The influence of socioeconomic status and gender on incidence and survival in bladder cancer: a longitudinal study based on the Hamburg Cancer Registry.

BACKGROUND: To investigate the influence of socioeconomic status (SES) and gender on the incidence and survival of patients with bladder cancer on a small scale within the city of Hamburg, Germany. METHODS: Patients documented in the Hamburg Cancer Registry aged ≥ 18 years with primary bladder carcinoma (ICD-10: C67, D09.0), diagnosed in the period 2004-2020 (follow-up until 31.12.2021), and residing in Hamburg were included. The patients were divided into three groups (low, intermediate, and high SES) based on the socioeconomic situation at the district level, defined by the proportion of unemployed individuals, social housing, benefit recipients according to law, etc. Relative survival in the years 2004-2020 was calculated using a period approach. RESULTS: Among the 10,659 patients included, age-standardized 5-year relative survival (5YRS) in 2004-2020 correlated with SES. The age-standardized 5YRS differed significantly between patients with high and intermediate SES vs low SES. Women with low SES had the worst 5YRS at 58.2%, while men with high SES presented the best relative 5YRS at 73.5%. This effect remained after stratification by UICC stages. Concerning incidence, there is an indication that women with low SES were more often diagnosed in higher UICC stages III or IV than women with high SES (18.3% versus 12.6%). CONCLUSIONS: The socioeconomic situation at the time of diagnosis, as well as gender, has a substantial impact on the incidence and cancer survival rates in patients with bladder cancer. Further research, including the study of patient care, is needed to better understand and address these inequalities.

Development of indicators to assess quality and patient pathways in interdisciplinary care for patients with 14 ambulatory-care-sensitive conditions in Germany.

BACKGROUND: In settings like the ambulatory care sector in Germany, where data on the outcomes of interdisciplinary health services provided by multiple office-based physicians are not always readily available, our study aims to develop a set of indicators of health care quality and utilization for 14 groups of ambulatory-care-sensitive conditions based on routine data. These may improve the provision of health care by informing discussions in quality circles and other meetings of networks of physicians who share the same patients. METHODS: Our set of indicators was developed as part of the larger Accountable Care in Deutschland (ACD) project using a pragmatic consensus approach. The six stages of the approach drew upon a review of the literature; the expertise of physicians, health services researchers, and representatives of physician associations and statutory health insurers; and the results of a pilot study with six informal network meetings of office-based physicians who share the same patients. RESULTS: The process resulted in a set of 248 general and disease specific indicators for 14 disease groups. The set provides information on the quality of care provided and on patient pathways, covering patient characteristics, physician visits, ambulatory care processes, pharmaceutical prescriptions and outcome indicators. The disease groups with the most indicators were ischemic heart diseases, diabetes and heart failure. CONCLUSION: Our set of indicators provides useful information on patients' health care use, health care processes and health outcomes for 14 commonly treated groups of ambulatory-care-sensitive conditions. This information can inform discussions in interdisciplinary quality circles in the ambulatory sector and foster patient-centered care.

Improving the continuity and coordination of ambulatory care through feedback and facilitated dialogue-a study protocol for a cluster-randomised trial to evaluate the ACD study (Accountable Care in Germany).

