Risk of developing myelodysplastic syndrome (MDS) is significantly increased in both multiple myeloma (MM) and monoclonal gammopathy of undetermined significance, suggesting that it is therapy ...independent. However, the incidence and sequelae of dysplastic hematopoiesis at diagnosis are unknown. Here, we used multidimensional flow cytometry (MFC) to prospectively screen for the presence of MDS-associated phenotypic alterations (MDS-PA) in the bone marrow of 285 patients with MM enrolled in the PETHEMA/GEM2012MENOS65 trial (#NCT01916252). We investigated the clinical significance of monocytic MDS-PA in a larger series of 1252 patients enrolled in 4 PETHEMA/GEM protocols. At diagnosis, 33 (11.6%) of 285 cases displayed MDS-PA. Bulk and single-cell–targeted sequencing of MDS recurrently mutated genes in CD34+ progenitors (and dysplastic lineages) from 67 patients revealed clonal hematopoiesis in 13 (50%) of 26 cases with MDS-PA vs 9 (22%) of 41 without MDS-PA; TET2 and NRAS were the most frequently mutated genes. Dynamics of MDS-PA at diagnosis and after autologous transplant were evaluated in 86 of 285 patients and showed that in most cases (69 of 86 80%), MDS-PA either persisted or remained absent in patients with or without MDS-PA at diagnosis, respectively. Noteworthy, MDS-associated mutations infrequently emerged after high-dose therapy. Based on MFC profiling, patients with MDS-PA have altered hematopoiesis and T regulatory cell distribution in the tumor microenvironment. Importantly, the presence of monocytic MDS-PA at diagnosis anticipated greater risk of hematologic toxicity and was independently associated with inferior progression-free survival (hazard ratio, 1.5; P = .02) and overall survival (hazard ratio, 1.7; P = .01). This study reveals the biological and clinical significance of dysplastic hematopoiesis in newly diagnosed MM, which can be screened with moderate sensitivity using cost-effective MFC.
•Approximately 1 of 10 patients with MM displays MDS-associated phenotypic abnormalities at diagnosis and have inferior survival.•MDS-associated phenotypic abnormalities modify the tumor microenvironment and induce greater risk of hematologic toxicity from treatment.
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Background
Immunotherapy has become a standard treatment for lung cancer; however, the high cost makes it necessary to assess health outcomes.
Objective
The aim of this study was to evaluate the ...effectiveness, safety and economic cost of nivolumab in real-world clinical practice.
Setting
Fifteen regional and academic hospitals from Spain participated in this study.
Methods
This study was a retrospective, multicentre and observational study involving patients who experienced progression after first-line therapy for non-small-cell lung cancer and were treated with nivolumab between January 2016 and July 2017. Effectiveness and safety were evaluated by the oncologist, and the data from the electronic clinical records of the patients were collected by the research team. Economic cost was calculated using the cost of acquiring nivolumab for the public health system.
Main outcome measures
Effectiveness variables were overall survival (OS) and progression-free survival (PFS). The safety variable was the incidence of adverse events (AEs), and the cost per life-year gained (LYG) was the economic variable.
Results
A total of 221 patients were enrolled (83.7% men). The mean age was 64.5 years, and 84.6% of the patients had an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0–1. Squamous tumours accounted for 59.7% of the total, and 78.7% of the patients presented a time since platinum therapy (TPT) > 6 months. The mean nivolumab dose was 216 mg (SD 211), and the treatment duration was 7.0 months (95% CI 5.8–8.1). The median PFS was 5.3 months (95% CI 3.2–7.3), and OS was 9.7 months (95% CI 7.6–11.8). The median PFS and OS values were statistically significantly superior for patients with an ECOG score of 0–1 and for patients with a TPT > 6 months. The median OS was also statistically significantly superior for patients with non-squamous histology. Regarding safety, 71% of the patients presented AEs of any grade, and in 18.6%, the nivolumab treatment had to be delayed or discontinued. The cost of nivolumab per patient was €19,910.00 (SD 19,369), and the cost per LYG was €110,026.00 (€77,557.00–€231,171.00).
