702 results
D.1 Efficacy, safety, and tolerability of subcutaneous efgartigimod in chronic inflammatory demyelinating polyneuropathy: results from the ADHERE trial
- Z Siddiqi, JA Allen, I Basta, C Eggers, J Guptill, K Gwathmey, C Hewamadduma, E Hofman, Y Hussain, S Kuwabara, F Leypoldt, J Lin, M Lipowska, M Lowe, G Lauria Pinter, L Querol, N Suresh, T Chang, A Tse, P Ulrichts, PA van Doorn, B Van Hoorick, R Yamasaki, RA Lewis
-
- Journal:
- Canadian Journal of Neurological Sciences / Volume 51 / Issue s1 / June 2024
- Published online by Cambridge University Press:
- 24 May 2024, pp. S8-S9
-
- Article
-
- You have access Access
- Export citation
-
Background: Efgartigimod, a human immunoglobulin G (IgG)1 antibody Fc fragment, blocks the neonatal Fc receptor, decreasing IgG recycling and reducing pathogenic IgG autoantibody levels. ADHERE assessed the efficacy and safety of efgartigimod PH20 subcutaneous (SC; co-formulated with recombinant human hyaluronidase PH20) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: ADHERE enrolled participants with CIDP (treatment naive or on standard treatments withdrawn during run-in period) and consisted of open-label Stage A (efgartigimod PH20 SC once weekly [QW]), and randomized (1:1) Stage B (efgartigimod or placebo QW). Primary outcomes were clinical improvement (assessed with aINCAT, I-RODS, or mean grip strength; Stage A) and time to first aINCAT score deterioration (relapse; Stage B). Secondary outcomes included treatment-emergent adverse events (TEAEs) incidence. Results: 322 participants entered Stage A. 214 (66.5%) were considered responders, randomized, and treated in Stage B. Efgartigimod significantly reduced the risk of relapse (HR: 0.394; 95% CI: 0.25–0.61) versus placebo (p=0.000039). Reduced risk of relapse occurred in participants receiving corticosteroids, intravenous or SC immunoglobulin, or no treatment before study entry. Most TEAEs were mild to moderate; 3 deaths occurred, none related to efgartigimod. Conclusions: Participants treated with efgartigimod PH20 SC maintained a clinical response and remained relapse-free longer than those treated with placebo.
B.6 Long-term risk of subsequent stroke after transient ischemic attack or minor stroke: a systematic review and meta-analysis
- F Khan, V Yogendrakumar, R Lun, A Ganesh, V Lioutas, N Vinding, A Algra, C Weimar, J Ögren, J Edwards, R Swartz, A Ois, E Giralt-Steinhauer, H Bae, M Kamouchi, F de Leeuw, J Verhoeven, T Uehara, K Minematsu, S Fandler-Höfler, M Foschi, W Whiteley, F Purroy, J Jing, Y Wang, M Baik, Y Kim, M Spampinato, F Ildstad, Y Hasegawa, K Perera, H Park, D Dutta, P Barber, S Coutts, M Hill
-
- Journal:
- Canadian Journal of Neurological Sciences / Volume 51 / Issue s1 / June 2024
- Published online by Cambridge University Press:
- 24 May 2024, p. S6
-
- Article
-
- You have access Access
- Export citation
-
Background: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of subsequent stroke is uncertain. Methods: Electronic databases were searched for observational studies reporting subsequent stroke during a minimum follow-up of 1 year in patients with TIA or minor stroke. Unpublished data on number of stroke events and exact person-time at risk contributed by all patients during discrete time intervals of follow-up were requested from the authors of included studies. This information was used to calculate the incidence of stroke in individual studies, and results across studies were pooled using random-effects meta-analysis. Results: Fifteen independent cohorts involving 129794 patients were included in the analysis. The pooled incidence rate of subsequent stroke per 100 person-years was 6.4 events in the first year and 2.0 events in the second through tenth years, with cumulative incidences of 14% at 5 years and 21% at 10 years. Based on 10 studies with information available on fatal stroke, the pooled case fatality rate of subsequent stroke was 9.5% (95% CI, 5.9 – 13.8). Conclusions: One in five patients is expected to experience a subsequent stroke within 10 years after a TIA or minor stroke, with every tenth patient expected to die from their subsequent stroke.
Head and Neck Cancer: United Kingdom National Multidisciplinary Guidelines, Sixth Edition
- Jarrod J Homer, Stuart C Winter, Elizabeth C Abbey, Hiba Aga, Reshma Agrawal, Derfel ap Dafydd, Takhar Arunjit, Patrick Axon, Eleanor Aynsley, Izhar N Bagwan, Arun Batra, Donna Begg, Jonathan M Bernstein, Guy Betts, Colin Bicknell, Brian Bisase, Grainne C Brady, Peter Brennan, Aina Brunet, Val Bryant, Linda Cantwell, Ashish Chandra, Preetha Chengot, Melvin L K Chua, Peter Clarke, Gemma Clunie, Margaret Coffey, Clare Conlon, David I Conway, Florence Cook, Matthew R Cooper, Declan Costello, Ben Cosway, Neil J A Cozens, Grant Creaney, Daljit K Gahir, Stephen Damato, Joe Davies, Katharine S Davies, Alina D Dragan, Yong Du, Mark R D Edmond, Stefano Fedele, Harriet Finze, Jason C Fleming, Bernadette H Foran, Beth Fordham, Mohammed M A S Foridi, Lesley Freeman, Katherine E Frew, Pallavi Gaitonde, Victoria Gallyer, Fraser W Gibb, Sinclair M Gore, Mark Gormley, Roganie Govender, J Greedy, Teresa Guerrero Urbano, Dorothy Gujral, David W Hamilton, John C Hardman, Kevin Harrington, Samantha Holmes, Jarrod J Homer, Deborah Howland, Gerald Humphris, Keith D Hunter, Kate Ingarfield, Richard Irving, Kristina Isand, Yatin Jain, Sachin Jauhar, Sarra Jawad, Glyndwr W Jenkins, Anastasios Kanatas, Stephen Keohane, Cyrus J Kerawala, William Keys, Emma V King, Anthony Kong, Fiona Lalloo, Kirsten Laws, Samuel C Leong, Shane Lester, Miles Levy, Ken Lingley, Gitta Madani, Navin Mani, Paolo L Matteucci, Catriona R Mayland, James McCaul, Lorna K McCaul, Pádraig McDonnell, Andrew McPartlin, Valeria Mercadante, Zoe Merchant, Radu Mihai, Mufaddal T Moonim, John Moore, Paul Nankivell, Sonali Natu, A Nelson, Pablo Nenclares, Kate Newbold, Carrie Newland, Ailsa J Nicol, Iain J Nixon, Rupert Obholzer, James