A study protocol to develop and test an e-health intervention in follow-up service for intensive care survivors' relatives.

BACKGROUND: The negative impact on long-term health-related outcomes among relatives of critically ill patients in the intensive care unit (ICU) has been well described. High-quality ICU specialized follow-up care, which is easily accessible with digital innovation and which is designed by and with relevant stakeholders (i.e., ICU patients' relatives and nurses), should be considered to reduce these impairments in the psychological and social domains. AIM: The programme's aim is to develop and test an e-health intervention in a follow-up service to support ICU patients' relatives. Here, the protocol for the overall study programme will be described. STUDY DESIGN: The overall study comprises a mixed-methods, multicentre research design with qualitative and quantitative study parts. The study population is ICU patients' adult relatives and ICU nurses. The main outcomes are the experiences of these stakeholders with the newly developed e-health intervention. There will be no predefined selection based on age, gender, and level of education to maximize diversity throughout the study programme. After the participants provide informed consent, data will be gathered through focus groups (n = 5) among relatives and individual interviews (n = 20) among nurses exploring the needs and priorities of a digital follow-up service. The findings will be explored further for priority considerations among members of the patient/relative organization (aiming n = 150), which will serve as a basis for digital prototypes of the e-health intervention. Assessment of the intervention will be followed during an iterative process with investigator-developed questionnaires. Finally, symptoms of anxiety and depression will be measured with the 14-item Dutch version of the 'Hospital Anxiety and Depression Scale', and symptoms of posttraumatic stress will be measured with the 21-item Dutch version of the 'Impact of Events Scale-Revised' to indicate the effectiveness of digital support among ICU patients' relatives. RELEVANCE TO CLINICAL PRACTICE: The e-health intervention to be developed during this research programme can possibly bridge the gap in integrated ICU follow-up care by providing relevant information, self-monitoring and stimulating self-care among ICU patients' relatives.

Intensive Care Unit-Specific Virtual Reality for Critically Ill Patients With COVID-19: Multicenter Randomized Controlled Trial.

BACKGROUND: Although psychological sequelae after intensive care unit (ICU) treatment are considered quite intrusive, robustly effective interventions to treat or prevent these long-term sequelae are lacking. Recently, it was demonstrated that ICU-specific virtual reality (ICU-VR) is a feasible and acceptable intervention with potential mental health benefits. However, its effect on mental health and ICU aftercare in COVID-19 ICU survivors is unknown. OBJECTIVE: This study aimed to explore the effects of ICU-VR on mental health and on patients' perceived quality of, satisfaction with, and rating of ICU aftercare among COVID-19 ICU survivors. METHODS: This was a multicenter randomized controlled trial. Patients were randomized to either the ICU-VR (intervention) or the control group. All patients were invited to an COVID-19 post-ICU follow-up clinic 3 months after hospital discharge, during which patients in the intervention group received ICU-VR. One month and 3 months later (4 and 6 months after hospital discharge), mental health, quality of life, perceived quality, satisfaction with, and rating of ICU aftercare were scored using questionnaires. RESULTS: Eighty-nine patients (median age 58 years; 63 males, 70%) were included. The prevalence and severity of psychological distress were limited throughout follow-up, and no differences in psychological distress or quality of life were observed between the groups. ICU-VR improved satisfaction with (mean score 8.7, SD 1.6 vs 7.6, SD 1.6 [ICU-VR vs control]; t64=-2.82, P=.006) and overall rating of ICU aftercare (mean overall rating of aftercare 8.9, SD 0.9 vs 7.8, SD 1.7 [ICU-VR vs control]; t64=-3.25; P=.002) compared to controls. ICU-VR added to the quality of ICU aftercare according to 81% of the patients, and all patients would recommend ICU-VR to other ICU survivors. CONCLUSIONS: ICU-VR is a feasible and acceptable innovative method to improve satisfaction with and rating of ICU aftercare and adds to its perceived quality. We observed a low prevalence of psychological distress after ICU treatment for COVID-19, and ICU-VR did not improve psychological recovery or quality of life. Future research is needed to confirm our results in other critical illness survivors to potentially facilitate ICU-VR's widespread availability and application during follow-up. TRIAL REGISTRATION: Netherlands Trial Register NL8835; https://www.trialregister.nl/trial/8835. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-021-05271-z.

CO-FLOW: COvid-19 Follow-up care paths and Long-term Outcomes Within the Dutch health care system: study protocol of a multicenter prospective cohort study following patients 2 years after hospital discharge.

