Protocol: Value Stream Maping in Healthcare. A systematic literature review

[EN] Until 2016, very few works had investigated the use of the VSM. With this research, we will discover if the situation has changed in the last 3 years. In the lean manufacturing context, different techniques that help the continuous improvement process can be used (MarinGarcia & Bonavia, 2011; Marin-Garcia & Carneiro, 2010; Marin-Garcia et al., 2012; Scott, 2001). One is the Value Stream Map (VSM) (Coetzee et al., 2016; Marin-Garcia & Mateo Martínez, 2013; Vidal-Carreras et al., 2015). This publication is a protocol (MarinGarcia, 2015; Marin-Garcia, 2019) that aims to promote research transparency and replication. The concepts investigated in it are defined (VSM and health services sector), a research niche is justified, and the search and codification procedure of the systematic literature review is established. Although there are different versions of the VSM (DinisCarvalho et al., 2018; Hines & Rich, 1997; Shou et al., 2017), we will focus on that proposed by Rother and Shook (1998). The main peculiarity of the version by Rother and Shook (1998) is that it graphically shows the flow of information and the flow of materials in the same diagram (Lucherini & Rapaccini, 2017; Shou et al., 2017; Vidal-Carreras et al., 2015), which is necessary to complete a project, a product or a service (Bevilacqua et al., 2014; Lucherini & Rapaccini, 2017). It is also very intuitive and easy to understand, even by non-technical people (Lucherini & Rapaccini, 2017). The VSM version that we have chosen is usually applied via standardized symbols (Lucherini & Rapaccini, 2017; Vidal-Carreras et al., 2015) following a 4-stage procedure (Rother & Shook, 1998; Shou et al., 2017): 1) select a product family (each VSM represents a family of sufficiently homogeneous products to represent the process); 2) draw the current VSM; 3) model the improved process by drawing the desirable future VSM; 4) implement actions to obtain a similar process to the future VSM. These four stages can be split into eight in other implementation versions (Tapping, 2007; Tapping et al., 2002; Tapping & Shuker, 2003). The above procedure allows value-added (VA) and nonvalueadded (NVA) activities and initiating actions to be identified to improve the proportion of VA versus NVA (Bevilacqua et al., 2014; Shou et al., 2017; Vidal-Carreras et al., 2015). Our goal is to include any healthcare level (primary care, secondary care - medical specialists, hospitals, referral centers for rare diseases, and geriatric or disability care). We wish to explore the use in organizations of any country worldwide whose ownership is public, private or a nonprofit foundation. We will focus on patient health services. We will not include the pharmaceutical industry or the operation of governmental or nongovernmental public health structures (e.g. ministries, the Red Cross or similar). Different literature reviews on the VSM have been published. Some focus on analyzing several sectors, predominantly manufacturing. Previous research seems to indicate that the VSM allows the transparency of the process to improve by making it much more understandable for the agents involved in it (Shou et al., 2017; Vidal-Carreras et al., 2015); reduce process times (lead times) (Shou et al., 2017) and inventories (Shou et al., 2017). However, these results come mostly from repetitive manufacturing contexts (linked to the automotive or consumer electronics sectors, or their auxiliary industries), and normally from Anglo-Saxon countries. There do not seem to be enough publications in order to generalize these results to all kinds of contexts. Some publications reveal that the barriers from using such tools can overcome facilitators in public service contexts (MarinGarcia et al., 2018b). Very few reviews have focused specifically on the VSM and the health services sector (Nowak et al., 2017; Vidal-Carreras et al., 2015). Both conclude that there is not enough material to provide evidence for and a conclusive answer to our research questions. The systematic review that we propose in this protocol intends to answer (in a future publication) the following questions: 1) what is the VSM research gap that applies to the health services sector that currently exists?; 2) is the VSM being used in hospitals or other health centers?; 3) what VSM version is common in health sector publications?; 4) collect examples of the VSM in hospitals/heath centers; 5) how was the VSM used in the hospitals/health centers that have applied it?; 6) what problems and/or difficulties have arisen while drawing the VSM or after drawing it? Different programs will be used for the bibliometric analysis (see details in Marin-Garcia and Alfalla-Luque (2019)). First, the R Bibliometrix package (Aria & Cuccurullo, 2017; Garfield, 2004; Wulff Barreiro, 2007) and also the suitability of SciMAT (Cobo et al., 2012; Santana & Lopez-Cabrales, 2019) to visualize thematic maps and strategic maps will be tested.Marín García, JA.; Vidal Carreras, PI.; García Sabater, JJ.; Escribano-Martinez, J. (2019). Protocol: Value Stream Maping in Healthcare. A systematic literature review. WPOM-Working Papers on Operations Management. 