Studies In Clinical Populations Research Articles

The state of cancer care in Russia: pancreas cancer (C25). The survival rate of patients, taking into account the stage, localization and histological structure. Part II (clinical-population study)

The state of cancer care in Russia: pancreas cancer (C25). The survival rate of patients, taking into account the stage, localization and histological structure. Part II (clinical-population study)

Psychometric evaluation of the German version of the Questionnaire of Cognitive and Affective Empathy (QCAE)

Empathy as a central element of social cognition plays a decisive role in various psychosocial areas and interpersonal dynamics, especially within the context of psychotherapy. Despite the controversy surrounding a standardized definition, empathy is generally regarded as a multidimensional concept that encompasses both cognitive and affective dimensions. This differentiation between cognitive and affective facets is addressed by a widely used and internationally well-established self-report measure of empathy, the Questionnaire of Cognitive and Affective Empathy (QCAE). This study focuses on evaluating the psychometric properties of the German version of the QCAE. In a convenience sample (N=1300), the postulated confirmatory five-factor model showed an adequate fit to the underlying structure. The subscales of the QCAE exhibited satisfactory internal consistency and convergent validity with other instruments measuring empathy. Despite certain methodological limitations, our findings suggest that the German version of the QCAE is suitable as a reliable and valid instrument for measuring empathy. Further studies in population-representative samples and clinical populations are required before a clear recommendation regarding its utilization can be provided.

Experiencing Psychosis and Shame: A Systematic Review and Meta-analysis of the Strength and Patterns of Association.

Shame has been linked to the experience of psychosis, with implications for clinical outcomes, however, a meta-analysis of the relationship has not yet been conducted. This systematic review and meta-analysis aimed to examine the strength of the association between shame and psychosis, and any variations between clinical and non-clinical populations and shame type (internal vs external shame). Searches were conducted in CINAHL, EMBASE, PsycInfo, PubMed, Scopus, and Web of Science from the inception of the e-databases until July 2023. For inclusion, studies reported a quantitative association between psychosis and shame, or data that could be used to identify a relationship. From 11372 unique retrieved records, 40 articles met the inclusion criteria and 38 were included in the meta-analyses. A significant large pooled estimate of the psychosis-shame association was identified (Zr = 0.36, [95% CI: 0.28, 0.44], P < .001), indicating that higher levels of shame were associated with greater severity of psychotic symptoms. The strength of the association was similar across clinical and non-clinical populations, however, differed by type of shame and psychosis symptom measured. External shame was strongly associated with paranoia suggesting possible confounding. Only a minority of studies met the highest quality criteria. Shame is strongly associated with the severity of psychotic symptoms in clinical and non-clinical populations. Given the overlap with paranoia, measurement of external shame alone is not advised. Larger studies in clinical populations, with measures of a range of psychosis symptoms, are needed to better understand the relationship between shame and specific symptoms.

Multilayer meta-matching: Translating phenotypic prediction models from multiple datasets to small data

Abstract Resting-state functional connectivity (RSFC) is widely used to predict phenotypic traits in individuals. Large sample sizes can significantly improve prediction accuracies. However, for studies of certain clinical populations or focused neuroscience inquiries, small-scale datasets often remain a necessity. We have previously proposed a “meta-matching” approach to translate prediction models from large datasets to predict new phenotypes in small datasets. We demonstrated a large improvement over classical kernel ridge regression (KRR) when translating models from a single source dataset (UK Biobank) to the Human Connectome Project Young Adults (HCP-YA) dataset. In the current study, we propose two meta-matching variants (“meta-matching with dataset stacking” and “multilayer meta-matching”) to translate models from multiple source datasets across disparate sample sizes to predict new phenotypes in small target datasets. We evaluate both approaches by translating models trained from five source datasets (with sample sizes ranging from 862 participants to 36,834 participants) to predict phenotypes in the HCP-YA and HCP-Aging datasets. We find that multilayer meta-matching modestly outperforms meta-matching with dataset stacking. Both meta-matching variants perform better than the original “meta-matching with stacking” approach trained only on the UK Biobank. All meta-matching variants outperform classical KRR and transfer learning by a large margin. In fact, KRR is better than classical transfer learning when less than 50 participants are available for finetuning, suggesting the difficulty of classical transfer learning in the very small sample regime. The multilayer meta-matching model is publicly available at https://github.com/ThomasYeoLab/Meta_matching_models/tree/main/rs-fMRI/v2.0.