BACKGROUND: First studies indicate that up to 6 months after hospital discharge, coronavirus disease 2019 (COVID-19) causes severe physical, cognitive, and psychological impairments, which may affect participation and health-related quality of life (HRQoL). After hospitalization for COVID-19, a number of patients are referred to medical rehabilitation centers or skilled nursing facilities for further treatment, while others go home with or without aftercare. The aftercare paths include 1] community-based rehabilitation; 2] in- and outpatient medical rehabilitation; 3] inpatient rehabilitation in skilled nursing facilities; and 4] sheltered care (inpatient). These aftercare paths and the trajectories of recovery after COVID-19 urgently need long-term in-depth evaluation to optimize and personalize treatment. CO-FLOW aims, by following the outcomes and aftercare paths of all COVID-19 patients after hospital discharge, to systematically study over a 2-year period: 1] trajectories of physical, cognitive, and psychological recovery; 2] patient flows, healthcare utilization, patient satisfaction with aftercare, and barriers/facilitators regarding aftercare as experienced by healthcare professionals; 3] effects of physical, cognitive, and psychological outcomes on participation and HRQoL; and 4] predictors for long-term recovery, health care utilization, and patient satisfaction with aftercare. METHODS: CO-FLOW is a multicenter prospective cohort study in the mid-west of the Netherlands with a 2-year follow-up period. Measurements comprise non-invasive clinical tests and patient reported outcome measures from a combined rehabilitation, pulmonary, and intensive care perspective. Measurements are performed at 3, 6, 12, and 24 months after hospital discharge and, if applicable, at rehabilitation discharge. CO-FLOW aims to include at least 500 patients who survived hospitalization for COVID-19, aged ≥18 years. DISCUSSION: CO-FLOW will provide in-depth knowledge on the long-term sequelae of COVID-19 and the quality of current aftercare paths for patients who survived hospitalization. This knowledge is a prerequisite to facilitate the right care in the right place for COVID-19 and comparable future infectious diseases. TRIAL REGISTRATION: The Netherlands Trial Register (NTR), https://www.trialregister.nl . Registered: 12-06-2020, CO-FLOW trialregister no. NL8710.

The effect of the TIM program (Transfer ICU Medication reconciliation) on medication transfer errors in two Dutch intensive care units: design of a prospective 8-month observational study with a before and after period.

BACKGROUND: The transfer of patients to and from the Intensive Care Unit (ICU) is prone to medication errors. The aim of the present study is to determine whether the number of medication errors at ICU admission and discharge and the associated potential harm and costs are reduced by using the Transfer ICU and Medication reconciliation (TIM) program. METHODS: This prospective 8-month observational study with a pre- and post-design will assess the effects of the TIM program compared with usual care in two Dutch hospitals. Patients will be included if they are using at least one drug before hospital admission and will stay in the ICU for at least 24 h. They are excluded if they are transferred to another hospital, admitted and discharged in the same weekend or unable to communicate in Dutch or English. In the TIM program, a clinical pharmacist reconciles patient's medication history within 24 h after ICU admission, resulting in a "best possible" medication history and presents it to the ICU doctor. At ICU discharge the clinical pharmacist reconciles the prescribed ICU medication and the medication history with the ICU doctor, resulting in an ICU discharge medication list with medication prescription recommendations for the general ward doctor. Primary outcome measures are the proportions of patients with one or more medication transfer errors 24 h after ICU admission and 24 h after ICU discharge. Secondary outcome measures are the proportion of patients with potential adverse drug events, the severity of potential adverse drug events and the associated costs. For the primary outcome relative risks and 95% confidence intervals will be calculated. DISCUSSION: Strengths of this study are the tailor-made design of the TIM program and two participating hospitals. This study also has some limitations: A potential selection bias since this program is not performed during the weekends, collecting of potential rather than actual adverse drug events and finally a relatively short study period. Nevertheless, the findings of this study will provide valuable information on a crucial safety intervention in the ICU. TRIAL REGISTRATION: Dutch trial register: NTR4159 , 5 September 2013.

