Clinical Scale Research Articles

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.

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. The objective of this study was to explore potential sleep typing and its influencing factors in patients with MCI using latent class analysis. 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. 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. 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.

Precise prediction of cerebrospinal fluid amyloid beta protein for early Alzheimer's disease detection using multimodal data.

Alzheimer's disease (AD) constitutes a neurodegenerative disorder marked by a progressive decline in cognitive function and memory capacity. The accurate diagnosis of this condition predominantly relies on cerebrospinal fluid (CSF) markers, notwithstanding the associated burdens of pain and substantial financial costs endured by patients. This study encompasses subjects exhibiting varying degrees of cognitive impairment, encompassing individuals with subjective cognitive decline, mild cognitive impairment, and dementia, constituting a total sample size of 82 participants. The primary objective of this investigation is to explore the relationships among brain atrophy measurements derived from magnetic resonance imaging, atypical electroencephalography (EEG) patterns, behavioral assessment scales, and amyloid β-protein (Aβ) indicators. The findings of this research reveal that individuals displaying reduced Aβ1-42/Aβ-40 levels exhibit significant atrophy in the frontotemporal lobe, alongside irregularities in various parameters related to EEG frequency characteristics, signal complexity, inter-regional information exchange, and microstates. The study additionally endeavors to estimate Aβ1-42/Aβ-40 content through the application of a random forest algorithm, amalgamating structural data, electrophysiological features, and clinical scales, achieving a remarkable predictive precision of 91.6%. In summary, this study proposes a cost-effective methodology for acquiring CSF markers, thereby offering a valuable tool for the early detection of AD.

Quantitative Assessment via Multi-Domain Fusion of Muscle Synergy Associated With Upper-Limb Motor Function for Stroke Rehabilitation.

Quantitative assessment of upper limb motor function aids therapists in providing appropriate rehabilitation strategies, which plays an essential role in post-stroke rehabilitation. Traditional assessments, relying on clinical scales or kinematic metrics, often involve subjective scores or are influenced by compensatory strategies. Recently, the use of muscle synergies, representing simplified neuromuscular control, has emerged as a promising approach for post-stroke assessment. In general, muscle synergies are decomposed into two components: synergy vectors and synergy activation. Synergy vectors represent the relative weighting of each muscle within each synergy, that is muscle coordination; synergy activation represents the recruitment of the muscle synergy over time, that is muscle activation strength. Both components are vital for adequately assessing patients' motor function. Therefore, we integrate the spatial domain and temporal domain features extracted from synergy vectors and synergy activation, constructing a multi-domain assessment system using a Random Forest classifier, which may provide great qualitative classification accuracy. Furthermore, a novel functional score is generated from the probabilities belonging to the pathological group. Finally, A study involving ten healthy subjects and ten post-stroke patients validates the proposed method. The experimental results show that the classification accuracy was enhanced to 98.56% by fusing the characteristics derived from different domains, which was higher than that based on spatial domain (94.90%) and temporal domain (91.08%), respectively. Furthermore, the assessment score generated by multi-domain fusion framework exhibited a significant correlation with the clinical score. These promising results show the potential of applying the proposed method to clinical assessments for post-stroke patients.

An integrated approach to the assessment of balance and functional mobility in individuals with history of severe traumatic brain injury

Individuals who experienced severe Traumatic Brain Injury (sTBI) are often characterized by relevant motor dysfunctions which are likely to negatively affect activities of daily living and quality of life and often persist for years. However, detailed objective information about their magnitude are scarce. The aim of this study was to quantitatively assess the extent of motor deficits in terms of postural control effectiveness under static and dynamic conditions and to investigate the existence of possible correlations between the results of clinical tests and instrumental measures. Postural sway and functional mobility (i.e., instrumented Timed Up and Go test, iTUG) were objectively measured in 18 individuals with sTBI and 18 healthy controls using a pressure plate and a wearable inertial sensor. Additionally, participants with history of sTBI completed the Rivermead Mobility Index (RMI). One-way ANOVA and Spearman's rank correlation analysis were employed to examine differences between the two groups and determine potential correlations between the instrumental tests and clinical scales.The results show that people with sTBI were characterized by larger sway area and longer iTUG walking sub-phase. Significant correlations were also detected between RMI scores and iTUG total duration, as well as the walking phase. Taken together, these findings suggest that, even years after the initial injury, individuals with sTBI appear characterized by impaired postural control and functional mobility, which appears correlated with the RMI score. The integration of instrumental measures with clinical scales in the routine assessment and treatment of individuals with sTBI would result in more comprehensive, objective, and sensitive evaluations, thus improving precision in treatment planning, enabling ongoing progress monitoring, and highlighting the presence of motor deficits even years after the initial injury. Such integration is of importance for enhancing the long-term quality of life for individuals with sTBI.

