Smoking is associated with higher risk of contracting bacterial infection and pneumonia, intensive care unit admission and death.

BACKGROUND: Smoking has been associated with a higher risk of contracting pneumonia, but contradictory results have shown that smoking may or may not decrease the risk of dying in pneumonia. The aim of this study is to investigate how smoking is associated with contracting any infection and pneumonia and death. METHOD AND FINDINGS: Participants were drawn from the population-based Cohort of Swedish Men and the Swedish Mammography Cohort, which are representative of the Swedish population. Participants have answered detailed lifestyle questionnaires and have been followed in national registers, such as the Patient Register, Cause of Death register and Swedish Intensive Care Registry. The risks of contracting infection and pneumonia or dying in infection and pneumonia were assessed using Cox regression. Of 62,902 cohort participants, 25,297 contracted an infection of which 4,505 died; and 10,471 contracted pneumonia of which 2,851 died. Compared to never smokers, former smokers at baseline had hazard ratio (HR) 1.08 (95% confidence interval (CI) 1.05-1.12) of contracting and HR 1.19 (95% CI 1.11-1.28) of dying in infection and HR 1.17 (95% CI 1.12-1.23) of contracting and HR 1.16 (95% CI 1.06-1.27) of dying in pneumonia during follow-up. Compared to never smokers, current smokers at baseline had HR 1.17 (95% CI 1.13-1.21) of contracting infection and HR 1.64 (95% CI 1.52-1.77) dying in infection; HR 1.42 (95% CI 1.35-1.49) of contracting pneumonia and HR 1.70 (95% CI 1.55-1.87) of dying in pneumonia during follow-up. The risk of contracting and dying in infection and pneumonia increased in a dose-response manner with number of pack years smoked and decreased with years since smoking cessation. CONCLUSION: Smoking is associated with contracting and dying in any infection and pneumonia and the risk increases with pack years smoked, highlighting the importance of both primary prevention and smoking cessation.

Metabolomic pattern associated with physical sequelae in patients presenting with respiratory symptoms validates the aestivation concept in dehydrated patients.

BACKGROUND: Hypertonic dehydration is associated with muscle wasting and synthesis of organic osmolytes. We recently showed a metabolic shift to amino acid production and urea cycle activation in COVID-19, consistent with the aestivation response. The aim of the present investigation was to validate the metabolic shift and development of long-term physical outcome in the non-COVID cohort of the Biobanque Québécoise de la COVID-19 (BQC19). METHODS: We included 824 patients from BQC19, where of 571 patients had data of dehydration in the form of estimated osmolality (eOSM = 2Na+2K+glucose+urea), and 284 patients had metabolome data and long-term follow-up. We correlated the degree of dehydration to mortality, invasive mechanical ventilation, acute kidney injury, and long-term symptoms. RESULTS: As found in the COVID cohort, higher eOSM correlated with higher proportion of urea and glucose of total eOSM and an enrichment of amino acids compared to other metabolites. Sex stratified analysis indicated that women may show a weaker aestivation response. More severe dehydration was associated with mortality, invasive mechanical ventilation, and acute kidney injury during the acute illness. Importantly, more severe dehydration was associated with physical long-term symptoms but not mental long-term symptoms after adjustment for age, sex, and disease severity. CONCLUSIONS: Patients with water deficit in the form of increased eOSM tend to have more severe disease and experience more physical symptoms after an acute episode of care. This is associated with amino acid and urea production indicating dehydration induced muscle wasting.

The Human Phospholipase B-II Precursor (HPLBII-P) in Urine as a Novel Biomarker of Glomerular Activity in COVID-19 and Diabetes Mellitus.