T O'Hara, S Orr, Vinidh Paleri, James Palmer, Rachel S Parry, Claire Paterson, Gillian Patterson, Joanne M Patterson, Miranda Payne, L Pearson, David N Poller, Jonathan Pollock, Stephen Ross Porter, Matthew Potter, Robin J D Prestwich, Ruth Price, Mani Ragbir, Meena S Ranka, Max Robinson, Justin W G Roe, Tom Roques, Aleix Rovira, Sajid Sainuddin, I J Salmon, Ann Sandison, Andy Scarsbrook, Andrew G Schache, A Scott, Diane Sellstrom, Cherith J Semple, Jagrit Shah, Praveen Sharma, Richard J Shaw, Somiah Siddiq, Priyamal Silva, Ricard Simo, Rabin P Singh, Maria Smith, Rebekah Smith, Toby Oliver Smith, Sanjai Sood, Francis W Stafford, Neil Steven, Kay Stewart, Lisa Stoner, Steve Sweeney, Andrew Sykes, Carly L Taylor, Selvam Thavaraj, David J Thomson, Jane Thornton, Neil S Tolley, Nancy Turnbull, Sriram Vaidyanathan, Leandros Vassiliou, John Waas, Kelly Wade-McBane, Donna Wakefield, Amy Ward, Laura Warner, Laura-Jayne Watson, H Watts, Christina Wilson, Stuart C Winter, Winson Wong, Chui-Yan Yip, Kent Yip
-
- Journal:
- The Journal of Laryngology & Otology / Volume 138 / Issue S1 / April 2024
- Published online by Cambridge University Press:
- 14 March 2024, pp. S1-S224
- Print publication:
- April 2024
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
Efficacy and safety of transcranial magnetic stimulation on cognition in mild cognitive impairment, Alzheimer’s disease, Alzheimer’s disease-related dementias, and other cognitive disorders: a systematic review and meta-analysis
- Sandeep R. Pagali, Rakesh Kumar, Allison M. LeMahieu, Michael R. Basso, Bradley F. Boeve, Paul E. Croarkin, Jennifer R. Geske, Leslie C. Hassett, John Huston III, Simon Kung, Brian N. Lundstrom, Ronald C. Petersen, Erik K. St. Louis, Kirk M. Welker, Gregory A. Worrell, Alvaro Pascual-Leone, Maria I. Lapid
-
- Journal:
- International Psychogeriatrics , First View
- Published online by Cambridge University Press:
- 08 February 2024, pp. 1-49
-
- Article
- Export citation
-
Objective:
We aim to analyze the efficacy and safety of TMS on cognition in mild cognitive impairment (MCI), Alzheimer’s disease (AD), AD-related dementias, and nondementia conditions with comorbid cognitive impairment.
Design:Systematic review, Meta-Analysis
Setting:We searched MEDLINE, Embase, Cochrane database, APA PsycINFO, Web of Science, and Scopus from January 1, 2000, to February 9, 2023.
Participants and interventions:RCTs, open-label, and case series studies reporting cognitive outcomes following TMS intervention were included.
Measurement:Cognitive and safety outcomes were measured. Cochrane Risk of Bias for RCTs and MINORS (Methodological Index for Non-Randomized Studies) criteria were used to evaluate study quality. This study was registered with PROSPERO (CRD42022326423).
Results:The systematic review included 143 studies (n = 5,800 participants) worldwide, encompassing 94 RCTs, 43 open-label prospective, 3 open-label retrospective, and 3 case series. The meta-analysis included 25 RCTs in MCI and AD. Collectively, these studies provide evidence of improved global and specific cognitive measures with TMS across diagnostic groups. Only 2 studies (among 143) reported 4 adverse events of seizures: 3 were deemed TMS unrelated and another resolved with coil repositioning. Meta-analysis showed large effect sizes on global cognition (Mini-Mental State Examination (SMD = 0.80 [0.26, 1.33], p = 0.003), Montreal Cognitive Assessment (SMD = 0.85 [0.26, 1.44], p = 0.005), Alzheimer’s Disease Assessment Scale–Cognitive Subscale (SMD = −0.96 [−1.32, −0.60], p < 0.001)) in MCI and AD, although with significant heterogeneity.
Conclusion:The reviewed studies provide favorable evidence of improved cognition with TMS across all groups with cognitive impairment. TMS was safe and well tolerated with infrequent serious adverse events.
4 Evaluating Plasma GFAP for the Detection of Alzheimer’s Disease Dementia
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Ann C. McKee, Thor D. Stein, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Michael L. Alosco
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 408-409
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Blood-based biomarkers represent a scalable and accessible approach for the detection and monitoring of Alzheimer’s disease (AD). Plasma phosphorylated tau (p-tau) and neurofilament light (NfL) are validated biomarkers for the detection of tau and neurodegenerative brain changes in AD, respectively. There is now emphasis to expand beyond these markers to detect and provide insight into the pathophysiological processes of AD. To this end, a reactive astrocytic marker, namely plasma glial fibrillary acidic protein (GFAP), has been of interest. Yet, little is known about the relationship between plasma GFAP and AD. Here, we examined the association between plasma GFAP, diagnostic status, and neuropsychological test performance. Diagnostic accuracy of plasma GFAP was compared with plasma measures of p-tau181 and NfL.
Participants and Methods:This sample included 567 participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry, including individuals with normal cognition (n=234), mild cognitive impairment (MCI) (n=180), and AD dementia (n=153). The sample included all participants who had a blood draw. Participants completed a comprehensive neuropsychological battery (sample sizes across tests varied due to missingness). Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa platform. Binary logistic regression analyses tested the association between GFAP levels and diagnostic status (i.e., cognitively impaired due to AD versus unimpaired), controlling for age, sex, race, education, and APOE e4 status. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate diagnostic groups compared with plasma p-tau181 and NfL. Linear regression models tested the association between plasma GFAP and neuropsychological test performance, accounting for the above covariates.
