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1.
J Intensive Care Med ; : 8850666241253541, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38778678

ABSTRACT

Purpose: The purpose of this study was to evaluate rates of delirium or coma-free days between continuous infusion sedative-dose ketamine and continuous infusion benzodiazepines in critically ill patients. Materials and Methods: In this single-center, retrospective cohort adult patients were screened for inclusion if they received continuous infusions of either sedative-dose ketamine or benzodiazepines (lorazepam or midazolam) for at least 24 h, were mechanically ventilated for at least 48 h and admitted to the intensive care unit of a large quaternary academic center between 5/5/2018 and 12/1/2021. Results: A total of 165 patients were included with 64 patients in the ketamine group and 101 patients in the benzodiazepine group (lorazepam n = 35, midazolam n = 78). The primary outcome of median (IQR) delirium or coma-free days within the first 28 days of hospitalization was 1.2 (0.0, 3.7) for ketamine and 1.8 (0.7, 4.6) for benzodiazepines (p = 0.13). Patients in the ketamine arm spent a significantly lower proportion of time with RASS -3 to +4, received significantly higher doses and longer durations of propofol and fentanyl infusions, and had a significantly longer intensive care unit length of stay. Conclusions: The use of sedative-dose ketamine had no difference in delirium or coma-free days compared to benzodiazepines.

3.
Neurology ; 102(10): e209386, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38710005

ABSTRACT

BACKGROUND AND OBJECTIVES: Updated criteria for the clinical-MRI diagnosis of cerebral amyloid angiopathy (CAA) have recently been proposed. However, their performance in individuals without symptomatic intracerebral hemorrhage (ICH) presentations is less defined. We aimed to assess the diagnostic performance of the Boston criteria version 2.0 for CAA diagnosis in a cohort of individuals ranging from cognitively normal to dementia in the community and memory clinic settings. METHODS: Fifty-four participants from the Mayo Clinic Study of Aging or Alzheimer's Disease Research Center were included if they had an antemortem MRI with gradient-recall echo sequences and a brain autopsy with CAA evaluation. Performance of the Boston criteria v2.0 was compared with v1.5 using histopathologically verified CAA as the reference standard. RESULTS: The median age at MRI was 75 years (interquartile range 65-80) with 28/54 participants having histopathologically verified CAA (i.e., moderate-to-severe CAA in at least 1 lobar region). The sensitivity and specificity of the Boston criteria v2.0 were 28.6% (95% CI 13.2%-48.7%) and 65.3% (95% CI 44.3%-82.8%) for probable CAA diagnosis (area under the receiver operating characteristic curve [AUC] 0.47) and 75.0% (55.1-89.3) and 38.5% (20.2-59.4) for any CAA diagnosis (possible + probable; AUC 0.57), respectively. The v2.0 Boston criteria were not superior in performance compared with the prior v1.5 criteria for either CAA diagnostic category. DISCUSSION: The Boston criteria v2.0 have low accuracy in patients who are asymptomatic or only have cognitive symptoms. Additional biomarkers need to be explored to optimize CAA diagnosis in this population.


Subject(s)
Cerebral Amyloid Angiopathy , Magnetic Resonance Imaging , Humans , Cerebral Amyloid Angiopathy/diagnostic imaging , Cerebral Amyloid Angiopathy/pathology , Aged , Female , Male , Magnetic Resonance Imaging/standards , Aged, 80 and over , Sensitivity and Specificity , Brain/diagnostic imaging , Brain/pathology , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/pathology
4.
J Stroke Cerebrovasc Dis ; 33(6): 107716, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38604350

