Clinical Scale Research Articles

Brain structure comparison among Parkinson disease, essential tremor, and healthy controls using 7T MRI.

Both Parkinson disease (PD) and Essential tremor (ET) are movement disorders causing tremors in elderly individuals. Although PD and ET are different disease, they often present with similar initial symptoms, making their differentiation challenging with magnetic resonance imaging (MRI) techniques. This study aimed to identify structural brain differences among PD, ET, and health controls (HCs) using 7-Tesla (T) MRI. We assessed the whole-brain parcellation in gray matter volume, thickness, subcortical volume, and small regions of basal ganglia in PD (n = 18), ET (n = 15), and HCs (n = 18), who were matched for age and sex. Brain structure analysis was performed automatic segmentation through Freesurfer software. Small regions of basal ganglia were manually segmented by ITK-SNAP. Additionally, we examined the associations between clinical indicators (symptom duration, unified Parkinson diseases rating scale (UPDRS), and clinical rating scale for tremor (CRST)) and brain structure. PD showed a significant reduction in gray matter volume in the postcentral region compared to ET. ET showed a significant reduction in cerebellum volume compared to HCs. There was a negative correlation between CRST scores (B and C) and gray matter thickness in right superior frontal in ET. This study demonstrated potential of 7T MRI in differentiating brain structure differences among PD, ET, and HCs. Specific findings, such as parietal lobe atrophy in PD compared to ET and cerebellum atrophy in ET compared to HCs, the importance of advanced imaging techniques in accurately diagnosing and distinguishing between movement disorders that present with similar initial symptoms.

Efficacy of antipsychotics in delusional infestation.

Data remain scarce for the first-line antipsychotic choice in treating delusional infestation (DI). We evaluated the treatment responses associated with different antipsychotics in DI patients. We undertook a multicentre, retrospective observational study using anonymised electronic patient records from two hospitals in the United Kingdom from 1 January 2011 to 1 January 2023. Eligible participants were adults (≥18 years) diagnosed with DI treated with an antipsychotic, and had both an assigned baseline and follow-up Clinical Global Impression Scale (CGI-S) score. The CGI-S is a validated psychiatric research tool. Participants were excluded if they had known limited or non-adherence to an antipsychotic, or if no CGI-S scores were present at follow-up. First clinic visits before the initiation of an antipsychotic were assigned as the baseline CGI-S score. The last available CGI-S score before the patient either changed antipsychotic or left the clinic for any reason was used to assign follow-up CGI-S scores. The primary outcome was the response to each individual antipsychotic treatment, measured by the difference in the baseline and last available follow-up CGI-S scores. Differences in CGI-S changes between antipsychotic episodes were tested by analysis of variance (ANOVA). In total, 414 patient records were analysed, and data were extracted. The mean age was 61.8 years (SD 14.1). One hundred seventy (41%) of 414 patients were men and 244 (59%) were women. In total, 156 (38%) of 414 patients were eligible, yielding a total of 315 antipsychotic prescribing episodes. The ANOVA, ranking in order of treatment response, showed that the highest mean score (expressing highest treatment response) was observed in amisulpride (31 [67%] of 46) and risperidone (95 [57%] of 167), followed by some distance by quetiapine (9 [36%] of 25), aripiprazole (13 [28%] of 46) and olanzapine (7 [25%] of 28). Amisulpride and risperidone were associated with a higher treatment response than quetiapine, aripiprazole and olanzapine. Amisulpride and risperidone should therefore be considered the first-line treatment options in DI patients.

Abnormal dynamic functional connectivity in young nondisabling intracerebral hemorrhage patients.

Previous resting-state functional magnetic resonance imaging studies on intracerebral hemorrhage patients have focused more on the static characteristics of brain activity, while the time-varying effects during scanning have received less attention. Therefore, the current study aimed to explore the dynamic functional network connectivity changes of intracerebral hemorrhage patients. Using independent component analysis, the sliding window approach, and the k-means clustering analysis method, different dynamic functional network connectivity states were detected from resting-state functional magnetic resonance imaging data of 37 intracerebral hemorrhage patients and 44 healthy controls. The inter-group differences in dynamic functional network connectivity patterns and temporal properties were investigated, followed by correlation analyses between clinical scales and abnormal functional indexes. Ten resting-state networks were identified, and the dynamic functional network connectivity matrices were clustered into four different states. The transition numbers were decreased in the intracerebral hemorrhage patients compared with healthy controls, which was associated with trail making test scores in patients. The cerebellar network and executive control network connectivity in State 1 was reduced in patients, and this abnormal dynamic functional connectivity was positively correlated with the animal fluency test scores of patients. The current study demonstrated the characteristics of dynamic functional network connectivity in intracerebral hemorrhage patients and revealed that abnormal temporal properties and functional connectivity may be related to the performance of different cognitive domains after ictus. These results may provide new insights into exploring the neurocognitive mechanisms of intracerebral hemorrhage.

