Plan de Intervención Comunitaria para el manejo de la EPOC estable: protocolo de coordinación asistencial y derivación entre farmacias comunitarias y centros de salud / Community Intervention Plan for the management of stable COPD: protocol for care coordination and referral between community pharmacies and health centres

La enfermedad pulmonar obstructiva crónica (EPOC) es una enfermedad frecuente y progresiva, pero prevenible y tratable. Sin embargo, se han detectado importantes áreas de mejora en su diagnóstico, tratamiento y seguimiento, así como en la adherencia terapéutica. Con el propósito de aumentar la detección precoz de la EPOC y su manejo adecuado en España, se ha diseñado un Plan de intervención comunitaria (PIC) para la colaboración entre farmacias comunitarias y centros de salud de atención primaria. El PIC incluye un procedimiento normalizado de trabajo (PNT), desarrollado por un grupo de profesionales de farmacia comunitaria, medicina de familia, neumología y enfermería de atención primaria. En él se describe el algoritmo que guiará la actuación de los farmacéuticos comunitarios, incluyendo las pruebas y dispositivos para el cribado poblacional de la EPOC, la evaluación de la enfermedad, la adhesión a inhaladores y la detección de errores críticos en el uso de inhaladores entre otros aspectos. El PNT incluye también un formulario para la derivación del paciente al centro de salud correspondiente, donde se llevarán a cabo una serie de acciones preestablecidas en el plan de actuación según el escenario clínico. Además, se propone evaluar la efectividad de la intervención con unos indicadores recogidos en el centro de salud y en farmacia comunitaria. Por último, se recomienda establecer un plan formativo en EPOC para la óptima implementación del plan y una encuesta a pacientes sobre su grado de satisfacción con la intervención. En conclusión, la implantación del PIC podría reducir el infradiagnóstico en EPOC y optimizar el manejo de los pacientes diagnosticados en España, donde los farmacéuticos comunitarios tendrían una función esencial en el abordaje de estos pacientes. (AU)

Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos / Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients (AU)

La pandemia por COVID-19 ha provocado el ingreso de un elevado número de pacientes en UCI, generalmente por insuficiencia respiratoria severa. Desde la aparición de los primeros casos de infección por SARS-CoV-2, a finales de 2019, en China, se ha publicado una cantidad ingente de recomendaciones de tratamiento de esta entidad, no siempre respaldadas por evidencia científica suficiente ni con el rigor metodológico necesario. Gracias al esfuerzo de distintos grupos de investigadores, actualmente disponemos de resultados de ensayos clínicos, y otro tipo de estudios, de mayor calidad. Consideramos necesario realizar un documento que incluya recomendaciones que recojan estas evidencias en cuanto al diagnóstico y el tratamiento de COVID-19, pero también aspectos que otras guías no han contemplado y que consideramos fundamentales en el manejo del paciente crítico con COVID-19. Para ello se ha creado un comité redactor, conformado por miembros de los Grupos de Trabajo de SEMICYUC más directamente relacionados con diferentes aspectos específicos del manejo de estos pacientes (AU)

[Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units]. / Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

The Impact of Culturing the Organ Preservation Fluid on Solid Organ Transplantation: A Prospective Multicenter Cohort Study.

BACKGROUND: We analyzed the prevalence, etiology, and risk factors of culture-positive preservation fluid and their impact on the management of solid organ transplant recipients. METHODS: From July 2015 to March 2017, 622 episodes of adult solid organ transplants at 7 university hospitals in Spain were prospectively included in the study. RESULTS: The prevalence of culture-positive preservation fluid was 62.5% (389/622). Nevertheless, in only 25.2% (98/389) of the cases were the isolates considered "high risk" for pathogenicity. After applying a multivariate regression analysis, advanced donor age was the main associated factor for having culture-positive preservation fluid for high-risk microorganisms. Preemptive antibiotic therapy was given to 19.8% (77/389) of the cases. The incidence rate of preservation fluid-related infection was 1.3% (5 recipients); none of these patients had received preemptive therapy. Solid organ transplant (SOT) recipients with high-risk culture-positive preservation fluid receiving preemptive antibiotic therapy presented both a lower cumulative incidence of infection and a lower rate of acute rejection and graft loss compared with those who did not have high-risk culture-positive preservation fluid. After adjusting for age, sex, type of transplant, and prior graft rejection, preemptive antibiotic therapy remained a significant protective factor for 90-day infection. CONCLUSIONS: The routine culture of preservation fluid may be considered a tool that provides information about the contamination of the transplanted organ. Preemptive therapy for SOT recipients with high-risk culture-positive preservation fluid may be useful to avoid preservation fluid-related infections and improve the outcomes of infection, graft loss, and graft rejection in transplant patients.

