Predicting the outcome in poisoned patients: look at the past!

INTRODUCTION: When predicting future events, we often rely on analyzing past occurrences and projecting them forward. This methodology is crucial in various fields, including toxicology, in which predicting outcomes in poisoned patients plays a vital role in guiding treatment decisions and improving patient care. IMPORTANCE OF PREDICTING OUTCOMES IN POISONED PATIENTS: In cases of poisoning, understanding a patient's medical history, current physiological status, and the toxicokinetics of the ingested substance is essential for predicting potential outcomes and determining appropriate interventions. WHAT TO PREDICT?: Predicting whether an intoxicated patient needs (further) treatment or even admission to the hospital is one of the most difficult decisions a clinician needs to make. The prediction of the course of an intoxication often lacks crucial information, leaving physicians with a sense of uncertainty in treating and advising patients. A significant source of this uncertainty stems from patients' limited awareness of the specific chemical(s) causing their symptoms, making a targeted approach challenging. Adding to the complexity, both patients and physicians frequently lack knowledge of the exposure dose, onset time, and potential interactions, further complicating the prediction of symptom progression. Patients are commonly placed in observation wards until the pharmacodynamic effects have diminished, leading to extended observation periods and unnecessary healthcare utilization and costs. Therefore, a key objective of a predictive model is to determine the necessity for intensive care unit admission. PREDICTING THE REQUIREMENT FOR ADMISSION TO AN INTENSIVE CARE UNIT: Factors such as age, Glasgow Coma Scale, and specific comorbidities like dysrhythmias and chronic respiratory insufficiency significantly influence the likelihood of intensive care unit admission. By examining a patient's trajectory based on past medical history and organ function deterioration, clinicians can better anticipate the need for critical care support. ENHANCING PREDICTION MODELS FOR IMPROVED PATIENT CARE: To enhance prediction models, leveraging modern methodologies like machine learning on large datasets (big data) are crucial. These advanced techniques can uncover previously unknown patient groups with similar outcomes or treatment responses, leading to more personalized and effective interventions. Regular updates to clustering, discrimination, and calibration processes ensure that predictive models remain accurate and relevant as new data emerges. CONCLUSIONS: The field of clinical toxicology stands to benefit greatly from the creation and integration of large datasets to advance toxicological prognostication. By embracing innovative approaches and incorporating diverse data sources, clinicians can enhance their ability to predict outcomes in poisoned patients and improve overall patient management strategies.

Tacrolimus Variability and Clinical Outcomes in the Early Post-lung Transplantation Period: Oral Versus Continuous Intravenous Administration.

BACKGROUND AND OBJECTIVE: High variability in tacrolimus pharmacokinetics directly after lung transplantation (LuTx) may increase the risk for acute kidney injury (AKI) and transplant rejection. The primary objective was to compare pharmacokinetic variability in patients receiving tacrolimus orally versus intravenously early after LuTx. METHODS: Pharmacokinetic and clinical data from 522 LuTx patients transplanted between 2010 and 2020 in two university hospitals were collected to compare orally administered tacrolimus to intravenous tacrolimus early post-transplantation. Tacrolimus blood concentration variability, measured as intrapatient variability (IPV%) and  percentage of time within the therapeutic range (TTR%), was analyzed within the first 14 days after LuTx. Secondary outcomes were AKI, acute rejection, length of stay in the intensive care unit (ICU), and mortality in the ICU and during hospital admission. RESULTS: We included 224 patients in the oral and 298 in the intravenous group. The mean adjusted IPV% was 10.8% (95% confidence interval [CI] 6.9-14.6; p < 0.001) higher in the oral group (27.2%) than the intravenous group (16.4%). The mean TTR% was 7.3% (95% CI - 11.3 to - 3.4; p < 0.001) lower in the oral group (39.6%) than in the intravenous group (46.9%). The incidence of AKI was 46.0% for oral and 42.6% for intravenous administration (adjusted odds ratio [OR] 1.2; 95% CI 0.8-1.8; p = 0.451). The frequencies of clinically diagnosed acute rejection in the oral and intravenous groups were nonsignificant (24.6% vs 17.8%; OR 1.5 [95% CI 1.0-2.3; p = 0.059]). ICU and hospital mortality rate and ICU length of stay were similar. CONCLUSIONS: Administering tacrolimus orally directly after LuTx leads to a higher variability in blood concentrations compared to intravenous administration. There was no difference in the occurrence of AKI or transplant rejection.

Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM.

PURPOSE: The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs). METHODS: After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method. RESULTS: Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies.

The association of premorbid conditions with 6-month mortality in acutely admitted ICU patients over 80 years.

BACKGROUND: Premorbid conditions influence the outcome of acutely ill adult patients aged 80 years and over who are admitted to the ICU. The aim of this study was to determine the influence of such premorbid conditions on 6 month survival. METHODS: Prospective cohort study in 242 ICUs from 22 countries including patients 80 years or above, admitted over a 6 months period to an ICU between May 2018 and May 2019. Only emergency (acute) ICU admissions in adult patients ≥ 80 years of age were eligible. Patients who were admitted after planned/elective surgery were excluded. We measured the Clinical Frailty Scale (CFS), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), disability with the Katz activities of daily living (ADL) score, comorbidities and a Polypharmacy Score (CPS). RESULTS: Overall, the VIP2 study included 3920 patients. During ICU stay 1191 patients died (30.9%), and another 436 patients (11.1%) died after ICU discharge but within the first 30 days of admission, and an additional 895 patients died hereafter but within the first 6 months after admission (22.8%). The 6 months mortality was 64%. The median CFS was 4 (IQR 3-6). Frailty (CFS ≥ 5) was present in 26.6%. Cognitive decline (IQCODE above 3.5) was found in 30.2%. The median IQCODE was 3.19. A Katz ADL of 4 or less was present in 27.7%. Patients who surviving > 6 months were slightly younger (median age survivors 84 with IQR 81-86) than patients dying within the first 6 months (median age 84, IQR 82-87, p = 0.013), were less frequently frail (CFS > 5 in 19% versus 34%, p < 0.01) and were less dependent based on their Katz activities of daily living measurement (median Katz score 6, IQR 5-6 versus 6 points, IQR 3-6, p < 0.01). CONCLUSIONS: We found that Clinical Frailty Scale, age, and SOFA at admission were independent prognostic factors for 6 month mortality after ICU admission in patients age 80 and above. Adding other geriatric syndromes and scores did not improve the model. This information can be used in shared-decision making. CLINICALTRIALS: gov: NCT03370692.

Risk factors for deliberate self-poisoning among children and adolescents in The Netherlands.

INTRODUCTION: In the past decade, the number of deliberate self-poisonings involving young people has increased strongly worldwide. This study aimed to gain insight into risk factors associated with deliberate self-poisonings among children and adolescents reported to the Dutch Poisons Information Center. METHODS: A study was performed between 1 February 2022 and 31 January 2023 involving those aged 8-17 years of age with deliberate self-poisoning. Data were collected on patient characteristics (age, gender, body mass index and living situation) and exposure characteristics (type of toxicant, way of acquiring toxicant and day of exposure). RESULTS: The Dutch Poisons Information Center was consulted about 1,424 deliberate self-poisonings among children and adolescents (10-17 years old). A high percentage of patients were female (85 percent), had a body mass index classified as overweight/obese (27 percent) and lived in a mental healthcare facility (13 percent). Patients mainly exposed themselves to pharmaceuticals, especially over-the-counter medications such as paracetamol (46 percent) and ibuprofen (15 percent). Young people living with parents/caregivers had higher odds of ingesting prescription pharmaceuticals or over-the-counter medication, while those living in a mental healthcare facility were more likely to ingest household products, personal care products or foreign bodies (predominantly batteries). DISCUSSION: This study sheds light on the pervasive issue of deliberate self-poisoning among children and adolescents, advocating for poisoning prevention strategies and promoting mental health of youth. Limitations include reliance on self-reported data from patients and the absence of clinical outcome data. CONCLUSIONS: Female gender, a high body mass index and living in a mental healthcare facility are associated with in increased risk of deliberate self-poisonings in children and adolescents (10-17 years old). Prevention of deliberate self-poisonings among youth could focus on restricting access to medication and other potentially hazardous non-pharmaceuticals, such as household products and batteries, as well as limiting the sales of over-the-counter medication, especially paracetamol, to this young population.

30-day mortality among very old patients admitted to European intensive care units for major trauma.

