Sex differences in cardiologic medication provision for adults with coronary heart disease: an analysis of health claims data from 2018 to 2020 in Saxony-Anhalt, Germany.

BACKGROUND: Coronary heart diseases (CHDs) have experienced the largest increase worldwide as a cause of death, accounting for 16% of all deaths. In Saxony-Anhalt, a federal state in Germany, both CHD morbidity and acute myocardial infarction mortality rates are particularly high. Several risk factors associated with CHDs have been studied in Saxony-Anhalt, but sex differences in service use and medication have not been investigated. This study therefore aimed to investigate sex differences in the quality and quantity of cardiological care provided to adults with CHD. METHODS: This study used health claims data from 2018 to 2020 to analyse the utilisation of healthcare services and adherence to medication-related guideline recommendations in primary and specialist care. The sample included 133,661 individuals with CHD from a major statutory health insurance company (Germany). RESULTS: Almost all CHD patients (> 99%) received continuous primary care. Continuous cardiologist utilisation was lower for females than for males, with 15.0% and 22.2%, respectively, and sporadic utilisation showed greater differences, with 33.5% of females and 43.4% of males seeking sporadic cardiologist consultations. Additionally, 43.1% of the identified CHD patients participated in disease management programmes (DMPs). The study also examined the impact of DMP participation and cardiologist care on medication uptake and revealed that sex differences in medication uptake, except for statin use, were mitigated by these factors. Statins were prescribed to 42.9% of the CHD patients eligible for statin prescription in accordance with the QiSA indicator for statin prescription eligibility. However, there were significant sex differences in statin utilisation. Female CHD patients were less likely to use statins (35.2%) than male CHD patients were (50.1%). The difference in statin utilisation persisted after adjustment for DMP participation and cardiologist consultation. CONCLUSIONS: This study highlights sex differences in the utilisation of cardiological healthcare services for patients with CHD in the Saxony-Anhalt cohort. These findings underscore the continuing need for interventions to reduce sex inequalities in accessing healthcare and providing health care for patients with CHD. Factors at the health care system, patient, and physician levels should be further investigated to eventually improve statin prescription in people with CHD, especially women.

Glucose stress causes mRNA retention in nuclear Nab2 condensates.

Nuclear mRNA export via nuclear pore complexes is an essential step in eukaryotic gene expression. Although factors involved in mRNA transport have been characterized, a comprehensive mechanistic understanding of this process and its regulation is lacking. Here, we use single-RNA imaging in yeast to show that cells use mRNA retention to control mRNA export during stress. We demonstrate that, upon glucose withdrawal, the essential RNA-binding factor Nab2 forms RNA-dependent condensate-like structures in the nucleus. This coincides with a reduced abundance of the DEAD-box ATPase Dbp5 at the nuclear pore. Depleting Dbp5, and consequently blocking mRNA export, is necessary and sufficient to trigger Nab2 condensation. The state of Nab2 condensation influences the extent of nuclear mRNA accumulation and can be recapitulated in vitro, where Nab2 forms RNA-dependent liquid droplets. We hypothesize that cells use condensation to regulate mRNA export and control gene expression during stress.

[Utilization of pre-hospital emergency medical services: Secondary data analysis of health insurance data from Saxony-Anhalt]. / Inanspruchnahme der bodengebundenen Notfallrettung ­ Sekundärdatenanalyse der Versichertenkohorte AOK Sachsen-Anhalt.

BACKGROUND: Utilization of emergency care is subject to demographic changes. In Germany, there was an increase of 4% to 6% annually between the years 2000 and 2017. Studies revealed that age and regional structures were related to utilization. The aim of this cross-sectional study was to analyze utilization of pre-hospital emergency medical services in Saxony-Anhalt and to identify associated factors. METHOD: Based on data from the AOK Saxony-Anhalt for 2019, transportation with ground ambulances of insured persons living in Saxony-Anhalt were identified and recorded. Insured time of all AOK insured persons living in Saxony-Anhalt was used to determine incidence rates. For the multivariate analysis of associated factors, a Poisson regression model was adapted. RESULTS: 112,575 transportations of patients were identified; an average of 1.53 events per person or 149.6 per 1,000 person years. Inpatient hospital treatment was provided for 53.2% of emergency patients and outpatient hospital treatment for 37.1%. Frequent users represented 14.6% of the events. The incidence rate was highest for older persons and those with care dependency. In addition, the risk of using emergency services was higher among men and in suburban and urban regions (compared with rural regions), even after adjustment. CONCLUSIONS: Utilization is higher in the cohort studied compared to that found in other studies. The high proportion where inpatient hospital treatment is not necessary, as well as the clear association with care dependency and age, offer possible angles of approach for interventions to relieve the burden on emergency services.

