. To assess PC needs, physicians used the "Palliative Care Screening Tool for HF Patients". RESULTS: We included 259 patients, of whom 137 (53%) were enrolled at the Heart Failure Unit (HFU), and 122 (47%) at the outpatient clinic (OC). Mean age was 63 years, 72% were male. New York Heart Association class III or IV symptoms were present in 56%. With a mean 5-year survival 64% (HFU) vs. 69% (OC) calculated by the Seattle Heart Failure Model, estimated prognosis was comparatively good. Symptom burden (MIDOS score 8.0 vs. 5.4, max. 30 points, p < 0.001) and level of distress (DT score 6.0 vs. 4.8, max. 10 points, p < 0.001) were higher in hospitalised patients. Clinically relevant distress was detected in the majority of patients (HFU 76% vs. OC 57%, p = 0.001), and more than one third exhibited at least mild symptoms of depression or anxiety. Screening for PC needs revealed 82% of in- and 52% of outpatients fulfil criteria for specialized palliative support. CONCLUSION: Despite a good prognosis, we found multiple undetected and unaddressed needs in an advanced HF cohort. This study's tools and screening results may help to early explore these needs, to further improve integrated HF care.

Fluorite-related iridate Pr3IrO7: crystal growth, structure, magnetism, thermodynamic, and optical properties.

Spin-orbit coupling in heavy 5dmetal oxides, in particular, iridates have received tremendous interest in recent years due to the realization of exotic electronic and magnetic phases. Here, we report the synthesis, structural, magnetic, thermodynamic, and optical properties of the ternary iridate Pr3IrO7. Single crystals of Pr3IrO7have been grown by the KF flux method. Structural analysis shows that Pr3IrO7crystallizes in an orthorhombic phase withCmcmsymmetry. The electron energy loss spectroscopy study indicates that Pr is in a 3+ valence state, which implies a 5+ oxidation state of Ir. Magnetization data measured at high and low magnetic fields do not exhibit any bifurcation betweenMZFCandMFC, however, a weak hump inM(T) is observed atT∗∼10.4 K. The specific heat data reveal two maxima at ∼253 and ∼4.8 K. The optical conductivityσ1(ω)spectrum shows 24 infrared-active phonon modes and reveals an insulating behavior with an optical gapΔOPof size ∼500 meV. During cooling down, the temperature-dependent reflectivity spectrum reveals eight extra phonon modes below the structural phase transition (∼253 K). An anomaly is observed at aroundT∗in the temperature evolution of infrared-active mode frequencies suggesting the presence of significant spin-phonon coupling in the system.

National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany - study protocol of a mixed-methods project.

BACKGROUND: In the SARS-CoV-2 pandemic, general and specialist Palliative Care (PC) plays an essential role in health care, contributing to symptom control, psycho-social support, and providing support in complex decision making. Numbers of COVID-19 related deaths have recently increased demanding more palliative care input. Also, the pandemic impacts on palliative care for non-COVID-19 patients. Strategies on the care for seriously ill and dying people in pandemic times are lacking. Therefore, the program 'Palliative care in Pandemics' (PallPan) aims to develop and consent a national pandemic plan for the care of seriously ill and dying adults and their informal carers in pandemics including (a) guidance for generalist and specialist palliative care of patients with and without SARS-CoV-2 infections on the micro, meso and macro level, (b) collection and development of information material for an online platform, and (c) identification of variables and research questions on palliative care in pandemics for the national pandemic cohort network (NAPKON). METHODS: Mixed-methods project including ten work packages conducting (online) surveys and qualitative interviews to explore and describe i) experiences and burden of patients (with/without SARS-CoV-2 infection) and their relatives, ii) experiences, challenges and potential solutions of health care professionals, stakeholders and decision makers during the SARS-CoV-2 pandemic. The work package results inform the development of a consensus-based guidance. In addition, best practice examples and relevant literature will be collected and variables for data collection identified. DISCUSSION: For a future "pandemic preparedness" national and international recommendations and concepts for the care of severely ill and dying people are necessary considering both generalist and specialist palliative care in the home care and inpatient setting.