Gender Differences in Prevalence and Associated Factors of Dyslipidemia in Initial-Treatment and Drug-Naïve Schizophrenia Patients.

Dyslipidemia is frequently comorbid with schizophrenia (SCZ), and both conditions often demonstrate significant gender differences in their clinical features. This study specifically focuses on investigating the prevalence of dyslipidemia and the factors that contribute to it in initial-treatment and drug-naïve (ITDN) SCZ patients, specifically focusing on gender differences. A total of 224 male ITDN SCZ patients and 424 female ITDN SCZ patients were included in this study. Socio-demographic and general clinical data of the patients were collected, and routine biochemical parameters, such as lipid levels, fasting blood glucose, thyroid function, renal function, and blood cell counts, were measured. Patients were also assessed for psychopathology and disease severity using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale - Severity of Illness (CGI-SI), respectively. In addition, a lipids score was calculated for assessing the severity of dyslipidemia. The study revealed that the prevalence of dyslipidemia in male patients was 34.02% (83/224), whereas 33.25% (141/424) in females, indicating no statistically significant difference (χ2 = 0.04, p = 0.841). For males, the risk factors for dyslipidemia were high education levels and diastolic blood pressure (DBP), while red blood cell count (RBC) as a protective factor. Additionally, DBP was identified as a risk factor for dyslipidemia score. In females, systolic blood pressure (SBP) was identified as a risk factor for dyslipidemia, while being married and creatinine (CRE) levels were found to be protective factors. Moreover, SBP was revealed as a risk factor for dyslipidemia score. No significant gender differences were observed in the prevalence of dyslipidemia among the ITDN SCZ patients. However, notable gender differences were identified in the factors influencing dyslipidemia and its severity within this group. These findings suggest the necessity of implementing gender-specific interventions to address the potential risk factors associated with dyslipidemia.

Neurocognitive Functioning in Adults with Trichotillomania: Predictors of Treatment Response and Symptom Severity in a Randomized Control Trial

Trichotillomania (TTM) is associated with impairments in response inhibition and cognitive flexibility, but it is unclear how such impairments relate to treatment outcome. The present study examined pre-treatment response inhibition and cognitive flexibility as predictors of treatment outcome, change in these domains from pre- to post-treatment, and associations with TTM severity. Participants were drawn from a randomized controlled trial comparing acceptance-enhanced behavior therapy (AEBT) to psychoeducation and supportive therapy (PST) for TTM. Adults completed assessments at pre-treatment (n=88) and following 12 weeks of treatment (n=68). Response inhibition and cognitive flexibility were assessed using the Stop Signal Task and Object Alternation Task, respectively. Participants completed the MGH-Hairpulling Scale. Independent evaluators administered the NIMH-Trichotillomania Severity Scale and Clinical Global Impressions-Improvement Scale. Higher pre-treatment TTM severity was associated with poorer pre-treatment cognitive flexibility, but not response inhibition. Better pre-treatment response inhibition performance predicted positive treatment response and lower post-treatment TTM symptom severity, irrespective of treatment assignment. Cognitive flexibility did not predict treatment response. After controlling for age, neither neurocognitive variable changed during treatment. Response inhibition and cognitive flexibility appear uniquely related to hair pulling severity and treatment response in adults with TTM. Implications for treatment delivery and development are discussed.

A novel high-precision fiber tractography for nuclear localization in transcranial magnetic resonance-guided focused ultrasound surgery: a pilot study.