Background: The human phospholipase B-II precursor (HPLBII-P) was originally purified from white blood cells but is also found in other cellular structures, such as kidney glomeruli and tubuli. The objective of this report was to investigate the relationship of HPLBII-P in urine to acute kidney injury in patients with COVID-19. Methods: Urine was collected at admission from 132 patients with COVID-19 admitted to the intensive care units (ICUs) because of respiratory failure. HPLBII-P was measured using a sensitive ELISA. For comparison, human neutrophil lipocalin (HNL) was measured in urine, using the ELISA configured with the monoclonal antibody 763/8F, as a sign of tubular affection in addition to routine biomarkers of kidney disease. Results: Overall, the concentrations of urinary HPLBII-P were almost 3-fold higher in patients with COVID-19 compared to healthy controls (p < 0.0001) and with significantly higher concentrations even in patients with COVID-19 without signs of acute kidney injury (AKI) (p < 0.001). HPLBII-P was further increased in patients with AKI (p < 0.02). HPLBII-P was significantly increased in patients with diabetes mellitus (p = 0.0008) and correlated to plasma glucose (r = 0.29, p = 0.001) and urine albumin concentrations (r = 0.55, p < 0.001). Conclusions: Urine concentrations of HPLBII-P are highly raised in the urine of patients with COVID-19 and relate to AKI and diabetes mellitus. HPLBII-P may reflect glomerular injury and/or increased glomerular cell activity in SARS-CoV-2 infections.

Audio podcast and procedural video use in anaesthesiology and intensive care: A nationwide survey of Swedish anaesthetists.

BACKGROUND: Digital modalities which enable asynchronous learning, such as audio podcasts and videos demonstrating procedures, may benefit acquisition and retention of knowledge and clinical skills. The main objective of this nationwide cross-sectional survey study was to evaluate key aspects and factors related to usage of audio podcasts and procedural videos in anaesthesiology and intensive care. METHODS: A 20-item multiple-choice-question online survey was created through a consensus process including pilot testing among residents and consultants. Data were collected over a 3-month period, September-November 2023. RESULTS: The survey was completed by 466 anaesthetists. More than a third reported using procedural videos ≥1 time per week, whereas fewer than one in four participants used audio podcasts at least once per week. Multivariable logistic regression analysis showed that working at a university hospital, male sex, and younger age were independently associated with podcast use ≥1 time per week, with the highest odds ratio (OR) for younger age (<40 years vs. ≥40 years old; OR 5.86 (95% confidence interval 3.55-9.67), p < .001). Younger age was also significantly associated with higher frequency of video use (OR 1.71 (1.13-2.58), p = .011), while working predominantly in intensive care was associated with a lower frequency of video use. Podcasts were often used during commuting (42.3%), household work (30.7%), and exercise (24.9%), indicating a role in multi-tasking. Approximately half of respondents expressed that audio podcast-based learning has a moderate to very large positive impact on acquisition of theoretical knowledge, as well as practical skills. A vast majority, 85.2%, reported that procedural videos have a moderate to very large impact on development of clinical skills. CONCLUSION: Audio podcasts and procedural videos are appreciated tools with potential to supplement more traditional didactic techniques in anaesthesiology and intensive care. Procedural video use is common, with perceived large effects on development of clinical skills. Further data are needed to fully understand learning outcomes, quality of peer-review processes, and potential sex-differences.

Physical activity is associated with a lower risk of contracting and dying in infection and sepsis: a Swedish population-based cohort study.

