Missing nurses cause missed care: is that it? Non-trivial configurations of reasons associated with missed care in Austrian hospitals - a qualitative comparative analysis.

BACKGROUND: Errors of omissions affect the quality of nursing care in hospitals. The Missed Nursing Care Model explains that the reasons for missed care are linked with 1) demand for patient care, 2) labor resource allocation, 3) material resource allocation, and 4) relationship and communication factors. Scientific evidence points to a lack of adequate nursing staffing as the most important factor triggering missed care. However, it remains unclear how the different theoretical reasons for missed care are interlinked with reports on missed care from the perspective of nurses in acute care settings. The aim of this study was to explore non-trivial configurations of reasons for missed care that are associated with missed care interventions from the perspective of nurses working in general units in Austrian hospitals. METHODS: A cross-sectional study was conducted. Data collection was performed using the revised MISSCARE-Austria questionnaire. Our sample consisted of 401 nurses who provided complete data. Data were analyzed using qualitative comparative analysis. Configurational models of contextual factors, reasons for missed care, and missed nursing interventions were analyzed. RESULTS: In our study contextual factors were not consistent precursors of the reasons for missed care. Missed care was consistently present when the demand for patient care was high. A lack of labor resources, in combination with the other known reasons for missed care, was consistently observed when missed care occurred. Different configurations of reasons were found to be non-trivially associated with different types and frequencies of missed care. CONCLUSIONS: To understand the complexity of the causal mechanisms of missed care, complexity theory may be necessary. Accordingly, a theoretical framework that acknowledges that complex systems, such as missed care, are composed of multiple interacting causal components must be further developed to guide new methodical approaches to enlighten its causal mechanisms.

Developing a Cell-Microcarrier Tissue-Engineered Product for Muscle Repair Using a Bioreactor System.

Fecal incontinence, although not life-threatening, has a high impact on the economy and patient quality of life. So far, available treatments are based on both surgical and nonsurgical approaches. These can range from changes in diet, to bowel training, or sacral nerve stimulation, but none of which provides a long-term solution. New regenerative medicine-based therapies are emerging, which aim at regenerating the sphincter muscle and restoring continence. Usually, these consist of the administration of a suspension of expanded skeletal-derived muscle cells (SkMDCs) to the damaged site. However, this strategy often results in a reduced cell viability due to the need for cell harvesting from the expansion platform, as well as the non-native use of a cell suspension to deliver the anchorage-dependent cells. In this study, we propose the proof-of-concept for the bioprocessing of a new cell delivery method for the treatment of fecal incontinence, obtained by a scalable two-step process. First, patient-isolated SkMDCs were expanded using planar static culture systems. Second, by using a single-use PBS-MINI Vertical-Wheel® bioreactor, the expanded SkMDCs were combined with biocompatible and biodegradable (i.e., directly implantable) poly(lactic-co-glycolic acid) microcarriers prepared by thermally induced phase separation. This process allowed for up to 80% efficiency of SkMDCs to attach to the microcarriers. Importantly, SkMDCs were viable during all the process and maintained their myogenic features (e.g., expression of the CD56 marker) after adhesion and culture on the microcarriers. When SkMDC-containing microcarriers were placed on a culture dish, cells were able to migrate from the microcarriers onto the culture surface and differentiate into multinucleated myotubes, which highlights their potential to regenerate the damaged sphincter muscle after administration into the patient. Overall, this study proposes an innovative method to attach SkMDCs to biodegradable microcarriers, which can provide a new treatment for fecal incontinence.

Bioprocessing Considerations towards the Manufacturing of Therapeutic Skeletal and Smooth Muscle Cells.

Tissue engineering approaches within the muscle context represent a promising emerging field to address the current therapeutic challenges related with multiple pathological conditions affecting the muscle compartments, either skeletal muscle or smooth muscle, responsible for involuntary and voluntary contraction, respectively. In this review, several features and parameters involved in the bioprocessing of muscle cells are addressed. The cell isolation process is depicted, depending on the type of tissue (smooth or skeletal muscle), followed by the description of the challenges involving the use of adult donor tissue and the strategies to overcome the hurdles of reaching relevant cell numbers towards a clinical application. Specifically, the use of stem/progenitor cells is highlighted as a source for smooth and skeletal muscle cells towards the development of a cellular product able to maintain the target cell's identity and functionality. Moreover, taking into account the need for a robust and cost-effective bioprocess for cell manufacturing, the combination of muscle cells with biomaterials and the need for scale-up envisioning clinical applications are also approached.

(How) Do We Theorize?: A Focused Mapping Review and Synthesis of Theoretical Nursing Research in the German-Speaking Area.

