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BACKGROUND: The NHS is the first public body globally to commit to net zero. AIM: This study aimed to explore the environmental sustainability impact of a hospital scholarship programme. METHOD: A sustainable quality improvement value framework was used to measure the programme's environmental, social and financial effects. RESULTS: The social impact through face-to-face contact was most valued by scholars; there were also savings in carbon emissions and costs. DISCUSSION: Training in sustainability is essential for the workforce but little infrastructure and expertise are available within organisations to support staff to provide sustainable healthcare in day-to-day practice. CONCLUSION: Sustainable healthcare should be supported by education and national guidance and implementation plans should be drawn up to this end. The social impact of the framework used is often seen as less important than its environmental and financial components; however, as its value to scholars illustrates, the components are intertwined and should be considered of equal importance.
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Becas , Medicina Estatal , Humanos , Investigación sobre Servicios de Salud , Reino Unido , Mejoramiento de la Calidad , Evaluación de Programas y Proyectos de SaludRESUMEN
We evaluated 58 patients with relapsed or refractory (r/r) acute B-lymphoblastic leukemia (B-ALL; median age, 42.5 years; range, 16-69 years), treated with inotuzumab ozogamicin (INO) between 2016-2022 and who received an allogeneic hematopoietic stem cell transplantation (allo-HCT) consecutively. Forty-seven (81%) of the 58 patients were heavily pretreated receiving intensive chemotherapy +/- TKI, blinatumomab in 24 (41%) and allo-HCT at first-line in 11 (19%) patients. Complete remission (CR) rate prior to allo-HCT was 84%. Median follow-up was 30.5 months and median overall survival (OS) measured from start of INO was 11.2 months. Oneand 2-years OS rates were 50% (95%-CI, 38.4-56.1%) and 36.7% (95%-CI, 25.5-52.9%), respectively. Sinusoidal obstruction syndrome/venous occlusive disease (SOS/VOD) after allo-HCT occurred in 17 (29%) patients. Of those, 9 (53%) patients died due to SOS/VOD and multi-organ failure. Two had received >2 INO cycles (3 cycles, 5 cycles, n=1, each), all others ≤2 INO cycles prior to allo-HCT. Logistic regression analysis revealed conditioning with double alkylators (P=0.038) and allo-HCT during first-line therapy (P=0.050) as significant risk factors for SOS/VOD and in trend allo-HCT ≤ 60 days from last INO application (P=0.07), whereas number of INO cycles before allo-HCT and time between last INO application and allo-HCT were not significant. Relapse/progressive disease occurred in 20 (34%) patients. Of those, five (25%) patients are still alive, whereas 15 succumbed of their disease. Treatment with INO seems to be an effective approach with successful bridge-to-transplant. However, risk of SOS/VOD is high, necessitating continuous monitoring and recognition of SOS/VOD risk factors.
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Acute lymphoblastic leukemia (ALL) can relapse in the extramedullary compartment, with or without medullary involvement. Response to treatment may be individual. We evaluated response to inotuzumab ozogamicin in 31 patients with relapsed/refractory B-ALL with extramedullary disease. Median age was 31 years (range, 19-81). All patients were heavily pretreated, including allogeneic hematopoietic stem cell transplantation (HSCT; n=18). Overall response rate after two cycles of inotuzumab ozogamicin was 84% (complete remission, 55%; partial remission, 29%; resistant disease, 13%; early death, 3%). The median follow-up was 29 months and median overall survival was 12.8 months. One-year and 2-year overall survival rates were 53% (95% CI: 37-76%) and 18% (95% CI: 8-43%), respectively. Age had no impact on overall survival when assessed as a continuous variable or dichotomized at 60 years. Twelve patients proceeded to allogeneic HSCT (complete remission, n=6; partial remission, n=3; resistant disease, n=3). Prior to allogeneic HSCT, eight patients received two or fewer cycles and four patients received three or four cycles of inotuzumab ozogamicin. Sinusoidal obstruction syndrome was reported in three patients, including one after transplantation. Allogeneic HSCT, evaluated as a time-dependent variable, had no impact on overall survival. Inotuzumab ozogamicin seems to be effective as a debulking strategy in relapsed/refractory ALL with extramedullary disease. However, inotuzumab ozogamicin followed by allogeneic HSCT seems not to be effective in maintaining long-term disease control.
