Search

OBJECTIVES:. Septic shock is a common condition necessitating timely management including hemodynamic support with vasopressors. Despite the high prevalence and mortality, there is limited data characterizing patients who require three or more vasopressors. We sought to define the demographics, outcomes, and prognostic determinants associated with septic shock requiring three or more vasopressors. DESIGN:. This is a multicenter retrospective cohort of two ICU databases, Medical Information Mart for Intensive Care IV (MIMIC-IV) and electronic ICU-Clinical Research Database, which include over 400,000 patients admitted to 342 ICUs. PATIENTS:. Inclusion criteria entailed patients who were: 1) age 18 years old and older, 2) admitted to any ICU, 3) administered at least three vasopressors for at least 2 hours at any time during their ICU stay, and 4) identified to have sepsis based on the Sepsis-3 criteria. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. A total of 3447 patients met inclusion criteria. The median age was 67 years, 60.5% were male, and 96.6% had full code orders at the time of the third vasopressor initiation. Septic shock requiring three or more vasopressors was associated with 57.6% in-hospital mortality. Code status changes occurred in 23.9% of patients following initiation of a third vasopressor. Elevated lactate upon ICU admission (odds ratio [95% CI], 2.79 [2.73–2.85]), increased duration of time between ICU admission and third vasopressor initiation (1.78 [1.69–1.87]), increased serum creatinine (1.61 [1.59–1.62]), and age above 60 years (1.47 [1.41–1.54]) were independently associated with an increased risk of mortality based on analysis of the MIMIC-IV database. Non-White race and Richmond Agitation-Sedation Scale scores were not associated with mortality. CONCLUSIONS:. Septic shock requiring three vasopressors is associated with exceptionally high mortality. Knowledge of patients at highest risk of mortality in this population may inform management and expectations conveyed in shared decision-making.

Abstract Background Assessment of dynamic parameters to guide fluid administration is one of the mainstays of current resuscitation strategies. Each test has its own limitations, but passive leg raising (PLR) has emerged as one of the most versatile preload responsiveness tests. However, it requires real-time cardiac output (CO) measurement either through advanced monitoring devices, which are not routinely available, or echocardiography, which is not always feasible. Analysis of the hepatic vein Doppler waveform change, a simpler ultrasound-based assessment, during a dynamic test such as PLR could be useful in predicting preload responsiveness. The objective of this study was to assess the diagnostic accuracy of hepatic vein Doppler S and D-wave velocities during PLR as a predictor of preload responsiveness. Methods Prospective observational study conducted in two medical–surgical ICUs in Chile. Patients in circulatory failure and connected to controlled mechanical ventilation were included from August to December 2023. A baseline ultrasound assessment of cardiac function was performed. Then, simultaneously, ultrasound measurements of hepatic vein Doppler S and D waves and cardiac output by continuous pulse contour analysis device were performed during a PLR maneuver. Results Thirty-seven patients were analyzed. 63% of the patients were preload responsive defined by a 10% increase in CO after passive leg raising. A 20% increase in the maximum S wave velocity after PLR showed the best diagnostic accuracy with a sensitivity of 69.6% (49.1–84.4) and specificity of 92.8 (68.5–99.6) to detect preload responsiveness, with an area under curve of receiving operator characteristic (AUC–ROC) of 0.82 ± 0.07 (p = 0.001 vs. AUC–ROC of 0.5). D-wave velocities showed worse diagnostic accuracy. Conclusions Hepatic vein Doppler assessment emerges as a novel complementary technique with adequate predictive capacity to identify preload responsiveness in patients in mechanical ventilation and circulatory failure. This technique could become valuable in scenarios of basic hemodynamic monitoring and when echocardiography is not feasible. Future studies should confirm these results.

Abstract Background The use of ultrasound assessment, including the Venous Excess Ultrasound (VEXUS) score, is increasingly being utilised as part of fluid status assessment in clinical practice. We aimed to evaluate the ability of the VEXUS score to track fluid removal during the course of the dialysis session and explore the relationship between traditional measures of fluid status and venous congestion. Methods Single-centre, observational study in patients undergoing intermittent haemodialysis, who presented above their target dry weight. Patients had serial assessment using VEXUS, lung ultrasound and selected echocardiographic measures, before, during and after fluid removal. Results Amongst 33 patients analysed, 5 (15%) had an elevated VEXUS score (> 0). There was no difference in starting weight, dry weight or amount of fluid removed in patients with a normal VEXUS score and those with an elevated VEXUS score. In all patients with elevated VEXUS scores, the degree of venous congestion improved during the course of fluid removal. All patients with an elevated VEXUS score had evidence of both right and left ventricular systolic impairment. Conclusion In patients with ESRF undergoing haemodialysis, the incidence of venous congestion as measured by the VEXUS is low. In patients with elevated VEXUS scores, removal of fluid through haemodialysis improves the venous congestion score. The pattern of LV and RV systolic dysfunction suggests that VEXUS may be a reflection of cardiac failure rather than venous volume status. Trial registration Ethical approval was provided by South Central-Berkshire Research and Ethics Committee and registered on clinicaltrials.org (IRAS305720). Trial registration: ISRCTN14351189 – Retrospectively registered on 30/11/2023.

Abstract Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021).

Polypropylene is extensively used in aerospace, automotive and construction applications due to its versatile properties. This project aims to reduce plastic and oil palm waste and promote the development of strong, sustainable and eco-friendly construction materials. The objective of this project is to develop a sustainable yet high-performance construction material by incorporating polypropylene particles, oil palm empty fruit bunch (OPEFB) fibres and oil palm shell (OPS) particles into epoxy composites through the hand lay-up method. The composite specimens undergo ASTM D638 tensile test to determine the tensile properties. The addition of PP particles in varying weights shows decrease in tensile strength, likely due to poor dispersion and compatibility with the epoxy matrix. Incorporating 3 wt% OPEFB fibres with fibre length from 2mm to 4mm improves tensile strength by 2.32% and 23.36% respectively at higher PP particle loadings which are 15 wt% and 25 wt%. Adding 1 wt% and 3 wt% OPS particles improves the tensile strength by 2.96% and 4.68% respectively, in composites with 10 wt% PP particles and 3 wt% OPEFB fibres. The tensile performance may be improved by treating PP particles with compatibilizers such as silane or maleic anhydride grafted polypropylene.

