The impact of high versus standard enteral protein provision on functional recovery following intensive care admission: Protocol for a pre-planned secondary Bayesian analysis of the PRECISe trial.

BACKGROUND: The PRECISe trial is a pragmatic, multicenter randomized controlled trial that evaluates the effect of high versus standard enteral protein provision on functional recovery in adult, mechanically ventilated critically ill patients. The current protocol presents the rationale and analysis plan for an evaluation of the primary and secondary outcomes under the Bayesian framework, with an emphasis on clinically important effect sizes. METHODS: This protocol was drafted in agreement with the ROBUST-statement, and is submitted for publication before database lock and primary data analysis. The primary outcome is health-related quality of life as measured by the EQ-5D-5L health utility score and is longitudinally assessed. Secondary outcomes comprise the 6-min walking test and handgrip strength over the entire follow-up period (longitudinal analyses), and 60-day mortality, duration of mechanical ventilation, and EQ-5D-5L health utility scores at 30, 90 and 180 days (cross-sectional). All analyses will primarily be performed under weakly informative priors. When available, informative priors elicited from contemporary literature will also be incorporated under alternative scenarios. In all other cases, objectively formulated skeptical and enthusiastic priors will be defined to assess the robustness of our results. Relevant identified subgroups were: patients with acute kidney injury, severe multi-organ failure and patients with or without sepsis. Results will be presented as absolute risk differences, mean differences, and odds ratios, with accompanying 95% credible intervals. Posterior probabilities will be estimated for clinically important benefit and harm. DISCUSSION: The proposed secondary, pre-planned Bayesian analysis of the PRECISe trial will provide additional information on the effects of high protein on functional and clinical outcomes in critically ill patients, such as probabilistic interpretation, probabilities of clinically important effect sizes, and the integration of prior evidence. As such, it will complement the interpretation of the primary outcome as well as several secondary and subgroup analyses.

The effect of anesthesia on hemodynamics and outcome of patients undergoing thrombectomy after acute ischemic stroke: a retrospective analysis.

BACKGROUND: Anesthesia during thrombectomy remains a matter of debate. We retrospectively investigated the influence of intraprocedural blood pressure and type of anaesthetic agent on 3-month functional outcome and mortality in stroke patients undergoing mechanical thrombectomy under general anesthesia in a single center study. METHODS: All patients suffering from stroke who presented between January 2019 and July 2021 at Ziekenhuis Oost-Limburg Genk, Belgium and who received thrombectomy were included. Patient's characteristics and outcome data had been collected for benchmarking. Detailed perioperative data were exported from the electronic anesthesia records and clinically validated. Patients were stratified by peri-operative presence of hypotension (MAP < 65 mmHg at any time point) versus no-hypotension (MAP ≥ 65 mmHg). RESULTS: All 98 patients received mechanical thrombectomy under general anesthesia. Thirty-six percent (n = 35) was hypotensive peri-operatively at any time point. Proportion of sevoflurane use was higher in non-hypotensive patients compared to hypotensive patients (73% (n = 45) vs. 51% (n = 18), p = 0.04). Peri-operative use of vasopressors was higher in the hypotensive group compared to non-hypotensive (88% (n = 30) vs. 63% (n = 39), p = 0.008). Proportion of patients with good functional outcome at 3 months (mRS 0-2) was higher in non-hypotensive patients compared to hypotensive patients 44% (n = 27) vs. 24% (n = 8), p < 0.05. 90-day mortality was lower in non-hypotensive patients compared to hypotensive patients 21% (n = 13) vs. 43% (n = 15), (p = 0.02). CONCLUSION: Patients who are hypotensive at any given time during thrombectomy under general anesthesia may have worse neurological outcome compared to non-hypotensive patients. The best anaesthetic management for mechanical thrombectomy needs to be clarified prospectively in large multicenter studies.

Comprehensive antibody and cytokine profiling in hospitalized COVID-19 patients in relation to clinical outcomes in a large Belgian cohort.

