Dipeptide-catalysed Michael reaction under physiological conditions: Examination of potential bioorthogonality.

Reactions for drug synthesis under cell-like conditions or even inside living cells can potentially be used e.g., to minimize toxic side effects, to maximize bioactive compound efficacy and/or to address drug delivery problems. Those reactions should be bioorthogonal to enable the generation of drug-like compounds with sufficiently good yields. In the known bioorthogonal Michael reactions, using thiols and phosphines as nucleophiles (e.g., in CS and CP bond formation reactions) is very common. No bioorthogonal Michael addition with a carbon nucleophile is known yet. Therefore, the development of such a reaction might be interesting for future drug discovery research. In this work, the metal-free Michael addition between cyclohexanone and various trans-ß-nitrostyrenes (CC bond formation reaction), catalysed by a dipeptide salt H-Pro-Phe-O-Na+, was investigated for the first time in the presence of glutathione (GSH) and in phosphate-buffered saline (PBS). We demonstrated that with electron-withdrawing substituents on the aromatic ring and in ß-position of the trans-ß-nitrostyrene yields up to 64% can be obtained under physiological conditions, indicating a potential bioorthogonality of the studied Michael reaction. In addition, the selected Michael products demonstrated activity against human ovarian cancer cells A2780. This study opens up a new vista for forming bioactive compounds via CC bond formation Michael reactions under physiological (cell-like) conditions.

Attitudes of psychiatrists towards people with mental illness: a cross-sectional, multicentre study of stigma in 32 European countries.

Background: Mental health-related stigma occurs among the public and professionals alike. The lived experience of mental illness has been linked to less stigmatising attitudes. However, data on psychiatrists and the relationship between stigmatising attitudes and psychotherapeutic activity or case discussion groups remains scarce. Methods: A cross-sectional multicentre study was performed in 32 European countries to investigate the lived experiences and attitudes of psychiatrists toward patients with mental illness as well as the relationship between stigma, psychosocial and professional factors. The self-reported, anonymous, internet-based Opening Minds Stigma Scale for Health Care Providers was used to measure the stigmatising attitudes. The survey was translated into the local language of each participating country. All participants were practising specialists and trainees in general adult or child and adolescent psychiatry. The study took place between 2nd October, 2019 and 9th July, 2021 and was preregistered at ClinicalTrial.gov (NCT04644978). Findings: A total of 4245 psychiatrists completed the survey. The majority, 2797 (66%), had completed training in psychiatry, and 3320 (78%) worked in adult psychiatry. The final regression model showed that across European countries more favourable attitudes toward people with mental illness were statistically significantly associated with the lived experience of participants (including seeking help for their own mental health conditions (d = -0.92, 95% confidence interval (CI) = -1.68 to -0.15, p = 0.019), receiving medical treatment for a mental illness (d = -0.88, 95% CI = -1.71 to -0.04, p = 0.040), as well as having a friend or a family member similarly affected (d = -0.68, 95% CI = -1.14 to -0.22, p = 0.004)), being surrounded by colleagues who are less stigmatising (d = -0.98, 95% CI = -1.26 to -0.70, p < 0.001), providing psychotherapy to patients (d = -1.14, 95% CI = -1.63 to -0.65 p < 0.001), and being open to (d = -1.69, 95% CI = -2.53 to -0.85, p < 0.001) and actively participating in (d = -0.94, 95% CI = -1.45 to -0.42, p < 0.001) case discussion, supervision, or Balint groups. Interpretation: Our study highlights the importance of psychotherapy training, supervision, case discussions and Balint groups in reducing the stigmatising attitudes of psychiatrists toward patients. As the findings represent cross-national predictors, Europe-wide policy interventions, national psychiatric education systems and the management of psychiatric institutions should take these findings into consideration. Funding: National Youth Talent Award (Ministry of Human Resources, Hungary, (NTP-NFTÖ-20-B-0134). All authors received no funding for their contribution.

Psychometric properties of the Opening Minds Stigma Scale for Health Care Providers in 32 European countries - A bifactor ESEM representation.

