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Impact of gender on patients hospitalized for SARS-COV-2 infection: A prospective observational study.
Giacomelli, A, De Falco, T, Oreni, L, Pedroli, A, Ridolfo, AL, Calabrò, E, Carrozzo, G, Bonazzetti, C, Antinori, S, Brucato, A
Journal of medical virology. 2021;(7):4597-4602
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Abstract
Biological sex could affect the natural history of severe acute respiratory syndrome coronavirus 2 infection. We enrolled all COVID-19 patients admitted to two COVID-19 hospitals in Milan in a prospective observational study. The primary outcome was death during the study period and the secondary outcome was critical disease at hospital admission. The association(s) between clinically relevant, noncollinear variables, and the primary outcome was assessed with uni- and multivariable Logistic regression models. A total of 520 patients were hospitalized of whom 349 (67%) were males with a median age 61 (interquartile range: 50-72). A higher proportion of males presented critically ill when compared to females (30.1% vs. 18.7%, p < .046). Death occurred in 86 (24.6%) males and 27 (15.8%) females (p = .024). In multivariable analysis age (per 10 years more) (adjusted odds ratio [AOR]: 1.83 [95% confidence interval {CI}: 1.42-2.35], p < .0001), obesity (AOR: 2.17 [95% CI: 1.10-4.31], p = .026), critical disease at hospital admission (AOR 6.34 [95% CI: 3.50-11.48], p < .0001) were independently associated to higher odds of death whereas gender was not. In conclusion, a higher proportion of males presented critically ill at hospital admission. Age, critical disease at hospital admission, obesity, anemia, D-dimer, estimated glomerular filtration rate, lactate dehydrogenase, and creatine kinase predicted death in hospitalized COVID-19 patients.
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Mortality associated with new risk classification of developing refeeding syndrome in critically ill patients: A cohort study.
Yoshida, M, Izawa, J, Wakatake, H, Saito, H, Kawabata, C, Matsushima, S, Suzuki, A, Nagatomi, A, Yoshida, T, Masui, Y, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(3):1207-1213
Abstract
BACKGROUND & AIMS Although refeeding syndrome (RFS) has been recognized as a potentially fatal metabolic complication, the definition of RFS has remained unclear. Recently, European researchers suggested an evidence-based and consensus-supported algorithm that consisted of a new RFS risk classification and treatment strategies for medical inpatients. The classification was based on the National Institute for Health and Clinical Excellence (NICE) criteria for patients at risk of developing RFS. In this study, we aimed to investigate the frequency of each applied new risk group and the association between the new classification and mortality in critically ill patients. METHODS This cohort study was conducted at a Japanese metropolitan tertiary-care university hospital from December 2016 to December 2018. We included critically ill adult patients who were admitted to the intensive care unit (ICU) via the emergency department and who stayed in the ICU for 24 h or longer. We applied the new risk classification based on the NICE RFS risk factors on ICU admission. The main exposure was risk classification of RFS: no risk, low risk, high risk, or very high risk. The primary outcome was in-hospital mortality censored at day 30 after ICU admission. We performed a multivariable analysis using Cox proportional hazard regression. RESULTS We analyzed 542 patients who met the eligibility criteria. The prevalence of the four RFS risk classification groups was 25.8% for no risk, 25.7% for low risk, 46.5% for high risk, and 2.0% for very high risk. The 30-day mortality was 5.0%, 7.2%, 16.3%, and 27.3%, respectively (log-rank trend test: p < 0.001). In the multivariable Cox regression, adjusted hazard ratios with no risk group as a reference were 1.28 (95% CI 0.48-3.38) for low risk, 2.81 (95% CI 1.24-6.35) for high risk, and 3.17 (95% CI 0.78-12.91) for very high risk. CONCLUSIONS Approximately half the critically ill patients were categorized as high or very high risk based on the new risk classification. Furthermore, as the risk categories progressed, the 30-day in-hospital mortality increased. Early recognition of patients at risk of developing RFS may improve patient outcomes through timely and optimal nutritional treatment.