INTRODUCTION: Cases of major trauma in the very old (over 80 years) are increasingly common in the intensive care unit. Predicting outcome is challenging in this group of patients as chronological age is a poor marker of health and poor predictor of outcome. Increasingly, decisions are guided with the use of organ dysfunction scores of both the acute condition (e.g. Sequential Organ Failure Assessment (SOFA) score) and chronic health issues (e.g. clinical frailty scale, (CFS)). Recent work suggests that increased CFS is associated with a worse outcome in elderly major trauma patients. We aimed to test whether this association held true in the very old (over 80) or whether SOFA had a stronger association with 30-day outcome. METHODS: Data from the VIP-1 and VIP-2 studies for patients over 80 years old with major trauma admissions were merged. These participants were recruited from 20 countries across Europe. Baseline characteristics, level of care provided and outcome (ICU and 30-day mortality) were summarised. Uni- and multi- variable regression analysis were undertaken to determine associations between CFS and SOFA score in the first 24-hours, type of major trauma and outcomes. RESULTS: Of the 8062 acute patients recruited to the two VIP studies, 498 patients were admitted to intensive care because of major trauma. Median age was 84 years; median SOFA score was 6 (IQR 3,9) and median CFS was 3 (IQR 2,5). Survival to 30-days was 54%. Median and inter-quartile range of CFS was the same in survivors and non-survivors. In the logistic regression analysis, CFS was not associated with increased mortality. SOFA score (p<0.001) and trauma with head injury (p<0.01) were associated with increased mortality. CONCLUSIONS: Major trauma admissions in the very old are not uncommon and 30-day mortality is high. We found that CFS was not a helpful predictor of mortality. SOFA and trauma with head injury were associated with worse outcomes in this patient group.

Epidemiology and risk factors for mortality in critically ill patients with pancreatic infection.

Background: The AbSeS-classification defines specific phenotypes of patients with intra-abdominal infection based on the (1) setting of infection onset (community-acquired, early onset, or late-onset hospital-acquired), (2) presence or absence of either localized or diffuse peritonitis, and (3) severity of disease expression (infection, sepsis, or septic shock). This classification system demonstrated reliable risk stratification in intensive care unit (ICU) patients with intra-abdominal infection. This study aimed to describe the epidemiology of ICU patients with pancreatic infection and assess the relationship between the components of the AbSeS-classification and mortality. Methods: This was a secondary analysis of an international observational study ("AbSeS") investigating ICU patients with intra-abdominal infection. Only patients with pancreatic infection were included in this analysis (n=165). Mortality was defined as ICU mortality within 28 days of observation for patients discharged earlier from the ICU. Relationships with mortality were assessed using logistic regression analysis and reported as odds ratio (OR) and 95% confidence interval (CI). Results: The overall mortality was 35.2% (n=58). The independent risk factors for mortality included older age (OR=1.03, 95% CI: 1.0 to 1.1 P=0.023), localized peritonitis (OR=4.4, 95% CI: 1.4 to 13.9 P=0.011), and persistent signs of inflammation at day 7 (OR=9.5, 95% CI: 3.8 to 23.9, P<0.001) or after the implementation of additional source control interventions within the first week (OR=4.0, 95% CI: 1.3 to 12.2, P=0.013). Gram-negative bacteria were most frequently isolated (n=58, 49.2%) without clinically relevant differences in microbial etiology between survivors and non-survivors. Conclusions: In pancreatic infection, a challenging source/damage control and ongoing pancreatic inflammation appear to be the strongest contributors to an unfavorable short-term outcome. In this limited series, essentials of the AbSeS-classification, such as the setting of infection onset, diffuse peritonitis, and severity of disease expression, were not associated with an increased mortality risk.ClinicalTrials.gov number: NCT03270345.

Characteristics and outcome of COVID-19 patients admitted to the ICU: a nationwide cohort study on the comparison between the consecutive stages of the COVID-19 pandemic in the Netherlands, an update.

