Factores que afectan a la calidad del sueño en las unidades de cuidados intensivos / Factors affecting sleep quality in Intensive Care Units

Objetivos: Describir la calidad del sueño e identificar los factores que la afectan. Diseño Estudio observacional descriptivo y transversal realizado con una muestra de conveniencia de 129 pacientes. La diferencia entre los 3tiempos se calculó mediante la prueba de Wilcoxon y la correlación entre variables mediante la r de Spearman. Con análisis de regresión múltiple se relacionaron las variables independientes con «calidad del sueño». Ámbito Servicio de Medicina Intensiva de un hospital terciario. Participantes Pacientes ingresados en la unidad entre febrero de 2016 y diciembre de 2017. Intervenciones Administración de un cuestionario. Variables Ítems del cuestionario Freedman modificado, variables demográficas y de episodio. Resultados Los factores que más afectaron a la calidad del sueño en los 3tiempos de forma constante fueron el ruido y la luz. Hubo diferencias entre los 3 tiempos para los cuidados (p=0,005) y actividades de enfermería (p=0,019). Mediante el modelo de regresión múltiple se encontró que otros factores que influían en la calidad del sueño eran la edad (p=0,012), la ingesta habitual de alcohol (p=0,023), la administración de benzodiacepinas en UCI (p=0,01) y la comorbilidad (p=0,005). Resultaron diferencias significativas en somnolencia entre el alta y el primer día (p≤0,029), y entre el alta y la mitad de la estancia (p=0,001). Conclusiones La somnolencia disminuyó al final de la estancia. Aunque el ruido y la luz fueron los factores más molestos, solo los cuidados y actividades de enfermería resultaron significativos. La edad, la ingesta habitual de alcohol, la administración de benzodiacepinas en UCI y un mayor índice de comorbilidad interfieren negativamente en la calidad del sueño. (AU)

Objective: To report sleep quality and identify related factors. Design A descriptive cross-sectional study was made with a convenience sample of 129 patients. The differences between 3periods were evaluated using the Wilcoxon test and Spearman correlation r. Multiple regression analyses were performed to relate independent variables to sleep quality. Setting The Department of Intensive Care Medicine of a tertiary hospital. Participants Patients admitted between February 2016 and December 2017. Interventions Questionnaire administration. Variables Items of the modified Freedman questionnaire, and demographic and clinical variables. Results External factors interfering with sleep quality were noise and constant light exposure in the 3periods, with significant differences between these periods in nursing care (P=0.005) and nursing activities (P=0.019). The other factors affecting sleep quality and identified by the multivariate regression model were age (P=0.012), daily alcohol intake (P=0.023), benzodiazepine use during admission to the ICU (P=0.01) and comorbidities (P=0.005). There were significant differences in sleepiness between discharge and the first day (P≤0.029) and between discharge and half stay (P=0.001). Conclusions Noise and light were the most annoying factors, but statistical significance was only reached for nursing activities and care. Age, alcohol intake, benzodiazepine use in the ICU and a higher comorbidity index had a negative impact upon sleep. Sleepiness was reduced at the end of stay. (AU)

Factors affecting sleep quality in Intensive Care Units.

OBJECTIVE: To report sleep quality and identify related factors. DESIGN: A descriptive cross-sectional study was made with a convenience sample of 129 patients. The differences between 3 periods were evaluated using the Wilcoxon test and Spearman correlation r. Multiple regression analyses were performed to relate independent variables to sleep quality. SETTING: The Department of Intensive Care Medicine of a tertiary hospital. PARTICIPANTS: Patients admitted between February 2016 and December 2017. INTERVENTIONS: Questionnaire administration. VARIABLES: Items of the modified Freedman questionnaire, and demographic and clinical variables. RESULTS: External factors interfering with sleep quality were noise and constant light exposure in the 3 periods, with significant differences between these periods in nursing care (P = 0.005) and nursing activities (P = 0.019). The other factors affecting sleep quality and identified by the multivariate regression model were age (P = 0.012), daily alcohol intake (P = 0.023), benzodiazepine use during admission to the ICU (P = 0.01) and comorbidities (P = 0.005). There were significant differences in sleepiness between discharge and the first day (P ≤ 0.029) and between discharge and half stay (P = 0.001). CONCLUSIONS: Noise and light were the most annoying factors, but statistical significance was only reached for nursing activities and care. Age, alcohol intake, benzodiazepine use in the ICU and a higher comorbidity index had a negative impact upon sleep. Sleepiness was reduced at the end of stay.