Evaluation of two different semi-automated homogenization techniques in microbiological diagnosis of periprosthetic joint infection: disperser vs. bead milling method.

BACKGROUND: In microbiological diagnosis of periprosthetic joint infection (PJI) there is no consensus regarding the most suitable and optimal number of specimens to be cultured or the most effective technique of tissue processing. This comparative study analysed the accuracy of two semi-automated homogenization methods with special focus on the volume and exact origin of each sample. METHODS: We investigated a total of 722 periprosthetic tissue samples. PJI was defined according to the new scoring system for preoperative and intraoperative criteria. We compared the performance of our routinely used single tissue processing by disposable high-frequency disperser with the bead milling method. RESULTS: Eighty patients were included. Among forty classified PJIs, 34 patients yielded positive culture results. In 23 cases (68%) exact concordant results were generated with both techniques. However, in seven cases (20%) processing by the disperser and in four cases (12%) by bead milling provided additional positive samples, but without significant difference since the major definition criteria were met in all cases. The percentage of positive results was influenced by the volume and origin of the tissue samples. Results for small tissue samples tended to be better using the bead milling method. This might lead to improved preoperative arthroscopic diagnosis, as the volume of biopsies is generally limited. Six patients had negative results due to previous antimicrobial therapy. Forty other patients were classified as aseptic failures. Neither procedure resulted in any contamination. CONCLUSION: Both methods enable reliable processing of tissue samples for diagnosis of PJI and are suitable for routine use.

Probing Liquid-Liquid Phase Separation of RNA-Binding Proteins In Vitro and In Vivo.

Biomolecular condensates and the concept of liquid-liquid phase separation (LLPS) have transformed cell biology in recent years. Condensates organize cellular content and compartmentalize biochemical reactions, in particular many processes involving RNA. This protocol is aimed at readers new to the LLPS field who want to test their protein or cellular structure of interest. We describe the basic principles of liquid-liquid phase separation, and outline initial approaches-both in vitro and in yeast cells-for the characterization of a candidate cellular condensate. First, we focus on strategies to purify phase-separating proteins and to reconstitute condensates from recombinant proteins in vitro for observation by light microscopy. Second, we describe in vivo experiments (including fluorescence recovery after photobleaching (FRAP) microscopy and 1,6-Hexanediol treatment) to test whether a subcellular structure displays liquid-like behavior in cells.

Case management for people with dementia living at home and their informal caregivers: A scoping review.

Case management is a complex intervention aimed at addressing a variety of health needs of people in their social environment. Case management for people with dementia is often poorly defined and insufficiently described. The crucial process steps are often not well understood. We aim to map and compare the key components, processes and contextual factors of case management programmes for dementia and to explore aspects of the interventions' generalisability. Our search covered the databases PubMed, CINAHL, Cochrane and GeroLit, as well as policy papers from international organisations. We included qualitative, quantitative and mixed-methods studies in the English or German language that was published between 1999 and 2020. The programmes were analysed according to programme characteristics, case management intervention and the structural and processing conditions. We identified 67 studies dealing with 25 programmes. Approximately half of the programmes were investigated in randomised controlled trials, two programmes used a mixed-methods design and the remaining were the subject of pre-post cohort studies. Participants in the studies were predominantly dyads of people with dementia and their informal caregivers. About half of the programmes reported a theoretical framework. All the programmes were derived from case management approaches or referred to such approaches. Despite huge differences in implementation, all the programmes covered the case management steps. In 14 out of 25 programmes, case management was carried out without additional intervention, the other programmes provided mainly education and training for informal caregivers. Costs of the case management interventions were stated in more than half of the programmes.The effectiveness and generalisability of dementia-specific case management interventions could be enhanced if the framework introduced in the review was used in the future by policy, practice and research.