BACKGROUND: Previously, we reported a decreased mortality rate among patients with COVID-19 who were admitted at the ICU during the final upsurge of the second wave (February-June 2021) in the Netherlands. We examined whether this decrease persisted during the third wave and the phases with decreasing incidence of COVID-19 thereafter and brought up to date the information on patient characteristics. METHODS: Data from the National Intensive Care Evaluation (NICE)-registry of all COVID-19 patients admitted to an ICU in the Netherlands were used. Patient characteristics and rates of in-hospital mortality (the primary outcome) during the consecutive periods after the first wave (periods 2-9, May 25, 2020-January 31, 2023) were compared with those during the first wave (period 1, February-May 24, 2020). RESULTS: After adjustment for patient characteristics and ICU occupancy rate, the mortality risk during the initial upsurge of the third wave (period 6, October 5, 2021-January, 31, 2022) was similar to that of the first wave (ORadj = 1.01, 95%-CI [0.88-1.16]). The mortality rates thereafter decreased again (e.g., period 9, October 5, 2022-January, 31, 2023: ORadj = 0.52, 95%-CI [0.41-0.66]). Among the SARS-CoV-2 positive patients, there was a huge drop in the proportion of patients with COVID-19 as main reason for ICU admission: from 88.2% during the initial upsurge of the third wave to 51.7%, 37.3%, and 41.9% for the periods thereafter. Restricting the analysis to these patients did not modify the results on mortality. CONCLUSIONS: The results show variation in mortality rates among critically ill COVID-19 patients across the calendar time periods that is not explained by differences in case-mix and ICU occupancy rates or by varying proportions of patients with COVID-19 as main reason for ICU admission. The consistent increase in mortality during the initial, rising phase of each separate wave might be caused by the increased virulence of the contemporary virus strain and lacking immunity to the new strain, besides unmeasured patient-, treatment- and healthcare system characteristics.

Strain on Scarce Intensive Care Beds Drives Reduced Patient Volumes, Patient Selection, and Worse Outcome: A National Cohort Study.

OBJECTIVES: Strain on ICUs during the COVID-19 pandemic required stringent triage at the ICU to distribute resources appropriately. This could have resulted in reduced patient volumes, patient selection, and worse outcome of non-COVID-19 patients, especially during the pandemic peaks when the strain on ICUs was extreme. We analyzed this potential impact on the non-COVID-19 patients. DESIGN: A national cohort study. SETTING: Data of 71 Dutch ICUs. PARTICIPANTS: A total of 120,393 patients in the pandemic non-COVID-19 cohort (from March 1, 2020 to February 28, 2022) and 164,737 patients in the prepandemic cohort (from January 1, 2018 to December 31, 2019). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Volume, patient characteristics, and mortality were compared between the pandemic non-COVID-19 cohort and the prepandemic cohort, focusing on the pandemic period and its peaks, with attention to strata of specific admission types, diagnoses, and severity. The number of admitted non-COVID-19 patients during the pandemic period and its peaks were, respectively, 26.9% and 34.2% lower compared with the prepandemic cohort. The pandemic non-COVID-19 cohort consisted of fewer medical patients (48.1% vs. 50.7%), fewer patients with comorbidities (36.5% vs. 40.6%), and more patients on mechanical ventilation (45.3% vs. 42.4%) and vasoactive medication (44.7% vs. 38.4%) compared with the prepandemic cohort. Case-mix adjusted mortality during the pandemic period and its peaks was higher compared with the prepandemic period, odds ratios were, respectively, 1.08 (95% CI, 1.05-1.11) and 1.10 (95% CI, 1.07-1.13). CONCLUSIONS: In non-COVID-19 patients the strain on healthcare has driven lower patient volume, selection of fewer comorbid patients who required more intensive support, and a modest increase in the case-mix adjusted mortality.

Adverse drug events caused by three high-risk drug-drug interactions in patients admitted to intensive care units: A multicentre retrospective observational study.

AIMS: Knowledge about adverse drug events caused by drug-drug interactions (DDI-ADEs) is limited. We aimed to provide detailed insights about DDI-ADEs related to three frequent, high-risk potential DDIs (pDDIs) in the critical care setting: pDDIs with international normalized ratio increase (INR+ ) potential, pDDIs with acute kidney injury (AKI) potential, and pDDIs with QTc prolongation potential. METHODS: We extracted routinely collected retrospective data from electronic health records of intensive care units (ICUs) patients (≥18 years), admitted to ten hospitals in the Netherlands between January 2010 and September 2019. We used computerized triggers (e-triggers) to preselect patients with potential DDI-ADEs. Between September 2020 and October 2021, clinical experts conducted a retrospective manual patient chart review on a subset of preselected patients, and assessed causality, severity, preventability, and contribution to ICU length of stay of DDI-ADEs using internationally prevailing standards. RESULTS: In total 85 422 patients with ≥1 pDDI were included. Of these patients, 32 820 (38.4%) have been exposed to one of the three pDDIs. In the exposed group, 1141 (3.5%) patients were preselected using e-triggers. Of 237 patients (21%) assessed, 155 (65.4%) experienced an actual DDI-ADE; 52.9% had severity level of serious or higher, 75.5% were preventable, and 19.3% contributed to a longer ICU length of stay. The positive predictive value was the highest for DDI-INR+ e-trigger (0.76), followed by DDI-AKI e-trigger (0.57). CONCLUSION: The highly preventable nature and severity of DDI-ADEs, calls for action to optimize ICU patient safety. Use of e-triggers proved to be a promising preselection strategy.

