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Association of Neighborhood Socioeconomic Status With Withdrawal of Life-Sustaining Therapies After Intracerebral Hemorrhage

Melmed, Kara R; Lewis, Ariane; Kuohn, Lindsey; Marmo, Joanna; Rossan-Raghunath, Nirmala; Torres, Jose; Muralidharan, Rajanandini; Lord, Aaron S; Ishida, Koto; Frontera, Jennifer A
BACKGROUND AND OBJECTIVES/OBJECTIVE:Mortality after intracerebral hemorrhage (ICH) is common. Neighborhood socioeconomic status (nSES) is an important social determinant of health (SDoH) that can affect clinical outcome. We hypothesize that SDoH, including nSES, contribute to differences in withdrawal of life-sustaining therapies (WLSTs) and mortality in patients with ICH. METHODS:tests. We performed multivariable analysis using backward stepwise logistic regression. RESULTS:≤ 0.01 for both). In multivariable analysis adjusting for age and clinical severity scores, patients who lived in zip codes with high-income levels were more likely to have WLST (adjusted odds ratio [aOR] 1.88; 95% CI 1.29-2.74) and mortality before discharge (aOR 1.5; 95% CI 1.06-2.13). DISCUSSION/CONCLUSIONS:SDoH, including nSES, are associated with WLST after ICH. This has important implications for the care and management of patients with ICH.
PMID: 38237088
ISSN: 1526-632x
CID: 5624412

Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study

Yaghi, Shadi; Shu, Liqi; Mandel, Daniel M; Leon Guerrero, Christopher R; Henninger, Nils; Muppa, Jayachandra; Affan, Muhammad; Ul Haq Lodhi, Omair; Heldner, Mirjam R; Antonenko, Kateryna; Seiffge, David J; Arnold, Marcel; Salehi Omran, Setareh; Crandall, Ross Curtiss; Lester, Evan; Lopez Mena, Diego; Arauz, Antonio; Nehme, Ahmad; Boulanger, Marion; Touzé, Emmanuel; Sousa, João André; Sargento-Freitas, Joao; Barata, Vasco; Castro-Chaves, Paulo; Brito, Maria Teresa Álvares Pereira; Khan, Muhib; Mallick, Dania; Rothstein, Aaron; Khazaal, Ossama; Kaufmann, Josefin; Engelter, Stefan T; Traenka, Christopher; Aguiar de Sousa, Diana; Soares, Mafalda; Rosa, Sara Db; Zhou, Lily W; Gandhi, Preet; Field, Thalia S; Mancini, Steven; Metanis, Issa; Leker, Ronen R; Pan, Kelly; Dantu, Vishnu; Baumgartner, Karl Viktor; Burton, Tina M; Freiin von Rennenberg, Regina; Nolte, Christian H; Choi, Richard K; MacDonald, Jason A; Bavarsad Shahripour, Reza; Guo, Xiaofan; Ghannam, Malik; AlMajali, Mohammad; Samaniego, Edgar A; Sanchez, Sebastian; Rioux, Bastien; Zine-Eddine, Faycal; Poppe, Alexandre Y; Fonseca, Ana Catarina; Baptista, Maria; Cruz, Diana; Romoli, Michele; De Marco, Giovanna; Longoni, Marco; Keser, Zafer; Griffin, Kim J; Kuohn, Lindsey; Frontera, Jennifer A; Amar, Jordan; Giles, James A; Zedde, Marialuisa; Pascarella, Rosario; Grisendi, Ilaria; Nzwalo, Hipólito; Liebeskind, David S; Molaie, Amir M; Cavalier, Annie; Kam, Wayneho; Mac Grory, Brian; Al Kasab, Sami; Anadani, Mohammad; Kicielinski, Kimberly P; Eltatawy, Ali Rada; Chervak, Lina M; Chulluncuy-Rivas, Roberto; Aziz, Yasmin Ninette; Bakradze, Ekaterina; Tran, Thanh Lam; Rodrigo-Gisbert, Marc; Requena, Manuel; Saleh Velez, Faddi Ghassan; Ortiz Garcia, Jorge G; Muddasani, Varsha; de Havenon, Adam; Vishnu, Venugopalan Y; Yaddanapudi, Sridhara S; Adams, Latasha; Browngoehl, Abigail; Ranasinghe, Tamra; Dunston, Randy; Lynch, Zachary; Penckofer, Mary; Siegler, James E; Mayer, Silvia V; Willey, Joshua Z; Zubair, Adeel S; Cheng, Yee Kuang; Sharma, Richa; Marto, João Pedro; Mendes Ferreira, Vitor; Klein, Piers; Nguyen, Thanh N; Asad, Syed Daniyal; Sarwat, Zoha; Balabhadra, Anvesh; Patel, Shivam; Secchi, Thais Leite; Martins, Sheila Co; Mantovani, Gabriel Paulo; Kim, Young Dae; Krishnaiah, Balaji; Elangovan, Cheran; Lingam, Sivani; Qureshi, Abid Y; Fridman, Sebastian; Alvarado-Bolaños, Alonso; Khasiyev, Farid; Linares, Guillermo; Mannino, Marina; Terruso, Valeria; Vassilopoulou, Sofia; Tentolouris-Piperas, Vasileios; Martínez-Marino, Manuel; Carrasco Wall, Víctor A; Indraswari, Fransisca; El Jamal, Sleiman; Liu, Shilin; Alvi, Muhammad; Ali, Farman; Sarvath, Mohammed Madani; Morsi, Rami Z; Kass-Hout, Tareq; Shi, Feina; Zhang, Jinhua; Sokhi, Dilraj; Said, Jamil; Simpkins, Alexis N; Gomez, Roberto; Sen, Shayak; Ghani, Mohammad Ravi; Elnazeir, Marwa; Xiao, Han; Kala, Narendra Sharma; Khan, Farhan; Stretz, Christoph; Mohammadzadeh, Nahid; Goldstein, Eric D; Furie, Karen L
PMID: 38335240
ISSN: 1524-4628
CID: 5632012