Evaluación psicométrica del cuestionario Freedman para la valoración del sueño en el paciente crítico / Psychometric evaluation of the Freedman questionnaire to assess sleep in critical patients

OBJETIVO: Evaluar las características psicométricas del cuestionario Freedman modificado para la valoración del sueño en el paciente crítico. DISEÑO: Estudio psicométrico. Se exploró la validez de contenido mediante un grupo de expertos y la consistencia interna fue evaluada mediante el coeficiente alfa de Cronbach. Se realizó un análisis factorial para evaluar la validez de constructo; la estabilidad fue medida con análisis test-retest mediante el índice de correlación intraclases. Ámbito: Servicio de Medicina Intensiva de un hospital de referencia. PARTICIPANTES: Pacientes ingresados entre el 23 de febrero de 2016 y el 20 de diciembre de 2017. INTERVENCIONES: Administración de un cuestionario. VARIABLES: Ítems del cuestionario Freedman modificado. RESULTADOS: La pertinencia de los ítems y su definición obtuvieron valores superiores a 3, en una escala tipo Likert con valor máximo de 4 puntos. El alfa de Cronbach indicó un valor global de 0,933. El índice de correlación intraclases obtuvo valores superiores a 0,75 en la mayoría de los ítems del cuestionario. El análisis factorial obtuvo asociación entre las variables analizadas y los 4 factores. CONCLUSIONES: El cuestionario Freedman modificado presentó unas buenas características psicométricas. Puede resultar un instrumento fiable para evaluar la calidad del sueño en el paciente crítico, así como los factores ambientales relacionados

AIM: A study was made of the psychometric characteristics of the modified Freedman questionnaire to assess sleep in critical patients. DESIGN: A psychometric study was carried out, with content validity being explored by a group of experts, and internal consistency based on Cronbach's alpha coefficient. Factor analysis was performed to explore construct validity, and stability was assessed by test-retest analysis. SETTING: The Department of Intensive Care Medicine of a reference hospital. PARTICIPANTS: Patients admitted between 23 February 2016 and 20 December 2017. INTERVENTIONS: Questionnaire administration. VARIABLES: Items of the modified Freedman questionnaire. RESULTS: Item relevance and definition yielded scores > 3 (Likert scale maximum = 4). Cronbach's alpha showed a global value of 0.933. The intraclass correlation index was > 0.75 for most of the items of the questionnaire. Factor analysis allowed the detection of specific associations between the studied variables and the four factors. CONCLUSIONS: The modified Freedman questionnaire showed good psychometric characteristics. It may be a reliable instrument for assessing the quality of sleep in critically ill patients, as well as the environmental factors

Mesenchymal stromal cells for articular cartilage repair: preclinical studies.

Rheumatic diseases such as osteoarthritis (OA) are a major social and economic burden because of the population aging and the lack of curative solutions. An effective cell therapy may be the best treatment option for OA and other cartilage diseases. However, the main cellular strategy used to repair articular cartilage, the transplantation of autologous chondrocytes, is limited to a small number of patients with traumatic lesions. The use of joint replacement after years of disease progression proves the great medical need in current practice. Mesenchymal stromal/stem cells (MSCs) provide an alternative cell source for cartilage regeneration due to numerous advantages, comprising relative ease to isolate and culture, chondrogenic capacity, and anti-inflammatory effects. Initial clinical trials with MSCs have led to encouraging results, but many variables have to be considered to attain true amelioration of disease or repair (type and status of cartilage disease, source and conditions of cells, administration regime, combinatorial approaches). Particularly, allogeneic MSCs are an advantageous cellular product. The animal models chosen for preclinical evaluation are also relevant for successful translation into clinical practice. Considering the limitations in the field, rigorous comparative and validating studies in well-established animal models (including large animals) are still needed to set up the bases for additional clinical trials. The present review of studies performed in small and large animal models should help clarify the applicability of MSC-based therapies for articular cartilage repair.

Factors affecting sleep quality in Intensive Care Units. / Factores que afectan a la calidad del sueño en las unidades de cuidados intensivos.