Digoxin-specific antibodies: a novel dosing strategy.

Digoxin-specific antibodies (digoxin-Fabs) are of value in the treatment of a strongly suspected or a known, potentially life-threatening digoxin toxicity. These antibodies are not registered for use in Europe; therefore Dutch hospital pharmacies are not allowed to keep them in stock. In the Netherlands, digoxin-Fabs are stored in a national calamity stock of emergency medicines at the National Institute for Public Health and the Environment. In the case of a medical emergency, digoxin-Fabs are available after contact with the Dutch Poisons Information Centre. Recent studies have shown that the dose of digoxin-Fabs required to effectively treat digoxin toxicity is lower than previously thought. In this article, we present the adjusted digoxin-Fab dosing strategy currently recommended by the Dutch Poisons Information Centre ( www.vergiftigingen.info ). This new dose titration strategy is safe and effective and has a cost-saving side-effect.

Quality improvement of Dutch ICUs from 2009 to 2021: A registry based observational study.

PURPOSE: To investigate the development in quality of ICU care over time using the Dutch National Intensive Care Evaluation (NICE) registry. MATERIALS AND METHODS: We included data from all ICU admissions in the Netherlands from those ICUs that submitted complete data between 2009 and 2021 to the NICE registry. We determined median and interquartile range for eight quality indicators. To evaluate changes over time on the indicators, we performed multilevel regression analyses, once without and once with the COVID-19 years 2020 and 2021 included. Additionally we explored between-ICU heterogeneity by calculating intraclass correlation coefficients (ICC). RESULTS: 705,822 ICU admissions from 55 (65%) ICUs were included in the analyses. ICU length of stay (LOS), duration of mechanical ventilation (MV), readmissions, in-hospital mortality, hypoglycemia, and pressure ulcers decreased significantly between 2009 and 2019 (OR <1). After including the COVID-19 pandemic years, the significant change in MV duration, ICU LOS, and pressure ulcers disappeared. We found an ICC ≤0.07 on the quality indicators for all years, except for pressure ulcers with an ICC of 0.27 for 2009 to 2021. CONCLUSIONS: Quality of Dutch ICU care based on seven indicators significantly improved from 2009 to 2019 and between-ICU heterogeneity is medium to small, except for pressure ulcers. The COVID-19 pandemic disturbed the trend in quality improvement, but unaltered the between-ICU heterogeneity.

Acute kidney injury associated with nephrotoxic drugs in critically ill patients: a multicenter cohort study using electronic health record data.

Background: Nephrotoxic drugs frequently cause acute kidney injury (AKI) in adult intensive care unit (ICU) patients. However, there is a lack of large pharmaco-epidemiological studies investigating the associations between drugs and AKI. Importantly, AKI risk factors may also be indications or contraindications for drugs and thereby confound the associations. Here, we aimed to estimate the associations between commonly administered (potentially) nephrotoxic drug groups and AKI in adult ICU patients whilst adjusting for confounding. Methods: In this multicenter retrospective observational study, we included adult ICU admissions to 13 Dutch ICUs. We measured exposure to 44 predefined (potentially) nephrotoxic drug groups. The outcome was AKI during ICU admission. The association between each drug group and AKI was estimated using etiological cause-specific Cox proportional hazard models and adjusted for confounding. To facilitate an (independent) informed assessment of residual confounding, we manually identified drug group-specific confounders using a large drug knowledge database and existing literature. Results: We included 92 616 ICU admissions, of which 13 492 developed AKI (15%). We found 14 drug groups to be associated with a higher hazard of AKI after adjustment for confounding. These groups included established (e.g. aminoglycosides), less well established (e.g. opioids) and controversial (e.g. sympathomimetics with α- and ß-effect) drugs. Conclusions: The results confirm existing insights and provide new ones regarding drug associated AKI in adult ICU patients. These insights warrant caution and extra monitoring when prescribing nephrotoxic drugs in the ICU and indicate which drug groups require further investigation.