BACKGROUND: Sepsis is a condition where the immune response to infection becomes dysregulated and life-threatening. It is not known whether lifestyle factors influence the risk of sepsis. The aim of the present study is to investigate the association between physical activity and the risk of acquiring and dying in infection or sepsis. METHODS: The population-based Swedish Mammography Cohort and Cohort of Swedish Men sent participants lifestyle questionnaires in 1997 and have subsequently followed participants in national Swedish registers, including the National Patient Register, the Swedish Intensive Care Registry and the Cause of Death Register. The risk of contracting infection and sepsis, the risk of intensive care unit admission and the risk of death were estimated using multivariable Cox regression. RESULTS: Among 64,850 cohort participants, 26,124 individuals suffered at least one episode of infection or sepsis and 4708 individuals died of infection or sepsis during the study period. In adjusted analyses, compared to exercising less than one hour per week, stated exercise one hour per week was associated with lower risk of contracting infection or sepsis, hazard ratio (HR) 0.93 (95% confidence interval (CI) 0.90-0.97), and lower risk of dying in infection or sepsis, HR 0.87 (95% CI 0.80-0.96). Further exercise was associated with even lower risk, and similar patterns were observed for walking. The population-attributable risks of contracting and dying in infection or sepsis for not exercising were 2.6% and 4.5%, respectively. CONCLUSIONS: Exercise and walking demonstrate inverse dose-response associations with both the risk of contracting and dying in infection and sepsis, presenting possible preventative interventions for this critical condition.

Tumor Predisposing Post-Zygotic Chromosomal Alterations in Bladder Cancer-Insights from Histologically Normal Urothelium.

Bladder urothelial carcinoma (BLCA) is the 10th most common cancer with a low survival rate and strong male bias. We studied the field cancerization in BLCA using multi-sample- and multi-tissue-per-patient protocol for sensitive detection of autosomal post-zygotic chromosomal alterations and loss of chromosome Y (LOY). We analysed 277 samples of histologically normal urothelium, 145 tumors and 63 blood samples from 52 males and 15 females, using the in-house adapted Mosaic Chromosomal Alterations (MoChA) pipeline. This approach allows identification of the early aberrations in urothelium from BLCA patients. Overall, 45% of patients exhibited at least one alteration in at least one normal urothelium sample. Recurrence analysis resulted in 16 hotspots composed of either gains and copy number neutral loss of heterozygosity (CN-LOH) or deletions and CN-LOH, encompassing well-known and new BLCA cancer driver genes. Conservative assessment of LOY showed 29%, 27% and 18% of LOY-cells in tumors, blood and normal urothelium, respectively. We provide a proof of principle that our approach can characterize the earliest alterations preconditioning normal urothelium to BLCA development. Frequent LOY in blood and urothelium-derived tissues suggest its involvement in BLCA.

Uromodulin in sepsis and severe pneumonia: a two-sample Mendelian randomization study.

The outcome for patients with sepsis-associated acute kidney injury in the intensive care unit (ICU) remains poor. Low serum uromodulin (sUMOD) protein levels have been proposed as a causal mediator of this effect. We investigated the effect of different levels of sUMOD on the risk of sepsis and severe pneumonia and outcomes in these conditions. A two-sample Mendelian randomization (MR) study was performed. Single-nucleotide polymorphisms (SNPs) associated with increased levels of sUMOD were identified and used as instrumental variables for association with outcomes. Data from different cohorts were combined based on disease severity and meta-analyzed. Five SNPs associated with increased sUMOD levels were identified and tested in six datasets from two biobanks. There was no protective effect of increased levels of sUMOD on the risk of sepsis [two cohorts, odds ratio (OR) 0.99 (95% confidence interval 0.95-1.03), P = 0.698, and OR 0.95 (0.91-1.00), P = 0.060, respectively], risk of sepsis requiring ICU admission [OR 1.04 (0.93-1.16), P = 0.467], ICU mortality in sepsis [OR 1.00 (0.74-1.37), P = 0.987], risk of pneumonia requiring ICU admission [OR 1.05 (0.98-1.14), P = 0.181], or ICU mortality in pneumonia [OR 1.17 (0.98-1.39), P = 0.079]. Meta-analysis of hospital-admitted and ICU-admitted patients separately yielded similar results [OR 0.98 (0.95-1.01), P = 0.23, and OR 1.05 (0.99-1.12), P = 0.86, respectively]. Among patients with sepsis and severe pneumonia, there was no protective effect of different levels of sUMOD. Results were consistent regardless of geographic origins and not modified by disease severity. NEW & NOTEWORTHY The presence of acute kidney injury in severe infections increases the likelihood of poor outcome severalfold. A decrease in serum uromodulin (sUMOD), synthetized in the kidney, has been proposed as a mediator of this effect. Using the Mendelian randomization technique, we tested the hypothesis that increased sUMOD is protective in severe infections. Analyses, however, showed no evidence of a protective effect of higher levels of sUMOD in sepsis or severe pneumonia.