Results:The mean (SD) age of the sample was 74.34 (7.54), 319 (56.3%) were female, 75 (13.2%) were Black, and 223 (39.3%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having cognitive impairment (GFAP z-score transformed: OR=2.233, 95% CI [1.609, 3.099], p<0.001; non-z-transformed: OR=1.004, 95% CI [1.002, 1.006], p<0.001). ROC analyses, comprising of GFAP and the above covariates, showed plasma GFAP discriminated the cognitively impaired from unimpaired (AUC=0.75) and was similar, but slightly superior, to plasma p-tau181 (AUC=0.74) and plasma NfL (AUC=0.74). A joint panel of the plasma markers had greatest discrimination accuracy (AUC=0.76). Linear regression analyses showed that higher GFAP levels were associated with worse performance on neuropsychological tests assessing global cognition, attention, executive functioning, episodic memory, and language abilities (ps<0.001) as well as higher CDR Sum of Boxes (p<0.001).
Conclusions:Higher plasma GFAP levels differentiated participants with cognitive impairment from those with normal cognition and were associated with worse performance on all neuropsychological tests assessed. GFAP had similar accuracy in detecting those with cognitive impairment compared with p-tau181 and NfL, however, a panel of all three biomarkers was optimal. These results support the utility of plasma GFAP in AD detection and suggest the pathological processes it represents might play an integral role in the pathogenesis of AD.
4 Risk Factor and Biomarker Correlates of FLAIR White Matter Hyperintensities in Former American Football Players
- Monica T Ly, Fatima Tuz-Zahra, Yorghos Tripodis, Charles H Adler, Laura J Balcer, Charles Bernick, Elaine Peskind, Megan L Mariani, Rhoda Au, Sarah J Banks, William B Barr, Jennifer V Wethe, Mark W Bondi, Lisa Delano-Wood, Robert C Cantu, Michael J Coleman, David W Dodick, Michael D McClean, Jesse Mez, Joseph N Palmisano, Brett Martin, Kaitlin Hartlage, Alexander P Lin, Inga K Koerte, Jeffrey L Cummings, Eric M Reiman, Martha E Shenton, Robert A Stern, Sylvain Bouix, Michael L Alosco
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 608-610
-
- Article
-
- You have access Access
- Export citation
-
Objective:
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
2 Higher White Matter Hyperintensity Load Adversely Affects Pre-Post Proximal Cognitive Training Performance in Healthy Older Adults
- Emanuel M Boutzoukas, Andrew O’Shea, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Hanna K Hausman, Alejandro Albizu, Emily J Van Etten, Pradyumna K Bharadwaj, Samantha G Smith, Hyun Song, Eric C Porges, Alex Hishaw, Steven T DeKosky, Samuel S Wu, Michael Marsiske, Gene E Alexander, Ronald Cohen, Adam J Woods
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 671-672
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Cognitive training has shown promise for improving cognition in older adults. Aging involves a variety of neuroanatomical changes that may affect response to cognitive training. White matter hyperintensities (WMH) are one common age-related brain change, as evidenced by T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR) MRI. WMH are associated with older age, suggestive of cerebral small vessel disease, and reflect decreased white matter integrity. Higher WMH load associates with reduced threshold for clinical expression of cognitive impairment and dementia. The effects of WMH on response to cognitive training interventions are relatively unknown. The current study assessed (a) proximal cognitive training performance following a 3-month randomized control trial and (b) the contribution of baseline whole-brain WMH load, defined as total lesion volume (TLV), on pre-post proximal training change.
Participants and Methods:Sixty-two healthy older adults ages 65-84 completed either adaptive cognitive training (CT; n=31) or educational training control (ET; n=31) interventions. Participants assigned to CT completed 20 hours of attention/processing speed training and 20 hours of working memory training delivered through commercially-available Posit Science BrainHQ. ET participants completed 40 hours of educational videos. All participants also underwent sham or active transcranial direct current stimulation (tDCS) as an adjunctive intervention, although not a variable of interest in the current study. Multimodal MRI scans were acquired during the baseline visit. T1- and T2-weighted FLAIR images were processed using the Lesion Segmentation Tool (LST) for SPM12. The Lesion Prediction Algorithm of LST automatically segmented brain tissue and calculated lesion maps. A lesion threshold of 0.30 was applied to calculate TLV. A log transformation was applied to TLV to normalize the distribution of WMH. Repeated-measures analysis of covariance (RM-ANCOVA) assessed pre/post change in proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures in the CT group compared to their ET counterparts, controlling for age, sex, years of education and tDCS group. Linear regression assessed the effect of TLV on post-intervention proximal composite and sub-composite, controlling for baseline performance, intervention assignment, age, sex, years of education, multisite scanner differences, estimated total intracranial volume, and binarized cardiovascular disease risk.
Results:RM-ANCOVA revealed two-way group*time interactions such that those assigned cognitive training demonstrated greater improvement on proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures compared to their ET counterparts. Multiple linear regression showed higher baseline TLV associated with lower pre-post change on Processing Speed Training sub-composite (ß = -0.19, p = 0.04) but not other composite measures.
Conclusions:These findings demonstrate the utility of cognitive training for improving postintervention proximal performance in older adults. Additionally, pre-post proximal processing speed training change appear to be particularly sensitive to white matter hyperintensity load versus working memory training change. These data suggest that TLV may serve as an important factor for consideration when planning processing speed-based cognitive training interventions for remediation of cognitive decline in older adults.
5 Antemortem Plasma GFAP Predicts Alzheimer’s Disease Neuropathological Changes
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Bertran R. Huber, Ann C. McKee, Thor D. Stein, Michael L. Alosco
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 409-410
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).
Participants and Methods:This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.
Results:Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.
Conclusions:The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.