Targeting Oliguria Reversal in Goal-Directed Hemodynamic Management Does Not Reduce Renal Dysfunction in Perioperative and Critically Ill Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: We investigated whether resuscitation protocols to achieve and maintain urine output above a predefined threshold-including oliguria reversal as a target--prevent acute renal failure (ARF). METHODS: We performed a systematic review and meta-analysis using studies found by searching MEDLINE, EMBASE, and references in relevant reviews and articles. We included all studies that compared "conventional fluid management" (CFM) with "goal-directed therapy" (GDT) using cardiac output, urine output, or oxygen delivery parameters and reported the occurrence of ARF in critically ill or surgical patients. We divided studies into groups with and without oliguria reversal as a target for hemodynamic optimization. We calculated the combined odds ratio (OR) and 95% confidence intervals (CIs) using random-effects meta-analysis. RESULTS: We based our analyses on 28 studies. In the overall analysis, GDT resulted in less ARF than CFM (OR, 0.58; 95% CI, 0.44-0.76; P < 0.001; I = 34.3%; n = 28). GDT without oliguria reversal as a target resulted in less ARF (OR, 0.45; 95% CI, 0.34-0.61; P < 0.001; I = 7.1%; n = 7) when compared with CFM with oliguria reversal as a target. The studies comparing GDT with CFM in which the reversal of oliguria was targeted in both or in neither group did not provide enough evidence to conclude a superiority of GDT (targeting oliguria reversal in both protocols: OR, 0.63; 95% CI, 0.36-1.10; P = 0.09; I = 48.6%; n = 9, and in neither protocol: OR, 0.66; 95% CI, 0.37-1.16; P = 0.14; I = 20.2%; n = 12). CONCLUSIONS: Current literature favors targeting circulatory optimization by GDT without targeting oliguria reversal to prevent ARF. Future studies are needed to investigate the hypothesis that targeting oliguria reversal does not prevent ARF in critically ill and surgical patients.

Targeting oliguria reversal in perioperative restrictive fluid management does not influence the occurrence of renal dysfunction: A systematic review and meta-analysis.

BACKGROUND: Interest in perioperative fluid restriction has increased, but it could lead to hypovolaemia. Urine output is viewed as a surrogate for renal perfusion and is frequently used to guide perioperative fluid therapy. However, the rationale behind targeting oliguria reversal - achieving and maintaining urine output above a previously defined threshold by additional fluid boluses - is often questioned. OBJECTIVE: We assessed whether restrictive fluid management had an effect on oliguria, acute renal failure (ARF) and fluid intake. We also investigated whether targeting oliguria reversal affected these parameters. DESIGN: Systematic review of randomised controlled trials with meta-analyses. We used the definitions of restrictive and conventional fluid management as provided by the individual studies. DATA SOURCES: We searched MEDLINE (1966 to present), EMBASE (1980 to present), and relevant reviews and articles. ELIGIBILITY CRITERIA: We included randomised controlled trials with adult patients undergoing surgery comparing restrictive fluid management with a conventional fluid management protocol and also reporting the occurrence of postoperative ARF. RESULTS: We included 15 studies with a total of 1594 patients. There was insufficient evidence to associate restrictive fluid management with an increase in oliguria [restrictive 83/186 vs. conventional 68/230; odds ratio (OR) 2.07; 95% confidence interval (CI), 0.97 to 4.44; P = 0.06; I = 23.7%; Nstudies = 5]. The frequency of ARF in restrictive and conventional fluid management was 20/795 and 20/799, respectively (OR 1.07; 95% CI, 0.60 to 1.92; P = 0.8; I = 17.5%; Nstudies = 15). There was no statistically significant difference in ARF occurrence between studies targeting oliguria reversal and not targeting oliguria reversal (OR 0.31; 95% CI, 0.08 to 1.22; P = 0.088). Intraoperative fluid intake was 1.89 l lower in restrictive than in conventional fluid management when not targeting oliguria reversal (95% CI, -2.59 to -1.20 l; P < 0.001; I = 96.6%; Nstudies = 7), and 1.63 l lower when targeting oliguria reversal (95% CI, -2.52 to -0.74 l; P < 0.001; I = 96.6%; Nstudies = 6). CONCLUSION: Our data suggest that, even though event numbers are small, perioperative restrictive fluid management does not increase oliguria or postoperative ARF while decreasing intraoperative fluid intake, irrespective of targeting reversal of oliguria or not.

Postural change in volunteers: sympathetic tone determines microvascular response to cardiac preload and output increases.

