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Abstract Background Coronary heart disease (CHD) is often associated with mental disorders (MDs). Comorbid MDs reduce the quality of life and increase cardiac morbidity and mortality. Nevertheless, there is little and inconsistent research on the management of MDs in CHD patients. To bridge this gap, this study aims to gain insight into the long-term course of MD-related health care for patients with CHD, in order to identify opportunities for care improvement. Methods In this prospective cohort study, we investigated whether CHD patients with or without expert-rated MD at baseline (N = 364) received different MD-related health care from either their general practitioner (GP) or cardiologist at follow-up, M = 2.7 [2.0–4.0] years later. In the follow-up assessment, N = 131 CHD patients participated and received questionnaires capturing sociodemographic, mental health, and MD-related health care characteristics. Descriptive statistics, t-tests and chi-squared tests were used for analyses. Results We found significant differences in MD-related health care. CHD patients with MD were more likely to be examined psychologically/psychiatrically (MD 55.9%, non-MD 16.7%, p =

Abstract Background The reasons for developing depression are not fully understood. However, it is known that the serotonergic system plays a role in the etiology, but the endocannabinoid system receives attention. Method In this study, 161 patients with a depressive disorder and 161 healthy participants were examined for the distribution of the CNR1 rs4940353, 5‐HT2A rs6311, and 5‐HT1A rs6295 by high‐resolution melting genotyping. The concentration of arachidonoyl ethanolamide (AEA) and 2‐arachidonoylglycerol (2‐AG) in the blood was measured by liquid chromatography–tandem mass spectrometry. Additionally, depression and anxiety symptoms were evaluated based on self‐questionnaires. Fifty‐nine patients participated in a second appointment to measure the concentration of AEA, 2‐AG, and symptoms of depression and anxiety. Results We observed higher AEA and decreased 2‐AG concentrations in patients with depression compared to healthy participants. During the treatment, the concentrations of AEA and 2‐AG did not change significantly. In patients higher symptoms of anxiety correlated with lower concentrations of 2‐AG. Gender differences were found concerning increased 2‐AG concentration in male patients and increased anxiety symptoms in female patients. Genotypic variations of 5‐HT1A rs6295 and 5‐HT2A rs6311 are associated with altered serotonergic activity and serotonin content in patients. Conclusion In conclusion, it seems that the endocannabinoid system, especially the endocannabinoids 2‐AG and AEA, and genetic variations of the 5‐HT1A and 5‐HT2A could play a role in patients with depression and may be involved in a depressive disorder.

Abstract Introduction This mixed‐method study explores psychological needs, access and barriers in coronary heart disease (CHD) patients with and without mental health issues (MHI) within the German healthcare system. Methods This study was conducted in three different healthcare settings: two hospitals, two rehabilitation clinics and three cardiology practices in Cologne, Germany. Patients were screened for angiographically documented CHD and other inclusion criteria. In total, 364 CHD patients took part in this study. It consisted of two parts: In the first part, participants filled in a newly developed questionnaire about their psychological needs, access and barriers within the healthcare system and their contact with their doctor in these matters. Then, patients were screened for MHIs with the help of the Hospital Anxiety and Depression Scale (HADS). When a score above seven was scored on the HADS, patients were additionally screened for specific MHIs using the Structured Clinical Interview for DSM‐IV Axis I Disorders. In the second part, 20 participants were subsequently interviewed in a semi‐structured interview to generate more in‐depth findings. Results The interviews show that CHD patients with and without MHI experienced a cardiac event as life‐changing and had an urgent need to talk about CHD with their doctor, mostly the general practitioner (GP). When the GP spoke to the patient shortly after the cardiac event, patients experienced relief and were better able to cope with their illness. Only 9.1% reported being aided in their search for psychotherapeutic treatment or drug treatment (4.1%). Conclusion The needs of CHD patients with and without MHI were not adequately satisfied within our sample. Psychological measures are necessary for sufficient improvement, such as training of doctors in doctor–patient communication (e.g., better support in coping with MHI/CHD), improvements in the procedure (more time for conversations during doctor contacts), and improvement of structural requirements (referring patients faster to psychotherapists). Patient or Public Contribution We received input from patients during pretests and used the feedback to tailor our questionnaire and the interview guidelines. Afterwards, we disseminated the main results for the patient and public involvement (e.g., public lectures, leaflets for self‐help groups, etc.).

