Psychological stress of general practitioners in the care of patients with palliative care needs: an exploratory study.

BACKGROUND: In Germany, general practitioners play a pivotal role in palliative care provision. Caring for patients with palliative care needs can be a burden for general practitioners, highlighting the importance of self-care and mental health support. This study aimed to explore the role of palliative care in general practitioners' daily work, the stressors they experience, their coping mechanisms, and the potential benefits of Advance Care Planning in this context. METHODS: An exploratory approach was employed, combining a short quantitative survey with qualitative interviews. The analysis was based on a structuring qualitative content analysis, following a deductive-inductive procedure and integrating the Stress-Strain Model and Lazarus' Transactional Model of Stress and Coping. We recruited eleven general practitioners to take part in the study. RESULTS: General practitioners viewed palliative care as integral to their practice but faced challenges such as time constraints and perceived expertise gaps. Societal taboos often hindered conversations on the topic of death. Most general practitioners waited for their patients to initiate the topic. Some general practitioners viewed aspects of palliative care as potentially distressing. They used problem-focused (avoiding negative stressors, structuring their daily schedules) and emotion-focused (discussions with colleagues) coping strategies. Still, general practitioners indicated a desire for specific psychological support options. Advance Care Planning, though relatively unfamiliar, was acknowledged as valuable for end-of-life conversations. CONCLUSIONS: Palliative care can be associated with negative psychological stress for general practitioners, often coming from external factors. Despite individual coping strategies in place, it is advisable to explore concepts for professional psychological relief. TRIAL REGISTRATION: Not registered.

[" Not Even in The Corridor!" - Subjective Perception Of Institutional Measures During The Covid-19 Pandemic Of Nursing Home Residents: A Qualitative Study]. / " nicht mal auf den Gang!" ­ Das subjektive Empfinden institutioneller Maßnahmen während der Covid-19 Pandemie von Pflegeheimbewohnern. Eine qualitative Studie.

BACKGROUND: In the context of the Covid-19 pandemic, institutional measures were decreed to protect nursing home residents from infection. Their appropriateness has been a subject of controversy. The aim of this work was to better understand the subjective perception of the protective measures during the Covid-19 pandemic by the nursing home residents in Bavaria and to shed light on the role of nursing staff and general practitioners in coping with the crisis. METHODS: Semi-structured interviews were conducted with residents of inpatient long-term care facilities. Data analysis was carried out by means of structured content analysis according to Kuckartz. RESULTS: A total of ten nursing home residents with various degrees of care were interviewed, five of whom had already been infected with Covid-19 at the time of the survey. The respondents reported, on the one hand, their need for protection and, on the other hand, the isolation they experienced during the pandemic. Trust in the care provided by the nursing staff was emphasized. A reliable personal contact to already known general practitioners was missing. CONCLUSION: The role of nurses and general practitioners deserves more attention and may be a key to better acceptance and management of such crisis situations.

Patient-reported reactogenicity and safety of COVID-19 vaccinations vs. comparator vaccinations: a comparative observational cohort study.

BACKGROUND: In the course of the SARS-CoV-2 pandemic, multiple vaccines were developed. Little was known about reactogenicity and safety in comparison to established vaccines, e.g. influenza, pneumococcus, or herpes zoster. Therefore, the present study aimed to compare self-reported side effects in persons vaccinated against SARS-CoV-2 with the incidence of side effects in persons receiving one of the established vaccines. METHODS: A longitudinal observational study was conducted over a total of 124 days using web-based surveys. Persons receiving either a vaccination against SARS-CoV-2 or one of the established vaccines (comparator group) were included. In the first questionnaire (short-term survey), 2 weeks after vaccination, mainly local and systemic complaints were evaluated. The long-term survey (42 days after vaccination) and follow-up survey (124 weeks after vaccination) focused on medical consultations for any reason. Multivariate analyses were conducted to determine the influence of the vaccine type (SARS-CoV-2 vs. comparator) and demographic factors. RESULTS: In total, data from 16,636 participants were included. Self-reported reactogenicity was lowest in the comparator group (53.2%) and highest in the ChAdOx1 group (85.3%). Local reactions were reported most frequently after mRNA-1273 (73.9%) and systemic reactions mainly after vector-based vaccines (79.8%). Almost all SARS-CoV-2 vaccines showed increased odds of reporting local or systemic reactions. Approximately equal proportions of participants reported medical consultations. None in the comparator group suspected a link to vaccination, while this was true for just over one in 10 in the mRNA-1273 group. The multivariate analysis showed that people with SARS-CoV-2 vaccination were not more likely to report medical consultations; patients who had received a regimen with at least one ChAdOx1 were even less likely to report medical consultations. Younger age, female gender and higher comorbidity were mostly associated with higher odds of medical consultations. CONCLUSION: The rate of adverse reactions after established vaccinations was roughly comparable to previous studies. Two weeks after vaccination, participants in the SARS-CoV-2 vaccination group reported more local and systemic local reactions than participants in the comparator group. In the further course, however, there were no higher odds of medical consultations in either of the two groups. Thus, altogether, we assume comparable safety. TRIAL REGISTRATION: DRKS-ID DRKS00025881 and DRKS-ID DRKS00025373.