BACKGROUND: Patients in Germany are free to seek care from any office-based physician and can always ask for multiple opinions on a diagnosis or treatment. The high density of physicians and the freedom to choose among them without referrals have led to a need for better coordination between the multiple health professionals treating any given patient. The objectives of this study are to (1) identify informal networks of physicians who treat the same patient population, (2) provide these physicians with feedback on their network and patients, using routine data and (3) give the physicians the opportunity to meet one another in facilitated network meetings. METHODS: The Accountable Care Deutschland (ACD) study is a prospective, non-blinded, cluster-randomised trial comprising a process and economic evaluation of informal networks among 12,525 GPs and office-based specialists and their 1.9 million patients. The units of allocation are the informal networks, which will be randomised either to the intervention (feedback and facilitated meetings) or control group (usual care). The informal networks will be generated by identifying connections between office-based physicians using complete datasets from the Regional Associations of Statutory Health Insurance (SHI) Physicians in Hamburg, Schleswig Holstein, North Rhine and Westphalia Lip, as well as data from three large statutory health insurers in Germany. The physicians will (a) receive feedback on selected indicators of their own treatment activity and that of the colleagues in their network and (b) will be invited to voluntary, facilitated network meetings by their Regional Association of SHI physicians. The primary outcome will be ambulatory-care-sensitive hospitalisations at baseline, at the end of the 2-year intervention period, and at six months and at 12 months after the end of the intervention period. Data will be analysed using the intention-to-treat principle. A pilot study preceded the ACD study. DISCUSSION: Cochrane reviews show that feedback can improve everyday medical practice by shedding light on previously unknown relationships. Providing physicians with information on how they are connected with their colleagues and what the outcomes are of care delivered within their informal networks can help them make these improvements, as well as strengthen their awareness of possible discontinuities in the care they provide. TRIAL REGISTRATION: German Clinical Trials Register DRKS00020884 . Registered on 25 March 2020-retrospectively registered.

RNA structural requirements for the association of the spliceosomal hPrp31 protein with the U4 and U4atac small nuclear ribonucleoproteins.

The kink-turn, a stem I-internal loop-stem II structure of the 5 ' stem-loop of U4 and U4atac small nuclear (sn) RNAs bound by 15.5K protein is required for binding of human Prp31 protein (hPrp31) during U4 and U4atac snRNP assembly. In box C/D snoRNPs a similar kink-turn with bound 15.5K protein is required for selective binding of proteins NOP56 and NOP58. Here we analyzed RNA structural requirements for association of hPrp31 with U4 snRNP in vitro by hydroxyl radical footprinting. hPrp31 induced protection of the terminal penta-loop, as well as of stems I and II flanking the kink-turn. Similar protection was found with U4/U6 snRNA duplex prebound with 15.5K protein. A detailed mutational analysis of the U4 snRNA elements by electrophoretic mobility shift analysis revealed that stem I could not be shortened, although it tolerated sequence alterations. However, introduction of a third Watson-Crick base pair into stem II significantly reduced hPrp31 binding. While stem I of U4atac snRNA showed relaxed binding requirements, its stem II requirements were likewise restricted to two base pairs. In contrast, as shown previously, stem II of the kink-turn motif in box C/D snoRNAs is comprised of three base pairs, and NOP56 and NOP58 require a G-C pair at the central position. This indicates that hPrp31 binding specificity is achieved by the recognition of the two base pair long stem II of the U4 and U4atac snRNAs and suggests how discrimination is achieved by RNA structural elements during assembly of U4/U6 and U4atac/U6atac snRNPs and box C/D snoRNPs.

Protein-protein and protein-RNA contacts both contribute to the 15.5K-mediated assembly of the U4/U6 snRNP and the box C/D snoRNPs.

The k-turn-binding protein 15.5K is unique in that it is essential for the hierarchical assembly of three RNP complexes distinct in both composition and function, namely, the U4/U6 snRNP, the box C/D snoRNP, and the RNP complex assembled on the U3 box B/C motif. 15.5K interacts with the cognate RNAs via an induced fit mechanism, which results in the folding of the surrounding RNA to create a binding site(s) for the RNP-specific proteins. However, it is possible that 15.5K also mediates RNP formation via protein-protein interactions with the complex-specific proteins. To investigate this possibility, we created a series of 15.5K mutations in which the surface properties of the protein had been changed. We assessed their ability to support the formation of the three distinct RNP complexes and found that the formation of each RNP requires a distinct set of regions on the surface of 15.5K. This implies that protein-protein contacts are essential for RNP formation in each complex. Further supporting this idea, direct protein-protein interaction could be observed between hU3-55K and 15.5K. In conclusion, our data suggest that the formation of each RNP involves the direct recognition of specific elements in both 15.5K protein and the specific RNA.