Antimicrobial Therapeutic Drug Monitoring in critically ill adult patients -an international perspective on access, utilisation, and barriers.

BACKGROUND: Therapeutic drug monitoring (TDM) is an effective method for individualizing antimicrobial therapy in critically ill patients. The 2021 ADMIN-ICU survey studied a wide range of intensive care unit (ICU) clinicians worldwide to gain their perspectives on antimicrobial TDM. This paper reports the responses from this survey relating to TDM access, utilisation, barriers, and clinical value. METHODS: An online survey consisted of multiple-choice questions and 5-point Likert scales. The survey examined respondent's access to minimum inhibitory concentration (MIC) results, drug assays and dosing software, as well as barriers to TDM. RESULTS: The survey included 538 clinicians from 409 hospitals in 45 countries, with 71% physicians and 29% pharmacists. Despite most respondents having access to assays, 21% and 26% of respondents lacked access to vancomycin and aminoglycosides, respectively. In lower-income countries, almost 40% reported no access. Delayed drug assay turnaround time was the most significant barrier to TDM, particularly in lower-income countries. Routine access to MIC results was unavailable for 41% of respondents, with 25% of lower-income country respondents having no access to MIC or susceptibility reports. CONCLUSIONS: This global survey indicated that consistent TDM usage is hindered by assay access in some sites, and timeliness of assay results in others. Addressing barriers to TDM, particularly in low-income countries, should be a priority to ensure equitable access to affordable TDM.

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.

30-day Morbidity and Mortality after Cholecystectomy for Benign Gallbladder Disease (AMBROSE): A Prospective, International Collaborative Cohort Study.

OBJECTIVE: This study aimed to assess 30-day morbidity and mortality rates following cholecystectomy for benign gallbladder disease and identify the factors associated with complications. SUMMARY BACKGROUND DATA: Although cholecystectomy is common for benign gallbladder disease, there is a gap in the knowledge of the current practice and variations on a global level. METHODS: A prospective, international, observational collaborative cohort study of consecutive patients undergoing cholecystectomy for benign gallbladder disease from participating hospitals in 57 countries between January 1 and June 30, 2022, was performed. Univariate and multivariate logistic regression models were used to identify preoperative and operative variables associated with 30-day postoperative outcomes. RESULTS: Data of 21,706 surgical patients from 57 countries were included in the analysis. A total of 10,821 (49.9%), 4,263 (19.7%), and 6,622 (30.5%) cholecystectomies were performed in the elective, emergency, and delayed settings, respectively. Thirty-day postoperative complications were observed in 1,738 patients (8.0%), including mortality in 83 patients (0.4%). Bile leaks (Strasberg grade A) were reported in 278 (1.3%) patients and severe bile duct injuries (Strasberg grades B-E) were reported in 48 (0.2%) patients. Patient age, ASA physical status class, surgical setting, operative approach and Nassar operative difficulty grade were identified as the five predictors demonstrating the highest relative importance in predicting postoperative complications. CONCLUSION: This multinational observational collaborative cohort study presents a comprehensive report of the current practices and outcomes of cholecystectomy for benign gallbladder disease. Ongoing global collaborative evaluations and initiatives are needed to promote quality assurance and improvement in cholecystectomy.

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.

Measurements of Surgical Volume in Low- and Middle-Income Countries, a Systematic Review.