PURPOSE: Microvascular perfusion may be a non-invasive indicator of fluid responsiveness. We aimed to investigate which of the microvascular perfusion parameters truly reflects fluid responsiveness independent of sympathetic reflexes. METHODS: Fifteen healthy volunteers underwent a postural change from head up tilt (HUT) to the supine position, diminishing sympathetic tone, followed by a 30° passive leg raising (PLR) with unaltered tone. Prior to and after the postural changes, stroke volume (SV) and cardiac output (CO) were measured, as well as sublingual microcirculatory perfusion (sidestream dark field imaging), skin perfusion, and oxygenation (laser Doppler flowmetry and reflectance spectroscopy). RESULTS: In responders (subjects with >10 % increase in CO), the HUT to supine change increased CO, SV, and pulse pressure, while heart rate, systemic vascular resistance, and mean arterial pressure decreased. Additionally, microvascular flow index, laser Doppler flow, and microvascular hemoglobin oxygen saturation and concentration also increased. CONCLUSION: When preload and forward flow increase in association with a decrease in sympathetic activity, microvascular blood flow increases in the skin and in the sublingual area. When preload and forward flow increase with little to no change in sympathetic activity, only sublingual functional capillary density increases. Therefore, our results indicate that sublingual functional capillary density is the best parameter to use when evaluating fluid responsiveness independent of changes in sympathetic tone.

Peripheral Perfusion Index Predicts Hypotension during Fluid Withdrawal by Continuous Veno-Venous Hemofiltration in Critically Ill Patients.

AIM: Peripheral perfusion may predict harmful hypovolemic hypotension during fluid withdrawal by continuous veno-venous hemofiltration (CVVH) in critically ill patients with acute kidney injury. METHODS: Twenty-three critically ill AKI patients were subjected to progressive fluid withdrawal. Systemic hemodynamics and peripheral perfusion index (PPI) by pulse oximetry, forearm-to-fingertip skin temperature gradient (Tskin-diff) and tissue oxygen saturation (StO2, near infra-red spectroscopy) were measured. RESULTS: Most hemodynamic values decreased with fluid withdrawal, particularly in the hypotensive group, except for stroke volume (SV) and cardiac output, which decreased to a great extent in the non-hypotensive patients. Increases in systemic vascular resistance (SVR) were less in hypotension. Baseline pulse pressure and PPI were lower in hypotensive (n = 10) than non-hypotensive patients and subsequent PPI values paralleled SV decreases. A baseline PPI ≤0.82 AU predicted hypotension with a sensitivity of 70%, and a specificity of 92% (AUC 0.80 ± 0.11, p = 0.004). CONCLUSION: Progressive fluid withdrawal during CVVH is poorly tolerated in patients with less increases in SVR. The occurrence of hypotension can be predicted by low baseline PPI.

Tissue perfusion and oxygenation to monitor fluid responsiveness in critically ill, septic patients after initial resuscitation: a prospective observational study.

Fluid therapy after initial resuscitation in critically ill, septic patients may lead to harmful overloading and should therefore be guided by indicators of an increase in stroke volume (SV), i.e. fluid responsiveness. Our objective was to investigate whether tissue perfusion and oxygenation are able to monitor fluid responsiveness, even after initial resuscitation. Thirty-five critically ill, septic patients underwent infusion of 250 mL of colloids, after initial fluid resuscitation. Prior to and after fluid infusion, SV, cardiac output sublingual microcirculatory perfusion (SDF: sidestream dark field imaging) and skin perfusion and oxygenation (laser Doppler flowmetry and reflectance spectroscopy) were measured. Fluid responsiveness was defined by a ≥5 or 10% increase in SV upon fluids. In responders to fluids, SDF-derived microcirculatory and skin perfusion and oxygenation increased, but only the increase in cardiac output, mean arterial and pulse pressure, microvascular flow index and relative Hb concentration and oxygen saturation were able to monitor a SV increase. Our proof of principle study demonstrates that non-invasively assessed tissue perfusion and oxygenation is not inferior to invasive hemodynamic measurements in monitoring fluid responsiveness. However skin reflectance spectroscopy may be more helpful than sublingual SDF.

Microvascular perfusion as a target for fluid resuscitation in experimental circulatory shock.