Frailty's influence on 30-day mortality in old critically ill ICU patients: a bayesian analysis evaluating the clinical frailty scale.

INTRODUCTION: Frailty is widely acknowledged as influencing health outcomes among critically ill old patients. Yet, the traditional understanding of its impact has predominantly been through frequentist statistics. We endeavored to explore this association using Bayesian statistics aiming to provide a more nuanced understanding of this multifaceted relationship. METHODS: Our analysis incorporated a cohort of 10,363 older (median age 82 years) patients from three international prospective studies, with 30-day all-cause mortality as the primary outcome. We defined frailty as Clinical Frailty Scale ≥ 5. A hierarchical Bayesian logistic regression model was employed, adjusting for covariables, using a range of priors. An international steering committee of registry members reached a consensus on a minimal clinically important difference (MCID). RESULTS: In our study, the 30-day mortality was 43%, with rates of 38% in non-frail and 51% in frail groups. Post-adjustment, the median odds ratio (OR) for frailty was 1.60 (95% CI 1.45-1.76). Frailty was invariably linked to adverse outcomes (OR > 1) with 100% probability and had a 90% chance of exceeding the minimal clinically important difference (MCID) (OR > 1.5). For the Clinical Frailty Scale (CFS) as a continuous variable, the median OR was 1.19 (1.16-1.22), with over 99% probability of the effect being more significant than 1.5 times the MCID. Frailty remained outside the region of practical equivalence (ROPE) in all analyses, underscoring its clinical importance regardless of how it is measured. CONCLUSIONS: This research demonstrates the significant impact of frailty on short-term mortality in critically ill elderly patients, particularly when the Clinical Frailty Scale (CFS) is used as a continuous measure. This approach, which views frailty as a spectrum, enables more effective, personalized care for this vulnerable group. Significantly, frailty was consistently outside the region of practical equivalence (ROPE) in our analysis, highlighting its clinical importance.

Outcomes of patients aged ≥80 years with respiratory failure initially treated with non-invasive ventilation in European intensive care units before and during COVID-19 pandemic.

BACKGROUND: Non-invasive ventilation (NIV) has been commonly used to treat acute respiratory failure due to COVID-19. In this study we aimed to compare outcomes of older critically ill patients treated with NIV before and during the COVID-19 pandemic. METHODS: We analysed a merged cohort of older adults admitted to intensive care units (ICUs) due to respiratory failure. Patients were enrolled into one of two prospective observational studies: before COVID-19 (VIP2-2018 to 2019) and admitted due to COVID-19 (COVIP-March 2020 to January 2023). The outcomes included: 30-day mortality, intubation rate and NIV failure (death or intubation within 30 days). RESULTS: The final cohort included 1986 patients (1292 from VIP2, 694 from COVIP) with a median age of 83 years. NIV was used as a primary mode of respiratory support in 697 participants (35.1%). ICU admission due to COVID-19 was associated with an increased 30-day mortality (65.5% vs. 36.5%, HR 2.18, 95% CI 1.71 to 2.77), more frequent intubation (36.9% vs. 17.5%, OR 2.63, 95% CI 1.74 to 3.99) and NIV failure (76.2% vs. 45.3%, OR 4.21, 95% CI 2.84 to 6.34) compared to non-COVID causes of respiratory failure. Sensitivity analysis after exclusion of patients in whom life supporting treatment limitation was introduced during primary NIV confirmed higher 30-day mortality in patients with COVID-19 (52.5% vs. 23.4%, HR 2.64, 95% CI 1.83 to 3.80). CONCLUSION: The outcomes of patients aged ≥80 years treated with NIV during COVID-19 pandemic were worse compared then those treated with NIV in the pre-pandemic era.

Preventing occupational chemical eye injuries: important lessons from poison information centres.