In transcranial MR-guided focused ultrasound (TcMRgFUS), fiber tractography using diffusion tensor imaging (DTI) has been proposed as a direct method to identify the ventral intermediate nucleus (Vim), the ventral caudal nucleus (Vc), and the pyramidal tract (PT). However, the limitations of the DTI algorithm affect the accuracy of visualizing anatomical structures due to its low-quality fiber tractography, whereas the application of the generalized q-sampling imaging (GQI) algorithm enables the visualization of high-quality fiber tracts, offering detailed insights into the spatial distribution of motor cortex fibers. This retrospective study aimed to investigate the usefulness of high-precision fiber tractography using the GQI algorithm as a planning image in TcMRgFUS to achieve favorable clinical outcomes. This study included 20 patients who underwent TcMRgFUS. The Clinical Rating Scale for Tremor (CRST) scores and MR images were evaluated pretreatment and at 24 hours and 3-6 months after treatment. Cases were classified based on the presence and adversity of adverse events (AEs): no AEs, mild AEs without additional treatment, and severe AEs requiring prolonged hospitalization. Fiber tractography of the Vim, Vc, and PT was visualized using the DTI and GQI algorithm. The overlapping volume between Vim fibers and the lesion was measured, and correlation analysis was performed. The relationship between AEs and the overlapping volume of the Vc and PT fibers within the lesions was examined. The cutoff value to achieve a favorable clinical outcome and avoid AEs was determined using receiver operating characteristic curve analysis. All patients showed improvement in tremors 24 hours after treatment, with 3 patients experiencing mild AEs and 1 patient experiencing severe AEs. At the 3- to 6-month follow-up, 5 patients experienced recurrence, and 2 patients had persistent mild AEs. Although fiber visualization in the motor cortex using the DTI algorithm was insufficient, the GQI algorithm enabled the visualization of significantly higher-quality fibers. A strong correlation was observed between the overlapping volume that intersects the lesion and Vim fibers and the degree of tremor improvement (r = 0.72). Higher overlapping volumes of Vc and PT within the lesion were associated with an increased likelihood of AEs (p < 0.05); the cutoff volume of Vim fibers within the lesion for a favorable clinical outcome was 401 mm3, while the volume of Vc and PT within the lesion to avoid AEs was 99 mm3. This pilot study suggests that incorporating the high-precision GQI algorithm for fiber tractography as a planning imaging technique for TcMRgFUS has the potential to enhance targeting precision and achieve favorable clinical outcomes.

Lung outcomes and related risk factors in patients after SARS-CoV-2 infection: a hospitalised single-centre cohort from Johannesburg, South Africa

Sequelae post-SARS-CoV-2 infection, including lung and functional impairment, pose a significant challenge post-recovery. We explored the burden and risk factors for post-COVID-19 sequelae in an African population with prevalent comorbidities including tuberculosis (TB) and HIV. We conducted an observational cohort study on hospitalised adults with confirmed SARS-CoV-2 infection from 20 March to 06 October 2021at Chris Hani Baragwanath Academic Hospital, South Africa. We collected data on comorbidities, and COVID-19 severity using the World Health Organization (WHO) clinical progression scale. Prospectively, we followed up all participants within 40-days post-discharge to assess body mass index (BMI), COVID-19 symptoms and quality of life using St George's Respiratory Questionnaire (SGRQ), 6-min walking-test (6MWT), and spirometry. A subsequent in-depth visit assessed plethysmography, diffusing capacity for the lung for carbon monoxide (DLCO), and high-resolution chest-CT. We followed up 111 participants, where 65.8% were female, median age 50.5 years, and predominantly black-African (92.8%). Relevant comorbidities included TB disease (18.9%) and HIV infection (36%). SGRQ total scores were elevated in 78.9%, median 6MWT distance was reduced at 300m (IQR 210-400), and nearly half (49.5%) exhibited spirometry findings below the lower limit of normal (LLN). In-depth pulmonary assessment for 61 participants revealed abnormalities in total lung capacity (31.6%<80% predicted), DLCO (53.4%<80% predicted), and chest-CT (86.7% abnormal). Significant risk factors for individual abnormal outcomes, adjusted for age and sex, were TB disease, HIV with CD4 <200cells/mm3, BMI <18.5kg/m2 and >35kg/m2, and initial COVID-19 severity. This study demonstrates substantial lung and functional morbidity within the first weeks post-COVID-19, particularly in individuals with pre-existing comorbidities including TB, HIV, and low or high BMI. Chest-CT and DLCO show best early potential at reflecting COVID-19-related pathologies. The Bavarian State Ministry of Science and Arts.

Validation of a Supportive and Palliative Care Indicator Tool among hospitalized patients with heart failure

BackgroundPalliative care including symptom alleviation and advance care planning is relevant for patients with heart failure (HF). The Supportive and Palliative Care Indicator Tool (SPICT) is a tool for identifying patients who may benefit from palliative care assistance but is not validated in patients hospitalized for HF. Methods and ResultsClinical backgrounds, symptom burdens, and outcomes were evaluated using SPICT assessed on admission in consecutive hospitalized patients with HF. SPICT positive was defined as two or more general indicators and a New York Heart Association ≥III were present. Of 601 hospitalized patients with HF (mean age: 79±12 years, male: 314 [52%], and mean left ventricular ejection fraction: 44±18%), 100 (17%) patients were SPICT-positive. SPICT-positive patients were older (85±9 vs. 78±12 years; P<0.001) with higher clinical frailty scale (6±1 vs. 4±1 points; P<0.001), while symptom burdens assessed by the Integrated Palliative care Outcome Scale were not different (17 [13, 28] vs. 20 [11, 26] points; P=0.97) when compared with SPICT-negative. During the median follow-up period of 518 days, 178 patients (30%) died. SPICT positive was independently associated with higher all-cause mortality (hazard ratio: 3.49, 95% confidence interval: 2.41-5.05; P<0.001) after adjusting for age, sex, New York Heart Association class IV, Get-With-The-Guideline risk score, N-terminal pro B-type natriuretic peptide level, and left ventricular ejection fraction. ConclusionsIn patients admitted for HF, SPICT positive was significantly associated with higher all-cause mortality, suggesting the utility of SPICT as an indicator to initiate advance care planning for end-of-life care among hospitalized patients with HF.

