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1.
Artigo em Inglês | MEDLINE | ID: mdl-34622441

RESUMO

BACKGROUND: The prediction of in-hospital mortality for ICU patients with COVID-19 is fundamental to treatment and resource allocation. The main purpose was to develop an easily implemented score for such prediction. METHODS: This was an observational, multicenter, development and validation study on a national critical care dataset of COVID-19 patients. A systematic literature review was performed to determine variables possibly important for COVID-19 mortality prediction. Using a logistic multivariable model with a LASSO penalty, we developed the Rapid Evaluation of Coronavirus Illness Severity (RECOILS) score and compared its performance against published scores. RESULTS: Our development (validation) cohort consisted of 1480 (937) adult patients from 14 (11) Dutch ICUs admitted between March 2020 and April 2021. Median age was 65 (65) years, 31% (26%) died in hospital, 74% (72%) were males, average length of ICU stay was 7.83 (10.25) days and average length of hospital stay was 15.90 (19.92) days. Age, platelets, PaO2/FiO2 ratio, pH, blood urea nitrogen, temperature, PaCO2, Glasgow Coma Scale (GCS) score measured within +/- 24 hours of ICU admission were used to develop the score. The AUROC of RECOILS score was 0.75 (CI 0.71-0.78) which was higher than that of any previously reported predictive scores (0.68 (CI 0.64-0.71), 0.61 (CI 0.58-0.66), 0.67 (CI 0.63-0.70), 0.70 (CI 0.67-0.74) for ISARIC 4C Mortality Score, SOFA, SAPS-III, and age, respectively). CONCLUSIONS: Using a large dataset from multiple Dutch ICUs, we developed a predictive score for mortality of COVID-19 patients admitted to ICU, which outperformed other predictive scores reported so far.

2.
BMJ Open ; 11(9): e049704, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34588250

RESUMO

INTRODUCTION: Intensive care unit (ICU) admission of a relative might lead to psychological distress and complicated grief (post-intensive care syndrome-family; PICS-F). Evidence suggests that increased distress during ICU stay increases risk of PICS-F, resulting in difficulty returning to their normal lives after the ICU experience. Effective interventions to improve PICS-F are currently lacking. In the present trial, we hypothesised that information provision using ICU-specific Virtual Reality for Family members/relatives (ICU-VR-F) may improve understanding of the ICU and subsequently improve psychological well-being and quality of life in relatives of patients admitted to the ICU. METHODS AND ANALYSIS: This multicentre, clustered randomised controlled trial will be conducted from January to December 2021 in the mixed medical-surgical ICUs of four hospitals in Rotterdam, the Netherlands. We aim to include adult relatives of 160 ICU patients with an expected ICU length of stay over 72 hours. Participants will be randomised clustered per patient in a 1:1 ratio to either the intervention or control group. Participants allocated to the intervention group will receive ICU-VR-F, an information video that can be watched in VR, while the control group will receive usual care. Initiation of ICU-VR-F will be during their hospital visit unless participants cannot visit the hospital due to COVID-19 regulations, then VR can be watched digitally at home. The primary objective is to study the effect of ICU-VR-F on psychological well-being and quality of life up to 6 months after the patients' ICU discharge. The secondary outcome is the degree of understanding of ICU treatment and ICU modalities. ETHICS AND DISSEMINATION: The Medical Ethics Committee of the Erasmus Medical Centre, Rotterdam, the Netherlands, approved the study and local approval was obtained from each participating centre (NL73670.078.20). Our findings will be disseminated by presentation of the results at (inter)national conferences and publication in scientific, peer-reviewed journals. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (TrialRegister.nl, NL9220).


Assuntos
COVID-19 , Realidade Virtual , Adulto , Estado Terminal , Humanos , Unidades de Terapia Intensiva , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2
3.
Trials ; 22(1): 546, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407846

RESUMO

BACKGROUND: High-dose intravenous vitamin C directly scavenges and decreases the production of harmful reactive oxygen species (ROS) generated during ischemia/reperfusion after a cardiac arrest. The aim of this study is to investigate whether short-term treatment with a supplementary or very high-dose intravenous vitamin C reduces organ failure in post-cardiac arrest patients. METHODS: This is a double-blind, multi-center, randomized placebo-controlled trial conducted in 7 intensive care units (ICUs) in The Netherlands. A total of 270 patients with cardiac arrest and return of spontaneous circulation will be randomly assigned to three groups of 90 patients (1:1:1 ratio, stratified by site and age). Patients will intravenously receive a placebo, a supplementation dose of 3 g of vitamin C or a pharmacological dose of 10 g of vitamin C per day for 96 h. The primary endpoint is organ failure at 96 h as measured by the Resuscitation-Sequential Organ Failure Assessment (R-SOFA) score at 96 h minus the baseline score (delta R-SOFA). Secondary endpoints are a neurological outcome, mortality, length of ICU and hospital stay, myocardial injury, vasopressor support, lung injury score, ventilator-free days, renal function, ICU-acquired weakness, delirium, oxidative stress parameters, and plasma vitamin C concentrations. DISCUSSION: Vitamin C supplementation is safe and preclinical studies have shown beneficial effects of high-dose IV vitamin C in cardiac arrest models. This is the first RCT to assess the clinical effect of intravenous vitamin C on organ dysfunction in critically ill patients after cardiac arrest. TRIAL REGISTRATION: ClinicalTrials.gov NCT03509662. Registered on April 26, 2018. https://clinicaltrials.gov/ct2/show/NCT03509662 European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL.