Impact of clinical frailty scale on short and long term outcome in patients with acute coronary syndrome

Abstract Funding Acknowledgements None. Background As recently outlined in the European Society of Cardiology (ESC) guidelines on acute coronary syndrome (ACS), scarce data still exits about the prognostic role of frailty to guide clinical decision-making for patients with ACS. Purpose To assess the potential predictive value of frailty both for short, and long term all-cause mortality, in a contemporary ACS population. Methods All consecutive admissions due to ACS, from 01/01/2019 to 31/12/2021, were retrospectively reviewed from an internal database of a tertiary cardiac center in Salerno (Italy). Logistic and Cox proportional regression analysis were performed in order to assess the contribution of frailty on 30-days and long term mortality. Frailty was assessed using the Clinical Frailty Scale (CFS) and patients were classified as non frail (CFS 1-4), and frail (CFS 5-9). Both logistic and Cox regression analysis were adjusted for age, gender, GRACE risk score, comorbidity burden, defined by the Charlson comorbidity score (CCS), and all other relevant covariates associated with outcomes of interest in the univariate analysis. In order to estimate the survival rates during the follow-up, a Kaplan Meyer analysis was carried out and differences between the CFS groups were assessed using the log-rank test. Robustness of the results were assessed through an internal validation procedure with bootstrapping. All statistical analyses were performed using SPSS software version 25.0 (SPPS Inc., Chicago, Illinois) and R version 4.0.5 (R Foundation for Statistical Computing, Vienna, Austria). A p-value of less than 0.05 was considered significant. Results 1366 patients were identified. The median age was 68 (58-77). Of these patients, 1087 (79,6%) were classified as non-frail (CFS 1-4), and 279 (20,4%) as frail (CFS 5-9). 120 (8,8%) and 140 (11,2%) deaths occurred, respectively, during the first 30 days from admission, and during long term follow-up (median follow-up time: 15 months; IQR: 10-24). After multivariate regression analysis the CFS was associated with both short and long-term mortality (OR: 1,6, 95% CI: 1,34-1,91; p<0,001 and HR: 1,37, 95% CI: 1,18-1,58; p<0,001, Fig. 1). Patients with CFS ≥ 5 showed significant higher mortality rate during long term follow-up (p<0.001; Fig.2). Conclusions The CFS is a strong predictor of both short and long-term mortality in patients affected by ACS also after comprehensive adjustment for baseline differences in other risk factors.Fig. 2

Time‑dependent ROC curve analysis to determine the predictive capacity of seven clinical scales for mortality in patients with COVID‑19: Study of a hospital cohort with very high mortality

Time‑dependent ROC curve analysis to determine the predictive capacity of seven clinical scales for mortality in patients with COVID‑19: Study of a hospital cohort with very high mortality

Bimanual coordinated motor skill learning in patients with a chronic cerebellar stroke.

Cerebellar strokes induce coordination disorders that can affect activities of daily living. Evidence-based neurorehabilitation programs are founded on motor learning principles. The cerebellum is a key neural structure in motor learning. It is unknown whether and how well chronic cerebellar stroke individuals (CCSIs) can learn to coordinate their upper limbs through bimanual motor skill learning. The aim was to determine whether CCSIs could achieve bimanual skill learning through a serious game with the REAplan® robot and to compare CCSIs with healthy individuals (HIs). Over three consecutive days, sixteen CCSIs and eighteen HIs were trained on an asymmetric bimanual coordination task ("CIRCUIT" game) with the REAplan® robot, allowing quantification of speed, accuracy and coordination. The primary outcomes were the bimanual speed/accuracy trade-off (BiSAT) and bimanual coordination factor (BiCo). They were also evaluated on a bimanual REACHING task on Days 1 and 3. Correlation analyses between the robotic outcomes and clinical scale scores were computed. Throughout the sessions, BiSAT and BiCo improved during the CIRCUIT task in both HIs and CCSIs. On Day 3, HIs and CCSIs showed generalization of BiSAT, BiCo and transferred to the REACHING task. There was no significant between-group difference in progression. Four CCSIs and two HIs were categorized as "poor learners" according to BiSAT and/or BiCo. Increasing age correlated with reduced BiSAT but not BiCo progression. Over three days of training, HIs and CCSIs improved, retained, generalized and transferred a coordinated bimanual skill. There was no between-group difference, suggesting plastic compensation in CCSIs. Clinical trial NCT04642599 approved the 24th of November 2020.