Ultrasonography is becoming an essential part of the management of critically ill patients. There has been a sufficient body of evidence to support the incorporation of point-of-care ultrasound (POCUS) in anaesthesia and intensive care medicine training programme. Recently the European Society of Intensive Care Medicine reco­gnized POCUS as an essential skill for European Intensive Care Medicine specialists and updated Competency Based Training in Intensive Care (CoBaTrICe). Following European training standards, the Ultrasound and Echocardiography Committee of the Polish Society of Anaesthesiology and Intensive Therapy issued this Position Statement for recommendations for the accreditation process in POCUS in Poland.

Abstract Background Right ventricular (RV) dysfunction is common in critically ill patients and is associated with poor outcomes. RV function is usually evaluated by Tricuspid Annular Plane Systolic Excursion (TAPSE) which can be obtained using critical care echocardiography (CCE). Myocardial deformation imaging, measuring strain, is suitable for advanced RV function assessment and has widely been studied in cardiology. However, it is relatively new for the Intensive Care Unit (ICU) and little is known about RV strain in critically ill patients. Therefore, the objectives of this study were to evaluate the feasibility of RV strain in critically ill patients using tissue-Doppler imaging (TDI) and explore the association between RV strain and conventional CCE measurements representing RV function. Methods This is a single-center sub-study of two prospective observational cohorts (Simple Intensive Care Studies (SICS)-I and SICS-II). All acutely admitted adults with an expected ICU stay over 24 h were included. CCE was performed within 24 h of ICU admission. In patients in which CCE was performed, TAPSE, peak systolic velocity at the tricuspid annulus (RV s’) and TDI images were obtained. RV free wall longitudinal strain (RVFWSL) and RV global four-chamber longitudinal strain (RV4CSL) were measured during offline analysis. Results A total of 171 patients were included. Feasibility of RVFWSL and RV4CSL was, respectively, 62% and 56% in our population; however, when measurements were performed, intra- and inter-rater reliability based on the intraclass correlation coefficient were good to excellent. RV dysfunction based on TAPSE or RV s’ was found in 56 patients (33%) and 24 patients (14%) had RV dysfunction based on RVFWSL or RV4CSL. In 14 patients (8%), RVFWSL, RV4CSL, or both were reduced, despite conventional RV function measurements being preserved. These patients had significantly higher severity of illness scores. Sensitivity analysis with fractional area change showed similar results. Conclusions TDI RV strain imaging in critically ill patients is challenging; however, good-to-excellent reproducibility was shown when measurements were adequately obtained. Future studies are needed to elucidate the diagnostic and prognostic value of RV strain in critically ill patients, especially to outweigh the difficulty and effort of imaging against the clinical value.

OBJECTIVES:. Clinical decision support systems (CDSSs) are used in various aspects of healthcare to improve clinical decision-making, including in the ICU. However, there is growing evidence that CDSS are not used to their full potential, often resulting in alert fatigue which has been associated with patient harm. Clinicians in the ICU may be more vulnerable to desensitization of alerts than clinicians in less urgent parts of the hospital. We evaluated facilitators and barriers to appropriate CDSS interaction and provide methods to improve currently available CDSS in the ICU. DESIGN:. Sequential explanatory mixed-methods study design, using the BEhavior and Acceptance fRamework. SETTING:. International survey study. PATIENT/SUBJECTS:. Clinicians (pharmacists, physicians) identified via survey, with recent experience with clinical decision support. INTERVENTIONS:. An initial survey was developed to evaluate clinician perspectives on their interactions with CDSS. A subsequent in-depth interview was developed to further evaluate clinician (pharmacist, physician) beliefs and behaviors about CDSS. These interviews were then qualitatively analyzed to determine themes of facilitators and barriers with CDSS interactions. MEASUREMENTS AND MAIN RESULTS:. A total of 48 respondents completed the initial survey (estimated response rate 15.5%). The majority believed that responding to CDSS alerts was part of their job (75%) but felt they experienced alert fatigue (56.5%). In the qualitative analysis, a total of five facilitators (patient safety, ease of response, specificity, prioritization, and feedback) and four barriers (excess quantity, work environment, difficulty in response, and irrelevance) were identified from the in-depth interviews. CONCLUSIONS:. In this mixed-methods survey, we identified areas that institutions should focus on to improve appropriate clinician interactions with CDSS, specific to the ICU. Tailoring of CDSS to the ICU may lead to improvement in CDSS and subsequent improved patient safety outcomes.