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Relationship between CRP Albumin Ratio and the Mortality in Critically Ill Patients with AKI: A Retrospective Observational Study.
Wang, J, Zhao, K, Mao, X, Zhang, Y, Shao, J, Fan, W, Wang, Y
BioMed research international. 2021;:9957563
Abstract
BACKGROUND AKI is known to be associated with inflammation and nutritional status. The novel inflammatory prognostic score CAR (CRP/albumin ratio), which combines inflammation and nutritional status, was hypothesized to be associated with mortality in critically ill AKI patients in this study. METHODS The included cases were patients admitted to the ICU of Shandong Provincial Hospital from January 2016 to November 2018 and diagnosed with AKI within 48 hours of ICU admission. From the electronic case database of Shandong Provincial Hospital, we extracted the baseline demographic information, vital signs, routine laboratory parameters, complications, and other data. The above records are measured within 48 hours of admission to ICU. The clinical endpoint was the total cause mortality rate in hospital and 2 years. We constructed two multivariate regression models to determine the statistically significant correlation between CAR and mortality and conducted subgroup analysis to determine the mortality among different subgroups. RESULTS A total of 580 patients were included in this study. In multivariate regression analysis, higher CAR was associated with an increase in hospital and two-year all-cause mortality in critically ill patients with AKI after adjusting gender, age, respiratory frequency, temperature, and other confounding factors (tertile 3 versus tertile 1: OR, 95% CI: 2.97, 1.70-5.17; 3.03, 1.68-5.47, respectively; P < 0.001). Subgroup analysis showed that the CAR level in each subgroup increases with hospital mortality in critically ill patients with AKI. CONCLUSION The increase of CAR in critically ill patients with AKI was associated with an increased risk of all-cause death.
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Assessment of Sarcopenia in the Intensive Care Unit and 1-Year Mortality in Survivors of Critical Illness.
Yanagi, N, Koike, T, Kamiya, K, Hamazaki, N, Nozaki, K, Ichikawa, T, Matsunaga, A, Kuroiwa, M, Arai, M
Nutrients. 2021;(8)
Abstract
Skeletal muscle wasting in the intensive care unit (ICU) has been associated with mortality, but it is unclear whether sarcopenia, defined by skeletal muscle mass and function, is useful for detailed risk stratification after ICU discharge. In this cohort study, 72 critically ill patients with an ICU stay of ≥48 h were identified. Skeletal muscle mass was assessed from the muscle thickness (MT) of the patients' quadriceps using ultrasound images before ICU discharge. Skeletal muscle function was assessed from the patients' muscle strength (MS) before ICU discharge according to the Medical Research Council sum score. A diagnosis of sarcopenia in the ICU was made in patients with low MT and low MS. The study endpoint was 1-year mortality. Sarcopenia in the ICU was diagnosed in 26/72 patients (36%). After adjusting for covariates in the Cox regression, sarcopenia in the ICU was significantly associated with 1-year mortality (hazard ratio 3.82; 95% confidence interval, 1.40-10.42). Sarcopenia in the ICU, defined by low skeletal muscle mass and function, was associated with 1-year mortality in survivors of critical illness. Skeletal muscle mass and function assessed at the bedside could be used to identify higher-risk patients in the ICU.
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Association Between an Increase in Serum Sodium and In-Hospital Mortality in Critically Ill Patients.
