Longitudinal Lower Airway Microbial Signatures of Acute Cellular Rejection in Lung Transplantation.

Rationale: Acute cellular rejection (ACR) after lung transplant is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objectives: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple time points. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired 1 month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) than those with current or future (beyond 1 mo) ACR. However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusions: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.

Clinical Impact of the Implementation Strategies Used to Apply the 2013 Pain, Agitation/Sedation, Delirium or 2018 Pain, Agitation/Sedation, Delirium, Immobility, Sleep Disruption Guideline Recommendations: A Systematic Review and Meta-Analysis.

OBJECTIVES: To summarize the effectiveness of implementation strategies for ICU execution of recommendations from the 2013 Pain, Agitation/Sedation, Delirium (PAD) or 2018 PAD, Immobility, Sleep Disruption (PADIS) guidelines. DATA SOURCES: PubMed, CINAHL, Scopus, and Web of Science were searched from January 2012 to August 2023. The protocol was registered with PROSPERO (CRD42020175268). STUDY SELECTION: Articles were included if: 1) design was randomized or cohort, 2) adult population evaluated, 3) employed recommendations from greater than or equal to two PAD/PADIS domains, and 4) evaluated greater than or equal to 1 of the following outcome(s): short-term mortality, delirium occurrence, mechanical ventilation (MV) duration, or ICU length of stay (LOS). DATA EXTRACTION: Two authors independently reviewed articles for eligibility, number of PAD/PADIS domains, quality according to National Heart, Lung, and Blood Institute assessment tools, implementation strategy use (including Assess, prevent, and manage pain; Both SAT and SBT; Choice of analgesia and sedation; Delirium: assess, prevent, and manage; Early mobility and exercise; Family engagement and empowerment [ABCDEF] bundle) by Cochrane Effective Practice and Organization of Care (EPOC) category, and clinical outcomes. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. DATA SYNTHESIS: Among the 25 of 243 (10.3%) full-text articles included ( n = 23,215 patients), risk of bias was high in 13 (52%). Most studies were cohort ( n = 22, 88%). A median of 5 (interquartile range [IQR] 4-7) EPOC strategies were used to implement recommendations from two (IQR 2-3) PAD/PADIS domains. Cohort and randomized studies were pooled separately. In the cohort studies, use of EPOC strategies was not associated with a change in mortality (risk ratio [RR] 1.01; 95% CI, 0.9-1.12), or delirium (RR 0.92; 95% CI, 0.82-1.03), but was associated with a reduction in MV duration (weighted mean difference [WMD] -0.84 d; 95% CI, -1.25 to -0.43) and ICU LOS (WMD -0.77 d; 95% CI, -1.51 to 0.04). For randomized studies, EPOC strategy use was associated with reduced mortality and MV duration but not delirium or ICU LOS. CONCLUSIONS: Using multiple implementation strategies to adopt PAD/PADIS guideline recommendations may reduce mortality, duration of MV, and ICU LOS. Further prospective, controlled studies are needed to identify the most effective strategies to implement PAD/PADIS recommendations.

Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation.

OBJECTIVES: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet). METHODS: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. RESULTS: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (adjusted hazard ratio [aHR] = 2.74, 95% confidence interval = 1.76-4.26) and ischemic stroke (aHR = 1.29, 95% confidence interval = 1.04-1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleed burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2 to 4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥ 11 microbleeds (94 vs 48 per 1,000 patient-years). INTERPRETATION: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. ANN NEUROL 2023;94:61-74.

Evaluation of Clinical Outcomes Associated With Phenobarbital With Taper Compared to No Taper for the Management of Alcohol Withdrawal Syndrome.

