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1.
Front Neurol ; 12: 731013, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34819906

RESUMO

Objective: Extracellular vesicles (EV) are sub-1 µm bilayer lipid coated particles and have been shown play a role in long-term cardiovascular outcome after ischemic stroke. However, the dynamic change of EV after stroke and their implications for functional outcome have not yet been elucidated. Methods: Serial blood samples from 110 subacute ischemic stroke patients enrolled in the prospective BAPTISe study were analyzed. All patients participated in the PHYS-STROKE trial and received 4-week aerobic training or relaxation sessions. Levels of endothelial-derived (EnV: Annexin V+, CD45-, CD41-, CD31+/CD144+/CD146+), leukocyte-derived (LV: Annexin V+, CD45+, CD41-), monocytic-derived (MoV: Annexin V+, CD41-, CD14+), neuronal-derived (NV: Annexin V+, CD41-, CD45-, CD31-, CD144-, CD146-, CD56+/CD171+/CD271+), and platelet-derived (PV: Annexin V+, CD41+) EV were assessed via fluorescence-activated cell sorting before and after the trial intervention. The levels of EV at baseline were dichotomized at the 75th percentile, with the EV levels at baseline above the 75th percentile classified as "high" otherwise as "low." The dynamic of EV was classified based on the difference between baseline and post intervention, defining increases above the 75th percentile as "high increase" otherwise as "low increase." Associations of baseline levels and change in EV concentrations with Barthel Index (BI) and cardiovascular events in the first 6 months post-stroke were analyzed using mixed model regression analyses and cox regression. Results: Both before and after intervention PV formed the largest population of vesicles followed by NV and EnV. In mixed-model regression analyses, low NV [-8.57 (95% CI -15.53 to -1.57)] and low PV [-6.97 (95% CI -13.92 to -0.01)] at baseline were associated with lower BI in the first 6 months post-stroke. Patients with low increase in NV [8.69 (95% CI 2.08-15.34)] and LV [6.82 (95% CI 0.25-13.4)] were associated with reduced BI in the first 6 months post-stroke. Neither baseline vesicles nor their dynamic were associated with recurrent cardiovascular events. Conclusion: This is the first report analyzing the concentration and the dynamic of EV regarding associations with functional outcome in patients with subacute stroke. Lower levels of PV and NV at baseline were associated with a worse functional outcome in the first 6 months post-stroke. Furthermore, an increase in NV and LV over time was associated with worse BI in the first 6 months post-stroke. Further investigation of the relationship between EV and their dynamic with functional outcome post-stroke are warranted. Clinical Trial Registration: clinicaltrials.gov/, identifier: NCT01954797.

2.
Front Neurol ; 12: 730923, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744972

RESUMO

Background and Purpose: In the setting of acute ischemic stroke, increased blood-brain barrier permeability (BBBP) as a sign of injury is believed to be associated with increased risk of poor outcome. Pre-clinical studies show that selected serum biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), matrix metallopeptidases (MMP), and vascular endothelial growth factors (VEGFs) may play a role in BBBP post-stroke. In the subacute phase of stroke, increased BBBP may also be caused by regenerative mechanisms such as vascular remodeling and therefore may improve functional recovery. Our aim was to investigate the evolution of BBBP in ischemic stroke using contrast-enhanced (CE) magnetic resonance imaging (MRI) and to analyze potential associations with blood-derived biomarkers as well as functional recovery in subacute ischemic stroke patients. Methods: This is an exploratory analysis of subacute ischemic stroke patients enrolled in the BAPTISe study nested within the randomized controlled PHYS-STROKE trial (interventions: 4 weeks of aerobic fitness training vs. relaxation). Patients with at least one CE-MRI before (v1) or after (v2) the intervention were eligible for this analysis. The prevalence of increased BBBP was visually assessed on T1-weighted MR-images based on extent of contrast-agent enhancement within the ischemic lesion. The intensity of increased BBBP was assessed semi-quantitatively by normalizing the mean voxel intensity within the region of interest (ROI) to the contralateral hemisphere ("normalized CE-ROI"). Selected serum biomarkers (high-sensitive CRP, IL-6, TNF-α, MMP-9, and VEGF) at v1 (before intervention) were analyzed as continuous and dichotomized variables defined by laboratory cut-off levels. Functional outcome was assessed at 6 months after stroke using the modified Rankin Scale (mRS). Results: Ninety-three patients with a median baseline NIHSS of 9 [IQR 6-12] were included into the analysis. The median time to v1 MRI was 30 days [IQR 18-37], and the median lesion volume on v1 MRI was 4 ml [IQR 1.2-23.4]. Seventy patients (80%) had increased BBBP visible on v1 MRI. After the trial intervention, increased BBBP was still detectable in 52 patients (74%) on v2 MRI. The median time to v2 MRI was 56 days [IQR 46-67]. The presence of increased BBBP on v1 MRI was associated with larger lesion volumes and more severe strokes. Aerobic fitness training did not influence the increase of BBBP evaluated at v2. In linear mixed models, the time from stroke onset to MRI was inversely associated with normalized CE-ROI (coefficient -0.002, Standard Error 0.007, p < 0.01). Selected serum biomarkers were not associated with the presence or evolution of increased BBBP. Multivariable regression analysis did not identify the occurrence or evolution of increased BBBP as an independent predictor of favorable functional outcome post-stroke. Conclusion: In patients with moderate-to-severe subacute stroke, three out of four patients demonstrated increased BBB permeability, which decreased over time. The presence of increased BBBP was associated with larger lesion volumes and more severe strokes. We could not detect an association between selected serum biomarkers of inflammation and an increased BBBP in this cohort. No clear association with favorable functional outcome was observed. Trial registration: NCT01954797.