The immune response in patients with Coronavirus Disease 2019 (COVID-19) is highly variable and is linked to disease severity and mortality. However, antibody and cytokine responses in the early disease stage and their association with disease course and outcome are still not completely understood. In this large, multi-centre cohort study, blood samples of 434 Belgian COVID-19 hospitalized patients with different disease severities (ranging from asymptomatic/mild to critically ill) from the first wave of the COVID-19 pandemic were obtained. Baseline antibody and cytokine responses were characterized and associations with several clinical outcome parameters were determined. Anti-spike immunoglobulin (Ig)G and IgM levels were elevated in patients with a more severe disease course. This increased baseline antibody response however was associated with decreased odds for hospital mortality. Levels of the pro-inflammatory cytokines IL-6, IP-10 and IL-8, the anti-inflammatory cytokine IL-10 and the antiviral cytokines IFN-α, IFN-ß and IFN-λ1 were increased with disease severity. Remarkably, we found significantly lower levels of IFN-λ2,3 in critically ill patients compared to patients of the moderate and severe disease category. Finally, levels of IL-8, IL-6, IP-10, IL-10, IFN-α, IFN-ß, IFN-γ and IFN-λ1 at baseline were positively associated with mortality, whereas higher IFN-λ2,3 levels were negatively associated with mortality.

The effect of spinal versus general anaesthesia on perioperative muscle weakness in patients having bilateral total hip arthroplasty: a single center randomized clinical trial.

BACKGROUND: Perioperative neuro-endocrine stress response may contribute to acquired muscle weakness. Regional anaesthesia has been reported to improve the outcome of patients having total hip arthroplasty. In this study, it was hypothesized that spinal anaesthesia (SA) decreases the perioperative neuro-endocrine stress response and perioperatively acquired muscle weakness (PAMW), as compared to general anaesthesia (GA). METHODS: Fifty subjects undergoing bilateral total hip arthroplasty (THA) were randomly allocated to receive a standardized SA (n = 25) or GA (n = 25). Handgrip strength was assessed preoperatively, on the first postoperative day (primary endpoint) and on day 7 and 28. Respiratory muscle strength was measured by maximal inspiratory pressure (MIP). Stress response was assessed by measuring levels of Adrenocorticotropic hormone (ACTH), cortisol and interleukin-6 (IL-6). RESULTS: Handgrip strength postoperatively (day 1) decreased by 5.4 ± 15.9% in the SA group, versus 15.2 ± 11.7% in the GA group (p = 0.02). The handgrip strength returned to baseline at day 7 and did not differ between groups at day 28. MIP increased postoperatively in patients randomized to SA by 11.7 ± 48.3%, whereas it decreased in GA by 12.2 ± 19.9% (p = 0.04). On day 7, MIP increased in both groups, but more in the SA (49.0 ± 47.8%) than in the GA group (14.2 ± 32.1%) (p = 0.006). Postoperatively, the levels of ACTH, cortisol and IL-6 increased in the GA, but not in the SA group (p < 0.004). CONCLUSION: In patients having bilateral THA, SA preserved the postoperative respiratory and peripheral muscle strength and attenuated the neuro-endocrine and inflammatory responses. TRIAL REGISTRATION: clinicaltrials.gov NCT03600454.

The impact of high versus standard enteral protein provision on functional recovery following intensive care admission (PRECISE trial): study protocol for a randomized controlled, quadruple blinded, multicenter, parallel group trial in mechanically ventilated patients.