A nationwide cohort study on the association between intensive care treatments and mental distress linked psychiatric disorders.

Given the psychic strain patients experience in the intensive care unit (ICU), a potential risk of mental disorders has been suggested. However, the effects of intensive care treatment per se are unknown. We investigated whether the level of intensive care treatments is an independent risk factor for developing long-term mental disorders after intensive care. In a national cohort of adult ICU patients we combined data on diagnoses, treatment, and causes of death. We defined extensive ICU treatment as being treated with invasive ventilation for > 24 h, continuous renal replacement therapy, or both. The primary outcome was incident mental disorder 1 year after ICU admission. Extensive ICU treatment was found to be associated with a decreased risk of developing a mental disorder ≥ 1 year after ICU admission (HR 0.90, 95% CI 0.82-0.99, p = 0.04), and increasing severity of acute illness (HR 1.18, 95% CI 1.06-1.32, p < 0.001) were associated with an increased risk of mental disorders. Because death acted as a competing risk for mental illness, mortality might help explain the apparent protective effect of extensive ICU care.Trial registration Clinical Trials Registry (Identification number NCT05137977). Registered 16 November 2021. As a registry trial the patients were already included at the trial registration i.e. it was retrospectively registered.

Surviving COVID-19: patients' experiences of care and path to recovery.

PURPOSE: To examine patients' experiences of receiving care on an ICU for COVID-19 and the subsequent rehabilitation process. METHODS: An explorative and inductive design was used. Participants were recruited from two university hospitals in Sweden. Patients admitted to the ICU due to COVID-19 from March 2020 to April 2021, who enrolled in the ICU follow-up, and understood and spoke Swedish were invited to participate. In total, 20 participants completed a semi-structured interview, of whom 18 were included in the thematic analysis. RESULTS: The analysis resulted in two themes: "An isolated world with silver linings" and "Recovery in the wake of the pandemic". Findings show that patients cared for on an ICU for COVID-19 during the pandemic felt safe but experienced a sense of vulnerability. After discharge, physical rehabilitation was a slow process with frustrating day-to-day fluctuations. Mentally, participants felt isolated, fatigued, and emotionally sensitive. Patients reported that love and support from family and friends were crucial for the recovery process. CONCLUSIONS: This study highlights the challenges of recovering from COVID-19, emphasizing the importance of continued support from health care, public services, family and friends. It provides important insights into patients' experiences and can inform future healthcare strategies and policies.

Therapeutic drug monitoring of vancomycin and meropenem: Illustration of the impact of inaccurate information in dose administration time.

OBJECTIVES: To illustrate the impact of errors in documented dose administration time on therapeutic drug monitoring (TDM)-based target attainment evaluation for vancomycin and meropenem, and to explore the influence of drug and patient characteristics, and TDM sampling strategies. METHODS: Bedside observations of errors in documented dose administration times were collected. Population pharmacokinetic simulations were performed for vancomycin and meropenem, evaluating different one- and two-sampling strategies for populations with estimated creatinine clearance (CLcr) of 30, 80 or 130 mL/min. The impact of errors was evaluated as the proportion of individuals incorrectly considered to have reached the target. RESULTS: Of 143 observed dose administrations, 97% of doses were given within ±30 min of the documented time. For vancomycin, a +30 min error was predicted to result in a 0.1-3.9 percentage point increase of cases incorrectly evaluated as reaching area under the concentration-time curve during a 24-hour period (AUC24)/minimum inhibitory concentration (MIC) >400, with the largest increase for patients with augmented renal clearance and peak and trough sampling. For meropenem, a +30 min error resulted in a 1.3-6.4 and 0-20 percentage point increase of cases incorrectly evaluated as reaching 100% T>MIC, and 50% T>MIC, respectively. Overall, mid-dose and trough sampling was most favourable for both antibiotics. CONCLUSIONS: For vancomycin, simulations indicate that TDM-based target attainment evaluation is robust with respect to the observed errors in dose administration time of ±30 min; however, the errors had a potentially clinically important impact in patients with augmented renal clearance. For meropenem, extra measures to promote correct documentation are warranted when using TDM, as the impact of errors was evident even in patients with normal renal function.

