Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial.

BACKGROUND: Most patients with chronic lymphocytic leukaemia progress after treatment or retreatment with targeted therapy or chemoimmunotherapy and have limited subsequent treatment options. Response levels to the single-agent venetoclax in the relapsed setting is unknown. We aimed to assess venetoclax activity in patients with or without previous B-cell receptor-associated kinase inhibitor (BCRi) treatment. METHODS: This multicentre, open-label, single-arm, phase 3b trial (VENICE-1) assessed activity and safety of venetoclax monotherapy in adults with relapsed or refractory chronic lymphocytic leukaemia, stratified by previous exposure to a BCRi. Eligible participants were aged 18 years or older with previously treated relapsed or refractory chronic lymphocytic leukaemia. Presence of del(17p) or TP53 aberrations and previous BCRi treatment were permitted. Patients received 5-week ramp-up to 400 mg of oral venetoclax once daily and were treated for up to 108 weeks, with 2 years follow-up after discontinuation, or optional extended access. The primary activity endpoint was complete remission rate (complete remission or complete remission with incomplete marrow recovery) in BCRi-naive patients. Analyses used the intent-to-treat (ie, all enrolled patients, which coincided with those who received at least one dose of venetoclax). This study was registered with ClinicalTrials.gov, NCT02756611, and is complete. FINDINGS: Between June 22, 2016, and March 11, 2022, we enrolled 258 patients with relapsed or refractory chronic lymphocytic leukaemia (180 [70%] were male; 252 [98%] were White; 191 were BCRi-naive and 67 were BCRi-pretreated). Median follow-up in the overall cohort was 49·5 months (IQR 47·2-54·1), 49·2 months (47·2-53·2) in the BCRi-naive group, and 49·7 months (47·4-54·3) in the BCRi-pretreated group. Of 191 BCRi-naive patients, 66 (35%; 95% CI 27·8-41·8) had complete remission or complete remission with incomplete marrow recovery. 18 (27%; 95% CI 16·8-39·1) of 67 patients in the BCRi-pretreated group had complete remission or complete remission with incomplete marrow recovery. Grade 3 or worse treatment-emergent adverse events were reported in 203 (79%) and serious adverse events were reported in 136 (53%) of 258 patients in the overall cohort. The most common treatment-emergent adverse event was neutropenia (96 [37%]) and the most common and serious adverse event was pneumonia (21 [8%]). There were 13 (5%) deaths reported due to adverse events; one of these deaths (autoimmune haemolytic anaemia) was possibly related to venetoclax. No new safety signals were identified. INTERPRETATION: These data demonstrate deep and durable responses with venetoclax monotherapy in patients with relapsed or refractory chronic lymphocytic leukaemia, including BCRi-pretreated patients, suggesting that venetoclax monotherapy is an effective strategy for treating BCRi-naive and BCRi-pretreated patients. FUNDING: AbbVie.

Digital transformation in organizational health and safety to mitigate Burnout Syndrome.

In 2000, the World Health Organization (WHO) identified Burnout Syndrome as an occupational risk factor, affecting an estimated 10% of workers, resulting in lost productivity and increased costs due to sick leave. Some claim that Burnout Syndrome has reached epidemic proportions in workplaces around the world. While signs of burnout are not difficult to identify and palliate, its real impact is not easy to measure, generating a number of risks for companies from possible loss of human talent to decreased productivity and diminished quality of life. Given the complexity of Burnout Syndrome, it must be addressed in a creative, innovative and systematic way; traditional approaches cannot be expected to deliver different results. This paper describes the experience where an innovation challenge was launched to collect creative ideas to identify, prevent or mitigate Burnout Syndrome through the use of technological tools and software. The challenge was endowed with an economic award and its guidelines stated that the proposals must be both creative and feasible from an economic and organizational point of view. A total of twelve creative projects were submitted, including each of them, the analysis, design and management plans, to envision an idea that is feasible and with the appropriate budget, implemented. In this paper, we present a summary of these creative projects and how the IRSST (Instituto Regional de Seguridad y Salud en el Trabajo) experts and leaders in OHS in the Madrid Region (Spain) envision their potential impact on improving the OHS landscape.