BACKGROUND: Phenobarbital (PHB) has been shown to be an effective treatment of alcohol withdrawal syndrome (AWS), with multiple dosing strategies used (e.g., single-dose and symptom-triggered). Studies have often used tapered doses, typically following a front-loaded dose, despite PHB's long half-life which should lead to an ability to auto-taper. OBJECTIVE: The purpose of this study was to compare clinical outcomes associated with two PHB dosing strategies (taper [T], no taper [NT]) for AWS. METHODS: This retrospective cohort study compared adult patients admitted to the ICU from October 2017 to May 2019 who received an initial loading dose of PHB for AWS. The use of PHB was at the discretion of the clinician per our institutional guidelines. Prior to November 2018, patients were prescribed a PHB taper, while after this period, the taper was no longer recommended. The primary outcome was the proportion of patients requiring rescue PHB or adjunctive medications for AWS. Secondary outcomes included number of adjunctive agents used, prevalence of severe manifestations of AWS, ICU and hospital lengths of stay, and incidence of potentially significant drug interactions. RESULTS: A total of 172 patients were included (T: n = 81, NT: n = 91). Baseline characteristics were similar between groups, including history of severe AWS and cumulative benzodiazepine dose pre-PHB. There was no difference in the primary outcome between groups (T: 70.4% vs NT: 59.3%, P = 0.152). The median number of adjunctive agents per patient, severe manifestations, and ICU and hospital length of stay did not differ between groups. Twenty-five patients (14.5%) had potentially significant drug interactions. CONCLUSION AND RELEVANCE: The use of a PHB loading dose without a taper may be comparable to a taper strategy on clinical outcomes. Prospective studies are needed to further delineate the optimal dose of PHB for AWS.

Antithrombotic and hemostatic stewardship: Evaluation of romiplostim for treatment of thrombocytopenia at a large academic medical center.

Romiplostim is indicated for immune thrombocytopenia (ITP), though is often used off-label for other indications such as chemotherapy-induced thrombocytopenia (CIT) and thrombocytopenia post hematopoietic stem cell transplantation (HSCT). Although romiplostim is FDA approved at a starting dose of 1 mcg/kg, it is often initiated at 2-4 mcg/kg depending on the severity of thrombocytopenia in clinical practice. Given the limited data, but interest in higher doses of romiplostim for indications other than ITP, we aimed to assess our inpatient romiplostim utilization at NYU Langone Health.This was a single-center, retrospective review of 84 adult patients from January 2019 to July 2021. The top three indications were ITP (51, 60.7%), CIT (13, 15.5%), and HSCT (10, 11.9%). The median initial romiplostim dose was 3.8 mcg/kg (range, 0.9-10.8). 51% of patients achieved a platelet count of ≥50 × 109/L by the end of week 1 of therapy. For patients achieving goal platelets by the end of week 1, the median dose of romiplostim was 2.4 mcg/kg (range, 0.9-10.8). There was 1 episode of thrombosis and 1 episode of stroke.We found that higher than FDA-recommended initial doses should be considered to achieve a platelet response. It appears to be safe to initiate romiplostim as higher doses, and to increase doses by greater increments than 1 mcg/kg in order to achieve a platelet response. Future prospective studies are needed to confirm the safety and efficacy of romiplostim in off-label indications and should evaluate clinical outcomes such as bleeding and need for transfusions.

More than a piece of cake: Noun classifier processing in primary progressive aphasia.

INTRODUCTION: Clinical understanding of primary progressive aphasia (PPA) has been primarily derived from Indo-European languages. Generalizing certain linguistic findings across languages is unfitting due to contrasting linguistic structures. While PPA patients showed noun classes impairments, Chinese languages lack noun classes. Instead, Chinese languages are classifier language, and how PPA patients manipulate classifiers is unknown. METHODS: We included 74 native Chinese speakers (22 controls, 52 PPA). For classifier production task, participants were asked to produce the classifiers of high-frequency items. In a classifier recognition task, participants were asked to choose the correct classifier. RESULTS: Both semantic variant (sv) PPA and logopenic variant (lv) PPA scored significantly lower in classifier production task. In classifier recognition task, lvPPA patients outperformed svPPA patients. The classifier production scores were correlated to cortical volume over left temporal and visual association cortices. DISCUSSION: This study highlights noun classifiers as linguistic markers to discriminate PPA syndromes in Chinese speakers. HIGHLIGHTS: Noun classifier processing varies in the different primary progressive aphasia (PPA) variants. Specifically, semantic variant PPA (svPPA) and logopenic variant PPA (lvPPA) patients showed significantly lower ability in producing specific classifiers. Compared to lvPPA, svPPA patients were less able to choose the accurate classifiers when presented with choices. In svPPA, classifier production score was positively correlated with gray matter volume over bilateral temporal and left visual association cortices in svPPA. Conversely, classifier production performance was correlated with volumetric changes over left ventral temporal and bilateral frontal regions in lvPPA. Comparable performance of mass and count classifier were noted in Chinese PPA patients, suggesting a common cognitive process between mass and count classifiers in Chinese languages.