3.
Neurosurg Rev ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550492

RESUMO

Stereoscopic imaging has increasingly been used in anatomical teaching and neurosurgery. The aim of our study was to analyze the potential utility of stereoscopic imaging as a tool for memorizing neurosurgical patient cases compared to conventional monoscopic visualization. A total of 16 residents and 6 consultants from the Department of Neurosurgery at Charité - Universitätsmedizin Berlin were recruited for the study. They were divided into two equally experienced groups. A comparative analysis of both imaging modalities was conducted in which four different cases were assessed by the participants. Following the image assessment, two questionnaires, one analyzing the subjective judgment using the 5-point Likert Scale and the other assessing the memorization and anatomical accuracy, were completed by all participants. Both groups had the same median year of experience (5) and stereoacuity (≤ 75 s of arc). The analysis of the first questionnaire demonstrated significant subjective superiority of the monoscopic imaging in evaluation of the pathology (median: monoscopic: 4; stereoscopic: 3; p = 0.020) and in handling of the system (median: monoscopic: 5; stereoscopic: 2; p < 0.001). The second questionnaire showed that the anatomical characterization of the pathologies was comparable between both visualization methods. Most participants rated the stereoscopic visualization as worse compared to the monoscopic visualization, probably due to a lack of familiarity with the newer technique. Stereoscopic imaging, however, was not objectively inferior to traditional monoscopic imaging for anatomical comprehension. Further methodological developments and incorporation in routine clinical workflows will most likely enhance the usability and acceptance of stereoscopic visualization.

4.
Sci Rep ; 11(1): 16039, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362979

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) induces lung injury of varying severity, potentially causing severe acute respiratory distress syndrome (ARDS). Pulmonary injury patterns in COVID-19 patients differ from those in patients with other causes of ARDS. We aimed to explore the frequency and pathogenesis of cavitary lung lesions in critically ill patients with COVID-19. Retrospective study in 39 critically ill adult patients hospitalized with severe acute respiratory syndrome coronavirus 2 including lung injury of varying severity in a tertiary care referral center during March and May 2020, Berlin/Germany. We observed lung cavitations in an unusually large proportion of 22/39 (56%) COVID-19 patients treated on intensive care units (ICU), including 3/5 patients without mechanical ventilation. Median interquartile range (IQR) time between onset of symptoms and ICU admission was 11.5 (6.25-17.75) days. In 15 patients, lung cavitations were already present on the first CT scan, performed after ICU admission; in seven patients they developed during a subsequent median (IQR) observation period of 48 (35-58) days. In seven patients we found at least one cavitation with a diameter > 2 cm (maximum 10 cm). Patients who developed cavitations were older and had a higher body mass index. Autopsy findings in three patients revealed that the cavitations reflected lung infarcts undergoing liquefaction, secondary to thrombotic pulmonary artery branch occlusions. Lung cavitations appear to be a frequent complication of severely ill COVID-19 patients, probably related to the prothrombotic state associated with COVID-19.


