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Potential of Transcranial Direct Current Stimulation in Alzheimer's Disease: Optimizing Trials Toward Clinical Use

Pilloni, Giuseppina; Charvet, Leigh E; Bikson, Marom; Palekar, Nikhil; Kim, Min-Jeong
Transcranial direct current stimulation (tDCS) is a safe and well-tolerated noninvasive method for stimulating the brain that is rapidly developing into a treatment method for various neurological and psychiatric conditions. In particular, there is growing evidence of a therapeutic role for tDCS in ameliorating or delaying the cognitive decline in Alzheimer's disease (AD). We provide a brief overview of the current development and application status of tDCS as a nonpharmacological therapeutic method for AD and mild cognitive impairment (MCI), summarize the levels of evidence, and identify the improvements needed for clinical applications. We also suggest future directions for large-scale controlled clinical trials of tDCS in AD and MCI, and emphasize the necessity of identifying the mechanistic targets to facilitate clinical applications.
PMCID:9262447
PMID: 35796264
ISSN: 1738-6586
CID: 5280512

Case Conference: The "Noise" of Medicine

Kister, Ilya; Biller, Jose
ORIGINAL:0015910
ISSN: 1474-7766
CID: 5308142

Tracking transitional probabilities and segmenting auditory sequences are dissociable processes in adults and neonates

Benjamin, Lucas; Fló, Ana; Palu, Marie; Naik, Shruti; Melloni, Lucia; Dehaene-Lambertz, Ghislaine
Since speech is a continuous stream with no systematic boundaries between words, how do pre-verbal infants manage to discover words? A proposed solution is that they might use the transitional probability between adjacent syllables, which drops at word boundaries. Here, we tested the limits of this mechanism by increasing the size of the word-unit to four syllables, and its automaticity by testing asleep neonates. Using markers of statistical learning in neonates' EEG, compared to adult behavioral performances in the same task, we confirmed that statistical learning is automatic enough to be efficient even in sleeping neonates. We also revealed that: (1) Successfully tracking transition probabilities (TP) in a sequence is not sufficient to segment it. (2) Prosodic cues, as subtle as subliminal pauses, enable to recover words segmenting capacities. (3) Adults' and neonates' capacities to segment streams seem remarkably similar despite the difference of maturation and expertise. Finally, we observed that learning increased the overall similarity of neural responses across infants during exposure to the stream, providing a novel neural marker to monitor learning. Thus, from birth, infants are equipped with adult-like tools, allowing them to extract small coherent word-like units from auditory streams, based on the combination of statistical analyses and auditory parsing cues. RESEARCH HIGHLIGHTS: Successfully tracking transitional probabilities in a sequence is not always sufficient to segment it. Word segmentation solely based on transitional probability is limited to bi- or tri-syllabic elements. Prosodic cues, as subtle as subliminal pauses, enable to recover chunking capacities in sleeping neonates and awake adults for quadriplets.
PMID: 35772033
ISSN: 1467-7687
CID: 5281302

Recent Use of Non-Vitamin K Antagonist Oral Anticoagulants and Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase [Comment]

Frontera, Jennifer A; Ahuja, Tania
PMID: 35727285
ISSN: 1538-3598
CID: 5281922

Assessment of Smartphone Apps for Common Neurologic Conditions (Headache, Insomnia, and Pain): Cross-sectional Study