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Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Crisis Blástica , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Inotuzumab Ozogamicina , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Inducción de RemisiónRESUMEN
BACKGROUND: The Covid-19 pandemic has created an unprecedented challenge for health and social care systems globally. There is an urgent need for research on experiences of COVID-19 at different levels of health systems, including lessons from professional, organisational and local system responses, that can be used to inform managerial and policy responses. METHODS: This paper presents the findings from a thematic analysis of front-line staff experiences working across the Norfolk and Waveney integrated care system (ICS) in the East of England during April and October 2020 to address the question "What are the experiences and perceptions of partner organisations and practitioners at multiple levels of the health system in responding to COVID-19 during the first wave of the pandemic?" This question was posed to learn from how practitioners, interdependent partner organisations and the system experienced the pandemic and responded. 176 interview transcripts derived from one to one and focus group interviews, meeting notes and feedback from a "We Care Together" Instagram campaign were submitted for qualitative thematic analysis to an external research team at a regional University commissioned to undertake an independent evaluation. Three phases of qualitative analysis were systematically undertaken to derive the findings. FINDINGS: Thirty-one themes were distilled highlighting lessons learned from things that went well compared with those that did not; challenges compared with the celebrations and outcomes; learning and insights gained; impact on role; and system headlines. The analysis supported the ICS to inform and capitalise on system wide learning for integration, improvement and innovations in patient and care home resident safety, and staff wellbeing to deal with successive waves of the pandemic as well as prioritising workforce development priorities as part of its People Plan. CONCLUSIONS: The findings contribute to a growing body of knowledge about what impact the pandemic has had on health and social care systems and front-line practitioners globally. It is important to understand the impact at all three levels of the system (micro, meso and macro) as it is the meso and macro system levels that ultimately impact front line staff experiences and the ability to deliver person centered safe and effective care in any context. The paper presents implications for future workforce and health services policy, practice innovation and research.
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COVID-19 , COVID-19/epidemiología , Inglaterra/epidemiología , Humanos , Pandemias , Investigación Cualitativa , Desarrollo de PersonalRESUMEN
Allogeneic stem cell transplantation (allo-SCT) is the most successful and widely used immunotherapy for the treatment of acute myeloid leukemia (AML), as a result of its anti-leukemic properties driven by T cells and natural killer (NK) cells, leading to a graft-vs-leukemia (GVL) effect. Despite its essential role in AML treatment, relapse after allo-SCT is common and associated with a poor prognosis. There is longstanding interest in developing immunologic strategies to augment the GVL effect post-transplant to prevent relapse and improve outcomes. In addition to prophylactic maintenance strategies, the GVL effect can also be used in relapsed patients to reinduce remission. While immune checkpoint inhibitors and other novel immune-targeted agents have been successfully used in the post-transplant setting to augment the GVL effect and induce remission in small clinical trials of relapsed patients, exacerbations of graft-vs-host disease (GVHD) have limited their broader use. Here we review advances in three areas of immunotherapy that have been studied in post-transplant AML: donor lymphocyte infusion (DLI), immune checkpoint inhibitors, and other monoclonal antibodies (mAbs), including antibody-drug conjugates (ADCs) and ligand receptor antagonists. We also discuss additional therapies with proposed immunologic mechanisms, such as hypomethylating agents, histone deacetylase inhibitors, and the FLT3 inhibitor sorafenib.
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Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/terapia , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , HumanosRESUMEN
In this study, we evaluated the abilities of a series of chalcones to inhibit the activity of the enzyme xanthine oxidase (XO) and to scavenge radicals. 20 mono- and polyhydroxylated chalcone derivatives were synthesized by Claisen-Schmidt condensation reactions and then tested for inhibitory potency against XO, a known generator of reactive oxygen species (ROS). In parallel, the ability of the synthesized chalcones to scavenge a stable radical was determined. Structure-activity relationship analysis in conjunction with molecular docking indicated that the most active XO inhibitors carried a minimum of three hydroxyl groups. Moreover, the most effective radical scavengers had two neighboring hydroxyl groups on at least one of the two phenyl rings. Since it has been proposed previously that XO inhibition and radical scavenging could be useful properties for reduction of ROS-levels in tissue, we determined the chalcones' effects to rescue neurons subjected to ROS-induced stress created by the addition of ß-amyloid peptide. Best protection was provided by chalcones that combined good inhibitory potency with high radical scavenging ability in a single molecule, an observation that points to a potential therapeutic value of this compound class.