BACKGROUND: Occupational exposure to hazardous substances is a major public health problem. In the workplace, eye exposures are common and can be a major cause of morbidity and disability. This commentary discusses the role of poison information centres in providing valuable information on the circumstances and causes of these incidents. OCCUPATIONAL HEALTH SURVEILLANCE: As many eye exposures are easily preventable, there is a need to establish better safety practices in the workplace. Currently, both governments and labour organizations primarily employ injury statistics for the purpose of occupational health surveillance. Identifying risk factors associated with acute exposures in the workplace requires a comprehensive approach using a variety of information resources. Using information from poison information centres can provide invaluable insight into the specifics of the exposure, including the route(s) of exposure, the substances involved and the cause of the exposure. CIRCUMSTANCES OF OCCUPATIONAL EYE EXPOSURES: Exposure to hazardous substances can occur at various time points during work. A prospective study performed by the Dutch Poisons Information Centre showed that cleaning is a high-risk activity for occupational eye exposure. Patients were often exposed to chemical mixtures that frequently contained alkalis or acids. CHEMICAL EYE INJURIES: Symptoms following eye contact with chemicals can vary greatly depending on factors such as the type and concentration of the substance(s) involved, the duration of exposure and the time and duration of irrigation (first-aid measure). Eye contact will usually cause irritation, but in more severe cases, chemical burns will result. Recent studies demonstrate that occupational eye exposures often result in only relatively mild symptoms, such as pain, redness, lacrimation or temporary loss of vision. More severe symptoms, such as corneal abrasion, were reported rarely, which may be explained by prompt eye irrigation. ROOT CAUSES OF OCCUPATIONAL EYE EXPOSURES: To control risks to workers, a hierarchy of prevention and control measures has been established, which employers must take. If elimination or substitution of the dangerous substance is not possible, the exposure can be prevented or reduced by taking organizational (e.g., providing work instructions), technical (e.g., ventilation) and personal (e.g., wearing personal protective equipment) measures. The study performed by the Dutch Poisons Information Centre showed that organizational factors (such as lack of work instructions) and personal factors (such as time pressure and fatigue, and not (adequately) using personal protective equipment), were the main causes of occupational eye exposure. CONCLUSIONS: Poison information centres provide valuable information that can be used to develop prevention strategies to reduce the number of acute occupational exposures in the future. A multidisciplinary approach is essential to ensure that these preventive measures are actually applied in practice. Therefore, all organizations involved (including governments, labour organizations, medical professionals, occupational physicians, occupational hygienists, safety experts and poison information centres) must work closely together.

The impact of age-related syndromes on ICU process and outcomes in very old patients.

In this narrative review, we describe the most important age-related "syndromes" found in the old ICU patients. The syndromes are frailty, comorbidity, cognitive decline, malnutrition, sarcopenia, loss of functional autonomy, immunosenescence and inflam-ageing. The underlying geriatric condition, together with the admission diagnosis and the acute severity contribute to the short-term, but also to the long-term prognosis. Besides mortality, functional status and quality of life are major outcome variables. The geriatric assessment is a key tool for long-term qualitative outcome, while immediate severity accounts for acute mortality. A poor functional baseline reduces the chances of a successful outcome following ICU. This review emphasises the importance of using a geriatric assessment and considering the older patient as a whole, rather than the acute illness in isolation, when making decisions regarding intensive care treatment.

Age-specific severity of severe acute respiratory syndrome coronavirus 2 in February 2020 to June 2021 in the Netherlands.

Background: The severity of Severe Acute Respiratory Syndrome Coronavirus 2 infection varies with age and time. Here, we quantify how age-specific risks of hospitalization, intensive care unit (ICU) admission, and death upon infection changed from February 2020 to June 2021 in the Netherlands. Methods: A series of large representative serology surveys allowed us to estimate age-specific numbers of infections in three epidemic periods (late-February 2020 to mid-June 2020, mid-June 2020 to mid-February 2021, and mid-February 2021 to late-June 2021). We accounted for reinfections and breakthrough infections. Severity measures were obtained by combining infection numbers with age-specific numbers of hospitalization, ICU admission, and excess all-cause deaths. Results: There was an accelerating, almost exponential, increase in severity with age in each period. The rate of increase with age was the highest for death and the lowest for hospitalization. In late-February 2020 to mid-June 2020, the overall risk of hospitalization upon infection was 1.5% (95% confidence interval [CI] 1.3-1.8%), the risk of ICU admission was 0.36% (95% CI: 0.31-0.42%), and the risk of death was 1.2% (95% CI: 1.0-1.4%). The risk of hospitalization was significantly increased in mid-June 2020 to mid-February 2021, while the risk of ICU admission remained stable over time. The risk of death decreased over time, with a significant drop among ≥70-years-olds in mid-February 2021 to late-June 2021; COVID-19 vaccination started early January 2021. Conclusion: Whereas the increase in severity of Severe Acute Respiratory Syndrome Coronavirus 2 with age remained stable, the risk of death upon infection decreased over time. A significant drop in risk of death among elderly coincided with the introduction of COVID-19 vaccination.