RED-EMAR - A Chilean pilot initiative of early detection and intervention in clinical high-risk subjects

The COVID-19 crisis has had a significant impact on the mental health of adolescents and young adults in South America. As a result, the appearance of a higher incidence of anxiety and depressive disorders in these countries have been documented and could lead to the appearance of severe mental health disorders. In this context, the prevention and early intervention in mental health is a current challenge in Central and South America. Since the last decade, the existence of initiatives in this field has been mapped in Mexico, Brazil, Chile and Argentina, mostly in first episode psychosis programs. However, Chile is the only country in South America with a multicentre prospective initiative for early detection and intervention in clinical high-risk subjects (called RED-EMAR). The aim of RED-EMAR is disseminate the value of the at-risk mental state concept (abbreviated to EMAR in Spanish), establish agreed therapeutic strategies in this field, and establish potential new evidence-based local interventions. The successful experiences of this network include the monitoring and discussion of clinical cases in telemedicine and the development of mental health psychoeducation guidelines. However, Insufficient resources, stigma, and the lack of mental health public policies are some of the weaknesses of this initiatives in South America. The development and access to early detection and intervention services in South America could be a window of opportunity to reduce the impact of severe mental health disorders such as psychosis and related disorders and move towards an approach aimed at prevention or delaying its onset.

An observer comparison study to evaluate a machine learning model to quantify the infected pneumonia on lung CT images

Quantification of infected lung volume using computed tomography (CT) images can play a critical role in predicting the severity of pulmonary infectious disease. Manual segmentation of infected areas from several CT image slices, however, is not efficient and viable in clinical practice. To assist clinicians in overcoming this challenge, we developed a new method to automatically segment and quantify the percentage of the infected lung volume. First, we used a public dataset of 20 COVID-19 patients, which consists of manually annotated lung and infection masks, to train a new joint deep learning (DL) model for lung and infection segmentation. As for lung segmentation, a Mask-RCNN model was applied to the lung volume with a novel postprocessing technique. Following that, an ensemble model with a customized residual attention UNet model and feature pyramid network (FPN) models was employed for infection segmentation. Next, we assembled another set of 80 CT scans of Covid-19 patients. Two chest radiologists manually evaluated each CT scan and reported the infected lung volume percentage using a customized graphical user interface (GUI). The developed DL-model was also employed to process these CT images. Then, we compared the agreement between the radiologist (manual) and model-based (automated) percentages of diseased regions. Additionally, the GUI was used to let radiologists rate acceptance of the DL-model generated segmentation results. Analyzing the results demonstrate that the agreement between manual and automated segmentation is >95% in 28 testing cases. Furthermore, >53% of testing cases received the top assessment rating scores from two radiologists (between four-five- score). Thus, this study illustrates the feasibility of developing a DL-model based automated tool to effectively provide quantitative evaluation of infected lung regions to assist in improving the efficiency of radiologists in infection diagnosis. © COPYRIGHT SPIE. Downloading of the is permitted for personal use only.

Experiencia En Vida Real De La Eficacia, Seguridad Y Datos Farmacocineticos Del Cambio De Infliximab Intravenoso a Subcutaneo En Pacientes Con Enfermedad Inflamatoria Intestinal Inactiva. Resultados Del Registro Eneida