Guidelines for Seizure Prophylaxis in Adults Hospitalized with Moderate-Severe Traumatic Brain Injury: A Clinical Practice Guideline for Health Care Professionals from the Neurocritical Care Society

Frontera, Jennifer A; Gilmore, Emily J; Johnson, Emily L; Olson, DaiWai; Rayi, Appaji; Tesoro, Eljim; Ullman, Jamie; Yuan, Yuhong; Zafar, Sahar F; Rowe, Shaun
BACKGROUND:There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASMs) in patients with moderate-severe traumatic brain injury (TBI). METHODS:We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with moderate-severe TBI (acute radiographic findings and requiring hospitalization). The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM versus no ASM be used in patients with moderate-severe TBI and no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? (3) If an ASM is used, should a long versus short (> 7 vs. ≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure, late seizure, adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations. RESULTS:The initial literature search yielded 1998 articles, of which 33 formed the basis of the recommendations: PICO 1: We did not detect any significant positive or negative effect of ASM compared to no ASM on the outcomes of early seizure, late seizure, adverse events, or mortality. PICO 2: We did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or mortality, though point estimates suggest fewer late seizures and fewer adverse events with LEV. PICO 3: There were no significant differences in early or late seizures with longer versus shorter ASM use, though cognitive outcomes and adverse events appear worse with protracted use. CONCLUSIONS:Based on GRADE criteria, we suggest that ASM or no ASM may be used in patients hospitalized with moderate-severe TBI (weak recommendation, low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days, weak recommendation, low quality of evidence).
PMID: 38316735
ISSN: 1556-0961
CID: 5632812

The American Society of Transplant Surgeons Consensus Statement on Normothermic Regional Perfusion

Wall, Anji E; Adams, Bradley L; Brubaker, Aleah; Chang, Cherylee W J; Croome, Kristopher P; Frontera, Jennifer; Gordon, Elisa; Hoffman, Jordan; Kaplan, Lewis J; Kumar, Deepali; Levisky, Josh; Miñambres, Eduardo; Parent, Brendan; Watson, Christopher; Zemmar, Ajmal; Pomfret, Elizabeth A
On June 3, 2023, the American Society of Transplant Surgeons convened a meeting in San Diego, California to (1) develop a consensus statement with supporting data on the ethical tenets of thoracoabdominal normothermic regional perfusion (NRP) and abdominal NRP; (2) provide guidelines for the standards of practice that should govern thoracoabdominal NRP and abdominal NRP; and (3) develop and implement a central database for the collection of NRP donor and recipient data in the United States. National and international leaders in the fields of neuroscience, transplantation, critical care, NRP, Organ Procurement Organizations, transplant centers, and donor families participated. The conference was designed to focus on the controversial issues of neurological flow and function in donation after circulatory death donors during NRP and propose technical standards necessary to ensure that this procedure is performed safely and effectively. This article discusses major topics and conclusions addressed at the meeting.
PMID: 38254280
ISSN: 1534-6080
CID: 5624742