Abstract Background Personal last wishes of people facing a life-limiting illness may change closer to death and may vary across different forms of specialist palliative care (SPC). Aims To explore the presence and common themes of last wishes over time and according to the SPC settings (inpatient vs. home-based SPC), and to identify factors associated to having a last wish. Methods Patients enrolled in a longitudinal study completed questionnaires at the onset (baseline, t0) and within the first 6 weeks (follow-up, t1) of SPC including an open-ended question on their personal last wishes. Last wishes were content analyzed, and all wishes were coded for presence or absence of each of the identified themes. Changes of last wishes (t0-t1) were analyzed by a McNemar test. The chi-square-test was used to compare the two SPC settings. Predictors for the presence of a last wish were identified by logistic regression analysis. Results Three hundred sixty-one patients (mean age, 69.5 years; 49% female) answered at t0, and 130 at t1. In cross-sectional analyses, the presence of last wishes was higher at t0 (67%) than at t1 (59%). Comparisons revealed a higher presence of last wishes among inpatients than those in home-based SPC at t0 (78% vs. 62%; p = .002), but not at t1. Inpatient SPC (OR = 1.987, p = .011) and greater physical symptom burden over the past week (OR = 1.168, p

Being able to accurately control the interaction of spin waves is a crucial challenge for magnonics in order to offer an alternative wave-based computing scheme for certain technological applications. Especially in neural networks and neuromorphic computing, wave-based approaches can offer significant advantages over traditional CMOS-based binary computing schemes with regard to performance and power consumption. In this work, we demonstrate precise modulation of phase- and amplitude-sensitive interference of coherent spin waves in a yttrium–iron–garnet based magnonic analog adder device, while also showing the feasibility of frequency-division multiplexing. Using time-resolved scanning transmission x-ray microscopy, the interference was directly observed, giving an important proof of concept for this kind of analog computing device and its underlying working principle. This constitutes a step toward wave-based analog computing using magnons as an information carrier.

Abstract Background We investigated the need for additional professional support and associated factors in patients (pts) at initiation and in the course of in- and outpatient specialist palliative care (I-SPC/O-SPC). Methods Pts entering an urban SPC network consecutively completed questionnaires on psychosocial/spiritual problems and support needs within 72 h (T0) as well as within the first 6 weeks (T1) of SPC. Hierarchical linear regression analysis was used to investigate the impact of sociodemographic / disease-related variables, psychological / physical burden, social support, and SPC setting on the extent of support needs. Results Four hundred twenty-five pts (70 years, 48% female, 91% cancer, 67% O-SPC) answered at T0, and 167 at T1. At T0, main problems related to transportation, usual activities, and dependency (83–89%). At T1, most prevalent problems also related to transportation and usual activities and additionally to light housework (82–86%). At T0, support needs were highest for transportation, light housework, and usual activities (35–41%). Cross-sectional comparisons of SPC settings revealed higher problem scores in O-SPC compared to I-SPC at T0 (p = .039), but not at T1. Support need scores were higher in O-SPC at T0 (p

Objectives The healthcare system is characterised by a high degree of complexity and involves various actors at different institutional levels and in different care contexts. To implement patient-centred care (PCC) successfully, a multidimensional consideration of influencing factors is required. Our qualitative study aims to identify system-level determinants of PCC implementation from the perspective of different health and social care organisations (HSCOs).Design A qualitative study using n=20 semistructured face-to-face interviews with n=24 participants was carried out between August 2017 and May 2018. Interview data were analysed based on concepts of qualitative content analysis using an inductive and deductive approach.Setting and participants Interviews were conducted with clinical and managerial decision makers from multiple HSCOs in the model region of Cologne, Germany. Participants were recruited via networks of practice partners and cold calling.Results This study identified various determinants on the system level that are associated with PCC implementation. Decision makers described external regulations as generating an economically controlled alignment of the healthcare system. The availability and qualification of staff resources and patient-related incentives of financial resources were identified as an eminent requirement for providers to deliver PCC. Participants considered the strict separation of financing and delivery of healthcare into inpatient and outpatient sectors to be a barrier to PCC. Interorganisational collaboration and information exchange were identified as facilitators of PCC, as they enable continuous patient care cycles.Conclusion The results showed the necessity of enforcing paradigm changes at the system level from disease-centredness to patient-centredness while aligning policy and reimbursement decisions directly with patient needs and values. A systematic, long-term planned strategy that extends across all organisations is lacking, rather each organisation seeks its own possibilities to implement PCC activities under external restrictions.Trial registration numberDRKS00011925