Background and aims: Recent preclinical studies and meta-analysis of clinical trials suggested that acupuncture may improve cognition in cerebral small vessel disease (CSVD). We investigated the cerebral hemodynamics of acupuncture in subjects with CSVD and compared its impact upon the cerebral hemodynamics in normal elderly subjects Methods: 10 subjects with CSVD (CSVD group) and 10 aged-matched control subjects who had no or insignificant CSVD (control group) were recruited. A single session of acupuncture was applied for 30 min in both groups. We assessed the effect of our acupuncture intervention on cerebral hemodynamics by transcranial Doppler ultrasound (TCD). Peak systolic velocity (PSV) and pulsatility index (PI) of the middle cerebral artery (MCA) were assessed Results: We observed that PSV increased by a maximum of 39% at 20 min (p

Objective: To compare bioelectrical impedance analysis (BIA)-derived parameters in healthy volunteers and critically ill patients and to assess its prognostic value in an ICU patient cohort. Design: Retrospective, observational data analysis. Setting: Single centre, tertiary-level ICU (Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg Hospital). Patients: 101 patients and 101 healthy subjects, participants of International Fluid Academy Days. Measurements and main results: Compared to healthy volunteers, both male and female ICU patients had significantly higher values for total body water (TBW), extracellular water (ECW), extracellular fluid (ECF), plasma, and interstitial fluid volumes. The phase angle was significantly lower and the malnutrition index was significantly higher in ICU patients, regardless of gender. Non-survivors in the ICU had significantly higher extracellular water content (ECW, 50.7 ± 5.1 vs. 48.9 ± 4.3%, p = 0.047) and accordingly significantly lower intracellular water (ICW, 49.2 ± 5.1 vs. 51.1 ± 4.3%, p = 0.047). The malnutrition index was also significantly higher in non-survivors compared to survivors (0.94 ± 0.17 vs. 0.87 ± 0.16, p = 0.048), as was the capillary leak index (ECW/ICW). Conclusions: Compared to healthy volunteers, this study observed a higher malnutrition index and TBW in ICU patients with an accumulation of fluids in the extracellular compartment. ICU non-survivors showed similar results, indicating that ICU patients and a fortiori non-survivors are generally overhydrated, with increased TBW and ECW, and more undernourished, as indicated by a higher malnutrition index.

The COVID-19 pandemic has tested the very elements of human factors and ergonomics (HFE) to their maximum. HFE is an established scientific discipline that studies the interrelationship between humans, equipment, and the work environment. HFE includes situation awareness, decision making, communication, team working, leadership, managing stress, and coping with fatigue, empathy, and resilience. The main objective of HF is to optimise the interaction of humans with their work environment and technical equipment in order to maximise patient safety and efficiency of care. This paper reviews the importance of HFE in helping intensivists and all the multidisciplinary ICU teams to deliver high-quality care to patients in crisis situations.

Critically ill patients are often presumed to be in a state of “constant dehydration” or in need of fluid, thereby justifying a continuous infusion with some form of intravenous (IV) fluid, despite their clinical data suggesting otherwise. Overzealous fluid administration and subsequent fluid accumulation and overload are associated with poorer outcomes. Fluids are drugs, and their use should be tailored to meet the patient’s individualized needs; fluids should never be given as routine maintenance unless indicated. Before prescribing any fluids, the physician should consider the patient’s characteristics and the nature of the illness, and assess the risks and benefits of fluid therapy. Decisions regarding fluid therapy present a daily challenge in many hospital departments: emergency rooms, regular wards, operating rooms, and intensive care units. Traditional fluid prescription is full of paradigms and unnecessary routines as well as malpractice in the form of choosing the wrong solutions for maintenance or not meeting daily requirements. Prescribing maintenance fluids for patients on oral intake will lead to fluid creep and fluid overload. Fluid overload, defined as a 10% increase in cumulative fluid balance from baseline weight, is an independent predictor for morbidity and mortality, and thus hospital cost. In the last decade, increasing evidence has emerged supporting a restrictive fluid approach. In this manuscript, we aim to provide a pragmatic description of novel concepts related to the use of IV fluids in critically ill patients, with emphasis on the different indications and common clinical scenarios. We also discuss active deresuscitation, or the timely cessation of fluid administration, with the intention of achieving a zero cumulative fluid balance.

Abstract. Age-related sporadic cerebral small vessel disease (CSVD) has gained increasing attention over the past decades because of its increasing prevalence associated with an aging population. The widespread application of and advances in brain magnetic resonance imaging in recent decades have significantly increased researchers’ understanding in the in vivo evolution of CSVD, its impact upon the brain, its risk factors, and the mechanisms that explain the various clinical manifestation associated with sporadic CSVD. In this review, we aimed to provide an update on the pathophysiology, risk factors, biomarkers, and the determinants and spectrum of the clinical manifestation of sporadic CSVD.

Abstract COVID-19 has caused great devastation in the past year. Multi-organ point-of-care ultrasound (PoCUS) including lung ultrasound (LUS) and focused cardiac ultrasound (FoCUS) as a clinical adjunct has played a significant role in triaging, diagnosis and medical management of COVID-19 patients. The expert panel from 27 countries and 6 continents with considerable experience of direct application of PoCUS on COVID-19 patients presents evidence-based consensus using GRADE methodology for the quality of evidence and an expedited, modified-Delphi process for the strength of expert consensus. The use of ultrasound is suggested in many clinical situations related to respiratory, cardiovascular and thromboembolic aspects of COVID-19, comparing well with other imaging modalities. The limitations due to insufficient data are highlighted as opportunities for future research.

Abstract Critical care ultrasound (CCUS) is an essential component of intensive care practice. Although existing international guidelines have focused on training principles and determining competency in CCUS, few countries have managed to operationalize this guidance into an accessible, well-structured programme for clinicians training in multidisciplinary intensive care. We seek to update and reaffirm appropriate CCUS scope so that it may be integrated into the international Competency-based Training in Intensive Care Medicine. The resulting recommendations offer the most contemporary and evolved set of core CCUS competencies for an intensive care clinician yet described. Importantly, we discuss the rationale for inclusion but also exclusion of competencies listed. Background/aim Critical care ultrasound (CCUS) is an essential component of intensive care practice. The purpose of this consensus document is to determine those CCUS competencies that should be a mandatory part of training in multidisciplinary intensive care. Methods A three-round Delphi method followed by face-to-face meeting among 32 CCUS experts nominated by the European Society of Intensive Care Medicine. Agreement of at least 90% of experts was needed in order to enlist a competency as mandatory. Results The final list of competencies includes 15 echocardiographic, 5 thoracic, 4 abdominal, deep vein thrombosis diagnosis and central venous access aid. Conclusion The resulting recommendations offer the most contemporary and evolved set of core CCUS competencies for an intensive care clinician yet described.