9 Connecting memory and functional brain networks in older adults: a resting state fMRI study
- Jori L Waner, Hanna K Hausman, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Andrew O’Shea, Alejandro Albizu, Emanuel M Boutzoukas, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Steven T DeKosky, Georg A Hishaw, Samuel S Wu, Michael Marsiske, Ronald Cohen, Gene E Alexander, Eric C Porges, Adam J Woods
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 527-528
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Nonpathological aging has been linked to decline in both verbal and visuospatial memory abilities in older adults. Disruptions in resting-state functional connectivity within well-characterized, higherorder cognitive brain networks have also been coupled with poorer memory functioning in healthy older adults and in older adults with dementia. However, there is a paucity of research on the association between higherorder functional connectivity and verbal and visuospatial memory performance in the older adult population. The current study examines the association between resting-state functional connectivity within the cingulo-opercular network (CON), frontoparietal control network (FPCN), and default mode network (DMN) and verbal and visuospatial learning and memory in a large sample of healthy older adults. We hypothesized that greater within-network CON and FPCN functional connectivity would be associated with better immediate verbal and visuospatial memory recall. Additionally, we predicted that within-network DMN functional connectivity would be associated with improvements in delayed verbal and visuospatial memory recall. This study helps to glean insight into whether within-network CON, FPCN, or DMN functional connectivity is associated with verbal and visuospatial memory abilities in later life.
Participants and Methods:330 healthy older adults between 65 and 89 years old (mean age = 71.6 ± 5.2) were recruited at the University of Florida (n = 222) and the University of Arizona (n = 108). Participants underwent resting-state fMRI and completed verbal memory (Hopkins Verbal Learning Test - Revised [HVLT-R]) and visuospatial memory (Brief Visuospatial Memory Test - Revised [BVMT-R]) measures. Immediate (total) and delayed recall scores on the HVLT-R and BVMT-R were calculated using each test manual’s scoring criteria. Learning ratios on the HVLT-R and BVMT-R were quantified by dividing the number of stimuli (verbal or visuospatial) learned between the first and third trials by the number of stimuli not recalled after the first learning trial. CONN Toolbox was used to extract average within-network connectivity values for CON, FPCN, and DMN. Hierarchical regressions were conducted, controlling for sex, race, ethnicity, years of education, number of invalid scans, and scanner site.
Results:Greater CON connectivity was significantly associated with better HVLT-R immediate (total) recall (ß = 0.16, p = 0.01), HVLT-R learning ratio (ß = 0.16, p = 0.01), BVMT-R immediate (total) recall (ß = 0.14, p = 0.02), and BVMT-R delayed recall performance (ß = 0.15, p = 0.01). Greater FPCN connectivity was associated with better BVMT-R learning ratio (ß = 0.13, p = 0.04). HVLT-R delayed recall performance was not associated with connectivity in any network, and DMN connectivity was not significantly related to any measure.
Conclusions:Connectivity within CON demonstrated a robust relationship with different components of memory function as well across verbal and visuospatial domains. In contrast, FPCN only evidenced a relationship with visuospatial learning, and DMN was not significantly associated with memory measures. These data suggest that CON may be a valuable target in longitudinal studies of age-related memory changes, but also a possible target in future non-invasive interventions to attenuate memory decline in older adults.
The Mopra Southern Galactic Plane CO Survey – data release 4– complete survey
- K. O. Cubuk, M. G. Burton, C. Braiding, G. F. Wong, G. Rowell, N. I. Maxted, D. Eden, R. Z. E. Alsaberi, R. Blackwell, R. Enokiya, K. Feijen, M. D. Filipović, M. S. R. Freeman, S. Fujita, M. Ghavam, B. Gunay, B. Indermuehle, K. Hayashi, M. Kohno, T. Nagaya, A. Nishimura, K. Okawa, D. Rebolledo, D. Romano, H. Sano, C. Snoswell, N. F. H. Tothill, K. Tsuge, F. Voisin, Y. Yamane, S. Yoshiike
-
- Journal:
- Publications of the Astronomical Society of Australia / Volume 40 / 2023
- Published online by Cambridge University Press:
- 22 August 2023, e047
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
We present observations of the Mopra carbon monoxide (CO) survey of the Southern Galactic Plane, covering Galactic longitudes spanning $l = 250^{\circ}$ ($-110^{\circ}$) to $l = 355^{\circ}$ ($-5^{\circ}$), with a latitudinal coverage of at least $|b|<1^\circ$, totalling an area of $>$210 deg$^{2}$. These data have been taken at 0.6 arcmin spatial resolution and 0.1 km s$^{-1}$ spectral resolution, providing an unprecedented view of the molecular gas clouds of the Southern Galactic Plane in the 109–115 GHz $J = 1-0$ transitions of $^{12}$CO, $^{13}$CO, C$^{18}$O, and C$^{17}$O.
Agricultural Research Service Weed Science Research: Past, Present, and Future
- Stephen L. Young, James V. Anderson, Scott R. Baerson, Joanna Bajsa-Hirschel, Dana M. Blumenthal, Chad S. Boyd, Clyde D. Boyette, Eric B. Brennan, Charles L. Cantrell, Wun S. Chao, Joanne C. Chee-Sanford, Charlie D. Clements, F. Allen Dray, Stephen O. Duke, Kayla M. Eason, Reginald S. Fletcher, Michael R. Fulcher, John F. Gaskin, Brenda J. Grewell, Erik P. Hamerlynck, Robert E. Hoagland, David P. Horvath, Eugene P. Law, John D. Madsen, Daniel E. Martin, Clint Mattox, Steven B. Mirsky, William T. Molin, Patrick J. Moran, Rebecca C. Mueller, Vijay K. Nandula, Beth A. Newingham, Zhiqiang Pan, Lauren M. Porensky, Paul D. Pratt, Andrew J. Price, Brian G. Rector, Krishna N. Reddy, Roger L. Sheley, Lincoln Smith, Melissa C. Smith, Keirith A. Snyder, Matthew A. Tancos, Natalie M. West, Gregory S. Wheeler, Martin M. Williams, Julie Wolf, Carissa L. Wonkka, Alice A. Wright, Jing Xi, Lew H. Ziska
-
- Journal:
- Weed Science / Volume 71 / Issue 4 / July 2023
- Published online by Cambridge University Press:
- 16 August 2023, pp. 312-327
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
Translation and validation of Greek version of the Pandemic Grief Scale
- K. S. Kitsou, M. Bakola, C. Kalogirou, S. Aggelakou-Vaitsi, N. Vaitsis, K. Argyropoulos, M. Kampouraki, E. Gkatsi, K. Tsolaki, M. Vakas, A. Theochari, K. Mavridou, M. Siali, S. Karatzeni, M. Chalkidou, V. Karagianni, N. Kioses, P. Gourzis, E. Jelastopulu
-
- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S474
-
- Article
-
- You have access Access
- Open access
- Export citation
-
Introduction
Those who have lost loved ones to COVID-19 may be considered at risk of complicated grief. A 5-item mental health screening tool called the Pandemic Grief Scale (PGS) was developed to find likely instances of dysfunctional grief during the pandemic.