BACKGROUND: Critically ill patients are subject to severe skeletal muscle wasting during intensive care unit (ICU) stay, resulting in impaired short- and long-term functional outcomes and health-related quality of life. Increased protein provision may improve functional outcomes in ICU patients by attenuating skeletal muscle breakdown. Supporting evidence is limited however and results in great variety in recommended protein targets. METHODS: The PRECISe trial is an investigator-initiated, bi-national, multi-center, quadruple-blinded randomized controlled trial with a parallel group design. In 935 patients, we will compare provision of isocaloric enteral nutrition with either a standard or high protein content, providing 1.3 or 2.0 g of protein/kg/day, respectively, when fed on target. All unplanned ICU admissions with initiation of invasive mechanical ventilation within 24 h of admission and an expected stay on ventilator support of at least 3 days are eligible. The study is designed to assess the effect of the intervention on functional recovery at 1, 3, and 6 months following ICU admission, including health-related quality of life, measures of muscle strength, physical function, and mental health. The primary endpoint of the trial is health-related quality of life as measured by the Euro-QoL-5D-5-level questionnaire Health Utility Score. Overall between-group differences will be assessed over the three time points using linear mixed-effects models. DISCUSSION: The PRECISe trial will evaluate the effect of protein on functional recovery including both patient-centered and muscle-related outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04633421 . Registered on November 18, 2020. First patient in (FPI) on November 19, 2020. Expected last patient last visit (LPLV) in October 2023.

Multicentric validation of a reduced features case-mix set for predicting functional outcome after ischemic stroke in Belgium.

INTRODUCTION: Ischemic stroke is the second cause of death and leading cause of severe disability worldwide. A reduced features set of CT-DRAGON (age, NIHSS on admission and pre-stroke mRS) predicts 90-day functional outcome after stroke in a single center. The current study was designed to validate this adapted CT-DRAGON score in three major Belgian hospitals, in the framework of future case-mix adjustment. METHODS: This retrospective study included stroke patients, treated by thrombolysis, thrombectomy, a combination of both or neither thrombolysis or thrombectomy (conservative treatment) in 2019. Patient characteristics and 90-day mRS were collected. Multivariable logistic regression analysis of 90-day mRS 0-2 vs. 3-6 and 0-5 vs. 6 with the reduced features set was performed. Discriminative performance was assessed by the area under the receiver operating characteristic curve (AUROC). RESULTS: Thirty-three percent of patients (413/1243) underwent treatment. Majority of strokes was treated conservatively (n = 830, 67%), 18% (n = 225) was treated by thrombolysis, 7% (n = 88) by thrombectomy and 8% (n = 100) by thrombolysis and thrombectomy. Age, NIHSS and pre-stroke mRS were independently associated with 90-day mRS 0-2 (all p ≤ 0.0001, AUROC 0.88). When treatment modality was added in the model, age, NIHSS, pre-stroke mRS and treatment modality were independently associated with 90-day mRS 0-2 (p < 0.0001, p < 0.0001, p < 0.0001 and p = 0.0001) AUROC 0.89). Age, NIHSS, pre-stroke mRS and treatment modality were independently associated with 90-day survival (p = 0.0001, p < 0.0001, p < 0.0001 and p = 0.008, AUROC 0.86). DISCUSSION: The reduced features set (age, NIHSS and pre-mRS) was independently associated with long-term functional outcome in a Belgian multicentric cohort, making it useful for case-mix adjustments in Belgian stroke centers. Treatment modality was associated with long-term outcome.

Long-Term Outcome in Patients With Spinal Cord Stimulation for Failed Back Surgery Syndrome: A 20-Year Audit of a Single Center.