Assuntos
COVID-19/patologia , Pulmão/patologia , Embolia Pulmonar/patologia , Idoso , COVID-19/complicações , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/etiologia , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação
5.
J Crit Care ; 65: 49-55, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34082255

RESUMO

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a risk factor for acquiring multiple drug resistant bacteria. The main objective of this analysis was to question a beneficial outcome in the routine use of antipseudomonal antibiotics in the empiric treatment of severe AECOPD in Intensive Care Unit patients. MATERIAL AND METHODS: We report a retrospective, observational cohort study in adult patients with severe AECOPD admitted to ICU at a tertiary care university hospital. Antibiotic treatment on admission as well as microbiology samples were analyzed. The influence of SOFA score at admission, age, sex and antibiotic choice upon survival was investigated by multivariable analysis. RESULTS: 437 patients were included. Mean age was 68 years (±10), 46.5% were female. 271/437 patients (62%) were initially treated with antibiotics covering Pseudomonas aeruginosa. Overall, positive microbiology samples were found in 107 patients (24.5%). P. aeruginosa was only found in 3.7%. There was no significant difference in 30-day ICU mortality after adjusting for age, sex and severity of illness (20.4% ± 11.6 in patients with Pseudomonas inactive antibiotics versus 29.3% ± 10.8 in patients with PAA, p=0.113). CONCLUSIONS: Empiric use of antipseudomonal antibiotics did not result in improved ICU survival in this retrospective analysis.


Assuntos
Antibacterianos , Doença Pulmonar Obstrutiva Crônica , Adulto , Idoso , Antibacterianos/uso terapêutico , Feminino , Humanos , Unidades de Terapia Intensiva , Pseudomonas aeruginosa , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos Retrospectivos
6.
Sci Rep ; 11(1): 13325, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172793

RESUMO

COVID 19 is associated with a hypercoagulable state and frequent thromboembolic complications. For how long this acquired abnormality lasts potentially requiring preventive measures, such as anticoagulation remains to be delineated. We used viscoelastic rotational thrombelastometry (ROTEM) in a single center cohort of 13 critical ill patients and performed follow up examinations three months after discharge from ICU. We found clear signs of a hypercoagulable state due to severe hypofibrinolysis and a high rate of thromboembolic complications during the phase of acute illness. Three month follow up revealed normalization of the initial coagulation abnormality and no evidence of venous thrombosis in all thirteen patients. In our cohort the coagulation profile was completely normalized three months after COVID-19. Based on these findings, discontinuation of anticoagulation can be discussed in patients with complete venous reperfusion.


Assuntos
Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea , COVID-19 , Tromboelastografia , Tromboembolia , Trombose Venosa , Idoso , Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/patologia , COVID-19/sangue , COVID-19/tratamento farmacológico , COVID-19/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Tromboembolia/tratamento farmacológico , Tromboembolia/patologia , Trombose Venosa/tratamento farmacológico , Trombose Venosa/patologia
7.
J Am Heart Assoc ; 10(10): e018326, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33982599

RESUMO

Background Recent evidence suggests cardiac troponin levels to be a marker of increased vascular risk. We aimed to assess whether levels of high-sensitivity cardiac troponin T (hs-cTnT) are associated with recurrent vascular events and death in patients with first-ever, mild to moderate ischemic stroke. Methods and Results We used data from the PROSCIS-B (Prospective Cohort With Incident Stroke Berlin) study. We computed Cox proportional hazards regression analyses to assess the association between hs-cTnT levels upon study entry (Roche Elecsys, upper reference limit, 14 ng/L) and the primary outcome (composite of recurrent stroke, myocardial infarction, and all-cause death). A total of 562 patients were analyzed (mean age, 67 years [SD 13]; 38.6% women; median National Institutes of Health Stroke Scale=2; hs-cTnT above upper reference limit, 39.2%). During a mean follow-up of 3 years, the primary outcome occurred in 89 patients (15.8%), including 40 (7.1%) recurrent strokes, 4 (0.7%) myocardial infarctions, and 51 (9.1%) events of all-cause death. The primary outcome occurred more often in patients with hs-cTnT above the upper reference limit (27.3% versus 10.2%; adjusted hazard ratio, 2.0; 95% CI, 1.3-3.3), with a dose-response relationship when the highest and lowest hs-cTnT quartiles were compared (15.2 versus 1.8 events per 100 person-years; adjusted hazard ratio, 4.8; 95% CI, 1.9-11.8). This association remained consistent in sensitivity analyses, which included age matching and stratification for sex. Conclusions Hs-cTnT is dose-dependently associated with an increased risk of recurrent vascular events and death within 3 years after first-ever, mild to moderate ischemic stroke. These findings support further studies of the utility of hs-cTnT for individualized risk stratification after stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01363856.