Poster con relevancia para la practica clinica Introduccion: Recientemente, se ha aprobado una formulacion subcutanea de infliximab biosimilar (CT-P13) (IFX- SC, dosis 120 mg) para la enfermedad inflamatoria intestinal (EII). Objetivos: Evaluar la eficacia, seguridad, farmacocinetica y experiencia de los pacientes tras el cambio a IFX-SC estando en remision clinica con tratamiento intravenoso. Metodos: Estudio multicentrico, descriptivo y observacional que incluyo a pacientes con enfermedad de Crohn (EC) y colitis ulcerosa (CU) que iban a ser cambiados de la via iv (IFX-IV) a la subcutanea (IFX-SC) a partir de datos obtenidos del registro ENEIDA (base de datos nacional, de recogida prospectiva por el Grupo Espanol de Trabajo en EII-GETECCU). Todos los pacientes estaban en remision clinica y biologica al menos 24 semanas antes del cambio. Se recogieron datos demograficos y de la enfermedad, actividad clinica (mediante indice de Harvey-Bradshaw para la EC e indice de mayo para la CU), datos analiticos (proteina C reactiva [PCR] y calprotectina fecal [CF]), asi como niveles valle al inicio, a las 12 y a las 24 semanas. Resultados: Se incluyeron 155 pacientes: 54 CU (35%) y 91 (65%) EC;44% mujeres;edad 45,5 anos (32-55). La indicacion del IFX-IV fue principalmente por enfermedad activa (72%) y perianal (7%), tratados durante 32 meses [14-56]. Pre- cambio, 78 (50,3%) recibian IFX-IV cada 8 semanas, 77 (49,7%) dosis intensificada. La mitad llevaban tratamiento inmunomodulador concomitante. El IFX-SC se cambio por mejorar adherencia durante la pandemia de COVID-19 (60%), para aumentar niveles (15%) o a peticion del paciente (25%). Permanecieron con dosis estandar 140 pacientes (90%), 8 (5%) requirieron intensificacion (120 mg semanal 4 y 240 mg cada 2 semanas 4) y en 7 (4,5%) se hizo una desescalada exitosa (120 mg cada 3 semanas en 4 y 120 mg cada 4 semanas en 3). Los indices clinicos, los niveles de PCR y la FC se mantuvieron sin cambios. Los niveles de IFXSC aumentaron significativamente de 4,5 μg/dl [2,6-9,2] basal a 14 μg/dl [9,5-16,2] a las 12 semanas y 13,2 μg/dl [10,4-19,7] a las 24 semanas. Ningun factor analizado (inmunosupresor concomitante, indice de masa corporal, localizacion de la enfermedad) se asocio con el aumento de niveles valle. Durante el seguimiento, suspendieron tratamiento inmunosupresor 16 de 78 (20,5%). Se registraron acontecimientos adversos en 9 pacientes (5,8%) y hubo 4 (2,6%) hospitalizaciones y 4 (2,6%) cirugias (1 de ellas perianal). Suspendieron tratamiento 9 pacientes (5,8%): 1 fracaso primario, 2 perdida de respuesta, 4 acontecimientos adversos, 1 voluntariamente y 1 cirugia. Conclusiones: El cambio de IFX IV a IFX SC mantiene la remision clinica de forma segura en la EII, ofrece mayores niveles de farmaco y una buena aceptacion por parte de los pacientes. El significado de los niveles mas altos con IFX-SC requiere una mayor exploracion.Copyright © 2023 Elsevier Espana, S.L.U. Todos los derechos reservados.

[Impact of days elapsed from the onset of symptoms to hospitalization in COVID-19 in-hospital mortality: Time matters]. / Impacto de los días transcurridos desde el inicio de los síntomas hasta la hospitalización en la mortalidad hospitalaria por COVID-19: el tiempo importa.

Background: COVID-19 shows different clinical and pathophysiological stages over time. Theeffect of days elapsed from the onset of symptoms (DEOS) to hospitalization on COVID-19prognostic factors remains uncertain. We analyzed the impact on mortality of DEOS to hospital-ization and how other independent prognostic factors perform when taking this time elapsedinto account. Methods: This retrospective, nationwide cohort study, included patients with confirmed COVID-19 from February 20th and May 6th, 2020. The data was collected in a standardized online datacapture registry. Univariate and multivariate COX-regression were performed in the generalcohort and the final multivariate model was subjected to a sensitivity analysis in an earlypresenting (EP; < 5 DEOS) and late presenting (LP; ≥5 DEOS) group. Results: 7915 COVID-19 patients were included in the analysis, 2324 in the EP and 5591 in theLP group. DEOS to hospitalization was an independent prognostic factor of in-hospital mortalityin the multivariate Cox regression model along with other 9 variables. Each DEOS incrementaccounted for a 4.3% mortality risk reduction (HR 0.957; 95% CI 0.93---0.98). Regarding variationsin other mortality predictors in the sensitivity analysis, the Charlson Comorbidity Index onlyremained significant in the EP group while D-dimer only remained significant in the LP group. Conclusion: When caring for COVID-19 patients, DEOS to hospitalization should be consideredas their need for early hospitalization confers a higher risk of mortality. Different prognosticfactors vary over time and should be studied within a fixed timeframe of the disease.