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Chalconas/farmacología , Inhibidores Enzimáticos/farmacología , Depuradores de Radicales Libres/farmacología , Xantina Oxidasa/antagonistas & inhibidores , Animales , Bovinos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Chalconas/síntesis química , Chalconas/química , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/química , Hidroxilación , Ratones , Simulación del Acoplamiento Molecular , Estructura Molecular , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad , Xantina Oxidasa/metabolismoRESUMEN
BACKGROUND: Health and care staff have limited opportunities to design, deliver and lead critical enquiry activities. AIMS: To explore barriers and enablers of building capacity, capability and confidence of these practitioners who wish to undertake critical enquiry activity. METHODS: A realist conceptual framework including the development of middle range theory allowed analysis of the scholarship process and outcomes. Data were collected through snap surveys, interviews (face to face and online) and project output (posters). RESULTS: Nine scholars completed the programme and all participated in the study. They all experienced an increase in capacity, capability and confidence in critical enquiry activity. Six overarching themes arose from analysis of the interviews and snap survey data: value; expertise; attitudes; meaningful, responsive support; brain space; and skill and knowledge acquisition. DISCUSSION: A combined focus on people and project while staff remained embedded in their work area was key for the growth of skills and knowledge and creating impact from projects. Guilt at having dedicated time to take part in the programme was a self-imposed barrier to building capacity and capability. Social capital (gained from bringing together individuals from different groups with shared values) facilitated bonding, which increased psychological safety and helped enable capability and confidence. CONCLUSION: The combination of theory and practice embedded in a real-world context led to positive outcomes for staff, patients, carers and the facilitation team as real-life changes were made in clinical environments.
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Creación de Capacidad , Humanos , Reino Unido , Competencia ClínicaRESUMEN
BH3 mimetics, including the BCL2/BCLXL/BCLw inhibitor navitoclax and MCL1 inhibitors S64315 and tapotoclax, have undergone clinical testing for a variety of neoplasms. Because of toxicities, including thrombocytopenia after BCLXL inhibition as well as hematopoietic, hepatic and possible cardiac toxicities after MCL1 inhibition, there is substantial interest in finding agents that can safely sensitize neoplastic cells to these BH3 mimetics. Building on the observation that BH3 mimetic monotherapy induces AMP kinase (AMPK) activation in multiple acute leukemia cell lines, we report that the AMPK inhibitors (AMPKis) dorsomorphin and BAY-3827 sensitize these cells to navitoclax or MCL1 inhibitors. Cell fractionation and phosphoproteomic analyses suggest that sensitization by dorsomorphin involves dephosphorylation of the proapoptotic BCL2 family member BAD at Ser75 and Ser99, leading BAD to translocate to mitochondria and inhibit BCLXL. Consistent with these results, BAD knockout or mutation to BAD S75E/S99E abolishes the sensitizing effects of dorsomorphin. Conversely, dorsomorphin synergizes with navitoclax or the MCL1 inhibitor S63845 to induce cell death in primary acute leukemia samples ex vivo and increases the antitumor effects of navitoclax or S63845 in several xenograft models in vivo with little or no increase in toxicity in normal tissues. These results suggest that AMPK inhibition can sensitize acute leukemia to multiple BH3 mimetics, potentially allowing administration of lower doses while inducing similar antineoplastic effects.
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Proteínas Quinasas Activadas por AMP , Compuestos de Anilina , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Pirimidinas , Sulfonamidas , Proteína bcl-X , Humanos , Animales , Compuestos de Anilina/farmacología , Sulfonamidas/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Ratones , Proteína bcl-X/metabolismo , Proteína bcl-X/antagonistas & inhibidores , Línea Celular Tumoral , Pirimidinas/farmacología , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/antagonistas & inhibidores , Pirazoles/farmacología , Proteína Letal Asociada a bcl/metabolismo , Apoptosis/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Leucemia/tratamiento farmacológico , Leucemia/patología , Leucemia/metabolismo , Fosforilación/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Sinergismo FarmacológicoRESUMEN
To determine whether the therapeutic activity of αB crystallin, small heat shock protein B5 (HspB5), was shared with other human sHsps, a set of seven human family members, a mutant of HspB5 G120 known to exhibit reduced chaperone activity, and a mycobacterial sHsp were expressed and purified from bacteria. Each of the recombinant proteins was shown to be a functional chaperone, capable of inhibiting aggregation of denatured insulin with varying efficiency. When injected into mice at the peak of disease, they were all effective in reducing the paralysis in experimental autoimmune encephalomyelitis. Additional structure activity correlations between chaperone activity and therapeutic function were established when linear regions within HspB5 were examined. A single region, corresponding to residues 73-92 of HspB5, forms amyloid fibrils, exhibited chaperone activity, and was an effective therapeutic for encephalomyelitis. The linkage of the three activities was further established by demonstrating individual substitutions of critical hydrophobic amino acids in the peptide resulted in the loss of all of the functions.