Rapid Formation of Non-canonical Phospholipid Membranes by Chemoselective Amide-Forming Ligations with Hydroxylamines.

There has been increasing interest in methods to generate synthetic lipid membranes as key constituents of artificial cells or to develop new tools for remodeling membranes in living cells. However, the biosynthesis of phospholipids involves elaborate enzymatic pathways that are challenging to reconstitute in vitro. An alternative approach is to use chemical reactions to non-enzymatically generate natural or non-canonical phospholipids de novo. Previous reports have shown that synthetic lipid membranes can be formed in situ using various ligation chemistries, but these methods lack biocompatibility and/or suffer from slow kinetics at physiological pH. Thus, it would be valuable to develop chemoselective strategies for synthesizing phospholipids from water-soluble precursors that are compatible with synthetic or living cells Here, we demonstrate that amide-forming ligations between lipid precursors bearing hydroxylamines and α-ketoacids (KAs) or potassium acyltrifluoroborates (KATs) can be used to prepare non-canonical phospholipids at physiological pH conditions. The generated amide-linked phospholipids spontaneously self-assemble into cell-like micron-sized vesicles similar to natural phospholipid membranes. We show that lipid synthesis using KAT ligation proceeds extremely rapidly, and the high selectivity and biocompatibility of the approach facilitates the in situ synthesis of phospholipids and associated membranes in living cells.

Real-Time Ultrasound Guidance as Compared With Landmark Technique for Subclavian Central Venous Cannulation: A Systematic Review and Meta-Analysis With Trial Sequential Analysis.

OBJECTIVES: We conducted a systematic review and meta-analysis to assess the effectiveness of real-time dynamic ultrasound-guided subclavian vein cannulation as compared to landmark technique in adult patients. DATA SOURCES: PubMed and EMBASE until June 1, 2022, with the EMBASE search restricted to the last 5 years. STUDY SELECTION: We included randomized controlled trials (RCTs) comparing the two techniques (real-time ultrasound-guided vs landmark) for subclavian vein cannulation. The primary outcomes were overall success rate and complication rate, whereas secondary outcomes included success at first attempt, number of attempts, and access time. DATA EXTRACTION: Independent extraction by two authors according to prespecified criteria. DATA SYNTHESIS: After screening, six RCTs were included. Two further RCTs using a static ultrasound-guided approach and one prospective study were included in the sensitivity analyses. The results are presented in the form of risk ratio (RR) or mean difference (MD) with 95% CI. Real-time ultrasound guidance increased the overall success rate for subclavian vein cannulation as compared to landmark technique (RR = 1.14; [95% CI 1.06-1.23]; p = 0.0007; I2 = 55%; low certainty) and complication rates (RR = 0.32; [95% CI 0.22-0.47]; p < 0.00001; I2 = 0%; low certainty). Furthermore, ultrasound guidance increased the success rate at first attempt (RR = 1.32; [95% CI 1.14-1.54]; p = 0.0003; I2 = 0%; low certainty), reduced the total number of attempts (MD = -0.45 [95% CI -0.57 to -0.34]; p < 0.00001; I2 = 0%; low certainty), and access time (MD = -10.14 s; [95% CI -17.34 to -2.94]; p = 0.006; I2 = 77%; low certainty). The Trial Sequential Analyses on the investigated outcomes showed that the results were robust. The evidence for all outcomes was considered to be of low certainty. CONCLUSIONS: Real-time ultrasound-guided subclavian vein cannulation is safer and more efficient than a landmark approach. The findings seem robust although the evidence of low certainty.

Comparison of COVID-19 Preprint and Peer-Reviewed Versions of Studies on Therapies for Critically Ill Patients.