A pre-registered short-term forecasting study of COVID-19 in Germany and Poland during the second wave.

Disease modelling has had considerable policy impact during the ongoing COVID-19 pandemic, and it is increasingly acknowledged that combining multiple models can improve the reliability of outputs. Here we report insights from ten weeks of collaborative short-term forecasting of COVID-19 in Germany and Poland (12 October-19 December 2020). The study period covers the onset of the second wave in both countries, with tightening non-pharmaceutical interventions (NPIs) and subsequently a decay (Poland) or plateau and renewed increase (Germany) in reported cases. Thirteen independent teams provided probabilistic real-time forecasts of COVID-19 cases and deaths. These were reported for lead times of one to four weeks, with evaluation focused on one- and two-week horizons, which are less affected by changing NPIs. Heterogeneity between forecasts was considerable both in terms of point predictions and forecast spread. Ensemble forecasts showed good relative performance, in particular in terms of coverage, but did not clearly dominate single-model predictions. The study was preregistered and will be followed up in future phases of the pandemic.

Pitfalls in accelerometer-based measurement of physical activity: The presence of reactivity in an adult population.

When a behavior is monitored, it is likely to change, even if no change may be intended. This phenomenon is known as measurement reactivity. We investigated systematic changes in accelerometer-based measures over the days of monitoring as an indicator of measurement reactivity in an adult population. One hundred seventy-one participants from the general population (65% women; mean age = 55 years, range: 42-65 years) wore accelerometers for 7 consecutive days to measure sedentary behavior and physical activity (PA). Latent growth models were used (a) to investigate changes in accelerometer wear time over the measurement days and (b) to identify measurement reactivity indicated by systematic changes in sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). Over the measurement days, participants reduced accelerometer wear time by trend (rate of change [b] = -4.7 min/d, P = .051, Cohen's d = .38), increased ST (b = 2.4 min/d, P = .018, d = .39), and reduced LPA (b = -2.4 min/d, P = .015, d = .38). Participants did not significantly reduce MVPA (P = .537). Our data indicated that accelerometry might generate reactivity. Small effects on ST and LPA were found. Thus, the validity of accelerometer-based data on ST and LPA may be compromised. Systematic changes observed in accelerometer wear time may further bias accelerometer-based measures. MVPA seems to be less altered due to the presence of an accelerometer.

Intestinal and hepatic contributions to the pharmacokinetic interaction between gamithromycin and rifampicin after single-dose and multiple-dose administration in healthy foals.

BACKGROUND: Standard treatment of foals with severe abscessing lung infection caused by Rhodococcus equi using rifampicin and a macrolide antibiotic can be compromised by extensive inhibition and/or induction of drug metabolising enzymes (e.g. CYP3A4) and transport proteins (e.g. P-glycoprotein), as has been shown for rifampicin and clarithromycin. The combination of rifampicin with the new, poorly metabolised gamithromycin, a long-acting analogue of azithromycin and tulathromycin with lower pharmacokinetic interaction potential, might be a suitable alternative. OBJECTIVES: To evaluate the pharmacokinetic interactions and pulmonary distribution of rifampicin and gamithromycin in healthy foals, and to investigate the cellular uptake of gamithromycin in vitro. STUDY DESIGN: Controlled, four-period, consecutive, single-dose and multiple-dose study. METHODS: Pharmacokinetics and lung distribution of rifampicin (10 mg/kg) and gamithromycin (6 mg/kg) were measured in nine healthy foals using LC-MS/MS. Enzyme induction was confirmed using the 4ß-OH-cholesterol/cholesterol ratio. Affinity of gamithromycin to drug transport proteins was evaluated in vitro using equine hepatocytes and MDCKII-cells stably transfected with human OATP1B1, OATP1B3 and OATP2B1. RESULTS: Rifampicin significantly (P<0.05) increased the plasma exposure of gamithromycin (16.2 ± 4.77 vs. 8.57 ± 3.10 µg × h/mL) by decreasing the total body clearance. Otherwise, gamithromycin significantly lowered plasma exposure of single- and multiple-dose rifampicin (83.8 ± 35.3 and 112 ± 43.1 vs. 164 ± 96.7 µg × h/mL) without a change in metabolic ratio and half-life. Gamithromycin was identified as an inhibitor of human OATP1B1, OATP1B3 and OATP2B1 and as a substrate of OATP2B1. In addition, it was extracted by equine hepatocytes via a mechanism which could be inhibited by rifampicin. MAIN LIMITATIONS: Influence of gamithromycin on pulmonary distribution of rifampicin was not evaluated. CONCLUSION: The plasma exposure of gamithromycin is significantly increased by co-administration of rifampicin which is most likely caused by inhibition of hepatic elimination.