Code ICH: A Call to Action

Li, Qi; Yakhkind, Aleksandra; Alexandrov, Anne W; Alexandrov, Andrei V; Anderson, Craig S; Dowlatshahi, Dar; Frontera, Jennifer A; Hemphill, J Claude; Ganti, Latha; Kellner, Chris; May, Casey; Morotti, Andrea; Parry-Jones, Adrian; Sheth, Kevin N; Steiner, Thorsten; Ziai, Wendy; Goldstein, Joshua N; Mayer, Stephan A
Intracerebral hemorrhage is the most serious type of stroke, leading to high rates of severe disability and mortality. Hematoma expansion is an independent predictor of poor functional outcome and is a compelling target for intervention. For decades, randomized trials aimed at decreasing hematoma expansion through single interventions have failed to meet their primary outcomes of statistically significant improvement in neurological outcomes. A wide range of evidence suggests that ultra-early bundled care, with multiple simultaneous interventions in the acute phase, offers the best hope of limiting hematoma expansion and improving functional recovery. Patients with intracerebral hemorrhage who fail to receive early aggressive care have worse outcomes, suggesting that an important treatment opportunity exists. This consensus statement puts forth a call to action to establish a protocol for Code ICH, similar to current strategies used for the management of acute ischemic stroke, through which early intervention, bundled care, and time-based metrics have substantially improved neurological outcomes. Based on current evidence, we advocate for the widespread adoption of an early bundle of care for patients with intracerebral hemorrhage focused on time-based metrics for blood pressure control and emergency reversal of anticoagulation, with the goal of optimizing the benefit of these already widely used interventions. We hope Code ICH will endure as a structural platform for continued innovation, standardization of best practices, and ongoing quality improvement for years to come.
PMID: 38099439
ISSN: 1524-4628
CID: 5588962

Optimal Dosing of Levetiracetam for Seizure Prophylaxis in Critically Ill Patients: A Prospective Observational Study

Valdes, Eduard; Fang, Taolin; Boffa, Michael; Frontera, Jennifer A
OBJECTIVES/OBJECTIVE:Critically ill patients eliminate levetiracetam (LEV) more rapidly than healthy controls, yet low doses are commonly used for seizure prophylaxis in the ICU setting. We compared the rates of achievement of target serum levels and new onset seizure (clinical and/or electrographic) among patients who received low (500 mg bid) versus high (750-1,000 mg bid) dose LEV. DESIGN/METHODS:Prospective, observational study. SETTING/METHODS:Tertiary care, academic center. PATIENTS/METHODS:We included patients who received prophylactic LEV following traumatic brain injury, intracerebral hemorrhage, spontaneous subarachnoid hemorrhage, or supratentorial neurosurgery between 2019 and 2021. Patients with a history of seizure, antiseizure medication use, or renal failure requiring dialysis were excluded. INTERVENTIONS/METHODS:None. MEASUREMENTS/METHODS:LEV levels were obtained at steady state. The impact of low-dose versus high-dose LEV on the primary outcome of target LEV levels (12-46 μg/mL), and the secondary outcome of clinical and/or electrographic seizure, were assessed using multivariable logistic regression analyses adjusting for age, LEV loading dose, BMI, primary diagnosis and creatinine clearance (CrCl). MAIN RESULTS/RESULTS:Of the 205 subjects included in analyses, n = 106 (52%) received LEV 500 mg bid (median 13 mg/kg/d), and n = 99 (48%) received LEV 750-1,000 mg bid (median 25 mg/kg/d). Overall, 111 of 205 patients (54%) achieved target levels: 48 (45%) from the low-dose group versus 63 (64%) from the high-dose group (odds ratio [OR] 2.1; 95% CI, 1.1-3.7; p = 0.009). In multivariable analyses, high-dose LEV predicted target levels (adjusted OR [aOR] 2.23; 95% CI, 1.16-4.27; p = 0.016), and was associated with lower seizure odds (aOR 0.32; 95% CI, 0.13-0.82; p = 0.018) after adjusting for age, loading dose, BMI, diagnosis, and CrCl. CONCLUSIONS:Underdosing of LEV was common, with only 54% of patients achieving target serum levels. Higher doses (750-1,000 mg bid) were more than twice as likely to lead to optimal drug levels and reduced the odds of seizure by 68% compared with low-dose regimens (500 mg bid).
PMID: 37734033
ISSN: 1530-0293
CID: 5613032

