Applying Value Stream Mapping to Improve the Delivery of Patient Care in the Oncology Day Hospital.

Improving the delivery of patient care is an ongoing challenge in the National Health Service (NHS). This challenge is not insignificant in the process of chemotherapy administration for oncology patients. The present research is motivated by a public Spanish hospital in which oncology patients receive medical care in the Oncology Day Hospital (ODH). At the ODH, oncology patients receive different health services by different specialists on a single day. Any discoordination in patient flow will contribute to longer waiting times and stays in the ODH. As oncology patients tend to have special health conditions, any extra time in the hospital is a source of risk and discomfort. This study applies value stream mapping methodology in a Spanish ODH to improve this situation, reducing hospital waiting times and shorting the length of stay. For that purpose, the path of the oncology patients is mapped and the current state of the system is analyzed. Working at takt time and levelling the workload are proposed for improving the working conditions for healthcare personnel. As a result, the quality of service for oncology patients who need a well-defined care profile is improved. The singular characteristics of the Spanish NHS make it challenging to implement new ways of working, so this study has significant theoretical and managerial implications offering directions in which improvement is possible.

Three-dimensional numerical analysis as a tool for optimization of acoustophoretic separation in polymeric chips.

Polymeric separators have been developed since 2010 to produce acoustophoretic separation of particles or cells in suspension with high efficiency. They rely on three-dimensional (3D) resonances of their whole structure actuated by ultrasounds. In this paper, a numerical 3D analysis is presented and validated as the only tool for optimization of these polymeric chips to perform efficient separation applications. In contrast to conventional acoustophoretic techniques based on the establishment of standing waves in the liquid phase of the channel (requiring rigid chip materials, such as silicon or glass), whole-structure resonances of the chip allow the use of materials that are acoustically soft and of low acoustic impedance, which is close to that of the liquid samples hosted. The resonance requirement is not restricted to the liquid phase in the polymeric chips, but it extends to the 3D whole structure, allowing any material. It provides significant advantages in the design and manufacture of our chips, allowing the use of low-cost materials and cheap manufacturing processes and even printing of devices. The extraordinary complexity of their multiple resonances requires theoretical approaches to optimize their acoustophoretic performance. Hence, the importance of 3D numerical analyses, which are capable of predicting the acoustic behavior of these chips, is to perform acoustophretica separation in suspensions.

The Role of Value Stream Mapping in Healthcare Services: A Scoping Review.

Lean healthcare aims to manage and improve the processes in the healthcare sector by eliminating everything that adds no value by improving quality of services, ensuring patient safety and facilitating health professionals' work to achieve a flexible and reliable organization. Value Stream Mapping (VSM) is considered the starting point of any lean implementation. Some papers report applications of VSM in healthcare services, but there has been less attention paid to their contribution on sustainability indicators. The purpose of this work is to analyze the role of VSM in this context. To do so, a scoping review of works from recent years (2015 to 2019) was done. The results show that most applications of VSM reported are in the tertiary level of care, and the United States of America (USA) is the country which leads most of the applications published. In relation with the development of VSM, a heterogeneity in the maps and the sustainability indicators is remarkable. Moreover, only operational and social sustainability indicators are commonly included. We can conclude that more standardization is required in the development of the VSM in the healthcare sector, also including the environmental indicators.

Long-Term Human Hematopoietic Stem Cell Culture in Microdroplets.

We previously reported a new approach for micromanipulation and encapsulation of human stem cells using a droplet-based microfluidic device. This approach demonstrated the possibility of encapsulating and culturing difficult-to-preserve primary human hematopoietic stem cells using an engineered double-layered bead composed by an inner layer of alginate and an outer layer of Puramatrix. We also demonstrated the maintenance and expansion of Multiple Myeloma cells in this construction. Here, the presented microfluidic technique is applied to construct a 3D biomimetic model to recapitulate the human hematopoietic stem cell niche using double-layered hydrogel beads cultured in 10% FBS culture medium. In this model, the long-term maintenance of the number of cells and expansion of hHSCS encapsulated in the proposed structures was observed. Additionally, a phenotypic characterization of the human hematopoietic stem cells generated in the presented biomimetic model was performed in order to assess their long-term stemness maintenance. Results indicate that the ex vivo cultured human CD34+ cells from bone marrow were viable, maintained, and expanded over a time span of eight weeks. This novel long-term stem cell culture methodology could represent a novel breakthrough to improve Hematopoietic Progenitor cell Transplant (HPT) as well as a novel tool for further study of the biochemical and biophysical factors influencing stem cell behavior. This technology opens a myriad of new applications as a universal stem cell niche model potentially able to expand other types of cells.

Influence of Hydrodynamics and Hematocrit on Ultrasound-Induced Blood Plasmapheresis.