Assuntos
Síndrome Pós-Parada Cardíaca , Ácido Ascórbico , Método Duplo-Cego , Humanos , Estudos Multicêntricos como Assunto , Escores de Disfunção Orgânica , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
4.
JAMA ; 326(10): 940-948, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34463696

RESUMO

Importance: Hyperoxemia may increase organ dysfunction in critically ill patients, but optimal oxygenation targets are unknown. Objective: To determine whether a low-normal Pao2 target compared with a high-normal target reduces organ dysfunction in critically ill patients with systemic inflammatory response syndrome (SIRS). Design, Setting, and Participants: Multicenter randomized clinical trial in 4 intensive care units in the Netherlands. Enrollment was from February 2015 to October 2018, with end of follow-up to January 2019, and included adult patients admitted with 2 or more SIRS criteria and expected stay of longer than 48 hours. A total of 9925 patients were screened for eligibility, of whom 574 fulfilled the enrollment criteria and were randomized. Interventions: Target Pao2 ranges were 8 to 12 kPa (low-normal, n = 205) and 14 to 18 kPa (high-normal, n = 195). An inspired oxygen fraction greater than 0.60 was applied only when clinically indicated. Main Outcomes and Measures: Primary end point was SOFARANK, a ranked outcome of nonrespiratory organ failure quantified by the nonrespiratory components of the Sequential Organ Failure Assessment (SOFA) score, summed over the first 14 study days. Participants were ranked from fastest organ failure improvement (lowest scores) to worsening organ failure or death (highest scores). Secondary end points were duration of mechanical ventilation, in-hospital mortality, and hypoxemic measurements. Results: Among the 574 patients who were randomized, 400 (70%) were enrolled within 24 hours (median age, 68 years; 140 women [35%]), all of whom completed the trial. The median Pao2 difference between the groups was -1.93 kPa (95% CI, -2.12 to -1.74; P < .001). The median SOFARANK score was -35 points in the low-normal Pao2 group vs -40 in the high-normal Pao2 group (median difference, 10 [95% CI, 0 to 21]; P = .06). There was no significant difference in median duration of mechanical ventilation (3.4 vs 3.1 days; median difference, -0.15 [95% CI, -0.88 to 0.47]; P = .59) and in-hospital mortality (32% vs 31%; odds ratio, 1.04 [95% CI, 0.67 to 1.63]; P = .91). Mild hypoxemic measurements occurred more often in the low-normal group (1.9% vs 1.2%; median difference, 0.73 [95% CI, 0.30 to 1.20]; P < .001). Acute kidney failure developed in 20 patients (10%) in the low-normal Pao2 group and 21 patients (11%) in the high-normal Pao2 group, and acute myocardial infarction in 6 patients (2.9%) in the low-normal Pao2 group and 7 patients (3.6%) in the high-normal Pao2 group. Conclusions and Relevance: Among critically ill patients with 2 or more SIRS criteria, treatment with a low-normal Pao2 target compared with a high-normal Pao2 target did not result in a statistically significant reduction in organ dysfunction. However, the study may have had limited power to detect a smaller treatment effect than was hypothesized. Trial Registration: ClinicalTrials.gov Identifier: NCT02321072.


Assuntos
Estado Terminal/terapia , Oxigenoterapia/métodos , Oxigênio/administração & dosagem , Idoso , Estado Terminal/classificação , Feminino , Humanos , Hiperóxia/etiologia , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/prevenção & controle , Escores de Disfunção Orgânica , Oxigênio/sangue , Oxigenoterapia/efeitos adversos , Respiração Artificial , Síndrome de Resposta Inflamatória Sistêmica
5.
Crit Care ; 25(1): 304, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425864