Assuntos
AVC Isquêmico/sangue , Medição de Risco/métodos , Troponina T/sangue , Doenças Vasculares/epidemiologia , Idoso , Berlim/epidemiologia , Biomarcadores/sangue , Causas de Morte/tendências , Feminino , Seguimentos , Humanos , Incidência , AVC Isquêmico/complicações , AVC Isquêmico/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Doenças Vasculares/sangue , Doenças Vasculares/etiologia
8.
J Intensive Care Soc ; 22(2): 159-174, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34025756

RESUMO

Background: There is no consensus on the instruments for diagnosis of post-intensive care syndrome (PICS). We present a proposal for a set of outcome measurement instruments of PICS in outpatient care. Methods: We conducted a three-round, semi-structured consensus-seeking process with medical experts, followed each by exploratory feasibility investigations with intensive care unit survivors (n1 = 5; n2 = 5; n3 = 7). Fourteen participants from nine stakeholder groups participated in the first and second consensus meeting. In the third consensus meeting, a core group of six clinical researchers refined the final outcome measurement instrument set proposal. Results: We suggest an outcome measurement instrument set used in a two-step process. First step: Screening with brief tests covering PICS domains of (1) mental health (Patient Health Questionnaire-4 (PHQ-4)), (2) cognition (MiniCog, Animal Naming), (3) physical function (Timed Up-and-Go (TUG), handgrip strength), and (4) health-related quality of life (HRQoL) (EQ-5D-5L). Single items measure subjective health before and after the intensive care unit stay. If patients report new or worsened health problems after intensive care unit discharge and show relevant impairment in at least one of the screening tests, a second extended assessment follows: (1) Mental health (Patient Health Questionnaire-8 (PHQ-8), Generalized Anxiety Disorder Scale-7 (GAD-7), Impact of Event Scale - revised (IES-R)); (2) cognition (Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Trail Making Test (TMT) A and B); (3) physical function (2-Minute Walk Test (2-MWT), handgrip strength, Short Physical Performance Battery (SPPB)); and (4) HRQoL (EQ-5D-5L, 12-Item WHO Disability Assessment Schedule (WHODAS 2.0)). Conclusions: We propose an outcome measurement instrument set used in a two-step measurement of PICS, combining performance-based and patient-reported outcome measures. First-step screening is brief, free-of-charge, and easily applicable by health care professionals across different sectors. If indicated, specialized healthcare providers can perform the extended, second-step assessment. Usage of the first-step screening of our suggested outcome measurement instrument set in outpatient clinics with subsequent transfer to specialists is recommended for all intensive care unit survivors. This may increase awareness and reduce the burden of PICS. Trial registration: This study was registered at ClinicalTrials.gov (Identifier: NCT04175236; first posted 22 November 2019).

9.
Eur J Anaesthesiol ; 38(9): 943-956, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33534264

RESUMO

BACKGROUND: Anecdotally, cholinergic stimulation has been used to treat delirium and reduce cognitive dysfunction. OBJECTIVE: The aim of this investigation was to evaluate whether physostigmine reduced the incidence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) in patients undergoing liver resection. DESIGN: This was a double-blind, randomised, placebo-controlled trial. Between 11 August 2009 and 3 March 2016, patients were recruited at the Charité - Universitätsmedizin Berlin in Germany. Follow-ups took place at 1 week (T1), 90 days (T2) and 365 days (T3) after surgery. SETTING: This single-centre study was conducted at an academic medical centre. PARTICIPANTS: In total, 261 participants aged at least 18 years scheduled for elective liver surgery were randomised. The protocol also included 45 non-surgical matched controls to provide normative data for POCD and neurocognitive deficit (NCD). INTERVENTION: Participants were allocated to receive either intravenous physostigmine, as a bolus of 0.02 mg kg-1 body weight followed by 0.01 mg kg-1 body weight per hour (n = 130), or placebo (n = 131), for 24 h after induction of anaesthesia. MAIN OUTCOMES AND MEASURES: Primary outcomes were POD, assessed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-4-TR) twice daily up to day 7 after surgery, and POCD assessed via the CANTAB neuropsychological test battery, and two paper pencil tests on the day before surgery, and on postoperative days 7, 90 and 365. RESULTS: In total, 261 patients were randomised, 130 to the physostigmine and 131 to the placebo group. The incidence of POD did not differ significantly between the physostigmine and placebo groups (20 versus 15%; P = 0.334). Preoperative cognitive impairment and POCD frequencies did not differ significantly between the physostigmine and placebo groups at any time. Lower mortality rates were found in the physostigmine group compared with placebo at 3 months [2% (95% confidence interval (CI), 0 to 4) versus 11% (95% CI, 6 to 16), P = 0.002], and 6 months [7% (95% CI, 3 to 12) versus 16% (95% CI, 10 to 23), P = 0.012] after surgery. CONCLUSION: Physostigmine had no effect on POD and POCD when applied after induction of anaesthesia up to 24 h. TRIAL REGISTRATION: DOI 10.1186/ISRCTN18978802, EudraCT 2008-007237-47, Ethics approval ZS EK 11 618/08 (15 January 2009).