Novel members of quinoline compound family enhance insulin secretion in RIN-5AH beta cells and in rat pancreatic islet microtissue.

According to clinical data, some tyrosine kinase inhibitors (TKIs) possess antidiabetic effects. Several proposed mechanisms were assigned to them, however their mode of action is not clear. Our hypothesis was that they directly stimulate insulin release in beta cells. In our screening approach we demonstrated that some commercially available TKIs and many novel synthesized analogues were able to induce insulin secretion in RIN-5AH beta cells. Our aim was to find efficient, more selective and less toxic compounds. Out of several hits, we chose members from a compound family with quinoline core structure for further investigation. Here we present the studies done with these novel compounds and reveal structure activity relationships and mechanism of action. One of the most potent compounds (compound 9) lost its affinity to kinases, but efficiently increased calcium influx. In the presence of calcium channel inhibitors, the insulinotropic effect was attenuated or completely abrogated. While the quinoline TKI, bosutinib substantially inhibited tyrosine phosphorylation, compound 9 had no such effect. Molecular docking studies further supported our data. We confirmed that some TKIs possess antidiabetic effects, moreover, we present a novel compound family developed from the TKI, bosutinib and optimized for the modulation of insulin secretion.

[Rehabilitation Processes in Out- and Inpatient Rehabilitation after Radical Prostatectomy]. / Rehabilitationsprozesse in ambulanter und stationärer Rehabilitation nach radikaler Prostatovesikulektomie.

We evaluated processes in in- and outpatient rehabilitation after radical prostatectomy. Overall, we analyzed motivation and expectations of 119 in- and 719 outpatients (aged≤64) at the beginning of rehabilitation as well as satisfaction and the amount of interventions at the end. Compared to inpatients outpatients had a higher socio-economic status and better physical condition. Both groups reported similar outcomes regarding motivation, expectation and satisfaction. Furthermore in- and outpatients got a comparable amount of interventions, but both groups differed to some extent in regard to the kind of interventions. In- and outpatients are comparable in regard to their received amount of interventions. Discrepancies concerning the kind of interventions are due to differences between in- and outpatients. The results indicate specific patients' characteristics in both settings, but more research is needed to verify these findings.

[Collaborative Goal Setting in Rehabilitation (ParZivar II): Evaluation of an Intervention in Patients with Chronic Back Pain]. / Partizipative Zielvereinbarung in der Rehabilitation (ParZivar II): Evaluation einer Intervention bei Patienten mit chronischen Rückenschmerzen.

OBJECTIVE: The "ParZivar II" project had 2 aims: optimization of the "ParZivar I" intervention by individual coaching of physicians, and evaluation of the optimized intervention. METHODS: The intervention was evaluated in a sequential control group design in 4 rehabilitation facilities with 3 measurement points. A total of n=279 patients with chronic low back pain participated in the study. RESULTS: The optimized intervention shows the potential to statistically significantly improve proximal outcomes (e. g. goal-centric processes or patient-physician interaction). Regarding distal outcomes, no statistically significant differences were found. CONCLUSION: The "ParZivar" intervention is a suitable approach to increase participative goal setting. Due to the complexity of the intervention, problems of dissemination and the potential for improvement in study design, there is a need for further research.