Results After Implementing a Program of Intensive Care to Facilitate Organ Donation.

A program of intensive care to facilitate organ donation (ICOD) represents one of the ways to increase donation rate following brain death (BD). OBJECTIVES: To analyze the impact and cost-effectiveness of setting up an ICOD strategy. METHOD: Retrospective cases of BD donors from the Spanish region La Rioja were included, after implementation of an ICOD program (2011-2016). This was activated in cases of devastating neurologic injury where treatment had been rejected following therapeutic futility criteria. Follow-up of kidney and liver transplant patients with the obtained grafts was carried out. RESULTS: A total of 134 potential donors were admitted to intensive care unit (ICU), of whom 106 were selected under the ICOD strategy. BD was diagnosed in 108 cases (25 conventional donors, 83 ICOD donors). A total of 21.6% of potential ICOD donors did not evolve to BD, subsequently dying in the ICU. ICOD cases accounted for more than 50% of donors each year. This cohort had an average stay of 2.4 days in the ICU and accounted for a small proportion of total ICU admissions. A total of 68 (81.9%) ICOD donors were finally effective and 146 grafts were extracted, the majority being abdominal organs (liver and kidney). Probability of survival 1 year after liver transplant (ICOD donor) was 90.9%, with 1 case of primary graft failure. Survival 1 year after kidney transplant (ICOD donor) was 92.7%. No differences were detected in survival rates of kidney and liver transplant patients regarding donor type (ICOD vs conventional). CONCLUSIONS: Implementation of an ICOD program allows an increase in the pool of valid and quality grafts for transplant as well as implying a minimum consumption of intensive medicine resources. The results in transplant patients support this strategy.

Static Cold Storage vs Ex Vivo Machine Perfusion: Results From a Comparative Study on Renal Transplant Outcome in a Controlled Donation After Circulatory Death Program.

INTRODUCTION: We aimed to evaluate if ex vivo machine perfusion could minimize the negative impact of cold ischemia on those renal grafts obtained from controlled donation after circulatory death (cDCD). MATERIAL AND METHODS: Prospective observational paired study of kidney transplants from cDCD performed in our center. The kidney from each pair preserved on ice was transplanted first within the first few hours following procurement, while the contralateral kidney was machine-perfused with a LifePort device (Organ Recovery Systems, Brussels, Belgium) and transplanted the following day. RESULTS: A total of 12 cDCDs were included. No differences were observed in delayed graft dysfunction or graft survival between the 2 groups. CONCLUSION: The use of ex vivo perfusion devices is simple and they do not require any large infrastructural or high economic investments, considering the fact that it allows a better selection of recipients and viable organs no longer need to be discarded because of prolonged warm ischemia times.

Improving the Outcomes of Organs Obtained From Controlled Donation After Circulatory Death Donors Using Abdominal Normothermic Regional Perfusion.

The use of donation after circulatory death (DCD) has increased significantly during the past decade. However, warm ischemia results in a greater risk for transplantation. Indeed, controlled DCD (cDCD) was associated with inferior outcomes compared with donation after brain death. The use of abdominal normothermic regional perfusion (nRP) to restore blood flow before organ recovery in cDCD has been proposed as better than rapid recovery to reverse the effect of ischemia and improve recipients' outcome. Here, the first Spanish series using abdominal nRP as an in situ conditioning method is reported. A specific methodology to avoid restoring circulation to the brain after death determination is described. Twenty-seven cDCD donors underwent abdominal nRP during at least 60 min. Thirty-seven kidneys, 11 livers, six bilateral lungs, and one pancreas were transplanted. The 1-year death-censored kidney survival was 91%, and delayed graft function rate was 27%. The 1-year liver survival rate was 90.1% with no cases of ischemic cholangiopathy. Transplanted lungs and pancreas exhibited primary function. The use of nRP may represent an advance to increase the number and quality of grafts in cDCD. Poor results in cDCD livers could be reversed with nRP. Concerns about restoring brain circulation after death are easily solved.

Effects of antibiotic administration delay and inadequacy upon the survival of septic shock patients.