[Dementia Care Nurse - Feasibility study of outreach assistance for people with dementia and their family carers]. / Dementia Care Nurse.

Dementia Care Nurse - Feasibility study of outreach assistance for people with dementia and their family carers Abstract. Background: Case management for dementia is stipulated in the German national dementia strategy. The effectiveness of case management has been investigated many times, yet the results are heterogeneous. On the contrary, the implementation processes of case management concepts have to date rarely been described or evaluated in detail. Aim: The aim of the project was to analyze the implementation of an outreaching assistance for people with dementia and to explore the changes in care, acceptance, and also facilitators and barriers to the implementation. Methods: Between 08 / 2018 and 07 / 2019, outreaching assistance for people with dementia and their family carers was implemented. Quantitative and qualitative data were prospectively collected using semi-standardised interviews in the context of outreach assistance. Results: A total of 113 people with dementia were included in the study, and for the most part family carers could be involved. On average, eight contacts took place over a period of 74 days. The areas of need and support were diverse. The use of support services increased by 19 % after the end of the intervention. Conclusions: The implementation of continuous and processual support for people with dementia and their carers is possible, whereby the structure and procedure should be transparent. A comprehensive orientation and networking is beneficial. The effectiveness of the intervention remains to be investigated in a controlled study.

Microbiological diagnosis of polymicrobial periprosthetic joint infection revealed superiority of investigated tissue samples compared to sonicate fluid generated from the implant surface.

OBJECTIVES: In the microbiological diagnosis of periprosthetic joint infection (PJI), there is much discussion about the methodology of obtaining proper specimens, the processing technique, and suitable culture media. This retrospective study was conducted to analyse the accuracy of our culture techniques. METHODS: Tissue samples and components from 258 patients after revision arthroplasty of the hip, knee, and shoulder were investigated, and the results of tissue cultures (TC) were compared to those of sonicate fluid cultures (SFC). Furthermore, an evaluation was performed of the influence of different culture media on the detection rate. RESULTS: PJI was confirmed in 186 patients. The overall sensitivity of TC was no different to that of SFC (91.3% vs 90.8%, P = 1). In 153 cases (82.3%), TC and SFC showed concordant positive results. Results were discordant in 33 cases (17.7%). When differentiated according to the type of infection, TC showed significantly better results than SFC in detecting polymicrobial infections (97.0% vs 67.0%, P = 0.004). There were also significant differences between the culture media regarding the yield of microorganisms. CONCLUSIONS: TC was more effective in detecting co-infections. The best results were obtained using both TC and SFC. The choice of culture media has a significant influence on the quality of results.

Membraneless organelles: phasing out of equilibrium.

Over the past years, liquid-liquid phase separation (LLPS) has emerged as a ubiquitous principle of cellular organization implicated in many biological processes ranging from gene expression to cell division. The formation of biological condensates, like the nucleolus or stress granules, by LLPS is at its core a thermodynamic equilibrium process. However, life does not operate at equilibrium, and cells have evolved multiple strategies to keep condensates in a non-equilibrium state. In this review, we discuss how these non-equilibrium drivers counteract solidification and potentially detrimental aggregation, and at the same time enable biological condensates to perform work and control the flux of substrates and information in a spatial and temporal manner.

Die Lebenssituation von Menschen mit Demenz und pflegenden Angehörigen während der Coronavirus-Pandemie Eine qualitative Studie.