Influenza-associated invasive aspergillosis in patients admitted to the intensive care unit in Sweden: a prospective multicentre cohort study.

BACKGROUND: The purpose of this study was to prospectively investigate the incidence of influenza-associated pulmonary aspergillosis (IAPA) in influenza patients admitted to intensive care units in Sweden. METHODS: The study included consecutive adult patients with PCR-verified influenza A or B in 12 Swedish intensive care units (ICUs) over four influenza seasons (2019-2023). Patients were screened using serum galactomannan and ß-d-glucan tests and fungal culture of a respiratory sample at inclusion and weekly during the ICU stay. Bronchoalveolar lavage was performed if clinically feasible. IAPA was classified according to recently proposed case definitions. RESULTS: The cohort included 55 patients; 42% were female, and the median age was 59 (IQR 48-71) years. All patients had at least one galactomannan test, ß-d-glucan test and respiratory culture performed. Bronchoalveolar lavage was performed in 24 (44%) of the patients. Five (9%, 95% CI 3.8% - 20.4%) patients were classified as probable IAPA, of which four lacked classical risk factors. The overall ICU mortality was significantly higher among IAPA patients than non-IAPA patients (60% vs 8%, p = 0.01). CONCLUSIONS: The study represents the first prospective investigation of IAPA incidence. The 9% incidence of IAPA confirms the increased risk of invasive pulmonary aspergillosis among influenza patients admitted to the ICU. Therefore, it appears reasonable to implement a screening protocol for the early diagnosis and treatment of IAPA in influenza patients receiving intensive care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04172610, registered November 21, 2019.

Correction: Berghäll et al. The Evolution of Blood Cell Phenotypes, Intracellular and Plasma Cytokines and Morphological Changes in Critically Ill COVID-19 Patients. Biomedicines 2022, 10, 934.

In original publication [...].

Swedish multicentre study of target attainments with ß-lactams in the ICU: which MIC parameter should be used?

BACKGROUND: Therapeutic drug monitoring (TDM) has been suggested to optimize antimicrobial target attainment, typically using 100%T>MIC, in ß-lactam treatment in the ICU. The MIC parameter used in this equation is mostly the worst case scenario MIC (MICWCS)-the highest MIC the empirical treatment should cover. However, the impact of the MIC parameter used in pharmacokinetic/pharmacodynamic calculations has been poorly investigated. OBJECTIVES: To assess the influence of target attainment rates for two different MIC parameters using actual MICs of the causative pathogens as the primary reference. METHODS: In a Swedish multicentre study of target attainment for 138 ICU patients treated with ß-lactams, the causative pathogen was isolated and subjected to reference MIC testing. Whenever the strain belonged to the WT distribution, we assigned it to the category MICECOFF (epidemiological cut-off value). In the calculations we compared the MICECOFF and the MICWCS. RESULTS: The proportion of patients with target attainment failure for all antibiotics using 100%T>MIC was 45% (95% CI, 37%-53%) for MICWCS and 23% (95% CI, 16%-31%) for MICECOFF. When the target 50%T>4×MIC was used, corresponding attainment failures were 57% (95% CI, 49%-66%) and 25% (95% CI, 17%-32%) for MICWCS and MICECOFF, respectively. CONCLUSIONS: MICWCS can overestimate target attainment failure. The use of MICWCS could be one reason for the difficulties in establishing a relationship between target failure and mortality in other studies. Based on findings herein, the MICECOFF, which is based on the MIC of the causative pathogen, should be considered a more suitable alternative. When no pathogen is detected, the MICECOFF of likely pathogens according to infection type should be used.