PURPOSE: Significant increases in the volume of preprint articles due to the COVID-19 pandemic, we examined the reliability of preprint articles compared to their peer-reviewed publications. MATERIALS AND METHODS: Preprint articles evaluating experimental studies of select treatment options (anticoagulation, dexamethasone, hydroxychloroquine, remdesivir, and tocilizumab) for COVID-19 in the critically ill, available in a peer-reviewed publication were screened for inclusion within Altmetric (n = 2040). A total of 40 articles met inclusion criteria, with 21 being randomly selected for evaluation. The primary outcome of this evaluation was a change in a study's reported primary outcome or statistical significance between preprint and peer-reviewed articles. Secondary outcomes included changes in primary/secondary outcome effect size and change in study conclusion. RESULTS: One article (4.8%, 95% CI 0.12%-23.8%) had a change in the primary outcome. Seven articles (33.3%, 95% CI 14.6%-57.0%) had a change in the primary outcome's effect measure. Five studies (23.8%, 95% CI 8.2%-47.2%) had changes in statistical significance of at least one secondary outcome. Four studies (19.0%, 95% CI 5.4%-41.9%) had a change in study conclusion. CONCLUSIONS: In preprint articles of COVID-19 treatments, the provided primary outcome is generally reliable, while interpretation of secondary outcomes should be made with caution, while awaiting completion of the peer-review process.

Intensive care nurse-led point of care ultrasound in the assessment and management of the critically ill COVID-19 patient: A single centre case series.

Focused ultrasound can be used to rapidly diagnose COVID-19 disease, assess disease severity, and inform management of COVID-19 and associated pathologies, reducing radiation exposure from other imaging modalities and minimizing spread of infection. Ultrasound examinations performed by trained nurses in the intensive care unit (ICU) enable more patients to receive these assessments. This case series evaluates the use of nurse-led focused cardiac and lung ultrasound for clinical management of ICU patients with COVID-19. We describe common pathophysiological findings and how findings were used to inform clinical decision-making. An ultrasound trained ICU nurse performed Focused Ultrasound in Intensive Care (FUSIC) cardiac and lung scans enabling calculation of a lung severity score on adult ICU patients with a confirmed COVID-19 diagnosis in a single-centre setting. Fifteen scans were performed on 15 patients. Thirteen (87%) patients had normal left ventricular function; 12 (80%) normal right ventricular function. All 15 (100%) scans identified abnormal lung findings including irregular thickened pleura, B-lines, sub-pleural consolidation and hepatization. Worse lung severity scores were correlated with higher Acute Physiology and Chronic Health Evaluation (APACHE II) scores (r = 0.70; p = .003). Of the 15 scans, 10 (67%) identified abnormal pathology contributing to a change in clinical management. This included targeted fluid removal (4, 27%), change in respiratory management (3, 20%) and need for formal echocardiographic assessment (3, 20%). Findings from five (33%) scans required no intervention. This case series demonstrates nurse-led ultrasound could be a useful adjunct in the management of the COVID-19 patient.

Evaluation of Digital Drawing Tests and Paper-and-Pencil Drawing Tests for the Screening of Mild Cognitive Impairment and Dementia: A Systematic Review and Meta-analysis of Diagnostic Studies.

Digital drawing tests have been proposed for cognitive screening over the past decade. However, the diagnostic performance is still to clarify. The objective of this study was to evaluate the diagnostic performance among different types of digital and paper-and-pencil drawing tests in the screening of mild cognitive impairment (MCI) and dementia. Diagnostic studies evaluating digital or paper-and-pencil drawing tests for the screening of MCI or dementia were identified from OVID databases, included Embase, MEDLINE, CINAHL, and PsycINFO. Studies evaluated any type of drawing tests for the screening of MCI or dementia and compared with healthy controls. This study was performed according to PRISMA and the guidelines proposed by the Cochrane Diagnostic Test Accuracy Working Group. A bivariate random-effects model was used to compare the diagnostic performance of these drawing tests and presented with a summary receiver-operating characteristic curve. The primary outcome was the diagnostic performance of clock drawing test (CDT). Other types of drawing tests were the secondary outcomes. A total of 90 studies with 22,567 participants were included. In the screening of MCI, the pooled sensitivity and specificity of the digital CDT was 0.86 (95% CI = 0.75 to 0.92) and 0.92 (95% CI = 0.69 to 0.98), respectively. For the paper-and-pencil CDT, the pooled sensitivity and specificity of brief scoring method was 0.63 (95% CI = 0.49 to 0.75) and 0.77 (95% CI = 0.68 to 0.84), and detailed scoring method was 0.63 (95% CI = 0.56 to 0.71) and 0.72 (95% CI = 0.65 to 0.78). In the screening of dementia, the pooled sensitivity and specificity of the digital CDT was 0.83 (95% CI = 0.72 to 0.90) and 0.87 (95% CI = 0.79 to 0.92). The performances of the digital and paper-and-pencil pentagon drawing tests were comparable in the screening of dementia. The digital CDT demonstrated better diagnostic performance than paper-and-pencil CDT for MCI. Other types of digital drawing tests showed comparable performance with paper-and-pencil formats. Therefore, digital drawing tests can be used as an alternative tool for the screening of MCI and dementia.