RESUMO

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has underlined the urgent need for reliable, multicenter, and full-admission intensive care data to advance our understanding of the course of the disease and investigate potential treatment strategies. In this study, we present the Dutch Data Warehouse (DDW), the first multicenter electronic health record (EHR) database with full-admission data from critically ill COVID-19 patients. METHODS: A nation-wide data sharing collaboration was launched at the beginning of the pandemic in March 2020. All hospitals in the Netherlands were asked to participate and share pseudonymized EHR data from adult critically ill COVID-19 patients. Data included patient demographics, clinical observations, administered medication, laboratory determinations, and data from vital sign monitors and life support devices. Data sharing agreements were signed with participating hospitals before any data transfers took place. Data were extracted from the local EHRs with prespecified queries and combined into a staging dataset through an extract-transform-load (ETL) pipeline. In the consecutive processing pipeline, data were mapped to a common concept vocabulary and enriched with derived concepts. Data validation was a continuous process throughout the project. All participating hospitals have access to the DDW. Within legal and ethical boundaries, data are available to clinicians and researchers. RESULTS: Out of the 81 intensive care units in the Netherlands, 66 participated in the collaboration, 47 have signed the data sharing agreement, and 35 have shared their data. Data from 25 hospitals have passed through the ETL and processing pipeline. Currently, 3464 patients are included in the DDW, both from wave 1 and wave 2 in the Netherlands. More than 200 million clinical data points are available. Overall ICU mortality was 24.4%. Respiratory and hemodynamic parameters were most frequently measured throughout a patient's stay. For each patient, all administered medication and their daily fluid balance were available. Missing data are reported for each descriptive. CONCLUSIONS: In this study, we show that EHR data from critically ill COVID-19 patients may be lawfully collected and can be combined into a data warehouse. These initiatives are indispensable to advance medical data science in the field of intensive care medicine.


Assuntos
COVID-19/epidemiologia , Estado Terminal/epidemiologia , Data Warehousing/estatística & dados numéricos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Cuidados Críticos , Humanos , Países Baixos
6.
Ned Tijdschr Geneeskd ; 1652021 04 29.
Artigo em Holandês | MEDLINE | ID: mdl-34346627

RESUMO

BACKGROUND: The decision to attempt or refrain from resuscitation is preferably based on prognostic factors for outcome and subsequently communicated with patients. Both patients and physicians consider good communication important, however little is known about patient involvement in and understanding of cardiopulmonary resuscitation (CPR) directives. AIM: To determine the prevalence of Do Not Resuscitate (DNR)-orders, to describe recollection of CPR-directive conversations and factors associated with patient recollection and understanding. METHODS: This was a two-week nationwide multicentre cross-sectional observational study using a study-specific survey. The study population consisted of patients admitted to non-monitored wards in 13 hospitals. Data were collected from the electronic medical record (EMR) concerning CPR-directive, comorbidity and at-home medication. Patients reported their perception and expectations about CPR-counselling through a questionnaire. RESULTS: A total of 1136 patients completed the questionnaire. Patients' CPR-directives were documented in the EMR as follows: 63.7% full code, 27.5% DNR and in 8.8% no directive was documented. DNR was most often documented for patients >80 years (66.4%) and in patients using >10 medications (45.3%). Overall, 55.8% of patients recalled having had a conversation about their CPR-directive and 48.1% patients reported the same CPR-directive as the EMR. Most patients had a good experience with the CPR-directive conversation in general (66.1%), as well as its timing (84%) and location (94%) specifically. CONCLUSIONS: The average DNR-prevalence is 27.5%. Correct understanding of their CPR-directive is lowest in patients aged ≥80 years and multimorbid patients. CPR-directive counselling should focus more on patient involvement and their correct understanding.


Assuntos
Reanimação Cardiopulmonar , Ordens quanto à Conduta (Ética Médica) , Comunicação , Estudos Transversais , Hospitais , Humanos
7.
PLoS One ; 16(8): e0255774, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34379644

RESUMO

INTRODUCTION: Illnesses requiring hospitalization are known to negatively impact psychological well-being and health-related quality of life (HRQoL) after discharge. The impact of hospitalization during the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) pandemic on psychological well-being and health-related quality of life is expected to be higher due to the exceptional circumstances within and outside the hospital during the pandemic surge. The objective of this study was to quantify psychological distress up to three months after discharge in patients hospitalized during the first coronavirus disease 2019 (COVID-19) pandemic wave. We also aimed to determine HRQoL, to explore predictors for psychological distress and HRQoL, and to examine whether psychological distress was higher in COVID-19 confirmed patients, and in those treated in Intensive Care Units (ICUs). METHODS: In this single-center, observational cohort study, adult patients hospitalized with symptoms suggestive of COVID-19 between March 16 and April 28, 2020, were enrolled. Patients were stratified in analyses based on SARS-CoV-2 PCR results and the necessity for ICU treatment. The primary outcome was psychological distress, expressed as symptoms of post-traumatic stress disorder (PTSD), anxiety, and depression, up to three months post-discharge. Health-related quality of life (HRQoL) was the secondary outcome. Exploratory outcomes comprised predictors for psychological distress and HRQoL. RESULTS: 294 of 622 eligible patients participated in this study (median age 64 years, 36% female). 16% and 13% of these patients reported probable PTSD, 29% and 20% probable anxiety, and 32% and 24% probabledepression at one and three months after hospital discharge, respectively. ICU patients reported less frequently probable depression, but no differences were found in PTSD, anxiety, or overall HRQoL. COVID-19 patients had a worse physical quality of life one month after discharge, and ICU patients reported a better mental quality of life three months after discharge. PTSD severity was predicted by time after discharge and being Caucasian. Severity of anxiety was predicted by time after discharge and being Caucasian. Depression severity was predicted by time after discharge and educational level. CONCLUSION: COVID-19 suspected patients hospitalized during the pandemic frequently suffer from psychological distress and poor health-related quality of life after hospital discharge. Non-COVID-19 and non-ICU patients appear to be at least as affected as COVID-19 and ICU patients, underscoring that (post-)hospital pandemic care should not predominantly focus on COVID-19 infected patients.