Health-related quality of life after surviving intensive care for COVID-19: a prospective multicenter cohort study.

In survivors of severe coronavirus disease 2019 (COVID-19) incomplete mental and physical recovery may considerably impact daily activities and health-related quality of life (HRQoL). HRQoL can be evaluated with the RAND-36 questionnaire, a multidimensional instrument that assesses physical and mental aspects of health in eight dimensions. The objective was to investigate HRQoL in intensive care patients previously treated for COVID-19 at three Nordic university hospitals, in a prospective multi-center cohort study. HRQoL was measured using RAND-36, 3-9 months after discharge from intensive care units (ICU). One hospital performed a second follow-up 12 months after discharge. A score under the lower limit of the 95% confidence interval in the reference cohorts was considered as significantly reduced HRQoL. We screened 542 and included 252 patients. There was more than twice as many male (174) as female (78) patients and the median age was 61 (interquartile range, IQR 52-69) years. Hypertension was the most common comorbidity observed in 132 (52%) patients and 121 (48%) patients were mechanically ventilated for a median of 8 (IQR 4-14) days. In RAND-36 physical functioning, physical role functioning, general health (p < 0.001 for all) and social functioning (p < 0.05) were below reference, whereas bodily pain, emotional role functioning and mental health were not. In a time-to-event analysis female sex was associated with a decreased chance of reaching the reference HRQoL in the physical function, bodily pain and mental health dimensions. Higher body mass index was found in the physical functioning dimension and hypertension in the physical functioning, vitality and social functioning dimensions. Similar results were seen for diabetes mellitus in general health, vitality and mental health dimensions, as well as pulmonary illness in the physical role functioning dimension and psychiatric diagnosis in the social functioning dimension. Mechanical ventilation was associated with a decreased likelihood of achieving reference HRQoL in the bodily pain and physical functioning dimensions. Patients treated in an ICU because of COVID-19 had lower HRQoL 3-9 months after ICU discharge than 95% of the general population. Physical dimensions were more severely affected than mental dimensions. Female sex and several comorbidities were associated with a slower rate of recovery.Study registration: clinicaltrials.gov: NCT04316884 registered on the 13th of March 2020, NCT04474249 registered on the 29th of June 2020 and NCT04864938 registered on the 4th of April 2021.

Risk of malignant disease in 1-year sepsis survivors, a registry-based nationwide follow-up study.

BACKGROUND: Cancer and sepsis share risk factors, and sepsis patients may have impaired immune response and increased morbidity long after intensive care. This study aimed to assess whether sepsis survivors are at increased risk for cancer. Our objective was to assess the incidence of new cancer in 1-year sepsis survivors and test the hypothesis that it is higher than that of the general population. METHODS: We obtained data on ICU admissions of adult patients from Swedish Intensive care registry (SICR) from 2005 to 2017. We included patients with an explicit ICD-10 code for sepsis for the primary ICU admission. We obtained data on cancer diagnoses (2001-2018), death (2005-2018) and emigration (2005-2018) from Cancer and Cause of death and National Patient Registry databases of the National Board of Health and Welfare; age and sex-specific cancer incidence rates in Sweden from NORDCAN registry from 2006 to 2018. One-year survivors formed the final cohort, that was followed for new cancer diagnoses until death, emigration, or end of 2018, whichever came first. The main outcome measure was standardized incidence rate ratio (SIR) to compare the incidence of cancer in 1-year sepsis survivors to that in the general population (NORDCAN). We also performed several sensitivity analyses. RESULTS: In a cohort of 18,550 1-year survivors, 75,427 person years accumulated during a median follow-up (FU) of 3.36 years (IQR 1.72-5.86), 6366 (34.3%) patients died, and 1625 (8.8%) patients were diagnosed with a new cancer after a median FU of 2.51 (IQR 1.09-4.48) years. The incidence ratio of any new cancer over the whole FU was 1.31 (95% CI 1.23-1.40) for men and 1.74 (95% CI 1.61-1.88) for women. The difference in incidence rates persisted in several sensitivity analyses. The SIRs were highest in cancers of gastrointestinal tract, genital organs, and skin. CONCLUSION AND RELEVANCE: Compared to general population, incidence of cancer is increased in 1-year sepsis survivors. Variation in the findings depending on follow-up time suggests that factors other than sepsis alone are involved. Surveillance for malignant disease may be warranted in sepsis survivors.