STUDY DESIGN: This is a retrospective, observational study. INTRODUCTION: Spinal cord stimulation (SCS) has found its application in chronic pain treatment, with failed back surgery syndrome (FBSS) as one of the most important indications. However, to date, little is known about the long-term effectiveness of the treatment. The aim of this study is to analyze retrospectively the long-term outcomes of SCS treatment in a single multidisciplinary pain center on predominant radicular pain, using devices of a single manufacturer. MATERIALS AND METHODS: Patient data on overall patient satisfaction, pain intensity, and adverse events were retrospectively collected in our clinical practice between January 1998 and January 2018, for 191 patients who received a permanent SCS implant. Secondary health measures included the influence of opioid and nicotine use on pain reduction after therapy. RESULTS: The trial-to-implant ratio was 93.6%. At a mean follow-up of 10.6 years, 78.5% of the patients were satisfied with the treatment outcome, with a significant pain reduction of an average three points on a Numeric Rating Scale. Opioid and nicotine usage did not have a significant link with the pain reduction one year after the treatment. Furthermore, devices had an average battery lifespan of 8.4 years. A total of 248 revisions were recorded. A total of 24 patients (11.7%) acquired an infection; 7 of 204 patients had an infection during the trial period, 2 of 191 patients had an infection in the first postoperative year, and 15 of 191 patients had an infection after the first year. The average time to infection, if not in the first year, was 10.1 years. CONCLUSIONS: A successful long-term outcome regarding pain relief in patients with predominant radicular pain due to FBSS is established with SCS therapy.

A comparative study of patient satisfaction about anesthesia with dexmedetomidine for ambulatory dental surgery.

OBJECTIVE: Intranasal administration of dexmedetomidine for monitored anesthesia care (MAC) appears to be an effective, safe, and appropriate alternative to general anesthesia (GA) for ambulatory dental surgery. Based on the available evidence we evaluated a new MAC protocol with intranasal dexmedetomidine as the primary choice. To assess a difference in patient satisfaction and anesthesia-related discomfort between GA and MAC in ambulatory dental surgery, a study was conducted among patients undergoing various dental procedures. Patient satisfaction and anesthesia-related discomfort were assessed on the first postoperative day using the Bauer patient satisfaction questionnaire. RESULTS: Although the differences were small, patients in the MAC group were overall more satisfied with the general care compared to the GA group (p < 0.02). Patients in the MAC group reported more postoperative drowsiness compared to the GA group (p < 0.05), but less postoperative hoarseness and sore throat (p = 0.005 and p < 0.001, respectively). Moreover, postoperative thirst was more common in the GA group (p = 0.002). In conclusion, the differences in patient satisfaction and anesthesia-related discomfort between GA and MAC in this implementation study were small but appeared to favor MAC with intranasal dexmedetomidine over GA as anesthesia method during dental ambulatory surgery.

Modulation of thromboinflammation in hospitalized COVID-19 patients with aprotinin, low molecular weight heparin, and anakinra: The DAWn-Antico study.

Background: Thromboinflammation plays a central role in severe COVID-19. The kallikrein pathway activates both inflammatory pathways and contact-mediated coagulation. We investigated if modulation of the thromboinflammatory response improves outcomes in hospitalized COVID-19 patients. Methods: In this multicenter open-label randomized clinical trial (EudraCT 2020-001739-28), patients hospitalized with COVID-19 were 1:2 randomized to receive standard of care (SOC) or SOC plus study intervention. The intervention consisted of aprotinin (2,000,000 IE IV four times daily) combined with low molecular weight heparin (LMWH; SC 50 IU/kg twice daily on the ward, 75 IU/kg twice daily in intensive care). Additionally, patients with predefined hyperinflammation received the interleukin-1 receptor antagonist anakinra (100 mg IV four times daily). The primary outcome was time to a sustained 2-point improvement on the 7-point World Health Organization ordinal scale for clinical status, or discharge. Findings: Between 24 June 2020 and 1 February 2021, 105 patients were randomized, and 102 patients were included in the full analysis set (intervention N = 67 vs. SOC N = 35). Twenty-five patients from the intervention group (37%) received anakinra. The intervention did not affect the primary outcome (HR 0.77 [CI 0.50-1.19], p = 0.24) or mortality (intervention n = 3 [4.6%] vs. SOC n = 2 [5.7%], HR 0.82 [CI 0.14-4.94], p = 0.83). There was one treatment-related adverse event in the intervention group (hematuria, 1.49%). There was one thrombotic event in the intervention group (1.49%) and one in the SOC group (2.86%), but no major bleeding. Conclusions: In hospitalized COVID-19 patients, modulation of thromboinflammation with high-dose aprotinin and LMWH with or without anakinra did not improve outcome in patients with moderate to severe COVID-19.