Assuntos
COVID-19/diagnóstico , Angústia Psicológica , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/etiologia , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/virologia , Estudos de Coortes , Depressão/etiologia , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Alta do Paciente , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Transtornos de Estresse Pós-Traumáticos/etiologia
8.
Resuscitation ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34271127

RESUMO

INTRODUCTION: In-hospital cardiac arrest (IHCA) is an adverse event associated with high mortality. Because of the impact of IHCA more data is needed on incidence, outcomes and associated factors that are present prior to cardiac arrest. The aim was to assess one-year survival, patient-centred outcomes after IHCA and their associated pre-arrest factors. METHODS: A multicentre prospective cohort study in 25 hospitals between January 1st 2017 and May 31st 2018. Patients ≥ 18 years receiving cardiopulmonary resuscitation (CPR) for IHCA were included. Data were collected using Utstein and COSCA-criteria, supplemented by pre-arrest Modified Rankin Scale (MRS, functional status) and morbidity through the Charlson Comorbidity Index (CCI). Main outcomes were survival, health-related quality of life (HRQoL, EuroQoL) and functional status (MRS) after one-year. RESULTS: A total of 713 patients were included, 64.5% was male, median age was 63 years (IQR 52-72) and 72.8% had a non-shockable rhythm, 394 (55.3%) achieved ROSC, 231 (32.4%) survived to hospital discharge and 198 (27.8%) survived one year after cardiac arrest. Higher pre-arrest MRS, age and CCI were associated with mortality. At one year, patients rated HRQoL 72/100 points on the EQ-VAS and 69.7% was functionally independent. CONCLUSION: One-year survival after IHCA in this study is 27.8%, which is relatively high compared to previous studies. Survival is associated with a patient's pre-arrest functional status and morbidity. HRQoL appears acceptable, however functional rehabilitation warrants attention. These findings provide a comprehensive insight in in-hospital cardiac arrest prognosis.

9.
PLoS One ; 16(5): e0250740, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33983967

RESUMO

OBJECTIVE: In the context of an ongoing debate on the potential risks of hypoxemia and hyperoxemia, it seems prudent to maintain the partial arterial oxygen pressure (PaO2) in a physiological range during administration of supplemental oxygen. The PaO2 and peripheral oxygen saturation (SpO2) are closely related and both are used to monitor oxygenation status. However, SpO2 values cannot be used as an exact substitute for PaO2. The aim of this study in acutely ill and stable patients was to determine at which SpO2 level PaO2 is more or less certain to be in the physiological range. METHODS: This is an observational study prospectively collecting data pairs of PaO2 and SpO2 values in patients admitted to the emergency room or intensive care unit (Prospective Inpatient Acutely ill cohort; PIA cohort). A second cohort of retrospective data of patients who underwent pulmonary function testing was also included (Retrospective Outpatient Pulmonary cohort; ROP cohort). Arterial hypoxemia was defined as PaO2 < 60 mmHg and hyperoxemia as PaO2 > 125 mmHg. The SpO2 cut-off values with the lowest risk of hypoxemia and hyperoxemia were determined as the 95th percentile of the observed SpO2 values corresponding with the observed hypoxemic and hyperoxemic PaO2 values. RESULTS: 220 data pairs were collected in the PIA cohort. 95% of hypoxemic PaO2 measurements occurred in patients with an SpO2 below 94%, and 95% of hyperoxemic PaO2 measurements occurred in patients with an SpO2 above 96%. Additionally in the 1379 data pairs of the ROP cohort, 95% of hypoxemic PaO2 measurements occurred in patients with an SpO2 below 93%. CONCLUSION: The SpO2 level marking an increased risk of arterial hypoxemia is not substantially different in acutely ill versus stable patients. In acutely ill patients receiving supplemental oxygen an SpO2 target of 95% maximizes the likelihood of maintaining PaO2 in the physiological range.