Polysomnographic parameters associated with cognitive function in patients with major depression and insomnia.

To examine whether objective sleep parameters are associated with cognitive function (CF) in patients with major depressive disorder (MDD) with chronic insomnia (CI) and whether the severity of these disorders is related to CF. Thirty patients with MDD with CI attending a tertiary care institution underwent two consecutive nights of polysomnographic (PSG) recording and a battery of neuropsychological tests, which included episodic memory, sustained attention, working memory, and executive function. The severity of MDD and CI was assessed by clinical scales. We examined the relationship between PSG parameters and CF, as well as whether the severity of the disorders is related to CF. Linear regression analysis revealed that total sleep time (TST) was positively associated with higher learning and recall of episodic memory, as well as better attention. Slow-wave sleep (SWS) showed a positive association with better working memory. Furthermore, wake after sleep onset (WASO) was negatively associated with episodic memory and lower attention. No significant relationships were found between the severity of MDD or CI with CF. Both sleep duration and depth are positively associated with several aspects of CF in patients with MDD with CI. Conversely, a lack of sleep maintenance is negatively related to CF in these patients. These findings could help identify modifiable therapeutic targets to reduce CF impairment.

Hypo-connectivity of the primary somatosensory cortex in Parkinson's disease: a resting-state functional MRI study.

Parkinson's disease (PD) is characterized by a range of motor symptoms as well as documented sensory dysfunction. This sensory dysfunction can present itself either as a "pure" sensory disturbance or as a consequence of sensory-motor integration within the central nervous system. This study aims to investigate changes in the functional connectivity of the primary somatosensory cortex (S1) and its clinical significance in Parkinson's disease (PD), an area that has received limited attention in previous neuroimaging studies. This study included thirty-three patients with PD and thirty-four healthy controls (HCs). Clinical evaluations were conducted to assess the clinical manifestations, severity, and functional capacity of all the patients. Resting-state functional MRI (fMRI) was employed to evaluate the functional connectivity of six paired S1 subregions in the participants. Seed-based correlation (SBC) analysis was utilized to construct the correlation matrix among the subregions and to generate connectivity maps between the subregions and the remaining brain voxels. Finally, the study employed partial least-squares (PLS) correlation analysis to investigate the association between modified functional connectivity and clinical characteristics in PD patients. In the correlation matrix, patients with PD demonstrated a notable decrease in functional connectivity across various S1 subregions in comparison to HCs (p < 0.001, corrected using network-based methods). In connectivity maps, hypo-connectivity was primarily observed in the sensorimotor network as common patterns (p < 0.001, corrected for false discovery rate) and in the default mode network (DMN) as distinct patterns. Moreover, this study identified a negative association between the correlation matrix within S1 subregions and the scores for axial symptoms and postural instability/gait difficulty (PIGD) in PD patients. Nevertheless, a direct relationship between the connectivity maps of S1 subregions and clinical assessment scales was not established. This study offers novel insights into the neurobiological mechanisms that contribute to S1 dysfunction in PD, highlighting the significant involvement of S1 hypo-connectivity in the motor disturbances observed in PD patients.

Comparative Study of Clinical Frailty in Elderly Patients with Mild Cognitive Impairment and Dementia

Abstract Background: Health-harming stressors increase frailty in the elderly, which is linked to dementia progression. Objectives: The aim of this study was to evaluate a clinical frailty scale in elderly patients with mild cognitive impairment (MCI) and dementia compared to those without cognitive impairment. Methods: An analytical, individual-based, observational study was conducted on 212 elderly individuals (82 with normal cognition, 64 with MCI, and 66 with dementia), matched for age, sex, and schooling. Results: When comparing the groups of normal and demented patients, individuals with MCI exhibited an intermediate level of functionality (p-value &lt; 0.001) and clinical frailty (p-value &lt; 0.001), as determined by statistical analysis using ANOVA and Tukey's post hoc test. Conclusion: The findings suggest that the intermediate degree of functionality and clinical frailty observed in patients with MCI enables the implementation of individual multidomain intervention programs. These interventions may potentially mitigate the progressive decline associated with dementia. Keywords: Elderly, Dementia, Frail elderly, Memory disorder, Observational study.