Biochemical, Hematological, Inflammatory, and Gut Permeability Biomarkers in Patients with Alcohol Withdrawal Syndrome with and without Delirium Tremens

Background: Delirium Tremens (DT) is known to be a serious complication of alcohol withdrawal syndrome (AWS). Neurotransmitter abnormalities, inflammation, and increased permeability are associated with the pathogenesis of AWS and DT. However, the biomarkers of these conditions are still poorly understood. Methods: In this work, biochemical, hematologic, inflammatory, and gut permeability biomarkers were investigated in the following three groups: healthy controls (n = 75), severe AWS patients with DT (n = 28), and mild/moderate AWS without DT (n = 97). Blood sampling was performed after resolution of the acute condition (on 5 ± 1 day after admission) to collect clinical information from patients and to investigate associations with clinical scales. Biomarker analysis was performed using automated analyzers and ELISA. Inflammatory biomarkers included the erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), and platelet-to-lymphocyte ratio (PLR). Results: Among the biochemical biomarkers, only glucose, total cholesterol, and alanine aminotransferase (ALT) changed significantly in the analyzed groups. A multiple regression analysis showed that age and ALT were independent predictors of the CIWA-Ar score. Hematologic biomarker analysis showed an increased white blood cell count, and the elevated size and greater size variability of red blood cells and platelets (MCV, RDWc, and PDWc) in two groups of patients. Gut permeability biomarkers (FABP2, LBP, and zonulin) did not change, but were associated with comorbid pathologies (alcohol liver disease and pancreatitis). The increase in inflammatory biomarkers (ESR and PLR) was more evident in AWS patients with DT. Cluster analysis confirmed the existence of a subgroup of patients with evidence of high inflammation, and such a subgroup was more frequent in DT patients. Conclusions: These findings contribute to the understanding of biomarker variability in AWS patients with and without DT and support the heterogeneity of patients by the level of inflammation.

Rapid Initiation of Injection Naltrexone for Opioid Use Disorder

Injectable extended-release (XR)-naltrexone is an effective treatment option for opioid use disorder (OUD), but the need to withdraw patients from opioid treatment prior to initiation is a barrier to implementation. To compare the effectiveness of the standard procedure (SP) with the rapid procedure (RP) for XR-naltrexone initiation. The Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone study was an optimized stepped-wedge cluster randomized trial conducted at 6 community-based inpatient addiction treatment units. Units using the SP were randomly assigned at 14-week intervals to implement the RP. Participants admitted with OUD received the procedure the unit was delivering at the time of their admission. Participant recruitment took place between March 16, 2021, and July 18, 2022. The last visit was September 21, 2022. Standard procedure, based on the XR-naltrexone package insert (approximately 5-day buprenorphine taper followed by a 7- to 10-day opioid-free period and RP, defined as 1 day of buprenorphine at minimum necessary dose, 1 opioid-free day, and ascending low doses of oral naltrexone and adjunctive medications (eg, clonidine, clonazepam, antiemetics) for opioid withdrawal. Receipt of XR-naltrexone injection prior to inpatient discharge (primary outcome). Secondary outcomes included opioid withdrawal scores and targeted safety events and serious adverse events. All analyses were intention-to-treat. A total of 415 participants with OUD were enrolled (mean [SD] age, 33.6 [8.48] years; 205 [49.4%] identified sex as male); 54 [13.0%] individuals identified as Black, 91 [21.9%] as Hispanic, 290 [69.9%] as White, and 22 [5.3%] as multiracial. Rates of successful initiation of XR-naltrexone among the RP group (141 of 225 [62.7%]) were noninferior to those of the SP group (68 of 190 [35.8%]) (odds ratio [OR], 3.60; 95% CI, 2.12-6.10). Withdrawal did not differ significantly between conditions (proportion of days with a moderate or greater maximum Clinical Opiate Withdrawal Scale score (>12) for RP vs SP: OR, 1.25; 95% CI, 0.62-2.50). Targeted safety events (RP: 12 [5.3%]; SP: 4 [2.1%]) and serious adverse events (RP: 15 [6.7%]; SP: 3 [1.6%]) were infrequent but occurred more often with RP than SP. In this trial, the RP of XR-naltrexone initiation was noninferior to the standard approach and saved time, although it required more intensive medical management and safety monitoring. The results of this trial suggest that rapid initiation could make XR-naltrexone a more viable treatment for patients with OUD. ClinicalTrials.gov Identifier: NCT04762537.