10(2):36-54. https://doi.org/10.4995/wpom.v10i2.12297OJS3654102Ahluwalia, S. C., Damberg, C. L., Silverman, M., Motala, A., & Shekelle, P. G. (2017). What defines a high-performing health care delivery system: A systematic review. The Joint Commission Journal on Quality and Patient Safety, 43(9), 450-459. https://doi.org/10.1016/j.jcjq.2017.03.010Aloini, D., Cannavacciuolo, L., Gitto, S., Lettieri, E., Malighetti, P., & Visintin, F. (2018). Evidence-based management for performance improvement in healthcare. Management Decision, 56(10), 2063-2068. https://doi.org/10.1108/MD-10-2018-004Andreu Andres, M. A., Garcia-Carbonell, A., González-Ladrón-de-Guevara, F., & Watts, F. (2018). Contrasting innovation competence fincoda model in software engineering: Narrative review. Journal of Industrial Engineering and Management, 11(4), 715-734. https://doi.org/10.3926/jiem.2656Aria, M., & Cuccurullo, C. (2017). Bibliometrix: An r-tool for comprehensive science mapping analysis. Journal of Informetrics, 11(4), 959-975. https://doi.org/10.1016/j.joi.2017.08.007Bevilacqua, M., Ciarapica, F. E., Germani, M., Mazzuto, G., & Paciarotti, C. (2014). Relation of project managers' personality and project performance: An approach based on value stream mapping. Journal of Industrial Engineering and Management, 7(4), 34. https://doi.org/10.3926/jiem.1005Borenstein, M., Hedges, L. V., Higgins, J. P. T., & Rothstein, H. R. (2009). Introduction to meta-analysis. UK: John Wiley & Sons. https://doi.org/10.1002/9780470743386Cobo, M. J., López-Herrera, A. G., Herrera-Viedma, E., & Herrera, F. (2012). Scimat: A new science mapping analysis software tool. Journal of the American Society for Information Science and Technology, 63(8), 1609-1630. https://doi.org/10.1002/asi.22688Coetzee, R., van der Merwe, K., & van Dyk, L. (2016). Lean implementation strategies: How are the toyota way principles addressed? South African Journal of Industrial Engineering, 27(3), 79-91. https://doi.org/10.7166/27-3-1641Cringles, M. C. (2002). Developing an integrated care pathway to manage cancer pain across primary, secondary and tertiary care. International Journal of Palliative Nursing, 8(5), 247-255. https://doi.org/10.12968/ijpn.2002.8.5.10372De Steur, H., Wesana, J., Dora, M. K., Pearce, D., & Gellynck, X. (2016). Applying value stream mapping to reduce food losses and wastes in supply chains: A systematic review. Waste Management, 58, 359-368. https://doi.org/10.1016/j.wasman.2016.08.025Dinis-Carvalho, J., Guimaraes, L., Sousa, R. M., & Leao, C. P. (2018). Waste identification diagram and value stream mapping: A comparative analysis. International Journal of Lean Six Sigma. https://doi.org/10.1108/IJLSS-04-2017-0030Dogan, N. O., & Unutulmaz, O. (2016). Lean production in healthcare: A simulation-based value stream mapping in the physical therapy and rehabilitation department of a public hospital. Total Quality Management & Business Excellence, 27(1-2), 64-80. https://doi.org/10.1080/14783363.2014.945312Fadahunsi, K. P., Akinlua, J. T., O'Connor, S., Wark, P. A., Gallagher, J., Carroll, C., . . . O'Donoghue, J. (2019). Protocol for a systematic review and qualitative synthesis of information quality frameworks in ehealth. Bmj Open, 9(3). https://doi.org/10.1136/bmjopen-2018-024722Garfield, E. (2004). Historiographic mapping of knowledge domains literature. 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The seven value stream mapping tools. International Journal of Operations and Production Management, 17(1), 46-64. https://doi.org/10.1108/01443579710157989Knight, C., Patterson, M., & Dawson, J. (2019). Work engagement interventions can be effective: A systematic review. European Journal of Work and Organizational Psychology, 28(3), 348-372. https://doi.org/10.1080/1359432X.2019.1588887Losilla, J.-M., Oliveras, I., Marin-Garcia, J. A., & Vives, J. (2018). Three risk of bias tools lead to opposite conclusions in observational research synthesis. Journal of Clinical Epidemiology(101), 61-72. https://doi.org/10.1016/j.jclinepi.2018.05.021Lucherini, F., & Rapaccini, M. (2017). Exploring the impact of lean manufacturing on flexibility in smes. Journal of Industrial Engineering and Management, 10(5), 27. https://doi.org/10.3926/jiem.2119Lummus, R. R., Vokurka, R. J., & Rodeghiero, B. (2006). Improving quality through value stream mapping: A case study of a physician's clinic. Total Quality Management and Business Excellence, 17(8), 1063-1075. https://doi.org/10.1080/14783360600748091Makwana, A. D., & Patange, G. S. (2019). A methodical literature review on application of lean & six sigma in various industries. Australian Journal of Mechanical Engineering. https://doi.org/10.1080/14484846.2019.1585225Marin-Garcia, J. A. (2015). Publishing in two phases for focused research by means of "research collaborations". WPOM-Working Papers on Operations Management, 6(2), 76-80. https://doi.org/10.4995/wpom.v6i2.4459Marin-Garcia, J. A. (2016). Upvx-mooc course: Research methodologies-systematic literature review https://www.upvx.es/courses/course-v1:ManagementEducation+researchmethodologies+2016-01/about: UPVx Formación Online. Universitat Politécnica de ValenciaMarin-Garcia, J. A. (2019). Publishing in three stages to support evidence based practice in om, hrm and teaching&learning innovation. WPOM-Working Papers on Operations Management, 10(2), in press.Marin-Garcia, J. A., & Alfalla-Luque, R. (2019). Protocol: How to deal with partial least squares (pls) research in operations management. A guide for sending papers to academic journals. WPOM-Working Papers on Operations Management, 10(1), 29-69. https://doi.org/10.4995/wpom.v10i1.10802Marin-Garcia, J. A., Betancour, E., & Giraldo-OMeara, M. (2018a). Protocol: Literature review on the psychometric properties of the short versions of the scales of social desirability in the answers to competency self-assessment questionnaires. WPOM-Working Papers on Operations Management, 9(1), 14-29. https://doi.org/10.4995/wpom.v9i1.9172Marin-Garcia, J. A., & Bonavia, T. (2011). Strategic priorities and lean manufacturing practices in automotive suppliers. Ten years after. In M. Chiaberge (Ed.), New trends and developments in automotive engineering: InTechMarin-Garcia, J. A., & Carneiro, P. (2010). Desarrollo y validación de un modelo multidimensional de la producción ajustada. Intangible Capital, 6(1), 78-127. https://doi.org/10.3926/ic.2010.v6n1.p78-127Marin-Garcia, J. A., Carneiro, P., & Miralles, C. (2012). Effect of lean manufacturing practices on non-financial performance results: Empirical study in spanish sheltered work centers. In G. Mejia & N. Velasco (Eds.), Production systems and supply chain management in emerging countries: Best practices (pp. 3-24): Springer. https://doi.org/10.1007/978-3-642-26004-9_1Marin-Garcia, J. A., Garcia-Sabater, J. J., & Maheut, J. (2018b). Protocol: Action planning for action research about kaizen in public organizations. The case of higher education. WPOM-Working Papers on Operations Management, 9(1), 13. https://doi.org/10.4995/wpom.v9i1.8990Marin-Garcia, J. A., & Martinez Tomas, J. (2016). Deconstructing amo framework: A systematic review. Intangible Capital, 12(4), 1040-1087. https://doi.org/10.3926/ic.838Marin-Garcia, J. A., & Mateo Martínez, R. (2013). Barreras y facilitadores de la implantación del tpm. Intangible Capital, 9(3), 823-853. https://doi.org/10.3926/ic.360Martinez-Tomas, J., & Marin-Garcia, J. A. (2019). Protocol: What does the wage structure depend on? Evidence from the ine salary national survey (pilot study with 2006 data). WPOM-Working Papers on Operations Management, 10(1), 70-103. https://doi.org/10.4995/wpom.v10i1.11753Martínez Jurado, P. J., & Moyano Fuentes, J. (2017). Aprendiendo a enseñar lean management mediante juegos: Revisión sistemática de la literatura learning to teach lean management through games: Systematic literature review. WPOM-Working Papers on Operations Management, 8, 164-170. https://doi.org/10.4995/wpom.v8i0.7199Medina-López, C., Marin-Garcia, J. A., & Alfalla-Luque, R. (2010). Una propuesta metodológica para la realización de búsquedas sistemáticas de bibliografía (a methodological proposal for the systematic literature review). WPOM-Working Papers on Operations Management, 1(2), 13-30. https://doi.org/10.4995/wpom.v1i2.786Nowak, M., Pfaff, H., & Karbach, U. (2017). Does value stream mapping affect the structure, process, and outcome quality in care facilities? A systematic review. Systematic Reviews, 6, 11. https://doi.org/10.1186/s13643-017-0563-yPatterson, M., Rick, J., Wood, S., Carroll, C., Balain, S., & Booth, A. (2010). Systematic review of the links between human resource management practices and performance: Health Technology Assessment, 14 (51). https://doi.org/10.3310/hta14510Poksinska, B. (2010). The current state of lean implementation in health care: Literature review. Quality Management in Health Care, 19(4), 319-329. https://doi.org/10.1097/QMH.0b013e3181fa07bbPrajogo, D. I., & McDermott, C. M. (2008). The relationships between operations strategies and operations activities in service context. International Journal of Service Industry Management, 19(4), 506-520. https://doi.org/10.1108/09564230810891932Rafique, M. Z., Ab Rahman, M. N., Saibani, N., & Arsad, N. (2019). A systematic review of lean implementation approaches: A proposed technology combined lean implementation framework. Total Quality Management & Business Excellence, 30(3-4), 386-421. https://doi.org/10.1080/14783363.2017.1308818Reijula, J., Nevala, N., Lahtinen, M., Ruohom Aki, V., & Reijula, K. (2014). Lean design improves both health-care facilities and processes: A literature review. Intelligent Buildings International, 6(3), 170-185. https://doi.org/10.1080/17508975.2014.901904Romero, L. F., & Arce, A. (2017). Applying value stream mapping in manufacturing: A systematic literature review. IFAC-PapersOnLine, 50(1), 1075-1086. https://doi.org/10.1016/j.ifacol.2017.08.385Rother, M., & Shook, J. (1998). Learning to see. Value stream mapping to create value and eliminate muda. 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Cellular and humoral immunogenicity of the mRNA-1273 SARS-CoV-2 vaccine in patients with hematologic malignancies