Agile Delphi methodology: A case study on how technology impacts burnout syndrome in the post-pandemic era.

Introduction: In the post-pandemic era, many habits in different areas of our lives have changed. The exponential growth in the use of technology to perform work activities is one of them. At the same time, there has been a marked increase in burnout syndrome. Is this a coincidence? Could they be two interconnected developments? What if they were? Can we use technology to mitigate this syndrome? This article presents the agile Delphi methodology (MAD), an evolved version of the Delphi method, adapted to the needs of modern-day society. Methods: To drive Occupational Health and Safety (OHS) experts to reach a consensus on what technological and non-technological factors could be causing the burnout syndrome experienced by workers in the post-pandemic era, MAD has been used in a specific case study. This study formally presents MAD and describes the stages enacted to run Delphi experiments agilely. Results: MAD is more efficient than the traditional Delphi methodology, reducing the time taken to reach a consensus and increasing the quality of the resulting products. Discussion: OHS experts identified factors that affect and cause an increase in burnout syndrome as well as mechanisms to mitigate their effects. The next step is to evaluate whether, as the experts predict, burnout syndrome decreases with the mechanisms identified in this case study.

Smart occupational health and safety for a digital era and its place in smart and sustainable cities.

As innovative technologies emerge, there is a need to evolve the environments in which these technologies are used. The trend has shifted from considering technology as a support service towards making it the means for transforming all complex systems. Smart cities focus their development on the use of technology to transform every aspect of society and embrace the complexity of these transformations towards something leading to the well-being and safety of people inhabiting these cities. Occupational Health and Safety (OHS) is an essential aspect to be considered in the design of a smart city and its digital ecosystems, however, it remains unconsidered in most smart city's frameworks, despite the need for a specific space for smart OHS. This paper summarizes a 9-month process of generation of a value proposition for evolving the sector of OHS based on a value-map in whose creation several stakeholders have participated. They focused on identifying the products, the methods, the organizational structures and the technologies required to develop an updated, dynamic and robust prevention model focused on workers in smart and complex contexts, and to improve the organizations' capability to guarantee safety even in the most changing, digital and disruptive settings. To assess the relevance and validity of this value-map, a study was carried out to match the set of its elements and its specific and conceptual products discovered, considering also the definition of the past needs and future trends of the sector that a set of renowned stakeholders and key opinion leaders (with mastery in OHS from several companies and industries) have recently defined for the decade of 2020. A prospective analysis of this match is presented, revealing that there is still an existing gap to be covered in the context of smart cities design: the explicit guarantee of safety for workers.

Early decompressive craniectomy for neurotrauma: an institutional experience.

BACKGROUND: Neurotrauma centers have developed management protocols on the basis of evidence obtained from literature analysis and institutional experience. This article reviews our institutional experience in the management of severe traumatic brain injury (TBI) at Simòn Bolivar Hospital, the district trauma center for Bogotá's north zone. METHODS: This is a case control study comparing a group of patients (n: 16) operated for severe TBI between January 2002 and July 2004 according to an institutional management protocol characterized by an early decompressive craniectomy (DC) approach versus a historical control group (n: 20) managed before the implementation of such protocol. Mortality and Glasgow Outcome Score (GOS) at 6 months were used as the main outcome variables. RESULTS: An early DC protocol implemented within 12 hours from injury in 16 patients with severe isolated TBI and a Marshall score between III or IV was associated with a lesser mortality than the conventional approach with ventriculostomy and Intensive Care Unit (ICU) management alone. The GOS was significantly better in the DC group (p=0.0002) than in the control group. CONCLUSION: The use of an early DC protocol for severe TBI patients (Glasgow Coma Scale <9) had a significantly improved outcome compared with the conventional approach with ventriculostomy and ICU management in Simòn Bolivar Hospital in Bogotá, Colombia.

Treatment of seven patients with coarctation of the aorta treated using a Mexican-made platinum/iridium stent.