ObjectivesTo develop a Greek version of PGS and to explore the validity and reliability among the general population in Greece in order to further use it as clinical mental health screener.
MethodsWe conducted a cross-sectional study between January and April 2022, and 342 persons were recruited. The questionnaire included socio-demographic parameters, the PGS, the Brief Resilience Coping Scale to capture tendencies to cope with stress and the Athens Insomnia Scale to assess the insomnia symptoms. Based on experiences over the previous two weeks, each PGS item is scored on a 4-point scale, from 0 (not at all) to 3 (almost every day), with higher rating and a cut-off of 7 indicating dysfunctional grief. Prior to the psychometric validation a linguistic validation and adaptation in Greek was performed.
ResultsA total of 342 patients participated in the study, 67.8 % were females and 27.8% were 18-30 years old. Coefficient Validity Ratio (CVR) results showed that 100% (n = 5) of items were acceptable. Value of Cronbach’s alpha was found 0.848. A one-factor model was conducted by Confirmatory Factor Analysis (CFA), giving acceptable global fit indices. The resulting global fit indices [Standardized Root Mean Square Residual (SRMR) = 0.037, Comparative Fit Index (CFI) = 0.952, Tucker–Lewis Index (TLI)= 0.903] showed that the 5 items in one-factor solution proposed by the primary researchers shouldn’t be rejected for the Greek version. The Bartlett Test of Sphericity was 758.08 (p <0.001). The Kaiser-Meyer-Olkin Measure of Sampling Adequacy was 0.826, showing that the data is suitable for factor analysis. The one-factor solution derived in our study consisted of 5 items. The total explained variance was 64.3 %.
ConclusionsThe findings of this research support the PGS psychometric validity and reliability. PGS is suitable to be used in healthcare to identify and assist individuals, who are experiencing this type of pandemic-related dysfunctional grief as it is a screening tool that it’s simple to use, access, and understand.
Disclosure of InterestNone Declared
The Role of Social Defeat in Neurological differences in Psychotic Patients
- A. Malaviya, P. A. Lalousis, S. J. Wood, A. Bertolino, S. B. Borgwardt, P. Brambilla, J. Kambeitz, R. Lencer, C. Pantelis, S. Ruhrmann, R. K. Salokangas, F. Schultze-Lutter, E. Meisenzahl, N. Koutsouleris, R. Upthegrove
-
- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S183
-
- Article
-
- You have access Access
- Open access
- Export citation
-
Introduction
The social defeat hypothesis (SDH) suggests that a chronic experience of social defeat increases the likelihood of the development of psychosis. The SDH indicates that a negative experience of exclusion leads to an increase in the baseline activity of the mesolimbic dopamine system (MDS), which in turn leads to the onset of psychosis. Social defeat models have previously been produced using animal models and preclinical literature; however, these theories have not fully been tested in human clinical samples. There have been studies implying changes in brain structure due to social defeat interactions; however, research evidence is varied.
ObjectivesThis study aims to uncover whether exposure to SoDe has an impact on brain structure. Furthermore, we hope to understand if these changes are relevant to other mental health disorders.
Methods698 (506 no SoDe, 191 SoDe) participants between the ages of 15-41 were recruited from the PRONIA-FP7 study. SoDe was measured from the self-reported questionnaires’ Bullying Scale’ and ‘The Everyday Discrimination Scale’. T1-weighted structural MRI data were processed; five 2 sample t-test analyses were carried out to compare the GMV differences in the entire sample and between the four groups.
ResultsThe VBM analysis showed significant group interactions in the right thalamus proper when comparing participants who had experience SoDe to participants who had not experienced SoDe including all 4 groups along with left cerebral white matter differences. In the ROP subgroup, significant group interactions in the left cerebellum white matter were found along with right cerebral white matter, left cerebral white matter and right Thalamus proper.
ConclusionsThe findings suggest that there are significant group interactions in thalamus and cerebral white matter. This is in keeping with some previous research suggesting volumetric changes in the thalamus due to stress and psychosis. Similarly for white matter there is some evidence suggesting differences due to SoDe and psychosis. However, there is a scarcity of research in this area with different research suggesting distinctive findings and therefore the evidence is inconclusive. In the ROP group analysis significant group interactions were present in the cerebellum due to SoDe experience. There is research suggesting the cerebellum’s role in multiple different aspects like social interaction, higher-order cognition, working memory, cognitive flexibility, and psychotic symptoms, with every research suggesting multiple different things the role of the cerebellum in SoDe in the ROP population is in question. Nonetheless this large-scale research presents some interesting novel finding and leads the way to a new area of research. Further analysis will explore the relationship between groups on markers of stress (CRP) and neuroinflammation as potential mediation of the environmental effects of SoDe.
Disclosure of InterestNone Declared
Prevalence of mental health effects among healthcare professionals during the COVID-19 pandemic
- M. Bakola, K. S. Kitsou, C. Kalogirou, N. Vaitsis, S. Aggelakou-Vaitsi, K. Argyropoulos, M. Kampouraki, E. Gkatsi, K. Tsolaki, M. Vakas, A. Theochari, K. Mavridou, S. Karatzeni, M. Siali, X. Bazoukis, M. Chalkidou, V. Karagianni, P. Gourzis, E. Jelastopulu
-
- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S543-S544
-
- Article
-
- You have access Access
- Open access
- Export citation
-
Introduction
The COVID-19 pandemic has placed extraordinary mental health burdens on healthcare professionals. For women, it is a major challenge to reconcile the diverse roles of a professional, mother, and wife. The COVID-19 pandemic has exacerbated this, increasing their vulnerability to mental health issues.