A Retrospective Comparison of the Effectiveness and Safety of Intravenous Olanzapine Versus Intravenous Haloperidol for Agitation in Adult Intensive Care Unit Patients.

OBJECTIVE: Intravenous (IV) olanzapine could be an alternative to first-generation antipsychotics for the management of agitation in intensive care unit (ICU) patients. We compared the effectiveness and safety of IV olanzapine to IV haloperidol for agitation management in adult patients in the ICU at a tertiary academic medical center. METHODS: A retrospective cohort study was conducted. The primary outcome was the proportion of patients who achieved a Richmond Agitation Sedation Scale (RASS) score of < +1 within 4 hours of IV olanzapine or IV haloperidol administration. Secondary outcomes included the proportion of patients who required rescue medications for agitation within 4 hours of initial IV olanzapine or IV haloperidol administration, incidence of adverse events and ICU length of stay. RESULTS: In the 192 patient analytic cohort, there was no difference in the proportion of patients who achieved a RASS score of < +1 within 4 hours of receiving IV olanzapine or IV haloperidol (49% vs. 42%, p = 0.31). Patients in the IV haloperidol group were more likely to receive rescue medications (28% vs 55%, p < 0.01). There was no difference in the incidence of respiratory events or hypotension between IV olanzapine and IV haloperidol. Patients in the IV olanzapine group experienced more bradycardia (11% vs. 3%, p = 0.04) and somnolence (9% vs. 1%, p = 0.02) compared to the IV haloperidol group. Patients in the IV olanzapine group had a longer median ICU length of stay (7.5 days vs. 5 days, p = 0.04). CONCLUSION: In this retrospective cohort study, there was no difference in the effectiveness of IV olanzapine compared to IV haloperidol for the management of agitation. IV olanzapine was associated with an increased incidence of bradycardia and somnolence.

Research Needs for Inpatient Management of Severe Alcohol Withdrawal Syndrome: An Official American Thoracic Society Research Statement.

Background: Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum. Goals: This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research in each domain of the Institute of Medicine T0-T4 continuum to advance the care of hospitalized patients who experience SAWS. Methods: Clinicians and researchers with unique and complementary expertise in basic, clinical, and implementation research related to unhealthy alcohol consumption and alcohol withdrawal were invited to participate in a workshop at the American Thoracic Society 2019 International Conference. The committee was subdivided into four groups on the basis of interest and expertise: T0-T1 (basic science research with translation to humans), T2 (research translating to patients), T3 (research translating to clinical practice), and T4 (research translating to communities). A medical librarian conducted a pragmatic literature search to facilitate this work, and committee members reviewed and supplemented the resulting evidence, identifying key knowledge gaps. Results: The committee identified several investigative opportunities to advance the care of patients with SAWS in each domain of the translational science spectrum. Major themes included 1) the need to investigate non-γ-aminobutyric acid pathways for alcohol withdrawal syndrome treatment; 2) harnessing retrospective and electronic health record data to identify risk factors and create objective severity scoring systems, particularly for acutely ill patients with SAWS; 3) the need for more robust comparative-effectiveness data to identify optimal SAWS treatment strategies; and 4) recommendations to accelerate implementation of effective treatments into practice. Conclusions: The dearth of evidence supporting management decisions for hospitalized patients with SAWS, many of whom require critical care, represents both a call to action and an opportunity for the American Thoracic Society and larger scientific communities to improve care for a vulnerable patient population. This report highlights basic, clinical, and implementation research that diverse experts agree will have the greatest impact on improving care for hospitalized patients with SAWS.

Future developments in the imaging of the gastrointestinal tract: the role of ultrasound.

