Understanding health care pathways of patients with sepsis: protocol of a mixed-methods analysis of health care utilization, experiences, and needs of patients with and after sepsis.

BACKGROUND: Sepsis is associated with about 20% of deaths worldwide. It often presents with non-specific initial symptoms, making its emergency treatment an interdisciplinary and cross-sectoral challenge. Three in four sepsis survivors suffers from new cognitive, psychological, or physical sequelae for which specific treatment concepts are scarce. The AVENIR project aims to improve the understanding of patient pathways, and subjective care experiences and needs along the entire healthcare pathway before, with and after sepsis. Based on this, concrete recommendations for the organization of care and patient information materials will be developed with close patient participation. METHODS: Mixed-methods study including (1) analysis of anonymized nationwide health claims data from Germany, (2) linkage of health claims data with patient care reports (PCR) of emergency medical services from study regions in two federal states within Germany, and (3) qualitative exploration of the patient, relative, and care provider perspective on sepsis care. In (1), we analyze inpatient and outpatient health care utilization until 30 days pre-sepsis; clinical sepsis care including intra- and inter-hospital transfers; and rehabilitation, inpatient and outpatient aftercare of sepsis survivors as well as costs for health care utilization until 24 months post-sepsis. We attempt to identify survivor classes with similar health care utilization by Latent Class Analyses. In (2), PCR are linked with health claims data to establish a comprehensive database outlining care pathways for sepsis patients from pre-hospital to follow-up. We investigate e.g., whether correct initial assessment is associated with acute (e.g., same-day lethality) and long-term (e.g., new need for care, long-term mortality) outcomes of patients. We compare the performance of sepsis-specific screening tools such as qSOFA, NEWS-2 or PRESEP in the pre-clinical setting. In (3), semi-structured interviews as well as synchronous and asynchronous online focus groups are conducted and analyzed using qualitative content analyses techniques. DISCUSSION: The results of the AVENIR study will contribute to a deeper understanding of sepsis care pathways in Germany. They may serve as a base for improvements and innovations in sepsis care, that in the long-term can contribute to reduce the personal, medical, and societal burden of sepsis and its sepsis sequelae. TRIAL REGISTRATION: Registered at German Clinical Trial Register (ID: DRKS00031302, date of registration: 5th May 2023).

Patient characteristics as predictors of sleep disturbances in multimorbid primary care patients - A secondary analysis.

OBJECTIVE: The aim of the study was to identify patient characteristics (adult attachment, health status, number and severity of chronic conditions, social support) predictive sleep disturbances after 12 months. METHODS: In a secondary analysis of a prospective longitudinal study dealing with adult attachment and self-management, attachment- and health-related characteristics, socio-demographic data at baseline and symptoms of insomnia at the follow up (12 month later) was recorded by 219 patients between the ages of 50 and 85 years with multimorbidity in primary care. Adult attachment was measured by the ECR-RD12. The overall health status was measured using a visual analogue scale (VAS) and a standardized list of chronic conditions. The number and severity of chronic diseases (CIRS-G) was assessed by general practitioners (GPs). Sleep disturbances was measured by the ISI 12 month later. RESULTS: Approximately 19% of the respondents were found to have clinically relevant symptoms of insomnia, and a further 34% to be subclinical insomnia. Attachment-related anxiety, a poorer perceived social support, the number of chronic conditions and a better general health status could predict higher levels of sleep disturbance after 12 month. CONCLUSION: Sleep disorders can play a major role in patients with multimorbidity. Attachment anxiety and lack of social support may also be possible risk factors for the development of sleep disturbances.

RNA-based drug screening using automated RNA purification and real-time RT-PCR1.

A new system has been developed for RNA-based drug screening, and the feasibility of this approach has been demonstrated by the identification of new immunomodulating compounds. Peripheral blood mononuclear cells were chosen as the cellular assay system. Cells were either stimulated by TPA/ionomycin to produce T cell cytokines as asthma targets or stimulated by lipopolysaccharide to produce proinflammatory cytokines as targets for chronic obstructive pulmonary disease (COPD). The authors developed a new fully automated system for RNA purification from cells grown in 96-well plates. Gene expression was determined in 384-well plates using real-time quantitative one-tube RT-PCR. Small interdonor variation could be demonstrated. The assay system was validated with known immunosuppressants cyclosporine and dexamethasone. Screening of 800 compounds resulted in 9.5% compounds inhibiting the induction of at least 1 T cell derived cytokine and 6.8% compounds inhibiting at least 1 cytokine relevant for COPD. All these compounds were retested by analyzing remaining RNA from the 1st round of screening. The reproducibility of hits was between 56% and 74% for different cytokines. One compound selectively inhibited TNF, which was confirmed by IC(50) determination. Analyzing its effect on cells from different donors revealed little interdonor variation. In conclusion, the authors established fully automated RNA isolation and precise gene expression profiling using real-time RT-PCR for drug screening.