OBJECTIVE: To report sleep quality and identify related factors. DESIGN: A descriptive cross-sectional study was made with a convenience sample of 129 patients. The differences between 3periods were evaluated using the Wilcoxon test and Spearman correlation r. Multiple regression analyses were performed to relate independent variables to sleep quality. SETTING: The Department of Intensive Care Medicine of a tertiary hospital. PARTICIPANTS: Patients admitted between February 2016 and December 2017. INTERVENTIONS: Questionnaire administration. VARIABLES: Items of the modified Freedman questionnaire, and demographic and clinical variables. RESULTS: External factors interfering with sleep quality were noise and constant light exposure in the 3periods, with significant differences between these periods in nursing care (P=0.005) and nursing activities (P=0.019). The other factors affecting sleep quality and identified by the multivariate regression model were age (P=0.012), daily alcohol intake (P=0.023), benzodiazepine use during admission to the ICU (P=0.01) and comorbidities (P=0.005). There were significant differences in sleepiness between discharge and the first day (P≤0.029) and between discharge and half stay (P=0.001). CONCLUSIONS: Noise and light were the most annoying factors, but statistical significance was only reached for nursing activities and care. Age, alcohol intake, benzodiazepine use in the ICU and a higher comorbidity index had a negative impact upon sleep. Sleepiness was reduced at the end of stay.

Psychometric evaluation of the Freedman questionnaire to assess sleep in critical patients. / Evaluación psicométrica del cuestionario Freedman para la valoración del sueño en el paciente crítico.

AIM: A study was made of the psychometric characteristics of the modified Freedman questionnaire to assess sleep in critical patients. DESIGN: A psychometric study was carried out, with content validity being explored by a group of experts, and internal consistency based on Cronbach's alpha coefficient. Factor analysis was performed to explore construct validity, and stability was assessed by test-retest analysis. SETTING: The Department of Intensive Care Medicine of a reference hospital. PARTICIPANTS: Patients admitted between 23 February 2016 and 20 December 2017. INTERVENTIONS: Questionnaire administration. VARIABLES: Items of the modified Freedman questionnaire. RESULTS: Item relevance and definition yielded scores >3 (Likert scale maximum=4). Cronbach's alpha showed a global value of 0.933. The intraclass correlation index was >0.75 for most of the items of the questionnaire. Factor analysis allowed the detection of specific associations between the studied variables and the four factors. CONCLUSIONS: The modified Freedman questionnaire showed good psychometric characteristics. It may be a reliable instrument for assessing the quality of sleep in critically ill patients, as well as the environmental factors.

Practical considerations for clinical use of mesenchymal stem cells: From the laboratory to the horse.

Since the clinical use of mesenchymal stem cells (MSCs) for treating musculoskeletal injuries is gaining popularity, practitioners should be aware of the factors that may affect MSCs from tissue harvesting for MSC isolation to cell delivery into the injury site. This review provides equine practitioners with up-to-date, practical knowledge for the treatment of equine patients using MSCs. A brief overview of laboratory procedures affecting MSCs is provided, but the main focus is on shipping conditions, routes of administration, injection methods, and which commonly used products can be combined with MSCs and which products should be avoided as they have deleterious effects on cells. There are still several knowledge gaps regarding MSC-based therapies in horses. Therefore, it is important to properly manage the factors which are currently known to affect MSCs, to further strengthen the evidence basis of this treatment.

Comparison of autologous bone marrow and adipose tissue derived mesenchymal stem cells, and platelet rich plasma, for treating surgically induced lesions of the equine superficial digital flexor tendon.

Several therapies have been investigated for equine tendinopathies, but satisfactory long term results have not been achieved consistently and a better understanding of the healing mechanism elicited by regenerative therapies is needed. The aim of this study was to assess the separate effects of autologous bone marrow (BM) and adipose tissue (AT) derived mesenchymal stem cells (MSCs), and platelet rich plasma (PRP), for treating lesions induced in the superficial digital flexor tendon (SDFT) of horses. Lesions were created surgically in both SDFTs of the forelimbs of 12 horses and were treated with BM-MSCs (six tendons), AT-MSCs (six tendons) or PRP (six tendons). The remaining six tendons received lactated Ringer's solution as control. Serial ultrasound assessment was performed prior to treatment and at 2, 6, 10, 20 and 45 weeks post-treatment. At 45 weeks, histopathology and gene expression analyses were performed. At week 6, the ultrasound echogenicity score in tendons treated with BM-MSCs suggested earlier improvement, whilst all treatment groups reached the same level at week 10, which was superior to the control group. Collagen orientation scores on histological examination suggested a better outcome in treated tendons. Gene expression was indicative of better tissue regeneration after all treatments, especially for BM-MSCs, as suggested by upregulation of collagen type I, decorin, tenascin and matrix metalloproteinase III mRNA. Considering all findings, a clear beneficial effect was elicited by all treatments compared with the control group. Although differences between treatments were relatively small, BM-MSCs resulted in a better outcome than PRP and AT-MSCs.