Abstract Background Cognitive impairment is common in multiple sclerosis (MS). However, the relationship between cognitive deficits and microstructural abnormalities in Chinese MS patients remains unclear. We aimed to investigate the importance of microstructural abnormalities and the associations with cognitive impairment in Chinese MS patients. Methods Three‐dimensional T1‐weighted magnetic resonance imaging (MRI) scans were obtained from 36 relapsing remitting MS patients. Diffusion tensor imaging (DTI) scans were acquired for 29 (81%) patients. Cognitive impairment was assessed using a comprehensive neuropsychological battery. Patients were classified into cognitively impaired (CI) group and cognitively preserved (CP) group. Using volBrain and FSL software, we assessed white matter lesion burden, white matter (WM) and gray matter (GM) volumetric as well as microstructural diffusivity. MRI variables explaining cognitive impairment were analyzed. Results Fifteen (42%) patients were classified as CI. Verbal learning and memory was the most commonly impaired domain (n = 16, 44%). CI patients had lower mean skeleton fractional anisotropy (FA) value than CP patients (275.45 vs. 283.61 × 10−3, P = 0.023). The final predicting model including demographic variables and global skeleton mean diffusivity (MD) explained 43.6% of variance of the presence of cognitive impairment (β = 0.131, P = 0.041). CI patients showed a widespread change of microstructural integrity comparing to CP patients, which was rarely overlapping with lesion probability map. Microstructural abnormalities in corpus callosum were associated with performance in verbal learning and memory, processing speed and selective attention (P

Abstract Intravenous fluid administration should be considered as any other pharmacological prescription. There are three main indications: resuscitation, replacement, and maintenance. Moreover, the impact of fluid administration as drug diluent or to preserve catheter patency, i.e., fluid creep, should also be considered. As for antibiotics, intravenous fluid administration should follow the four Ds: drug, dosing, duration, de-escalation. Among crystalloids, balanced solutions limit acid–base alterations and chloride load and should be preferred, as this likely prevents renal dysfunction. Among colloids, albumin, the only available natural colloid, may have beneficial effects. The last decade has seen growing interest in the potential harms related to fluid overloading. In the perioperative setting, appropriate fluid management that maintains adequate organ perfusion while limiting fluid administration should represent the standard of care. Protocols including a restrictive continuous fluid administration alongside bolus administration to achieve hemodynamic targets have been proposed. A similar approach should be considered also for critically ill patients, in whom increased endothelial permeability makes this strategy more relevant. Active de-escalation protocols may be necessary in a later phase. The R.O.S.E. conceptual model (Resuscitation, Optimization, Stabilization, Evacuation) summarizes accurately a dynamic approach to fluid therapy, maximizing benefits and minimizing harms. Even in specific categories of critically ill patients, i.e., with trauma or burns, fluid therapy should be carefully applied, considering the importance of their specific aims; maintaining peripheral oxygen delivery, while avoiding the consequences of fluid overload.

Abstract Background Critical care ultrasonography (CCUS) is increasingly applied also in the intensive care unit (ICU) and performed by non-experts, including even medical students. There is limited data on the training efforts necessary for novices to attain images of sufficient quality. There is no data on medical students performing CCUS for the measurement of cardiac output (CO), a hemodynamic variable of importance for daily critical care. Objective The aim of this study was to explore the agreement of cardiac output measurements as well as the quality of images obtained by medical students in critically ill patients compared to the measurements obtained by experts in these images. Methods In a prospective observational cohort study, all acutely admitted adults with an expected ICU stay over 24 h were included. CCUS was performed by students within 24 h of admission. CCUS included the images required to measure the CO, i.e., the left ventricular outflow tract (LVOT) diameter and the velocity time integral (VTI) in the LVOT. Echocardiography experts were involved in the evaluation of the quality of images obtained and the quality of the CO measurements. Results There was an opportunity for a CCUS attempt in 1155 of the 1212 eligible patients (95%) and in 1075 of the 1212 patients (89%) CCUS examination was performed by medical students. In 871 out of 1075 patients (81%) medical students measured CO. Experts measured CO in 783 patients (73%). In 760 patients (71%) CO was measured by both which allowed for comparison; bias of CO was 0.0 L min−1 with limits of agreement of − 2.6 L min−1 to 2.7 L min−1. The percentage error was 50%, reflecting poor agreement of the CO measurement by students compared with the experts CO measurement. Conclusions Medical students seem capable of obtaining sufficient quality CCUS images for CO measurement in the majority of critically ill patients. Measurements of CO by medical students, however, had poor agreement with expert measurements. Experts remain indispensable for reliable CO measurements. Trial registration Clinicaltrials.gov; http://www.clinicaltrials.gov; registration number NCT02912624