ABSTRACT

OBJECTIVES: Stroke is a leading cause of mortality and disability globally, with limited treatment options available for acute ischemic stroke (AIS) patients. Type 2 diabetes mellitus (T2DM) is not only widespread but also a known risk factor for stroke. Our meta-analysis aims to assess the influence of pre-stroke metformin use on the clinical outcomes in AIS patients with T2DM. MATERIALS AND METHODS: We conducted this study following PRISMA guidelines, searching the following databases: Medline, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials up to February 29, 2024. All studies providing separate data on AIS patients using metformin were included, and statistical analysis was conducted using R software to pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: Out of 1051 studies, 7 met the inclusion criteria for our meta-analysis with a total of 11589 diabetic patients, including 5445 patients taking metformin and 6144 diabetic patients in the non-metformin group. Compared to the non-metformin group, the metformin group had a significantly higher rate of mRS 0-2 score at discharge (OR 1.56; 95% CI 1.25:1.95; p=< 0.01) and a lower rate of 90-day mortality (OR 0.51; 95% CI 0.42:0.61; p=< 0.01), with no significant difference in sICH (OR 0.88; 95% CI 0.47:1.64; p= 0.68) between the two groups. CONCLUSIONS: Our meta-analysis demonstrated that pre-stroke metformin use is associated with higher functional independence and lower mortality in AIS patients with T2DM.


Subject(s)
Diabetes Mellitus, Type 2 , Hypoglycemic Agents , Ischemic Stroke , Metformin , Humans , Metformin/therapeutic use , Metformin/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/complications , Ischemic Stroke/mortality , Ischemic Stroke/diagnosis , Ischemic Stroke/drug therapy , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Treatment Outcome , Risk Factors , Male , Aged , Female , Middle Aged , Risk Assessment , Time Factors , Recovery of Function , Disability Evaluation , Aged, 80 and over , Functional Status
5.
J Neurol ; 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658432

ABSTRACT

BACKGROUND: Mechanical Thrombectomy (MT) has improved outcomes in acute ischemic stroke (AIS) due to Large Vessel Obstruction (LVO). However, there is limited data on the safety and outcomes of MT in AIS patients with thrombocytopenia. This study aims to assess the efficacy and safety of MT in this population. METHODS: Following the PRISMA guidelines, a comprehensive systematic review was conducted using PubMed, Embase, Web of Science, and Scopus. Studies meeting inclusion criteria underwent rigorous risk of bias assessment using the ROBINS-I tool. We compared outcomes between patients with and without thrombocytopenia undergoing MT. Using the R software version 4.3.1, meta-analyses were conducted employing random-effect models. RESULTS: This meta-analysis encompassed data from 5 studies. Thrombocytopenic AIS patients who underwent MT (n = 974) exhibited lower rates of functional independence (OR 0.83, 95% CI 0.71-0.98; p = 0.030) compared to patients with normal platelet counts (n = 2036). In addition, the thrombocytopenic group experienced higher mortality as compared to the group with normal platelet counts (OR 1.76, 95% CI 1.26-2.45; p < 0.001). Rates of sICH were found to be similar between groups (OR 1.20, 95% CI 0.74-1.93; p = 0.456), as were rates of successful recanalization (OR 0.94, 95% CI 0.47-1.87; p = 0.863). Lastly, no significant differences were observed in procedure times between thrombocytopenic and non-thrombocytopenic groups. CONCLUSION: As compared to patients without thrombocytopenia, thrombocytopenic AIS patients undergoing MT displayed lower functional independence and higher mortality rates, with no significant differences in sICH or successful recanalization.

6.
Neurosurgery ; 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38529956

ABSTRACT

Moderate traumatic brain injury (TBI) is a diagnosis that describes diverse patients with heterogeneity of primary injuries. Defined by a Glasgow Coma Scale between 9 and 12, this category includes patients who may neurologically worsen and require increasing intensive care resources and/or emergency neurosurgery. Despite the unique characteristics of these patients, there have not been specific guidelines published before this effort to support decision-making in these patients. A Delphi consensus group from the Latin American Brain Injury Consortium was established to generate recommendations related to the definition and categorization of moderate TBI. Before an in-person meeting, a systematic review of the literature was performed identifying evidence relevant to planned topics. Blinded voting assessed support for each recommendation. A priori the threshold for consensus was set at 80% agreement. Nine PICOT questions were generated by the panel, including definition, categorization, grouping, and diagnosis of moderate TBI. Here, we report the results of our work including relevant consensus statements and discussion for each question. Moderate TBI is an entity for which there is little published evidence available supporting definition, diagnosis, and management. Recommendations based on experts' opinion were informed by available evidence and aim to refine the definition and categorization of moderate TBI. Further studies evaluating the impact of these recommendations will be required.