10.
Trials ; 22(1): 328, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952318

RESUMO

BACKGROUND: The SARS-CoV-2 outbreak has resulted in a tremendous increase in hospital and intensive care unit (ICU) admissions all over the world. Patients with severe coronavirus disease 2019 (COVID-19) warranting ICU treatment usually have prolonged mechanical ventilation and are expected to be prone to develop psychological impairments, such as post-traumatic stress disorder (PTSD), anxiety and depression, which negatively impact quality of life. To date, no effective treatment strategy is available. In the current trial, we aim to assess the effect of an ICU-specific virtual reality (ICU-VR) intervention on psychological well-being and quality of life after COVID-19 ICU treatment. METHODS: In this multicentre, randomized controlled trial, we aim to examine whether COVID-19-specific ICU-VR, offered 3 months after hospital discharge, improves psychological well-being and quality of life. Secondary objectives are, firstly, to examine the intra-group changes in psychological well-being and quality of life and the inter-group differences in psychological well-being and quality of life during follow-up, up to 12 months after hospital discharge, and secondly, to examine patients' satisfaction with and rating of ICU care and aftercare and patients' perspectives on ICU-VR. Eighty adult patients treated for COVID-19 in the mixed-surgical ICUs of four hospitals in Rotterdam, the Netherlands, will be included and randomized (1:1) to either early or late ICU-VR between June 29 and December 31, 2020. Patients randomized to early ICU-VR will receive the ICU-VR intervention during an outpatient clinic visit 3 months after hospital discharge, whereas patients randomized to late ICU-VR will receive ICU-VR 6 months after hospital discharge. Primary outcomes of this study are psychological well-being, assessed using the Impact of Event Scale-Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS), and quality of life, assessed using the European Quality of Life 5 Dimensions (EQ-5D) and RAND-36 questionnaires, up to 6 months after hospital discharge. DISCUSSION: Currently, an effective treatment for psychological sequelae after ICU treatment for specific illnesses is unavailable. Results from this study will provide insight whether virtual reality is a modality that can be used in ICU aftercare to improve psychological well-being and quality of life, or satisfaction, after ICU treatment for specific illnesses such as COVID-19. TRIAL REGISTRATION: This trial has been retrospectively registered on the Netherlands Trial Register on August 14, 2020 ( NL8835 ).


Assuntos
COVID-19 , Realidade Virtual , Adulto , Humanos , Unidades de Terapia Intensiva , Estudos Multicêntricos como Assunto , Países Baixos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Sobreviventes
11.
Intensive Crit Care Nurs ; 61: 102925, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32868188

RESUMO

OBJECTIVES: This study aimed to determine the prevalence, risk factors of delirium and current practice of delirium management in intensive care units of various levels of care. RESEARCH METHODOLOGY/DESIGN: Prospective multicentre cohort study. SETTING: In all adult patients admitted to one of the participating intensive care units on World Delirium Awareness Day 2018, delirium point and period prevalence rates were measured between ICU admission and seven days after the index day. RESULTS: In total, 28 (33%) Dutch intensive care units participated in this study. Point-prevalence was 23% (range 41), and period-prevalence was 42% (range 70). University intensive care units had a significantly higher delirium point-prevalence compared with non-university units (26% vs.15%, p = 0.02). No significant difference were found in period prevalence (50% vs. 39%, p = 0.09). Precipitating risk factors, infection and mechanical ventilation differed significantly between delirium and non-delirium patients. No differences were observed for predisposing risk factors. A delirium protocol was present in 89% of the ICUs. Mean delirium assessment compliance measured was 84% (±19) in 14 units and estimated 59% (±29) in the other 14. CONCLUSION: Delirium prevalence in Dutch intensive care units is substantial and occurs with a large variation, with the highest prevalence in university units. Precipitating risk factors were more frequent in patients with delirium. In the majority of units a delirium management protocol is in place.