Assuntos
Disfunção Cognitiva , Delírio , Adolescente , Adulto , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/prevenção & controle , Humanos , Fígado , Fisostigmina , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle
10.
Crit Care ; 24(1): 676, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287877

RESUMO

BACKGROUND: There is emerging evidence for enhanced blood coagulation in coronavirus 2019 (COVID-19) patients, with thromboembolic complications contributing to morbidity and mortality. The mechanisms underlying this prothrombotic state remain enigmatic. Further data to guide anticoagulation strategies are urgently required. METHODS: We used viscoelastic rotational thromboelastometry (ROTEM) in a single-center cohort of 40 critically ill COVID-19 patients. RESULTS: Clear signs of a hypercoagulable state due to severe hypofibrinolysis were found. Maximum lysis, especially following stimulation of the extrinsic coagulation system, was inversely associated with an enhanced risk of thromboembolic complications. Combining values for maximum lysis with D-dimer concentrations revealed high sensitivity and specificity of thromboembolic risk prediction. CONCLUSIONS: The study identifies a reduction in fibrinolysis as an important mechanism in COVID-19-associated coagulopathy. The combination of ROTEM and D-dimer concentrations may prove valuable in identifying patients requiring higher intensity anticoagulation.


Assuntos
COVID-19/complicações , Fibrinólise/fisiologia , Tromboelastografia/métodos , Tromboembolia/diagnóstico , Coagulação Sanguínea/fisiologia , Testes de Coagulação Sanguínea/métodos , Testes de Coagulação Sanguínea/normas , COVID-19/diagnóstico por imagem , COVID-19/fisiopatologia , Estudos de Coortes , Estado Terminal/epidemiologia , Estado Terminal/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistemas Automatizados de Assistência Junto ao Leito/normas , Sistemas Automatizados de Assistência Junto ao Leito/estatística & dados numéricos , Tromboembolia/diagnóstico por imagem , Substâncias Viscoelásticas/análise , Substâncias Viscoelásticas/uso terapêutico
11.
J Thromb Haemost ; 18(12): 3316-3324, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32935900

RESUMO

BACKGROUND: Though risk for recurrent vascular events is high following ischemic stroke, little knowledge about risk factors for secondary events post-stroke exists. OBJECTIVES: Coagulation factors XII, XI, and VIII (FXII, FXI, and FVIII) have been implicated in first thrombotic events, and our aim was to estimate their effects on vascular outcomes within 3 years after first stroke. PATIENTS/METHODS: In the Prospective Cohort with Incident Stroke Berlin (PROSCIS-B) study, we followed participants aged 18 and older for 3 years after first mild to moderate ischemic stroke event or until occurrence of recurrent stroke, myocardial infarction, or all-cause mortality. We compared high coagulation factor activity levels to normal and low levels and also analyzed activities as continuous variables. We used Cox proportional hazards models adjusted for age, sex, and cardiovascular risk factors to estimate hazard ratios (HRs) for the combined endpoint. RESULTS: In total, 94 events occurred in 576 included participants, resulting in an absolute rate of 6.6 events per 100 person-years. After confounding adjustment, high FVIII activity showed the strongest relationship with the combined endpoint (HR = 2.05, 95% confidence interval [CI] 1.28-3.29). High FXI activity was also associated with a higher hazard (HR = 1.80, 95% CI 1.09-2.98), though high FXII activity was not (HR = 0.86, 95% CI 0.49-1.51). Continuous analyses yielded similar results. CONCLUSIONS: In our study of mild to moderate ischemic stroke patients, high activity levels of FXI and FVIII but not FXII were associated with worse vascular outcomes in the 3-year period after first ischemic stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Adolescente , Isquemia Encefálica/diagnóstico , Fator XI , Fator XII , Humanos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico
12.
Medicina (Kaunas) ; 56(8)2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32823781

RESUMO

Background and objectives: The use of delirium screening instruments (DSIs) is recommended in critical care practice for a timely detection of delirium. We hypothesize that the patient-related factors "level of sedation" and "mechanical ventilation" impact test validity of DSIs. Materials and Methods: This is a prospective, bi-center observational study (clinicaltrials.gov: NCT01720914). Critically ill patients were screened for delirium daily for up to seven days after enrollment using the Nursing Delirium Screening Scale (Nu-DESC), Intensive Care Delirium Screening Checklist (ICDSC), and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Reference standard for delirium diagnosis was the neuropsychiatric examination using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Immediately before delirium assessment, ventilation status and sedation levels were documented. Results: 160 patients were enrolled and 151 patients went into final analysis. Delirium incidence was 23.2%. Nu-DESC showed a sensitivity and specificity of 88.5%, a positive predictive value (PPV) of 71.9%, and a negative predictive value (NPV) of 95.8%. ICDSC had a sensitivity of 62.5%, a specificity of 92.4%, a PPV of 71.4%, and a NPV of 89.0%. CAM-ICU showed a sensitivity of 75.0%, a specificity of 94.7%, a PPV of 85.7%, and a NPV of 90.0%. For Nu-DESC and ICDSC, test validity was significantly better for non-sedated patients (Richmond Agitation Sedation Scale (RASS) 0/-1), whereas test validity for CAM-ICU in a severity scale version showed no significant differences for different sedation levels. No DSI showed a significant difference in test validity between noninvasively and invasively ventilated patients. Conclusions: Test validities of DSIs were comparable to previous studies. The observational scores ICDSC and Nu-DESC showed a significantly better performance in awake and drowsy patients (RASS 0/-1) when compared with other sedation levels. Physicians should refrain from sedation whenever possible to avoid suboptimal performance of DSIs.