Reactogenicity and safety of COVID-19 primary immunisation and booster vaccination regimens: a comparative observational cohort study.

BACKGROUND: Since the beginning of the COVID-19 vaccination campaigns, recommendations regarding the vaccination have been very dynamic. Although the safety and efficacy of different vaccines have been analysed, data were scarce for vaccine regimens combining different vaccines. We therefore aimed to evaluate and compare the perceived reactogenicity and need for medical consultation after the most frequently applied homologous and heterologous COVID-19 vaccination regimens. METHODS: In an observational cohort study, reactogenicity and safety were assessed within a maximum follow-up time of 124 days using web-based surveys. Reactogenicity was assessed for different vaccination regimens 2 weeks after a vaccination (short-term survey). The following surveys, long-term and follow-up surveys, focused on the utilisation of medical services, including those that were not suspected to be vaccine-related. RESULTS: Data of 17,269 participants were analysed. The least local reactions were seen after a ChAdOx1 - ChAdOx1 regimen (32.6%, 95% CI [28.2, 37.2]) and the most after the first dose with mRNA-1273 (73.9%, 95% CI [70.5, 77.2]). Systemic reactions were least frequent in participants with a BNT162b2 booster after a homologous primary immunisation with ChAdOx1 (42.9%, 95% CI [32.1, 54.1]) and most frequent after a ChAdOx1 - mRNA-1273 (85.5%, 95% CI [82.9, 87.8]) and mRNA-1273/mRNA-1273 regimen (85.1%, 95% CI [83.2, 87.0]). In the short-term survey, the most common consequences were medication intake and sick leave (after local reactions 0% to 9.9%; after systemic reactions 4.5% to 37.9%). In the long-term and follow-up surveys, between 8.2 and 30.9% of participants reported consulting a doctor and between 0% and 5.4% seeking hospital care. The regression analyses 124 days after the first and after the third dose showed that the odds for reporting medical consultation were comparable between the vaccination regimens. CONCLUSIONS: Our analysis revealed differences in reactogenicity between the COVID-19 vaccines and vaccination regimens in Germany. The lowest reactogenicity as reported by participants was seen with BNT162b2, especially in homologous vaccination regimens. However, in all vaccination regimens reactogenicity rarely led to medical consultations. Small differences in seeking any medical consultation after 6 weeks diminished during the follow-up period. In the end, none of the vaccination regimens was associated with a higher risk for medical consultation. TRIAL REGISTRATION: DRKS DRKS00025881 ( https://drks.de/search/de/trial/DRKS00025373 ). Registered on 14 October 2021. DRKS DRKS00025373 ( https://drks.de/search/de/trial/DRKS00025881 ). Registered on 21 May 2021. Registered retrospectively.

Physicians' assessment of the Bavarian drug-expenditure control system: a qualitative study.