Abstract Background In critically ill patients, auscultation might be challenging as dorsal lung fields are difficult to reach in supine-positioned patients, and the environment is often noisy. In recent years, clinicians have started to consider lung ultrasound as a useful diagnostic tool for a variety of pulmonary pathologies, including pulmonary edema. The aim of this study was to compare lung ultrasound and pulmonary auscultation for detecting pulmonary edema in critically ill patients. Methods This study was a planned sub-study of the Simple Intensive Care Studies-I, a single-center, prospective observational study. All acutely admitted patients who were 18 years and older with an expected ICU stay of at least 24 h were eligible for inclusion. All patients underwent clinical examination combined with lung ultrasound, conducted by researchers not involved in patient care. Clinical examination included auscultation of the bilateral regions for crepitations and rhonchi. Lung ultrasound was conducted according to the Bedside Lung Ultrasound in Emergency protocol. Pulmonary edema was defined as three or more B lines in at least two (bilateral) scan sites. An agreement was described by using the Cohen κ coefficient, sensitivity, specificity, negative predictive value, positive predictive value, and overall accuracy. Subgroup analysis were performed in patients who were not mechanically ventilated. Results The Simple Intensive Care Studies-I cohort included 1075 patients, of whom 926 (86%) were eligible for inclusion in this analysis. Three hundred seven of the 926 patients (33%) fulfilled the criteria for pulmonary edema on lung ultrasound. In 156 (51%) of these patients, auscultation was normal. A total of 302 patients (32%) had audible crepitations or rhonchi upon auscultation. From 130 patients with crepitations, 86 patients (66%) had pulmonary edema on lung ultrasound, and from 209 patients with rhonchi, 96 patients (46%) had pulmonary edema on lung ultrasound. The agreement between auscultation findings and lung ultrasound diagnosis was poor (κ statistic 0.25). Subgroup analysis showed that the diagnostic accuracy of auscultation was better in non-ventilated than in ventilated patients. Conclusion The agreement between lung ultrasound and auscultation is poor. Trial registration NCT02912624. Registered on September 23, 2016.

Abstract Introduction The Meta VCI Map consortium performs meta‐analyses on strategic lesion locations for vascular cognitive impairment using lesion‐symptom mapping. Integration of data from different cohorts will increase sample sizes, to improve brain lesion coverage and support comprehensive lesion‐symptom mapping studies. Methods Cohorts with available imaging on white matter hyperintensities or infarcts and cognitive testing were invited. We performed a pilot study to test the feasibility of multicenter data processing and analysis and determine the benefits to lesion coverage. Results Forty‐seven groups have joined Meta VCI Map (stroke n = 7800 patients; memory clinic n = 4900; population‐based n = 14,400). The pilot study (six ischemic stroke cohorts, n = 878) demonstrated feasibility of multicenter data integration (computed tomography/magnetic resonance imaging) and achieved marked improvement of lesion coverage. Discussion Meta VCI Map will provide new insights into the relevance of vascular lesion location for cognitive dysfunction. After the successful pilot study, further projects are being prepared. Other investigators are welcome to join.

Abstract Introduction Only two studies investigated the associations between peak width of skeletonized mean diffusivity (PSMD) and age‐related cognitive alterations, whereas none of the studies investigated the association with vascular risk factors. Methods We evaluated 801 stroke‐ and dementia‐free elderlies with baseline and 3‐year follow‐up assessments. Regression analyses were used to assess the association between age‐related cognitive functions and PSMD. Simple mediation models were used to study the mediation effect of PSMD between vascular risk factors and age‐related cognitive outcomes. Results PSMD was negatively associated with processing speed at baseline and negatively associated with processing and memory scores at 3‐year follow‐up. The association between vascular risk factors and age‐related cognition was mediated by PSMD, as well as other diffusion tensor imaging markers. Discussion PSMD is preferred over other diffusion tensor imaging markers as it is sensitive to age‐related cognitive alterations and calculation is fully automated. PSMD is proposed as a research tool to monitor age‐related cognitive alterations.

PICO question In dogs with osteoarthritis how effective is treatment with tramadol in reducing the severity of the clinical signs associated with pain when compared to no treatment? Clinical bottom line Category of research question Treatment The number and type of study designs reviewed Two papers were critically reviewed. There was one randomised crossover controlled trial and one non-randomised controlled trial Strength of evidence Strong Outcomes reported Budsberg et al. (2018) found no significant differences in the objective gait analyses (vertical ground reaction forces, and peak vertical force) between baseline and end of treatment, between tramadol and placebo. Similarly, there was no significant difference in the proportion of dogs with positive response based on the subjective Canine Brief Pain Inventory questionnaire (CBPI) between tramadol and placebo. The positive control of carprofen yielded significant differences to both placebo and tramadol in all outcomes measured. Malek et al. (2012) found no significant differences in the objective outcomes measured (gait analyses, and total daily activity) between tramadol and placebo. There were significant improvements in the subjective CBPI (total score, pain severity and pain interference score) between the baseline and end of treatment, within the tramadol group. However, there was no significant difference in the percentage change of the total score, pain severity or pain interference score between all treatment groups including tramadol and placebo Conclusion In dogs with osteoarthritis, the use of tramadol alone did not demonstrate any significant analgesic effects How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Background: General pathophysiological mechanisms regarding associations between fluid administration and intra-abdominal hypertension (IAH) are evident, but specific effects of type, amount, and timing of fluids are less clear. Objectives: This review aims to summarize current knowledge on associations between fluid administration and intra-abdominal pressure (IAP) and fluid management in patients at risk of intra-abdominal hypertension and abdominal compartment syndrome (ACS). Methods: We performed a structured literature search from 1950 until May 2021 to identify evidence of associations between fluid management and intra-abdominal pressure not limited to any specific study or patient population. Findings were summarized based on the following information: general concepts of fluid management, physiology of fluid movement in patients with intra-abdominal hypertension, and data on associations between fluid administration and IAH. Results: We identified three randomized controlled trials (RCTs), 38 prospective observational studies, 29 retrospective studies, 18 case reports in adults, two observational studies and 10 case reports in children, and three animal studies that addressed associations between fluid administration and IAH. Associations between fluid resuscitation and IAH were confirmed in most studies. Fluid resuscitation contributes to the development of IAH. However, patients with IAH receive more fluids to manage the effect of IAH on other organ systems, thereby causing a vicious cycle. Timing and approach to de-resuscitation are of utmost importance, but clear indicators to guide this decision-making process are lacking. In selected cases, only surgical decompression of the abdomen can stop deterioration and prevent further morbidity and mortality. Conclusions: Current evidence confirms an association between fluid resuscitation and secondary IAH, but optimal fluid management strategies for patients with IAH remain controversial.