OBJECTIVE: To assess how antibiotic administration delay and inadequacy influence survival in septic shock patients. DESIGN: A prospective, observational cohort study was carried out between September 2005 and September 2010. SCOPE: Patients admitted to the ICU of a third level hospital. PATIENTS: A total of 342 septic shock patients INTERVENTIONS: None VARIABLES OF INTEREST: The time to antibiotic administration (difference between septic shock presentation and first administered dose of antibiotic) and its adequacy (in vitro susceptibility testing of isolated pathogens) were determined. RESULTS: ICU and hospital mortality were 26.4% and 33.5%, respectively. The median delay to administration of the first antibiotic dose was 1.7h. Deceased patients received antibiotics significantly later than survivors (1.3±14.5h vs. 5.8±18.02h; P=.001). Percentage drug inadequacy was 12%. Those patients who received inadequate antibiotics had significantly higher mortality rates (33.8% vs. 51.2%; P=.03). The coexistence of treatment delay and inadequacy was associated to lower survival rates. CONCLUSIONS: Both antibiotic administration delay and inadequacy exert deleterious effects upon the survival of septic shock patients, independently of their characteristics or severity.

Experience of a Maastrich type II non heart beating donor program in a small city: preliminary results.

OBJECTIVE: To study the results of a non-controlled cardiac death (Maastricht type II) donor program in a city of 200,000 inhabitants. The study was initially focused on lung donation and was extended to kidney donation after 9 months. DESIGN: A prospective observational study was conducted between October 2012 and December 2013. SETTING: The Intensive Care Unit of Marqués de Valdecilla University Hospital in Santander (Spain), and surrounding areas. POPULATIONS: Patients (< 55 years) who died of out-of-hospital cardiac arrest. INTERVENTIONS: All out-of-hospital cardiac arrests were treated with mechanical cardiac compression (LUCAS II). The diagnosis of death and organ preservation were performed in the ICU. RESULTS: A total of 14 calls were received, of which three were discarded. Of the 11 potential donors, 7 were effective donors with a median age of 39.5 years (range: 32-48). A total of 5 single lung transplants and four kidney transplants were performed. In addition, corneas and tissues were harvested. The non-valid donors were rejected mainly due to technical problems. There were no donation refusals on the part of the patient relatives. The lung transplant patient survival rate was 100% after one month and 80% after one year. One month after transplantation, the kidney recipients had a serum creatinine concentration of<2mg/dl. The interval from cardiac arrest to renal preservation was 80minutes (range: 71-89), and the interval from cardiac arrest to lung preservation was 84minutes (range: 77-94). CONCLUSIONS: A Maastricht type II donation program in a small city is viable for both abdominal and thoracic organs. The program was initially very cautious, but its potential is easily improvable by increasing donor and by equipping mobile ICU ambulances with mechanical cardiac compression systems. Full management of the donor in the ICU, avoiding the emergency department or operating rooms, reduces the warm ischemia time, thereby improving transplant outcomes.

[Antifungal prophylaxis in the postoperative period of lung transplant surgery in Spain]. / Profilaxis antifúngica en el postoperatorio de trasplante de pulmón en España.

OBJECTIVES: To examine the type and duration of antifungal prophylaxis provided during the postoperative period of lung transplant recipients, together with the most frequent complications during admission to Intensive Care Units in Spain. PATIENTS AND METHODS: A questionnaire was developed including demographic data on each transplant center, the type of antifungal prophylaxis used, its duration, and the most frequent complications. The questionnaire was distributed among the 7 Spanish national lung transplant centers, followed by analysis of the results obtained. RESULTS: All 7 centers completed the questionnaire. All of them provided universal prophylaxis in lung transplant patients. Monotherapy was the most widely used protocol (5/7; 71.4%), with amphotericin B in liposomal or conventional form being the most frequent drug, administered via the inhalatory route. In the case of combination therapy, a great diversity of drugs was observed. The most frequently administered second choice drug was anidulafungin (3/7; 43%), followed by voriconazole (2/7; 28.5%). Antifungal therapy was maintained on an indefinite basis by 43% of the centers. Invasive fungal infection (IFI) in the postoperative period of transplantation during admission to the Intensive Care Unit was suspected in 5-10% of the cases but was confirmed in less than 5%. Among other complications registered in these patients in the Intensive Care Unit, the most frequent problems were respiratory infections (5/7; 71.5%). CONCLUSIONS: Antifungal prophylaxis during the postoperative period of lung transplantation is provided on a universal basis, though consensus is lacking as to the drug of choice, the administration route and the duration of such treatment.

Prediction of kidney transplant outcome by donor quality scoring systems: expanded criteria donor and deceased donor score.