Abstract Background Mental disorders (MD), such as depression, anxiety, and cognitive impairment, are highly prevalent in patients with coronary heart disease (CHD). Current guidelines on cardiovascular diseases recommend screening and appropriate treatment of MD; however, the degree of implementation of such recommendations in clinical practice is unknown. This study aims to analyze the quality of health care of patients with CHD and MD. Specifically, we aim to analyze (1) the quality of care, (2) trajectories of care, and (3) barriers regarding the detection and treatment of MD. Moreover, we want to identify potentials of changes in health care delivery towards more patient-centered care. The results of this study shall be the first step towards value-based care of people with CHD and comorbid mental disorders. Methods We aim to include the following participants: adult patients with CHD (n = 400), their relatives (n = 350) and physicians (n = 80). A particular focus will be on the vulnerable subgroups of patients with CHD and congestive heart failure (left ventricular ejection fraction

IntroductionThe Managing Cancer and Living Meaningfully (CALM) therapy for patients with advanced cancer was tested against a supportive psycho-oncological counseling intervention (SPI) in a randomized controlled trial (RCT). We investigated whether CALM was delivered as intended (therapists’ adherence); whether CALM therapists with less experience in psycho-oncological care show higher adherence scores; and whether potential overlapping treatment elements between CALM and SPI can be identified (treatment differentiation).MethodsTwo trained and blinded raters assessed on 19 items four subscales of the Treatment Integrity Scale covering treatment domains of CALM (SC: Symptom Management and Communication with Health Care Providers; CSR: Changes in Self and Relationship with Others; SMP: Spiritual Well-being and Sense of Meaning and Purpose; FHM: Preparing for the Future, Sustaining Hope and Facing Mortality). A random sample of 150 audio recordings (75 CALM, 75 SPI) were rated on a three-point Likert scale with 1 = “adherent to some extent,” 2 = “adherent to a sufficient extent,” 3 = “very adherent.”ResultsAll 19 treatment elements were applied, but in various frequencies. CALM therapists most frequently explored symptoms and/or relationship to health care providers (SC_1: n_applied = 62; 83%) and allowed expression of sadness and anxiety about the progression of disease (FHM_2: n_applied = 62; 83%). The exploration of CALM treatment element SC_1 was most frequently implemented in a satisfactory or excellent manner (n_sufficient or very adherent = 34; 45%), whereas the treatment element SMP_4: Therapist promotes acknowledgment that some life goals may no longer be achievable (n_sufficient or very adherent = 0; 0%) was not implemented in a satisfactory manner. In terms of treatment differentiation, no treatment elements could be identified which were applied significantly more often by CALM therapists than by SPI therapists.ConclusionResults verify the application of CALM treatment domains. However, CALM therapists’ adherence scores indicated manual deviations. Furthermore, raters were not able to significantly distinguish CALM from SPI, implying that overlapping treatment elements were delivered to patients.

Objectives To set up a pragmatic Plan–Do–Study–Act cycle by analysing patient experiences and determinants of satisfaction with care in the last year of life.Design Cross-sectional postbereavement survey.Setting Regional health services research and development structure representing all health and social care providers involved in the last year of life in Cologne, a city with 1 million inhabitants in Germany.Participants 351 bereaved relatives of adult decedents, representative for age and gender, accidental and suspicious deaths excluded.Results For the majority (89%) of patients, home was the main place of care during their last year of life. Nevertheless, 91% of patients had at least one hospital admission and 42% died in hospital. Only 60% of informants reported that the decedent had been told that the disease was leading to death. Hospital physicians broke the news most often (58%), with their communication style often (30%) being rated as ‘not sensitive’. Informants indicated highly positive experiences with care provided by hospices (89% ‘good’) and specialist palliative home care teams (87% ‘good’). This proportion dropped to 41% for acute care hospitals, this rating being determined by the feeling of not being treated with respect and dignity (OR=23.80, 95% CI 7.503 to 75.498) and the impression that hospitals did not work well together with other services (OR=8.37, 95% CI 2.141 to 32.71).Conclusions Following those data, our regional priority for action now is improvement of care in acute hospitals, with two new projects starting, first, how to recognise and communicate a limited life span, and second, how to improve care during the dying phase. Results and further improvement projects will be discussed in a working group with the city of Cologne, and repeating this survey in 2 years will be able to measure regional achievements.Trial registration number DRKS00011925.