Recent studies have shown a suboptimal humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in patients diagnosed with hematologic malignancies; however, data about cellular immunogenicity are scarce. The aim of this study was to evaluate both the humoral and cellular immunogenicity 1 month after the second dose of the mRNA-1273 vaccine. Antibody titers were measured by using the Elecsys and LIAISON anti–SARS-CoV-2 S assays, and T-cell response was assessed by using interferon-γ release immunoassay technology. Overall, 76.3% (184 of 241) of patients developed humoral immunity, and the cellular response rate was 79% (184 of 233). Hypogammaglobulinemia, lymphopenia, active hematologic treatment, and anti-CD20 therapy during the previous 6 months were associated with an inferior humoral response. Conversely, age >65 years, active disease, lymphopenia, and immunosuppressive treatment of graft-versus-host disease (GVHD) were associated with an impaired cellular response. A significant dissociation between the humoral and cellular responses was observed in patients treated with anti-CD20 therapy (the humoral response was 17.5%, whereas the cellular response was 71.1%). In these patients, B-cell aplasia was confirmed while T-cell counts were preserved. In contrast, humoral response was observed in 77.3% of patients undergoing immunosuppressive treatment of GVHD, whereas only 52.4% had a cellular response. The cellular and humoral responses to the SARS-CoV-2 mRNA-1273 vaccine in patients with hematologic malignancies are highly influenced by the presence of treatments such as anti-CD20 therapy and immunosuppressive agents. This observation has implications for the further management of these patients.The authors also thank the Cellex Foundation for providing research facilities and equipment and the CERCA Programme/Generalitat de Catalunya for institutional support

