The KINETIC phase 2 randomized controlled trial of oral pamapimod-pioglitazone in non-critically ill COVID-19 inpatients.

The combination of pamapimod and pioglitazone (KIN001) has a synergetic antiviral, anti-inflammatory, and antifibrotic activity, which may prevent evolution toward COVID-19-associated severe respiratory failure. In a randomized, placebo-controlled, double-blind, phase 2, multicenter trial, 128 non-critically ill hospitalized patients with confirmed COVID-19 were treated with KIN001 or a placebo for 28 days. The proportion of patients alive and free of oxygen or respiratory support at the end of the therapy was lower than anticipated but not different in the two groups (KIN001 n = 19, 29%, placebo n = 21, 33%). 85 participants had at least one adverse event, with no difference in the number and distribution of events between the two groups. The clinical trial was stopped for futility, mainly due to a lower-than-expected incidence of the primary endpoint. KIN001 was safe and well-tolerated but had no significant effect on clinical outcome.

[Classic ventilatory modes for invasive mechanical ventilation]. / Modes ventilatoires de base en ventilation mécanique invasive.

Invasive mechanical ventilation is part of the daily practice of the intensivist and anesthetist. The comprehensive knowledge of ventilatory modes is mandatory for managing the ventilated patients. The objective of this article is to explain the characteristics of the barometric and volumetric modes and the differences between controlled, assist-controlled, and assisted ventilation. The most common modes (volume and pressure assist-control, dual modes and pressure support) are described in detail. Parameters that must be set and those that must be monitored in each mode are also described. Finally, suggestions for initial settings are provided in order to offer the reader unfamiliar with mechanical ventilation a practical decision-making aid.

La ventilation mécanique invasive est un outil indispensable à la pratique de l'intensiviste et de l'anesthésiste. La connaissance des modes ventilatoires est nécessaire pour la prise en charge des patients ventilés. L'objectif de cet article est, d'une part, de distinguer les caractéristiques des modes barométriques et volumétriques, et de comprendre les différences entre les modes contrôlé, assisté-contrôlé et assisté et, d'autre part, de distinguer les paramètres qui doivent être réglés de ceux qui doivent être monitorés. Les modes les plus utilisés (volume contrôlé, pression contrôlée, modes mixtes et aide inspiratoire) font l'objet d'une description détaillée. Des suggestions de réglages initiaux sont proposées pour ces modes afin d'offrir au lecteur peu familier avec la ventilation mécanique une aide décisionnelle pratique.

Early mobilisation and rehabilitation in Swiss intensive care units: a cross-sectional survey.

BACKGROUND: Patients in intensive care units (ICUs) are at high risk of developing physical, functional, cognitive, and mental impairments. Early mobilisation aims to improve patient outcomes and is increasingly considered the standard of care. This survey aimed to investigate the characteristics, current use and variations of early mobilisation and rehabilitation in Swiss ICUs. METHODS: We conducted a cross-sectional survey among all ICU lead physicians, who provided data on their institutional characteristics, early mobilisation and rehabilitation practices, and their perceptions of the use and variation of early rehabilitation practices in Switzerland. RESULTS: The survey response rate was 44% (37/84). Among ICUs caring for adults (34/37), 26 were in the German-speaking region, five in the French-speaking region, and three in the Italian-speaking region. All ICUs regularly involved physiotherapy in the rehabilitation process and 50% reported having a specialised physiotherapy team. All ICUs reported performing early mobilisation, starting within the first 7 days after ICU admission. About half reported the use of a rehabilitation (45%) or early mobilisation protocol (50%). Regular, structured, interdisciplinary rounds or meetings of the ICU care team to discuss rehabilitation measures and goals for patients were stated to be held by 53%. The respondents stated that 82% of their patients received early mobilisation measures during their ICU stay. Most frequently provided mobilisation measures included passive range of motion (97%), passive chair position in bed (97%), active range of motion muscle activation and training (88%), active side to side turning (91%), sitting on the edge of the bed (94%), transfer from bed to a chair (97%), and ambulation (94%). The proportion of ICUs providing a specific early mobilisation measure, the proportion of patients receiving it, and the time dedicated to it varied across language regions, hospital types, ICU types, and ICU sizes. Almost one third of the ICU lead physicians considered early rehabilitation to be underused in their own ICU and about half considered it to be underused in Switzerland more generally. ICU lead physicians stressed lack of personnel, financial resources, and time as key causes for underuse. Moreover, they highlighted the importance of early and systematic or protocol-based rehabilitation and interprofessional approaches that are adaptive to the patients' rehabilitation needs and potential. CONCLUSION: This survey suggests that almost all ICUs in Switzerland practice some form of early mobilisation with the aim of early rehabilitation. However, the described approaches, as well as the reported use of early mobilisation measures were heterogenous across Swiss ICUs.