PURPOSE OF REVIEW: The purpose of this review is to summarize the utilization and most recent developments with regard to the use of ultrasound when imaging the abdomen and gastrointestinal tract. RECENT FINDINGS: Although the use of ultrasound to assess the anatomy of the various abdominal organs is well established within radiology and critical care, its use as part of functional and physiological assessment is still evolving. Recent developments have extended the use of ultrasound beyond standard B-mode/2D imaging techniques to incorporate more functional and haemodynamic assessment. These include the use of contrast-enhanced ultrasound (CEUS), elastography, and colour Doppler techniques. SUMMARY: Whilst Doppler techniques are reasonably well established within critical care ultrasound (CCUS), especially in echocardiography, CEUS and elastography are less well known. CEUS utilizes a purely intravascular contrast agent whilst elastography measures the degree of deformation or stiffness in various organs. Whilst their use individually may be limited; they may play a role in a multiparametric assessment. Mirroring the overall trends in critical care ultrasound development, abdominal ultrasound assessment is best integrated in a holistic approach and adapted to the individual patient.

Dexmedetomidine for Facilitating Mechanical Ventilation Extubation in Difficult-to-Wean ICU Patients: Systematic Review and Meta-Analysis of Clinical Trials.

BACKGROUND: Agitation and delirium are common in mechanically ventilated adult intensive care unit (ICU) patients and may contribute to delayed extubation times. Difficult-to-wean ICU patients have been associated with an increased risk of longer ICU length of stays and mortality. The purpose of this systematic review and meta-analysis is to evaluate the evidence of dexmedetomidine facilitating successful mechanical ventilation extubation in difficult-to-wean ICU patients and clinical outcomes. METHODS: A literature search was conducted using MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Global Health, Cochrane Central Register of Controlled Trials, Clinical Trial Registries, and the Health Technology Assessment Database from inception to December 5, 2019. Randomized controlled trials evaluating dexmedetomidine with the intended purpose to facilitate mechanical ventilation liberation in adult ICU patients (≥18 years) experiencing extubation failure were included. The primary outcome of time to extubation was evaluated using the weighted mean difference (WMD), with a random effects model. Secondary analyses included hospital and ICU length of stay, in-hospital mortality, hypotension, and bradycardia. RESULTS: A total of 6 trials (n = 306 patients) were included. Dexmedetomidine significantly reduced the time to extubation (WMD: -11.61 hours, 95% CI: -16.5 to -6.7, P = .005) and ICU length of stay (WMD: -3.04 days; 95% CI: -4.66 to -1.43). Hypotension risk was increased with dexmedetomidine (risk ratio [RR]: 1.62, 95% CI: 1.05-2.51), but there was no difference in bradycardia risk (RR: 3.98, 95% CI: 0.70-22.78). No differences were observed in mortality rates (RR: 1.30, 95% CI: 0.45-3.75) or hospital length of stay (WMD: -2.67 days; 95% CI: -7.73 to 2.39). CONCLUSIONS: Dexmedetomidine was associated with a significant reduction in the time to extubation and shorter ICU stay in difficult-to-wean ICU patients. Although hypotension risk was increased with dexmedetomidine, no differences in other clinical outcomes were observed.

Correction: Electronic Cognitive Screen Technology for Screening Older Adults With Dementia and Mild Cognitive Impairment in a Community Setting: Development and Validation Study.

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Robust forecasting using predictive generalized synchronization in reservoir computing.

Reservoir computers (RCs) are a class of recurrent neural networks (RNNs) that can be used for forecasting the future of observed time series data. As with all RNNs, selecting the hyperparameters in the network to yield excellent forecasting presents a challenge when training on new inputs. We analyze a method based on predictive generalized synchronization (PGS) that gives direction in designing and evaluating the architecture and hyperparameters of an RC. To determine the occurrences of PGS, we rely on the auxiliary method to provide a computationally efficient pre-training test that guides hyperparameter selection. We provide a metric for evaluating the RC using the reproduction of the input system's Lyapunov exponents that demonstrates robustness in prediction.

Perioperative management considerations in patients taking prescribed psychoactive medications (including those for depression and Parkinson's disease).