8.
Interv Neuroradiol ; : 15910199241236329, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38425287

ABSTRACT

BACKGROUND: Mechanical thrombectomy (MT) is a safe and effective treatment option for acute ischemic stroke due to large vessel occlusion. To investigate differences in outcomes between patients receiving left-sided and right-sided MT, we performed a systematic review and meta-analysis. METHODS: A systematic literature review was performed using Embase, PubMed, Scopus, and Web of Science databases. Additional literature was searched for manually. Studies reporting safety and efficacy metrics for MT were included. Data regarding the modified Rankin scale (mRS), thrombolysis in cerebral infarction (TICI), symptomatic intracranial hemorrhage (sICH), and 90-day mortality were included. A random-effects model was used to calculate pooled odds ratios (ORs), mean differences (MDs), and 95% confidence intervals (CIs). RESULTS: The literature search yielded 13 reports consisting of 19 studies ranging from 98 to 5590 patients. Patients presenting with left-sided stroke had a National Institutes of health stroke scale score 2.89 greater than patients presenting with right-sided stroke (MD = 2.89; 95% CI = 2.09-3.68; P-value < 0.001). There were no differences between left-sided and right-sided MT patients for mRS 0-2 (OR = 0.94; 95% CI = 0.85-1.04; P-value = 0.224), TICI 2b-3 (OR = 1.05; 95% CI = 0.88-1.25; P-value = 0.598), sICH (OR = 0.83; 95% CI = 0.61-1.14; P-value = 0.255), or 90-day mortality (OR = 1.06; 95% CI = 0.84-1.33; P-value = 0.610). CONCLUSIONS: There does not appear to be a difference in outcomes for patients undergoing left-sided or right-sided thrombectomy.

9.
JAMA Netw Open ; 7(2): e240179, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38386320

ABSTRACT

Importance: Endovascular thrombectomy (EVT) is standard treatment for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO), but optimal post-EVT blood pressure (BP) control remains debated. Objective: To assess the association of different systolic BP targets following EVT with functional outcomes, mortality, and complications in patients with AIS due to LVO. Data Sources: Systematic review and meta-analysis of databases (PubMed, Embase, Web of Science, Scopus, and Cochrane Library) to September 8, 2023. Study Selection: Inclusion criteria consisted of randomized clinical trials examining post-EVT management of systolic BP in patients with AIS and LVO comparing intensive vs conventional targets. Nonrandomized studies, observational studies, noninterventional trials, meeting abstracts, duplicate studies, studies with overlapping data, and non-English language studies were excluded. Two authors independently applied these criteria through a blinded review, with discrepancies resolved through consensus. The risk of bias in the included studies was assessed using the revised tool for assessing risk of bias in randomized trials. Data Extraction and Synthesis: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Three authors extracted data regarding study characteristics, baseline patient data, and outcomes of interest. The pooled data were analyzed using a random-effects meta-analysis. Main Outcomes and Measures: Rates of functional independence, 90-day mortality, symptomatic intracranial hemorrhage, and hypotensive events. Results: A total of 4 randomized clinical trials with 1571 initially enrolled patients were included in the analysis. Lower functional independence rates were observed in the intensive control group (relative risk [RR], 0.81 [95% CI, 0.67-0.98]). No significant differences were found in 90-day mortality (RR, 1.18 [95% CI, 0.92-1.52]), symptomatic intracranial hemorrhage (RR, 1.12 [95% CI, 0.75-1.67]), or hypotensive events (RR, 1.80 [95% CI, 0.37-8.76]). There was minimal heterogeneity among the studies included in the functional independence outcome (I2 = 13% and τ2 = 0.003), which was absent among other outcomes (I2 = 0 and τ2 = 0). Conclusions and Relevance: These findings suggest that intensive post-EVT BP reduction does not yield benefits and may carry risks. While awaiting the results of additional ongoing trials, a conservative BP management strategy after endovascular recanalization is favored in daily practice.