Grim, CCA, Termorshuizen, F, Bosman, RJ, Cremer, OL, Meinders, AJ, Nijsten, MWN, Pickkers, P, de Man, AME, Schultz, MJ, van Vliet, P, et al
Critical care medicine. 2021;(12):2070-2079
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Abstract
OBJECTIVES In critically ill patients, dysnatremia is common, and in these patients, in-hospital mortality is higher. It remains unknown whether changes of serum sodium after ICU admission affect mortality, especially whether normalization of mild hyponatremia improves survival. DESIGN Retrospective cohort study. SETTING Ten Dutch ICUs between January 2011 and April 2017. PATIENTS Adult patients were included if at least one serum sodium measurement within 24 hours of ICU admission and at least one serum sodium measurement 24-48 hours after ICU admission were available. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS A logistic regression model adjusted for age, sex, and Acute Physiology and Chronic Health Evaluation-IV-predicted mortality was used to assess the difference between mean of sodium measurements 24-48 hours after ICU admission and first serum sodium measurement at ICU admission (Δ48 hr-[Na]) and in-hospital mortality. In total, 36,660 patients were included for analysis. An increase in serum sodium was independently associated with a higher risk of in-hospital mortality in patients admitted with normonatremia (Δ48 hr-[Na] 5-10 mmol/L odds ratio: 1.61 [1.44-1.79], Δ48 hr-[Na] > 10 mmol/L odds ratio: 4.10 [3.20-5.24]) and hypernatremia (Δ48 hr-[Na] 5-10 mmol/L odds ratio: 1.47 [1.02-2.14], Δ48 hr-[Na] > 10 mmol/L odds ratio: 8.46 [3.31-21.64]). In patients admitted with mild hyponatremia and Δ48 hr-[Na] greater than 5 mmol/L, no significant difference in hospital mortality was found (odds ratio, 1.11 [0.99-1.25]). CONCLUSIONS An increase in serum sodium in the first 48 hours of ICU admission was associated with higher in-hospital mortality in patients admitted with normonatremia and in patients admitted with hypernatremia.
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Activity Levels in Survivors of the Intensive Care Unit.
Gandotra, S, Files, DC, Shields, KL, Berry, M, Bakhru, RN
Physical therapy. 2021;(9)
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OBJECTIVE Limited data exist on the quantification of activity levels and functional status in critically ill patients as they transition from the intensive care unit (ICU) to the wards and, subsequently, back into the community. The physical activity of critically ill patients from their ICU stay until 7 days after hospital discharge was characterized, as well as correlate physical activity levels with an objective measure of physical function. METHODS This prospective observational study of previously independent adults aged 55 or older, undergoing mechanical ventilation for up to 7 days, recruited participants at the time of spontaneous breathing trials or less than 24 hours after extubation. Participants received an accelerometer at enrollment to wear until 1 week after discharge. RESULTS Twenty-two participants received accelerometers; 15 were suitable for analysis. Participants had a mean (SD) age of 68 (9.6) years; 47% were female. Mean step counts were 95 (95% CI = 15-173) in the 3 days before ICU discharge, 257 (95% CI = 114-400) before hospital discharge, 1223 (95% CI = 376-2070) in the first 3 days at home, and 1278 (95% CI = 349-2207) between day 4 and 6 post-hospital discharge. Physical activity was significantly higher post- compared with pre-hospital discharge. Short Physical Performance Battery scores were poor at ICU and hospital discharge; however, they correlated moderately with physical activity levels immediately upon return home. CONCLUSIONS Physical activity remained low as survivors of critical illness transitioned from ICU to hospital wards, but significantly increased upon return to the community. Despite poor Short Physical Performance Battery scores at both ICU and hospital discharge, participants were significantly more active immediately after discharge than in their last 3 days of hospitalization. This may represent rapid functional improvement or, conversely, constrained physical activity in hospital. IMPACT This study highlights the need for further evaluation of physical activity constraints in hospital and ways to augment physical activity and function upon discharge. LAY SUMMARY Physical activity (step counts) increased modestly as survivors of critical illness transitioned from ICU to hospital wards, but significantly increased upon return to the community. This study highlights the need for further evaluation of physical activity constraints in the hospital setting and ways to augment physical activity and function postdischarge.