OBJECTIVES: To study regional perfusion during experimental endotoxemic and obstructive shock and compare the effect of initial cardiac output-targeted fluid resuscitation with optimal cardiac output-targeted resuscitation on different peripheral tissues. DESIGN: Controlled experimental study. SETTING: University-affiliated research laboratory. SUBJECTS: Fourteen fasted anesthetized mechanically ventilated domestic pigs. INTERVENTIONS: Domestic pigs were randomly assigned to the endotoxemic (n = 7) or obstructive shock (n = 7) model. Central and regional perfusion parameters were obtained at baseline, during greater than or equal to 50% reduction of cardiac output (T1), after initial resuscitation to baseline (T2), and after optimization of cardiac output (T3). MEASUREMENTS AND MAIN RESULTS: Regional perfusion was assessed in the sublingual, intestinal, and muscle vascular beds at the different time points and included visualization of the microcirculation, measurement of tissue oxygenation, and indirect assessments of peripheral skin perfusion. Hypodynamic shock (T1) simultaneously decreased all regional perfusion variables in both models. In the obstructive model, these variables returned to baseline levels at T2 and remained in this range after T3, similar to cardiac output. In the endotoxemic model, however, the different regional perfusion variables were only normalized at T3 associated with the hyperdynamic state at this point. The magnitude of changes over time between the different vascular beds was similar in both models, but the endotoxemic model displayed greater heterogeneity between tissues. CONCLUSIONS: This study demonstrates that the relationship between the systemic and regional perfusion is dependent on the underlying cause of circulatory shock. Further research will have to demonstrate whether different microvascular perfusion variables can be used as additional resuscitation endpoints.

Nitroglycerin reverts clinical manifestations of poor peripheral perfusion in patients with circulatory shock.

INTRODUCTION: Recent clinical studies have shown a relationship between abnormalities in peripheral perfusion and unfavorable outcome in patients with circulatory shock. Nitroglycerin is effective in restoring alterations in microcirculatory blood flow. The aim of this study was to investigate whether nitroglycerin could correct the parameters of abnormal peripheral circulation in resuscitated circulatory shock patients. METHODS: This interventional study recruited patients who had circulatory shock and who persisted with abnormal peripheral perfusion despite normalization of global hemodynamic parameters. Nitroglycerin started at 2 mg/hour and doubled stepwise (4, 8, and 16 mg/hour) each 15 minutes until an improvement in peripheral perfusion was observed. Peripheral circulation parameters included capillary refill time (CRT), skin-temperature gradient (Tskin-diff), perfusion index (PI), and tissue oxygen saturation (StO2) during a reactive hyperemia test (RincStO2). Measurements were performed before, at the maximum dose, and after cessation of nitroglycerin infusion. Data were analyzed by using linear model for repeated measurements and are presented as mean (standard error). RESULTS: Of the 15 patients included, four patients (27%) responded with an initial nitroglycerin dose of 2 mg/hour. In all patients, nitroglycerin infusion resulted in significant changes in CRT, Tskin-diff, and PI toward normal at the maximum dose of nitroglycerin: from 9.4 (0.6) seconds to 4.8 (0.3) seconds (P < 0.05), from 3.3 °C (0.7 °C) to 0.7 °C (0.6 °C) (P < 0.05), and from [log] -0.5% (0.2%) to 0.7% (0.1%) (P < 0.05), respectively. Similar changes in StO2 and RincStO2 were observed: from 75% (3.4%) to 84% (2.7%) (P < 0.05) and 1.9%/second (0.08%/second) to 2.8%/second (0.05%/second) (P < 0.05), respectively. The magnitude of changes in StO2 was more pronounced for StO2 of less than 75%: 11% versus 4%, respectively (P < 0.05). CONCLUSIONS: Dose-dependent infusion of nitroglycerin reverted abnormal peripheral perfusion and poor tissue oxygenation in patients following circulatory shock resuscitation. Individual requirements of nitroglycerin dose to improve peripheral circulation vary between patients. A simple and fast physical examination of peripheral circulation at the bedside can be used to titrate nitroglycerin infusion.

Clinical assessment of peripheral perfusion to predict postoperative complications after major abdominal surgery early: a prospective observational study in adults.