Minen, Mia T; George, Alexis; Camacho, Erica; Yao, Leslie; Sahu, Ananya; Campbell, Maya; Soviero, Mia; Hossain, Quazi; Verma, Deepti; Torous, John
BACKGROUND:There are thousands of apps for individuals struggling with headache, insomnia, and pain, but it is difficult to establish which of these apps are best suited for patients' specific needs. If clinicians were to have access to a platform that would allow them to make an informed decision on the efficacy and feasibility of smartphone apps for patient care, they would feel confident in prescribing specific apps. OBJECTIVE:We sought to evaluate the quality of apps for some of the top common, disabling neurologic conditions (headache, insomnia, and pain) based on principles derived from the American Psychiatric Association's (APA) app evaluation model. METHODS:We used the Mobile Health Index and Navigation database and expanded upon the database's current supported conditions by adding 177 new app entries. Each app was rated for consistency with the APA's app evaluation model, which includes 105 objective questions based on the following 5 major classes of consideration: (1) accessibility, (2) privacy and security, (3) clinical foundation, (4) engagement style, and (5) interoperability. These characteristics were evaluated to gain a broader understanding of the significant features of each app category in comparison against a control group. RESULTS:Approximately 90% (187/201) of all apps evaluated were free to download, but only 50% (63/201) of headache- and pain-related apps were truly free. Most (87/106, 81%) sleep apps were not truly free to use. The apps had similar limitations with limited privacy, accessibility, and crisis management resources. For example, only 17% (35/201) of the apps were available in Spanish. The apps offered mostly self-help tools with little tailoring; symptom tracking was the most common feature in headache- (32/48, 67%) and pain-related apps (21/47, 45%), whereas mindfulness was the most common feature in sleep-related apps (73/106, 69%). CONCLUSIONS:Although there are many apps for headache, pain, and insomnia, all 3 types of apps have room for improvement around accessibility and privacy. Pain and headache apps share many common features, whereas insomnia apps offer mostly mindfulness-based resources. Given the many available apps to pick from, clinicians and patients should seek apps that offer the highest-quality features, such as complete privacy, remedial features, and the ability to download the app at no cost. These results suggest that there are many opportunities for the improvement of apps centered on headache, insomnia, and pain.
PMCID:9257611
PMID: 35727625
ISSN: 2291-5222
CID: 5278002

An overview of systematic reviews on the pharmacological randomized controlled trials for reducing intracranial pressure after traumatic brain injury

Kim, Sonya; Mortera, Marianne; Heyn, Patricia; Sood, Pallavi; Wen, Pey-Shan; Chen Wong, Diana; Tanveer, Sarah; Hu, Xiaolei
BACKGROUND/UNASSIGNED:There is a need for an overview of systematic reviews (SRs) examining randomized clinical trials (RCTs) of pharmacological interventions in the treatment of intracranial pressure (ICP) post-TBI. OBJECTIVES/UNASSIGNED:To summarize pharmacological effectiveness in decreasing ICP in SRs with RCTs and evaluate study quality. METHODS/UNASSIGNED:Comprehensive literature searches were conducted in MEDLINE, PubMed, EMBASE, PsycINFO, and Cochrane Library databases for English SRs through October 2020. Inclusion criteria were SRs with RCTs that examined pharmacological interventions to treat ICP in patients post-TBI. Data extracted were participant characteristics, pharmacological interventions, and ICP outcomes. Study quality was assessed with AMSTAR-2. RESULTS/UNASSIGNED:Eleven SRs between 2003 and 2020 were included. AMSTAR-2 ratings revealed 3/11 SRs of high quality. Pharmacological interventions included hyperosmolars, neuroprotectives, anesthetics, sedatives, and analgesics. Study samples ranged from 7 to 1282 patients. Hyperosmolar agents and sedatives were beneficial in lowering elevated ICP. High bolus dose opioids had a more deleterious effect on ICP. Neuroprotective agents did not show any effects in ICP management. RCT sample sizes and findings in the SRs varied. A lack of detailed data syntheses was noted. AMSTAR-2 analysis revealed moderate-to-high quality in most SRs. Future SRs may focus on streamlined reporting of dosing and clearer clinical recommendations. CONCLUSIONS/UNASSIGNED:PROSPERO-Registration: CRD42015017355.
PMID: 35708261
ISSN: 1362-301x
CID: 5249902

Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

Winkler, Thomas W; Rasheed, Humaira; Teumer, Alexander; Gorski, Mathias; Rowan, Bryce X; Stanzick, Kira J; Thomas, Laurent F; Tin, Adrienne; Hoppmann, Anselm; Chu, Audrey Y; Tayo, Bamidele; Thio, Chris H L; Cusi, Daniele; Chai, Jin-Fang; Sieber, Karsten B; Horn, Katrin; Li, Man; Scholz, Markus; Cocca, Massimiliano; Wuttke, Matthias; van der Most, Peter J; Yang, Qiong; Ghasemi, Sahar; Nutile, Teresa; Li, Yong; Pontali, Giulia; Günther, Felix; Dehghan, Abbas; Correa, Adolfo; Parsa, Afshin; Feresin, Agnese; de Vries, Aiko P J; Zonderman, Alan B; Smith, Albert V; Oldehinkel, Albertine J; De Grandi, Alessandro; Rosenkranz, Alexander R; Franke, Andre; Teren, Andrej; Metspalu, Andres; Hicks, Andrew A; Morris, Andrew P; Tönjes, Anke; Morgan, Anna; Podgornaia, Anna I; Peters, Annette; Körner, Antje; Mahajan, Anubha; Campbell, Archie; Freedman, Barry I; Spedicati, Beatrice; Ponte, Belen; Schöttker, Ben; Brumpton, Ben; Banas, Bernhard; Krämer, Bernhard K; Jung, Bettina; Åsvold, Bjørn Olav; Smith, Blair H; Ning, Boting; Penninx, Brenda W J H; Vanderwerff, Brett R; Psaty, Bruce M; Kammerer, Candace M; Langefeld, Carl D; Hayward, Caroline; Spracklen, Cassandra N; Robinson-Cohen, Cassianne; Hartman, Catharina A; Lindgren, Cecilia M; Wang, Chaolong; Sabanayagam, Charumathi; Heng, Chew-Kiat; Lanzani, Chiara; Khor, Chiea-Chuen; Cheng, Ching-Yu; Fuchsberger, Christian; Gieger, Christian; Shaffer, Christian M; Schulz, Christina-Alexandra; Willer, Cristen J; Chasman, Daniel I; Gudbjartsson, Daniel F; Ruggiero, Daniela; Toniolo, Daniela; Czamara, Darina; Porteous, David J; Waterworth, Dawn M; Mascalzoni, Deborah; Mook-Kanamori, Dennis O; Reilly, Dermot F; Daw, E Warwick; Hofer, Edith; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P; Tai, E-Shyong; Catamo, Eulalia; Rizzi, Federica; Guo, Feng; Rivadeneira, Fernando; Guilianini, Franco; Sveinbjornsson, Gardar; Ehret, Georg; Waeber, Gerard; Biino, Ginevra; Girotto, Giorgia; Pistis, Giorgio; Nadkarni, Girish N; Delgado, Graciela E; Montgomery, Grant W; Snieder, Harold; Campbell, Harry; White, Harvey D; Gao, He; Stringham, Heather M; Schmidt, Helena; Li, Hengtong; Brenner, Hermann; Holm, Hilma; Kirsten, Holgen; Kramer, Holly; Rudan, Igor; Nolte, Ilja M; Tzoulaki, Ioanna; Olafsson, Isleifur; Martins, Jade; Cook, James P; Wilson, James F; Halbritter, Jan; Felix, Janine F; Divers, Jasmin; Kooner, Jaspal S; Lee, Jeannette Jen-Mai; O'Connell, Jeffrey; Rotter, Jerome I; Liu, Jianjun; Xu, Jie; Thiery, Joachim; Ärnlöv, Johan; Kuusisto, Johanna; Jakobsdottir, Johanna; Tremblay, Johanne; Chambers, John C; Whitfield, John B; Gaziano, John M; Marten, Jonathan; Coresh, Josef; Jonas, Jost B; Mychaleckyj, Josyf C; Christensen, Kaare; Eckardt, Kai-Uwe; Mohlke, Karen L; Endlich, Karlhans; Dittrich, Katalin; Ryan, Kathleen A; Rice, Kenneth M; Taylor, Kent D; Ho, Kevin; Nikus, Kjell; Matsuda, Koichi; Strauch, Konstantin; Miliku, Kozeta; Hveem, Kristian; Lind, Lars; Wallentin, Lars; Yerges-Armstrong, Laura M; Raffield, Laura M; Phillips, Lawrence S; Launer, Lenore J; Lyytikäinen, Leo-Pekka; Lange, Leslie A; Citterio, Lorena; Klaric, Lucija; Ikram, M Arfan; Ising, Marcus; Kleber, Marcus E; Francescatto, Margherita; Concas, Maria Pina; Ciullo, Marina; Piratsu, Mario; Orho-Melander, Marju; Laakso, Markku; Loeffler, Markus; Perola, Markus; de Borst, Martin H; Gögele, Martin; Bianca, Martina La; Lukas, Mary Ann; Feitosa, Mary F; Biggs, Mary L; Wojczynski, Mary K; Kavousi, Maryam; Kanai, Masahiro; Akiyama, Masato; Yasuda, Masayuki; Nauck, Matthias; Waldenberger, Melanie; Chee, Miao-Li; Chee, Miao-Ling; Boehnke, Michael; Preuss, Michael H; Stumvoll, Michael; Province, Michael A; Evans, Michele K; O'Donoghue, Michelle L; Kubo, Michiaki; Kähönen, Mika; Kastarinen, Mika; Nalls, Mike A; Kuokkanen, Mikko; Ghanbari, Mohsen; Bochud, Murielle; Josyula, Navya Shilpa; Martin, Nicholas G; Tan, Nicholas Y Q; Palmer, Nicholette D; Pirastu, Nicola; Schupf, Nicole; Verweij, Niek; Hutri-Kähönen, Nina; Mononen, Nina; Bansal, Nisha; Devuyst, Olivier; Melander, Olle; Raitakari, Olli T; Polasek, Ozren; Manunta, Paolo; Gasparini, Paolo; Mishra, Pashupati P; Sulem, Patrick; Magnusson, Patrik K E; Elliott, Paul; Ridker, Paul M; Hamet, Pavel; Svensson, Per O; Joshi, Peter K; Kovacs, Peter; Pramstaller, Peter P; Rossing, Peter; Vollenweider, Peter; van der Harst, Pim; Dorajoo, Rajkumar; Sim, Ralene Z H; Burkhardt, Ralph; Tao, Ran; Noordam, Raymond; Mägi, Reedik; Schmidt, Reinhold; de Mutsert, Renée; Rueedi, Rico; van Dam, Rob M; Carroll, Robert J; Gansevoort, Ron T; Loos, Ruth J F; Felicita, Sala Cinzia; Sedaghat, Sanaz; Padmanabhan, Sandosh; Freitag-Wolf, Sandra; Pendergrass, Sarah A; Graham, Sarah E; Gordon, Scott D; Hwang, Shih-Jen; Kerr, Shona M; Vaccargiu, Simona; Patil, Snehal B; Hallan, Stein; Bakker, Stephan J L; Lim, Su-Chi; Lucae, Susanne; Vogelezang, Suzanne; Bergmann, Sven; Corre, Tanguy; Ahluwalia, Tarunveer S; Lehtimäki, Terho; Boutin, Thibaud S; Meitinger, Thomas; Wong, Tien-Yin; Bergler, Tobias; Rabelink, Ton J; Esko, Tõnu; Haller, Toomas; Thorsteinsdottir, Unnur; Völker, Uwe; Foo, Valencia Hui Xian; Salomaa, Veikko; Vitart, Veronique; Giedraitis, Vilmantas; Gudnason, Vilmundur; Jaddoe, Vincent W V; Huang, Wei; Zhang, Weihua; Wei, Wen Bin; Kiess, Wieland; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Gao, Xin; Sim, Xueling; Wang, Ya Xing; Friedlander, Yechiel; Tham, Yih-Chung; Kamatani, Yoichiro; Okada, Yukinori; Milaneschi, Yuri; Yu, Zhi; Stark, Klaus J; Stefansson, Kari; Böger, Carsten A; Hung, Adriana M; Kronenberg, Florian; Köttgen, Anna; Pattaro, Cristian; Heid, Iris M
Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
PMCID:9192715
PMID: 35697829
ISSN: 2399-3642
CID: 5290962