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Nutritional state assessed by ultrasonography, but not by bioelectric impedance, predicts 28-day mortality in critically ill patients. Prospective cohort study.
da Silva Passos, LB, Macedo, TAA, De-Souza, DA
Clinical nutrition (Edinburgh, Scotland). 2021;(12):5742-5750
Abstract
BACKGROUND & AIMS Malnutrition is a disease associated with unfavorable outcomes and high prevalence among critically ill patients. The primary aim of the study was to correlate the nutritional status of patients recently admitted to the intensive care unit (ICU) with the 28-day mortality rate. The secondary aim was to establish cut-off values for the bioelectrical impedance analysis (BIA) and ultrasonography (USG) methods for the classification of the nutritional status of critically ill patients. METHODS Cohort-type prospective observational study design, with the inclusion of critically ill clinical-surgical patients, ≥18 years old, mechanically ventilated. Their nutritional status was assessed by phase angle and skeletal muscle mass (using BIA), and the sectional area of the rectus femoris muscle (RFM) (using USG) within the first 48 h of ICU admission. RESULTS Among the patients included (n = 160), the non-survivors had lower values related to the survivors for averages of the phase angle (4.4 ± 1.5° vs 4.9 ± 1.2°; p = 0.041) and sectional area of the RFM (6.1 ± 1.6 cm2/m2vs 7.4 ± 1.8 cm2/m2; p = 0.030). Cut-off values were identified using the ROC curves for phase angle (≤4.4°), skeletal muscle mass (≤19.2 kg/m2), and sectional area of the RFM (≤5.9 cm2/m2). In multivariate logistic regression analysis, the sectional area of the RFM (≤5.9 cm2/m2) was the only independent predictor of 28-day mortality (OR = 6.08; p = 0.028). In the survival analysis, greater survival at 28 days was demonstrated for patients with phase angle >4.4° (p = 0.020) and sectional area of the RFM >5.9 cm2/m2 (p = 0.001). Malnourished patients had higher mortality than nourished patients according to the phase angle (31.5% vs 15.1%, respectively; p = 0.015) and the sectional area of the RFM (38.9% vs 6.3%, respectively; p = 0.001). CONCLUSIONS The USG of the RFM is an efficient method for both classifying the nutritional status at ICU admission and assessing the prognosis of critically ill patients.
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Differences in mortality in critically ill elderly patients during the second COVID-19 surge in Europe.
Jung, C, Fjølner, J, Bruno, RR, Wernly, B, Artigas, A, Bollen Pinto, B, Schefold, JC, Wolff, G, Kelm, M, Beil, M, et al
Critical care (London, England). 2021;(1):344
Abstract
BACKGROUND The primary aim of this study was to assess the outcome of elderly intensive care unit (ICU) patients treated during the spring and autumn COVID-19 surges in Europe. METHODS This was a prospective European observational study (the COVIP study) in ICU patients aged 70 years and older admitted with COVID-19 disease from March to December 2020 to 159 ICUs in 14 European countries. An electronic database was used to register a number of parameters including: SOFA score, Clinical Frailty Scale, co-morbidities, usual ICU procedures and survival at 90 days. The study was registered at ClinicalTrials.gov (NCT04321265). RESULTS In total, 2625 patients were included, 1327 from the first and 1298 from the second surge. Median age was 74 and 75 years in surge 1 and 2, respectively. SOFA score was higher in the first surge (median 6 versus 5, p < 0.0001). The PaO2/FiO2 ratio at admission was higher during surge 1, and more patients received invasive mechanical ventilation (78% versus 68%, p < 0.0001). During the first 15 days of treatment, survival was similar during the first and the second surge. Survival was lower in the second surge after day 15 and differed after 30 days (57% vs 50%) as well as after 90 days (51% vs 40%). CONCLUSION An unexpected, but significant, decrease in 30-day and 90-day survival was observed during the second surge in our cohort of elderly ICU patients. The reason for this is unclear. Our main concern is whether the widespread changes in practice and treatment of COVID-19 between the two surges have contributed to this increased mortality in elderly patients. Further studies are urgently warranted to provide more evidence for current practice in elderly patients. TRIAL REGISTRATION NUMBER NCT04321265 , registered March 19th, 2020.
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Development of the Gastrointestinal Dysfunction Score (GIDS) for critically ill patients - A prospective multicenter observational study (iSOFA study).