INTRODUCTION: Altered peripheral perfusion is strongly associated with poor outcome in critically ill patients. We wanted to determine whether repeated assessments of peripheral perfusion during the days following surgery could help to early identify patients that are more likely to develop postoperative complications. METHODS: Haemodynamic measurements and peripheral perfusion parameters were collected one day prior to surgery, directly after surgery (D0) and on the first (D1), second (D2) and third (D3) postoperative days. Peripheral perfusion assessment consisted of capillary refill time (CRT), peripheral perfusion index (PPI) and forearm-to-fingertip skin temperature gradient (T(skin-diff)). Generalized linear mixed models were used to predict severe complications within ten days after surgery based on Clavien-Dindo classification. RESULTS: We prospectively followed 137 consecutive patients, from among whom 111 were included in the analysis. Severe complications were observed in 19 patients (17.0%). Postoperatively, peripheral perfusion parameters were significantly altered in patients who subsequently developed severe complications compared to those who did not, and these parameters persisted over time. CRT was altered at D0, and PPI and T(skin-diff) were altered on D1 and D2, respectively. Among the different peripheral perfusion parameters, the diagnostic accuracy in predicting severe postoperative complications was highest for CRT on D2 (area under the receiver operating characteristic curve = 0.91 (95% confidence interval (CI) = 0.83 to 0.92)) with a sensitivity of 0.79 (95% CI = 0.54 to 0.94) and a specificity of 0.93 (95% CI = 0.86 to 0.97). Generalized mixed-model analysis demonstrated that abnormal peripheral perfusion on D2 and D3 was an independent predictor of severe postoperative complications (D2 odds ratio (OR) = 8.4, 95% CI = 2.7 to 25.9; D2 OR = 6.4, 95% CI = 2.1 to 19.6). CONCLUSIONS: In a group of patients assessed following major abdominal surgery, peripheral perfusion alterations were associated with the development of severe complications independently of systemic haemodynamics. Further research is needed to confirm these findings and to explore in more detail the effects of peripheral perfusion-targeted resuscitation following major abdominal surgery.

Association between fat-free mass and survival in critically ill patients with COVID-19: A prospective cohort study.

BACKGROUND: Most critically ill patients with COVID-19 experience malnutrition and weight loss associated with negative clinical outcomes. Our primary aim was to assess body composition during acute and late phase of illness in these patients in relation to clinical outcome and secondary to tailored nutrition support. METHODS: This prospective cohort study included adult critically ill patients with COVID-19. Body composition (fat-free mass [FFM] [exposure of interest], fat mass [FM], skeletal muscle mass [SMM], and phase angle [PA]) was determined with multifrequency bioelectrical impedance analyses in the acute and late phase. Nutrition support data were collected simultaneously. Clinical outcome was defined as intensive care unit (ICU) survival (primary outcome) and 30-90 days thereafter, duration of mechanical ventilation, and length of ICU stay and length of hospital stay (LOS). Nonparametric tests and regression analyses were performed. RESULTS: We included 70 patients (73% male, median age 60 years). Upon admission, median BMI was 30 kg/m2 , 54% had obesity (BMI > 30 kg/m2 ). Median weight change during ICU stay was -3 kg: +3 kg FM and -6 kg FFM (-4 kg SMM). Body composition changed significantly (P < 0.001). Regarding clinical outcome, only low PA was associated with prolonged LOS (odds ratio = 0.83, 95% CI = 0.72-0.96; P = 0.015). Patients with optimal protein intake (>80%) during acute phase maintained significantly more FFM (2.7 kg, P = 0.047) in the late phase compared with patients who received <80%. CONCLUSION: FFM decreased significantly during acute and late phase of illness, but we observed no association with ICU survival. Only low PA was associated with prolonged LOS. FFM wasting likely occurred because of disease severity and immobility.

To warrant clinical adoption AI models require a multi-faceted implementation evaluation.

Despite artificial intelligence (AI) technology progresses at unprecedented rate, our ability to translate these advancements into clinical value and adoption at the bedside remains comparatively limited. This paper reviews the current use of implementation outcomes in randomized controlled trials evaluating AI-based clinical decision support and found limited adoption. To advance trust and clinical adoption of AI, there is a need to bridge the gap between traditional quantitative metrics and implementation outcomes to better grasp the reasons behind the success or failure of AI systems and improve their translation into clinical value.

Development and Validation of a Prediction Model for 1-Year Mortality in Patients With a Hematologic Malignancy Admitted to the ICU.

