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Optimal Design of Clinical Trials Involving Persons with Disorders of Consciousness

Cho, Sung-Min; Robba, Chiara; Diringer, Michael N; Hanley, Daniel F; Hemphill, J Claude; Horn, Janneke; Lewis, Ariane; Livesay, Sarah L; Menon, David; Sharshar, Tarek; Stevens, Robert D; Torner, James; Vespa, Paul M; Ziai, Wendy C; Spann, Marcus; Helbok, Raimund; Suarez, Jose I; ,
BACKGROUND:Limited data exist regarding the optimal clinical trial design for studies involving persons with disorders of consciousness (DoC), and only a few therapies have been tested in high-quality clinical trials. To address this, the Curing Coma Campaign Clinical Trial Working Group performed a gap analysis on the current state of clinical trials in DoC to identify the optimal clinical design for studies involving persons with DoC. METHODS:The Curing Coma Campaign Clinical Trial Working Group was divided into three subgroups to (1) review clinical trials involving persons with DoC, (2) identify unique challenges in the design of clinical trials involving persons with DoC, and (3) recommend optimal clinical trial designs for DoC. RESULTS:There were 3055 studies screened, and 66 were included in this review. Several knowledge gaps and unique challenges were identified. There is a lack of high-quality clinical trials, and most data regarding patients with DoC are based on observational studies focusing on patients with traumatic brain injury and cardiac arrest. There is a lack of a structured long-term outcome assessment with significant heterogeneity in the methodology, definitions of outcomes, and conduct of studies, especially for long-term follow-up. Another major barrier to conducting clinical trials is the lack of resources, especially in low-income countries. Based on the available data, we recommend incorporating trial designs that use master protocols, sequential multiple assessment randomized trials, and comparative effectiveness research. Adaptive platform trials using a multiarm, multistage approach offer substantial advantages and should make use of biomarkers to assess treatment responses to increase trial efficiency. Finally, sound infrastructure and international collaboration are essential to facilitate the conduct of trials in patients with DoC. CONCLUSIONS:Conduct of trials in patients with DoC should make use of master protocols and adaptive design and establish international registries incorporating standardized assessment tools. This will allow the establishment of evidence-based practice recommendations and decrease variations in care.
PMID: 37535178
ISSN: 1556-0961
CID: 5635052

Current state of the epilepsy drug and device pipeline

Terman, Samuel W; Kirkpatrick, Laura; Akiyama, Lisa F; Baajour, Wadih; Atilgan, Deniz; Dorotan, Maria Kristina C; Choi, Hyoung Won; French, Jacqueline A
The field of epilepsy has undergone substantial advances as we develop novel drugs and devices. Yet considerable challenges remain in developing broadly effective, well-tolerated treatments, but also precision treatments for rare epilepsies and seizure-monitoring devices. We summarize major recent and ongoing innovations in diagnostic and therapeutic products presented at the seventeenth Epilepsy Therapies & Diagnostics Development (ETDD) conference, which occurred May 31 to June 2, 2023, in Aventura, Florida. Therapeutics under development are targeting genetics, ion channels and other neurotransmitters, and many other potentially first-in-class interventions such as stem cells, glycogen metabolism, cholesterol, the gut microbiome, and novel modalities for delivering electrical neuromodulation.
PMID: 38345387
ISSN: 1528-1167
CID: 5635632