Prior physical illness predicts death better than acute physiological derangement on intensive care unit admission in COVID-19: A Swedish registry study.

COVID-19 is associated with prolonged intensive care unit (ICU) stay and considerable mortality. The onset of persistent critical illness, defined as when prior illness predicts death better than acute physiological derangement, has not been studied in COVID-19. This national cohort study based on the Swedish Intensive Care Registry (SIR) included all patients admitted to a Swedish ICU due to COVID-19 from 6 March 2020 to 9 November 2021. Simplified Acute Physiology Score-3 (SAPS3) Box 1 was used as a measure of prior illness and Box 3 as a measure of acute derangement to evaluate the onset and importance of persistent critical illness in COVID-19. To compare predictive capacity, the area under receiver operating characteristic (AUC) of SAPS3 and its constituent Box 1 and 3 was calculated for 30-day mortality. In 7 969 patients, of which 1 878 (23.6%) died within 30 days of ICU admission, the complete SAPS3 score had acceptable discrimination: AUC 0.75 (95% CI 0.74 to 0.76) but showed under prediction in low-risk patients and over prediction in high-risk patients. SAPS3 Box 1 showed markedly better discrimination than Box 3 (AUC 0.74 vs 0.65, P<0,0001). Using custom logistic models, the difference in predictive performance of prior and acute illness was validated, AUC 0.76 vs AUC 0.69, p<0.0001. Prior physical illness predicts death in COVID-19 better than acute physiological derangement during ICU stay, and the whole SAPS3 score is not significantly better than just prior illness. The results suggests that COVID-19 may exhibit similarities to persistent critical illness immediately from ICU admission, potentially because of long median ICU length-of-stay. Alternatively, the variables in the acute physiological derangement model may not adequately capture the severity of illness in COVID-19.

The burden of critical illness among adults in a Swedish region-a population-based point-prevalence study.

BACKGROUND: Patients with critical illness have a high risk of mortality. Key decision-making in the health system affecting the outcomes of critically ill patients requires epidemiological evidence, but the burden of critical illness is largely unknown. This study aimed to estimate the prevalence of critical illness in a Swedish region. Secondary objectives were to estimate the proportion of hospital inpatients who are critically ill and to describe the in-hospital location of critically ill patients. METHODS: A prospective, multi-center, population-based, point-prevalence study on specific days in 2017-2018. All adult (> 18 years) in-patients, regardless of admitting specially, in all acute hospitals in Sörmland, and the patients from Sörmland who had been referred to university hospitals, were included. Patients in the operating theatres, with a psychiatric cause of admission, women in active labor and moribund patients, were excluded. All participants were examined by trained data collectors. Critical illness was defined as "a state of ill health with vital organ dysfunction, a high risk of imminent death if care is not provided and a potential for reversibility". The presence of one or more severely deranged vital signs was used to classify critical illness. The prevalence of critical illness was calculated as the number of critically ill patients divided by the number of adults in the region. RESULTS: A total of 1269 patients were included in the study. Median age was 74 years and 50% of patients were female. Critical illness was present in 133 patients, resulting in an adult population prevalence of critical illness per 100,000 people of 19.4 (95% CI 16.4-23.0). The proportion of patients in hospital who were critically ill was 10.5% (95% CI 8.8-12.3%). Among the critically ill, 125 [95% CI 94.0% (88.4-97.0%)] were cared for in general wards. CONCLUSIONS: The prevalence of critical illness was higher than previous, indirect estimates. One in ten hospitalized patients were critically ill, the large majority of which were cared for in general wards. This suggests a hidden burden of critical illness of potential public health, health system and hospital management significance.