Exploring the impact of the COVID 19 pandemic on public bicycle sharing systems: the cases of Madrid (BiciMAD) and Buenos Aires (EcoBici)

Public bike-sharing systems (PBSS) allow the use of shared bicycles for a period of time without owning them. In Buenos Aires and Madrid, PBSS were implemented in 2010 and 2014 respectively, managed by public authorities and oriented to find alternatives to mass transit. The advantages offered by PBSS are multiple, and socially and environmentally friendly. The purpose of this article is to conduct an exploration and analysis of the temporal and spatial pattern of trips made using PBSS for both cities before and during the COVID 19 pandemic, in order to contribute to the state of the art. The temporal and spatial patterns in both cities were similar in pre-pandemic times. Both systems were negatively impacted in 2020 in terms of the number of trips due to lockdowns imposed. Both PBSS were closed during the pandemic, but as they were relaunched, bike usage increased. In both cities there is a correlation between the level of supply and the use of the system, and new micromobility spaces were identified. It is relevant to consider the lack of available datasets as well as information processing capabilities.

Impacto de los días transcurridos desde el inicio de los síntomas hasta la hospitalización en la mortalidad hospitalaria por COVID-19: el tiempo importa Impact of days elapsed from the onset of symptoms to hospitalization in COVID-19 in-hospital mortality: Time matters

Antecedentes La COVID-19 muestra diferentes fases clínicas y fisiopatológicas a lo largo del tiempo. El efecto de los días transcurridos desde el comienzo de los síntomas (DTCS) hasta la hospitalización sobre los factores pronósticos de la COVID-19 sigue siendo incierto. Analizamos el impacto en la mortalidad de los DTCS hasta la hospitalización y cómo se comportan otros factores pronósticos independientes al tener en cuenta dicho tiempo transcurrido. Métodos En este estudio de cohortes nacional retrospectivo se incluyó a pacientes con COVID-19 confirmada entre el 20 de febrero y el 6 de mayo de 2020. Los datos se recopilaron en un registro normalizado de captura de datos en línea. Se realizó una regresión de Cox uni y multifactorial en la cohorte general y el modelo multifactorial final se sometió a un análisis de sensibilidad en un grupo de presentación precoz (PP) < 5 DTCS y otro de presentación tardía (PT) ≥ 5 DTCS). Resultados En el análisis se incluyó a 7.915 pacientes con COVID-19, 2.324 en el grupo de PP y 5.591 en el de PT. Los DTCS hasta la hospitalización fueron un factor pronóstico independiente de mortalidad intrahospitalaria en el modelo de regresión de Cox multifactorial junto con otras nueve variables. Cada incremento en un DTCS supuso una reducción del riesgo de mortalidad del 4,3% (RRI = 0,957;IC 95%, 0,93-0,98). En cuanto a las variaciones de otros factores predictivos de la mortalidad en el análisis de sensibilidad, únicamente el índice de comorbilidad de Charlson siguió siendo significativo en el grupo de PP, mientras que únicamente el dímero D lo siguió siendo en el grupo de PT. Conclusiones Al atender a pacientes con COVID-19 hay que tener en cuenta los DTCS hasta la hospitalización porque la necesidad de hospitalización precoz confiere un mayor riesgo de mortalidad. Los diferentes factores pronósticos varían con el tiempo y deberían estudiarse dentro de un marco temporal fijo de la enfermedad.

Universities and Digital Skills' Development in Colombia

The development of human capital is a driver for economic growth. Future educational systems, based on digital platforms, can make us more resilient when confronting unforeseen crises such as the Covid-19 pandemic, which gave a sudden boost to digital transformation in society, in order to access services which had to be digitalized for external circumstances of isolation, highlighting gaps and the need to adapt to a new context. A great barrier is represented by the lack or insufficiency of digital skills in different age groups, which underlines the fundamental importance of training to improve quick access to these skills, and adequately face one's daily activities without running the risk of being expelled from the labor market. It is up to universities to deliver digital skills, to assess skills demand from job market to address right policies. In this work, we explore digital needs in Colombia and consider the alarming lack of skills in this sector, with its serious implications on social life. We administered a questionnaire to students of the Catholic University of Pereira (Colombia) to verify whether the high educational level they are involved in corresponds to an adequate development of digital skills. The study highlighted a gender gap in terms of perception by the students, especially related to advanced digital skills, such as the creation of new digital content, knowledge of programming languages and management of given tools. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Universities and Digital Skills' Development in Colombia