Predicting COVID-19 prognosis in the ICU remained challenging: external validation in a multinational regional cohort.

OBJECTIVES: Many prediction models for coronavirus disease 2019 (COVID-19) have been developed. External validation is mandatory before implementation in the intensive care unit (ICU). We selected and validated prognostic models in the Euregio Intensive Care COVID (EICC) cohort. STUDY DESIGN AND SETTING: In this multinational cohort study, routine data from COVID-19 patients admitted to ICUs within the Euregio Meuse-Rhine were collected from March to August 2020. COVID-19 models were selected based on model type, predictors, outcomes, and reporting. Furthermore, general ICU scores were assessed. Discrimination was assessed by area under the receiver operating characteristic curves (AUCs) and calibration by calibration-in-the-large and calibration plots. A random-effects meta-analysis was used to pool results. RESULTS: 551 patients were admitted. Mean age was 65.4 ± 11.2 years, 29% were female, and ICU mortality was 36%. Nine out of 238 published models were externally validated. Pooled AUCs were between 0.53 and 0.70 and calibration-in-the-large between -9% and 6%. Calibration plots showed generally poor but, for the 4C Mortality score and Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) score, moderate calibration. CONCLUSION: Of the nine prognostic models that were externally validated in the EICC cohort, only two showed reasonable discrimination and moderate calibration. For future pandemics, better models based on routine data are needed to support admission decision-making.

Population-wide persistent hemostatic changes after vaccination with ChAdOx1-S.

Various vaccines were developed to reduce the spread of the Severe Acute Respiratory Syndrome Cov-2 (SARS-CoV-2) virus. Quickly after the start of vaccination, reports emerged that anti-SARS-CoV-2 vaccines, including ChAdOx1-S, could be associated with an increased risk of thrombosis. We investigated the hemostatic changes after ChAdOx1-S vaccination in 631 health care workers. Blood samples were collected 32 days on average after the second ChAdOx1-S vaccination, to evaluate hemostatic markers such as D-dimer, fibrinogen, α2-macroglobulin, FVIII and thrombin generation. Endothelial function was assessed by measuring Von Willebrand Factor (VWF) and active VWF. IL-6 and IL-10 were measured to study the activation of the immune system. Additionally, SARS-CoV-2 anti-nucleoside and anti-spike protein antibody titers were determined. Prothrombin and fibrinogen levels were significantly reduced after vaccination (-7.5% and -16.9%, p < 0.0001). Significantly more vaccinated subjects were outside the normal range compared to controls for prothrombin (42.1% vs. 26.4%, p = 0.026) and antithrombin (23.9% vs. 3.6%, p = 0.0010). Thrombin generation indicated a more procoagulant profile, characterized by a significantly shortened lag time (-11.3%, p < 0.0001) and time-to-peak (-13.0% and p < 0.0001) and an increased peak height (32.6%, p = 0.0015) in vaccinated subjects compared to unvaccinated controls. Increased VWF (+39.5%, p < 0.0001) and active VWF levels (+24.1 %, p < 0.0001) pointed toward endothelial activation, and IL-10 levels were significantly increased (9.29 pg/mL vs. 2.43 pg/mL, p = 0.032). The persistent increase of IL-10 indicates that the immune system remains active after ChAdOx1-S vaccination. This could trigger a pathophysiological mechanism causing an increased thrombin generation profile and vascular endothelial activation, which could subsequently result in and increased risk of thrombotic events.

Acute kidney injury in critical COVID-19: a multicenter cohort analysis in seven large hospitals in Belgium.