BACKGROUND: In 2014 a new system for drug expenditures, the Wirkstoffvereinbarung (WSV, English: Active substance agreement) was implemented in Bavaria. In pre-defined indication groups, economic prescription of medications shall be enabled based on the selection, quantity, and proportion of an individual drug. Ambulatory care physicians receive quarterly trend reports on their prescribing behavior. This study examines physicians' perceptions of the WSV. METHODS: Qualitative interviews (n = 20) and seven focus groups (n = 36) were conducted with ambulatory care physicians (e.g. general practitioners, cardiologists, pulmonologists). The methodology followed Qualitative Content Analysis. RESULTS: Physicians generally accepted the necessity of prescribing economically. The majority of them rated the WSV positively and better than the previous system. As an improvement, they especially named timely feedback in form of easily understandable trend reports, encouraging self-reflection as well as allowing early control options. Problems perceived were drug discount contracts that were strongly criticized as leading to patients mixing up medications. Some perceived constraints of therapeutic freedom. CONCLUSIONS: The implementation of the WSV is mostly viewed positively by physicians. The restrictions of therapeutic freedom partially perceived might be met by improved information on the reasons why some drugs are rated as less economical than others. TRIAL REGISTRATION NUMBER: Main ID: DRKS00019820 (German Register of Clinical Studies and World Health Organization).

Reactogenicity after heterologous and homologous COVID-19 prime-boost vaccination regimens: descriptive interim results of a comparative observational cohort study.

BACKGROUND: Due to safety signals after vaccination with COVID-19 vector vaccines, several states recommended to complete the primary immunization series in individuals having received one dose of ChAdOx1 (AstraZeneca) with an mRNA vaccine. However, data on safety and reactogenicity of this heterologous regimen are still scarce. The aim of this study was therefore to compare the reactogenicity and the frequency of medical consultations after boost vaccination in a heterologous regimen with ChAdOx1 and mRNA-vaccines (BNT162b2, BioNTech/Pfizer or mRNA-1273, Moderna) to homologous regimens with ChAdOx1 or mRNA-vaccines, respectively. METHODS: In an observational cohort study reactogenicity and safety were assessed 14-19 days (short-term) and 40 to 56 days (long-term) after the boost vaccination using web-based surveys. In the short-term survey solicited and unsolicited reactions were assessed, while the long-term survey focussed on health problems leading to medical consultation after the vaccination, including those that were not suspected to be vaccine-related. RESULTS: In total, 9146 participants completed at least one of the surveys (ChAdOx1/ChAdOx1: n = 552, ChAdOx1/mRNA: n = 2382, mRNA/mRNA: n = 6212). In the short-term survey, 86% with ChAdOx1/mRNA regimen reported at least one reaction, in the ChAdOx1/ChAdOx1 and mRNA/mRNA cohorts 58% and 76%, respectively (age and sex adjusted p < 0.0001). In the long-term survey, comparable proportions of individuals reported medical consultation (ChAdOx1/ChAdOx1 vs. ChAdOx1/mRNA vs. mRNA/mRNA: 15% vs. 18% vs. 16%, age and sex adjusted p = 0.398). Female gender was associated with a higher reactogenicity and more medical consultations. Younger age was associated with a higher reactogenicity, whereas elderly people reported more medical consultations. CONCLUSION: Although the short-term reactogenicity was higher with the heterologous regimen than with the homologous regimens, other factors such as higher efficacy and limited resources during the pandemic may prevail in recommending specific regimens.

[Prescribing behavior of Bavarian general practitioners at the inpatient-outpatient interface within the context of the Bavarian active substance agreement-qualitative results of the WirtMed Study]. / Verordnungsverhalten von bayerischen Hausärzt*innen an der stationär-ambulanten Schnittstelle vor dem Hintergrund der Bayerischen Wirkstoffvereinbarung ­ Qualitative Ergebnisse der WirtMed-Studie.