There are increasing discussions on theory dynamics in nursing research. We aimed at mapping the theoretical publication output by nursing researchers from the European German-speaking area. We conducted a focused mapping review and synthesis, focusing on nursing journals articles with a theory-related aim. We identified 32 eligible publications, reflecting 2% of the nursing journal articles affiliated with researchers from our target region. Twenty-one articles involved an inductive approach. Eleven articles intended to test or revise a theory. The theoretical publication output with a theory-related aim was low. Theory-building efforts were fragmented and mostly without reference to a meta-theoretical level.

External influencing factors on missed care in Austrian hospitals: Testing the theoretical antecedents of missed care using structural equation modelling.

PROBLEM: Missed Nursing Care (MNC) is an error of omission which occurs when a necessary nursing intervention is not initiated, is not completed, or when it is delayed. The MNC model explains this problem and describes four antecedents that can lead to MNC: (1) demand for patient care, (2) available human resources, (3) material resources, and (4) and relationship and communication factors. AIMS: This study aims to test the relationship between the theoretical antecedents of MNC and their impact on MNC. DESIGN: A quantitative cross-sectional study. METHODS: The Austrian version of the revised MISSCARE Survey was completed by nurses working in general hospital units between May and July 2021. Recruitment followed a respondent-driven sample via Austrian nursing education institutions and social media. One thousand six nurses fulfilled inclusion criteria. The structure of the theoretical constructs of the MNC model was tested using a confirmatory factor analysis approach. The relationships between the four antecedents and MNC were explored using structural equation modelling with 427 complete cases. RESULTS: The results support the structural validity of the revised MISSCARE Austria concerning the defined theoretical constructs, although discriminant validity and measurement error should be further investigated. The antecedent "resource allocation: labor" had a statistically significant impact on MNC: The lack of adequate nursing staff played the most important role to explain missed care in our model. CONCLUSION: In our study in Austria, MNC was mostly influenced by a lack of appropriate labor resources. Further studies exploring mediation effects and non-linear relationships may contribute to better understanding of reasons for MNC. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

[Using the TRAPD method to translate the revised MISSCARE Survey from English into German: Revised MISSCARE-Austria]. / Übersetzung des revised MISSCARE Survey zum deutschsprachigen revised MISSCARE-Austria.

Using the TRAPD method to translate the revised MISSCARE Survey from English into German: Revised MISSCARE-Austria Abstract. Background: Questionnaire translations in German-speaking nursing science rely on methods using first- and back-translation techniques despite increasing criticism. In contrast, the TRAPD method is recognized as best practice in intercultural social research. However, experience with the application of this method in German-speaking nursing science is lacking. Aim: To describe the utilization of the TRAPD method using the example of the translation of the revised MISSCARE Survey from English into German and to discuss necessary adaptations, advantages, and limitations of this approach. Methods: An adapted version of the team-based translation method TRAPD was implemented through the steps: preparation, translation, review, adjudication, pretest, and documentation, based on the GESIS guidelines for intercultural questionnaire translation. Results: The new revised MISSCARE Austria instrument consists of 85 items. For the majority of the items, equivalent terms or phrases were found that allowed for a straightforward translation. For some items an adaptation was necessary due to cultural, measurement- and construct-related aspects. Translation equivalence regarding challenging items was examined with the first author and promoted by multiple cognitive pretesting with nurses. Conclusions: Our study strengthens the argument that the TRAPD method is appropriate for translating measurement instruments in German-speaking nursing science. However, this example shows that further experience with this method is necessary for its further development for our discipline.

Patient-Derived Breast Cancer Tissue Cultures for Anti-Endocrine Drug Assays.