The development of human capital is a driver for economic growth. Future educational systems, based on digital platforms, can make us more resilient when confronting unforeseen crises such as the Covid-19 pandemic, which gave a sudden boost to digital transformation in society, in order to access services which had to be digitalized for external circumstances of isolation, highlighting gaps and the need to adapt to a new context. A great barrier is represented by the lack or insufficiency of digital skills in different age groups, which underlines the fundamental importance of training to improve quick access to these skills, and adequately face one's daily activities without running the risk of being expelled from the labor market. It is up to universities to deliver digital skills, to assess skills demand from job market to address right policies. In this work, we explore digital needs in Colombia and consider the alarming lack of skills in this sector, with its serious implications on social life. We administered a questionnaire to students of the Catholic University of Pereira (Colombia) to verify whether the high educational level they are involved in corresponds to an adequate development of digital skills. The study highlighted a gender gap in terms of perception by the students, especially related to advanced digital skills, such as the creation of new digital content, knowledge of programming languages and management of given tools. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Covid-19 Infection in Kidney Transplant Recipients: A Single-Center Case Series of 10 Cases from Dominican Republic

Introduction: The coronavirus disease 2019 (COVID-19) has caused tremendous impact globally due to the significant morbidity and mortality caused by this virus. It is currently known that the probability of becoming seriously ill from this disease is higher in older adults, in people with pre-existing comorbidities, and those with a suppressed immune state. Therefore, transplant patients are not the exception. Considering the importance of this topic and the scarce information on the outcome of this type of patients, especially in Latin America, this series of cases is focused on our experience with 10 kidney transplant patients hospitalized for COVID-19. Method(s): We retrospectively reviewed the medical records of kidney transplant patients hospitalized for SARS-CoV-2 (COVID-19) between April 2020 and May 2021. Result(s): The age range of the patients was 41 to 68 years, where 8 of these were men. The most common admission symptoms were fever (80%), dyspnea (70%), myalgia/arthralgia (50%), and headache (50%). The most prevalent laboratory findings were lymphocytopenia and increased inflammatory markers such as D-dimer, LDH, procalcitonin, erythrocyte sedimentation, and ferritin. General management included supportive treatment, statins, and antithrombotic therapy, while the specific treatment options were hydroxychloroquine, antivirals, corticosteroids, Intravenous Immunoglobulin, tofacitinib, and convalescent plasma. All the patients improved and were discharged. Two of them went to the ICU and only one required mechanical ventilation. The majority of the patients (70%) remained with their baseline immunosuppression without dose reduction or suspension. Conclusion(s): Kidney transplant recipients are more susceptible to infections, along with increased disease severity. At the same time their immunosuppressed state may reduce the inflammatory response following this type of infection. Decisions were based on stopping or attenuating the viral load and the systemic inflammation caused by this virus, but at the same time protecting against acute allograft rejection and the coinfection with other pathogens. Our findings suggest that the use of statins and antithrombotic prophylaxis in all hospitalized transplant patients may be beneficial to reduce the risk of mortality in patients with COVID-19 infection. Also, the maintenance of immunosuppressive therapy was not associated with worse outcomes. No conflict of interestCopyright © 2023

The Impact of the Covid19 Pandemic on Patients with Peripheral Artery Disease

Background The impact of COVID-19 on major adverse lower extremity (MALE) and cardiovascular events (MACE) in patients with peripheral artery disease (PAD) is unknown. Methods Using the VA Corporate Data Warehouse, Veterans with PAD were identified. Rates of MALE (amputation or lower extremity revascularization [LER]), and MACE (death, MI, or coronary revascularization) were assessed in pre-pandemic (3/11/2019-3/10/2020), early-pandemic (3/11/2020-3/10/2021), and late-pandemic (3/11/2021-3/10/2022) periods. Outcomes were compared using Kaplan-Meier method. Results Of 418,042 Veterans (mean age 72 yrs) with PAD, 76.7% were white and 96.8% male. Furthermore, 89.2% had HTN, 60.4% diabetes, 49.3% CAD, 21.6% heart failure, and 20.5% atrial fibrillation. From 3/11/2019 to 3/10/2022, 3,100 had amputation, 8,187 had LER, & 2,229 had MACE. Amputation rates declined and continued to decline in early- and late-pandemic period (306 to 268 to 235;p<0.001;rates per 100k). Rates of LER declined initially and stabilized in late-pandemic period (951 to 587 to 609;p < 0.001;rates per 100k). MACE did not change significantly. (215 to 168 to 202;p<0.001;rates per 100k). Conclusion Amputation rates in Veterans with PAD did not increase despite a clinically significant decline in LER. Given the known efficacy of noninvasive therapies in PAD, these data suggest that there is a need to re-evaluate appropriate indications for LER and amputation. [Formula presented]Copyright © 2023 American College of Cardiology Foundation