Selective growth of MFU-4l single crystals on microstructured plasma polymer coatings.

Single crystals of the metal-organic framework Ulm-4l(arge) (MFU-4l) can be grown site selectively on microtextured plasma polymer coatings comprising a pattern of alternating hydrophilic and hydrophobic domains. The crystals grow preferentially on the hydrophilic parts of the film surface. X-ray diffraction (XRD) shows that the cubic crystals have a high propensity to adhere with 〈1 0 0〉 orientation to the coating.

["Active in rehab": development and formative evaluation of a patient education program to increase health literacy of patients with chronic illness]. / "Aktiv in der Reha": Entwicklung und formative Evaluation einer Patientenschulung zur Förderung der Gesundheitskompetenz von chronisch Kranken.

OBJECTIVE: The aim of the article is to describe the development, the process of manualisation and results from the formative evaluation of a patient-oriented patient education program to increase health literacy of patients with chronic illness ("Active in rehab"). METHODS: Themes of the patient education program were extracted from 17 focus groups. An expert meeting was conducted to validate the content of the patient education program. The formative evaluation was based on a questionnaire (N(max) = 295 patients and N(max) = 39 trainers). RESULTS: The patient education program includes 4 modules with 3 themes (bio-psycho-social model, rehabilitation goals, communication competencies). The evaluation of the modules was good to very good. An analysis of free texts and a follow-up survey among trainers helped us to infer important improvements to the patient education program. CONCLUSION: RESULTS from the formative evaluation show that the patient education program meets patients and trainers needs and is accepted.

LGALS3BP, lectin galactoside-binding soluble 3 binding protein, promotes oncogenic cellular events impeded by antibody intervention.

The extracellular matrix protein lectin galactoside-binding soluble 3 binding protein (LGALS3BP) constitutes a negative prognostic marker of cancer onset and progression with increasing value in clinical application. Since its discovery, however, although the glycoprotein has been implicated in a growing number of disease-related processes, its actual role and mechanism of action have remained ambiguous, thus hindering opportunities for therapeutic development. In this study, we have determined that LGALS3BP constitutes a novel ligand for integrins α1ß1, α5ß1, αvß1 and α6ß1 and have identified that these newly established partnerships at the membrane level are responsible for exerting the molecule's involvement in cancer through manipulation of multiple canonical 'outside-in' integrin signalling events. We demonstrate that LGALS3BP-mediated integrin activation results into signal transmission via Akt, JNK and the Ras cascade via the Raf-ERK axis while p38 activity is kept at baseline levels. Transient cellular adherence to LGALS3BP favours survival and proliferation signalling while apoptosis is kept at bay. Sustained cellular exposure to LGALS3BP significantly supports viability, motility and migration. Importantly, an anti-LGALS3BP antibody, SP2 is capable of impeding these newly defined LGALS3BP-driven processes without, however, compromising cell viability. These novel findings reveal the mechanism of action of LGALS3BP during cellular adherence and warrant its further validation as a potential pharmacological target for anticancer therapies.

Pharmacophore and binding analysis of known and novel B-RAF kinase inhibitors.