Due to disparity between organ supply and demand, use of kidneys from suboptimal donors has become increasingly common. Several donor quality systems have been developed to identify kidneys with an increased risk for graft dysfunction and loss. The purpose of our study was to compare the utility of deceased donor score (DDS) and expanded criteria donor (ECD) status to predict kidney transplant outcomes in a single center. We analysed 280 deceased donor renal transplantation procedures, collecting data from the prospectively maintained institutional database. Kidney transplant outcome variable included delayed graft function, 1-year glomerular filtration rate (GFR1y), and death-censored graft loss (DCGL). Kidneys were obtained from marginal donors in 45.7% of transplant recipients by DDS and in 24.9% by ECD. DDS-defined marginal donors suffered delayed graft function (DGF) more frequently than nonmarginal donors (40.8% vs 25.0%; P = .006), whereas ECD did not develop DGF at a greater rate. GFR1Y was significantly worse among patients receiving kidneys from marginal donors: DDS 40.3 ± 12.9 vs 57.7 ± 19.4 mL/min/1.73 m(2) (P < .001) and ECD 39.4 ± 14.1 vs 53.8 ± 19.1 mL/min/1.73 m(2) (P < .0001). The most severe donor category defined by DDS (grade D) showed an independently worse death-censored graft survival hazard rate [HR] 2.661, 95% confidence interval [CI], 1.076-6.582; P = .034). DDS and ECD scoring systems are based on donor information available at the time of transplantation that predict 1-year graft function. Moreover in our center, DDS was better to predict DGF and death-censored graft survival than ECD.

Prospective study of biomarkers of immune response in lung transplant recipients.

INTRODUCTION: Studies on biomarkers of tolerance in organ transplantation have been widely performed during the last decade. AIM: To assess biomarkers in relation to evolution of the immune response among lung transplant recipients. METHODS: This multicenter study included 27 lung transplant recipients followed before as well as at 7, 14, 30, 60, 90, and 180 days posttransplantation. Biomarkers of the immune response based on flow cytometry technology were validated in each center. They included intracellular cytokine expression, regulatory T-cell level, as well as lymphocyte surface antigen and CD28 expressions. RESULTS: The 13 patients who developed acute rejection episodes showed increased numbers of regulatory T cells at 12 months posttransplant. Sixteen patients experiencing infections displayed decreased expression of CD69 on CD8 T cells within the first year of follow-up. CONCLUSION: High Treg levels in the peripheral blood of lung transplant recipients were associated with an increased risk of rejection but not infection. Inversely, we observed low levels of activated CD8 T cells in infected patients.

Study of B-cell subpopulations in lung transplant recipients with posttransplant infection.

BACKGROUND: Posttransplant infection after lung transplantation is a common feature due to the immunodeficiency induced by the immunosuppressive load. AIM: To assess B-cell subsets in lung transplant recipients suffering at least one episode of infection within the first year posttransplantation. METHODS: Twenty-eight lung transplant recipients were enrolled in the study. Their overall mean age was 56.6 ± 10.7 years and 10 were women (35.7%). All recipients were treated with steroids, tacrolimus, and mycophenolate mofetil. B-cell subset levels were measured in peripheral blood before as well as 7, 14, 30, 60, 90, and 180 days posttransplantation. RESULTS: No difference in the absolute number of B-cell subsets was observed within the first year of follow-up. However, pre-germinal center-activated naïve B cells (Bm2'), defined as IgD(+)CD38(++), were increased among patients displaying infections within the first year. The increased Bm2' subset was accompanied by a decrease in the double negative (CD27(-)IgD(-)) B-cell population. CONCLUSION: Infections in lung transplant recipients were associated with an increase in the Bm2' subset even before transplantation. It is possible that Bm2' cells have a role in response to infection in lung transplantation.

Disfunción primaria del injerto tras el trasplante pulmonar / Primary graft dysfunction after lung transplantation

El trasplante pulmonar representa una opción terapéutica para procesos pulmonares en los que los tratamientos han fallado o que presenten una evolución rápidamente progresiva. Sin embargo, no está libre de complicaciones, siendo la disfunción primaria del injerto una de ellas. Se trata de una forma de lesión pulmonar aguda, y caracterizada por desarrollarse durante el postoperatorio inmediato, estar asociada a una alta morbi-mortalidad y aumentar el riesgo de bronquiolitis obliterante. Ha presentado diferentes acepciones terminológicas conduciendo a un documento de consenso que precisara su definición en el año 2005. En ese consenso se acordó considerar la disfunción primaria del injerto como edema pulmonar no cardiogénico en las primeras 72 horas de la reperfusión y debido a una alteración del propio parénquima pulmonar. Se han llevado a cabo estudios que tratan de identificar factores de riesgo y de conocer la fisiopatología subyacente para secundariamente desarrollar posibles opciones terapéuticas. Entre las opciones de tratamiento se encuentran el óxido nítrico o el surfactante pulmonar junto con las medidas de soporte como ventilación mecánica o la oxigenación extracórporea (AU)