Impact of days elapsed from the onset of symptoms to hospitalization in COVID-19 in-hospital mortality: time matters.

BACKGROUND: COVID-19 shows different clinical and pathophysiological stages over time. The effect of days elapsed from the onset of symptoms (DEOS) to hospitalization on COVID-19 prognostic factors remains uncertain. We analyzed the impact on mortality of DEOS to hospitalization and how other independent prognostic factors perform when taking this time elapsed into account. METHODS: This retrospective, nationwide cohort study, included patients with confirmed COVID-19 from February 20th and May 6th, 2020. The data was collected in a standardized online data capture registry. Univariate and multivariate COX-regression were performed in the general cohort and the final multivariate model was subjected to a sensitivity analysis in an early presenting (EP; <5 DEOS) and late presenting (LP; ≥5 DEOS) group. RESULTS: 7915 COVID-19 patients were included in the analysis, 2324 in the EP and 5591 in the LP group. DEOS to hospitalization was an independent prognostic factor of in-hospital mortality in the multivariate Cox regression model along with other 9 variables. Each DEOS increment accounted for a 4.3% mortality risk reduction (HR 0.957; 95% CI 0.93-0.98). Regarding variations in other mortality predictors in the sensitivity analysis, the Charlson Comorbidity Index only remained significant in the EP group while D-dimer only remained significant in the LP group. CONCLUSION: When caring for COVID-19 patients, DEOS to hospitalization should be considered as their need for early hospitalization confers a higher risk of mortality. Different prognostic factors vary over time and should be studied within a fixed timeframe of the disease.

TOURIST SATISFACTION DURING THE PANDEMIC: AN ANALYSIS OF THE EFFECTS OF MEASURES TO PREVENT COVID-19 IN A MEDITERRANEAN COASTAL DESTINATION

The impact of the COVID-19 on tourist satisfaction is a particular relevant issue, due to the role that elements such as the prevention measures implemented at the destination might play. For this reason, this article examines tourist satisfaction during the peak tourist season of 2020 in a mature coastal destination in Catalonia in relation to safety and prevention measures imposed due to the COVID-19 pandemic. We use explanatory factor analysis and partial least squares path modelling for comparing the determinants of tourist satisfaction prior and during the pandemic based on surveys conducted in 2019 (N = 1556) and 2020 (N = 2220). The results suggest that the determinants of overall tourist satisfaction in 2019 remained significant in 2020. Moreover, although tourists especially appreciated feeling safe in 2020, our results suggest that such a perception was unrelated to measures to prevent COVID-19. The paper raises concerns towards the management of situations such as the pandemic in tourist destinations, as a proper balance must be found between the need of making visitors feel safe, and avoiding measures that can be felt as invasive or annoying, hampering the tourist experience. © 2022 Editura Universitatii din Oradea. All rights reserved.

Bacterial Infections After Kidney Transplant Before and After the COVID-19 Pandemic