12.
J Intensive Care ; 8: 6, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31938546

RESUMO

Background: Because critical illness survivors frequently experience several long-term psychological impairments altering quality of life after ICU, there is a trend towards increasing follow-up care, mainly via ICU follow-up clinics. Despite these and other initiatives, understanding of patient's post-ICU needs to help them cope with their problems and subsequently improve quality of life is largely lacking. Our aim was therefore to assess the needs, expectations and wishes in ICU survivors to receive information with the purpose to help them better grasp ICU treatment. In addition, we assessed the perceived burden of psychological trauma after ICU treatment and the health-related quality of life (HRQoL) up to 2.5 years after ICU discharge. Methods: In a multicentre, retrospective cross-sectional cohort study, the needs and preferred intervention methods were assessed using a self-composed inventory in adult mechanically ventilated ICU survivors (n = 43). Additionally, the Impact of Event Scale Revised, the Beck Depression Inventory, the EuroQol-5D-5L, and the Short-Form 12 were used to assess psychological burden and HRQoL. Results: A substantial proportion of all ICU survivors (59%, 95% CI 44% to 74%) suffered from psychological impairments after ICU treatment. Seventy-five percent of these patients expressed a wish to receive information, but only 36% desired to receive this information using a commonly used information brochure. In contrast, 71% of these patients had a wish to receive information using a video film/VR. Furthermore, only 33% of these patients was satisfied with the information provided by their treating hospital. Patients with psychological PICS reported a worse HRQoL as compared to a normative Dutch sample (P < 0.001) and as compared to patients without psychological PICS (P < 0.01). Conclusions: In a Dutch cohort of critical illness survivors, a substantial part of ICU survivors suffer from psychological impairments, such as PTSD and depression, which was associated with a worse HRQoL. These patients are in need of information, have no desire using an information brochure, but are willing to receive information using a video film/virtual reality module. These results support the exploration of such an intervention.

14.
Biol Blood Marrow Transplant ; 18(1): 55-65, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21963880

RESUMO

Deficient thymopoiesis and retarded recovery of naive CD4(+) T cells are important determinants of insufficient immune-competence following hematopoietic stem cell transplantation (HSCT). Although keratinocyte growth factor (KGF) may protect the thymic epithelium, stem cell factor (SCF) is involved in early thymopoiesis. We evaluated whether KGF alone or combined with SCF would affect thymopoiesis and hematologic recovery following myeloablative autologous HSCT into rhesus macaques. Purpose-bred adult rhesus macaques received 10(6) autologous CD34(+)-selected mononuclear bone marrow cells (BMC)/kg after 9 Gy myeloablative conditioning. Animals were treated with phosphate-buffered saline (PBS) (n = 2), KGF alone (n = 2), or KGF combined with SCF (n = 2). KGF-treated animals showed accelerated hematologic recovery, improved thymopoiesis, and enhanced naive T-cell recovery following transplantation. Improved T cell recovery was not associated with protection against cytomegalovirus reactivation nor with improved antibody response to tetanus toxoid vaccination. Animals treated with KGF and SCF experienced severe adverse events that precluded evaluation of thymopoiesis and T cell recovery. Collectively, our data confirm that KGF may enhance thymopoiesis.


Assuntos
Fator 7 de Crescimento de Fibroblastos/farmacologia , Transplante de Células-Tronco Hematopoéticas/métodos , Fator de Células-Tronco/farmacologia , Linfócitos T/efeitos dos fármacos , Timo/citologia , Animais , Antígenos CD34/biossíntese , Antígenos CD34/imunologia , Macaca mulatta , Masculino , Linfócitos T/imunologia , Timo/efeitos dos fármacos , Timo/imunologia , Transplante Autólogo
15.
Haematologica ; 96(12): 1846-54, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21859737

RESUMO

BACKGROUND: Recovery of thymopoiesis after allogeneic hematopoietic stem cell transplantation is considered pivotal for full immune competence. However, it is still unclear to what extent insufficient recovery of thymopoiesis predicts for subsequent opportunistic infections and non-relapse mortality. DESIGN AND METHODS: A detailed survey of all post-engraftment infectious complications, non-relapse mortality and overall survival during long-term follow-up was performed in 83 recipients of allogeneic stem cell grafts after myeloablative conditioning. Recovery of thymopoiesis was assessed using analysis of signal joint T-cell receptor rearrangement excision circles. The impact of recovery of thymopoiesis at 2, 6, 9 and 12 months post-transplantation on clinical outcome beyond those time points was evaluated by univariate and multivariate Cox regression analyses. RESULTS: The cumulative incidence of severe infections at 12 months after transplantation was 66% with a median number of 1.64 severe infectious episodes per patient. Patients in whom thymopoiesis did not recover were at significantly higher risk of severe infections according to multivariable analysis. Hazard ratios indicated 3- and 9-fold increases in severe infections at 6 and 12 months, respectively. Impaired recovery of thymopoiesis also translated into a higher risk of non-relapse mortality and outweighed pre-transplant risk factors including age, donor type, and disease risk-status. CONCLUSIONS: These results indicate that patients who fail to recover thymopoiesis after allogeneic hematopoietic stem cell transplantation are at very high risk of severe infections and adverse clinical outcome.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Infecções Oportunistas/imunologia , Infecções Oportunistas/mortalidade , Recuperação de Função Fisiológica/imunologia , Timo/imunologia , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Seguimentos , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/etiologia , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Transplante Homólogo
16.
J Immunol ; 187(6): 2974-81, 2011 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-21859956