Development and Validation of SCACOMS, a Composite Scale for Assessing Disease Progression and Treatment Effects in Spinocerebellar Ataxia.

Spinocerebellar ataxias (SCA) are rare inherited neurodegenerative disorders characterized by a progressive impairment of gait, balance, limb coordination, and speech. There is currently no composite scale that includes multiple aspects of the SCA experience to assess disease progression and treatment effects. Applying the method of partial least squares (PLS) regression, we developed the Spinocerebellar Ataxia Composite Scale (SCACOMS) from two SCA natural history datasets (NCT01060371, NCT02440763). PLS regression selected items based on their ability to detect clinical decline, with optimized weights based on the item's degree of progression. Following model validation, SCACOMS was leveraged to examine disease progression and treatment effects in a 48-week SCA clinical trial cohort (NCT03701399). Items from the Clinical Global Impression-Global Improvement Scale (CGI-I), the Friedreich Ataxia Rating Scale (FARS) - functional stage, and the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) were objectively selected with weightings based on their sensitivity to clinical decline. The resulting SCACOMS exhibited improved sensitivity to disease progression and greater treatment effects (compared to the original scales from which they were derived) in a 48-week clinical trial of a novel therapeutic agent. The trial analyses also provided a SCACOMS-derived estimate of the temporal delay in SCA disease progression. SCACOMS is a useful composite measure, effectively capturing disease progression and highlighting treatment effects in patients with SCA. SCACOMS will be a powerful tool in future studies given its sensitivity to clinical decline and ability to detect a meaningful clinical impact of disease-modifying treatments.

INFLUENCE OF DURATION OF UNTREATED PSYCHOSIS ON THE SHORT-TERM OUTCOME IN FIRST-EPISODE SCHIZOPHRENIA

Objectives: Schizophrenia is a devastating disease and many patients present late for treatment due to difficulty in identifying symptoms by family members. The objective of this study is to find if there is an association between a longer duration of untreated psychosis (DUP) and poor treatment outcome in first-episode Schizophrenics and to find if there is an association between premorbid social adjustment on DUP. Methods: Anti-psychotic-naïve patients with an international classification of diseases-10 schizophrenia were evaluated 12 weeks after their first in-patient hospitalization. Association between untreated initial psychosis duration (measured from the beginning of first symptom as well as from first hospital admission) was examined by conducting the clinical interview, symptom severity by positive and negative syndrome scale, and clinical global impression scale, pre-morbid social adjustment by premorbid social adjustment (PSA) scale; and symptoms improvement after treatment by CGI-I scale. Results: Of the 57 patients studied, 57.9% showed improvement after treatment, paranoid type was more common, patients responded better when treated with combined typical and atypical antipsychotics and improvement was better when DUP was <2 years. There was a major negative correlation between positive syndrome scores and DUP. There was no association of DUP with negative syndrome score, psychopathology score and PSA score. Conclusion: DUP was an independent predictor of treatment outcome and early intervention is necessary for better prognosis.

D-serine and D-amino acid oxidase levels in patients with schizophrenia spectrum disorders in the first episode and 6-month follow-up

BackgroundD-serine and the D-amino acid oxidase (DAO) enzyme, which breaks down d-amino acids, may be involved in the pathophysiology of schizophrenia by affecting the N-methyl-D-aspartate (NMDA) receptor. The exact role of D-serine and DAO, as well as the consequences of increased DAO activity in patients with schizophrenia, remain unclear. We aimed to investigate D-serine and DAO levels in patients with first-episode schizophrenia spectrum disorders before treatment and after six months of treatment. MethodComparisons for the serum levels of D-serine and DAO were made between 81 healthy controls and 89 patients with first-episode schizophrenia spectrum disorders without a history of treatment. Further comparisons were made after 6 months for changes in these levels in the 41 patients in follow-up. The Positive and Negative Syndrome Scale (PANNS), Calgary Scale for Depression in Schizophrenia (CDSS), Montreal Cognitive Assessment Scale (MoCA), Global Assessment Scale (GAS), and Clinical Global Impression Scale (CGI) were used to evaluate the symptom severity and functionality. Secondary results included comparisons related to antipsychotic equivalent doses. ResultsBefore treatment, patients had significantly lower levels of D-serine, DAO, and D-serine/DAO ratio compared to healthy individuals (p < 0.001; p < 0.001; p = 0.004). DAO and D-serine levels of the patients were higher after six months of treatment (p = 0.025; p = 0.001). There was correlation of DAO levels with antipsychotic dosage and with PANSS negative and total subscale scores (rho = 0.421, p = 0.01; rho = 0.280, p = 0.008; rho = 0.371, p = 0.000). No correlation was found between serum D-serine level, DAO level, and the D-serine/DAO ratio with cognitive function. ConclusionsThe results suggest that D-serine and DAO may play a role that is sensitive to treatment effects in schizophrenia spectrum disorders. To gain a more comprehensive understanding of the impact antipsychotic drugs have on NMDA receptor dysfunction, there is a requirement for studies that directly evaluates the activity of the DAO enzyme.