Factors Associated With Anxiety After Hemorrhagic Stroke

Olivera, Anlys; Ecker, Sarah; Lord, Aaron; Gurin, Lindsey; Ishida, Koto; Melmed, Kara; Torres, Jose; Zhang, Cen; Frontera, Jennifer; Lewis, Ariane
OBJECTIVE/UNASSIGNED:A significant number of patients develop anxiety after stroke. The objective of this study was to identify risk factors for anxiety after hemorrhagic stroke that may facilitate diagnosis and treatment. METHODS/UNASSIGNED:Patients admitted between January 2015 and February 2021 with nontraumatic hemorrhagic stroke (intracerebral [ICH] or subarachnoid [SAH] hemorrhage) were assessed telephonically 3 and 12 months after stroke with the Quality of Life in Neurological Disorders Anxiety Short Form to evaluate the relationships between poststroke anxiety (T score >50) and preclinical social and neuropsychiatric history, systemic and neurological illness severity, and in-hospital complications. RESULTS/UNASSIGNED:Of 71 patients who completed the 3-month assessment, 28 (39%) had anxiety. There was a difference in Glasgow Coma Scale (GCS) scores on admission between patients with anxiety (median=14, interquartile range [IQR]=12-15) and those without anxiety (median=15, IQR=14-15) (p=0.034), and the incidence of anxiety was higher among patients with ICH (50%) than among those with SAH (20%) (p=0.021). Among patients with ICH, anxiety was associated with larger median ICH volume (25 cc [IQR=8-46] versus 8 cc [IQR=3-13], p=0.021) and higher median ICH score (2 [IQR=1-3] versus 1 [IQR=0-1], p=0.037). On multivariable analysis with GCS score, hemorrhage type, and neuropsychiatric history, only hemorrhage type remained significant (odds ratio=3.77, 95% CI=1.19-12.05, p=0.024). Of the 39 patients who completed the 12-month assessment, 12 (31%) had anxiety, and there was a difference in mean National Institutes of Health Stroke Scale scores between patients with (5 [IQR=3-12]) and without (2 [IQR=0-4]) anxiety (p=0.045). There was fair agreement (κ=0.38) between the presence of anxiety at 3 and 12 months. CONCLUSIONS/UNASSIGNED:Hemorrhage characteristics and factors assessed with neurological examination on admission are associated with the development of poststroke anxiety.
PMID: 37667629
ISSN: 1545-7222
CID: 5626372

Poor Accuracy of Manually Derived Head Computed Tomography Parameters in Predicting Intracranial Hypertension After Nontraumatic Intracranial Hemorrhage

Frontera, Jennifer A; Fang, Taolin; Grayson, Kammi; Lalchan, Rebecca; Dickstein, Leah; Hussain, M Shazam; Kahn, D Ethan; Lord, Aaron S; Mazzuchin, Daniel; Melmed, Kara R; Rutledge, Caleb; Zhou, Ting; Lewis, Ariane
BACKGROUND:The utility of head computed tomography (CT) in predicting elevated intracranial pressure (ICP) is known to be limited in traumatic brain injury; however, few data exist in patients with spontaneous intracranial hemorrhage. METHODS:We conducted a retrospective review of prospectively collected data in patients with nontraumatic intracranial hemorrhage (subarachnoid hemorrhage [SAH] or intraparenchymal hemorrhage [IPH]) who underwent external ventricular drain (EVD) placement. Head CT scans performed immediately prior to EVD placement were quantitatively reviewed for features suggestive of elevated ICP, including temporal horn diameter, bicaudate index, basal cistern effacement, midline shift, and global cerebral edema. The modified Fisher score (mFS), intraventricular hemorrhage score, and IPH volume were also measured, as applicable. We calculated the accuracy, positive predictive value (PPV), and negative predictive value (NPV) of these radiographic features for the coprimary outcomes of elevated ICP (> 20 mm Hg) at the time of EVD placement and at any time during the hospital stay. Multivariable backward stepwise logistic regression analysis was performed to identify significant radiographic factors associated with elevated ICP. RESULTS:Of 608 patients with intracranial hemorrhages enrolled during the study time frame, 243 (40%) received an EVD and 165 (n = 107 SAH, n = 58 IPH) had a preplacement head CT scan available for rating. Elevated opening pressure and elevated ICP during hospitalization were recorded in 48 of 152 (29%) and 103 of 165 (62%), respectively. The presence of ≥ 1 radiographic feature had only 32% accuracy for identifying elevated opening pressure (PPV 30%, NPV 58%, area under the curve [AUC] 0.537, 95% asymptotic confidence interval [CI] 0.436-0.637, P = 0.466) and 59% accuracy for predicting elevated ICP during hospitalization (PPV 63%, NPV 40%, AUC 0.514, 95% asymptotic CI 0.391-0.638, P = 0.820). There was no significant association between the number of radiographic features and ICP elevation. Head CT scans without any features suggestive of elevated ICP occurred in 25 of 165 (15%) patients. However, 10 of 25 (40%) of these patients had elevated opening pressure, and 15 of 25 (60%) had elevated ICP during their hospital stay. In multivariable models, mFS (adjusted odds ratio [aOR] 1.36, 95% CI 1.10-1.68) and global cerebral edema (aOR 2.93, 95% CI 1.27-6.75) were significantly associated with elevated ICP; however, their accuracies were only 69% and 60%, respectively. All other individual radiographic features had accuracies between 38 and 58% for identifying intracranial hypertension. CONCLUSIONS:More than 50% of patients with spontaneous intracranial hemorrhage without radiographic features suggestive of elevated ICP actually had ICP > 20 mm Hg during EVD placement or their hospital stay. Morphological head CT findings were only 32% and 59% accurate in identifying elevated opening pressure and ICP elevation during hospitalization, respectively.
PMID: 36577900
ISSN: 1556-0961
CID: 5409662