Background: Surgical volume is a surgical indicator that was described in the Lancet Commission on Global Surgery (LCoGS) and the World Bank World Development Indicators as an important metric for tracking the delivery of surgical care. Objectives: We aimed to characterize the reports on surgical volume (SV) in the existing literature by using a systematic review to assess studies that examine surgical procedures as a ratio of a population (procedures/100,000 population). Methods: The PRISMA guideline was employed in the systematic review of articles that addressed the measurement of SV in low- and middle-income countries (LMICs), with the primary outcome of surgical procedures/100,000 population. Findings: The search result consisted of 6,657 preliminary studies. Following the title and abstract screening, 6,464 articles were excluded, and the remaining 193 were included in the full text review. From the full text review of the 193, only 26 of these articles defined SV as the ratio of number of procedures per population of the catchment/geographical area. The reported SV was a mean of 765, with an SD of 1260 operations per 100,000. The median SV was 180 (min = 0.900, max = 4470). Conclusion: Our findings support the LCoGS assessment of the gap in surgical care. The target for SV is 5000 per 100,000 population, compared to the average of 765 per 100,000 population as found in this review. The challenges for assessing surgical volume gaps are vast, including the nature of written records, which limits SV reports to an absolute number of procedures per year without a reference to the catchment population. For the purpose of tracking SV, we recommend using proxies that account for the capacity of facilities to deliver care regardless of the catchment population.

Limiting life-sustaining treatment for very old ICU patients: cultural challenges and diverse practices.

BACKGROUND: Decisions about life-sustaining therapy (LST) in the intensive care unit (ICU) depend on predictions of survival as well as the expected functional capacity and self-perceived quality of life after discharge, especially in very old patients. However, prognostication for individual patients in this cohort is hampered by substantial uncertainty which can lead to a large variability of opinions and, eventually, decisions about LST. Moreover, decision-making processes are often embedded in a framework of ethical and legal recommendations which may vary between countries resulting in divergent management strategies. METHODS: Based on a vignette scenario of a multi-morbid 87-year-old patient, this article illustrates the spectrum of opinions about LST among intensivsts with a special interest in very old patients, from ten countries/regions, representing diverse cultures and healthcare systems. RESULTS: This survey of expert opinions and national recommendations demonstrates shared principles in the management of very old ICU patients. Some guidelines also acknowledge cultural differences between population groups. Although consensus with families should be sought, shared decision-making is not formally required or practised in all countries. CONCLUSIONS: This article shows similarities and differences in the decision-making for LST in very old ICU patients and recommends strategies to deal with prognostic uncertainty. Conflicts should be anticipated in situations where stakeholders have different cultural beliefs. There is a need for more collaborative research and training in this field.

Red Blood Cell Transfusion in the Intensive Care Unit.

Importance: Red blood cell (RBC) transfusion is common among patients admitted to the intensive care unit (ICU). Despite multiple randomized clinical trials of hemoglobin (Hb) thresholds for transfusion, little is known about how these thresholds are incorporated into current practice. Objective: To evaluate and describe ICU RBC transfusion practices worldwide. Design, Setting, and Participants: International, prospective, cohort study that involved 3643 adult patients from 233 ICUs in 30 countries on 6 continents from March 2019 to October 2022 with data collection in prespecified weeks. Exposure: ICU stay. Main Outcomes and Measures: The primary outcome was the occurrence of RBC transfusion during ICU stay. Additional outcomes included the indication(s) for RBC transfusion (consisting of clinical reasons and physiological triggers), the stated Hb threshold and actual measured Hb values before and after an RBC transfusion, and the number of units transfused. Results: Among 3908 potentially eligible patients, 3643 were included across 233 ICUs (median of 11 patients per ICU [IQR, 5-20]) in 30 countries on 6 continents. Among the participants, the mean (SD) age was 61 (16) years, 62% were male (2267/3643), and the median Sequential Organ Failure Assessment score was 3.2 (IQR, 1.5-6.0). A total of 894 patients (25%) received 1 or more RBC transfusions during their ICU stay, with a median total of 2 units per patient (IQR, 1-4). The proportion of patients who received a transfusion ranged from 0% to 100% across centers, from 0% to 80% across countries, and from 19% to 45% across continents. Among the patients who received a transfusion, a total of 1727 RBC transfusions were administered, wherein the most common clinical indications were low Hb value (n = 1412 [81.8%]; mean [SD] lowest Hb before transfusion, 7.4 [1.2] g/dL), active bleeding (n = 479; 27.7%), and hemodynamic instability (n = 406 [23.5%]). Among the events with a stated physiological trigger, the most frequently stated triggers were hypotension (n = 728 [42.2%]), tachycardia (n = 474 [27.4%]), and increased lactate levels (n = 308 [17.8%]). The median lowest Hb level on days with an RBC transfusion ranged from 5.2 g/dL to 13.1 g/dL across centers, from 5.3 g/dL to 9.1 g/dL across countries, and from 7.2 g/dL to 8.7 g/dL across continents. Approximately 84% of ICUs administered transfusions to patients at a median Hb level greater than 7 g/dL. Conclusions and Relevance: RBC transfusion was common in patients admitted to ICUs worldwide between 2019 and 2022, with high variability across centers in transfusion practices.