Purpose: Infectious complications are a major cause of mortality and morbidity after kidney transplantation. During the COVID-19 pandemia there were several changes in the management and behavior of patients after transplant. These included measures such as universal masking, social distancing and reinforcing hand hygiene. Our objective was to evaluate if these differences affected the incidence of infections after kidney transplant. Method(s): This is a retrospective cohort study of all kidney transplants performed in our institution from March 2017 to November 2020. We examined the incidence of wound infection, urinary tract infection (UTI), pneumonia, and gastrointestinal (GI) infections. Pediatric and multi-organ transplants were excluded. We used the Fisher test, Chi-squared test of independence and logistic regression models in the analysis. All tests were based on a level of significance of alpha=0.05. Result(s): A total of 185 deceased donor kidney transplant patients were reviewed, 153 before and 54 after the beginning of the COVID-19 pandemic in the United States. The incidence of wound infection, pneumonia and GI infection were similar before and after COVID (Table 1). There was a significant increase in UTI after the COVID pandemic, the main organisms isolated were Klebsiella pneumonia (50%) and E. coli (25%). Overall the presence of UTI and wound infection were significantly related (OR 4.2, p = 0.06). Other clinical variables such as age, BMI, KDPI, EPTS, and the occurrence of delayed graft function were not associated with UTI. COVID infection was present with similar incidence: 12% in patients transplanted before and 14.8% in patients transplanted after the onset of the pandemic. Induction with Thymoglobulin or Basiliximab was not significantly different before and after COVID, and the choice of induction was not associated with the rate of UTI. Conclusion(s): While multiple changes in the management of patients and patient behavior are different before and after the onset of the COVID-19 pandemic, this analysis did not find significant change in the incidence of infections except for UTI in comparative cohorts of kidney transplant recipients. This study did not identify specific factors associated with the increase of UTI in our population. However, in response certain measures were implemented, such as reducing the time to ureteral stent removal and giving 24 hrs of prophylactic antibiotics at the time of stent removal.

Women and Behavioural Addiction - New paths in research and treatment

Symposium summary: It becomes more and more obvious that a gendered approach to research, prevention and treatment is highly relevant to gain a better understanding of and be more responsive to female-specific aspects of behavioural addiction. Literature and studies on Women and Gambling Disorder and other Behavioural Addiction are scarce, both in Europe and all over the world. Moreover, the existing data are not specific to women but inferred from mostly male samples. Nevertheless, more and more women are affected by pathological gambling and other non-substance related addictions. Obviously, women have a crucial role in family and society, and their gambling or other addictive behaviours, which are often underestimated, may have a deep impact on their social and personal life. One key issue is that women often experience great difficulty in finding appropriate treatment services. Most health clinics are not female friendly, and treatment programs very rarely offer female-specific treatment approaches. In 2020 a pandemic struck all over the world. It deeply affected our lives and existence, our physical and mental health, in many ways. B.A. played an important role in women's life during the various COVID-19 lockdowns. Women paid high costs in this period and taking care of their health is now even more important. It's crucial to learn from your experiences as researchers and clinicians and to gather data from all over the world to enrich our shared understanding of these issues, to compare, discuss and improve research and treatment for the women on whose behalf we are working on.

Telephone medical consultation during the COVID-19 pandemic in Mexico

Background: Telephone consultation has emerged as an alternative method for outpatient medical follow-up during the COVID-19 pandemic, reinforcing the necessary distancing measures. However, there are multiple factors that the medical team must contend with, which could limit the monitoring of patients. Methods: We retrospectively analyzed the remote medical consultation database of a universitybased oncology referral center in northeast Mexico. The telephone calls were made from the medical center by specialized health personnel. The data obtained correspond to the monitoring conducted over six months. Results: We included 1,140 patients in the analysis, of which 79% were women and 21% were men;the median age was 55 years. All individuals had a pathology-confirmed diagnosis of cancer. The main oncological diagnoses were breast, cervix, and prostate cancer which corresponded to 46, 13, and 7% of the cases, respectively. Ninety-four percent of cases corresponded to cancer surveillance, while the remaining 6% were receiving active oncological treatment, administered orally. Ninety-three percent of the patients were from the city of Monterrey and its metropolitan area, 6% came from the rest of the municipalities of the state of Nuevo Leon, and 1% were from other states of the Mexican Republic. Ninety-eight percent of the patients had a public health insurance as a method of coverage for health services, while 2% received care through private health insurance. At remote follow-up, only 53% of the patients responded to the telephone calls, none of them reported a diagnosis or any symptom of SARS-CoV-2 infection. Among the 536 patients who had a telephone communication failure, 68% did not respond to the call after 4 attempts, while in 32% of these cases the number provided by the patient was incorrect or non-existent. Conclusions: The high rates of failure to establish telephone communication documented in our population of patients with cancer is a worrying phenomenon. As the COVID-19 pandemic progresses worldwide, we must seek to establish measures to optimize logistics for more effective remote communication, to achieve the best possible outcomes.