Subject(s)
Ischemic Stroke , Vascular Diseases , Humans , Blood Pressure , Ischemic Stroke/surgery , Thrombectomy , Intracranial Hemorrhages/surgery , Randomized Controlled Trials as Topic
10.
Interv Neuroradiol ; : 15910199231224826, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38179678

ABSTRACT

BACKGROUND: The modified Rankin Scale (mRS) score of ≤2 (functional independence) has been the most common primary endpoint of modern mechanical thrombectomy (MT) trials. However, unlike mRS 0-1, mRS score of 2 indicates disability. An important proportion of the mRS 2 patients are home dependent and report a significant decrease in their quality of life. PURPOSE: To investigate excellent outcome (mRS 0-1) rates after MT. METHODS: We systematically searched Ovid MEDLINE, Ovid EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science databases. Randomized controlled trials (RCTs) investigating the role of modern MT in acute ischemic stroke were screened. Posterior circulation and large-core infarct trials were excluded from the study. The data regarding excellent outcomes (mRS: 0-1), functional independence (mRS: 0-2), and reperfusion were collected. RESULTS: Twenty-two RCTs comprising 5692 patients were included in the meta-analysis. The overall mRS 0-1 rate was 31.24% (95% CI = 26.95-36.2). The rate of successful reperfusion was 81.8% (95% CI = 77.93-85.86). MT achieved significantly higher rates of mRS 0-1 compared to standard care alone (OR = 2.04; 95% CI = 1.64-2.55; P-value < 0.001), with no heterogeneity detected among studies (I2= 0%; P-value = 0.52). The direct MT and MT plus intravenous thrombolytic treatment groups' excellent outcome rates were comparable (OR = 0.98; 95% CI = 0.82-1.18; P-value = 0.863). Also, aspiration and stent retriever thrombectomy techniques provided similar excellent outcome rates (OR = 0.76; 95% CI = 0.55-1.05; P-value = 0.141). CONCLUSIONS: Our results prove the additional benefit of MT over standard care, using a stricter definition for favorable functional outcome. Nearly one-third of patients presenting with large artery occlusion and treated with MT had no disability at 90 days. While this is remarkable, our results also indicate that reperfusion alone is often not enough to prevent disability and underline the need for better neuroprotection strategies.

11.
J Intensive Care Med ; 39(5): 455-464, 2024 May.
Article in English | MEDLINE | ID: mdl-37964551

ABSTRACT

OBJECTIVE: The Pulmonary Embolism Severity Index (PESI) and simplified PESI (sPESI) predict mortality for patients with PE. We compared PESI/sPESI to the Acute Physiology and Chronic Health Evaluation IV (APACHE-IV) in predicting mortality in patients with PE admitted to the intensive care unit (ICU). Additionally, we assessed the performance of a novel ICU-sPESI score created by adding three clinical variables associated with acuity of PE presentation (intubation, confusion [altered mental status], use of vasoactive infusions) to sPESI. MATERIALS AND METHODS: Using the eICU Collaborative Research Database from 2014 to 2015, we conducted a large retrospective cohort study of adult patients admitted to the ICU with a primary diagnosis of PE. We calculated APACHE-IV, PESI, sPESI, and ICU-sPESI scores and compared their performance for predicting in-hospital mortality using area under the receiver operating characteristic (AUROC) curve. Score thresholds for >99% negative predictive values (NPV) were calculated for each score. Survival was estimated using the Kaplan-Meier method. RESULTS: We included 1424 PE cases. In-hospital mortality was 6.3% [95% CI: 5.1%-7.6%]. AUROC for APACHE-IV, PESI, and sPESI were 0.870, 0.848, and 0.777, respectively. APACHE-IV and PESI outperformed sPESI (P < 0.01 for both comparisons), while APACHE-IV and PESI demonstrated similar performance (P = 0.322). The ICU-sPESI performance was similar to APACHE-IV and PESI (AUROC = 0.847; AUROC comparison: APACHE-IV vs ICU-sPESI: P = 0.396; PESI vs ICU-sPESI: P = 0.945). Hospital mortality for ICU-sPESI scores 0-2 was 1.1%, and for scores 3, 4, 5, 6, and ≥7 was 8.6%, 11.7%, 29.2%, 37.5%, and 76.9%, respectively. Score thresholds for >99% NPV were ≤48 for APACHE-IV, ≤115 for PESI, and 0 points for sPESI and ICU-sPESI. CONCLUSIONS: By accounting for severity of PE presentation, our newly proposed ICU-sPESI score provided improved PE mortality prediction compared to the original sPESI score and offered excellent discrimination of mortality risk.