Analysis of Calprotectin as an Early Marker of Infections Is Economically Advantageous in Intensive Care-Treated Patients.

Calprotectin is released from neutrophil granulocytes upon activation. Several studies have indicated that plasma calprotectin is an early determinant of bacterial infections, which may serve as a diagnostic tool facilitating decision making on antibiotic treatment. The study objective was to explore the health and economic implications of calprotectin as a predictive tool to initiate antimicrobial therapy in a cohort of critically ill patients. Thus, data obtained from a previously published study on calprotectin as a hypothetical early biomarker of bacterial infections in critically ill patients were evaluated regarding the potential cost-effective impact of early analysis of calprotectin on an earlier start of antibiotic treatment. Under the assumption that calprotectin is used predictively and comparators (white blood cells, procalcitonin, and C-reactive protein) are used diagnostically, a cost-effective impact of EUR 11,000-12,000 per patient would be obtained. If calprotectin would be used predictively and comparators would be used predictively for 50% of patients, it is hypothesized that cost-effectiveness would be between EUR 6000 and 7000 per patient, based on reduced stay in the ICU and general ward, respectively. Furthermore, predictive use of calprotectin seems to reduce both mortality and the length of hospital stay. This health economic analysis on the predictive use of plasma calprotectin, which facilitates clinical decision making in cases of suspected sepsis, indicates that such determination has a cost-saving and life-saving impact on the healthcare system.

Central nervous system biomarkers GFAp and NfL associate with post-acute cognitive impairment and fatigue following critical COVID-19.

A high proportion of patients with coronavirus disease 2019 (COVID-19) experience post-acute COVID-19, including neuropsychiatric symptoms. Objective signs of central nervous system (CNS) damage can be investigated using CNS biomarkers such as glial fibrillary acidic protein (GFAp), neurofilament light chain (NfL) and total tau (t-tau). We have examined whether CNS biomarkers can predict fatigue and cognitive impairment 3-6 months after discharge from the intensive care unit (ICU) in critically ill COVID-19 patients. Fifty-seven COVID-19 patients admitted to the ICU were included with analysis of CNS biomarkers in blood at the ICU and at follow up. Cognitive dysfunction and fatigue were assessed with the Montreal Cognitive Assessment (MoCA) and the Multidimensional Fatigue inventory (MFI-20). Elevated GFAp at follow-up 3-6 months after ICU discharge was associated to the development of mild cognitive dysfunction (p = 0.01), especially in women (p = 0.005). Patients who experienced different dimensions of fatigue at follow-up had significantly lower GFAp in both the ICU and at follow-up, specifically in general fatigue (p = 0.009), physical fatigue (p = 0.004), mental fatigue (p = 0.001), and reduced motivation (p = 0.001). Women showed a more pronounced decrease in GFAp compared to men, except for in mental fatigue where men showed a more pronounced GFAp decrease compared to women. NfL concentration at follow-up was lower in patients who experienced reduced motivation (p = 0.004). Our findings suggest that GFAp and NfL are associated with neuropsychiatric outcome after critical COVID-19.Trial registration The study was registered à priori (clinicaltrials.gov: NCT04316884 registered on 2020-03-13 and NCT04474249 registered on 2020-06-29).