BACKGROUND: Acute kidney injury (AKI) has been reported as a frequent complication of critical COVID-19. We aimed to evaluate the occurrence of AKI and use of kidney replacement therapy (KRT) in critical COVID-19, to assess patient and kidney outcomes and risk factors for AKI and differences in outcome when the diagnosis of AKI is based on urine output (UO) or on serum creatinine (sCr). METHODS: Multicenter, retrospective cohort analysis of patients with critical COVID-19 in seven large hospitals in Belgium. AKI was defined according to KDIGO within 21 days after ICU admission. Multivariable logistic regression analysis was used to explore the risk factors for developing AKI and to assess the association between AKI and ICU mortality. RESULTS: Of 1286 patients, 85.1% had AKI, and KRT was used in 9.8%. Older age, obesity, a higher APACHE II score and use of mechanical ventilation at day 1 of ICU stay were associated with an increased risk for AKI. After multivariable adjustment, all AKI stages were associated with ICU mortality. AKI was based on sCr in 40.1% and UO in 81.5% of patients. All AKI stages based on sCr and AKI stage 3 based on UO were associated with ICU mortality. Persistent AKI was present in 88.6% and acute kidney disease (AKD) in 87.6%. Rapid reversal of AKI yielded a better prognosis compared to persistent AKI and AKD. Kidney recovery was observed in 47.4% of surviving AKI patients. CONCLUSIONS: Over 80% of critically ill COVID-19 patients had AKI. This was driven by the high occurrence rate of AKI defined by UO criteria. All AKI stages were associated with mortality (NCT04997915).

Hospital-acquired infections after acute ischaemic stroke and its association with healthcare-related costs and functional outcome.

INTRODUCTION: Acute ischaemic stroke is associated with important mortality, morbidity, and healthcare-related costs. Age, pre-stroke functionality and stroke severity are important contributors to functional outcome. Stroke patients also risk developing infections during hospitalization. We sought to explore possible predictors of post-stroke infections and the relationship of post-stroke infection with healthcare-related costs and functional outcome. METHODS: This single-centre retrospective study included 530 patients treated for ischaemic stroke between January 2017 and February 2019. Antibiotics' administration was used as a proxy for post-stroke infection. Functional outcome at 90 days was assessed by the modified Rankin Scale (mRS). Total healthcare-related costs were recorded for the index hospital stay. Multivariable analysis for post-stroke infection was done with the independent factors sex, age, pre-stroke mRS, National Institutes of Health Stroke Scale (NIHSS) and diabetes mellitus. RESULTS: Twenty percent of patients had a post-stroke infection. NIHSS (OR 1.10, 95%CI 1.06-1.13, p < 0.0001) and diabetes mellitus (OR 2.18, 95%CI 1.28-3.71, p = 0.0042) were independent predictors for post-stroke infection. Mean total healthcare-related costs were 15,374 euro (SD 19,968; IQR 3,380-18,165), with a mean of 31,061 euro (SD 29,995; IQR 12,584-42,843) in patients with infection, compared to 11,406 euro (SD 13,987; IQR 3,083-12,726) in patients without (p < 0.0001). Median 90-days mRS was 5 (IQR 3-6) in patients with infection versus 1 (IQR 0-3.5) in patients without (p < 0.0001). CONCLUSIONS: In patients, admitted for acute ischaemic stroke, stroke severity and diabetes mellitus were identified as the main predictors for post-stroke infection. Hospital-acquired infections were associated with increased costs and worse functional outcome.

The Potential and Limitations of Mobile Health and Insertable Cardiac Monitors in the Detection of Atrial Fibrillation in Cryptogenic Stroke Patients: Preliminary Results From the REMOTE Trial.