Inflammatory response to the administration of mesenchymal stem cells in an equine experimental model: effect of autologous, and single and repeat doses of pooled allogeneic cells in healthy joints.

BACKGROUND: Mesenchymal stem cells (MSCs) transplantation has become a promising therapeutic choice for musculoskeletal injuries. Joint-related disorders are highly prevalent in horses. Therefore, these animals are considered as suitable models for testing MSC-based therapies for these diseases. The aim of this study was to investigate the clinical and inflammatory responses to intra-articular single and repeat dose administration of autologous or of pooled allogeneic MSCs in healthy equine healthy joints. Six horses were intra-articularly injected with a single autologous dose of bone marrow derived MSCs (BM-MSCs) and two separate doses of allogeneic BM-MSCs pooled from several donors. All contralateral joints were injected with Lactated Ringer's Solution (LRS) as the control vehicle. Signs of synovitis and lameness were evaluated at days 0, 1, 2, 3, 5 and 10 after injection. Total protein (TP), white blood cell count (WBC) and neutrophil count (NC) in synovial fluid were also measured at the same time-points. RESULTS: A mild synovial effusion without associated lameness was observed after all BM-MSCs injections. The second allogeneic injection caused the lowest signs of synovitis. Local temperature slightly increased after all BM-MSCs treatments compared to the controls. TP, WBC and NC in synovial fluids also increased during days 1 to 5 after all BM-MSCs injections. Both, clinical and synovial parameters were progressively normalized and by day 10 post-inoculation appeared indistinguishable from controls. CONCLUSIONS: Intra-articular administration of an allogeneic pool of BM-MSCs represents a safe therapeutic strategy to enhance MSCs availability. Importantly, the absence of hypersensitivity response to the second allogeneic BM-MSCs injection validates the use of repeat dose treatments to potentiate the therapeutic benefit of these cells. These results notably contribute to the development of stem cell based therapies for equine and human joint diseases.

Effect of inflammatory environment on equine bone marrow derived mesenchymal stem cells immunogenicity and immunomodulatory properties.

Mesenchymal stem cells (MSCs) are being investigated for the treatment of equine joint diseases because of their regenerative potential. Recently, the focus mainly has addressed to their immunomodulatory capacities. Inflammation plays a central role in joint pathologies, since the release of proinflammatory mediators to the synovial fluid (SF) leads to the activation of enzymatic degradation of the cartilage. MSCs can modulate the local immune environment through direct or paracrine interaction with immune cells, suppressing their proliferation and re-addressing their functions. Proinflammatory molecules can induce MSC immunoregulatory potential, but they could also increase the expression of immunogenic molecules. Studying the effect of inflammatory environment on MSC immunomodulation and immunogenicity profiles is mandatory to improve cellular therapies. The aim of this study was to analyse the response of equine bone marrow MSCs (eBM-MSCs) to three inflammatory conditions. Equine BM-MSCs from three animals were exposed to: (a) 20% allogeneic inflammatory SF (SF); (b) 50 ng/ml of TNFα and IFNγ (CK50) and (c) 20 ng/ml of TNFα and IFNγ (CK20). After 72 h of exposure, expression of immunogenic and immunomodulation-related molecules, including cell-to-cell contact and paracrine signalling molecules, were analysed by RT-qPCR and flow cytometry. The gene expression of adhesion molecules was upregulated whereas MSC migration-related genes were downregulated by all inflammatory conditions tested. CK culture conditions significantly upregulated the expression of COX-2, iNOS, IDO and IL-6. MHC-I gene expression was upregulated by all conditions, whereas MHC-II was upregulated only after CK priming. The expression of CD40 did not significantly change, whereas the ligand, CD40L, was downregulated in CK conditions. Flow cytometry showed an increase in the percentage of positive cells and mean fluorescence intensity (MFI) of the MHC-I and MHC-II molecules at CK50 conditions, supporting the gene expression results. These outcomes reinforce the change of the immunophenotype of the eBM-MSCs according to the surrounding conditions. Inflammatory synovial environment did not lead to significant changes, so the environment found by eBM-MSCs when they are intraarticular administered may not be enough to activate their immunomodulatory potential. CK priming at tested doses enhances the immunoregulatory profile of eBM-MSCs, which may promote a therapeutic benefit. Even if CK priming induced an upregulation of MHC expression, costimulatory molecule expression however was not upregulated, suggesting that immunogenicity might not be increased. This study provides a better understanding about the behaviour of eBM-MSCs inside the inflamed joint and constitutes a first step to improve MSC-based therapies for equine joint diseases.