Objectives Previous studies on patient-centred care (PCC) and its facilitators and barriers usually considered specific patient groups, healthcare settings and aspects of PCC or focused on expert perspectives. The objective of this study was to analyse patients’ perspectives of facilitators and barriers towards implementing PCC.Design We conducted semistructured individual interviews with chronically ill patients. The interviewees were encouraged to share positive and negative experiences of care and the related facilitators and barriers in all settings including preventive, acute and chronic health issues. Interview data were analysed based on the concept of content analysis.Setting Interviews took place at the University Hospital Cologne, nursing homes, at participants’ homes or by telephone.Participants Any person with at least one chronic illness living in the region of Cologne was eligible for participation. 25 persons with an average age of 60 years participated in the interviews. The participants suffered from various chronic conditions including mental health problems, oncological, metabolic, neurological diseases, but also shared experiences related to acute health issues.Results Participants described facilitators and barriers of PCC on the microlevel (eg, patient–provider interaction), mesolevel (eg, health and social care organisation, HSCO) and macrolevel (eg, laws, financing). In addition to previous concepts, interviewees illustrated the importance of being an active patient by taking individual responsibility for health. Interviewees considered functioning teams and healthy staff members a facilitator of PCC as this can compensate stressful situations or lack of staff to some degree. A lack of transparency in financing and reimbursement was identified as barrier to PCC.Conclusion Individual providers and HSCOs can address many facilitators and barriers of PCC as perceived by patients. Large-scale changes such as reduction of administrative barriers, the expansion of care networks or higher mandatory nurse to patient ratios require political action and incentives.Trial registration number DRKS00011925

Mental disorders (MD) are associated with an increased risk of developing coronary heart disease (CHD) and with higher CHD-related morbidity and mortality. There is a strong recommendation to routinely screen CHD patients for MDs, diagnosis, and treatment by recent guidelines. The current study aimed at mapping CHD patients' (1) state of diagnostics and, if necessary, treatment of MDs, (2) trajectories and detection rate in healthcare, and (3) the influence of MDs and its management on quality of life and patient satisfaction. The design was a cross-sectional study in three settings (two hospitals, two rehabilitation clinics, three cardiology practices). CHD patients were screened for MDs with the Hospital Anxiety and Depression Scale (HADS), and, if screened-positive, examined for MDs with the Structured Clinical Interview for DSM-IV (SCID-I). Quality of Life (EQ-5D), Patient Assessment of Care for Chronic Conditions (PACIC), and previous routine diagnostics and treatment for MDs were examined. Descriptive statistics, Chi-squared tests, and ANOVA were used for analyses. Analyses of the data of 364 patients resulted in 33.8% positive HADS-screenings and 28.0% SCID-I diagnoses. The detection rate of correctly pre-diagnosed MDs was 49.0%. Physicians actively approached approximately thirty percent of patients on MDs; however, only 6.6% of patients underwent psychotherapy and 4.1% medication therapy through psychotherapists/psychiatrists. MD patients scored significantly lower on EQ-5D and the PACIC. The state of diagnostic and treatment of comorbid MDs in patients with CHD is insufficient. Patients showed a positive attitude towards addressing MDs and were satisfied with medical treatment, but less with MD-related advice. Physicians in secondary care need more training inadequately addressing mental comorbidity.

Enzyme-directed mutasynthesis is an emerging strategy for the targeted derivatization of natural products. Here, data on the synthesis of malonic acid derivatives for feeding studies in Saccharopolyspora erythraea , the mutagenesis of DEBS and bioanalytical data on the experimental investigation of studies on the biosynthetic pathway towards erythromycin are presented.