Assuntos
Cuidados Críticos/métodos , Estado Terminal/psicologia , Delírio/diagnóstico , Hipnóticos e Sedativos/administração & dosagem , Exame Neurológico , Respiração Artificial , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes
13.
J Crit Care ; 59: 124-129, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32619769

RESUMO

BACKGROUND: Clinical practice guidelines (CPGs) facilitate the provision of standardized, high-quality intensive care medicine. For the management of pain, agitation and delirium, several coexisting CPGs have been published. This study aims at the appraisal of CPGs on pain, agitation and delirium management in the intensive care unit to (a) identify high quality guidelines appropriate for clinical use and (b) identify potential areas for future improvement. METHODS: We performed a systematic literature search of Medline, three guideline registers and two grey-literature databases. The scope covered guidelines from 2007 to 2020 available in English or German. Identified CPGs were appraised by three independent reviewers using the appraisal of Guidelines Research and Evaluation (AGREE II) instrument. RESULTS: Eight CPGs were included in the final analysis. Three of the included guidelines exceeded the quality threshold of 60% in all six domains. The highest median [IQR] scores were achieved in the domain "Scope and Purpose" (84.3% [78.7-88.9]), whereas "Applicability" (45.8% [19.4-79.9]) received the lowest median score. CONCLUSION: Three of the eight reviewed guidelines exceeded the quality threshold in all domains, while the overall guideline quality was also very high. Focusing on guideline applicability and identifying strategies to facilitate implementation can improve future CPGs.


Assuntos
Cuidados Críticos/métodos , Unidades de Terapia Intensiva/normas , Manejo da Dor/métodos , Bases de Dados Factuais , Delírio , Humanos , Medicina , Dor , Guias de Prática Clínica como Assunto , Padrões de Referência
14.
Stroke ; 51(5): 1604-1607, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32279621

RESUMO

Background and Purpose- Our study aim was to assess whether high-sensitivity cardiac troponin T (hs-cTnT), a specific biomarker for myocardial injury, is associated with cognitive function in patients after mild-to-moderate first-ever ischemic stroke. Methods- We used data from PROSCIS-B (Prospective Cohort With Incident Stroke Berlin). Cognitive function was assessed by Mini-Mental-State-Examination at baseline, and Telephone Interview for Cognitive Status-modified after 1 to 3 years of follow-up. Patients were categorized according to hs-cTnT quartiles. We performed generalized linear regression to calculate risk ratios of cognitive impairment (Mini-Mental-State-Examination <27; Telephone Interview for Cognitive Status-modified <32). Association of hs-cTnT with cognitive function over time was estimated using a linear mixed model. Results- We included 555 patients (mean age, 67 years, 62% male, median National Institutes of Health Stroke Scale 2 [interquartile range, 1-5], hs-cTnT above upper reference limit 40%, baseline cognitive impairment 28%). Baseline Mini-Mental-State-Examination score and rate of cognitive impairment were lower in patients in the highest versus lowest hs-cTnT quartile (median Mini-Mental-State-Examination 27 versus 29, and 15.3% versus 43.0%, adjusted risk ratio, 1.76 [95% CI, 1.07-2.90], respectively). If anything, cognition seemed to improve in all groups, yet Telephone Interview for Cognitive Status-modified scores were consistently lower in patients within the highest versus lowest hs-cTnT quartile (adjusted ß, -1.33 [95% CI, -2.65 to -0.02]), without difference in the rate of change over time. Conclusions- In patients with mild-to-moderate first-ever ischemic stroke without dementia, higher hs-cTnT was associated with higher prevalence of cognitive impairment at baseline and lower Telephone Interview for Cognitive Status-modified during 3-year follow-up. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01363856.