ObjectivesThe aim of the study was to assess COVID-19-related mental health of healthcare professionals and to investigate whether possible gender differences as well as other parameters are associated with mental health disturbances.
MethodsWe conducted a nationwide cross-sectional study of healthcare professionals working in hospitals or primary care settings in Greece from April to June 2022. Participants answered a questionnaire that included socio-demographic and other parameters, the Coronavirus Anxiety Scale (CAS), the Coronavirus Reassurance-Seeking Behaviors Scale (CRBS), and the Obsession with COVID-19 scale (OCS).
ResultsA total of 464 healthcare professionals participated in the study, 71.2% were females and two-thirds were 31-50 years old. Elevated levels of anxiety, frequent reassurance seeking activities and persistent troubling thoughts related to COVID-19 were found in 5.8%, 3.2% and 6.1%, respectively. However, females reported significant higher mean levels on CAS and CRBS compared to males (2.41 vs 1.60, p=0.015, and 3.36 vs 2.64, p=0.041, respectively). Participants living in smaller areas had increased levels on all three scales (CAS, p < 0.001; CRBS, p = 0.007; OCS, p < 0.001), indicating thus higher coronaphobia, more frequent reassurance-seeking behaviors and disturbed thinking about COVID-19, compared to healthcare workers living in urban regions. Furthermore, lower educational level is also associated with higher values on CAS, CRBS and OCS (p < 0.003; p = 0.017; p < 0.023, respectively). Nurses experience higher anxiety scores (2.96) than physicians (1.92, p=0.013) or other healthcare workers (1.87, p=0.016). No dysfunctional thinking about COVID-19 is observed in medical doctors, whereas nurses and other healthcare workers experience higher levels on OCS.
ConclusionsOur study does not show any worrying increased psychological dysfunction related to COVID-19 pandemic among healthcare workers in general. However, females have increased levels than males. Thus, support and mental health protecting strategies should be applied primarily to female healthcare professionals when necessary.
Disclosure of InterestNone Declared
Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model
- D. Péricat, S. A. Leon-Icaza, M. Sánchez-Rico, C. Mühle, I. Zoicas, F. Schumacher, R. Planès, R. Mazars, G. Gros, A. Carpinteiro, K. A. Becker, J. Izopet, N. Strub-Wourgaft, P. Sjö, O. Neyrolles, B. Kleuser, F. Limosin, E. Gulbins, J. Kornhuber, E. Meunier, N. Hoertel, C. Cougoule
-
- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S119-S120
-
- Article
-
- You have access Access
- Open access
- Export citation
-
Introduction
The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world’s population is currently unvaccinated or incompletely vaccinated and has limited access to approved treatments against COVID-19, there is an urgent need to continue research on treatment options, especially those at low cost and which are immediately available to patients, particularly in low- and middle-income countries. Prior in vitro and observational studies have shown that fluoxetine, possibly through its inhibitory effect on the acid sphingomyelinase/ceramide system, could be a promising antiviral and anti-inflammatory treatment against COVID-19.
ObjectivesThe aim of this sudy was to test the potential antiviral and anti-inflammatory activities of fluoxetine against SARS-CoV-2 in a K18-hACE2 mouse model of infection, and against several variants of concern in vitro, and test the hypothesis of the implication of ceramides and/or their derivatives hexosylceramides.
MethodsWe evaluated the potential antiviral and anti-inflammatory activities of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and against variants of concern in vitro, i.e., SARS-CoV-2 ancestral strain, Alpha B.1.1.7, Gamma P1, Delta B1.617 and Omicron BA.5.
ResultsFluoxetine, administrated after SARS-CoV-2 infection, significantly reduced lung tissue viral titres (Figure 1) and expression of several inflammatory markers (i.e., IL-6, TNFα, CCL2 and CXCL10) (Figure 2). It also inhibited the replication of all variants of concern in vitro. A modulation of the ceramide system in the lung tissues, as reflected by the increase in the ratio HexCer 16:0/Cer 16:0 in fluoxetine-treated mice, may contribute to explain these effects (Figure 3).
Image:
Image 2:
Image 3:
ConclusionsOur findings demonstrate the antiviral and anti-inflammatory properties of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and its in vitro antiviral activity against variants of concern, establishing fluoxetine as a very promising candidate for the prevention and treatment of SARS-CoV-2 infection and disease pathogenesis.
Disclosure of InterestNone Declared
Changing trends of suicide mortality from 2011 to 2019: an analysis of 38 European Countries
- G. Fico, A. Gimenez-Palomo, R. Andra Bursan, C. R. Ionescu, F. Kraxner, P. Rolland, S. Gomes-Rodrigues, M. Batković, E. Metaj, S. Tanyeri Kayahan, A. Mamikonyan, P. Paribello, A. K. Sikora, C. M. Platsa, M. Spasic Stojakovic, A. H. Halt, M. Az, N. Ovelian, K. Melamud, M. Janusz, K. Hinkov, C. Gramaglia, J. Beezhold, J. L. Castroman, C. Hanon, D. Eraslan, E. Olie
-
- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S85-S86
-
- Article
-
- You have access Access
- Open access
- Export citation
-
Introduction
Suicide is a serious public health problem since it accounts for nearly 900,000 deaths each year worldwide. Globally in 2019, 10.7 persons out of 100,000 died by suicide. Psychiatric disorders are related to an overwhelming proportion of these cases. In the last years, several specific interventions and action plans for suicide prevention have been implemented in a number of European countries.
ObjectivesOur aim was to analyze recent epidemiologic trends of suicide mortality rates in Europe.
MethodsAnnual national statistics of suicide mortality rates derived from Eurostat public databases from 2011 to 2019 were analyzed for 38 European countries. The suicide mortality rate was estimated per year/100,000 population. Linear regression models were used to study temporal trends of suicidal mortality. Analyses were performed using RStudio.