Polyketides are biosynthesized through consecutive decarboxylative Claisen condensations between a carboxylic acid and differently substituted malonic acid thioesters, both tethered to the giant polyketide synthase enzymes. Individual malonic acid derivatives are typically required to be activated as coenzyme A-thioesters prior to their enzyme-catalyzed transfer onto the polyketide synthase. Control over the selection of malonic acid building blocks promises great potential for the experimental alteration of polyketide structure and bioactivity. One requirement for this endeavor is the supplementation of the bacterial polyketide fermentation system with tailored synthetic thioester-activated malonates. The membrane permeable N-acetylcysteamine has been proposed as a coenzyme A-mimic for this purpose. Here, the incorporation efficiency into different polyketides of N-acetylcysteamine activated methylmalonate is studied and quantified, showing a surprisingly high and transferable activity of these polyketide synthase substrate analogues in vivo.

Das Projektstudium ist seit der Einführung der Planungsstudiengänge ein zentraler Baustein des Studiums. Aktuell wird seine Ausgestaltung neu diskutiert. Mit Blick auf das ‚Dortmunder Modell‘ diskutieren wir das utopische Potenzial dieser Lehrform und argumentieren, dass das Projektstudium ein letzter, konsequent ‚weltfremder‘ Raum des freien Nachdenkens, Widerstehens und gelegentlich auch Scheiterns sein könnte. Dabei ist der ursprüngliche gesellschaftspolitische Anspruch an das Projekt im Laufe der Zeit einer Orientierung an Schlüsselkompetenzen für die berufliche Praxis gewichen. Ausdruck dessen ist die Einführung einer individuellen Benotung. Gerade angesichts der ‚bösartigen Probleme‘, mit denen Planung es zu tun hat, halten wir das Projektstudium nach wie vor für zentral, um auch Reflexions- und Kommunikationsfähigkeiten einzuüben. Inwieweit aktuelle Veränderungen das Potenzial dieser Lehrform verändern werden, bleibt abzuwarten.

Polyketides are a diverse class of medically important natural products whose biosynthesis is catalysed by polyketide synthases (PKSs), in a fashion highly analogous to fatty acid biosynthesis. In modular PKSs, the polyketide chain is assembled by the successive condensation of activated carboxylic acid-derived units, where chain extension occurs with the intermediates remaining covalently bound to the enzyme, with the growing polyketide tethered to an acyl carrier domain (ACP). Carboxylated acyl-CoA precursors serve as activated donors that are selected by the acyltransferase domain (AT) providing extender units that are added to the growing chain by condensation catalysed by the ketosynthase domain (KS). The action of ketoreductase (KR), dehydratase (DH), and enoylreductase (ER) activities can result in unreduced, partially reduced, or fully reduced centres within the polyketide chain depending on which of these enzymes are present and active. The PKS-catalysed assembly process generates stereochemical diversity, because carbon–carbon double bonds may have either cis- or trans- geometry, and because of the chirality of centres bearing hydroxyl groups (where they are retained) and branching methyl groups (the latter arising from use of propionate extender units). This review shall cover the studies that have determined the stereochemistry in many of the reactions involved in polyketide biosynthesis by modular PKSs.

Baeyer-Villiger monooxygenases (BVMOs) are extremely promising catalysts useful for enantioselective oxidation reactions of ketones, but organic chemists have not used them widely due to several reasons. These include instability of the enzymes in the case of in vitro and even in vivo systems, reactant/product inhibition, problems with upscaling and the necessity of using specialized equipment. The present study shows that the thermally stable phenylacetone monooxygenase (PAMO) and recently engineered mutants can be used as a practical catalysts for enantioselective Baeyer-Villiger oxidations of several ketones on a preparative scale under in vitro conditions. For this purpose several parameters such as buffer composition, the nature of the solvent system and the co-factor regeneration system were optimized. Overall a fairly versatile and efficient catalytic system for enantioselective laboratory scale BV-oxidations of ketones was developed, which can easily be applied even by those organic chemists who are not well versed in the use of enzymes.