[POCUS (Point-of-Care Ultrasonography) in internal general medicine: applications scope and training]. / POCUS (Point-of-care ultrasonography) en médecine interne générale†: champ d'application et formation.

POCUS is a valuable tool for the internist. Its field of application in internal medicine is multisystemic and requires rigorous training. This training includes an initiation phase, followed by a practical training phase for the acquisition of images from patients or simulators. Supervision by experts is vital for mastering the necessary skills for the safe use of POCUS. Although, supervisors are available in French speaking Switzerland, there are too few to meet training needs. Several associations provide training courses to obtain POCUS certification, the content of which has been established since 2018 in Switzerland. In order to maintain a high level of proficiency and to identify tomorrow's supervisors, it is essential to provide the necessary means to allow more internists to obtain POCUS certification.

Le POCUS (Point-of-care ultrasonography) est précieux dans la pratique de l'interniste. Son champ d'application en médecine interne est multisystémique et requiert une formation rigoureuse qui comporte une phase d'initiation et une phase de formation pratique pour l'acquisition des images sur patients ou simulateurs. La supervision par des experts est primordiale pour l'acquisition des compétences nécessaires à l'emploi sûr du POCUS. Les superviseurs existent en Romandie, mais sont trop peu nombreux pour répondre à la demande. Plusieurs associations offrent des formations pour l'obtention du certificat POCUS dont le contenu est établi depuis 2018 en Suisse. Il est essentiel d'engager les moyens nécessaires pour permettre à plus d'internistes d'obtenir cette certification POCUS, pour maintenir un niveau élevé de compétences et identifier les superviseurs de demain.

[Smarter Intensive Care Medicine: Choosing Wisely®, less is more, appropriate is better and so what? The current situation in the Swiss intensive care medicine!] / Smarter Intensive Care Medicine: Choosing Wisely®, less is more, appropriate is better and so what?

Smarter Intensive Care Medicine: Choosing Wisely®, less is more, appropriate is better … and so what? The current situation in the Swiss intensive care medicine! Abstract. The top 9 list of the Swiss Society for Intensive Care Medicine (SSICM) was published in 2017. What is the status of this initiative in terms of its implementation in Swiss intensive care units, its impact on patient care and on the costs of intensive care medicine? What developments in the published evidence justify updating the list and what measures are needed to continue this initiative in the coming years? This article provides an up-to-date overview of the SSICM's Choosing Wisely® initiative.

Near real-time observation reveals increased prevalence of young patients in the ICU during the emerging third SARS-CoV-2 wave in Switzerland.