Mentorship in rehabilitation psychology: Attitudes and perspectives

Kim, Sonya; Dudek, Emily; Kajankova, Maria; Channing, Tiffany; Tabio, Laura; Derbidge, Christina M
OBJECTIVE:To characterize how mentorship has been perceived, received, and practiced by individuals in the field of rehabilitation psychology across the career lifespan. METHOD/METHODS:Current members of the American Psychological Association Division 22 (Rehabilitation Psychology) were invited to complete an electronic survey via REDCap assessing individual experiences and perspectives on mentorship. Thematic analysis was used to identify key constructs and themes. RESULTS:= 25 mentors) completed the survey with valid responses. Participants spanned the career lifespan, ranging from predoctoral trainees to late-senior psychologists. Mentorship was generally perceived as helpful for both mentors and mentees. Several important qualities of mentors (e.g., availability, communication skills, self-disclosure, and emotional support) and mentees (e.g., flexibility, motivation, and openness to feedback) were identified. Among both groups, mentorship was viewed as especially beneficial for obtaining American Board of Professional Psychology (ABPP) board certification, which may reflect an aspect of mentoring unique to Division 22. Existing gaps in mentorship and key areas for improvement were also identified; access to mid- to late-career mentorship emerged as a notable gap in mentorship. Increased program structure, networking opportunities, and research mentorship were also identified as possible areas of growth. CONCLUSIONS:This study provides meaningful insights into mentorship within the field of rehabilitation psychology. Our findings demonstrate the value of mentorship across the career lifespan, and the beneficial role of mentorship in obtaining ABPP board certification. In addition, we identify key areas of growth that can inform and improve mentorship within the field. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
PMID: 38358712
ISSN: 1939-1544
CID: 5635862

Perspective: Efficacy and outcomes for different lumbar interspinous devices (ISD) vs. open surgery to treat lumbar spinal stenosis (LSS)

Epstein, Nancy E; Agulnick, Marc A
BACKGROUND/UNASSIGNED:Interspinous devices (ISD) constitute a minimally invasive (MI) alternative to open surgery (i.e., laminectomy/decompression with/without fusion (i.e., posterior lumbar interbody fusion (PLIF)/posterolateral instrumented fusion (PLF)) for treating lumbar spinal stenosis (LSS). Biomechanically, static and/or dynamic ISD "offload" pressure on the disc space, increase intervertebral foraminal/disc space heights, reverse/preserve lordosis, limit range of motion (ROM)/stabilize the surgical level, and reduce adjacent segment disease (ASD). Other benefits reported in the literature included; reduced operative time (OR Time), length of hospital stay (LOS), estimated blood loss (EBL), and improved outcomes (i.e., ODI (Oswestry Disability Index), VAS (Visual Analog Scale), and/or SF-36 (Short-Form 36)). METHODS/UNASSIGNED:Various studies documented the relative efficacy and outcomes of original (i.e., Wallis), current (i.e., X-STOP, Wallis, DIAM, Aperius PercLID), and new generation (i.e., Coflex, Superion Helifix, In-Space) ISD used to treat LSS vs. open surgery. RESULTS/UNASSIGNED:Although ISD overall resulted in comparable or improved outcomes vs. open surgery, the newer generation ISD provided the greatest reductions in critical cost-saving parameters (i.e., OR time, LOS, and lower reoperation rates of 3.7% for Coflex vs. 11.1% for original/current ISD) vs. original/current ISD and open surgery. Further, the 5-year postoperative study showed the average cost of new generation Coflex ISD/decompressions was $15,182, or $11,681 lower than the average $26,863 amount for PLF. CONCLUSION/UNASSIGNED:Patients undergoing new generation ISD for LSS exhibited comparable or better outcomes, but greater reductions in OR times, EBL, LOS, ROM, and ASD vs. those receiving original/current ISD or undergoing open surgery.
PMCID:10858763
PMID: 38344078
ISSN: 2229-5097
CID: 5635612

Pharmacologic Treatment for High BP and Risk of CVD [Comment]

Palma, Jose-Alberto; Kaufmann, Horacio
PMID: 38349377
ISSN: 1538-3598
CID: 5635282

Blood Pressure Trajectories and Outcomes After Endovascular Thrombectomy for Acute Ischemic Stroke