Breast cancer is a complex and heterogeneous pathology, characterized by a variety of histological and molecular phenotypes. The majority of the breast cancers express the estrogen receptor alpha (ER), which plays a pivotal role in the pathobiology of the disease and are therefore classified as ER-positive (ER+). In fact, targeting of the ER signaling pathway is the main therapeutic strategy for ER+ breast cancer. Despite the success of endocrine therapy, intrinsic and acquired resistance are reported in 30-50% of the ER+ breast cancers. However, the mechanisms underlying ER heterogeneity and therapeutic resistance are far from being fully disclosed, and efficacious clinical strategies to overcome resistance are still pending. One of the hurdles in studying ER+ breast cancer resistance is related with the scarcity of experimental models that can recapitulate ER heterogeneity and signaling. This is the case of ER+ breast cancer cell models, typically based on cells derived from metastasis, which also fail to recapitulate tumor complexity. Primary cultures of patient-derived breast cancer cells are difficult to establish, and generally characterized by stromal fibroblasts overgrowth and rapid loss of phenotypic and molecular traits of the tumor cells, including ER expression. Ex vivo cultures of breast cancer tissue have been reported to retain the tissue architecture, with preservation of the tumor microenvironment (TME) and ER expression for short periods of time.Given the cumulating evidence on the role of the TME in sustaining ER+ tumor cells, we hypothesized that TME preservation in culture would favor the long-term retention of ER expression and signaling. We employed alginate encapsulation to provide a supporting scaffold to breast cancer tissue microstructures, coupled to dynamic culture to improve the lifespan of the culture by avoiding diffusional limitations. In this chapter, we provide a detailed description of this culture methodology, which has been previously published by our group (Cartaxo et al., J Exp Clin Cancer Res 39:161, 2020), based on electrostatically driven breast cancer tissue encapsulation in alginate, coupled to culture under agitation in a defined culture medium. We also describe challenge of the ex vivo model with an ER activator and inhibitors (anti-endocrine drugs) and a gene expression endpoint of drug response using reverse transcription PCR-based analysis of three distinct genes downstream of ER.

A computational diffusion model to study antibody transport within reconstructed tumor microenvironments.

BACKGROUND: Antibodies revolutionized cancer treatment over the past decades. Despite their successfully application, there are still challenges to overcome to improve efficacy, such as the heterogeneous distribution of antibodies within tumors. Tumor microenvironment features, such as the distribution of tumor and other cell types and the composition of the extracellular matrix may work together to hinder antibodies from reaching the target tumor cells. To understand these interactions, we propose a framework combining in vitro and in silico models. We took advantage of in vitro cancer models previously developed by our group, consisting of tumor cells and fibroblasts co-cultured in 3D within alginate capsules, for reconstruction of tumor microenvironment features. RESULTS: In this work, an experimental-computational framework of antibody transport within alginate capsules was established, assuming a purely diffusive transport, combined with an exponential saturation effect that mimics the saturation of binding sites on the cell surface. Our tumor microenvironment in vitro models were challenged with a fluorescent antibody and its transport recorded using light sheet fluorescence microscopy. Diffusion and saturation parameters of the computational model were adjusted to reproduce the experimental antibody distribution, with root mean square error under 5%. This computational framework is flexible and can simulate different random distributions of tumor microenvironment elements (fibroblasts, cancer cells and collagen fibers) within the capsule. The random distribution algorithm can be tuned to follow the general patterns observed in the experimental models. CONCLUSIONS: We present a computational and microscopy framework to track and simulate antibody transport within the tumor microenvironment that complements the previously established in vitro models platform. This framework paves the way to the development of a valuable tool to study the influence of different components of the tumor microenvironment on antibody transport.

A novel culture method that sustains ERα signaling in human breast cancer tissue microstructures.

BACKGROUND: Estrogen receptor α (ERα) signaling is a defining and driving event in most breast cancers; ERα is detected in malignant epithelial cells of 75% of all breast cancers (classified as ER-positive breast cancer) and, in these cases, ERα targeting is the main therapeutic strategy. However, the biological determinants of ERα heterogeneity and the mechanisms underlying therapeutic resistance are still elusive, hampered by the challenges in developing experimental models recapitulative of intra-tumoral heterogeneity and in which ERα signaling is sustained. Ex vivo cultures of human breast cancer tissue have been proposed to retain the original tissue architecture, epithelial and stromal cell components and ERα. However, loss of cellularity, viability and ERα expression are well-known culture-related phenomena. METHODS: BC samples were collected and brought to the laboratory. Then they were minced, enzymatically digested, entrapped in alginate and cultured for 1 month. The histological architecture, cellular composition and cell proliferation of tissue microstructures were assessed by immunohistochemistry. Cell viability was assessed by measurement of cell metabolic activity and histological evaluation. The presence of ERα was accessed by immunohistochemistry and RT-qPCR and its functionality evaluated by challenge with 17-ß-estradiol and fulvestrant. RESULTS: We describe a strategy based on entrapment of breast cancer tissue microstructures in alginate capsules and their long-term culture under agitation, successfully applied to tissue obtained from 63 breast cancer patients. After 1 month in culture, the architectural features of the encapsulated tissue microstructures were similar to the original patient tumors: epithelial, stromal and endothelial compartments were maintained, with an average of 97% of cell viability compared to day 0. In ERα-positive cases, fibers of collagen, the main extracellular matrix component in vivo, were preserved. ERα expression was at least partially retained at gene and protein levels and response to ERα stimulation and inhibition was observed at the level of downstream targets, demonstrating active ER signaling. CONCLUSIONS: The proposed model system is a new methodology to study ex vivo breast cancer biology, in particular ERα signaling. It is suitable for interrogating the long-term effects of anti-endocrine drugs in a set-up that closely resembles the original tumor microenvironment, with potential application in pre- and co-clinical assays of ERα-positive breast cancer.