BACKGROUND AND OBJECTIVES: In 2014, the Association of Statutory Health Insurance Physicians of Bavaria introduced the active substance agreement (WSV) for the transparent control of pharmaceutical expenditure within the framework of the efficiency principle (§ 12 of the Fifth Book of the German Social Code [SGB V]). It replaced the prescribing target scheme. Regarding the role of the WSV, the article presents the reasons of the general practitioners (GPs) for or against a further prescription of drugs from the hospital. MATERIALS AND METHODS: In a qualitative study design, individual interviews (n = 18) and two focus groups (n = 10) were conducted with Bavarian GPs between November 2019 and March 2020 and evaluated according to qualitative content analysis. RESULTS: With the introduction of the WSV, recourse concerns decreased for GPs overall. Patient-oriented care and the professional correctness of therapy decisions are of great importance in prescribing, ahead of cost-effectiveness. Economic challenges arise with discharge medication, especially with the lead substance target of oral anticoagulants, the generic targets for antidiabetics, and for therapeutics for the cardiovascular system. Generally criticized are drug discount contracts, which often lead to drug changes after hospital discharge. There are individual reports of a "predominance" of hospital physicians when prescribing, which is contrary to their own economic actions as GPs. According to the GPs, there is a lack of cross-sectoral cost responsibility. CONCLUSIONS: In the view of GPs, a smooth interface transition is not yet available in the outpatient sector despite a framework agreement on discharge management and the new control system of the WSV. An economical supply of drugs continues to require political discussion across sectors, but also across federal states.

[Into the Garbage? - Reasons for the Non-use of Technical Innovations in Inpatient Care]. / "In den Müll?!" ­ Ursachenforschung zur Nicht-Nutzung technischer Innovationen in der stationären Pflege.

Despite the potentially positive effects of new technologies, innovations are often not well accepted by nurses. The aim of this study was to explore the reasons for not using a distributed alarm system and to derive recommendations for future projects. Three group discussions were held with 14 nurses. Content analysis was used to explore the data. The nursing staff was not involved in the selection and introduction of the technology. A lack of knowledge or interest was not the reason for not using the system. The technology rather interrupted work processes, led to additional workload and exposure to more noise pollution for employees and patients. Technologies must fit into daily work routines. Ideally, nurses should be involved in the development, but at the least, they should be consulted at the time of introduction.

Unveiling Human Cardiac Fibroblast Membrane Proteome.

Cardiac fibroblasts (CFs) are one of the main cell populations in the heart and play important roles in tissue homeostasis and myocardial fibrosis. The study of these cells has been hampered by the lack of reliable membrane markers: none of the antigens currently used for characterization and isolation of CFs is unique for this cell type. This issue has also raised doubts regarding a distinct identity of cardiac fibroblasts when compared to other myocardium cell populations with similar morphologies. In this work, we report a comprehensive description and functional analysis of human CFs (hCFs) membraneenriched fraction proteome by advanced mass spectrometry-based proteomic tools. A total number of 1478 proteins were identified, including 774 membrane proteins (52%). We also report the identification of a subset of 30 membrane proteins that in this workflow were only identified in hCFs by comparison with the membrane-enriched proteome lists of human cardiac stem cells, human mesenchymal stem cells, and human dermal fibroblasts. The data reported in this work are a valuable source of information for further studies aiming at defining a membrane molecular signature of human cardiac fibroblasts (hCFs), and a step forward in research regarding membrane proteins with key roles in hCF function in homeostasis and disease.

3D aggregate culture improves metabolic maturation of human pluripotent stem cell derived cardiomyocytes.

Three-dimensional (3D) cultures of human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) hold great promise for drug discovery, providing a better approximation to the in vivo physiology over standard two-dimensional (2D) monolayer cultures. However, the transition of CM differentiation protocols from 2D to 3D cultures is not straightforward. In this work, we relied on the aggregation of hPSC-derived cardiac progenitors and their culture under agitated conditions to generate highly pure cardiomyocyte aggregates. Whole-transcriptome analysis and 13 C-metabolic flux analysis allowed to demonstrate at both molecular and fluxome levels that such 3D culture environment enhances metabolic maturation of hiPSC-CMs. When compared to 2D, 3D cultures of hiPSC-CMs displayed down-regulation of genes involved in glycolysis and lipid biosynthesis and increased expression of genes involved in OXPHOS. Accordingly, 3D cultures of hiPSC-CMs had lower fluxes through glycolysis and fatty acid synthesis and increased TCA-cycle activity. Importantly, we demonstrated that the 3D culture environment reproducibly improved both CM purity and metabolic maturation across different hPSC lines, thereby providing a robust strategy to derive enriched hPSC-CMs with metabolic features closer to that of adult CMs.

'The health care system is more like a business'-medical overuse from the patients' perspective in Germany: a qualitative study.