AIMS OF THE STUDY: During the ongoing COVID-19 pandemic, the launch of a large-scale vaccination campaign and virus mutations have hinted at possible changes in transmissibility and the virulence affecting disease progression up to critical illness, and carry potential for future vaccination failure. To monitor disease development over time with respect to critically ill COVID-19 patients, we report near real-time prospective observational data from the RISC-19-ICU registry that indicate changed characteristics of critically ill patients admitted to Swiss intensive care units (ICUs) at the onset of a third pandemic wave. METHODS: 1829 of 3344 critically ill COVID-19 patients enrolled in the international RISC-19-ICU registry as of 31 May 2021 were treated in Switzerland and were included in the present study. Of these, 1690 patients were admitted to the ICU before 1 February 2021 and were compared with 139 patients admitted during the emerging third pandemic wave RESULTS: Third wave patients were a mean of 5.2 years (95% confidence interval [CI] 3.2–7.1) younger (median 66.0 years, interquartile range [IQR] 57.0–73.0 vs 62.0 years, IQR 54.5–68.0; p <0.0001) and had a higher body mass index than patients admitted in the previous pandemic period. They presented with lower SAPS II and APACHE II scores, less need for circulatory support and lower white blood cell counts at ICU admission. P/F ratio was similar, but a 14% increase in ventilatory ratio was observed over time (p = 0.03) CONCLUSION: Near real-time registry data show that the latest COVID-19 patients admitted to ICUs in Switzerland at the onset of the third wave were on average 5 years younger, had a higher body mass index, and presented with lower physiological risk scores but a trend towards more severe lung failure. These differences may primarily be related to the ongoing nationwide vaccination campaign, but the possibility that changes in virus-host interactions may be a co-factor in the age shift and change in disease characteristics is cause for concern, and should be taken into account in the public health and vaccination strategy during the ongoing pandemic. (ClinicalTrials.gov Identifier: NCT04357275).

Timing of VV-ECMO therapy implementation influences prognosis of COVID-19 patients.

INTRODUCTION: Current knowledge on the use of extracorporeal membrane oxygenation (ECMO) in COVID-19 remains limited to small series and registry data. In the present retrospective monocentric study, we report on our experience, our basic principles, and our results in establishing and managing ECMO in critically ill COVID-19 patients. METHODS: A cohort study was conducted in patients with severe acute respiratory distress syndrome (ARDS) related to COVID-19 pneumonia admitted to the ICU of the Geneva University Hospitals and supported by VV-ECMO from March 14 to May 31. The VV-ECMO implementation criteria were defined according to an institutional algorithm validated by the local crisis unit and the Swiss Society of Intensive Care Medicine. RESULTS: Out of 137 ARDS patients admitted to our ICU, 10 patients (age 57 ± 4 years, BMI 31.5 ± 5 kg/m2 , and SAPS II score 56 ± 3) were put on VV-ECMO. The mean duration of mechanical ventilation before ECMO and mean time under ECMO were 7 ± 3 days and 19 ± 11 days, respectively. The ICU and hospital length of stay were 26 ± 11 and 35 ± 10 days, respectively. The survival rate for patients on ECMO was 40%. The comparative analysis between survivors and non-survivors highlighted that survivors had a significantly shorter mechanical ventilation duration before ECMO (4 ± 2 days vs. 9 ± 2 days, p = 0.01). All the patients who had more than 150 h of mechanical ventilation before the application of ECMO ultimately died. CONCLUSION: The present results suggest that VV-ECMO can be safely utilized in appropriately selected COVID-19 patients with refractory hypoxemia. The main information for clinicians is that late VV-ECMO therapy (i.e., beyond the seventh day of mechanical ventilation) seems futile.

Machine learning using the extreme gradient boosting (XGBoost) algorithm predicts 5-day delta of SOFA score at ICU admission in COVID-19 patients.

Background: Accurate risk stratification of critically ill patients with coronavirus disease 2019 (COVID-19) is essential for optimizing resource allocation, delivering targeted interventions, and maximizing patient survival probability. Machine learning (ML) techniques are attracting increased interest for the development of prediction models as they excel in the analysis of complex signals in data-rich environments such as critical care. Methods: We retrieved data on patients with COVID-19 admitted to an intensive care unit (ICU) between March and October 2020 from the RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry. We applied the Extreme Gradient Boosting (XGBoost) algorithm to the data to predict as a binary outcome the increase or decrease in patients' Sequential Organ Failure Assessment (SOFA) score on day 5 after ICU admission. The model was iteratively cross-validated in different subsets of the study cohort. Results: The final study population consisted of 675 patients. The XGBoost model correctly predicted a decrease in SOFA score in 320/385 (83%) critically ill COVID-19 patients, and an increase in the score in 210/290 (72%) patients. The area under the mean receiver operating characteristic curve for XGBoost was significantly higher than that for the logistic regression model (0.86 vs. 0.69, P < 0.01 [paired t-test with 95% confidence interval]). Conclusions: The XGBoost model predicted the change in SOFA score in critically ill COVID-19 patients admitted to the ICU and can guide clinical decision support systems (CDSSs) aimed at optimizing available resources.