The extensively investigated serine/threonine kinase, B-RAF, is a member of the RAS/RAF/MEK/ERK pathway. It plays important role in the regulation of cell growth, differentiation and survival. The mutation of B-RAF occurs frequently in melanomas and colon tumors; therefore, it is considered as an outstanding therapeutic target. In recent years a great number of B-RAF inhibitors have been reported and this number is expected to increase. The aim of our work was to compare the structures and binding mode of the published B-RAF inhibitors, and then to apply the correlations found for the explanation of our experimental results. In the first part of this paper we describe the main pharmacophore features of the co-crysallized B-RAF inhibitors published in the literature, focusing on the binding modes and common structural elements. In the second part we present and characterize our recently developed B-RAF inhibitor family by application of in silico methods and in vitro kinetic profiling. The inhibitory activity of these compounds was determined in biochemical kinase- and cell-based assays. The docking and assay results support our conclusion that the presented compound family belongs to the type I 1/2 subgroup, they inhibit B-RAF and B-RAF(V600E) mutant in a sub-micromolar range and most of them show selectivity towards B-RAF(V600E) mutant expressing cell lines with equal or even better IC50 values than sorafenib.

[Quality of vocational education in speech therapy - development and implementation of a quality assurance programme]. / Therapeutenausbildung auf dem Prüfstand - Entwicklung und Umsetzung eines Verfahrens zur Qualitätssicherung der logopädischen Ausbildung.

The provision of high-quality health-services is only possible if it is based on vocational education of corresponding quality. To promote the quality of vocational education in speech therapy, a quality assurance programme was developed in a scientifically supervised multi-step process. The main goals of the quality assurance programme include: (i) external review of the quality of education by means of well-defined criteria, (ii) certification of schools that meet the requirements, and (iii) provision of feedback to schools about their results. A total of 208 quality indicators cover the essential aspects of vocational education in speech therapy, and apply to the structural, process and outcome quality. These indicators are based on a literature survey as well as on expert opinion, and are calibrated by data. The data are collected by using questionnaires (school management, teachers in speech therapy, students, consecutive patient sample) and are validated by specific document analyses and telephone audits. Each school receives an individual quality report of its achieved results benchmarked to other schools. Since the initial implementation in 2008, a total of 50 schools participated in the quality assurance programme and 41 achieved certification. Therefore, the defined set of quality criteria has been disseminated and utilized by about half of all German schools for vocational education in speech therapy. The evaluation of the data on quality collected across all schools highlights the strengths and weaknesses of vocational education as well as the demands for quality improvement.

[Evaluation of a Vocationally Oriented Concept within Inpatient Oncological Rehabilitation]. / Evaluation eines berufsbezogenen Konzepts im Rahmen der stationären onkologischen Rehabilitation.

AIM OF THE STUDY: We evaluated an occupation-related rehabilitation program, which has been designed to enhance the return to work of cancer patients. As return to work plays an important role to get back to normalcy after suffering from cancer, there is a substantial need for support and evaluated programs. METHODS: The study had a quasi-experimental design with an intervention group (IG) and a comparison group (CG). We defined performance-related outcomes (e. g. return to work, self-assessed working capacity), asked patients if they needed further vocational advice and how helpful they estimated the rehabilitation treatment. 1 year after the end of rehabilitation 309 employed patients had completed the study (65%). We addressed our research questions using non-parametric tests, t-tests, analyses of variance and logistic regressions. RESULTS: Of the 309 patients 58% started rehabilitation not later than 14 days after the end of acute treatment while the other 42% had finished their treatments at least some weeks or even months ago. Patients of the IG evaluated the work-related rehabilitation offers significantly better and needed less additional vocational advice after the end of rehabilitation (n. s.). Regarding the patients, who started rehabilitation not later than 14 days after the end of acute treatment (beginning of rehabilitation n=269, 12 months after rehabilitation n=174), the IG achieved a slightly higher return-to-work-rate 12 months after the end of rehabilitation (81% IG, 76% CG, n. s.). Above that the IG estimated their subjective working capacity significantly more often as fully re-established (IG 46%; CG 29%, p=0,030). CONCLUSIONS: A high percentage of the patients return to work (78%). These results show the success of oncological rehabilitation in helping patients to return to work. In addition, the occupation-related rehabilitation program enhances subjective variables as the satisfaction of the patients regarding the information and the improvement of the patients' working-capacity.