Conclusions
This study confirms that the efficacy and safety of nivolumab treatment in a real population are comparable to the results obtained in clinical trials. A greater clinical benefit of nivolumab therapy was observed in patients with an ECOG score of 0–1, a TPT > 6 months or non-squamous histology. Despite the benefit observed, the cost per LYG is above the threshold of efficiency established by public health institutes.
Introducción: Los pacientes sometidos a Trasplante de Células Madre Hematopoyéticas o trasplante de médula padecen varias complicaciones nutricionales. El objetivo del estudio fue realizar una ...descripción prospectiva en estos pacientes.Material y métodos: Se reclutaron 14 pacientes con una edad media de 48,0±9,8 años. Resultados: El 28,6% padecía sobrepeso, el 14,3% obesidad y el 57,1% tenía un peso normal, con una evoluciónentre -0,3±0,3 kg/m2 (normopeso) hasta -3,1±0,2 kg/m2 (obesidad). Se observó una pérdida de peso variable, de hasta 7,3±0,7% en pacientes con mayor Índice de Masa Corporal (IMC). La composición corporal también empeoró al alta, con una evolución de la circunferencia braquial de -1,7±0,4 cm en trasplantes alogénicos y -2±4,5 cm en trasplantes autólogos. Un 42,9% de hombres y 28,6% de mujeres eran dados de alta con un Índice de Masa Libre de Grasa (IMLG) por debajo de las recomendaciones, incrementándose desde el ingreso en hombres (desde un 14,3%). Se observa una pérdida de fuerza muscular, en trasplantes alogénicos de -5,0±1,5 kg en el caso de hombres, y -3,0±0,5 kg en mujeres; en autólogos, de -5 kg y -4 kg respectivamente. Sobre síntomas, al inicio existía una alta prevalencia de vómitos (71,4%), náuseas (42,9%) o saciedad temprana (57,1%); durante la hospitalización, destaca la saciedad temprana (92,9%), náuseas (71,4%), vómitos (71,4%), disgeusia (57,1%), diarrea (50%) y anorexia (50%). Conclusiones: Los pacientes admitidos para trasplante de médula ósea están aparentemente bien nutridos, y existe un deterioro durante la hospitalización; parece adecuado implementar estrategias dietéticas durante la hospitalización para optimizar la ingesta y prevenir la malnutrición.
Summary
The aim of the study was to analyse the epidemiology and prognosis of candidaemia in elderly patients. We performed a comparison of clinical presentation of candidaemia according to age and a ...study of hazard factors within a prospective programme performed in 29 hospitals. One hundred and seventy‐six episodes occurred in elderly patients (>75 years), 227 episodes in middle‐aged patients (61‐75 years) and 232 episodes in younger patients (16‐60 years). Central venous catheter, parenteral nutrition, neutropenia, immunosuppressive therapy and candidaemia caused by Candida parapsilosis were less frequent in elderly patients. These patients received inadequate antifungal therapy (57.3%) more frequently than middle‐aged and younger patients (40.5% P < .001). Mortality during the first week (20%) and 30 days (42%) was higher in elderly patients. The variables independently associated with mortality in elderly patients during the first 7 days were acute renal failure (OR: 2.64), Pitt score (OR: 1.57) and appropriate antifungal therapy (OR: 0.132). Primary candidaemia (OR: 2.93), acute renal failure (OR: 3.68), Pitt score (OR: 1.38), appropriate antifungal therapy (OR: 0.3) and early removal of the central catheter (OR: 0.47) were independently associated with 30‐day mortality.In conclussion, inadequate antifungal treatment is frequently prescribed to elderly patients with candidaemia and is related with early and late mortality.