Lung transplantation is a therapeutic option for pulmonary diseases in which the other treatment options have failed or in cases of rapid disease progression. However, transplantation is not free from complications, and primary graft dysfunction is one of them. Primary graft dysfunction is a form of acute lung injury. It characteristically develops during the immediate postoperative period, being associated to high morbidity and mortality, and increased risk of bronchiolitis obliterans. Different terms have been used in reference to primary graft dysfunction, leading to a consensus document to clarify the definition in 2005. This consensus document regards primary graft dysfunction as non-cardiogenic pulmonary edema developing within 72hours of reperfusion and intrinsically attributable to alteration of the lung parenchyma. A number of studies have attempted to identify risk factors and to establish the underlying physiopathology, with a view to developing potential therapeutic options. Such options include nitric oxide and pulmonary surfactant together with supportive measures such as mechanical ventilation or oxygenation bypass (AU)

Solid organ transplant training objectives for residents.

With the aim of analyzing the current state of the educational objectives in the training of medical residents in solid organ transplantation (SOT), we conducted a review of the status of the official programs of the specialities involved in SOT, focusing particularly on lung transplantation. A survey of medical residents was also conducted to allow reflexion about the topic. We obtained 44 surveys from 4 University Hospitals with active programs in SOT, mainly from intensive care medicine and anesthesiology residents. We detected an important number of courses oriented to organ donation but very limited in terms of basic training in the management of the immediate postoperative period, principles of immunosuppression and updates on immunosuppressive therapy and complications (particularly rejection and infection). We also identified that these educational aspects should be directed not only to medical residents from specialities with a close retation to SOT, but also to all who may at some time have a relation to such patients. The use of information and communication techniques (ICTs), on-line courses and also simulations should be instruments to take into account in the biomedical training of medical residents. We conclude that we need a specific training program in complications of SOT, as well as fundamental principles in immunology and immunosuppressor pharmacology.

Early identification of infectious complications in lung transplant recipients using procalcitonin.

OBJECTIVES: The purpose of this study was to determine how sequential measurements of procalcitonin (PCT) could improve the diagnosis of early infectious complications after lung transplantation, and to compare this molecule with other commonly used markers (serum C-reactive protein [CRP] and leukocyte count). METHODS: Prospective observational study in a 34-bed university hospital intensive care unit (ICU). All lung transplant (LT) recipients between January and November 2010 were included. Biomarkers were measured just before surgery, on ICU admission, and daily on postoperative days 2, 3, 4, and 7. RESULTS: A total of 25 patients were included. Those patients with infectious complications presented with significantly higher levels of PCT as early as the first day after transplantation and during subsequent days. The area under receiver operating characteristic curve for PCT as a predictor of infection ranged between 0.83 and 0.97. PCT cutoff of 8.18 ng/mL on day 2 had a sensitivity of 80% and specificity of 100% for prediction of infection development. Neither CRP levels nor leukocyte count could discriminate between the patients with and without infections at any time. CONCLUSIONS: In contrast with CRP levels and leukocyte counts, measurement of PCT appears to be a useful diagnostic tool in detecting early infectious complications in LT patients.

[Primary graft dysfunction after lung transplantation]. / Disfunción primaria del injerto tras el trasplante pulmonar.

Lung transplantation is a therapeutic option for pulmonary diseases in which the other treatment options have failed or in cases of rapid disease progression. However, transplantation is not free from complications, and primary graft dysfunction is one of them. Primary graft dysfunction is a form of acute lung injury. It characteristically develops during the immediate postoperative period, being associated to high morbidity and mortality, and increased risk of bronchiolitis obliterans. Different terms have been used in reference to primary graft dysfunction, leading to a consensus document to clarify the definition in 2005. This consensus document regards primary graft dysfunction as non-cardiogenic pulmonary edema developing within 72 hours of reperfusion and intrinsically attributable to alteration of the lung parenchyma. A number of studies have attempted to identify risk factors and to establish the underlying physiopathology, with a view to developing potential therapeutic options. Such options include nitric oxide and pulmonary surfactant together with supportive measures such as mechanical ventilation or oxygenation bypass.