Katsanos, Aristeidis H; Joundi, Raed A; Palaiodimou, Lina; Ahmed, Niaz; Kim, Joon-Tae; Goyal, Nitin; Maier, Ilko L; de Havenon, Adam; Anadani, Mohammad; Matusevicius, Marius; Mistry, Eva A; Khatri, Pooja; Arthur, Adam S; Sarraj, Amrou; Yaghi, Shadi; Shoamanesh, Ashkan; Catanese, Luciana; Psychogios, Marios-Nikos; Tsioufis, Konstantinos; Malhotra, Konark; Spiotta, Alejandro M; Sandset, Else Charlotte; Alexandrov, Andrei V; Petersen, Nils H; Tsivgoulis, Georgios
BACKGROUND/UNASSIGNED:Data on systolic blood pressure (SBP) trajectories in the first 24 hours after endovascular thrombectomy (EVT) in acute ischemic stroke are limited. We sought to identify these trajectories and their relationship to outcomes. METHODS/UNASSIGNED:We combined individual-level data from 5 studies of patients with acute ischemic stroke who underwent EVT and had individual blood pressure values after the end of the procedure. We used group-based trajectory analysis to identify the number and shape of SBP trajectories post-EVT. We used mixed effects regression models to identify associations between trajectory groups and outcomes adjusting for potential confounders and reported the respective adjusted odds ratios (aORs) and common odds ratios. RESULTS/UNASSIGNED:There were 2640 total patients with acute ischemic stroke included in the analysis. The most parsimonious model identified 4 distinct SBP trajectories, that is, general directional patterns after repeated SBP measurements: high, moderate-high, moderate, and low. Patients in the higher blood pressure trajectory groups were older, had a higher prevalence of vascular risk factors, presented with more severe stroke syndromes, and were less likely to achieve successful recanalization after the EVT. In the adjusted analyses, only patients in the high-SBP trajectory were found to have significantly higher odds of early neurological deterioration (aOR, 1.84 [95% CI, 1.20-2.82]), intracranial hemorrhage (aOR, 1.84 [95% CI, 1.31-2.59]), mortality (aOR, 1.75 [95% CI, 1.21-2.53), death or disability (aOR, 1.63 [95% CI, 1.15-2.31]), and worse functional outcomes (adjusted common odds ratio,1.92 [95% CI, 1.47-2.50]). CONCLUSIONS/UNASSIGNED:Patients follow distinct SBP trajectories in the first 24 hours after an EVT. Persistently elevated SBP after the procedure is associated with unfavorable short-term and long-term outcomes.
PMID: 38164751
ISSN: 1524-4563
CID: 5635172

Neural Mechanisms Determining the Duration of Task-free, Self-paced Visual Perception

Baror, Shira; Baumgarten, Thomas J; He, Biyu J
Humans spend hours each day spontaneously engaging with visual content, free from specific tasks and at their own pace. Currently, the brain mechanisms determining the duration of self-paced perceptual behavior remain largely unknown. Here, participants viewed naturalistic images under task-free settings and self-paced each image's viewing duration while undergoing EEG and pupillometry recordings. Across two independent data sets, we observed large inter- and intra-individual variability in viewing duration. However, beyond an image's presentation order and category, specific image content had no consistent effects on spontaneous viewing duration across participants. Overall, longer viewing durations were associated with sustained enhanced posterior positivity and anterior negativity in the ERPs. Individual-specific variations in the spontaneous viewing duration were consistently correlated with evoked EEG activity amplitudes and pupil size changes. By contrast, presentation order was selectively correlated with baseline alpha power and baseline pupil size. Critically, spontaneous viewing duration was strongly predicted by the temporal stability in neural activity patterns starting as early as 350 msec after image onset, suggesting that early neural stability is a key predictor for sustained perceptual engagement. Interestingly, neither bottom-up nor top-down predictions about image category influenced spontaneous viewing duration. Overall, these results suggest that individual-specific factors can influence perceptual processing at a surprisingly early time point and influence the multifaceted ebb and flow of spontaneous human perceptual behavior in naturalistic settings.
PMID: 38357932
ISSN: 1530-8898
CID: 5635852