Phase II trial of palbociclib in advanced sarcoma overexpressing CDK4 gene excluding dedifferentiated liposarcoma (DD LPS): A study from the Spanish Group for Research on Sarcoma (GEIS)

Background: CDK4/6 inhibitors showed a favorable progression-free survival (PFS) in DD LPS, a sarcoma bearing 12q 13-15 amplicon that implies CDK4 amplification. The median PFS was 4 and 7 months (m) for palbociclib and abemaciclib, respectively. Preclinical experiments in 10 sarcoma cell lines and 6 PDX models, including only one DD LPS, showed higher efficacy of anti-CDK4 in cases with high expression of CDK4 and low expression of p16. This rationale supported the design of a phase II trial exploring palbociclib in a wide range of sarcomas, excluding DD LPS. Methods: Progressing pretreated advanced soft tissue sarcoma, excluding DD LPS, or osteosarcoma adult patients (pts), whose tumors overexpressed CDK4 and underexpressed CDKN2A mRNA in a baseline mandatory biopsy, were enrolled. CDK4 and CDKN2A expression were assessed by qRT-PCR, using an external control as reference (Universal human reference RNA;Agilent Technologies). The primary endpoint was 6-m PFS rate. Minimax Simon's two-stage with type 1 and 2 errors of 10%, and null and alternative hypothesis of H0 15%, H1 40%, 6-month PFS rates were specified. The study will warrant further investigation if 6 or more pts had a PFS > 6 m from 21 evaluable pts. Palbociclib was administered orally at 125 mg/ day 21 out of 28 days. Pre-screening intended to increase the probability of positive profile in the baseline biopsy. Results: A total of 214 pts with 236 CDK4/ CDKN2A determinations were assessed for enrolment;141 for prescreening, in archive tumor sample, and 95 for screening, in a baseline biopsy. There were 38/141 (27%) and 28/95 (29%) pts with favorable mRNA profile from pre and screening, respectively. Twenty-two pts were enrolled with a median of previous systemic lines of 3 (1- 5). There were 9 different sarcoma subtypes, including 2 osteosarcomas. With a median FU of 10 m (0.4-23.3), the median PFS was 4.2 m (95% CI 0.9-7.4), while the 6- and 12-m PFS rates were 30% (95% CI 9-51) and 18% (95% CI 12-48) respectively. From 19 evaluable pts (1 early death by COVID, 1 withdrew consent and for 1 it was too early to be assessed) 11 had stable disease (58%) and 8 progressed (42%) as the best response. Patients with CDK4 expression above the median value had significantly longer mPFS in the univariate analysis: 5.9 m (95% CI 1.4-10.4) vs 1.9 m (95% CI 0.6- 3.2), p = 0.046;and longer OS: 15.5 m (95% CI 6.8-24.3) vs 10.6 m (95% CI 0-23.2), p = 0.047, respectively. The probability to find a positive profile in the screening was 29%, but this proportion increased up to 41% if in pre-screening had been positive. Conclusions: Palbociclib showed to be effective in a wide variety of sarcoma subtypes, other than DD LPS, selected by CDK4/CDKN2A biomarkers.

Construction of the historical-regulatory standard of the Expanded Family Health Center

This paper discusses the historical construction of the Expanded Family Health Center (NASF, in Portuguese), based on the analysis of 17 documents edited by the Ministry of Health (MH) between 2005 and 2021. This is a qualitative study of documental review that seeks to understand how the regulations and official instructive ma-nuals have been shaping the way NASF teams operate. It proposes to divide the NASF construction process into five periods: previous move-ments (2003 to 2007);support guidelines (2008 to 2011);the universalization of nasf (2012 to 2015);expansion of support (2016 to 2018);and the dismantling of NASF? (2019 to 2021). The results show changes in guidelines over the years of the team’s existence, especially in relation to the matrix support concept and its two dimensions: technical-pedagogical and clinical care. This study also demonstrates the effects of the Previne Brasil Program on the NASF, which resulted in the reduction of 379 teams in 2020 and 2021. Ad-ded to this scenario is the SARS-CoV-2 pandemic, which may be repositioning NASF interventions in the Brazilian Unified Health System (SUS, in Portuguese).