[Acute respiratory failure†: non-invasive hospital management]. / Insuffisance respiratoire aiguë†: prise en charge hospitalière non invasive.

Acute respiratory failure is a complex physiopathological process and the choice of the most appropriate therapy has to be made between standard oxygen therapy (SOT), high-flow oxygen therapy through nasal cannula (High-Flow Nasal Cannula (HFNC)), non- invasive ventilation (NIV) or invasive ventilation. HFNC can deliver a higher and consistent inspired fraction of oxygen than SOT, but has not clearly demonstrated a clinical advantage over other methods. NIV is a therapy of choice in the management of acute exacerbation of chronic obstructive pulmonary disease and acute cardiogenic pulmonary edema, but its effectiveness in other indications is questionable. In any case, early detection of treatment failure is essential to avoid late tracheal intubation, which is associated with increased mortality.

L'insuffisance respiratoire aiguë est un processus physiopatho logique complexe et le choix de la thérapie la plus indiquée doit être fait entre l'oxygénothérapie standard (OS), l'oxygénothérapie à haut débit par canule nasale (High-Flow Nasal Cannula (HFNC)), la ventilation non invasive (VNI) ou la ventilation invasive. Le HFNC permet de délivrer une fraction inspirée d'oxygène plus élevée et constante que l'OS, mais n'a pas clairement démontré d'avantage clinique par rapport aux autres méthodes. La VNI est une thérapie de choix lors d'exacerbation aiguë de bronchopneumopathie chronique obstructive et d'œdème aigu du poumon cardiogénique, mais son efficacité dans les autres indications reste discutée. Dans tous les cas, la détection précoce de l'échec thérapeutique est primordiale afin d'éviter une intubation trachéale tardive, associée à une augmentation de la mortalité.

Haemodynamic monitoring and management in COVID-19 intensive care patients: an International survey.

PURPOSE: To survey haemodynamic monitoring and management practices in intensive care patients with the coronavirus disease 2019 (COVID-19). METHODS: A questionnaire was shared on social networks or via email by the authors and by Anaesthesia and/or Critical Care societies from France, Switzerland, Belgium, Brazil, and Portugal. Intensivists and anaesthetists involved in COVID-19 ICU care were invited to answer 14 questions about haemodynamic monitoring and management. RESULTS: Globally, 1000 questionnaires were available for analysis. Responses came mainly from Europe (n = 460) and America (n = 434). According to a majority of respondents, COVID-19 ICU patients frequently or very frequently received continuous vasopressor support (56%) and had an echocardiography performed (54%). Echocardiography revealed a normal cardiac function, a hyperdynamic state (43%), hypovolaemia (22%), a left ventricular dysfunction (21%) and a right ventricular dilation (20%). Fluid responsiveness was frequently assessed (84%), mainly using echo (62%), and cardiac output was measured in 69%, mostly with echo as well (53%). Venous oxygen saturation was frequently measured (79%), mostly from a CVC blood sample (94%). Tissue perfusion was assessed biologically (93%) and clinically (63%). Pulmonary oedema was detected and quantified mainly using echo (67%) and chest X-ray (61%). CONCLUSION: Our survey confirms that vasopressor support is not uncommon in COVID-19 ICU patients and suggests that different haemodynamic phenotypes may be observed. Ultrasounds were used by many respondents, to assess cardiac function but also to predict fluid responsiveness and quantify pulmonary oedema. Although we observed regional differences, current international guidelines were followed by most respondents.