OBJECTIVES: Medical overuse exposes patients to unnecessary risks of harm. It is an open question whether and how patients perceive the concept of medical overuse, its causes and negative consequences. DESIGN: A qualitative study design, using elements of the Grounded Theory Approach by Strauss and Corbin. SETTING: Between May 2017 and January 2020, we recruited participants and conducted face-to-face interviews in the participants' homes. Data collection took place in Bavaria, Germany. PARTICIPANTS: We recruited 16 participants (female=8, male=8) with various characteristics for the study. We used different strategies such as flyers in supermarkets, pharmacies, participants spreading information about the study or local multipliers (snowball sampling). RESULTS: The participants mostly defined medical overuse as too much being done but understood the concept superficially. During the interviews, most participants could describe examples of medical overuse. They named a variety of direct and indirect drivers with economic factors suspected to be the main driver. As a consequence of medical overuse, participants named the physical and emotional harm (eg, side effects of medication). They found it difficult to formulate concrete solutions. In general, they saw themselves more in a passive role than being responsible for bringing about change and solutions themselves. Medical overuse is a 'problem of the others'. The participants emphasised that health education is important in reducing medical overuse. CONCLUSIONS: Medical overuse was little discussed among participants, although many participants reported experiences of too much medicine. Health education and strengthening the patients' self-responsibility can play a vital role in reducing medical overuse.

Development of a self-assessment tool to address the functioning of community-dwelling older adults in general practice: a validation study of the EFA23 questionnaire.

BACKGROUND: Multimorbidity is increasingly prevalent among ageing patients, leading to reduced daily functioning. To address the challenges posed by multimorbidity in older adults, a person- and context-centred approach is needed. This study aimed to develop a questionnaire as a self-assessment tool for older adults focusing on functioning in general practice based on the International Classification of Functioning, Disability and Health (ICF). METHODS: A mixed-methods approach was employed in the development and validation of the German EFA23 (Erfassung Funktionaler Gesundheit im Alter - 23 Fragen; Assessing Functional Health in Old Age - 23 questions) questionnaire. Based on an ICF subset developed in a preparatory phase and consensus study, questionnaire items were formulated and tested in a qualitative pretest, followed by a validation study. A workshop with general practitioners (GPs) was held to develop a supplementary manual for GPs on how to interpret the questionnaire results and discuss them with the patients. RESULTS: A total of 69 items were developed and tested in the qualitative pretest with 15 respondents, resulting in 37 items for the validation study. The validation study, involving 237 older adults, showed the presence of one significant principal component. It demonstrated good internal consistency (Cronbach's alpha = 0.967) and construct validity, showing positive correlations with established assessment tools. Descriptive statistics showed differences between the means of self-assessment by patients and an external GP assessment. The final EFA23 questionnaire consists of 23 items assessing limitations in functioning. CONCLUSIONS: The EFA23 questionnaire can be used as a valid self-assessment instrument to measure functioning in older adults, supporting a person- and context-centred approach in general practice.

Miniaturization of hiPSC-derived 3D neural cultures in stirred-tank bioreactors for parallelized preclinical assessment of rAAV.

Introduction: Engineered 3D models employing human induced pluripotent stem cell (hiPSC) derivatives have the potential to recapitulate the cell diversity and structure found in the human central nervous system (CNS). Therefore, these complex cellular systems offer promising human models to address the safety and potency of advanced therapy medicinal products (ATMPs), such as gene therapies. Specifically, recombinant adeno-associated viruses (rAAVs) are currently considered highly attractive for CNS gene therapy due to their broad tropism, low toxicity, and moderate immunogenicity. To accelerate the clinical translation of rAAVs, in-depth preclinical evaluation of efficacy and safety in a human setting is primordial. The integration of hiPSC-derived CNS models in rAAV development will require, amongst other factors, robust, small-scale, high-throughput culture platforms that can feed the preclinical trials. Methods: Herein, we pioneer the miniaturization and parallelization of a 200 mL stirred-tank bioreactor-based 3D brain cell culture derived from hiPSCs. We demonstrate the applicability of the automated miniaturized Ambr® 15 Cell Culture system for the maintenance of hiPSC-derived neurospheroids (iNSpheroids), composed of neuronal and glial cells. Critical process parameters were optimized, namely, cell density and agitation mode. Results: Under optimized conditions, stable iNSpheroid cultures were attained in the microbioreactors for at least 15 days, with high cell viability and astrocytic and neuronal phenotype maintenance. This culture setup allowed the parallelization of different rAAVs, in different multiplicity of infections (MOIs), to address rAAV-host interactions at a preclinical scale. The iNSpheroids were exposed to rAAV2- and rAAV9-eGFP in the microbioreactors. Transgene expression was detected 14 days post-transduction, revealing different astrocyte/neuron tropism of the two serotypes. Discussion: We advocate that the iNSpheroid cultures in miniaturized bioreactors are reliable and reproducible screening tools for addressing rAAV transduction and tropism, compatible with preclinical demands.