Assuntos
Disfunção Cognitiva/sangue , Acidente Vascular Cerebral/sangue , Troponina T/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Cognição , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Feminino , Seguimentos , Humanos , Modelos Lineares , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Prognóstico , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Adulto Jovem
15.
BMC Neurol ; 20(1): 75, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32126977

RESUMO

BACKGROUND: Neuroprotection and promotion of remyelination represent important therapeutic gaps in multiple sclerosis (MS). Acute optic neuritis (ON) is a frequent MS manifestation. Based on the presence and properties of sphingosine-1-phosphate receptors (S1PR) on astrocytes and oligodendrocytes, we hypothesized that remyelination can be enhanced by treatment with fingolimod, a S1PR modulator currently licensed for relapsing-remitting MS. METHODS: MOVING was an investigator-driven, rater-blind, randomized clinical trial. Patients with acute unilateral ON, occurring as a clinically isolated syndrome or MS relapse, were randomized to 6 months of treatment with 0.5 mg oral fingolimod or subcutaneous IFN-ß 1b 250 µg every other day. The change in multifocal visual evoked potential (mfVEP) latency of the qualifying eye was examined as the primary (month 6 vs. baseline) and secondary (months 3, 6 and 12 vs. baseline) outcome. In addition, full field visual evoked potentials, visual acuity, optical coherence tomography as well as clinical relapses and measures of disability, cerebral MRI, and self-reported visual quality of life were obtained for follow-up. The study was halted due to insufficient recruitment (n = 15), and available results are reported. RESULTS: Per protocol analysis of the primary endpoint revealed a significantly larger reduction of mfVEP latency at 6 months compared to baseline with fingolimod treatment (n = 5; median decrease, 15.7 ms) than with IFN-ß 1b treatment (n = 4; median increase, 8.15 ms) (p <  0.001 for interaction). Statistical significance was maintained in the secondary endpoint analysis. Descriptive results are reported for other endpoints. CONCLUSION: Preliminary results of the MOVING trial argue in support of a beneficial effect of fingolimod on optic nerve remyelination when compared to IFN-ß treatment. Interpretation is limited by the small number of complete observations, an unexpected deterioration of the control group and a difference in baseline mfVEP latencies. The findings need to be confirmed in larger studies. TRIAL REGISTRATION: The trial was registered as EUDRA-CT 2011-004787-30 on October 26, 2012 and as NCT01647880 on July 24, 2012.


Assuntos
Cloridrato de Fingolimode/uso terapêutico , Imunossupressores/uso terapêutico , Neurite Óptica/tratamento farmacológico , Adulto , Potenciais Evocados Visuais/efeitos dos fármacos , Feminino , Humanos , Interferon beta-1b/uso terapêutico , Masculino , Pessoa de Meia-Idade
17.
Minerva Anestesiol ; 86(4): 394-403, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32000470

RESUMO

BACKGROUND: Presurgical cognitive impairment (PreCI) is frequently seen in older age, but the influence on postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) remains unclear. The present study sought to determine the association between PreCI, POD and POCD with special focus to different PreCI domains. METHODS: We analyzed 934 patients with complete baseline neurocognitive assessment. PreCI was determined as cognitive performance of at least two standard deviation (SD) below the mean performance of non-surgical controls. POD was assessed according to the Diagnostic and Statistical Manual of Mental Disorders 4 (DSM-4). POCD at three months follow-up was calculated by the reliable change index (RCI). Associations between PreCI and POD or POCD were assessed using multivariable logistic regression models adjusted for age, sex, randomization, ASA status, type of anesthesia, and type of surgery. RESULTS: PreCI was significantly associated with POD [OR 1.936 (95%CI 1.119 to 3.348); P=0.015] and POCD [OR 3.091 (95%CI 1.287 to 7.426); P=0.012]. Patients with coincident PreCI and POD were significantly more likely to develop POCD [OR 6.131 (95%CI 1.476 to 22.364); P=0.007]. Differentiation between no PreCI, amnestic and non-amnestic PreCI revealed a sole influence of amnestic PreCI on POD and POCD. CONCLUSIONS: Patients ≥ 60 years with PreCI were more likely to develop POD and POCD, respectively. The odds for POCD were highest in patients with PreCI whom also suffered from POD. Amnestic rather than non-amnestic PreCI might play a key role in the development of POD and POCD. These results warrant further pathophysiological investigations and demand preventive strategies.


Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Delírio , Complicações Cognitivas Pós-Operatórias , Idoso , Delírio/diagnóstico , Previsões , Humanos , Pessoa de Meia-Idade , Complicações Cognitivas Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias
18.
Mult Scler J Exp Transl Clin ; 6(1): 2055217320903474, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32047645

RESUMO

Background: Epidemiological, preclinical, and non-interventional studies link vitamin D (VD) serum levels and disease activity in multiple sclerosis (MS). It is unclear whether high-dose VD supplementation can be used as an intervention to reduce disease activity. Objectives: The study aimed to compare the effects of every other day high- (20,400 IU) versus low-dose (400 IU) cholecalciferol supplementation on clinical and imaging markers of disease activity in patients with relapsing-remitting MS or clinically isolated syndrome. Methods: The EVIDIMS (efficacy of vitamin D supplementation in multiple sclerosis) trial was a multicentre randomized/stratified actively controlled explorative phase 2a pilot trial with a double-blind intervention period of 18 months, add on to interferon-ß1b. Results: Fifty-three patients were randomized, and 41 patients completed the study. Cholecalciferol supplementation was well tolerated and safe in both arms. After 18 months, clinical (relapse rates, disability progression) and radiographical (T2-weighted lesion development, contrast-enhancing lesion development, brain atrophy) did not differ between both treatment arms. Post-study power calculations suggested that the sample size was too low to prove the hypothesis. Conclusions: The results neither support nor disprove a therapeutic benefit of high-dose VD supplementation but provide a basis for sound sample size estimations in future confirmatory studies. www.clinicaltrials.gov/NCT01440062.

19.
Trials ; 21(1): 3, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898518

RESUMO

BACKGROUND: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting diets (FDs) and ketogenic diets (KDs) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KDs and FDs on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate whether a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression. METHODS: This study is a single-center, randomized, controlled, parallel-group study. One hundred and eleven patients with relapsing-remitting MS with current disease activity and stable immunomodulatory therapy or no disease-modifying therapy will be randomized to one of three 18-month dietary interventions: a KD with a restricted carbohydrate intake of 20-40 g/day; a FD with a 7-day fast every 6 months and 14-h daily intermittent fasting in between; and a fat-modified SD as recommended by the German Nutrition Society. The primary outcome measure is the number of new T2-weighted MRI lesions after 18 months. Secondary endpoints are safety, changes in relapse rate, disability progression, fatigue, depression, cognition, quality of life, changes of gut microbiome as well as markers of inflammation, oxidative stress and autophagy. Safety and feasibility will also be assessed. DISCUSSION: Preclinical data suggest that a KD and a FD may modulate immunity, reduce disease severity and promote remyelination in the mouse model of MS. However, clinical evidence is lacking. This study is the first clinical study investigating the effects of a KD and a FD on disease progression of MS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03508414. Retrospectively registered on 25 April 2018.


Assuntos
Dieta Cetogênica/métodos , Jejum , Esclerose Múltipla/dietoterapia , Qualidade de Vida , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
20.
Anesth Analg ; 130(2): 341-351, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30855340

RESUMO

BACKGROUND: Skeletal muscle failure in critical illness (intensive care unit-acquired weakness) is a well-known complication developing early during intensive care unit stay. However, muscle weakness during the perioperative setting has not yet been investigated. METHODS: We performed a subgroup investigation of a prospective observational trial to investigate perioperative muscle weakness. Eighty-nine patients aged 65 years or older were assessed for handgrip strength preoperatively, on the first postoperative day, at intensive care unit discharge, at hospital discharge, and at 3-month follow-up. Functional status was evaluated perioperatively via Barthel index, instrumental activities of daily living, Timed Up and Go test, and functional independence measure. After exclusion of patients with intensive care unit-acquired weakness or intensive care unit stay of ≥72 hours, 59 patients were included into our analyses. Of these, 14 patients had additional pulmonary function tests preoperatively and on postoperative day 1. Blood glucose was measured intraoperatively every 20 minutes. RESULTS: Handgrip strength significantly decreased after surgery on postoperative day 1 by 16.4% (P < .001). Postoperative pulmonary function significantly decreased by 13.1% for vital capacity (P = .022) and 12.6% for forced expiratory volume in 1 second (P = .001) on postoperative day 1. Handgrip strength remained significantly reduced at hospital discharge (P = .016) and at the 3-month follow-up (P = .012). Perioperative glucose levels showed no statistically significant impact on muscle weakness. Instrumental activities of daily living (P < .001) and functional independence measure (P < .001) were decreased at hospital discharge, while instrumental activities of daily living remained decreased at the 3-month follow-up (P = .026) compared to preoperative assessments. CONCLUSIONS: Perioperatively acquired weakness occurred, indicated by a postoperatively decreased handgrip strength, decreased respiratory muscle function, and impaired functional status, which partly remained up to 3 months.


Assuntos
Força da Mão/fisiologia , Debilidade Muscular/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Músculos Respiratórios/fisiologia , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva/tendências , Masculino , Debilidade Muscular/etiologia , Debilidade Muscular/fisiopatologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Estudos Prospectivos
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