Global Incidence and Risk Factors Associated With Postoperative Urinary Retention Following Elective Inguinal Hernia Repair: The Retention of Urine After Inguinal Hernia Elective Repair (RETAINER I) Study.

Importance: Postoperative urinary retention (POUR) is a well-recognized complication of inguinal hernia repair (IHR). A variable incidence of POUR has previously been reported in this context, and contradictory evidence surrounds potential risk factors. Objective: To ascertain the incidence of, explore risk factors for, and determine the health service outcomes of POUR following elective IHR. Design, Setting, and Participants: The Retention of Urine After Inguinal Hernia Elective Repair (RETAINER I) study, an international, prospective cohort study, recruited participants between March 1 and October 31, 2021. This study was conducted across 209 centers in 32 countries in a consecutive sample of adult patients undergoing elective IHR. Exposure: Open or minimally invasive IHR by any surgical technique, under local, neuraxial regional, or general anesthesia. Main Outcomes and Measures: The primary outcome was the incidence of POUR following elective IHR. Secondary outcomes were perioperative risk factors, management, clinical consequences, and health service outcomes of POUR. A preoperative International Prostate Symptom Score was measured in male patients. Results: In total, 4151 patients (3882 male and 269 female; median [IQR] age, 56 [43-68] years) were studied. Inguinal hernia repair was commenced via an open surgical approach in 82.2% of patients (n = 3414) and minimally invasive surgery in 17.8% (n = 737). The primary form of anesthesia was general in 40.9% of patients (n = 1696), neuraxial regional in 45.8% (n = 1902), and local in 10.7% (n = 446). Postoperative urinary retention occurred in 5.8% of male patients (n = 224), 2.97% of female patients (n = 8), and 9.5% (119 of 1252) of male patients aged 65 years or older. Risk factors for POUR after adjusted analyses included increasing age, anticholinergic medication, history of urinary retention, constipation, out-of-hours surgery, involvement of urinary bladder within the hernia, temporary intraoperative urethral catheterization, and increasing operative duration. Postoperative urinary retention was the primary reason for 27.8% of unplanned day-case surgery admissions (n = 74) and 51.8% of 30-day readmissions (n = 72). Conclusions: The findings of this cohort study suggest that 1 in 17 male patients, 1 in 11 male patients aged 65 years or older, and 1 in 34 female patients may develop POUR following IHR. These findings could inform preoperative patient counseling. In addition, awareness of modifiable risk factors may help to identify patients at increased risk of POUR who may benefit from perioperative risk mitigation strategies.

International survey of antibiotic dosing and monitoring in adult intensive care units.