Aims: To measure the stigma of healthcare providers toward people suffering from mental illness, the Opening Minds Stigma Scale for Health Care Providers (OMS-HC) is a commonly applied instrument. However, this scale has not been thoroughly validated in many European countries, its psychometric properties are still unknown and data on practicing psychiatrists is lacking. Therefore, this multicenter study aimed to assess the psychometric characteristics of the 15-item OMS-HC in trainees and specialists in adult and child psychiatry in 32 countries across Europe. Materials and methods: The OMS-HC was conducted as an anonymous online survey and sent via Email to European adult and child psychiatrists. Parallel analysis was used to estimate the number of OMS-HC dimensions. Separate for each country, the bifactor ESEM, a bifactor exploratory structural equation modeling approach, was applied to investigate the factor structure of the scale. Cross-cultural validation was done based on multigroup confirmatory factor analyses and reliability measures. Results: A total of 4,245 practitioners were included, 2,826 (67%) female, 1,389 (33%) male. The majority (66%) of participants were specialists, with 78% working in adult psychiatry. When country data were analyzed separately, the bifactor model (higher-order factor solution with a general factor and three specific factors) showed the best model fit (for the total sample χ2/df = 9.760, RMSEA = 0.045 (0.042-0.049), CFI = 0.981; TLI = 0.960, WRMR = 1.200). The average proportion of variance explained by the general factor was high (ECV = 0.682). This suggests that the aspects of 'attitude,' 'disclosure and help-seeking,' and 'social distance' could be treated as a single dimension of stigma. Among the specific factors, the 'disclosure and help-seeking' factor explained a considerable unique proportion of variance in the observed scores. Conclusion: This international study has led to cross-cultural analysis of the OMS-HC on a large sample of practicing psychiatrists. The bifactor structure displayed the best overall model fit in each country. Rather than using the subscales, we recommend the total score to quantify the overall stigmatizing attitudes. Further studies are required to strengthen our findings in countries where the proposed model was found to be weak.

How should patient decision aids for schizophrenia treatment be designed? - A scoping review.

Despite the clear rationale for applying shared decision-making in the context of the preference sensitive decision for or against antipsychotics and the upswing of patient decision aids (pDAs) to support this process, there is still a lack of knowledge regarding which key features are crucial for pDAs in schizophrenia treatment. A scoping review according to the PRISMA-SRc was conducted to inform on crucial key features and quality indicators. The review focussed on the following seven aspects for investigating pDAs: (1) Types of decision aids, (2) Values, (3) Decision Guidance, (4) Output of the decision aid, (5) Target group, (6) Effectiveness according to publication and (7) Decision aid evaluation. Eleven studies which addressed six unique decision aids met the eligibility criteria. There were major differences in the design as well as in the development of the decision aids. Three aspects emerged that should be given special consideration in the design of such tools for antipsychotics: the evidence used by the decision aid, the algorithm for translating evidence into a decision aid and finally the presentation of the evidence. We recommend the use of data with a high level of evidence and to combine it with individualized treatment by taking into account patient preferences and previous experiences as well as comparing them with clinical assessments. Fully computerized decision aids that use complicated algorithms, for example, by merging treatment effects with patient characteristics to suggest an appropriate treatment at the end, tend to be paternalistic and thus not appropriate for SDM, in our view. In addition, possible cognitive deficits need to be considered when presenting the output of decision aids for antipsychotics.

Informing the development of a decision aid: Expectations and wishes from service users and psychiatrists towards a decision aid for antipsychotics in the inpatient setting.

OBJECTIVES: Decision aids (DAs) are promising tools to foster evidence-based shared decision-making between practitioners and service users. Nevertheless, it is still obscure how an evidence-based DA for people with severe mental illness, especially psychosis, should look in an inpatient treatment setting to be useful and feasible. Therefore, we conducted focus groups with psychiatrists and service users to collect and assess their expectations and wishes regarding an evidence-based DA. From these findings, we derived immediate recommendations for the future development of DAs. METHODS: We held two group interviews with service users (n = 8) and three group interviews with psychiatrists (n = 10). We used an open, large-scale topic guide. First, we presented data from a current meta-analysis on antipsychotics to the interviewees and, in a second step, asked for their expectations and wishes towards a DA that integrates these data. RESULTS: Our thematic analysis revealed six key themes addressed by the respondents: (1) general considerations on the importance and usefulness of such a DA, (2) critical comments on psychiatry and psychopharmacotherapy, (3) communicative prerequisites for the use of a DA, (4) form and content of the DA, (5) data input, data processing and output as well as (6) application of the DA and possible obstacles. CONCLUSIONS: Participants identified several important features for the development of DAs for selecting antipsychotics in inpatient psychiatric treatment. The digital format was met with the greatest approval. Especially the adaptability to different needs, users and psychopathologies and the possibility to outsource information dissemination via app seemed to be a decisive convincing argument. Further research is required to test specific features of DAs to be developed in clinical settings.

Evidence-based Shared-Decision-Making Assistant (SDM-assistant) for choosing antipsychotics: protocol of a cluster-randomized trial in hospitalized patients with schizophrenia.