Evaluation and treatment approaches for neurological post-acute sequelae of COVID-19: A consensus statement and scoping review from the global COVID-19 neuro research coalition

Frontera, Jennifer A; Guekht, Alla; Allegri, Ricardo F; Ashraf, Mariam; Baykan, Betül; Crivelli, Lucía; Easton, Ava; Garcia-Azorin, David; Helbok, Raimund; Joshi, Jatin; Koehn, Julia; Koralnik, Igor; Netravathi, M; Michael, Benedict; Nilo, Annacarmen; Özge, Aynur; Padda, Karanbir; Pellitteri, Gaia; Prasad, Kameshwar; Romozzi, Marina; Saylor, Deanna; Seed, Adam; Thakur, Kiran; Uluduz, Derya; Vogrig, Alberto; Welte, Tamara M; Westenberg, Erica; Zhuravlev, Dmitry; Zinchuk, Mikhail; Winkler, Andrea S
Post-acute neurological sequelae of COVID-19 affect millions of people worldwide, yet little data is available to guide treatment strategies for the most common symptoms. We conducted a scoping review of PubMed/Medline from 1/1/2020-4/1/2023 to identify studies addressing diagnosis and treatment of the most common post-acute neurological sequelae of COVID-19 including: cognitive impairment, sleep disorders, headache, dizziness/lightheadedness, fatigue, weakness, numbness/pain, anxiety, depression and post-traumatic stress disorder. Utilizing the available literature and international disease-specific society guidelines, we constructed symptom-based differential diagnoses, evaluation and management paradigms. This pragmatic, evidence-based consensus document may serve as a guide for a holistic approach to post-COVID neurological care and will complement future clinical trials by outlining best practices in the evaluation and treatment of post-acute neurological signs/symptoms.
PMID: 37856998
ISSN: 1878-5883
CID: 5611562

Thoracoabdominal normothermic regional perfusion in donation after circulatory death does not restore brain blood flow

Frontera, Jennifer A; Lewis, Ariane; James, Les; Melmed, Kara; Parent, Brendan; Raz, Eytan; Hussain, Syed T; Smith, Deane E; Moazami, Nader
Use of thoracoabdominal normothermic regional perfusion (TA-NRP) during donation after circulatory death (DCD) is an important advance in organ donation. Prior to establishing TA-NRP, the brachiocephalic, left carotid, and left subclavian arteries are ligated, thereby eliminating anterograde brain blood flow via the carotid and vertebral arteries. While theoretical concerns have been voiced that TA-NRP after DCD may restore brain blood flow via collaterals, there have been no studies to confirm or refute this possibility. We evaluated brain blood flow using intraoperative transcranial Doppler (TCD) in two DCD TA-NRP cases. Pre-extubation, anterior and posterior circulation brain blood flow waveforms were present in both cases, similar to the waveforms detected in a control patient on mechanical circulatory support undergoing cardiothoracic surgery. Following declaration of death and initiation of TA-NRP, no brain blood flow was detected in either case. Additionally, there was absence of brainstem reflexes, no response to noxious stimuli and no respiratory effort. These TCD results demonstrate that DCD with TA-NRP did not restore brain blood flow.
PMID: 37211334
ISSN: 1557-3117
CID: 5543542