Abstract Introduction The benefit and risk of aerobic exercise among older people harboring advanced cerebral small vessel disease (CSVD) upon cognition, mood, and motor functions are unknown. Methods This rater‐blind randomized trial examined effects of a 24‐week aerobic exercise training (60 min/session, twice/week) upon clinical (cognition, mood, motor functions) and hemodynamic (pulse pressure [PP], blood pressure [BP], pulsatility index) measures in older people harboring moderate to severe CSVD, as evidenced by confluent white matter hyperintensity and/or ≥2 lacunes on magnetic resonance imaging. We further investigated interactions between treatment conditions and hemodynamics measures. Results Fifty‐three and 54 subjects were randomized into the active and control group, respectively. There was no between‐group difference in any of the clinical outcomes. The active group had a greater between‐group reduction in systolic BP and PP than the control group. Within‐group comparison showed that global cognition of the active group remained similar at end of the study compared to baseline, whereas it declined significantly in the control group. We observed “diverging” interaction effects in that greater reduction in systolic BP/PP was associated with greater improvement in memory functions and global cognition but worsening in processing speed in the active group. Side effects were comparable between the two groups. Discussion Future study should investigate the mechanisms of the diverging impacts of aerobic exercise upon different cognitive domains so that the benefit–risk ratio of aerobic exercise in older people harboring more advanced CSVD can be better defined.

Background. Coronavirus disease 2019 (COVID-19) had a significant impact on the National Health Service in the United Kingdom (UK), with over 35 000 cases reported in London by July 30, 2020. Detailed hospital-level information on patient characteristics, outcomes, and capacity strain is currently scarce but would guide clinical decision-making and inform prioritisation and planning. Methods. We aimed to determine factors associated with hospital mortality and describe hospital and ICU strain by conducting a prospective cohort study at a tertiary academic centre in London, UK. We included adult patients admitted to the hospital with laboratory-confirmed COVID-19 and followed them up until hospital discharge or 30 days. Baseline factors that are associated with hospital mortality were identified via semiparametric and parametric survival analyses. Results. Our study included 429 patients: 18% of them were admitted to the ICU, 52% met criteria for ICU outreach team activation, and 61% had treatment limitations placed during their admission. Hospital mortality was 26% and ICU mortality was 34%. Hospital mortality was independently associated with increasing age, male sex, history of chronic kidney disease, increasing baseline C-reactive protein level, and dyspnoea at presentation. COVID-19 resulted in substantial ICU and hospital strain, with up to 9 daily ICU admissions and 41 daily hospital admissions, to a peak census of 80 infected patients admitted in the ICU and 250 in the hospital. Management of such a surge required extensive reorganisation of critical care services with expansion of ICU capacity from 69 to 129 beds, redeployment of staff from other hospital areas, and coordinated hospital-level effort. Conclusions. COVID-19 is associated with a high burden of mortality for patients treated on the ward and the ICU and required substantial reconfiguration of critical care services. This has significant implications for planning and resource utilisation.

Background Weight management interventions involving behaviour change often utilise face to face interventions which include evidence based behaviour change strategies yet are costly and time intensive. In contrast, digital interventions cost less and have a wider reach yet tend to lack an evidence base and are less effective. Aims The present study therefore aimed to develop an evidence based behaviour change low cost app for weight management and to provide a preliminary analysis of its effectiveness. Methods The Ladle app was developed through evidence review and feedback from health care professionals and patients and consists of a 12 week course focusing on six habits and weight loss facilitated through 36 audio psychological lessons and 12 lessons specifically on the six habits. Each lesson was between 2–5 min (approx. 168 min of lessons). It was evaluated in terms of completion rate, weight loss, adoption of the six habits and participant feedback. Results The results showed a completion rate of 44%, that 52% of Completers showed weight loss of at least 5%, 79% showed weight loss of at least 3%, the median % weight lost was −5% and the median weight loss was −3.8 kg. Further, by the end of 12 weeks the majority (>80%) of participants had adopted four of the six habits for at least 5 days a week and nearly half (45%) had adopted the remaining two habits for at least 4 days out of 7. Feedback comments were mainly positive (n = 80) focusing mostly on the content of the lessons. Some comments were neutral (n = 56) and involved a statement of commitment or a description of a challenge and a minority were negative (n = 23) describing some technical issues which were addressed as the evaluation progressed. Conclusion The new Ladle app offers an evidenced based alternative to more intensive face to face interventions. On preliminary analysis it would seem to have lower completion rates than some more intensive interventions but comparable effectiveness for weight loss. It can also improve habits and is less time-intensive and costly to deliver. Participant feedback was generally positive.

White matter hyperintensities (WMH) are common in acute ischemic stroke patients. Although WMH volume has been reported to influence post-stroke cognition, it is still not clear whether WMH location, independent of acute ischemic lesion (AIL) volume and location, contributes to cognitive impairment after stroke. Here, we proposed a multiple-lesion symptom mapping model that considers both the presence of WMH and AIL to measure the additional contribution of WMH locations to post-stroke cognitive impairment. Seventy-six first-ever stroke patients with AILs in the left hemisphere were examined by Montreal Cognitive Assessment (MoCA) at baseline and 1 year after stroke. The association between the location of AIL and WMH and global cognition was investigated by a multiple-lesion symptom mapping (MLSM) model based on support vector regression (SVR). To explore the relative merits of MLSM over the existing lesion-symptom mapping approaches with only AIL considered (mass-univariate VLSM and SVR-LSM), we measured the contribution of the significant AIL and/or WMH clusters from these models to post-stroke cognitive impairment. In addition, we compared the significant WMH locations identified by the optimal SVR-MLSM model for cognitive impairment at baseline and 1 year post stroke. The identified strategic locations of WMH significantly contributed to the prediction of MoCA at baseline (short-term) and 1 year (long-term) after stroke independent of the strategic locations of AIL. The significant clusters of WMH for short-term and long-term post-stroke cognitive impairment were mainly in the corpus callosum, corona radiata, and posterior thalamic radiation. We noted that in some regions, the AIL clusters that were significant for short-term outcome were no longer significant for long-term outcome, and interestingly more WMH clusters in these regions became significant for long-term outcome compared to short-term outcome. This indicated that there are some regions where local WMH burden has larger impact than AIL burden on the long-term post-stroke cognitive impairment. In consequence, SVR-MLSM was effective in identifying the WMH locations that have additional impact on post-stroke cognition on top of AIL locations. Such a method can also be applied to other lesion-behavior studies where multiple types of lesions may have potential contributions to a specific behavior.