BACKGROUND: In recent years, numerous dosing studies have been conducted to optimize therapeutic antibiotic exposures in patients with serious infections. These studies have led to the inclusion of dose optimization recommendations in international clinical practice guidelines. The last international survey describing dosing, administration and monitoring of commonly prescribed antibiotics for critically ill patients was published in 2015 (ADMIN-ICU 2015). This study aimed to describe the evolution of practice since this time. METHODS: A cross-sectional international survey distributed through professional societies and networks was used to obtain information on practices used in the dosing, administration and monitoring of vancomycin, piperacillin/tazobactam, meropenem and aminoglycosides. RESULTS: A total of 538 respondents (71% physicians and 29% pharmacists) from 409 hospitals in 45 countries completed the survey. Vancomycin was mostly administered as an intermittent infusion, and loading doses were used by 74% of respondents with 25 mg/kg and 20 mg/kg the most favoured doses for intermittent and continuous infusions, respectively. Piperacillin/tazobactam and meropenem were most frequently administered as an extended infusion (42% and 51%, respectively). Therapeutic drug monitoring was undertaken by 90%, 82%, 43%, and 39% of respondents for vancomycin, aminoglycosides, piperacillin/tazobactam, and meropenem, respectively, and was more frequently performed in high-income countries. Respondents rarely used dosing software to guide therapy in clinical practice and was most frequently used with vancomycin (11%). CONCLUSIONS: We observed numerous changes in practice since the ADMIN-ICU 2015 survey was conducted. Beta-lactams are more commonly administered as extended infusions, and therapeutic drug monitoring use has increased, which align with emerging evidence.

Associations of anemia and blood transfusions with mortality in old, critically ill COVID-19 patients - Results from the prospective COVIP Study.

AIMS: Anemia is common in the old and often observed in critically ill patients. Increased age is associated with higher mortality following a COVID-19 infection, making old patients prone to poor outcomes. We investigated whether anemia at admission to the ICU or the need for blood transfusion was associated with 90-day mortality in older, critically ill COVID-19 patients. METHODS: In this prospective multicenter study, the 90-day mortality of COVID-19 patients≥70 years treated in 138 intensive care units (ICU) was analyzed. Associations between anemia (WHO definition) at admission and discharge from ICU and the use of red blood cell (RBC) transfusions with mortality were assessed. Hemoglobin thresholds of RBC transfusions in old, critically ill COVID-19 patients were recorded. RESULTS: In 493 patients (350 anemic, 143 non-anemic), anemia (WHO definition) at the time of ICU admission was not associated with impaired overall survival. Transfusion and severe anemia (hemoglobin≤10 g/dL) at ICU discharge were independently associated with a higher risk of 90-day mortality. CONCLUSION: The need for red blood cell transfusions and severe anemia at ICU discharge, but not at the timepoint of admission, were independently associated with 90-day mortality in critically-ill old COVID-19 patients.

Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study.

PURPOSE: In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials. METHODS: We carried out a prospective international cohort study of adult patients (≥ 18 years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021. RESULTS: 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp. (20.3%), Escherichia coli (15.8%), and Pseudomonas spp. (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) was present in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24 h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alive from hospital by day-28. CONCLUSIONS: HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes.

The association of prior paracetamol intake with outcome of very old intensive care patients with COVID-19: results from an international prospective multicentre trial.