The life situation of people with dementia and family carers during the coronavirus pandemic - A qualitative study Abstract. Background: The measures initiated as a result of the coronavirus pandemic have far-reaching consequences for the everyday life of people with dementia and their family carers. Both are usually among those who are the most vulnerable and thus are subject to rigorous restrictions. Their everyday life is made more difficult because care and respite services are currently suspended. In addition, people with dementia have difficulty understanding and implementing the restrictions and hygiene rules. AIMS: This study aims to describe the current life situation of family carers and people with dementia. METHODS: For this purpose, 21 telephone interviews with both family carers and people with dementia have been conducted twice during the spring of 2020 and were subsequently evaluated by a content analysis. RESULTS: The interviewees experienced the situation differently. Especially the social isolation, the higher amount of care, the uncertainty of the situation and the increase in psychological symptoms are described as being stressful. With regard to coping with the situation, discussions are taking place about the support from the social environment, alternative ways of communication, experiences with comparable crises, the stability of formal care and the handling of information. CONCLUSIONS: Family carers and people with dementia feel stressed due to the coronavirus pandemic, but many of them have coping strategies for this special situation. Informal support is a particularly important support mechanism.

Sonicate fluid inoculated into blood culture bottles does not improve diagnosis of periprosthetic joint infection caused by anaerobes. A retrospective analysis.

BACKGROUND: In microbiological diagnosis of periprosthetic joint infection (PJI) there is much controversial discussion about culture media and incubation time, especially if anaerobic bacteria are the causative agents. This retrospective analysis was conducted to compare the results obtained by inoculation of sonicate fluid from prosthetic components into BD Bactec blood culture bottles with those obtained by our culture method using sensitive supplemented growth media. METHODS: Twenty-eight cases were included in this study. For definition of PJI, the criteria of the Musculoskeletal Infection Society (MSIS) were considered. The quantity and time to positivity of anaerobes detected in sonicate fluid were monitored both from inoculated supplemented liver thioglycollate broth and anaerobic blood culture bottles. Furthermore, phenotypic testing was performed on the antimicrobial activity within the sonicate fluid. RESULTS: The most frequently isolated microbes were Cutibacterium species, followed by Finegoldia magna, Parvimonas micra, Robinsoniella peoriensis, Clostridium species, Peptoniphilus harei and Slackia exigua. In 24 cases, the microorganisms became detectable within five days (median time 3.2 days) when sonicate fluid was incubated in supplemented liver thioglycollate broth, regardless of whether the patients had taken antimicrobial agents prior to surgery. However, when sonicate fluid was inoculated into anaerobic Bactec bottles, the median time to positivity was 7.4 days and only 12 cases (43%) were correctly identified. Sixteen cases remained negative after 14 days of incubation. CONCLUSION: Depending on the pathogen, incubation of sonicate fluid using blood culture bottles can support diagnosis of PJI but compared with our culture medium it is less efficient if anaerobes are the suspected cause of infection. Microbiological expertise is therefore indispensable to ensure reliable detection of these microorganisms in PJI until a gold standard for laboratory handling of anaerobes has been established.

[Challenges in dementia care at home - The situation at home of a married couple]. / Herausforderungen bei Demenz in den eigenen vier Wänden.

Challenges in dementia care at home - The situation at home of a married couple Abstract. Background: People with dementia and their relatives are faced with major challenges due to complex dementia symptoms. Families need information and counselling in order to find adequate dementia care services tailored to their needs. AIM: This case report's objective is to exemplify the domestic situation of a married couple who is faced with significant challenges within the family and the care system due to the husband's dementia and Parkinson's disease. METHODS: The Dementia Care Nurse project included case monitoring; by means of different assessments relevant information was recorded and the family's situation described. RESULTS: The family's problems and their need for support were multifaceted and entailed reimbursement of costs, application for care services as well as management of challenging behaviours and reduction of the caregiver's psychosocial burden. CONCLUSIONS: The family, particularly the spouse caregiver, was effectively supported in meeting the challenges of dementia, e. g. by drawing on professional services and sorting out entitlement to benefits. From the perspective of the experience in the project, independent counselling structures such as a case management approach are indispenable in order to stabilise the domestic situation.

DEAD-box ATPases are global regulators of phase-separated organelles.