BACKGROUND: Nowadays, stenting is the treatment of choice in patients >15 years of age with coarctation of the aorta without hypoplastic aortic isthmus. The platinum/iridium stent manufactured in Mexico may be an affordable alternative with the same benefits as the imported stent. METHODS: This is a series of cases in which we present the immediate results of the first seven patients with coarctation of the aorta treated with the platinum/iridium stent manufactured in Mexico. The first four patients were selected and treated at the Cardiology Hospital of the National Medical Center during the year 2003, two more patients were selected and treated at the National Institute of Cardiology, and another patient was treated at the Military Hospital, Mexico City, in the year 2005. RESULTS: A total of seven patients were successfully treated with the platinum/iridium stent without any complications. Average initial gradient was 56.4 mmHg (range: 30-90 mmHg). In six patients, the final gradient was 0.0 mmHg and in one it was 2 mmHg. In the four patients treated in the Cardiology Hospital of the National Medical Center, mean follow-up time was 17.5 +/- 2.5 months, with a gradient of 0.0 mmHg. All patients are in NYHA Class I. At 12 months follow-up, the gradient remains as 0 mmHg and the patients are still in NYHA Class I functional state. CONCLUSIONS: This stent can be a safe and effective alternative to other stents available on the market for the treatment of coarctation of the aorta.

Estudio piloto preliminar en humanos con la prótesis endovascular coronaria (STENT SAQ). Resultados inmediatos y a mediano plazo / Pilot study with the use of coronary endovascular prhosthesis (STENT-SAQ). Shot term results

Presentamos los resultados obtenidos en 23 pacientes a los que se les colocaron 25 prótesis endovasculares (stent SAQ). Todos con enfermedad aterosclerosa coronaria y con diversas presentaciones clínicas como angina estable o inestable, infarto agudo del miocardio, como indicación primaria, y algunos casos de complicaciones postangioplastia coronaria con cualquiera de las patologías citadas. La mayoría de las lesiones eran complejas: obstrucciones totales, placas largas y enfermos en estado crítico. Los resultados inmediatos han sido satisfactorios ya que se logró mejoría angiográfica en todos los pacientes con respecto a la angioplastia convencional, con flujo TIMI 3 en 23 de las 25 lesiones tratadas y TIMI 2 en los dos restantes, en los que inicialmente fue TIMI 0. Se logró aumentar el diámetro arterial, comparado con el obtenido con la angioplastia convencional. Un enfermo presentó trombosis aguda, resuelta con nueva dilatación con balón, y en dos casos hubo protrusión de la placa aterosclerosa a través de las espirales del stent SAQ; en ambos, la obstrucción no fue significativa ni comprometió el flujo. Se tiene seguimiento clínico y pruebas de esfuerzo en todos los pacientes, realizadas en promedio tres meses después. A diez enfermos se les ha realizado angiografía coronaria, en cuatro por prueba de esfuerzo positiva, tres de ellos mostraron re-estenosis del SAQ, que se resolvió con dilatación con balón en forma exitosa, y otro se envió a tratamiento quirúrgico. En los seis enfermos restantes, se realizó la coronariografía por cumplir con el tiempo fijado por el protocolo; uno de ellos tiene dos stents, en ninguno encontramos re-estenosis.

Seguimiento de una cohorte de mujeres trabajadoras en cultivos de flores de la Sabana de Bogotá / Follow-up of a group of women working in floriculture on the Sabana de Bogotá

La presente investigación es un estudio descriptivo sobre las mujeres encontradas pertencientes a la cohorte de trabajadoras en cultivos de flores de la Sabana de Bogotá, estudiadas por el Grupo de Sanidad del Ambiente del Instituto Nacional de Salud hace 20 años. Se obtuvo información nueva de las mujeres que se lograron ubicar; se describieron las características generales de dicha población; se determinó la similitud entre la población encontrada y la no encontrada y se estableció la frecuencia y tipo de cáncer desarrollado en las mujeres. Se encontraron 1.218 (23,1 por ciento) mujeres del total de mujeres estudiadas en la cohorte inicial, con un promedio de edad de 44,5 años y un tiempo total de trabajo en cultivos de flores de 15 años en promedio, siendo las actividades que ocupan el mayor número de personas, las identificadas como de alta exposición a plaguicidas

Retardo del crecimiento intrauterino asociado con el consumo de pasta básica de cocaína por mujeres gestantes de Bogotá, D. C., Colombia / Association between the use of free base cocaine (basuco) by pregnant women and intrauterine growth retardation of newborns in Bogotá, D. C., Colombia