Subject(s)
Intensive Care Units , Pulmonary Embolism , Adult , Humans , Risk Assessment , Retrospective Studies , Prognosis , Severity of Illness Index , Hospitals , Pulmonary Embolism/complications , Predictive Value of Tests
12.
J Stroke Cerebrovasc Dis ; 33(1): 107489, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37980845

ABSTRACT

BACKGROUND AND PURPOSE: Predicting patient recovery and discharge disposition following mechanical thrombectomy remains a challenge in patients with ischemic stroke. Machine learning offers a promising prognostication approach assisting in personalized post-thrombectomy care plans and resource allocation. As a large national database, National Inpatient Sample (NIS), contain valuable insights amenable to data-mining. The study aimed to develop and evaluate ML models predicting hospital discharge disposition with a focus on demographic, socioeconomic and hospital characteristics. MATERIALS AND METHODS: The NIS dataset (2006-2019) was used, including 4956 patients diagnosed with ischemic stroke who underwent thrombectomy. Demographics, hospital characteristics, and Elixhauser comorbidity indices were recorded. Feature extraction, processing, and selection were performed using Python, with Maximum Relevance - Minimum Redundancy (MRMR) applied for dimensionality reduction. ML models were developed and benchmarked prior to interpretation of the best model using Shapley Additive exPlanations (SHAP). RESULTS: The multilayer perceptron model outperformed others and achieved an AUROC of 0.81, accuracy of 77 %, F1-score of 0.48, precision of 0.64, and recall of 0.54. SHAP analysis identified the most important features for predicting discharge disposition as dysphagia and dysarthria, NIHSS, age, primary payer (Medicare), cerebral edema, fluid and electrolyte disorders, complicated hypertension, primary payer (private insurance), intracranial hemorrhage, and thrombectomy alone. CONCLUSION: Machine learning modeling of NIS database shows potential in predicting hospital discharge disposition for inpatients with acute ischemic stroke following mechanical thrombectomy in the NIS database. Insights gained from SHAP interpretation can inform targeted interventions and care plans, ultimately enhancing patient outcomes and resource allocation.


Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Humans , Aged , United States , Ischemic Stroke/diagnosis , Ischemic Stroke/therapy , Stroke/diagnosis , Stroke/therapy , Inpatients , Patient Discharge , Treatment Outcome , Medicare , Thrombectomy/adverse effects , Hospitals , Retrospective Studies , Brain Ischemia/diagnosis , Brain Ischemia/therapy
13.
medRxiv ; 2023 Nov 10.
Article in English | MEDLINE | ID: mdl-37986913