The ability of proteins and nucleic acids to undergo liquid-liquid phase separation has recently emerged as an important molecular principle of how cells rapidly and reversibly compartmentalize their components into membrane-less organelles such as the nucleolus, processing bodies or stress granules1,2. How the assembly and turnover of these organelles are controlled, and how these biological condensates selectively recruit or release components are poorly understood. Here we show that members of the large and highly abundant family of RNA-dependent DEAD-box ATPases (DDXs)3 are regulators of RNA-containing phase-separated organelles in prokaryotes and eukaryotes. Using in vitro reconstitution and in vivo experiments, we demonstrate that DDXs promote phase separation in their ATP-bound form, whereas ATP hydrolysis induces compartment turnover and release of RNA. This mechanism of membrane-less organelle regulation reveals a principle of cellular organization that is conserved from bacteria to humans. Furthermore, we show that DDXs control RNA flux into and out of phase-separated organelles, and thus propose that a cellular network of dynamic, DDX-controlled compartments establishes biochemical reaction centres that provide cells with spatial and temporal control of various RNA-processing steps, which could regulate the composition and fate of ribonucleoprotein particles.

The selection and definition of indicators in public health monitoring for the 65+ age group in Germany.

Selecting relevant indicators is an important step in the development of public health monitoring for older people. Indicators can be used to combine information comprehensively from various data sources and enable recurring, comparable findings to be made about the health of older people. Indicators were systematically compiled from existing international monitoring systems. An indicator set on health in old age was developed using a multistage, structured consensus-based process together with an interdisciplinary panel of experts. The resulting 18 indicators were assigned to three health areas: (1) environmental factors, (2) activities and participation, and (3) personal factors. Data sources that can be used for the indicators are the health surveys within the framework of the Robert Koch Institute's (RKI) health monitoring system, as well as surveys from other research institutes and official statistics. In the future, the indicator set is to be developed further and integrated into an overall approach that is geared towards health reporting and the monitoring of chronic diseases in all phases of life.

Non-invasive measurement of mRNA decay reveals translation initiation as the major determinant of mRNA stability.

The cytoplasmic abundance of mRNAs is strictly controlled through a balance of production and degradation. Whereas the control of mRNA synthesis through transcription has been well characterized, less is known about the regulation of mRNA turnover, and a consensus model explaining the wide variations in mRNA decay rates remains elusive. Here, we combine non-invasive transcriptome-wide mRNA production and stability measurements with selective and acute perturbations to demonstrate that mRNA degradation is tightly coupled to the regulation of translation, and that a competition between translation initiation and mRNA decay -but not codon optimality or elongation- is the major determinant of mRNA stability in yeast. Our refined measurements also reveal a remarkably dynamic transcriptome with an average mRNA half-life of only 4.8 min - much shorter than previously thought. Furthermore, global mRNA destabilization by inhibition of translation initiation induces a dose-dependent formation of processing bodies in which mRNAs can decay over time.

Individualized support for informal caregivers of people with dementia - effectiveness of the German adaptation of REACH II.

BACKGROUND: Individualized, outreach and structured multicomponent interventions are a promising intervention approach to relieve the burden of informal caregivers of people with dementia. In this study, we adapted and evaluated a multicomponent intervention (Resources for Enhancing Alzheimer's Caregiver Health II, REACH II), which was developed in the USA, to the German health-care system. Therefore the project is called the German adaptation of REACH II (in German: Deutsche Adaptation der REACH II, DE-REACH). METHODS: The effectiveness of DE-REACH was examined in a randomized, controlled trial on 92 informal caregivers of people with dementia. The intervention comprised 12 individual two-weekly sessions (9 at home with the informal caregiver and 3 via telephone) and combined five modules. The reduction of the burden of the informal caregivers was chosen as the primary outcome. RESULTS: The results showed a great stabilizing effect of the intervention on caregiver burden (effect size d = 0.91), that is, comparing pre- and post-measurements the burden decreased very slightly in the intervention group whereas it increased very strongly in the control group. After a three-month follow-up period this effect decreased from a great to a moderate effect. There were also improvements as a result of the intervention in somatization, health-related psychological quality of life and the reaction of the informal caregivers in response to challenging behaviors of the relative with dementia. Moreover, the frequency of challenging behaviors of the affected person itself was reduced in favor of the intervention. CONCLUSION: The findings of this study provide further evidence for the impact of multicomponent support interventions for informal caregivers of people with dementia. CLINICAL TRIAL REGISTRATION: NCT01690117 . Registered September 17, 2012.