BACKGROUND: In the early COVID-19 pandemic concerns about the correct choice of analgesics in patients with COVID-19 were raised. Little data was available on potential usefulness or harmfulness of prescription free analgesics, such as paracetamol. This international multicentre study addresses that lack of evidence regarding the usefulness or potential harm of paracetamol intake prior to ICU admission in a setting of COVID-19 disease within a large, prospectively enrolled cohort of critically ill and frail intensive care unit (ICU) patients. METHODS: This prospective international observation study (The COVIP study) recruited ICU patients ≥ 70 years admitted with COVID-19. Data on Sequential Organ Failure Assessment (SOFA) score, prior paracetamol intake within 10 days before admission, ICU therapy, limitations of care and survival during the ICU stay, at 30 days, and 3 months. Paracetamol intake was analysed for associations with ICU-, 30-day- and 3-month-mortality using Kaplan Meier analysis. Furthermore, sensitivity analyses were used to stratify 30-day-mortality in subgroups for patient-specific characteristics using logistic regression. RESULTS: 44% of the 2,646 patients with data recorded regarding paracetamol intake within 10 days prior to ICU admission took paracetamol. There was no difference in age between patients with and without paracetamol intake. Patients taking paracetamol suffered from more co-morbidities, namely diabetes mellitus (43% versus 34%, p < 0.001), arterial hypertension (70% versus 65%, p = 0.006) and had a higher score on Clinical Frailty Scale (CFS; IQR 2-5 versus IQR 2-4, p < 0.001). Patients under prior paracetamol treatment were less often subjected to intubation and vasopressor use, compared to patients without paracetamol intake (65 versus 71%, p < 0.001; 63 versus 69%, p = 0.007). Paracetamol intake was not associated with ICU-, 30-day- and 3-month-mortality, remaining true after multivariate adjusted analysis. CONCLUSION: Paracetamol intake prior to ICU admission was not associated with short-term and 3-month mortality in old, critically ill intensive care patients suffering from COVID-19. TRIAL REGISTRATION: This prospective international multicentre study was registered on ClinicalTrials.gov with the identifier "NCT04321265" on March 25, 2020.

A retrospective cohort study comparing differences in 30-day mortality among critically ill patients aged ≥ 70 years treated in European tax-based healthcare systems (THS) versus social health insurance systems.

In Europe, tax-based healthcare systems (THS) and social health insurance systems (SHI) coexist. We examined differences in 30-day mortality among critically ill patients aged ≥ 70 years treated in intensive care units in a THS or SHI. Retrospective cohort study. 2406 (THS n = 886; SHI n = 1520) critically ill ≥ 70 years patients in 129 ICUs. Generalized estimation equations with robust standard errors were chosen to create population average adjusted odds ratios (aOR). Data were adjusted for patient-specific variables, organ support and health economic data. The primary outcome was 30-day-mortality. Numerical differences between SHI and THS in SOFA scores (6 ± 3 vs. 5 ± 3; p = 0.002) were observed, but clinical frailty scores were similar (> 4; 17% vs. 14%; p = 0.09). Higher rates of renal replacement therapy (18% vs. 11%; p < 0.001) were found in SHI (aOR 0.61 95%CI 0.40-0.92; p = 0.02). No differences regarding intubation rates (68% vs. 70%; p = 0.33), vasopressor use (67% vs. 67%; p = 0.90) and 30-day-mortality rates (47% vs. 50%; p = 0.16) were found. Mortality remained similar between both systems after multivariable adjustment and sensitivity analyses. The retrospective character of this study. Baseline risk and mortality rates were similar between SHI and THS. The type of health care system does not appear to have played a role in the intensive care treatment of critically ill patients ≥ 70 years with COVID-19 in Europe.

Consent is a confounding factor in a prospective observational study of critically ill elderly patients.

During analysis of a prospective multinational observation study of critically ill patients ≥80 years of age, the VIP2 study, we also studied the effects of differences in country consent for study inclusion. This is a post hoc analysis where the ICUs were analyzed according to requirement for study consent. Group A: ICUs in countries with no requirement for consent at admission but with deferred consent in survivors. Group B: ICUs where some form of active consent at admission was necessary either from the patient or surrogates. Patients' characteristics, the severity of disease and outcome variables were compared. Totally 3098 patients were included from 21 countries. The median age was 84 years (IQR 81-87). England was not included because of changing criteria for consent during the study period. Group A (7 countries, 1200 patients), and group B (15 countries, 1898 patients) were comparable with age and gender distribution. Cognition was better preserved prior to admission in group B. Group A suffered from more organ dysfunction at admission compared to group B with Sequential Organ Failure Assessment score median 8 and 6 respectively. ICU survival was lower in group A, 66.2% compared to 78.4% in group B (p<0.001). We hence found profound effects on outcomes according to differences in obtaining consent for this study. It seems that the most severely ill elderly patients were less often recruited to the study in group B. Hence the outcome measured as survival was higher in this group. We therefore conclude that consent likely is an important confounding factor for outcome evaluation in international studies focusing on old patients.