Repeated testing using the Montreal Cognitive Assessment (MoCA) increases risks for practice effects which may bias measurements of cognitive change. The objective of this study is to develop two alternate versions of the MoCA (Hong Kong version; HK-MoCA) and to investigate the validity and reliability of the alternate versions in patients with DSM-5 Mild Neurocognitive Disorder (Mild NCD) and cognitively healthy controls.Concurrent validity and inter-scale agreement were examined by Pearson correlation of the total scores between the original and alternate versions and the Bland-Altman Method. Criterion validity of the two alternate versions in differentiating patients with Mild NCD was tested using receiver operating characteristic curve (ROC) analysis. One-month test-retest and inter-rater reliability were examined in 20 participants. Internal consistency of the alternate versions was measured by the Cronbach's α.30 controls (age 73.4 [4.5] years, 60% female) and 30 patients (age 75.4 [5.5] years, 73% female) with Mild NCD were recruited. Both alternate versions significantly correlated with the original version (r = 0.79-0.87, p

White matter hyperintensities (WMHs) have been reported to be correlated with functional brain changes, but the association of the specific WMHs distribution pattern with regional functional changes remains uncertain. The aim of this study is to explore the possible spatial correlation of WMH with changes in cerebral blood flow (CBF) and spontaneous brain activities in elderly using a novel approach. The WMHs, CBF, and spontaneous brain activities measured by intrinsic connectivity contrast (ICC), were quantified using multimodal magnetic resonance imaging for 69 elderly subjects. Such approach enables us to expand our search for newly identified correlated areas by drawing strengths of different modes and provides a means for triangulation as well as complementary insights. The results showed significant positive correlations between WMH volumes in the right superior corona radiata and CBF in the left supplementary motor area, as well as between WMH volumes in left anterior limb internal capsule and CBF in the right putamen. Significant correlations of regional WMH volumes and ICC were also detected between the right anterior corona radiata and the left cuneus, and the right superior occipital cortex, as well as between the right superior corona radiata and the left superior occipital cortex. These findings may suggest a regional compensatory functional enhancement accounting for the maintenance of cognitively normal status, which can be supported by the widely observed phenomenon that mild to moderate WMH load could have little effect on global cognitive performance.

Nonmotor symptoms (NMS) of Parkinson’s disease (PD) have devastating impacts on both patients and their caregivers. Jiawei-Liujunzi Tang (JLT) has been used to treat some NMS of PD based on the Chinese medicine theory since Qing dynasty. Here we report a double-blind, randomized, placebo-controlled, add-on clinical trial aiming at evaluating the efficacy and safety of the JLT in treating NMS in PD patients. We randomly assigned 111 patients with idiopathic PD to receive either JLT or placebo for 32 weeks. Outcome measures were baseline to week 32 changes in Movement Disorder Society-Sponsored Revision of Unified PD Rating Scale (MDS-UPDRS) Parts I–IV and in NMS assessment scale for PD (NMSS). We observed improvements in the NMSS total score (p=0.019), mood/cognition (p=0.005), and reduction in hallucinations (p=0.024). In addition, post hoc analysis showed a significant reduction in constipation (p

Leisure activity participation has been shown to lower risks of cognitive decline in non-stroke populations. However, effects of leisure activities participation upon cognitive functions and risk of dementia after stroke are unclear. The purpose of this study is to examine the effects of recent past leisure activities participation upon cognitive functions and risk of incident dementia after stroke.Hospital-based, retrospective cohort study. 88 of 1,013 patients with stroke or TIA having no prestroke dementia were diagnosed to have incident poststroke dementia (PSD) 3-6 months after stroke. Regular participation (≥3 times per week) in intellectual, recreational, social and physical activities over the year before the index stroke was retrospectively recorded at 3-6 months after stroke.Logistic regression analyses showed that regular participation in intellectual (RR 0.36, 95%CI 0.20-0.63) and stretching & toning physical exercise (0.37, 0.21-0.64) was significantly associated with a reduced risk of PSD after controlling for age, education, prestroke cognitive decline, stroke subtype, prior strokes and chronic brain changes including white matter changes, old infarcts and global atrophy. Results were similar in patients with past strokes in unadjusted models. Participation in increased number of activities in general (r = 0.41, p