Influence of PDLA nanoparticles size on drug release and interaction with cells.

Polymeric nanoparticles (NPs) are strong candidates for the development of systemic and targeted drug delivery applications. Their size is a determinant property since it defines the NP-cell interactions, drug loading capacity, and release kinetics. Herein, poly(d,l-lactic acid) (PDLA) NPs were produced by the nanoprecipitation method, in which the influence of type and concentration of surfactant as well as PDLA concentration were assessed. The adjustment of these parameters allowed the successful production of NPs with defined medium sizes, ranging from 80 to 460 nm. The surface charge of the different NPs populations was consistently negative. Prednisolone was effectively entrapped and released from NPs with statistically different medium sizes (i.e., 80 or 120 nm). Release profiles indicate that these systems were able to deliver appropriate amounts of drug with potential applicability in the treatment of inflammatory conditions. Both NPs populations were cytocompatible with human endothelial and fibroblastic cells, in the range of concentrations tested (0.187-0.784 mg/mL). However, confocal microscopy revealed that within the range of sizes tested in our experiments, NPs presenting a medium size of 120 nm were able to be internalized in endothelial cells. In summary, this study demonstrates the optimization of the processing conditions to obtain PDLA NPs with narrow size ranges, and with promising performance for the treatment of inflammatory diseases. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 482-493, 2019.

Sleep in patients with large pleural effusion: impact of thoracentesis.

PURPOSE: This study aimed to evaluate the sleep quality and impact of thoracentesis on sleep in patients with a large pleural effusion. METHODS: Patients with large unilateral pleural effusion were evaluated by the Pittsburgh Sleep Quality Index (PSQI) questionnaire and dyspnea Borg scale. Full polysomnography (PSG) was performed on the night before and 36 h after thoracentesis. RESULTS: We studied 19 patients, 11 males and 8 females, age 55 ± 18 years and body mass index of 26 ± 5 kg/m(2). The baseline sleep quality was poor (PSQI = 9.1 ± 3.5). Thoracentesis removed 1.624 ± 796 mL of pleural fluid and resulted in a significant decrease in dyspnea Borg scale (2.3 ± 2.1 vs. 0.8 ± 0.9, p < 0.001). The PSG before and after thoracentesis showed no significant change in apnea-hypopnea index and sleep time with oxygen saturation <90%. There was a significant improvement in sleep efficiency (76% vs. 81%, p = 0.006), decrease percent sleep stage 1 (16% vs. 14%, p = 0.002), and a trend improvement in total sleep time (344 ± 92 vs. 380 ± 69 min, p = 0.056) and percentage of rapid eye movement sleep (15% vs. 20%, p = 0.053). No significant changes occurred in six patients that performed two consecutive PSG before thoracentesis. The improvement in sleep quality was not associated with the volume of pleural fluid withdrawn or changes in dyspnea. CONCLUSIONS: Patients with large pleural effusion have poor subjective and objective sleep quality that improves after thoracentesis.

Improvements in the 6-min walk test and spirometry following thoracentesis for symptomatic pleural effusions.

BACKGROUND: Impairment in pulmonary capacity due to pleural effusion compromises daily activity. Removal of fluid improves symptoms, but the impact, especially on exercise capacity, has not been determined. METHODS: Twenty-five patients with unilateral pleural effusion documented by chest radiograph were included. The 6-min walk test, Borg modified dyspnea score, FVC, and FEV(1) were analyzed before and 48 h after the removal of large pleural effusions. RESULTS: The mean fluid removed was 1,564 ± 695 mL. After the procedure, values of FVC, FEV(1), and 6-min walk distance increased (P < .001), whereas dyspnea decreased (P < .001). Statistical correlations (P < .001) between 6-min walk distance and FVC (r = 0.725) and between 6-min walk distance and FEV(1) (r = 0.661) were observed. Correlations also were observed between the deltas (prethoracentesis × postthoracentesis) of the 6-min walk test and the percentage of FVC (r = 0.450) and of FEV(1) (r = 0.472) divided by the volume of fluid removed (P < .05). CONCLUSION: In addition to the improvement in lung function after thoracentesis, the benefits of fluid removal are more evident in situations of exertion, allowing better readaptation of patients to routine activities.