Associations of Mental Health Issues with Health Literacy and Vaccination Readiness against COVID-19 in Long-Term Care Facilities-A Cross-Sectional Analysis.

Vaccinations against COVID-19 are of the utmost importance in long-term care facilities. During the pandemic, mental health issues increased significantly. This cross-sectional analysis aimed to assess the associations of depression and anxiety with health literacy in people in need of care and the association of depression and burnout with vaccination readiness against COVID-19 in health care workers (HCWs). Within our cross-sectional study, people in need of care were assessed for symptoms of depression (PHQ-9), anxiety (GAD-7), and health literacy (HLS-EU-Q16). Among HCWs, we assessed symptoms of depression (PHQ-9) and burnout (MBI-HSS), as well as psychological antecedents of vaccination (5C) to measure vaccination readiness against COVID-19. A multivariate regression analysis was performed. Symptoms of a major depression were significantly associated with reduced health literacy (p = 0.010) in people in need of care. Among HCWs, symptoms of depression and burnout reduced vaccination readiness against COVID-19 significantly. In particular, collective responsibility was reduced in HCWs suffering from burnout symptoms (p = 0.001). People in need of care and their HCWs could benefit from intensified target group-specific vaccination counseling. Additionally, more attention should be paid to the protection of mental health in long-term care facilities.

Associations of mental health with vaccination readiness in informal caregivers and the vaccination status of their care recipients during the Covid-19 pandemic - A cross sectional analysis.

INTRODUCTION: Vaccinations are important for informal caregivers and their care recipients. Mental health problems are common among care givers. The aim of this study was to investigate vaccination readiness in informal caregivers and associations with mental health issues. Associations between vaccination readiness in informal caregivers and the vaccination status of their aged care recipients were examined. METHODS: Within the multicenter prospective registry study 'Bavarian ambulatory Covid-19 Monitor (BaCoM) ', informal caregivers were asked for symptoms of depression (PHQ-9), burden of caretaking (BSFC-s), psychological antecedents of vaccination readiness (5C model) and previous Covid-19 infections of their care recipients. The vaccination status against Covid-19, seasonal influenza and pneumococcal disease was determined via vaccination certificates. Data analysis was performed using ordinal regressions and Mann-Whitney-U tests. RESULTS: Data of n = 91 informal caregivers, associated with n = 84 care recipients were collected. Symptoms of depression were associated with reduced vaccination readiness (Calculation: p = 0.026, OR = 1.18), as well as the perceived burden of caretaking (Confidence: p = 0.006, OR = 0.88). A previous Covid-19 infection of the care recipients was associated with decreased vaccination readiness of informal caregivers (Median (Q1-Q3) Confidence: 5.0 (4.5-6.0) vs. 4.0 (3.0-5.0); Calculation: 5.0 (3.0-6.0) vs. 4.0 (1.0-5.0)). The vaccination status of the care recipients interrelated significantly with vaccination readiness of their informal caregivers (Confidence: p < 0.001; Complacency: p < 0.01; Constraints p < 0.05). No significant interrelations between vaccination readiness and the vaccination status against seasonal influenza or pneumococcal disease occurred. CONCLUSION: Mental health issues of informal caregivers seem to be associated with the actual vaccination status against Covid-19 in their care recipients. Target group specific counselling as well as an active involvement of informal caregivers in shared decision-making processes can be of relevance, but even more attention should be paid to the protection of mental health for informal caregivers. TRIAL REGISTRATION NUMBER: German Register of Clinical Studies DRKS 26039.