How Common SOFA and Ventilator Time Trial Criteria would have Performed during the COVID-19 Pandemic: An Observational Simulated Cohort Study

Walsh, B Corbett; Pradhan, Deepak; Mukherjee, Vikramjit; Uppal, Amit; Nunnally, Mark E; Berkowitz, Kenneth A
OBJECTIVES/OBJECTIVE:To evaluate how key aspects of New York State Ventilator Allocation Guidelines (NYSVAG)-Sequential Organ Failure Assessment score criteria and ventilator time trials -might perform with respect to the frequency of ventilator reallocation and survival to hospital discharge in a simulated cohort of COVID-19 patients. METHODS:Single center retrospective observational and simulation cohort study of 884 critically-ill COVID-19 patients undergoing ventilator allocation per NYSVAG. RESULTS:742 patients (83.9%) would have had their ventilator reallocated during the 11-day observation period, 280 (37.7%) of whom would have otherwise survived to hospital discharge if provided a ventilator. Only 65 (18.1%) of the observed surviving patients would have survived by NYSVAG. Extending ventilator time trials from 2 to 5 days resulted in a 49.2% increase in simulated survival to discharge. CONCLUSIONS:In the setting of a protracted respiratory pandemic, implementation of NYSVAG or similar protocols could lead to a high degree of ventilator reallocation, including withdrawal from patients who might otherwise survive. Longer ventilator time trials might lead to improved survival for COVID-19 patients given their protracted respiratory failure. Further studies are needed to understand the survival of patients receiving reallocated ventilators to determine whether implementation of NYSVAG would improve overall survival.
PMID: 35678391
ISSN: 1938-744x
CID: 5248482