Sex-specific treatment characteristics and 30-day mortality outcomes of critically ill COVID-19 patients over 70 years of age-results from the prospective COVIP study.

PURPOSE: Older critically ill patients with COVID-19 have been the most vulnerable during the ongoing pandemic, with men being more prone to hospitalization and severe disease than women. We aimed to explore sex-specific differences in treatment and outcome after intensive care unit (ICU) admission in this cohort. METHODS: We performed a sex-specific analysis in critically ill patients ≥ 70 yr of age with COVID-19 who were included in the international prospective multicenter COVIP study. All patients were analyzed for ICU admission and treatment characteristics. We performed a multilevel adjusted regression analysis to elucidate associations of sex with 30-day mortality. RESULTS: A total of 3,159 patients (69.8% male, 30.2% female; median age, 75 yr) were included. Male patients were significantly fitter than female patients as determined by the Clinical Frailty Scale (fit, 67% vs 54%; vulnerable, 14% vs 19%; frail, 19% vs 27%; P < 0.001). Male patients more often underwent tracheostomy (20% vs 14%; odds ratio [OR], 1.57; P < 0.001), vasopressor therapy (69% vs 62%; OR, 1.25; P = 0.02), and renal replacement therapy (17% vs 11%; OR, 1.96; P < 0.001). There was no difference in mechanical ventilation, life-sustaining treatment limitations, and crude 30-day mortality (50% male vs 49% female; OR, 1.11; P = 0.19), which remained true after adjustment for disease severity, frailty, age and treatment limitations (OR, 1.17; 95% confidence interval, 0.94 to 1.45; P = 0.16). CONCLUSION: In this analysis of sex-specific treatment characteristics and 30-day mortality outcomes of critically ill patients with COVID-19 ≥ 70 yr of age, we found more tracheostomy and renal replacement therapy in male vs female patients, but no significant association of patient sex with 30-day mortality. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT04321265); registered 25 March 2020).

RéSUMé: OBJECTIF: Les patients âgés gravement malades atteints de la COVID-19 ont été les plus vulnérables pendant la pandémie actuelle, les hommes étant plus sujets à l'hospitalisation et aux maladies graves que les femmes. Nous avons cherché à explorer les différences spécifiques au sexe dans le traitement et les devenirs après l'admission à l'unité de soins intensifs (USI) dans cette cohorte. MéTHODE: Nous avons effectué une analyse spécifique au sexe chez des patients gravement malades âgés de ≥ 70 ans atteints de COVID-19 qui ont été inclus dans l'étude prospective multicentrique internationale COVIP. Tous les patients ont été analysés pour connaître les détails de leur admission à l'USI et les caractéristiques de leur traitement. Nous avons réalisé une analyse de régression ajustée à plusieurs niveaux pour élucider les associations entre le sexe et la mortalité à 30 jours. RéSULTATS: Au total, 3159 patients (69,8 % d'hommes, 30,2 % de femmes; âge médian, 75 ans) ont été inclus. Les patients de sexe masculin étaient significativement plus en forme que les patientes, tel que déterminé par l'échelle de fragilité clinique (bonne santé, 67 % vs 54 %; vulnérables, 14 % vs 19 %; fragiles, 19 % vs 27 %; P < 0,001). Les patients de sexe masculin ont plus souvent bénéficié d'une trachéostomie (20 % vs 14 %; rapport de cotes [RC], 1,57; P < 0,001), d'un traitement vasopresseur (69 % vs 62 %; RC, 1,25; P = 0,02) et d'un traitement substitutif de l'insuffisance rénale (17 % vs 11 %; RC, 1,96; P < 0,001). Il n'y avait aucune différence en matière de ventilation mécanique, de limites des traitements de maintien en vie et de mortalité brute à 30 jours (50 % d'hommes vs 49 % de femmes; RC, 1,11; P = 0,19), ce qui est demeuré le cas après ajustement pour tenir compte de la gravité de la maladie, de la fragilité, de l'âge et des limites du traitement (RC, 1,17 ; intervalle de confiance à 95 %, 0,94 à 1,45; P = 0,16). CONCLUSION: Dans cette analyse des caractéristiques de traitement spécifiques au sexe et des résultats de mortalité à 30 jours des patients gravement malades atteints de COVID-19 de ≥ 70 ans, nous avons noté un nombre plus élevé de trachéotomies et de traitements substitutifs de l'insuffisance rénale chez les hommes vs les femmes, mais aucune association significative entre le sexe des patients et la mortalité à 30 jours. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT04321265); enregistré le 25 mars 2020.