BACKGROUND:The objectives of this study are 1) to examine the frequencies of neuropsychiatric symptom clusters in patients with stroke or transient ischemic attack (TIA) by cognitive level and stroke subtype; and 2) to evaluate effect of demographic, clinical, and neuroimaging measures of chronic brain changes and amyloid upon neuropsychiatric symptom clusters. METHODS:Hospital-based, cross-sectional study. 518 patients were administered the Neuropsychiatric Inventory (NPI) 3-6 months post index admission. NPI symptoms were classified into four symptom clusters (Behavioral Problems, Psychosis, Mood Disturbance & Euphoria) derived from a confirmatory factor analysis of the 12 NPI items. Multivariable logistic regression was used to determine independent associations between demographic, clinical and neuroimaging measures of chronic brain changes (white matter changes, old infarcts, whole brain atrophy, medial temporal lobe atrophy [MTLA] and frontal lobe atrophy [FLA]) with the presence of NPI symptoms and all symptom clusters except euphoria. 11C-Pittsburg Compound B Positron Emission Tomography (11C-PiB PET) was performed in 24 patients to measure amyloid retention for Alzheimer's Disease (AD) pathology. RESULTS:50.6% of the whole sample, including 28.7% cognitively normal and 66.7% of patients with mild cognitive symptoms, had ≥1 NPI symptoms. Frequencies of symptom clusters were largely similar between stroke subtypes. Compared to patients with cardioembolic stroke and intracranial haemorrhage, those with TIA had less frequent mood disturbance. Stroke severity at admission and MTLA were the most robust correlates of symptoms. FLA was associated with behavioral problems cluster only. Frequency of symptom clusters did not differ between patients with and without significant amyloid retention. CONCLUSION:Frequency of neuropsychiatric symptoms increased with level of cognitive impairment but was largely similar between stroke subtypes. Stroke severity and MTLA were associated with neuropsychiatric symptoms. AD pathology appeared to be unrelated to neuropsychiatric manifestations but further studies with larger sample size are required to substantiate this finding.

Vincent Mok1, Adrian Wong1, Simon Ho2, Thomas Leung1, Wynnie WM Lam2, Ka Sing Wong11Department of Medicine and Therapeutics; 2Department of Radiology and Organ Imaging, The Chinese University of Hong Kong, Shatin, Hong Kong, ChinaBackground: We explored the efficacy and tolerability of rivastigmine among Chinese patients with subcortical vascular dementia.Methods: Forty subjects were randomized to either placebo (n = 20) or rivastigmine (n = 20) in a double-blind 26-week trial. Outcome measures were cognition (mini-mental state examination, frontal assessment battery), neuropsychiatric inventory (NPI), instrumental activities of daily living, clinical dementia rating scale, and adverse events.Results: No statistical significant benefit could be observed in the active group in any of the efficacy measures. A trend favoring active group was observed only in the NPI subscore of irritability (p = 0.066) and aberrant motor behavior (p = 0.068). Withdrawal rate was 30% and 15% in the active and placebo group, respectively.Conclusion: Among Chinese subcortical vascular dementia patients, there was no apparent cognitive benefit associated with use of rivastigmine over the 6 months period. A trend favoring rivastigmine was observed in certain behavioral measures. Rivastigmine was associated with more withdrawals relative to placebo.Keywords: rivastigmine, subcortical vascular dementia, Chinese

Diabetic patients with acute coronary syndrome (ACS) are at higher risk of poor outcome than are non-diabetic patients with ACS. Few studies have focused on sex-related ACS incidence, ACS-related mortality or risk factors to affects sex specific ACS in Chinese with Type 2 diabetes mellitus (T2DM). Based on a hospital-based cohort of Chinese patients with T2DM, we aimed to investigate whether there was sex difference in ACS or ACS-related mortality or risk factors of ACS.Totally 2,135 Hong Kong Chinese with T2DM were recruited during 1994-1996 and followed up until August 2012. We systematically analyzed sex-related ACS incidence and ACS-related mortality and risk factors with χ2-squared test, descriptive statistics and survival analysis.Regular follow-up was completed in 2,105 subjects (98.6%), with a median period of 14.53 years. The occurrence of ACS was recorded among 414 patients (19.7%) and ACS-related death among 104 patients (4.9%). ACS incidences increased with age in both men and women, and men had a higher prevalence of ACS than women across different age categories and different follow-up periods (log rank χ2=20.32, P

ObjectiveTo investigate whether asymptomatic middle cerebral artery (MCA) stenosis is associated with risk of cardiovascular disease (CVD) in Chinese with type 2 diabetes.MethodsIn this prospective cohort study, 2,144 Hong Kong Chinese with type 2 diabetes and without history of stroke or atrial fibrillation were recruited in 1994-1996 and followed up for a median of 14.51 years. Participants were assessed at baseline for MCA stenosis using transcranial Doppler. We performed survival analysis to assess the association between asymptomatic MCA stenosis and first CVD event, defined as ischemic stroke, acute coronary syndrome (ACS) or cardiovascular death.ResultsOf the 2,144 subjects, MCA stenosis at baseline was detected in 264 (12.3%). Rates of stroke, ACS and cardiovascular death per 100 were, respectively, 2.24, 2.92 and 1.11 among participants with stenosis, higher than among those without stenosis. Ten-year cumulative occurrence of stroke, ACS and cardiovascular death in subjects with MCA stenosis was 20%, 24% and 10%, respectively, higher than the corresponding values for subjects without stenosis(all PConclusionsAsymptomatic MCA stenosis is a risk factor for CVD in Chinese with type 2 diabetes, and detection of asymptomatic MCA stenosis by transcranial Doppler can identify diabetic individuals at high risk of future CVD. This finding is particularly important for diabetic individuals in Asia, where intracranial atherosclerosis is common.

Cognitive deficits are common after aneurysmal subarachnoid haemorrhage (aSAH), and clinical evaluation is important for their management. Our hypothesis was that the Montreal Cognitive Assessment (MoCa) is superior to the Mini-Mental State Examination (MMSE) in screening for cognitive domain deficit in aSAH patients.We carried out a prospective observational and diagnostic accuracy study on Hong Kong aSAH patients aged 21 to 75 years who had been admitted within 96 hours of ictus. The domain-specific neuropsychological assessment battery, the MoCA and MMSE were administered 2-4 weeks and 1 year after ictus. A cognitive domain deficit was defined as a cognitive domain z score