Investigating the association between subjective and objective performance-based cognitive function among former collegiate football players

Bryant, Andrew M; Kerr, Zachary Y; Walton, Samuel R; Barr, William B; Guskiewicz, Kevin M; McCrea, Michael A; Brett, Benjamin L
OBJECTIVE/UNASSIGNED:Studies have observed variable associations of prior contact sport participation with subjective and objective measures of cognitive function. This study directly investigated the association between subjective self-report and objective performance-based cognition among former collegiate football players, as well as its relationship to self-reported concussion history. METHODS/UNASSIGNED: = 1.49]) retired from sport 15-years prior were enrolled. Linear regression models examined associations between subjective cognition (Quality of Life in Neurological Disorders Cognitive Functioning-Short Form), and performance on a neuropsychological battery. Domain specific (executive function) metrics of subjective (Behavior Rating Inventory of Executive Function-Adult) and objective cognition were also exclusively examined. Associations between self-reported concussion history with subjective and objective measures were tested. Potential influential factors (sleep quality and distress) were included as covariates. RESULTS/UNASSIGNED:= .033). CONCLUSIONS/UNASSIGNED:Reliance on self-reported measures of cognitive functioning alone is insufficient when assessing cognition in former contact sport athletes. Assessment of other factors known to influence subjective cognitive complaints should also be examined in determining the presence of cognitive deficits.
PMID: 35670306
ISSN: 1744-4144
CID: 5283112

Radiographic and clinical outcomes with particle or liquid embolic agents for middle meningeal artery embolization of nonacute subdural hematomas

Scoville, Jonathan P; Joyce, Evan; A Tonetti, Daniel; Bounajem, Michael T; Thomas, Ajith; Ogilvy, Christopher S; Moore, Justin M; Riina, Howard A; Tanweer, Omar; Levy, Elad I; Spiotta, Alejandro M; Gross, Bradley A; Jankowitz, Brian T; Cawley, C Michael; Khalessi, Alexander A; Pandey, Aditya S; Ringer, Andrew J; Hanel, Ricardo; Ortiz, Rafael A; Langer, David; Levitt, Michael R; Binning, Mandy; Taussky, Philipp; Kan, Peter; Grandhi, Ramesh
BACKGROUND:Middle meningeal artery (MMA) embolization is an apparently efficacious minimally invasive treatment for nonacute subdural hematomas (NASHs), but how different embolisates affect outcomes remains unclear. Our objective was to compare radiographic and clinical outcomes after particle or liquid MMA embolization. METHODS:Patients who had MMA embolization for NASH were retrospectively identified from a multi-institution database. The primary radiographic and clinical outcomes-50% NASH thickness reduction and need for surgical retreatment within 90 days, respectively-were compared for liquid and particle embolizations in patients treated 1) without surgical intervention (upfront), 2) after recurrence, or 3) with concomitant surgery (prophylactic). RESULTS:The upfront, recurrent, and prophylactic subgroups included 133, 59, and 16 patients, respectively. The primary radiographic outcome was observed in 61.8%, 61%, and 72.7% of particle-embolized patients and 61.3%, 55.6%, and 20% of liquid-embolized patients, respectively (p = 0.457, 0.819, 0.755). Hazard ratios comparing time to reach radiographic outcome in the particle and liquid groups or upfront, recurrent, andprophylactic timing were 1.31 (95% CI 0.78-2.18; p = 0.310), 1.09 (95% CI 0.52-2.27; p = 0.822), and 1.5 (95% CI 0.14-16.54; p = 0.74), respectively. The primary clinical outcome occurred in 8.0%, 2.4%, and 0% of patients who underwent particle embolization in the upfront, recurrent, and prophylactic groups, respectively, compared with 0%, 5.6%, and 0% who underwent liquid embolization (p = 0.197, 0.521, 1.00). CONCLUSIONS:MMA embolization with particle and liquid embolisates appears to be equally effective in treatment of NASHs as determined by the percentage who reach, and the time to reach, 50% NASH thickness reduction and the incidence of surgical reintervention within 90 days.
PMID: 35673710
ISSN: 2385-2011
CID: 5248382