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Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/metabolismo , Parálisis/prevención & control , Cadena B de alfa-Cristalina/farmacología , Sustitución de Aminoácidos , Animales , Encefalomielitis Autoinmune Experimental/genética , Encefalomielitis Autoinmune Experimental/patología , Femenino , Humanos , Ratones , Mutación Missense , Parálisis/genética , Parálisis/metabolismo , Parálisis/patología , Cadena B de alfa-Cristalina/genéticaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Paro Cardíaco/etiología , Idarrubicina/efectos adversos , Miocarditis/inducido químicamente , Fibrilación Ventricular/inducido químicamente , Antagonistas Adrenérgicos beta/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Reanimación Cardiopulmonar , Dolor en el Pecho/etiología , Terapia Combinada , Citarabina/administración & dosificación , Desfibriladores Implantables , Ecocardiografía , Etopósido/administración & dosificación , Paro Cardíaco/terapia , Humanos , Idarrubicina/administración & dosificación , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Miocarditis/complicaciones , Miocarditis/diagnóstico por imagen , Fibrilación Ventricular/complicaciones , Fibrilación Ventricular/terapiaRESUMEN
Secondary hematologic malignancies, such as B-cell acute lymphoblastic leukemia/lymphoma (B-ALL), have been reported following multiple myeloma. Tyrosine kinase inhibitors have improved clinical outcomes of patients with Philadelphia-positive (Ph+) B-ALL. Therefore, recognition of the Ph chromosome in B-ALL patients is important for both prognosis and therapies. We present a case of a secondary Ph+ B-ALL following multiple myeloma that highlights a BCR::ABL1 fusion by a gene fusion assay to reveal a cryptic Ph chromosome, which may otherwise be missed by conventional cytogenetics and typical interphase fluorescence in situ hybridization.
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Linfoma de Burkitt , Linfoma , Mieloma Múltiple , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Proteínas de Fusión bcr-abl/genética , Hibridación Fluorescente in Situ , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Cromosoma FiladelfiaRESUMEN
Although DNA methyltransferase inhibitors (DNMTis), such as azacitidine and decitabine, are used extensively in the treatment of myelodysplastic syndromes and acute myeloid leukemia, there remain unanswered questions about DNMTi's mechanism of action and predictors of clinical response. Because patients often remain on single-agent DNMTis or DNMTi-containing regimens for several months before knowing whether clinical benefit can be achieved, the development and clinical validation of response-predictive biomarkers represents an important unmet need in oncology. In this review, we will summarize the clinical studies that led to the approval of azacitidine and decitabine, as well as the real-world experience with these drugs. We will then focus on biomarker development for DNMTis-specifically, efforts at determining exposure-response relationships and challenges that remain impacting the broader clinical translation of these methods. We will highlight recent progress in liquid-chromatography tandem mass spectrometry technology that has allowed for the simultaneous measurement of decitabine genomic incorporation and global DNA methylation, which has significant potential as a mechanism-of-action based biomarker in patients on DNMTis. Last, we will cover important research questions that need to be addressed in order to optimize this potential biomarker for clinical use.