Evolution of Quality of Life and Treatment Adherence after One Year of Intermittent Bladder Catheterisation in Functional Urology Unit Patients

Objective: To determine patient difficulties and concerns when performing IBC (Intermittent Bladder Catheterisation), as well as the evolution of adherence, quality of life, and emotional state of patients one year after starting IBC. Method: A prospective, observational, multicentre study conducted in 20 Spanish hospitals with a one-year follow-up. Data sources were patient records and the King's Health Questionnaire on quality of life, the Mini-Mental State Examination (MMSE), and the Hospital Anxiety and Depression Scale (HADS). Perceived adherence was measured using the ICAS (Intermittent Catheterization Adherence Scale) and perceived difficulties with IBC were assessed using the ICDQ (Intermittent Catheterization Difficulty Questionnaire). For data analysis, descriptive and bivariate statistics were performed for paired data at three points in time (T1: one month, T2: three months, T3: one year). Results: A total of 134 subjects initially participated in the study (T0), becoming 104 subjects at T1, 91 at T2, and 88 at T3, with a mean age of 39 years (standard deviation = 22.16 years). Actual IBC adherence ranged from 84.8% at T1 to 84.1% at T3. After one year of follow-up, a statistically significant improvement in quality of life (p <= 0.05) was observed in all dimensions with the exception of personal relationships. However, there were no changes in the levels of anxiety (p = 0.190) or depression (p = 0.682) at T3 compared to T0. Conclusions: Patients requiring IBC exhibit good treatment adherence, with a significant proportion of them performing self-catheterisation. After one year of IBC, a significant improvement in quality of life was noted, albeit with a significant impact on their daily lives and their personal and social relationships. Patient support programmes could be implemented to improve their ability to cope with difficulties and thus enhance both their quality of life and the maintenance of their adherence