Prognostic factors associated with mortality risk and disease progression in 639 critically ill patients with COVID-19 in Europe: Initial report of the international RISC-19-ICU prospective observational cohort.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a high disease burden with 10% of confirmed cases progressing towards critical illness. Nevertheless, the disease course and predictors of mortality in critically ill patients are poorly understood. METHODS: Following the critical developments in ICUs in regions experiencing early inception of the pandemic, the European-based, international RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry was created to provide near real-time assessment of patients developing critical illness due to COVID-19. FINDINGS: As of April 22, 2020, 639 critically ill patients with confirmed SARS-CoV-2 infection were included in the RISC-19-ICU registry. Of these, 398 had deceased or been discharged from the ICU. ICU-mortality was 24%, median length of stay 12 (IQR, 5-21) days. ARDS was diagnosed in 74%, with a minimum P/F-ratio of 110 (IQR, 80-148). Prone positioning, ECCO2R, or ECMO were applied in 57%. Off-label therapies were prescribed in 265 (67%) patients, and 89% of all bloodstream infections were observed in this subgroup (n = 66; RR=3·2, 95% CI [1·7-6·0]). While PCT and IL-6 levels remained similar in ICU survivors and non-survivors throughout the ICU stay (p = 0·35, 0·34), CRP, creatinine, troponin, d-dimer, lactate, neutrophil count, P/F-ratio diverged within the first seven days (p<0·01). On a multivariable Cox proportional-hazard regression model at admission, creatinine, d-dimer, lactate, potassium, P/F-ratio, alveolar-arterial gradient, and ischemic heart disease were independently associated with ICU-mortality. INTERPRETATION: The European RISC-19-ICU cohort demonstrates a moderate mortality of 24% in critically ill patients with COVID-19. Despite high ARDS severity, mechanical ventilation incidence was low and associated with more rescue therapies. In contrast to risk factors in hospitalized patients reported in other studies, the main mortality predictors in these critically ill patients were markers of oxygenation deficit, renal and microvascular dysfunction, and coagulatory activation. Elevated risk of bloodstream infections underscores the need to exercise caution with off-label therapies.

[Etiological diagnosis of thyroid nodules†: collaborative approach between the internist and specialists]. / Diagnostic étiologique des nodules thyroïdiens - Approche collaborative entre le médecin de premier recours et les spécialistes.

One or more thyroid nodules, most often asymptomatic, may be found in more than half of the population, and they usually do not require specific therapeutic management, except for cancerous nodules. In order to avoid under-diagnosis and over-treatment, we propose a diagnostic strategy in line with current recommendations, based on the collaboration between general internist, radiologist, and endocrinologist. In addition to clinical information and thyroid function tests, thyroid ultrasound remains the first step in assessing the risk of nodule malignancy and setting the indication for fine needle aspiration. Cytology then makes it possible to define the therapeutic strategy, from an observation of the evolution to interventional, surgical or radiofrequency management.

Un ou plusieurs nodules thyroïdiens, le plus souvent asymptomatiques, peuvent être découverts chez plus de la moitié de la population, et dans la plupart des cas, ils ne nécessitent pas de prise en charge thérapeutique spécifique, sauf pour les nodules cancéreux. Afin d'éviter à la fois le sous-diagnostic et le surtraitement, nous proposons une stratégie diagnostique basée sur les recommandations actuelles, faisant appel à la collaboration entre l'interniste généraliste, le radiologue et l'endocrinologue. En complément aux informations cliniques et aux tests de la fonction thyroïdienne, l'ultrason de la thyroïde est l'examen de premier choix pour évaluer le risque de malignité du nodule et pour poser l'indication à la ponction à l'aiguille fine. La cytologie permet alors de définir la stratégie thérapeutique entre une observation de l'évolution ou une prise en charge interventionnelle, chirurgicale ou par radiofréquence.