Whole-body magnetic resonance neurography in patients with chronic inflammatory demyelinating polyneuropathy.

Whole-body magnetic resonance neurography (MRN) is an imaging modality that shows peripheral nerve signal change in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We aimed to explore the diagnostic potential of whole-body MRN and its potential as a monitoring tool after immunotherapy in treatment-naïve CIDP patients. Whole-body MRN using coronal 3-dimensional short tau inversion recovery (STIR) sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE) techniques was performed in patients being investigated for CIDP and in healthy controls. Baseline clinical neuropathy scales and electrophysiologic parameters were collected, and MRN findings were compared before and after CIDP treatment. We found highly concordant symmetrical thickening and increased T2 signal intensities in the brachial/lumbosacral plexus, femoral, or sciatic nerves in five of the eight patients with a final diagnosis of CIDP and none of the healthy controls. There were no treatment-related imaging changes in five patients with CIDP who completed a follow-up study. Diffuse, symmetrical thickening, and increased T2 signal in root, plexus, and peripheral nerves were found in two patients ultimately excluded due to a diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome in addition to signal changes in the muscles, bony lesions, organomegaly, and lymphadenopathy. Whole-body MRN imaging shows promise in detecting abnormalities in proximal nerve segments in patients with CIDP. Future studies evaluating the role of MRN in assessing treatment response should consider follow-up scans after treatment durations of more than 4 months.

Latent Class Analysis of Sleep in Mild Cognitive Impairment Patients and its Influencing Factors

Background: Individuals with mild cognitive impairment (MCI) frequently experience sleep disorders, which may elevate the risk of developing Alzheimer’s disease. Yet, sleep types in MCI patients and the factors influencing them have not been sufficiently investigated. Objective: The objective of this study was to explore potential sleep typing and its influencing factors in patients with MCI using latent class analysis. Methods: A cross-sectional survey was conducted in Jiangsu Province, China. Cognitive function in older adults was assessed using neuropsychological tests, including the Montreal Cognitive Assessment Scale-Beijing version (MoCA), the Mini-Mental State Examination (MMSE), the Activities of Daily Living Scale (ADL), and the Clinical Dementia Rating Scale (CDR). Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). Latent class analysis based on PSQI scores and multinomial logistic regression analyses were employed to explore the influencing factors of sleep typing. Results: The study included a total of 611 patients with MCI. Latent class analysis identified three latent classes to categorize the sleep patterns of MCI patients: the good sleep type (56.6%), the insufficient sleep type (29.6%), and the difficulty falling asleep type (13.7%). Potential sleep typing is influenced by gender, chronic disease, physical exercise, social activity, brain exercise, smoking, frailty, subjective cognitive status, and global cognitive function. Conclusions: The findings of this study underscore the notable heterogeneity in the sleep patterns of patients with MCI. Future research may provide targeted prevention and interventions to address the characteristics and influencing factors of patients with different subtypes of sleep MCI.

The relationship between event-related potential components and suicide risk in major depressive disorder

BackgroundSuicide is a serious global issue, with major depressive disorder (MDD) being a significant risk factor for suicidal thoughts and behaviors. There is an urgent need to determine whether event-related potential components (ERPs) could be used as an indicator to assess suicidal risk. MethodsFrom 2020 to 2023, 258 participants in total were recruited into the study. All participants were divided into four groups: MDD patients at high (n = 66), moderate (n = 66), and low risk (n = 56) of suicide, and healthy controls (HCs)(n = 70). Each participant provided socio-demographic information and underwent evaluations using clinical psychological scales such as 7-item Generalized Anxiety Disorder (GAD-7), Health Questionnaire-9 items (PHQ-9), and Nurses' Global Assessment of Suicide Risk (NGASR). The auditory brainstem response test and ERP examination were performed for all subjects. ResultsOur study found that the amplitude of P2–P3 and N2–P3 was significantly reduced in MDD patients at moderate and high risk of suicide, and these were negatively correlated with NGASR total score (all P < 0.05). Point B latency was positively correlated with NGASR total score (P < 0.05). Patients with MDD patients at low risk for suicide had a lower A-B amplitude compared to HCs (P < 0.05). No differences were found in MMN or P50 components between the four groups (all P > 0.05). ConclusionsMDD patients at higher risk of suicide exhibited severe impairment of cognitive function. ERP indices, such as the amplitude of P2–P3 and N2–P3, could be associated with the risk of suicide in MDD patients.