PURPOSE OF REVIEW: Given the number of drugs available in the anaesthetist's armamentarium, drug interactions need to be managed. This is particularly true of psychoactive medications which primarily act on the central nervous system, targeting neurotransmitter pathways often affected by anaesthetic agents. This review gives an overview of the potential interactions of commonly used psychoactive medications with anaesthetic agents and hence their perioperative considerations. As anaesthetists will already be very familiar with the benzodiazepines, they will not be discussed here. Electroconvulsive therapy will also not be discussed. RECENT FINDINGS: A wide range of psychoactive medications can interact with drugs commonly used in perioperative care including anaesthetic agents. There is limited clinical research into their effects and hence these interactions are based on known pharmacological actions. SUMMARY: A cautious, pragmatic approach is recommended when managing patients on psychoactive medications requiring anaesthesia as part of their medical care.

Assessing the Predictive Validity of Simple Dementia Risk Models in Harmonized Stroke Cohorts.

BACKGROUND AND PURPOSE: Stroke is associated with an increased risk of dementia. To assist in the early identification of individuals at high risk of future dementia, numerous prediction models have been developed for use in the general population. However, it is not known whether such models also provide accurate predictions among stroke patients. Therefore, the aim of this study was to determine whether existing dementia risk prediction models that were developed for use in the general population can also be applied to individuals with a history of stroke to predict poststroke dementia with equivalent predictive validity. METHODS: Data were harmonized from 4 stroke studies (follow-up range, ≈12-18 months poststroke) from Hong Kong, the United States, the Netherlands, and France. Regression analysis was used to test 3 risk prediction models: the Cardiovascular Risk Factors, Aging and Dementia score, the Australian National University Alzheimer Disease Risk Index, and the Brief Dementia Screening Indicator. Model performance or discrimination accuracy was assessed using the C statistic or area under the curve. Calibration was tested using the Grønnesby and Borgan and the goodness-of-fit tests. RESULTS: The predictive accuracy of the models varied but was generally low compared with the original development cohorts, with the Australian National University Alzheimer Disease Risk Index (C-statistic, 0.66) and the Brief Dementia Screening Indicator (C-statistic, 0.61) both performing better than the Cardiovascular Risk Factors, Aging and Dementia score (area under the curve, 0.53). CONCLUSIONS: Dementia risk prediction models developed for the general population do not perform well in individuals with stroke. Their poor performance could have been due to the need for additional or different predictors related to stroke and vascular risk factors or methodological differences across studies (eg, length of follow-up, age distribution). Future work is needed to develop simple and cost-effective risk prediction models specific to poststroke dementia.

Statin Lipophilicity and the Risk of Incident Heart Failure.

BACKGROUND: To compare the risk of incident heart failure (HF) between initiators of hydrophilic and lipophilic statins. METHODS: Using claims data for commercial health insurance program enrollees in the USA (2005-2014), we identified new initiators of hydrophilic or lipophilic statins. Follow-up for the primary outcome of incident HF began after a lag period of 1 year after statin initiation. The outcome was defined as 1 inpatient or 2 outpatient diagnosis codes for HF and the use of loop diuretics. Propensity scores (PS) were used to account for confounding. Hazard ratios (HR) for incident HF were computed separately for low and high-intensity statin users, and then pooled to provide dose-adjusted effect estimates. RESULTS: A total of 7,820,204 patients met all our inclusion criteria for statin initiation (hydrophilic and lipophilic statins). Mean age was 58 years, 40% had hypertension, and 23% had diabetes mellitus. After PS matching, there were 691,584 patients in the low-intensity statin group and 807,370 patients in the high-intensity statin group. After a median follow-up of 725 days (IQR 500-1,153),there were 8,389 cases of incident HF (incidence rate 4.5/1,000 person years, 95% confidence interval [CI] 4.4-4.6). The unadjusted HR for the risk of HF was 0.77 (95% CI 0.76-0.79) and the pooled adjusted HR for incident HF after PS matching was 0.94 (95% CI 0.90-0.98) for hydrophilic versus lipophilic statins. The HR for incident HF was 1.06 (95% CI 1.00-1.12) for hydrophilic versus lipophilic statins for the low-intensity statin group and 0.82 (95% CI 0.78-0.87) for the high-intensity statin group. In subgroup analyses, a similar trend persisted for those younger and older than 65 years and when comparing rosuvastatin with atorvastatin. CONCLUSION: In this observational cohort study, hydrophilic statins were associated with a modest risk reduction in incident HF as compared to lipophilic statins. Future research replicating these findings in different populations is recommended.