ResultsAvailable data show a statistically significant reduction in suicide mortality rates from 2011 to 2019 in 15 European countries, and a significant increase for Turkey (ES=0.32, SD=0.06, p=0.037) (Fig 1). The greatest significant decrease was reported in Lithuania (ES=-1.42, SD=0.02, p=0.02), followed by Hungary (ES=-1.13, SD=0.11, p=0.0007), Latvia (ES=-0.76, SD=0.11, p=0.007), and Poland (ES=-0.73, SD=0.10, p=0.001). Italy reported the lowest significant reduction in suicide mortality rates (ES=-0.13, SD=0.018, p=0.003). The remaining 16 countries showed no significant changes in suicide mortality trends.
Image:
ConclusionsIn the last years, Europe registered an overall reduction in reported suicide rates. However, more recent data (i.e., suicide rates after COVID-19 pandemic, age and sex-related effect on suicide rates) should be analyzed and used to implement future recommendations. Current and future suicide prevention strategies aim to contribute to a greater reduction of suicide rates in the different European countries.
Disclosure of InterestNone Declared
Characteristics of Adults Hospitalized for a Major Depressive Disorder: Results from the Multicenter OASIS-D Study
- C. U. Correll, F. Bermpohl, N. Schoofs, R. Bathe-Peters, K. Pfeifer, P. Falkai, C. Schüle, F. Pan-Montojo, E. Y. M. Wang, A. Reif, C. Reif-Leonhard, S. Schillo, P. Getty, M. Adli, R. Papenfuß, F. Jessen, F. Salimi-Dafsari, M. Bauer, U. Lewitzka, C. Otte, L. Graumann, D. Piber, S. Weyn-Banningh, A. Meyer-Lindenberg, A. Böhringer, F. Heuer, V. B. Nöhles
-
- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S346-S347
-
- Article
-
- You have access Access
- Open access
- Export citation
-
Introduction
Major Depressive Disorder (MDD) is one of the most common mental illnesses worldwide and is strongly associated with suicidality. Commonly used treatments for MDD with suicidality include crisis intervention, oral antidepressants (although risk of suicidal behavior is high among non-responders and during the first 10-14 days of the treatment) benzodiazepines and lithium. Although several interventions addressing suicidality exist, only few studies have characterized in detail patients with MDD and suicidality, including treatment, clinical course and outcomes. Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression (OASIS-D)-study is an investigator-initiated trial funded by Janssen-Cilag GmbH.
ObjectivesFor population 1 out of 3 OASIS-D populations, to assess the sub-population of patients with suicidality and its correlates in hospitalized individuals with MDD.
MethodsThe ongoing OASIS-D study consecutively examines hospitalized patients at 8 German psychiatric university hospitals treated as part of routine clinical care. A sub-group of patients with persistent suicidality after >48 hours post-hospitalization are assessed in detail and a sub-group of those are followed for 6 months to assess course and treatment of suicidality associated with MDD. The present analysis focuses on a preplanned interim analysis of the overall hospitalized population with MDD.
ResultsOf 2,049 inpatients (age=42.5±15.9 years, females=53.2%), 68.0% had severe MDD without psychosis and 21.2% had moderately severe MDD, with 16.7% having treatment-resistant MDD. Most inpatients referred themselves (49.4%), followed by referrals by outpatient care providers (14.6%), inpatient care providers (9.0%), family/friends (8.5%), and ambulance (6.8%). Of these admissions, 43.1% represented a psychiatric emergency, with suicidality being the reason in 35.9%. Altogether, 72.4% had at least current passive suicidal ideation (SI, lifetime=87.2%), including passive SI (25.1%), active SI without plan (15.5%), active SI with plan (14.2%), and active SI with plan+intent (14.1%), while 11.5% had attempted suicide ≤2 weeks before admission (lifetime=28.7%). Drug-induced mental and behavioral disorders (19.6%) were the most frequent comorbid disorders, followed by personality disorders (8.2%). Upon admission, 64.5% were receiving psychiatric medications, including antidepressants (46.7%), second-generation antipsychotics (23.0%), anxiolytics (11.4%) antiepileptics (6.0%), and lithium (2.8%). Altogether, 9.8% reported nonadherence to medications within 6 months of admission.
ConclusionsIn adults admitted for MDD, suicidality was common, representing a psychiatric emergency in 35.9% of patients. Usual-care treatments and outcomes of suicidality in hospitalized adults with MDD require further study.
Disclosure of InterestNone Declared
Antidepressant Use and Its Association with 28-Day Mortality in Inpatients with SARS-CoV-2: Support for the FIASMA Model against COVID-19
- N. Hoertel, M. Sanchez-Rico, J. Kornhuber, E. Gulbins, A. Reiersen, E. Lenze, B. A. Fritz, F. Jalali, E. Mills, C. Cougoule, A. Carpinteiro, C. Mühle, K. A. Becker-Flegler, D. R. Boulware, C. Blanco, J. M. Alvarado, N. Strub-Wourgaft, C. Lemogne, F. Limosin
-
- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S118-S119
-
- Article
-
- You have access Access
- Open access
- Export citation
-
Introduction
To reduce Coronavirus Disease 2019 (COVID-19)-related mortality and morbidity, widely available oral COVID-19 treatments are urgently needed. Certain antidepressants, such as fluvoxamine or fluoxetine, may be beneficial against COVID-19.
ObjectivesThe main objective was two-fold: (i) to test the hypothesis that the prevalence of antidepressant use in patients hospitalized with COVID-19 would be lower than in patients with similar characteristics hospitalized without COVID-19, and (ii) to examine, among patients hospitalized with COVID-19, whether antidepressant use is associated with reduced 28-day mortality. Our secondary aim was to examine whether this potential association could only concern specific antidepressant classes or molecules, is dose-dependent, and/or only observed beyond a certain dose threshold.
MethodsWe included 388,945 adult inpatients who tested positive for SARS-CoV-2 at 36 AP–HP (Assistance Publique–Hôpitaux de Paris) hospitals from 2 May 2020 to 2 November 2021. We compared the prevalence of antidepressant use at admission in a 1:1 ratio matched analytic sample with and without COVID-19 (N = 82,586), and assessed its association with 28-day all-cause mortality in a 1:1 ratio matched analytic sample of COVID-19 inpatients with and without antidepressant use at admission (N = 1482) (Figure 1).