Internet-Delivered Exposure and Response Prevention for Pediatric Tourette Syndrome

Behavior therapy is a recommended intervention for Tourette syndrome (TS) and chronic tic disorder (CTD), but availability is limited and long-term effects are uncertain. To investigate the long-term efficacy and cost-effectiveness of therapist-supported, internet-delivered exposure and response prevention (ERP) vs psychoeducation for youths with TS or CTD. This 12-month controlled follow-up of a parallel group, superiority randomized clinical trial was conducted at a research clinic in Stockholm, Sweden, with nationwide recruitment. In total, 221 participants aged 9 to 17 years with TS or CTD were enrolled between April 26, 2019, and April 9, 2021, of whom 208 (94%) provided 12-month follow-up data. Final follow-up data were collected on June 29, 2022. Outcome assessors were masked to treatment allocation throughout the study. A total of 111 participants were originally randomly allocated to 10 weeks of therapist-supported, internet-delivered ERP and 110 participants to therapist-supported, internet-delivered psychoeducation. The primary outcome was within-group change in tic severity, measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS), from the 3-month follow-up to the 12-month follow-up. Treatment response was defined as 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement scale. Analyses were intention-to-treat and followed the plan prespecified in the published study protocol. A health economic evaluation was performed from 3 perspectives: health care organization (including direct costs for treatment provided in the study), health care sector (additionally including health care resource use outside of the study), and societal (additionally including costs beyond health care [eg, parent's absenteeism from work]). In total, 221 participants were recruited (mean [SD] age, 12.1 [2.3] years; 152 [69%] male). According to the YGTSS-TTSS, there were no statistically significant changes in tic severity from the 3-month to the 12-month follow-up in either group (ERP coefficient, -0.52 [95% CI, -1.26 to 0.21]; P = .16; psychoeducation coefficient, 0.00 [95% CI, -0.78 to 0.78]; P > .99). A secondary analysis including all assessment points (baseline to 12-month follow-up) showed no statistically significant between-group difference in tic severity from baseline to the 12-month follow-up (coefficient, -0.38 [95% CI, -1.11 to 0.35]; P = .30). Treatment response rates were similar in both groups (55% in ERP and 50% in psychoeducation; odds ratio, 1.25 [95% CI, 0.73-2.16]; P = .42) at the 12-month follow-up. The health economic evaluation showed that, from a health care sector perspective, ERP produced more quality-adjusted life years (0.01 [95% CI, -0.01 to 0.03]) and lower costs (adjusted mean difference -$84.48 [95% CI, -$440.20 to $977.60]) than psychoeducation at the 12-month follow-up. From the health care organization and societal perspectives, ERP produced more quality-adjusted life years at higher costs, with 65% to 78% probability of ERP being cost-effective compared with psychoeducation when using a willingness-to-pay threshold of US $79 000. There were no statistically significant changes in tic severity from the 3-month through to the 12-month follow-up in either group. The ERP intervention was not superior to psychoeducation at any time point. While ERP was not superior to psychoeducation alone in reducing tic severity at the end of the follow-up period, ERP is recommended for clinical implementation due to its likely cost-effectiveness and support from previous literature. ClinicalTrials.gov Identifier: NCT03916055.

Usefulness of the clinical frailty scale in patients with end-stage kidney disease