OBJECTIVES: To develop and validate a prediction model for 1-year mortality in patients with a hematologic malignancy acutely admitted to the ICU. DESIGN: A retrospective cohort study. SETTING: Five university hospitals in the Netherlands between 2002 and 2015. PATIENTS: A total of 1097 consecutive patients with a hematologic malignancy were acutely admitted to the ICU for at least 24 h. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We created a 13-variable model from 22 potential predictors. Key predictors included active disease, age, previous hematopoietic stem cell transplantation, mechanical ventilation, lowest platelet count, acute kidney injury, maximum heart rate, and type of malignancy. A bootstrap procedure reduced overfitting and improved the model's generalizability. This involved estimating the optimism in the initial model and shrinking the regression coefficients accordingly in the final model. We assessed performance using internal-external cross-validation by center and compared it with the Acute Physiology and Chronic Health Evaluation II model. Additionally, we evaluated clinical usefulness through decision curve analysis. The overall 1-year mortality rate observed in the study was 62% (95% CI, 59-65). Our 13-variable prediction model demonstrated acceptable calibration and discrimination at internal-external validation across centers (C-statistic 0.70; 95% CI, 0.63-0.77), outperforming the Acute Physiology and Chronic Health Evaluation II model (C-statistic 0.61; 95% CI, 0.57-0.65). Decision curve analysis indicated overall net benefit within a clinically relevant threshold probability range of 60-100% predicted 1-year mortality. CONCLUSIONS: Our newly developed 13-variable prediction model predicts 1-year mortality in hematologic malignancy patients admitted to the ICU more accurately than the Acute Physiology and Chronic Health Evaluation II model. This model may aid in shared decision-making regarding the continuation of ICU care and end-of-life considerations.

Peripheral perfusion index as an early predictor for central hypovolemia in awake healthy volunteers.

BACKGROUND: In healthy volunteers, we investigated the ability of the pulse oximeter-derived peripheral perfusion index (PPI) to detect progressive reductions in central blood volume. METHODS: Twenty-five awake, spontaneously breathing, healthy male volunteers were subjected to progressive reductions in central blood volume by inducing stepwise lower body negative pressure (LBNP) with 20 mm Hg for 5 minutes per step, from 0 to -20, -40, -60, and back to 0 mm Hg. Throughout the procedure, stroke volume (SV), heart rate (HR), and mean arterial blood pressure were recorded using volume-clamp finger plethysmography. Assessment of the PPI was done by pulse oximetry. Additionally, the forearm-to-fingertip skin-temperature gradient was measured. Data are presented as mean±SE. PPI underwent log transformation and is presented as median (25th-75th). RESULTS: Of the 25 subjects, one did not complete the study because of cardiovascular collapse. After the first LBNP step (-20 mm Hg), PPI decreased from 2.2 (1.6-3.3) to 1.2 (0.8-1.6) (P=0.007) and SV decreased from 116±3.0 mL to 104±2.6 mL (P=0.02). The magnitude of the PPI decrease (41%±6.0%) was statistically different from that observed for SV (9%±1.3%) and HR (3%±1.9%). During progression of LBNP, SV decreased and HR increased progressively with the increased applied negative pressure, whereas the PPI remained low throughout the remainder of the protocol and returned to baseline values when LBNP was released. At -60 mm Hg LBNP, SV decreased and HR increased by 36%±0.9% and 33%±2.4% from baseline, respectively. Mean arterial blood pressure remained in the same range throughout the experiment. CONCLUSIONS: These results indicate that the pulse oximeter-derived PPI may be a valuable adjunct diagnostic tool to detect early clinically significant central hypovolemia, before the onset of cardiovascular decompensation in healthy volunteers.

Cognitive and psychological recovery patterns across different care pathways 12 months after hospitalization for COVID-19: A multicenter cohort study (CO-FLOW).

BACKGROUND: The comparison of recovery patterns for different care pathways following COVID-19 is necessary for optimizing rehabilitation strategies. OBJECTIVES: To evaluate cognitive and psychological outcomes across different care pathways up to 12 months after hospitalization for COVID-19. METHODS: CO-FLOW is an ongoing multicenter prospective cohort study with assessments at 3, 6, and 12 months after hospitalization for COVID-19. The main outcomes are cognitive deficits (Montreal Cognitive Assessment, score <26), cognitive failure (Cognitive Failure Questionnaire, score >43), posttraumatic stress disorder (PTSD; Impact of Event Scale-Revised, score ≥33), and anxiety and depression (Hospital Anxiety and Depression Scale, subscale score ≥11). RESULTS: In total, data from 617 participants were analyzed. Mean age was 59.7 (SD 11.4) years and 188 (31%) were female. Significant recovery occurred within the first 6 months post-discharge (p ≤ 0.001). Cognitive deficits persisted in 21% (101/474), and psychological problems in 15% (74/482) of people at 12 months. Significantly improved cognition scores were reported for people who did not receive rehabilitation ('No-rehab'; 124/617, 20%; mean difference, MD 2.32, 95% CI 1.47 to 3.17; p<0.001), those who received community-based rehabilitation ('Com-rehab'; 327/617, 53%; MD 1.27, 95% CI 0.77 to 1.78; p<0.001), and those who received medical rehabilitation ('Med-rehab'; 86/617, 14%; MD 1.63, 95% CI 0.17 to 3.10; p = 0.029). Med-rehab participants experienced more cognitive failure from 3 to 6 months (MD 4.24, 95% 1.63 to 6.84; p = 0.001). Com-rehab showed recovery for PTSD (MD -2.43, 95% -3.50 to -1.37; p<0.001), anxiety (MD -0.67, 95% -1.02 to -0.32; p<0.001), and depression (MD -0.60, 95% -0.96 to -0.25; p<0.001), but symptoms persisted at 12 months. CONCLUSIONS: Survivors of COVID-19 showed cognitive and psychological recovery, especially within the first 6 months after hospitalization. Most persistent problems were related to cognitive functioning at 12 months. Recovery differed rehabilitation settings. Additional cognitive or psychological support might be warranted in people who medical or community-based rehabilitation.