4. Painful diabetic polyneuropathy

Zuidema, Xander; de Galan, Bastiaan; Brouwer, Brigitte; Cohen, Steven P; Eldabe, Sam; Argoff, Charles E; Huygen, Frank; Van Zundert, Jan
INTRODUCTION/BACKGROUND:Pain as a symptom of diabetic polyneuropathy (DPN) significantly lowers quality of life, increases mortality and is the main reason for patients with diabetes to seek medical attention. The number of people suffering from painful diabetic polyneuropathy (PDPN) has increased significantly over the past decades. METHODS:The literature on the diagnosis and treatment of diabetic polyneuropathy was retrieved and summarized. RESULTS:The etiology of PDPN is complex, with primary damage to peripheral nociceptors and altered spinal and supra-spinal modulation. To achieve better patient outcomes, the mode of diagnosis and treatment of PDPN evolves toward more precise pain-phenotyping and genotyping based on patient-specific characteristics, new diagnostic tools, and prior response to pharmacological treatments. According to the Toronto Diabetic Neuropathy Expert Group, a presumptive diagnosis of "probable PDPN" is sufficient to initiate treatment. Proper control of plasma glucose levels, and prevention of risk factors are essential in the treatment of PDPN. Mechanism-based pharmacological treatment should be initiated as early as possible. If symptomatic pharmacologic treatment fails, spinal cord stimulation (SCS) should be considered. In isolated cases, where symptomatic pharmacologic treatment and SCS are unsuccessful or cannot be used, sympathetic lumbar chain neurolysis and/or radiofrequency ablation (SLCN/SLCRF), dorsal root ganglion stimulation (DRGs) or posterior tibial nerve stimulation (PTNS) may be considered. However, it is recommended that these treatments be applied only in a study setting in a center of expertise. CONCLUSIONS:The diagnosis of PDPN evolves toward pheno-and genotyping and treatment should be mechanism-based.
PMID: 37859565
ISSN: 1533-2500
CID: 5635442

Factors Associated with Patient Adherence to Biofeedback Therapy Referral for Migraine: An Observational Study

Minen, Mia T; George, Alexis; Cuneo, Ami Z
Biofeedback has Grade A evidence for the treatment of migraine, yet few studies have examined the factors associated with patients' decisions to pursue biofeedback treatment recommendations. We sought to examine reasons for adherence or non-adherence to referral to biofeedback therapy as treatment for migraine. Patients with migraine who had been referred for biofeedback by a headache specialist/behavioral neurologist were interviewed in person or via Webex. Patients completed an enrollment questionnaire addressing demographics and questions related to their headache histories. At one month, patients were sent a follow-up questionnaire via REDCap and asked if they had pursued the recommendation for biofeedback therapy, their reasons for their decision, and their impressions about biofeedback for those who pursued it. Nearly two-thirds (65%; 33/51) of patients responded at one month. Of these, fewer than half (45%, 15/33) had contacted biofeedback providers, and only 18% (6/33) completed a biofeedback session. Common themes emerged for patients who did not pursue biofeedback, including feeling that they did not have time, concern for financial obstacles (e.g., treatment cost and/or insurance coverage), and having difficulty scheduling an appointment due to limited provider availability. When asked about their preference between type of biofeedback provider (e.g., a physical therapist or psychologist), qualitative responses were mixed; many patients indicated no preference as long as they took insurance and/or were experienced, while others indicated a specific preference for a physical therapist or psychologist due to familiarity, or prior experiences with that kind of provider. Patients with migraine referred for biofeedback therapy face numerous obstacles to pursuing treatment.
PMID: 38386246
ISSN: 1573-3270
CID: 5634452

Wearable Digital Health Technology for Epilepsy

Donner, Elizabeth; Devinsky, Orrin; Friedman, Daniel
PMID: 38381676
ISSN: 1533-4406
CID: 5634332