ResultsAntidepressant use was significantly less prevalent in inpatients with COVID-19 than in a matched control group of inpatients without COVID-19 (1.9% versus 4.8%; Odds Ratio (OR) = 0.38; 95%CI = 0.35–0.41, p < 0.001) (Figure 2). Antidepressant use was significantly associated with reduced 28-day mortality among COVID-19 inpatients (12.8% versus 21.2%; OR = 0.55; 95%CI = 0.41–0.72, p < 0.001), particularly at daily doses of at least 40 mg fluoxetine equivalents (Figure 3). Antidepressants with high FIASMA (Functional Inhibitors of Acid Sphingomyelinase) activity seem to drive both associations.
Image:
Image 2:
Image 3:
ConclusionsAntidepressant use is associated with a reduced likelihood of hospitalization in patients infected with SARS-CoV-2 and with a reduced risk of death in patients hospitalized with COVID-19. These associations were stronger for molecules with high FIASMA activity. These findings posit that prospective interventional studies of antidepressants with the highest FIASMA activity may be appropriate to help identify variant-agnostic, affordable, and scalable interventions for outpatient and inpatient therapy of COVID-19.
Disclosure of InterestNone Declared
A real-world data analysis of Clinical Global Impression-Severity (CGI-S) as a transdiagnostic predictor of psychiatric hospitalisation
- E. Palmer, M. Taquet, K. Griffiths, S. Ker, C. Liman, S. N. Wee, S. Kollins, R. Patel
-
- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S619-S620
-
- Article
-
- You have access Access
- Open access
- Export citation
-
Introduction
Preventing psychiatric admissions holds benefits for patients as well as healthcare systems. The Clinical Global Impression-Severity (CGI-S) scale is a 7-point measurement of symptom severity, independent of diagnosis, which has shown capability of predicting risk of hospitalisation in schizophrenia. Due to its routine use in clinical practice and ease of administration, it may have potential as a transdiagnostic predictor of hospitalisation.
ObjectivesTo investigate whether early trajectories of CGI-S scores predict risk of hospitalisation over a 6 month-follow-up period.
MethodsA retrospective cohort study was conducted, analysing Electronic Health Record (EHR) data from the NeuroBlu Database (Patel et al. BMJ Open 2022;12:e057227). Patients were included if they had a psychiatric diagnosis and at least 5 recorded CGI-S scores within a 2-month period, defined as the ‘index’ period. The relationship between early CGI-S trajectories and risk of hospitalisation was investigated using Cox regression. The analysis was adjusted for age, gender, race, number of years in education, and psychiatric diagnosis. Early CGI-S trajectories were estimated as clinical severity (defined as the mean CGI-S score during the index period) and clinical instability (defined as a generalised Root Mean Squared Subsequent Differences of all CGI-S scores recorded during the index period). The primary outcome was time to psychiatric hospitalisation up to 6 months following the index period. Patients who had been hospitalised before or within the index period were excluded.
ResultsA total of 36,914 patients were included (mean [SD] age: 29.7 [17.5] years; 57.3% female). Clinical instability (hazard ratio: 1.09, 95% CI 1.07-1.10, p<0.001) and severity (hazard ratio: 1.11, 95% CI 1.09-1.12, p<0.001) independently predicted risk of hospitalisation. These associations were consistent across all psychiatric diagnoses. Patients in the top 50% of severity and/or instability were at a 45% increased risk of hospitalisation compared to those in the bottom 50% (Figure 1).
Image:
ConclusionsEarly CGI-S trajectories reflecting clinical severity and instability independently predict risk of hospitalisation across diagnoses. This risk was compounded when instability and severity were present together. These results have translation potential in predicting individuals who are at high risk of hospitalisation and could benefit from preventative strategies to mitigate this risk.
Disclosure of InterestE. Palmer Employee of: Holmusk, M. Taquet Consultant of: Holmusk, K. Griffiths Employee of: Holmusk, S. Ker Employee of: Holmusk, C. Liman Employee of: Holmusk, S. N. Wee Employee of: Holmusk, S. Kollins Employee of: Holmusk, R. Patel Grant / Research support from: National Institute of Health Research (NIHR301690); Medical Research Council (MR/S003118/1); Academy of Medical Sciences (SGL015/1020); Janssen, Employee of: Holmusk
Exploring Decision-Making Strategies in the IOWA Gambling Task and Rat Gambling Task
- C. Hultman, N. Tjernström, S. Vadlin, M. Rehn, K. W. Nilsson, E. Roman, C. Åslund
-
- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S106-S107
-
- Article
-
- You have access Access
- Open access
- Export citation
-
Introduction
Impairments in decision-making processes are believed to play an important role in both substance use disorders and behavioral addictions. Clinical and pre-clinical experimental testing provide complimentary insights on the psychobiological mechanisms of decision-making. The IOWA Gambling Task (IGT) assesses decision-making under ambiguity and risk, in which individuals are faced with four card choices associated with varying monetary reinforcer/loss contingencies. The rat Gambling Task is a pre-clinical version using palatable reinforcers as wins and timeouts mimicking losses. However, studies with interspecies comparisons in these tasks are lacking, but important to facilitate translation of information that may help unravel the complex processes of decision-making and generate clinical advances.
ObjectivesThis study explores decision-making strategies among humans and rats performing the IGT and rGT.
MethodsA total of 270 young human adults performed a computerized version of the IGT, and 72 adult outbread male Lister Hooded rats performed the rGT. Performance was assessed and explored by normative scoring approaches and subgroup formations based on individual choices.
ResultsResults showed that most humans and rats learned to favor the advantageous choices, but the overall level of performance differed considerably. Humans displayed both exploration and learning as the task progressed, while rats showed relatively consistent pronounced preferences for the advantageous choices throughout the task. Nevertheless, variability in individual choice preferences during end performance were evident in both species.
ConclusionsResults are discussed in relation to procedural differences impacting performance and potential to study different aspects of decision-making. This is a first attempt to provide formal evaluation of similarities and differences regarding decision-making processes in the IGT and rGT from an explorative perspective.
Disclosure of InterestNone Declared