Acoustophoretic blood plasma separation is based on cell enrichment processes driven by acoustic radiation forces. The combined influence of hematocrit and hydrodynamics has not yet been quantified in the literature for these processes acoustically induced on blood. In this paper, we present an experimental study of blood samples exposed to ultrasonic standing waves at different hematocrit percentages and hydrodynamic conditions, in order to enlighten their individual influence on the acoustic response of the samples. The experiments were performed in a glass capillary (700 µm-square cross section) actuated by a piezoelectric ceramic at a frequency of 1.153 MHz, hosting 2D orthogonal half-wavelength resonances transverse to the channel length, with a single-pressure-node along its central axis. Different hematocrit percentages Hct = 2.25%, 4.50%, 9.00%, and 22.50%, were tested at eight flow rate conditions of Q = 0:80 µL/min. Cells were collected along the central axis driven by the acoustic radiation force, releasing plasma progressively free of cells. The study shows an optimal performance in a flow rate interval between 20 and 80 µL/min for low hematocrit percentages Hct ≤ 9.0%, which required very short times close to 10 s to achieve cell-free plasma in percentages over 90%. This study opens new lines for low-cost personalized blood diagnosis.

Droplet Microfluidics for the ex Vivo Expansion of Human Primary Multiple Myeloma Cells.

We previously reported a new approach for micromanipulation and encapsulation of human stem cells using a droplet-based microfluidic device We demonstrated the possibility of encapsulating and culturing difficult-to-preserve primary human hematopoietic stem cells using an engineered double layered bead composed by an inner layer of alginate and an outer layer of puramatrix constructed using a soft technology without the use of any external force. In this work, we use this micro manipulation technique to build a 3D scaffold as a biomimetic model to recapitulate the niche of patient-derived multiple myeloma cells (MM cell) using a multilayered 3D tissue scaffold constructed in a microfluidic device and cultured in 10% FBS culture medium. In the current study, we included the use of this biomimetic model comprising supporting human Mesenchymal stem cells to show the mid-term survival of MM cells in the proposed structures. We found that the generated microniches were suitable for the maintenance of MM cells with and without supporting cells. Additionally, cultured MM cells in droplets were exposed to both Bortezomib and Lenalidomide to test their toxicity in the cultured patient derived cells. Results indicate that the maintained MM cells were consistently responding to the applied medication, opening a wide field of possibilities to use the presented micro device as an ex vivo platform for drug screening.

A microfluidic device for self-synchronised production of droplets.

The primary requirement for a mixing operation in droplet-based microfluidic devices is an accurate pairing of droplets of reaction fluids over an extended period of time. In this paper, a novel device for self-synchronous production of droplets has been demonstrated. The device uses a change in impedance across a pair of electrodes introduced due to the passage of a pre-formed droplet to generate a second droplet at a second pair of electrodes. The device was characterised using image analysis. Droplets with a volume of ~23.5 ± 3.1 nl (i.e.~93% of the volume of pre-formed droplets) were produced on applying a voltage of 500 V. The synchronisation efficiency of the device was 83%. As the device enables self-synchronised production of droplets, it has a potential to increase the reliability and robustness of mixing operations in droplet-based microfluidic devices.

Comparación de citocinas plasmáticas en pacientes con neumonía adquirida en la comunidad con y sin diagnóstico previo de EPOC por una técnica multiplex / Comparison of plasma cytokines using a multiplex technique in patients with community acquired pneumonia with or without COPD

La enfermedad pulmonar obstructiva crónica (EPOC) se asocia con una mayor mortalidad en pacientes con neumonía adquirida en la comunidad (NAC). En este trabajo se comparan los valores plasmáticos de 9 citocinas en 10 pacientes ingresados en nuestro hospital por NAC diagnosticados previamente de EPOC y 10 pacientes también ingresados por NAC pero sin EPOC. Para ello se utilizó el equipo Th1/Th2 para deteccio´n mu´ltiple de citocinas de Biorad sobre una plataforma Luminex. Al ingreso, los pacientes con EPOC mostraron unos valores significativamente menores de interleucina-2, GM-CSF e IFN-γ que los pacientes sin EPOC. Estos mediadores contribuyen en gran manera a la inmunidad adaptativa y a la activación de linfocitos T, por lo que su menor concentración en plasma sugiere la existencia de una respuesta inmune empeorada en los pacientes con EPOC que presentan una NAC. Esta respuesta empeorada podría contribuir a explicar el aumento de mortalidad en estos pacientes. Nuestros resultados muestran también la utilidad de las técnicas multiplex para la detección simultánea de varios mediadores en la misma muestra en estudios de investigación clínica(AU)

Chronic obstructive pulmonary disease (COPD) is associated with increased mortality in patients with community acquired pneumonia (CAP). In this work we have compared the plasma levels of 9 cytokines in 10 patients admitted to our hospital with CAP and a previous diagnosis of COPD against the levels of 10 patients with CAP and no COPD. For this we used the Biorad TM Th1/Th2 kit for multiple detection of cytokines on a Luminex platform. At admission, patients with COPD showed significantly lower levels of IL-2, GM-CSF and IFN-γ than patients with no COPD. These mediators are key contributors to adaptive immunity and to T cell activation. As a result, their concentration in plasma suggests an impaired immune response in those patients with COPD suffering from CAP. This impaired response could help to explain the increased mortality observed in these patients. Our results also show the usefulness of multiplex methods for simultaneous detection of several mediators in the same sample in clinical research studies(AU)