Abstract Background The Frailty Index (FI) is commonly used to estimate frailty in end-stage kidney disease (ESKD) patients. The Clinical Frailty Scale (CFS) is a less time-consuming alternative. We aimed to determine the test performance of the CFS for (pre-) dialysis patients and patients receiving conservative therapy from the Dialysis Centre Apeldoorn. Methods In this cross-sectional study, haemodialysis, peritoneal dialysis, pre-dialysis patients and patients receiving conservative therapy from Dialysis Centre Apeldoorn were included and subjected to frailty score assessment. Nephrologists not familiar with the CFS completed the frailty score after medical consultation. The sensitivity, specificity and area under the curve (AUC) of the CFS were determined. The FI was used as the golden standard. Results Included were 144 patients of whom 60 (41.7%) were considered frail according to the FI. Mean age was 67.4 ± 13.5 years and 56 (38.9%) were females. The cut-off point of the CFS for ‘vulnerable’ (CFS ≥ 4) had a sensitivity of 63.3%, a specificity of 81.0% and an AUC of 0.72. The cut-off point of the CFS for ‘frail’ (CFS ≥ 5) had a sensitivity of 50.0%, a specificity of 91.7% and an AUC of 0.71. Conclusions The CFS is a quick and easy to use tool for the determination of frailty in ESKD patients with a high prevalence of frailty. Nevertheless, the sensitivity of the CFS in the present study was considered too low to implement into daily clinical practice. The sensitivity might be increased by training the nephrologists in using the CFS.

Abstract PO4-10-12: Value of Molecular Targets and Genome-Targeted Therapies FDA-Approved for Metastatic Breast Cancer, 2006-2023

Abstract Title: Value of Molecular Targets and Genome-Targeted Therapies FDA-Approved for Metastatic Breast Cancer, 2006-2023 Background: The number of FDA-approved genome-targeted cancer drugs for metastatic breast cancer has increased, providing the potential for personalized therapy. To help physicians, patients, and policymakers differentiate meaningful from trivial innovation in this field, we assessed the validity of the targets and value of the outcomes used in the pivotal trials supporting approval. Methods: We analyzed trials supporting genome-targeted breast cancer drugs FDA-approved between 2006-2023, defined as those using a genomic test in which the drug targeted a given genomic alteration. From FDA drug labels and trial reports, we extracted characteristics of pivotal trials. For Accelerated Approvals—a special FDA program allowing approval based on unvalidated surrogate measures—if the drug later received traditional approval based on a confirmatory trial, only the latter was analyzed. Strength of evidence supporting molecular targetability was evaluated using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT). Clinical benefit for approved indications was assessed using the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS). Molecular targets qualifying for ESCAT category level I-A or I-B associated with ESMO-MCBS grade 4 or 5 were rated as high-benefit genomic-targeted breast cancer treatments. Results: Fifteen genome-targeted drugs covered 17 indications and targeted 8 driver alterations. Among the 17 pivotal trials supporting these indications, most were randomized (11, 65%), phase 3 (11, 65%) and open-label (14, 82%). The most common primary endpoint leading to approval (10, 59%) was progression-free survival. Eleven trials (65%) had a I-A ESCAT targetability, 5 (29%) had a I-C targetability score and 1 (6%) was categorized as II-A. ERBB2 amplification, germline BRCA1/2 mutations, PIK3CA mutations, and ESR1 mutation were classified as tier I-A due to randomized trials demonstrating the effectiveness of approved targeted therapies in patients with these alterations. RET fusions, NTRK fusions, and microsatellite instability were classified as tier I-C, while high-tumor mutational burden was categorized as tier II-A. Eighteen percent of trials (3/17) demonstrated ESMO-MCBS grades 4-5. Overall, 3 of 17 (18%) indications had high-benefit genomic-based cancer treatments. Conclusions: Among molecular-targeted cancer therapies approved for metastatic breast cancer, fewer than a fifth demonstrated substantial patient benefits at approval. Benefit frameworks like ESCAT and ESMO-MCBS can help stakeholders identify therapies with the greatest potential. Citation Format: Ariadna Tibau, Thomas J. Hwang, Consolacion Molto Valiente, Jerry Avorn, Aaron Kesselheim. Value of Molecular Targets and Genome-Targeted Therapies FDA-Approved for Metastatic Breast Cancer, 2006-2023 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-10-12.

Abstract PO5-10-08: Clinical Value of Molecular Targets and Genome-Targeted Cancer Therapies Recommended by the National Comprehensive Cancer Network for Advanced Breast Cancer