RESUMO

Deficient thymopoiesis is a pivotal determinant of impaired immune competence following hematopoietic stem cell transplantation (HSCT). Stem cell factor (SCF) is essentially involved in early thymopoiesis. We evaluated whether SCF administration would improve recovery of thymopoiesis following HSCT in immunodeficient mice receiving: 1) bone marrow (BM) transplantation of congenic mice; or 2) human fetal liver HSCT in the human immune system mouse model. Following murine BM transplantation, SCF significantly enhanced thymopoiesis and peripheral T cell recovery in lymph nodes and spleen. SCF did not affect BM lymphoid progenitor recovery and/or expansion. Median thymic cellularity increased from 0.9 in PBS- to 266 × 10(4)/thymus in SCF-treated mice (p = 0.05). Following human HSCT in human immune system mice, higher thymic cellularity was observed in SCF-treated mice. Double-negative and early double-positive thymocyte subsets increased, but especially late double-positive, CD4 single-positive, and CD8 single-positive thymocyte subsets were significantly enhanced (p < 0.05). These results show that exogenous supply of SCF may significantly improve murine and human posttransplant thymopoiesis, for which the effect is probably exerted by directly promoting T cell development intrathymically rather than by enhanced entry of prethymically expanded lymphoid progenitors.


Assuntos
Transplante de Medula Óssea/imunologia , Transplante de Células-Tronco Hematopoéticas , Linfopoese/imunologia , Fator de Células-Tronco/imunologia , Timo/citologia , Animais , Diferenciação Celular/imunologia , Separação Celular , Citometria de Fluxo , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/cirurgia , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T/citologia
17.
Transpl Immunol ; 24(1): 9-16, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20801217

RESUMO

OBJECTIVE: The adoptive transfer of regulatory T cells (Treg) in murine models has been shown to ameliorate graft-versus-host disease while it may preserve the graft-versus-leukemia effect. However, the impact of Treg on infectious immunity after bone marrow transplantation (BMT) is still unclear. Immunocompetence against opportunistic viral infections depends on the kinetics of T cell recovery after BMT through two distinctive processes, i.e. lymphopenia-induced proliferation (LIP) of mature T cells and generation of T cells through thymopoiesis. METHODS: In this study, we set out to assess the effects of adoptively transferred Treg on T cell regeneration in a homeostatic peripheral T cell expansion model and a thymopoiesis-dependent BMT model, and on murine cytomegalovirus (mCMV) clearance and mortality following mCMV challenge. RESULTS: Using lymphopenic Rag-2(-/-)γc(-/-) mice that received a limited number of congenic T cells, we demonstrate that adoptively transferred Treg abrogate LIP of T cells. mCMV challenge resulted in a rapid increase of viral load and death in mice that received Treg, but not in controls. In contrast, following syngeneic T cell-depleted BMT in Rag-2(-/-)γc(-/-) mice, adoptively transferred Treg did not delay T cell reconstitution nor suppressed thymic output and had no effect on viral clearance and survival following mCMV-challenge. CONCLUSION: The effect of Treg on T cell-mediated immunocompetence against mCMV early after BMT depends on the relative contribution of peripheral expansion and thymopoiesis to T cell regeneration.


Assuntos
Transplante de Medula Óssea , Infecções por Herpesviridae/imunologia , Muromegalovirus/fisiologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo , Transferência Adotiva , Animais , Antígenos CD4/biossíntese , Sobrevivência Celular , Células Cultivadas , Fatores de Transcrição Forkhead/biossíntese , Linfopoese , Camundongos , Camundongos Endogâmicos BALB C , Muromegalovirus/patogenicidade , Regeneração , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia , Subpopulações de Linfócitos T/transplante , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Linfócitos T Reguladores/transplante , Timo/patologia , Carga Viral , Virulência
18.
Haematologica ; 92(8): 1099-106, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17650439

RESUMO

BACKGROUND AND OBJECTIVES: Interleukin-7 (IL-7) has been studied for its possible immunorestorative capacities following stem cell transplantation and has been shown to enhance post-transplant immune recovery predominantly by peripheral T-cell expansion. A major concern of IL-7 is its possible aggravating effect on graft-versus-host and host-versus-graft reactivity. DESIGN AND METHODS: To study the effect of IL-7 on host-versus-graft reactivity, we applied IL-7 in an experimental transplantation model using RAG-1-/- mice supplied with B6 CD45.1 congenic T cells as recipients of T-cell depleted allogeneic bone marrow grafts. RESULTS: Rejection of minor antigen-mismatched bone marrow was significantly reduced in IL-7 treated recipients compared with PBS treated control mice. Rejection was observed in 2 out of 18 IL-7 treated mice compared with 9 out of 17 PBS treated mice (11% vs. 53%; p=0.012). IL-7 administration resulted in enhanced recovery of peripheral blood CD4+CD25+ regulatory T cells (Treg) with a concomitant increase in peripheral blood Foxp3 mRNA expression. IL-7Ra (CD127) was expressed by the vast majority of CD4+Foxp3+ T cells. The incidence of graft rejection following fully MHC mismatched bone marrow transplantation was not reduced nor enhanced by IL-7 administration. INTERPRETATION AND CONCLUSIONS: Post-transplant IL-7 administration protects against minor antigen-mismatched bone marrow rejection, which may be due to enhanced Treg recovery.