Background Patients with polypharmacy suffer from complex medical conditions involving a large healthcare burden. This study aimed to describe the characteristics and utilization of primary care (PC) ...and hospital care (HC) and factors associated in chronic patients with polypharmacy, stratifying by adjusted morbidity groups (AMG) risk level, sex and age, and comparing with non-polypharmacy. Methods Cross-sectional study conducted in a Spanish basic healthcare area. Studied patients were those over 18 years with chronic diseases identified by the AMG tool from Madrid electronic clinical record, which was the data source. Sociodemographic, sociofunctional, clinical and healthcare utilization variables were described and compared by risk level, sex, age and having or not polypharmacy. Factors associated with healthcare utilization in polypharmacy patients were determined by a negative binomial regression model. Results In the area studied, 61.3% patients had chronic diseases, of which 16.9% had polypharmacy vs. 83.1% without polypharmacy. Patients with polypharmacy (vs. non-polypharmacy) mean age was 82.7 (vs. 52.7), 68.9% (vs. 60.7%) were women, and 22.0% (vs. 1.2%) high risk. Their average number of chronic diseases was 4.8 (vs. 2.2), and 95.6% (vs. 56.9%) had multimorbidity. Their mean number of annual healthcare contacts was 30.3 (vs. 10.5), 25.9 (vs. 8.8) with PC and 4.4 (vs. 1.7) with HC. Factors associated with a greater PC utilization in patients with polypharmacy were elevated complexity, high risk level and dysrhythmia. Variables associated with a higher HC utilization were also increased complexity and high risk, in addition to male sex, being in palliative care, having a primary caregiver, suffering from neoplasia (specifically lymphoma or leukaemia) and arthritis, whereas older age and immobilization were negatively associated. Conclusions Polypharmacy population compared to non-polypharmacy was characterized by a more advanced age, predominance of women, high-risk, complexity, numerous comorbidities, dependency and remarkable healthcare utilization. These findings could help healthcare policy makers to optimize the distribution of resources and professionals within PC and HC systems, aiming for the improvement of polypharmacy management and rational use of medicines while reducing costs attributed to healthcare utilization by these patients. Keywords: Polypharmacy, Chronic disease, Primary care, Hospital care, Healthcare utilization, Management, Morbidity grouper, Stratification
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Our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe ...the auditing systems developed by the Spanish VATS Group (GEVATS).
We conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for “90-day mortality” and “Grade IIIb-V complications”.
The series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres’ median recruitment rate was 99% (25–75th:76–100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95–100% rates as reference): grade IIIb-V OR=0.61 (p=0.081), 90-day mortality OR=0.46 (p=0.051).
More than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort.
Nuestro estudio buscó conocer el grado de implementación actual de la cirugía toracoscópica asistida por video (VATS, por sus siglas en inglés) para las resecciones pulmonares anatómicas en España. Presentamos nuestros resultados iniciales y describimos los sistemas de auditoría desarrollados por el grupo español de VATS (GEVATS).
Realizamos un estudio de cohortes prospectivo multicéntrico que incluyó pacientes que fueron tratados con resecciones pulmonares anatómicas entre el 20/12/2016 y el 20/03/2018. Los controles de calidad principales consistieron en determinar la tasa de reclutamiento de cada centro y la precisión de los datos perioperatorios recolectados en base a seis variables clave. Se analizaron las implicaciones de una baja tasa de reclutamiento para “mortalidad a los 90 días” y “complicaciones de grado IIIb-V”.
La serie estaba compuesta por 3533 casos (1917 VATS; 54,3%) en 33 servicios. La mediana de la tasa de reclutamiento de los centros fue del 99% (p25-p75: 76-100%), con una tasa de reclutamiento global del 83% y una precisión de los datos del 98%. No pudimos demostrar una asociación significativa entre la tasa de reclutamiento y el riesgo de morbi-mortalidad, pero se encontró una tendencia en el análisis no ajustado para aquellos centros con tasas de reclutamiento inferiores al 80% (usando los centros con tasas de 95-100% como referencia): OR=0,61 para el grado IIIb-V (p=0,081), OR=0,46 para la mortalidad a los 90 días (p=0,051).
Más de la mitad de las resecciones pulmonares anatómicas en España se realizan a través de VATS. Según nuestros resultados, la tasa de reclutamiento del centro y sus posibles implicaciones debido al sesgo de selección, deberían recibir más atención por parte de los principales estudios multicéntricos voluntarios de nuestra especialidad. La alta representatividad y la confiabilidad de los datos de GEVATS constituyen un punto de partida fundamental para esta cohorte nacional.
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