Abstract Background: Genomic testing has expanded the possibilities of precision cancer medicine, particularly for advanced, treatment-resistant breast cancer cases. However, the clinical significance of most genetic alterations remains uncertain, potentially overestimating tailored therapies. The National Comprehensive Cancer Network (NCCN) guidelines are evidence-based cancer-specific recommendations used in clinical practice and that are often determinative for insurance coverage. In this study, we assessed the validity of the targets and the clinical benefit of genome-targeted cancer drugs recommended in the NCCN guidelines for metastatic breast cancer. Methods: We identified genome-targeted oncology therapies supporting advanced breast cancer recommendations in the most recent NCCN breast cancer guideline (version 4.2023). Genome-targeted drugs were defined as involving use of a genomic test in which the drug targeted a genomic alteration. We analyzed data from trials supporting advanced genome-targeted breast cancer drugs recommendations. When multiple (or overlapping) articles for the same study were identified, the most recent publication was included. We extracted key details of each trial, including trial design, blinding, phase of clinical trial and primary efficacy end points. We cross-referenced the FDA-approved indications as of 30 June 2023 with the NCCN recommendations for each drug. Strength of evidence supporting molecular targetability was evaluated using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT). Clinical benefit for genome-targeted oncology therapies was assessed using the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS). We considered a substantial clinical benefit as a grade of 4 or 5. Molecular targets qualifying for ESCAT category level I-A and I-B associated with substantial clinical benefit by ESMO-MCBS were rated as high-benefit genomic-targeted breast cancer treatments. Results: We identified 47 recommendations supporting 17 genome-targeted drugs, which targeted 11 driver alterations. Out of these recommendations, 29 (62%) aligned with the FDA indications. We associated 47 trials with these recommendations, most randomized (24, 51%), phase 3 (23, 49%) and open-label (42, 89%). The most common primary endpoint (22, 47%) was overall response rate, followed by progression-free survival/time to progression (21, 45%). Twenty-four trials (51%) had a I-A ESCAT targetability, 7 (15%) had a I-B targetability, 6 (13%) had a I-C targetability score and 10 (21%) were categorized as II-B. ERBB2 amplification, germline BRCA1/2 mutations, PIK3CA mutations, and ESR1 mutation were mainly classified as tier I-A based on randomized trials demonstrating the effectiveness of approved targeted therapies in patients with these alterations. By contrast, RET fusions, NTRK fusions, high-tumor mutational burden and microsatellite instability were ranked as tier I-C and somatic BRCA mutations, germline PALB2 mutations and HER-2 mutations as II-B. Six trials (14%, 6/42) supporting drug approval demonstrated substantial ESMO-MCBS clinical benefit. Overall, 6 recommendations (14%) had high-benefit genomic-based cancer treatments. Conclusions: Fewer than one-fifth of molecular-targeted cancer therapies recommended in NCCN guidelines for metastatic breast cancer demonstrated substantial patient benefits. Value frameworks like ESCAT and ESMO-MCBS can help stakeholders identify therapies with the greatest potential. Citation Format: Ariadna Tibau, Thomas J. Hwang, Jerry Avorn, Aaron Kesselheim. Clinical Value of Molecular Targets and Genome-Targeted Cancer Therapies Recommended by the National Comprehensive Cancer Network for Advanced Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-10-08.

Effects of physiotherapy and home-based training in parkinsonian syndromes: protocol for a randomised controlled trial (MobilityAPP)

IntroductionGait and mobility impairment are pivotal signs of parkinsonism, and they are particularly severe in atypical parkinsonian disorders including multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). A pilot...

Risk factors for progressing to critical illness in patients with hospital-acquired COVID-19.

Risk factors for progression to critical illness in hospital-acquired coronavirus disease 2019 (COVID-19) remain unknown. Here, we assessed the incidence and risk factors for progression to critical illness and determined their effects on clinical outcomes in patients with hospital-acquired COVID-19. This retrospective cohort study analyzed patients admitted to the tertiary hospital between January 2020 and June 2022 with confirmed hospital-acquired COVID-19. The primary outcome was the progression to critical illness of hospital- acquired COVID-19. Patients were stratified into high-, intermediate-, or low-risk groups by the number of risk factors for progression to critical illness. In total, 204 patients were included and 37 (18.1%) progressed to critical illness. In the multivariable logistic analysis, patients with preexisting respiratory disease (OR, 3.90; 95% CI, 1.04-15.18), preexisting cardiovascular disease (OR, 3.49; 95% CI, 1.11-11.27), immunocompromised status (OR, 3.18; 95% CI, 1.11-9.16), higher sequential organ failure assessment (SOFA) score (OR, 1.56; 95% CI, 1.28-1.96), and higher clinical frailty scale (OR, 2.49; 95% CI, 1.62-4.13) showed significantly increased risk of progression to critical illness. As the risk of the groups increased, patients were significantly more likely to progress to critical illness and had higher 28-day mortality. Among patients with hospital-acquired COVID-19, preexisting respiratory disease, preexisting cardiovascular disease, immunocompromised status, and higher clinical frailty scale and SOFA scores at baseline were risk factors for progression to critical illness. Patients with these risk factors must be prioritized and appropriately isolated or treated in a timely manner, especially in pandemic settings.