Reintam Blaser, A, Padar, M, Mändul, M, Elke, G, Engel, C, Fischer, K, Giabicani, M, Gold, T, Hess, B, Hiesmayr, M, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(8):4932-4940
Abstract
BACKGROUND & AIMS To develop a five grade score (0-4 points) for the assessment of gastrointestinal (GI) dysfunction in adult critically ill patients. METHODS This prospective multicenter observational study enrolled consecutive adult patients admitted to 11 intensive care units in nine countries. At all sites, daily clinical data with emphasis on GI clinical symptoms were collected and intra-abdominal pressure measured. In five out of 11 sites, the biomarkers citrulline and intestinal fatty acid-binding protein (I-FABP) were measured additionally. Cox models with time-dependent scores were used to analyze associations with 28- and 90-day mortality. The models were estimated with stratification for study center. RESULTS We included 540 patients (224 with biomarker measurements) with median age of 65 years (range 18-94), the Simplified Acute Physiology Score II score of 38 (interquartile range 26-53) points, and Sequential Organ Failure Assessment (SOFA) score of 6 (interquartile range 3-9) points at admission. Median ICU length of stay was 3 (interquartile range 1-6) days and 90-day mortality 18.9%. A new five grade Gastrointestinal Dysfunction Score (GIDS) was developed based on the rationale of the previously developed Acute GI Injury (AGI) grading. Citrulline and I-FABP did not prove their potential for scoring of GI dysfunction in critically ill. GIDS was independently associated with 28- and 90-day mortality when added to SOFA total score (HR 1.40; 95%CI 1.07-1.84 and HR 1.40; 95%CI 1.02-1.79, respectively) or to a model containing all SOFA subscores (HR 1.48; 95%CI 1.13-1.92 and HR 1.47; 95%CI 1.15-1.87, respectively), improving predictive power of SOFA score in all analyses. CONCLUSIONS The newly developed GIDS is additive to SOFA score in prediction of 28- and 90-day mortality. The clinical usefulness of this score should be validated prospectively. TRIAL REGISTRATION NCT02613000, retrospectively registered 24 November 2015.
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A Model-Based Approach to Assess Unstable Creatinine Clearance in Critically Ill Patients.
Ullah, S, Zoller, M, Jaehde, U, Huseyn-Zada, M, Weig, T, Fuhr, U, Arshad, U, Zander, J, Taubert, M
Clinical pharmacology and therapeutics. 2021;(5):1240-1249
Abstract
Creatinine clearance is an important tool to describe the renal elimination of drugs in pharmacokinetic (PK) evaluations and clinical practice. In critically ill patients, unstable kidney function invalidates the steady-state assumption underlying equations, such as Cockcroft-Gault. Although measured creatinine clearance (mCrCL) is often used in nonsteady-state situations, it assumes that observed data are error-free, neglecting frequently occurring errors in urine collection. In contrast, compartmental nonlinear mixed effects models of creatinine allow to describe dynamic changes in kidney function while explicitly accounting for a residual error associated with observations. Based on 530 serum and 373 urine creatinine observations from 138 critically ill patients, a one-compartment creatinine model with zero-order creatinine generation rate (CGR) and first-order CrCL was evaluated. An autoregressive approach for interoccasion variability provided a distinct model improvement compared to a classical approach (Δ Akaike information criterion (AIC) -49.0). Fat-free mass, plasma urea concentration, age, and liver transplantation were significantly related to CrCL, whereas weight and sex were linked to CGR. The model-based CrCL estimates were superior to standard approaches to estimate CrCL (or glomerular filtration rate) including Cockcroft-Gault, mCrCL, four-variable modification of diet in renal disease (MDRD), six-variable MDRD, and chronic kidney disease epidemiology collaboration as a covariate to describe cefepime and meropenem PKs in terms of objective function value. In conclusion, a dynamic model of creatinine kinetics provides the means to estimate actual CrCL despite dynamic changes in kidney function, and it can easily be incorporated into population PK evaluations.