Extubation in neurocritical care patients: the ENIO international prospective study.

PURPOSE: Neurocritical care patients receive prolonged invasive mechanical ventilation (IMV), but there is poor specific information in this high-risk population about the liberation strategies of invasive mechanical ventilation. METHODS: ENIO (NCT03400904) is an international, prospective observational study, in 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Neurocritical care patients with a Glasgow Coma Score (GCS) ≤ 12, receiving IMV ≥ 24 h, undergoing extubation attempt or tracheostomy were included. The primary endpoint was extubation failure by day 5. An extubation success prediction score was created, with 2/3 of patients randomly allocated to the training cohort and 1/3 to the validation cohort. Secondary endpoints were the duration of IMV and in-ICU mortality. RESULTS: 1512 patients were included. Among the 1193 (78.9%) patients who underwent an extubation attempt, 231 (19.4%) failures were recorded. The score for successful extubation prediction retained 20 variables as independent predictors. The area under the curve (AUC) in the training cohort was 0.79 95% confidence interval (CI95) [0.71-0.87] and 0.71 CI95 [0.61-0.81] in the validation cohort. Patients with extubation failure displayed a longer IMV duration (14 [7-21] vs 6 [3-11] days) and a higher in-ICU mortality rate (8.7% vs 2.4%). Three hundred and nineteen (21.1%) patients underwent tracheostomy without extubation attempt. Patients with direct tracheostomy displayed a longer duration of IMV and higher in-ICU mortality than patients with an extubation attempt (success and failure). CONCLUSIONS: In neurocritical care patients, extubation failure is high and is associated with unfavourable outcomes. A score could predict extubation success in multiple settings. However, it will be mandatory to validate our findings in another prospective independent cohort.

Variation in communication and family visiting policies in intensive care within and between countries during the Covid-19 pandemic: The COVISIT international survey.

BACKGROUND: During the COVID-19 pandemic, intensive care units (ICU) introduced restrictions to in-person family visiting to safeguard patients, healthcare personnel, and visitors. METHODS: We conducted a web-based survey (March-July 2021) investigating ICU visiting practices before the pandemic, at peak COVID-19 ICU admissions, and at the time of survey response. We sought data on visiting policies and communication modes including use of virtual visiting (videoconferencing). RESULTS: We obtained 667 valid responses representing ICUs in all continents. Before the pandemic, 20% (106/525) had unrestricted visiting hours; 6% (30/525) did not allow in-person visiting. At peak, 84% (558/667) did not allow in-person visiting for patients with COVID-19; 66% for patients without COVID-19. This proportion had decreased to 55% (369/667) at time of survey reporting. A government mandate to restrict hospital visiting was reported by 53% (354/646). Most ICUs (55%, 353/615) used regular telephone updates; 50% (306/667) used telephone for formal meetings and discussions regarding prognosis or end-of-life. Virtual visiting was available in 63% (418/667) at time of survey. CONCLUSIONS: Highly restrictive visiting policies were introduced at the initial pandemic peaks, were subsequently liberalized, but without returning to pre-pandemic practices. Telephone became the primary communication mode in most ICUs, supplemented with virtual visits.