Significant contribution of the portal vein to blood flow through the common bile duct.

OBJECTIVE: The aim of this study was to determine the contribution of the hepatic artery, gastroduodenal artery, and portal vein to the microvascular blood flow in the common bile duct (CBD). BACKGROUND: Biliary complications are a common cause of graft loss after liver transplantation. The occurrence is, partly, attributed to hepatic artery thrombosis, which is considered to be the sole provider of blood flow to the bile ducts. However, the contribution of the portal vein and the gastroduodenal artery to the bile ducts is unknown. METHODS: Microvascular blood flow in the CBD was determined in 15 patients who underwent a pancreaticoduodenectomy with a combination of laser Doppler flowmetry and reflectance spectrophotometry. Microvascular blood flow was measured at baseline, during clamping the portal vein, during clamping the hepatic artery, and during clamping both. After transection of the CBD, these 4 measurements were repeated. RESULTS: Compared with baseline measurements, the microvascular blood flow through the CBD decreased to 62% after clamping the portal vein, 51% after clamping the hepatic artery, and 31% after clamping both. After the CBD was transected, these 3 measurements were 60%, 31%, and 20%, respectively. CONCLUSIONS: : Historically, the hepatic artery has been considered mainly responsible for biliary blood flow. We show that after transection of the CBD, mimicking the situation after liver transplantation, the contribution of the portal vein to the microvascular blood flow through the CBD is 40%. This study emphasizes the importance of the portal vein, and disturbances in portal venous blood flow could contribute to the formation of biliary complications after liver transplantation.

Persistent peripheral and microcirculatory perfusion alterations after out-of-hospital cardiac arrest are associated with poor survival.

OBJECTIVE: To evaluate sublingual microcirculatory and peripheral tissue perfusion parameters in relation to systemic hemodynamics during and after therapeutic hypothermia following out-of-hospital cardiac arrest. DESIGN: Prospective observational study. SETTING: Intensive cardiac care unit at a university teaching hospital. SUBJECTS: We followed 80 patients, of whom 25 were included after out-of-hospital cardiac arrest. INTERVENTION: In all patients, we induced therapeutic hypothermia to 33°C during the first 24 hrs of admission. MEASUREMENTS AND MAIN RESULTS: Complete hemodynamic measurements were obtained directly on intensive cardiac care unit admission (baseline), during induced hypothermia (T1), directly after rewarming (T2), and another 24 hrs later (T3). In addition, the sublingual microcirculation was observed using sidestream dark-field imaging, and peripheral tissue perfusion was monitored with the peripheral perfusion index, capillary refill time, tissue oxygen saturation, and forearm-to-fingertip skin temperature gradient. During hypothermia, all sublingual microcirculatory parameters decreased significantly together with peripheral capillary refill time and the peripheral perfusion index, followed by a significant increase at T2. Changes in sublingual and peripheral tissue perfusion parameters were significantly related to changes in central body temperature, but not to changes in systemic hemodynamic variables such as cardiac index or mean arterial pressure. Surprisingly, these parameters were significantly lower in nonsurvivors (n=6) at admission and after rewarming. Persistent alterations in these parameters were related with the prevalence of organ dysfunction and were highly predictive of mortality. CONCLUSIONS: Following out-of-hospital cardiac arrest, the early postresuscitation phase is characterized by abnormalities in sublingual microcirculation and peripheral tissue perfusion, which are caused by vasoconstriction due to induced systemic hypothermia and not by impaired systemic blood flow. Persistence of these alterations is associated with organ failure and death, independent of systemic hemodynamics.