Assuntos
Transplante de Medula Óssea/imunologia , Rejeição de Enxerto/prevenção & controle , Reação Hospedeiro-Enxerto/efeitos dos fármacos , Interleucina-7/uso terapêutico , Antígenos de Histocompatibilidade Menor/imunologia , Linfócitos T Reguladores/imunologia , Animais , Animais Congênicos , Antígenos CD4/análise , Avaliação Pré-Clínica de Medicamentos , Fatores de Transcrição Forkhead/biossíntese , Fatores de Transcrição Forkhead/genética , Rejeição de Enxerto/imunologia , Subunidade alfa de Receptor de Interleucina-2/análise , Interleucina-7/farmacologia , Subunidade alfa de Receptor de Interleucina-7/biossíntese , Subunidade alfa de Receptor de Interleucina-7/genética , Contagem de Linfócitos , Depleção Linfocítica , Camundongos , Camundongos Endogâmicos , Camundongos Knockout , Proteínas Recombinantes/uso terapêutico , Organismos Livres de Patógenos Específicos , Linfócitos T Reguladores/efeitos dos fármacos , Transplante Homólogo
19.
J Immunol ; 178(6): 3551-7, 2007 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-17339451

RESUMO

Deficient thymopoiesis and retarded recovery of newly developed CD4(+) T cells is one of the most important determinants of impaired immunocompetence after hemopoietic stem cell transplantation. Here we evaluated whether Fms-like tyrosine kinase 3 (Flt3) ligand (FL) alone or combined with IL-7 affects T cell recovery, thymopoiesis, and lymphoid progenitor expansion following bone marrow transplantation in immunodeficient mice. FL strongly accelerated and enhanced the recovery of peripheral T cells after transplantation of a low number of bone marrow cells. An additive effect on T cell recovery was not observed after coadministration of IL-7. Lineage(-)sca-1(+)c-kit(+)flt3(+) lymphoid progenitor cell numbers were significantly increased in bone marrow of FL-treated mice before recovery of thymopoiesis. Thymocyte differentiation was advanced to more mature stages after FL treatment. Improved T cell recovery resulted in better immunocompetence against a post-bone marrow transplantation murine CMV infection. Collectively, our data suggest that FL promotes T cell recovery by enhanced thymopoiesis and by expansion of lymphoid progenitors.


Assuntos
Transplante de Medula Óssea , Linfócitos T CD4-Positivos/imunologia , Linfopoese/imunologia , Proteínas de Membrana/imunologia , Recuperação de Função Fisiológica/imunologia , Timo/imunologia , Animais , Antígenos de Diferenciação de Linfócitos T/imunologia , Linfócitos T CD4-Positivos/citologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Humanos , Interleucina-7/farmacologia , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Recuperação de Função Fisiológica/efeitos dos fármacos , Timo/citologia
20.
Blood Rev ; 19(2): 89-98, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15603912

RESUMO

Treatment related mortality (TRM) has restricted the application of allogeneic hematopoietic stem cell transplantation (allo-SCT) as a treatment modality for patients with a variety of malignant and non-malignant hematological disorders. TRM is mainly caused by severe opportunistic infections, due to an impaired immune reconstitution. The extreme slow recovery of newly developed, donor stem cell derived naive T-cells is currently considered to be the most important determinant of the impaired immune competence after allo-SCT. Therefore, enhancing naive T-cell recovery following allo-SCT by improving thymopoiesis has recently gained new interest. Possible strategies to improve thymopoiesis may include approaches to protect the nursing stromal compartment and approaches to directly stimulate the differentiation and proliferation of T-cell progenitors intra-thymically. Among the latter is interleukin-7 (IL-7), which has appeared promising in preclinical experimental settings and is expected to enter early clinical studies soon. Keratinocyte growth factor (KGF) is an epithelial growth factor that may protect the thymic epithelium and thereby may preserve it's support of thymopoiesis. KGF has been evaluated clinically in the setting of autologous stem cell transplantation and studies in the setting of allo-SCT are awaited in the near future.


Assuntos
Transplante de Células-Tronco Hematopoéticas/tendências , Linfopoese , Timo/fisiologia , Citocinas/fisiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Linfócitos T , Timo/citologia , Transplante Homólogo
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