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Azacitidina , Leucemia Mieloide Aguda , Humanos , Decitabina/uso terapéutico , Azacitidina/uso terapéutico , Azacitidina/farmacología , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Metilación de ADN , ADN , MetiltransferasasRESUMEN
The combination of venetoclax and hypomethylating agent (HMA/venetoclax) has emerged as a treatment option for patients with de novo acute myeloid leukemia (AML) who are unfit to receive intensive chemotherapy. In this single-center retrospective study, we evaluated clinical outcomes following treatment with HMA/venetoclax in 35 patients with advanced myeloproliferative neoplasms, myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes or AML with extramedullary disease. The composite complete remission (CR) rate (including confirmed/presumed complete cytogenetic response, acute leukemia response-complete, CR and CR with incomplete hematologic recovery) was 42.9% with median overall survival (OS) of 9.7 months. Complex karyotype was associated with inferior median OS (3.7 versus 12.2 months; p = 0.0002) and composite CR rate (22% versus 50.0%; p = 0.2444). Although SRSF2 mutations were associated with higher composite CR rate (80.0% versus 28.0%; p = 0.0082), this was not associated with longer median OS (10.9 versus 8.0 months; p = 0.2269). Future studies should include these patient subgroups.
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Leucemia Mieloide Aguda , Trastornos Mieloproliferativos , Humanos , Estudios Retrospectivos , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Sulfonamidas , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Azacitidina/uso terapéuticoRESUMEN
BACKGROUND: Despite recent approval of several new agents, relapsed acute lymphoblastic leukemia (ALL) remains challenging to treat. Sapanisertib (MLN0128/TAK-228) is an oral TORC1/2 inhibitor that exhibited preclinical activity against ALL. METHODS: We conducted a single-arm multi-center Phase II study of sapanisertib monotherapy (3 mg orally daily of the milled formulation for 21 days every 28 days) in patients with ALL through the Experimental Therapeutics Clinical Trials Network (NCI-9775). RESULTS: Sixteen patients, 15 of whom were previously treated (median 3 prior lines of therapy), were enrolled. Major grade 3-4 non-hematologic toxicities included mucositis (3 patients) and hyperglycemia (2 patients) as well as hepatic failure, seizures, confusion, pneumonitis, and anorexia (1 patient each). Grade >2 hematological toxicity included leukopenia (3), lymphopenia (2), thrombocytopenia, and neutropenia (1). The best response was stable disease in 2 patients (12.5%), while only 3 patients (19%) were able to proceed to Cycle 2. Pharmacokinetic analysis demonstrated drug exposures similar to those observed in solid tumor patients. Immunoblotting in serially collected samples indicated limited impact of treatment on phosphorylation of mTOR pathway substrates such as 4EBP1, S6, and AKT. CONCLUSION: In summary, single-agent sapanisertib had a good safety profile but limited target inhibition or efficacy in ALL as a single agent. This trial was registered at ClinicalTrials.gov as NCT02484430.
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Benzoxazoles , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológicoRESUMEN
Patients age ≥55 years with acute lymphoblastic leukemia (ALL) fare poorly with conventional chemotherapy, with a 5-year overall survival (OS) of â¼20%. Tyrosine kinase inhibitors and novel B cell-targeted therapies can improve outcomes, but rates of relapse and death in remission remain high. Allogeneic blood or marrow transplantation (alloBMT) provides an alternative consolidation strategy, and post-transplantation cyclophosphamide (PTCy) facilitates HLA-mismatched transplantations with low rates of nonrelapse mortality (NRM) and graft-versus-host disease (GVHD). The transplantation database at Johns Hopkins was queried for patients age ≥55 years who underwent alloBMT for ALL using PTCy. The database included 77 such patients. Most received reduced-intensity conditioning (RIC) (88.3%), were in first complete remission (CR1) (85.7%), and had B-lineage disease (90.9%). For the entire cohort, 5-year relapse-free survival (RFS) and overall survival (OS) were 46% (95% confidence interval [CI], 34% to 57%) and 49% (95% CI, 37% to 60%), respectively. Grade III-IV acute GVHD occurred in only 3% of patients, and chronic GVHD occurred in 13%. In multivariable analysis, myeloablative conditioning led to worse RFS (hazard ratio [HR], 4.65; P = .001), whereas transplantation in CR1 (HR, .30; P = .004) and transplantation for Philadelphia chromosome-positive (Ph+) ALL versus T-ALL (HR, .29; P = .03) were associated with improved RFS. Of the 54 patients who underwent RIC alloBMT in CR1 for B-ALL, the 5-year RFS and OS were 62% (95% CI, 47% to 74%) and 65% (95% CI, 51% to 77%), respectively, with a 5-year relapse incidence of 16% (95% CI, 7% to 27%) and an NRM of 24% (95% CI, 13% to 36%). RIC alloBMT with PTCy in CR1 represents a promising consolidation strategy for B-ALL patients age ≥55 years.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Persona de Mediana Edad , Médula Ósea , Ciclofosfamida/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Recurrencia , Enfermedad AgudaRESUMEN
While much attention has been given to organisational culture, there has been less focus on workplace culture. Yet workplace culture strongly influences the way care is delivered, received and experienced. An effective workplace culture is crucial for the well-being of individual staff members and teams as well as for patients' experiences and outcomes of care. This article describes the 'Guiding Lights for effective workplace cultures' which were developed by the authors and provide a framework to assist in understanding and promoting effective workplace cultures and creating environments where staff and patients feel safe and valued. There are four Guiding Lights: 'collective leadership', 'living shared values', 'safe, critical, creative learning environments' and 'change for good that makes a difference'. Each one articulates what good workplace cultures are through descriptors and intermediate outcomes and together produce a set of ultimate outcomes. The Guiding Lights provide nurses working in older people's care settings with an opportunity to learn from, and celebrate, what is going well in their workplaces and to consider areas that require further development.