New GOLD classification: longitudinal data on group assignment

Rationale: Little is known about the longitudinal changes associated with using the 2013 update of the multidimensional GOLD strategy for chronic obstructive pulmonary disease (COPD). Objective: To determine the COPD patient distribution of the new GOLD proposal and evaluate how this classification changes over one year compared with the previous GOLD staging based on spirometry only. Methods: We analyzed data from the CHAIN study, a multicenter observational Spanish cohort of COPD patients who are monitored annually. Categories were defined according to the proposed GOLD: FEV1%, mMRC dyspnea, COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and exacerbations-hospitalizations. One-year follow-up information was available for all variables except CCQ data. Results: At baseline, 828 stable COPD patients were evaluated. On the basis of mMRC dyspnea versus CAT, the patients were distributed as follows: 38.2% vs. 27.2% in group A, 17.6% vs. 28.3% in group B, 15.8% vs. 12.9% in group C, and 28.4% vs. 31.6% in group D. Information was available for 526 patients at one year: 64.2% of patients remained in the same group but groups C and D show different degrees of variability. The annual progression by group was mainly associated with one-year changes in CAT scores (RR, 1.138; 95%CI: 1.074-1.206) and BODE index values (RR, 2.012; 95%CI: 1.487-2.722). Conclusions: In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment. A change in category after one year was associated with longitudinal changes in the CAT and BODE index

Targeting NAE1-mediated protein hyper-NEDDylation halts cholangiocarcinogenesis and impacts on tumor-stroma crosstalk in experimental models.

[EN] BACKGROUND & AIMS: Cholangiocarcinoma (CCA) comprises a heterogeneous group of malignant tumors associated with dismal prognosis. Alterations in post-translational modifications (PTMs), including NEDDylation, result in abnormal protein dynamics, cell disturbances and disease. Herein, we investigate the role of NEDDylation in CCA development and progression. METHODS: Levels and functions of NEDDylation, together with response to pevonedistat (NEDDylation inhibitor) or CRISPR/Cas9 against NAE1 were evaluated invitro, invivo and/or in patients with CCA. The development of preneoplastic lesions in Nae1+/- mice was investigated using an oncogene-driven CCA model. The impact of NEDDylation in CCA cells on tumor-stroma crosstalk was assessed using CCA-derived cancer-associated fibroblasts (CAFs). Proteomic analyses were carried out by mass-spectrometry. RESULTS: The NEDDylation machinery was found overexpressed and overactivated in human CCA cells and tumors. Most NEDDylated proteins found upregulated in CCA cells, after NEDD8-immunoprecipitation and further proteomics, participate in the cell cycle, proliferation or survival. Genetic (CRISPR/Cas9-NAE1) and pharmacological (pevonedistat) inhibition of NEDDylation reduced CCA cell proliferation and impeded colony formation invitro. NEDDylation depletion (pevonedistat or Nae1+/- mice) halted tumorigenesis in subcutaneous, orthotopic, and oncogene-driven models of CCA invivo. Moreover, pevonedistat potentiated chemotherapy-induced cell death in CCA cells invitro. Mechanistically, impaired NEDDylation triggered the accumulation of both cullin RING ligase and NEDD8 substrates, inducing DNA damage and cell cycle arrest. Furthermore, impaired NEDDylation in CCA cells reduced the secretion of proteins involved in fibroblast activation, angiogenesis, and oncogenic pathways, ultimately hampering CAF proliferation and migration. CONCLUSION: Aberrant protein NEDDylation contributes to cholangiocarcinogenesis by promoting cell survival and proliferation. Moreover, NEDDylation impacts the CCA-stroma crosstalk. Inhibition of NEDDylation with pevonedistat may represent a potential therapeutic strategy for patients with CCA. LAY SUMMARY: Little is known about the role of post-translational modifications of proteins in cholangiocarcinoma development and progression. Herein, we show that protein NEDDylation is upregulated and hyperactivated in cholangiocarcinoma, promoting tumor growth. Pharmacological inhibition of NEDDylation halts cholangiocarcinogenesis and could be an effective therapeutic strategy to tackle these tumors.This article is based upon work from the COST Action CA18122 European Cholangiocarcinoma Network supported by COST (European Cooperation in Science and Technology: www.cost.eu)