Aim: This paper presents the preliminary results from the ongoing REMOTE trial. It aims to explore the opportunities and hurdles of using insertable cardiac monitors (ICMs) and photoplethysmography-based mobile health (PPG-based mHealth) using a smartphone or smartwatch to detect atrial fibrillation (AF) in cryptogenic stroke and transient ischemic attack (TIA) patients. Methods and Results: Cryptogenic stroke or TIA patients (n = 39) received an ICM to search for AF and were asked to use a blinded PPG-based mHealth application for 6 months simultaneously. They were randomized to smartphone or smartwatch monitoring. In total, 68,748 1-min recordings were performed using PPG-based mHealth. The number of mHealth recordings decreased significantly over time in both smartphone and smartwatch groups (p < 0.001 and p = 0.002, respectively). Insufficient signal quality was more frequently observed in smartwatch (43.3%) compared to smartphone recordings (17.8%, p < 0.001). However, when looking at the labeling of the mHealth recordings on a patient level, there was no significant difference in signal quality between both groups. Moreover, the use of a smartwatch resulted in significantly more 12-h periods (91.4%) that were clinically useful compared to smartphone users (84.8%) as they had at least one recording of sufficient signal quality. Simultaneously, continuous data was collected from the ICMs, resulting in approximately 6,660,000 min of data (i.e., almost a 100-fold increase compared to mHealth). The ICM algorithm detected AF and other cardiac arrhythmias in 10 and 19 patients, respectively. However, these were only confirmed after adjudication by the remote monitoring team in 1 (10%) and 5 (26.3%) patients, respectively. The confirmed AF was also detected by PPG-based mHealth. Conclusion: Based on the preliminary observations, our paper illustrates the potential as well as the limitations of PPG-based mHealth and ICMs to detect AF in cryptogenic stroke and TIA patients in four elements: (i) mHealth was able to detect AF in a patient in which AF was confirmed on the ICM; (ii) Even state-of-the-art ICMs yielded many false-positive AF registrations; (iii) Both mHealth and ICM still require physician revision; and (iv) Blinding of the mHealth results impairs compliance and motivation.

Will Smartphone Applications Replace the Insertable Cardiac Monitor in the Detection of Atrial Fibrillation? The First Comparison in a Case Report of a Cryptogenic Stroke Patient.

Background and Case: This case report exemplifies the clinical application of non-invasive photoplethysmography (PPG)-based rhythm monitoring in the awakening mobile health (mHealth) era to detect symptomatic and asymptomatic paroxysmal atrial fibrillation (AF) in a cryptogenic stroke patient. Despite extensive diagnostic workup, the etiology remains unknown in one out of three ischemic strokes (i.e., cryptogenic stroke). Prolonged cardiac monitoring can reveal asymptomatic atrial fibrillation in up to one-third of this population. This case report describes a cryptogenic stroke patient who received prolonged cardiac monitoring with an insertable cardiac monitor (ICM) as standard of care. In the context of a clinical study, the patient simultaneously monitored his heart rhythm with a PPG-based smartphone application. AF was detected simultaneously on both the ICM and smartphone application after three days of monitoring. Similar AF burden was detected during follow-up (five episodes, median duration of 28 and 34 h on ICM and mHealth, respectively, p = 0.5). The detection prompted the initiation of oral anticoagulation and AF catheter ablation procedure. Conclusion: This is the first report of the cryptogenic stroke patient in whom PPG-based mHealth was able to detect occurrence and burden of the symptomatic and asymptomatic paroxysmal AF episodes with similar precision as ICM. It accentuates the potential role of PPG-based mHealth in prolonged cardiac rhythm monitoring in cryptogenic stroke patients.

Effect of Lidocaine 2% Versus Bupivacaine 0.5% and 1 Versus 2 Dual Separate Injections on Onset and Duration of Ultrasound-Guided Wrist Blocks: A Blinded 2 × 2 Factorial Randomized Clinical Trial.