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Liderazgo , Lugar de Trabajo , Anciano , Humanos , Cultura OrganizacionalRESUMEN
Background/Objective: Pemigatinib, a fibroblast growth factor receptor (FGFR) 1-3 inhibitor, is a novel therapeutic approach for treating cholangiocarcinoma when an FGFR fusion or gene rearrangement is identified. Although the most reported side effect of pemigatinib is hyperphosphatemia, tumoral calcinosis with soft tissue calcifications is not widely recognized as a complication. We report a case of patient with hyperphosphatemic tumoral calcinosis on pemigatinib. Case Report: A 59-year-old woman with progressive metastatic cholangiocarcinoma, despite receiving treatment with cisplatin and gemcitabine for 7 months, was found to have an FGFR2-BICC1 fusion in the tumor on next-generation sequencing. Pemigatinib was, therefore, initiated. Four months into the therapy, multiple subcutaneous nodules developed over the lower portion of her back, hips, and legs. Punch biopsies revealed deep dermal and subcutaneous calcifications. Investigations revealed elevated serum phosphorus (7.5 mg/dL), normal serum calcium (8.7 mg/dL), and elevated intact fibroblast growth factor-23 (FGF23, 1216 pg/mL; normal value <59 pg/mL) levels. Serum phosphorus levels improved with a low-phosphorus diet and sevelamer. Calcifications regressed with pemigatinib discontinuation. Discussion: Inhibition or deficiency of FGF-23 results in hyperphosphatemia and can lead to ectopic calcification. Pemigatinib, a potent inhibitor of FGFR-1-3, blocks the effect of FGF-23 leading to hyperphosphatemia and tumoral calcinosis as observed in our case. Treatment is aimed primarily at lowering serum phosphate levels through dietary restriction or phosphate binders; however, the regression of tumoral calcinosis can occur with pemigatinib cessation, as seen in this case. Conclusion: As the use of FGFR 1-3 inhibitors becomes more prevalent, we aim to raise attention to the potential side effects of tumoral calcinosis.
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BACKGROUND: Previous embedded researcher models have focused predominantly on an individual being a temporary team member and embedded for a project-limited short-term placement. AIM: To develop an innovative research capacity building model to address the challenges of developing, embedding and sustaining, research led by Nurses, Midwives, and Allied Health Professionals (NMAHPs) in complex clinical environments. This healthcare and academic research partnership model offers an opportunity to support the 'how' of enabling NMAHP research capacity building from within the researchers' clinical area of expertise. METHOD: Collaboration between three healthcare and academic organisations and the iterative process of cocreation, development and refinement took place over 6 months during 2021. The collaboration relied on virtual meetings, emails, telephone calls and document review. RESULTS: A codesigned NMAHP embedded research (ER) model is ready for trialling with the individual being an existing clinician working collaboratively within the healthcare setting and with academia to develop the skills to become the ER. CONCLUSION: This model supports NMAHP-led research activity in clinical organisations in a visible and manageable way. As a shared, long-term vision, the model will contribute to research capacity and capability of the wider healthcare workforce. It will lead, facilitate and support research in and across clinical organisations in collaboration with higher education institutions.