El objetivo de este estudio fue identificar una posible asociación entre el consumo de pasta básica de cocaína o basuco entre mujeres embarazadas y el crecimiento intrauterino de sus productos vivos en dos hospitales de tercer nivel en Bogotá, Colombia. con un diseño de cohorte retrospectiva, se encuestaron 1878 mujeres en el puerperio mediato para indagar, en otras variables, la historia sobre el consumo de drogas ilícitas. Tanto a las madres como a sus recién nacidos se les realizaron mediciones antropométricas estandarizadas. Se comparó la prevalencia de bajo peso al nacer (BPN), parto prematuro (PP) y retardo del crecimiento intrauterino (RCIU) con la historia de consumo de drogas ilícitas durante el embarazo por medio de modelos de regresión lineal múltiple y regresión logística múltiple, para ajustar el efecto de posibles confusores como edad materna, estado nutricional y patologías maternas, nivel socioeconómico, escolaridad y tabaquismo, entre otros. Los resultados mostraron que unda de cada 189 mujeres consumió sustancias ilegales durante el embarazo, comúnmente Cannabis sativa o pasta básica de cocaína. Las consumidoras de estos productos típicamente tenían menor escolaridad, eran de nivel socioeconómico más bajo, eran más delgadas, con una historia de control prenatal inadecuado, primigestantes o multigestantes y, con frecuencia, también fumaban tabaco y bebían alcohol. Se halló una asociación ente el consumo de la sustancias ilegales con RCIU (cociente de suertes de prevalencia de 5,24, IC95 por ciento: 1,3-21,0 y un d{eficit de 0,7 desv{ios est{andares del peso para la edad gestacional (p=0,03). Además, se encontró un cociente de suertes ajustado de 7,78 con IC95 por ciento: 1,0-62, entre el consumo de pasta básica de cocaína y RCIU. Aunque es probable que a través de entrevistas se subestime la prevalencia de consumo de drogas y a pesar del limitado poder del estudio, éste fue capaz de identificar un efecto importante del consumo de pasta básica de cocaína en el RCIU. Estos hallazgos tienen importancia para la salud pública dada la magnitud de proporciones epidémicas que ha cobrado el uso de esta forma de cocaína en las Américas

Radiocirugía: principios y aplicaciones en la práctica clínica

En los últimos años, la introducción de la radiocirugía, en combinación con la microneurocirugía y la neurorradiología intervencionista, ha hecho posible eltratamiento eficaz, de patologías de tipo vascular y tumoral al igual que trastornos funcionales, hasta hace poco intratables o tratables a costa de una elevada morbimortalidad para el paciente. En el presente artículo se hace una revisión de los conceptos básicos de física y radioterapia que debe conocer el médico para tener acceso en forma lógica y segura a esta tecnología. Se revisan las opciones de tratamiento con radiocirugía disponibles hoy día, sus indicaciones, resultados y efectos colaterales. El tema tratado posee enorme importancia para los médicos en general ya que desde hace poco esta tecnología ya está disponible en el país.

Desarrollo y de diseño de un stent (SAQ) para el tratamiento de obstrucciones arteriales aterosclerosas coronarias / Design and development of stent (SAQ) for the treatment of coronary artery obstructions

En la práctica de la angioplastía coronaria transluminal percutánea (ACTP), los problemas más importantes por resolver son la disección aguda, los resultados insatisfactorios y fundamentalmente el desarrollo de reestenosis; uno de los enfoques para resolver estas complicaciones ha sido el desarrollo de férulas endovasculares universalmente conocidas como stents (S). Esta tecnología es costosa para nuestro país, lo que estimuló el diseño y construcción de un S denominado SAQ que es motivo del estudio. Se presenta: La Metodología del desarrollo, fabricación y resultados in vitro y en vivo del SAQ; los resultados ex vivo, obtenidos en arterias coronarias de cerdo y en corazón humano; los resultados de dos modelos en animales: aorta de conejo y arterias periféricas en perro. En este trabajo se demuestra que el SAQ es seguro y efectivo, con propiedades generales semejantes a los existentes en el mercado