BACKGROUND: Local anesthetics are often selected or mixed to accomplish faster onset of anesthesia. However, with ultrasound guidance, local anesthetics are delivered with greater precision, which may shorten the onset time with all classes of local anesthetics. In this study, we compared onset time and duration of ultrasound-guided wrist blocks with a fast onset versus a longer lasting local anesthetic administered via single or dual (spatially separate) injections at the level of the midforearm. METHODS: In this randomized clinical trial, 36 subjects scheduled for carpal tunnel release were randomly assigned to receive ultrasound-guided median and ulnar nerve blocks with lidocaine 2% or bupivacaine 0.5% via single or dual injections (n = 9 in each group). Subjects fulfilled the study requirements. The main outcome variables were onset and duration of sensory blockade, which were tested separately in 2 (drug) × 2 (injection) analysis of variances (ANOVAs) with interaction terms. RESULTS: Sensory block onset time did not differ significantly between subjects given lidocaine 2% (9.2 ± 3.4 minutes) or bupivacaine 0.5% (9.5 ± 3.1 minutes) (P = .76; mean difference, -0.3 ± 1.1 minutes [95% confidence interval {CI}, -2.5 to 1.9]) or between the single- (9.6 ± 2.8 minutes) and dual- (9.1 ± 3.6 minutes) injection groups (P = .69; mean difference, -0.4 ± 1.1 minutes [95% CI, -1.8 to 2.6]). Sensory duration was longer for subjects in the bupivacaine 0.5% group (27.3 ± 11.6 hours) than for subjects in the lidocaine 2% group (8.4 ± 4.1 hours) (P < .001; 95% CI, 12.7-25.1). However, sensory duration in the single- (15.7 ± 12.5 hours) and dual- (19.4 ± 13.1 hours) injection groups did not differ significantly (P = .28; mean difference, -3.7 ± 4.3 hours [95% CI, -12.6 to 5.1]). CONCLUSIONS: No significant effect was found for onset time between lidocaine 2% and bupivacaine 0.5% used in ultrasound-guided wrist blocks. Dual injections did not shorten onset time. Since mean nerve block duration was longer with bupivacaine 0.5%, our results suggest that the selection of local anesthetic for the median and ulnar nerves at the level of the midforearm should be based on the desired duration of the block and not on its speed of onset.

Better COVID-19 Intensive Care Unit survival in females, independent of age, disease severity, comorbidities, and treatment.

Although male Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) patients have higher Intensive Care Unit (ICU) admission rates and a worse disease course, a comprehensive analysis of female and male ICU survival and underlying factors such as comorbidities, risk factors, and/or anti-infection/inflammatory therapy administration is currently lacking. Therefore, we investigated the association between sex and ICU survival, adjusting for these and other variables. In this multicenter observational cohort study, all patients with SARS-CoV-2 pneumonia admitted to seven ICUs in one region across Belgium, The Netherlands, and Germany, and requiring vital organ support during the first pandemic wave were included. With a random intercept for a center, mixed-effects logistic regression was used to investigate the association between sex and ICU survival. Models were adjusted for age, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, comorbidities, and anti-infection/inflammatory therapy. Interaction terms were added to investigate effect modifications by sex with country and sex with obesity. A total of 551 patients (29% were females) were included. Mean age was 65.4 ± 11.2 years. Females were more often obese and smoked less frequently than males (p-value 0.001 and 0.042, respectively). APACHE II scores of females and males were comparable. Overall, ICU mortality was 12% lower in females than males (27% vs 39% respectively, p-value < 0.01) with an odds ratio (OR) of 0.62 (95%CI 0.39-0.96, p-value 0.032) after adjustment for age and APACHE II score, 0.63 (95%CI 0.40-0.99, p-value 0.044) after additional adjustment for comorbidities, and 0.63 (95%CI 0.39-0.99, p-value 0.047) after adjustment for anti-infection/inflammatory therapy. No effect modifications by sex with country and sex with obesity were found (p-values for interaction > 0.23 and 0.84, respectively). ICU survival in female SARS-CoV-2 patients was higher than in male patients, independent of age, disease severity, smoking, obesity, comorbidities, anti-infection/inflammatory therapy, and country. Sex-specific biological mechanisms may play a role, emphasizing the need to address diversity, such as more sex-specific prediction, prognostic, and therapeutic approach strategies.