Variations in end-of-life care practices in older critically ill patients with COVID-19 in Europe.

BACKGROUND: Previous studies reported regional differences in end-of-life care (EoLC) for critically ill patients in Europe. OBJECTIVES: The purpose of this post-hoc analysis of the prospective multicentre COVIP study was to investigate variations in EoLC practices among older patients in intensive care units during the coronavirus disease 2019 pandemic. METHODS: A total of 3105 critically ill patients aged 70 years and older were enrolled in this study (Central Europe: n = 1573; Northern Europe: n = 821; Southern Europe: n = 711). Generalised estimation equations were used to calculate adjusted odds ratios (aORs) to population averages. Data were adjusted for patient-specific variables (demographic, disease-specific) and health economic data (gross domestic product, health expenditure per capita). The primary outcome was any treatment limitation, and 90-day mortality was a secondary outcome. RESULTS: The frequency of the primary endpoint (treatment limitation) was highest in Northern Europe (48%), intermediate in Central Europe (39%) and lowest in Southern Europe (24%). The likelihood for treatment limitations was lower in Southern than in Central Europe (aOR 0.39; 95% confidence interval [CI] 0.21-0.73; p = 0.004), even after multivariable adjustment, whereas no statistically significant differences were observed between Northern and Central Europe (aOR 0.57; 95%CI 0.27-1.22; p = 0.15). After multivariable adjustment, no statistically relevant mortality differences were found between Northern and Central Europe (aOR 1.29; 95%CI 0.80-2.09; p = 0.30) or between Southern and Central Europe (aOR 1.07; 95%CI 0.66-1.73; p = 0.78). CONCLUSION: This study shows a north-to-south gradient in rates of treatment limitation in Europe, highlighting the heterogeneity of EoLC practices across countries. However, mortality rates were not affected by these results.

Impact of lockdown due to the COVID-19 pandemic on mental health among the Libyan population.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic may have a potentially serious effect on mental health and increase the risk of anxiety, depression, and post-traumatic stress disorders in people. In this study, we aimed to determine the prevalence of psychological illness and the impact of the COVID-19 pandemic on the Libyan population's mental health. METHOD: A cross-sectional survey, conducted in both online and paper modes and consisting of five sections, was completed in more than 30 cities and towns across Libya. The first section consisted of questions on basic demographic characteristics. The second section contained a survey related to the lockdown status, activities, related stress levels, and quarantine. The third section comprised the self-administered 9-item Patient Health Questionnaire (PHQ-9). The fourth section contained the 7-item Generalized Anxiety Disorder Scale (GAD-7), and the fifth section contained the Impact of Event Scale-Revised (IES-R). RESULT: Of the 31,557 respondents, 4,280 (13.6%) reported severe depressive symptoms, with a mean [standard deviation (SD)] PHQ-9 score of 8.32 (5.44); 1,767 (5.6%) reported severe anxiety symptoms, with a mean (SD) GAD-7 score of 6 (4.6); and 6,245 (19.8%) of the respondents reported post-traumatic stress disorder (PTSD), with a mean (SD) score of 15.3 (18.85). In multivariate analysis, young age, being female, unmarried, educated, or victims of domestic violence or abuse, work suspension during the pandemic, and having increased workload, financial issues, suicidal thoughts, or a family member with or hospitalized due to COVID-19 were significantly associated with a high likelihood of depressive and anxiety symptoms, as well as PTSD. Internal displacement due to civil war was also associated with PTSD. CONCLUSION: To our knowledge, this is the first study to analyze the psychological impacts of the COVID-19 pandemic and civil war in Libya. Further study on the development of strategies and interventions aimed at reducing the mental disease burden on the Libyan population is warranted.