ABSTRACT

BACKGROUND: Updated criteria for the clinical-MRI diagnosis of cerebral amyloid angiopathy (CAA) have recently been proposed. However, their performance in individuals without intracerebral hemorrhage (ICH) or transient focal neurological episodes (TFNE) is unknown. We assessed the diagnostic performance of the Boston criteria version 2.0 for CAA diagnosis in a cohort of individuals presenting without symptomatic ICH. METHODS: Fifty-four participants from the Mayo Clinic Study of Aging or Alzheimer's Disease Research Center were included if they had an antemortem MRI with gradient-recall echo sequences and a brain autopsy with CAA evaluation. Performance of the Boston criteria v2.0 was compared to v1.5 using histopathologically verified CAA as the reference standard. RESULTS: Median age at MRI was 75 years (IQR 65-80) with 28/54 participants having histopathologically verified CAA (i.e., moderate-to-severe CAA in at least 1 lobar region). The sensitivity and specificity of the Boston criteria v2.0 were 28.6% (95%CI: 13.2-48.7%) and 65.3% (95%CI: 44.3-82.8%) for probable CAA diagnosis (AUC 0.47) and 75.0% (55.1-89.3) and 38.5% (20.2-59.4) for any CAA diagnosis (possible + probable; AUC: 0.57), respectively. The v2.0 Boston criteria was not superior in performance compared to the prior v1.5 criteria for either CAA diagnostic category. CONCLUSIONS: The Boston criteria v2.0 have low accuracy in patients who are asymptomatic or only have cognitive symptoms.. Additional biomarkers need to be explored to optimize CAA diagnosis in this population.

14.
West J Emerg Med ; 24(5): 939-949, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37788035

ABSTRACT

Background: There are no randomized trials comparing andexanet alfa and 4 factor prothrombin complex concentrate (4F-PCC) for the treatment of factor Xa inhibitor (FXa-I)-associated bleeds, and observational studies lack important patient characteristics. We pursued this study to demonstrate the feasibility of acquiring relevant patient characteristics from electronic health records. Secondarily, we explored outcomes in patients with life-threatening FXa-I associated bleeds after adjusting for these variables. Methods: We conducted a multicenter, chart review of 100 consecutive adult patients with FXa-I associated intracerebral hemorrhage (50) or gastrointestinal bleeding (50) treated with andexanet alfa or 4F-PCC. We collected demographic, clinical, laboratory, and imaging data including time from last factor FXa-I dose and bleed onset. Results: Mean (SD) age was 75 (12) years; 34% were female. Estimated time from last FXa-I dose to bleed onset was present in most cases (76%), and patients treated with andexanet alfa and 4F-PCC were similar in baseline characteristics. Hemostatic efficacy was excellent/good in 88% and 76% of patients treated with andexanet alfa and 4F-PCC, respectively (P = 0.29). Rates of thrombotic events within 90 days were 14% and 16% in andexanet alfa and 4F-PCC patients, respectively (P = 0.80). Survival to hospital discharge was 92% and 76% in andexanet alfa and 4F-PCC patients, respectively (P = 0.25). Inclusion of an exploratory propensity score and treatment in a logistic regression model resulted in an odds ratio in favor of andexanet alfa of 2.01 (95% confidence interval 0.67-6.06) for excellent/good hemostatic efficacy, although the difference was not statistically significant. Conclusion: Important patient characteristics are often documented supporting the feasibility of a large observational study comparing real-life outcomes in patients with FXa-I-associated bleeds treated with andexanet alfa or 4F-PCC. The small sample size in the current study precluded definitive conclusions regarding the safety and efficacy of andexanet alfa or 4F-PCC in FXa-I-associated bleeds.


Subject(s)
Factor Xa Inhibitors , Hemostatics , Adult , Humans , Female , Aged , Male , Factor Xa Inhibitors/adverse effects , Retrospective Studies , Feasibility Studies , Fibrinolytic Agents , Gastrointestinal Hemorrhage/chemically induced , Gastrointestinal Hemorrhage/drug therapy
15.
JAMA Neurol ; 80(12): 1263-1264, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37902729

ABSTRACT

This Viewpoint argues, in keeping with current stroke management guidelines, that patients with mild, nondisabling strokes should not receive thrombolysis, even when presenting within the time window for treatment.