BACKGROUND: Choosing an antipsychotic medication is an important medical decision in the treatment of schizophrenia. This decision requires risk-benefit assessments of antipsychotics, and thus, shared-decision making between physician and patients is strongly encouraged. Although the efficacy and side-effect profiles of antipsychotics are well-established, there is no clear framework for the communication of the evidence between physicians and patients. For this reason, we developed an evidence-based shared-decision making assistant (SDM-assistant) that presents high-quality evidence from network meta-analysis on the efficacy and side-effect profile of antipsychotics and can be used as a basis for shared-decision making between physicians and patients when selecting antipsychotic medications. METHODS: The planned matched-pair cluster-randomised trial will be conducted in acute psychiatric wards (n = 14 wards planned) and will include adult inpatients with schizophrenia or schizophrenia-like disorders (N = 252 participants planned). On the intervention wards, patients and their treating physicians will use the SDM-assistant, whenever a decision on choosing an antipsychotic is warranted. On the control wards, antipsychotics will be chosen according to treatment-as-usual. The primary outcome will be patients' perceived involvement in the decision-making during the inpatient stay as measured with the SDM-Q-9. We will also assess therapeutic alliance, symptom severity, side-effects, treatment satisfaction, adherence, quality of life, functioning and rehospitalizations as secondary outcomes. Outcomes could be analysed at discharge and at follow-up after three months from discharge. The analysis will be conducted per-protocol using mixed-effects linear regression models for continuous outcomes and logistic regression models using generalised estimating equations for dichotomous outcomes. Barriers and facilitators in the implementation of the intervention will also be examined using a qualitative content analysis. DISCUSSION: This is the first trial to examine a decision assistant specifically designed to facilitate shared-decision making for choosing antipsychotic medications, i.e., SDM-assistant, in acutely ill inpatients with schizophrenia. If the intervention can be successfully implemented, SDM-assistant could advance evidence-based medicine in schizophrenia by putting medical evidence on antipsychotics into the context of patient preferences and values. This could subsequently lead to a higher involvement of the patients in decision-making and better therapy decisions. TRIAL REGISTRATION: German Clinical Trials Register (ID: DRKS00027316 , registration date 26.01.2022).

Clinical Decision-Making During Psychiatric Ward Rounds.

Introduction: For psychiatric in-patients, ward rounds are a prominent occasion for decision making. As previous findings on shared decision-making (SDM) patterns mostly derive from out-patients and one-to-one-consultations, it was our aim to investigate SDM during psychiatric ward rounds. Methods: We conducted a cross-sectional study and included n = 62 in-patients from seven different psychiatric wards. We collected data from the patient and the treating physician before and after ward rounds and recorded the interaction. Results: We identified two groups of patients regarding their attitude toward ward rounds (no expectations vs. clear agenda). The latter showed higher active engagement, expected more decisions to be made and discussed more topics. Generally, observer rated SDM was low, with vast differences between the doctors' and the patients' perception. Conclusion: Doctors and patients perceive ward rounds differently and there is a discrepancy between subjective and objective involvement. A rather paternalistic doctor-patient-relationship is observed, while patients feel sufficiently involved and vastly satisfied. The potential of ward rounds maximizes if patients have an agenda. Consequently, motivating patients to prepare themselves toward ward rounds should be part of the weekly routine, as well as improving patient participation and information procedures during ward rounds.

'Triadic' shared decision making in mental health: Experiences and expectations of service users, caregivers and clinicians in Germany.

BACKGROUND: Shared decision making (SDM) in mental health may contribute to greater patient satisfaction and is sometimes associated with better health outcomes. Here, SDM should not only involve service users and clinicians but also involve the service users' caregivers. AIM: This study aimed to achieve better insight into the current SDM patterns of triads of service users, caregivers and clinicians in inpatient mental health care and the three parties' expectations towards the prospects of triadic SDM. DESIGN: The current research uses data from a representative cross-sectional study on caregivers in psychiatric inpatient treatment. We analysed data on n = 94 triads of service users, their caregivers and their clinicians. RESULTS: All three parties acknowledge caregivers to be of great support to monitor the progress with mental disease. The caregiver's role during consultations is most often described as being an expert, receiving or providing information and supporting service users. However, caregivers at times try to seek support for themselves during caregiver-clinician interaction, or their behaviour was described as unhelpful. The potential prospects of caregiver involvement are clearly acknowledged despite the low implementation of caregiver involvement in this sample (only in one-third of the cases). CONCLUSION: Triadic SDM rarely takes place in routine inpatient care. First, there should be a focus on interventions aiming at inviting caregivers to consultations. Only in the second step should a better conceptualisation of triadic SDM be undertaken. PUBLIC CONTRIBUTION: Early results were discussed with a local peer support group for caregivers of individuals living with mental illness.