Development of a subset of the international classification of functioning, disability and health as a basis for a questionnaire for community-dwelling older adults aged 75 and above in primary care: a consensus study.

OBJECTIVES: Functioning of older adults needs to be adequately described before it can become the focus of care. The International Classification of Functioning, Disability and Health (ICF) provides a basis for describing functioning. As the ICF is too extensive for daily practice in primary care, there is a need for a reduced number of categories. The aim is to develop an ICF-subset for community-dwelling older adults aged 75 and above in primary care. DESIGN: The scientific basis for decision-making in our consensus study was laid by four preparatory studies, identifying potentially relevant ICF categories from four perspectives (research, patients', experts' and clinical perspective). The results of the preparatory phase were discussed by an international expert panel in a consensus study following the Nominal Group Technique (NGT). SETTING: An international 1-day online consensus conference. PARTICIPANTS: International experts (n=7) participated in the consensus conference, meeting the following criteria: extensive expertise in the field of the ICF and/or caring for older adults, and being fluent in English. RESULTS: Each preparatory study yielded a different number of categories with some overlaps but also differences. The expert panel decided to: (1) restrict the subset to second-level categories and reduce the number of categories from the preparatory phase, (2) limit the subset to the component activities and participation and (3) weight the patients' perspective as the most relevant one. CONCLUSIONS: By using consensus techniques and the NGT, the process led to 51 second-level ICF categories to describe the functioning of community-dwelling older adults. The decisions made in the consensus conference emphasised the importance of considering the individual life situation from a more holistic perspective and addressing functioning as a focus of care. Next, the 51 categories will contribute to the development of an ICF-based questionnaire.

Identification of Mispairing Omic Signatures in Chinese Hamster Ovary (CHO) Cells Producing a Tri-Specific Antibody.

Monoclonal antibody-based therapy has shown efficacy against cancer, autoimmune, infectious, and inflammatory diseases. Multispecific antibodies (MsAbs), including trispecifics (tsAbs), offer enhanced therapeutic potential by targeting different epitopes. However, when co-expressed from three or more different polypeptide chains, MsAb production can lead to incorrect chain assembly and co-production of mispaired species with impaired biological activity. Moreover, mispairing carries significant challenges for downstream purification, decreasing yields and increasing the cost of bioprocess development. In this study, quantitative transcriptomics and proteomics analyses were employed to investigate which signaling pathways correlated with low and high mispairing clone signatures. Gene and protein expression profiles of Chinese hamster ovary (CHO) clones producing an tsAb were analyzed in the exponential growth and stationary (tsAb production) phase of fed-batch culture. Functional analysis revealed activated endoplasmic reticulum stress in high mispairing clones in both culture phases, while low mispairing clones exhibited expression profiles indicative of activated protein translation, as well as higher endocytosis and target protein degradation, suggesting the clearance of unfolded proteins through ubiquitin-mediated mechanisms. In addition, through transcriptomic profiling, we identified a group of genes that have the potential to be used as a biomarker panel tool for identifying high mispairing levels in the early stages of bioprocess development.

Detecting Medication Risks among People in Need of Care: Performance of Six Instruments.

INTRODUCTION: Numerous tools exist to detect potentially inappropriate medication (PIM) and potential prescribing omissions (PPO) in older people, but it remains unclear which tools may be most relevant in which setting. OBJECTIVES: This cross sectional study compares six validated tools in terms of PIM and PPO detection. METHODS: We examined the PIM/PPO prevalence for all tools combined and the sensitivity of each tool. The pairwise agreement between tools was determined using Cohen's Kappa. RESULTS: We included 226 patients in need of care (median (IQR age 84 (80-89)). The overall PIM prevalence was 91.6 (95% CI, 87.2-94.9)% and the overall PPO prevalence was 63.7 (57.1-69.9%)%. The detected PIM prevalence ranged from 76.5%, for FORTA-C/D, to 6.6% for anticholinergic drugs (German-ACB). The PPO prevalences for START (63.7%) and FORTA-A (62.8%) were similar. The pairwise agreement between tools was poor to moderate. The sensitivity of PIM detection was highest for FORTA-C/D (55.1%), and increased to 79.2% when distinct items from STOPP were added. CONCLUSION: Using a single screening tool may not have sufficient sensitivity to detect PIMs and PPOs. Further research is required to optimize the composition of PIM and PPO tools in different settings.