Subject(s)
Brain Ischemia , Stroke , Humans , Stroke/drug therapy , Fibrinolytic Agents/therapeutic use , Thrombolytic Therapy , Brain Ischemia/drug therapy
16.
Crit Care Explor ; 5(10): e0987, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37868026

ABSTRACT

IMPORTANCE: Protein binding of valproate varies among ICU patients, altering the biologically active free valproate concentration (VPAC). Free VPAC is measured at few laboratories and is often discordant with total VPAC. Existing equations to predict free VPAC are either not validated or are inaccurate in ICU patients. OBJECTIVES: We designed this study to derive and validate a novel equation to predict free VPAC using data from ICU patients and to compare its performance to published equations. DESIGN: Retrospective cohort study. SETTING: Two academic medical centers. PARTICIPANTS: Patients older than 18 years old with concomitant free and total VPACs measured in the ICU were included in the derivation cohort if admitted from 2014 to 2018, and the validation cohort if admitted from 2019 to 2022. MAIN OUTCOMES AND MEASURES: Multivariable linear regression was used to derive an equation to predict free VPAC. Modified Bland-Altman plots and the rate of therapeutic concordance between the measured and predicted free VPAC were compared. RESULTS: Demographics, median free and total VPACs, and valproate free fractions were similar among 115 patients in the derivation cohort and 147 patients in the validation cohort. The Bland-Altman plots showed the new equation performed better (bias, 0.3 [95% limits of agreement, -13.6 to 14.2]) than the Nasreddine (-9.2 [-26.5 to 8.2]), Kodama (-9.7 [-30.0 to 10.7]), Conde Giner (-7.9 [-24.9 to 9.1]), and Parent (-9.9 [-30.7 to 11.0]) equations, and similar to Doré (-2.0 [-16.0 to 11.9]). The Doré and new equations had the highest therapeutic concordance rate (73%). CONCLUSIONS AND RELEVANCE: For patients at risk of altered protein binding such as ICU patients, existing equations to predict free VPAC are discordant with measured free VPAC. A new equation had low bias but was imprecise. External validation should be performed to improve its precision and generalizability. Until then, monitoring free valproate is recommended during critical illness.

18.
Interv Neuroradiol ; : 15910199231206100, 2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37796821

ABSTRACT

BACKGROUND: Smoking represents a leading risk factor for acute ischemic stroke (AIS). Previous literature has described a "smoking paradox", wherein smokers experience better outcomes following intravenous thrombolysis for AIS. It is unclear whether such a phenomenon exists in smokers undergoing endovascular therapy (EVT) for AIS. To assess outcomes in smokers following EVT for AIS, we conducted a systematic review and meta-analysis. METHODS: Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, Embase Web of Science, and Scopus. Outcomes of interest included 90-day modified Rankin Scale (mRS) 0-2, thrombolysis in cerebral infarction (TICI) score 2b-3, symptomatic intracranial hemorrhage (sICH), and mortality. We calculated mean difference (MD), pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: Eight studies with 2633 patients comprised our analysis. On average, smokers were 10.14 years (MD = 10.14, [95% CI = -14.49 to -5.79], P-value < 0.001) younger than non-smokers. Smokers achieved mRS 0-2 (OR = 1.82, [95% CI, 1.34-2.48], P-value < 0.001) and TICI 2b-3 (OR = 1.61, [95% CI, 1.19-2.19], P-value = 0.002) at a higher rate than non-smokers. sICH rates were comparable between smokers and non-smokers (OR = 1.07, [95% CI, 0.62-1.85], P-value = 0.81). Smokers had a lower rate of 90-day mortality than non-smokers (OR = 0.54, [95% CI, 0.41-0.71], P-value < 0.001). CONCLUSIONS: In this meta-analysis of eight studies, we found that smokers with AIS undergoing EVT experienced better 90-day outcomes and higher rates of TICI 2b-3. This may be due to baseline differences between smokers and non-smokers, but future studies should explore alternative reasons that could explain this relationship between smoking and AIS treated with EVT.

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