Cognitive vulnerability in mental disorders

ABSTRACT: Introduction: Modes of cognitive vulnerability were evaluated in outpatients of psychological services centers with diagnoses of mental disorders. Objective: To establish components of cognitive vulnerability in different mental disorders. Method: The participants were 490 users of psychological services centers from twelve universities in Colombia. To identify the presence or absence of mental disorders, they completed the MINI International Neuropsychiatric Interview.The Young Schemes Questionnaire, the Core Beliefs Questionnaire for Personality Disorders, the Inventory of Automatic Thoughts, and the Coping Strategies Questionnaire were also applied. To establish distinctive characteristics among actual major depression, generalized anxiety disorder, panic disorder, social anxiety, and non-alcoholic substance abuse, a logistic regression analysis was conducted. Results: The results showed cognitive distinctive vulnerability profiles, according to the disorder. Conclusion: The hypothesis of cognitive specificity for the different mental disorders is confirmed.RESUMEN: Introducción: Se evaluaron los modos de vulnerabilidad cognitiva en usuarios de consulta externa en psicología, diagnosticados con trastornos mentales. Objetivo: Establecer componentes de vulnerabilidad cognitiva en diferentes trastornos mentales. Método: Participaron 490 usuarios de servicios psicológicos de doce universidades de Colombia. Se aplicó la Entrevista Neuropsiquiátrica Internacional para identificar la presencia o no de trastornos mentales; igualmente, se aplicaron el Cuestionario de Esquemas de Young, el Cuestionario de Creencias Centrales de Trastornos de la Personalidad, el Inventario de Pensamientos Automáticos y el Cuestionario de Estrategias de Afrontamiento. Se realizaron análisis de regresión logística para establecer características distintivas en los trastornos de depresión mayor actual, ansiedad generalizada, angustia, ansiedad social y abuso de sustancias no alcohólicas. Resultados: Se reportaron perfiles cognitivos de vulnerabilidad diferenciados de acuerdo con el trastorno. Conclusión: Se confirma la hipótesis de especificidad cognitiva para los diferentes trastornos mentales

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020; n = 769 (66%)) and later (July 2020–February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.Depto. de MedicinaFac. de MedicinaTRUEFundación Madrileña de Hematología y HemoterapiaFundación Leucemia y LinfomaAsociación Madrileña de Hematología y Hemoterapiapu

Nutrición parenteral domiciliaria en España, 2019: informe del Grupo de Nutrición Artificial Domiciliaria y Ambulatoria NADYA

RESUMEN Objetivo: comunicar los datos de nutrición parenteral domiciliaria (NPD) obtenidos del registro del grupo NADYA-SENPE (www.nadyasenpe.com) del año 2019. Material y métodos: análisis descriptivo de los datos recogidos de pacientes adultos y pediátricos con NPD en el registro NADYA-SENPE desde el 1 de enero al 31 de diciembre de 2019. Resultados: se registraron 283 pacientes (51,9 %, mujeres), 31 niños y 252 adultos procedentes de 47 hospitales españoles, lo que representa una tasa de prevalencia de 6,01 pacientes/millón de habitantes/año 2019. El diagnóstico más frecuente en los adultos fue “oncológico paliativo” y “otros” (21,0 %). En los niños fue la enfermedad de Hirschsprung junto a la enterocolitis necrotizante, las alteraciones de la motilidad intestinal y la pseudoobstrucción intestinal crónica, con 4 casos cada uno (12,9 %). El primer motivo de indicación fue el síndrome del intestino corto tanto en los niños (51,6 %) como en los adultos (37,3 %). El tipo de catéter más utilizado fue el tunelizado tanto en los niños (75,9 %) como en los adultos (40,8 %). Finalizaron 68 episodios, todos en adultos: la causa más frecuente fue el fallecimiento (54,4 %). Pasaron a la vía oral el 38,2 %. Conclusiones: el número de centros y profesionales colaboradores con el registro NADYA va incrementándose. Se mantienen estables las principales indicaciones y los motivos de finalización de la NPD

New GOLD classification: longitudinal data on group assignment

In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment. A change in category after one year was associated with longitudinal changes in the CAT and BODE index

Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/