Impact of the COVID-19 pandemic on people in need of care or support: protocol for a SARS-CoV-2 registry.

INTRODUCTION: People in need of care or support are severely affected by the COVID-19 pandemic. We lack valid data of long-term assessments. We present a register study to detect the physical and psychosocial impact of the COVID-19 pandemic on people in need of care or support in Bavaria, Germany. To describe the persons' life conditions comprehensively, we assess the perspectives and needs of the respective care teams too. Results will serve as evidence-based source to manage the pandemic and long-term prevention strategies. METHODS AND ANALYSIS: The 'Bavarian ambulatory COVID-19 Monitor' is a multicentre registry including a purposive sample of up to 1000 patient-participants across three study sites in Bavaria. The study group consists of 600 people in need of care with a positive SARS-CoV-2 PCR test. Control group 1 comprises 200 people in need of care with a negative SARS-CoV-2 PCR test, while control group 2 comprises 200 people with a positive SARS-CoV-2 PCR test but are not in need of care. We assess the clinical course of infection, psychosocial aspects and care needs using validated measures. Follow-up is every 6 months for up to 3 years. Additionally, we assess up to 400 people linked to these patient-participants (caregivers, general practitioners (GPs)) for their health and needs. Main analyses are stratified by level of care I-V (I=minor/V=most severe impairment of independence), inpatient/outpatient care setting, sex and age. We use descriptive and inferential statistics to analyse cross-sectional data and changes over time. In qualitative interviews with 60 stakeholders (people in need of care, caregivers, GPs, politicians), we explore interface problems of different functional logics, of everyday and professional perspectives. ETHICS AND DISSEMINATION: The Institutional Review Board of the University Hospital LMU Munich (#20-860) and the study sites (Universities of Wurzburg and Erlangen) approved the protocol. We disseminate the results by peer-reviewed publications, international conferences, governmental reports, etc.

Active monitoring of adverse reactions following COVID-19 and other vaccinations: a feasibility study as part of the CoVaKo project.

BACKGROUND: The Corona-Vakzin-Konsortium project (CoVaKo) analyses the efficacy and safety of COVID-19 vaccines in a real-world setting, as well as breakthrough infections in Bavaria, Germany. A subproject of CoVaKo aims to identify adverse reactions of the COVID-19 vaccine and compare these to adverse reactions of other vaccines in an online survey. In a preceding feasibility study, the study materials were tested for comprehensibility, visual design, and motivation to participate, as well as for their ability to be implemented and carried out in primary care practices and vaccination centres. METHODS: We used a mixed-methods research design. First, three focus groups consisting of general population participants were organised to evaluate the study materials and survey. Second, a test roll-out was conducted in vaccination centres and primary care practices that involved implementing and quantitatively evaluating the online survey. Third, interviews were conducted with participating general practitioners and heads of vaccination centres four weeks after the test roll-out. RESULTS: Parts of the information and registration form proved incomprehensible, specifically regarding the recruitment material and/or online survey. For example, headings were misleading given that, relative to other vaccinations, the COVID-19 vaccination was overemphasised in the title. Participants requested additional information regarding the procedure and completion time. Within 31 days, 2199 participants, who received either a COVID-19 vaccination (99%) or at least one of the control vaccinations (1%), registered for the study. Participants (strongly) agreed that the registration process was easy to understand, that the completion time was reasonable, and that the technical setup was straightforward. Physicians and heads of the vaccination centres perceived the study as easy to integrate into their workflow. The majority expressed willingness to participate in the main study. CONCLUSIONS: Our study indicated that identifying and documenting adverse reactions following vaccinations using an online survey is feasible. Testing materials and surveys provided valuable insight, enabling subsequent improvements. Participation from health professionals proved essential in ensuring the practicality of procedures. Lastly, adapting the study's organisation to external fluctuating structures and requirements confirmed necessary for a successful implementation, especially due to dynamic changes in the nation's COVID-19 vaccination strategies. TRIAL REGISTRATION: The trial was retrospectively registered at the "Deutsches Register Klinischer Studien" (DRKS-ID: DRKS00025881 ) on Oct 14, 2021.