Diatrack particle tracking software: Review of applications and performance evaluation.

Object tracking is an instrumental tool supporting studies of cellular trafficking. There are three challenges in object tracking: the identification of targets; the precise determination of their position and boundaries; and the assembly of correct trajectories. This last challenge is particularly relevant when dealing with densely populated images with low signal-to-noise ratios-conditions that are often encountered in applications such as organelle tracking, virus particle tracking or single-molecule imaging. We have developed a set of methods that can handle a wide variety of signal complexities. They are compiled into a free software package called Diatrack. Here we review its main features and utility in a range of applications, providing a survey of the dynamic imaging field together with recommendations for effective use. The performance of our framework is shown to compare favorably to a wide selection of custom-developed algorithms, whether in terms of localization precision, processing speed or correctness of tracks.

Temporal and spatial regulation of mRNA export: Single particle RNA-imaging provides new tools and insights.

The transport of messenger RNAs (mRNAs) from the nucleus to cytoplasm is an essential step in the gene expression program of all eukaryotes. Recent technological advances in the areas of RNA-labeling, microscopy, and sequencing are leading to novel insights about mRNA biogenesis and export. This includes quantitative single molecule imaging (SMI) of RNA molecules in live cells, which is providing knowledge of the spatial and temporal dynamics of the export process. As this information becomes available, it leads to new questions, the reinterpretation of previous findings, and revised models of mRNA export. In this review, we will briefly highlight some of these recent findings and discuss how live cell SMI approaches may be used to further our current understanding of mRNA export and gene expression.

Stem-loop RNA labeling can affect nuclear and cytoplasmic mRNA processing.

The binding of sequence-specific RNA-interacting proteins, such as the bacteriophage MS2 or PP7 coat proteins, to their corresponding target sequences has been extremely useful and widely used to visualize single mRNAs in vivo. However, introduction of MS2 stem-loops into yeast mRNAs has recently been shown to lead to the accumulation of RNA fragments, suggesting that the loops impair mRNA decay. This result was questioned, because fragment occurrence was mainly assessed using ensemble methods, and their cellular localization and its implications had not been addressed on a single transcript level. Here, we demonstrate that the introduction of either MS2 stem-loops (MS2SL) or PP7 stem-loops (PP7SL) can affect the processing and subcellular localization of mRNA. We use single-molecule fluorescence in situ hybridization (smFISH) to determine the localization of three independent mRNAs tagged with the stem-loop labeling systems in glucose-rich and glucose starvation conditions. Transcripts containing MS2SL or PP7SL display aberrant localization in both the nucleus and the cytoplasm. These defects are most prominent in glucose starvation conditions, with nuclear mRNA processing being altered and stem-loop fragments abnormally enriching in processing bodies (PBs). The mislocalization of SL-containing RNAs is independent of the presence of the MS2 or PP7 coat protein (MCP or PCP).

ATPase activity of the DEAD-box protein Dhh1 controls processing body formation.

Translational repression and mRNA degradation are critical mechanisms of posttranscriptional gene regulation that help cells respond to internal and external cues. In response to certain stress conditions, many mRNA decay factors are enriched in processing bodies (PBs), cellular structures involved in degradation and/or storage of mRNAs. Yet, how cells regulate assembly and disassembly of PBs remains poorly understood. Here, we show that in budding yeast, mutations in the DEAD-box ATPase Dhh1 that prevent ATP hydrolysis, or that affect the interaction between Dhh1 and Not1, the central scaffold of the CCR4-NOT complex and an activator of the Dhh1 ATPase, prevent PB disassembly in vivo. Intriguingly, this process can be recapitulated in vitro, since recombinant Dhh1 and RNA, in the presence of ATP, phase-separate into liquid droplets that rapidly dissolve upon addition of Not1. Our results identify the ATPase activity of Dhh1 as a critical regulator of PB formation.