Abstract PO1-28-01: MammaPrint and BluePrint identify racial disparities among women with HR+HER2- early-stage breast cancer

Abstract INTRODUCTION: Black women are 41% more likely to die from breast cancer compared to White women yet remain underrepresented in clinical trials and population studies. We have previously shown a higher proportion of Black women with HR+HER2- tumors further classify as Basal-Type compared with White women, using BluePrint molecular subtyping. Other studies have demonstrated higher 3-year recurrence rates in patients with BluePrint Basal-Type tumors compared to Luminal-Type. To determine whether the increased frequency of HR+/Basal-Type tumors impacts long-term outcomes in this cohort, we compared 3-year outcomes with BluePrint and the risk of distant recurrence signature, MammaPrint (MP), between Black and White women with HR+HER2- breast cancer. We also evaluated the association of MP and BluePrint with 10-year outcomes in a subset of Black women. METHODS: This study included 635 women with stage I-III, HR+HER2- breast cancer, of whom, 135 Black women were enrolled in the BEST study between 2005-2015 (R01-CA204819), and 120 Black women and 380 White women are enrolled in the ongoing FLEX study (NCT03053193). Each patient had MP and BluePrint testing. MP classifies tumors as having a Low Risk or High Risk of distant recurrence. BluePrint categorizes tumors as Luminal-Type, HER2-Type, or Basal-Type. Together, MP and BluePrint further stratify Luminal tumors into Luminal A-Type (MP Low Risk) and Luminal B-Type (MP High Risk). Recurrence-free survival (RFS) was the primary endpoint. Overall survival (OS) at 10 years was the secondary endpoint for those with long-term follow up. RFS and OS are defined per STEEP criteria. Survival curves were estimated using Kaplan-Meier analyses, and significance between groups was determined using log-rank test. RESULTS: Among all patients, 14.5% of Black women had BluePrint Basal-Type tumors compared to 5.8% of White women (p &amp;lt; 0.001). Median follow up was 3.0 years for patients in FLEX, and 10.1 years for patients in BEST. The unstratified 3-year RFS was 93.6% (95% CI 90.7 – 96.7) for Black patients and 93.6% (95% CI 91.1 – 96.3) for White patients. When further stratified by MP and BluePrint, 3-year RFS for patients with HR+HER2- tumors significantly differed (p=0.002). Patients with HR+/Luminal A tumors exhibited the best 3-year RFS (96.9%; 95% CI 95.0 – 98.9), followed by HR+/Luminal B tumors (91.6%; 95% CI 88.2 – 95.1), and HR+/Basal tumors (85.8%; 95% CI 77.2 – 95.5). For a subset of patients with 10-year follow up, we evaluated the association of MP and BluePrint with RFS (n=135) and OS (n=134). The unstratified 10-year RFS and OS rates for Black women were 88.4% (95% CI 82.9 – 94.2) and 89.0% (95% CI 83.7 – 94.7), respectively. When stratified by MP and BluePrint, Black patients with HR+/Luminal A tumors had a 10-year RFS of 97.7% (95% CI 93.4 – 100), versus 83.5% (95% CI 74.8 – 93.1) for patients with HR+/Luminal B, and 85.0% (95% CI 70.7 – 100) for patients with HR+/Basal tumors (p=0.080). Similarly, Black patients with HR+/Luminal A tumors exhibited excellent 10-year OS (100%), whereas OS for patients with HR+/Luminal B (83.5%; 95% CI 74.8 – 93.1) and HR+/Basal tumors (85.0%; 95% CI 70.7 – 100) were significantly lower (p=0.026). CONCLUSION: Survival outcomes at 3 years were comparable between Black and White patients. MP and BluePrint more precisely stratified tumors resulting in distinct 3- and 10-year outcomes, independent of race, beyond clinical subtype alone. Additionally, the subset of Black patients with Low Risk, Luminal A-Type tumors had excellent 10-year survival outcomes. Patients with HR+ tumors that further classify as Basal-Type, which occur more frequently in Black patients, have worse outcomes compared to Luminal A-Type tumors, and may warrant more aggressive treatment. These data highlight the importance of genomic testing to help optimize treatments and reduce outcome disparities in Black women. Citation Format: Sonya Reid, Xiao-Ou Shu, Lindsay Venton, Josien Haan, Andrea Menicucci, Patricia Dauer, William Audeh, Tuya Pal. MammaPrint and BluePrint identify racial disparities among women with HR+HER2- early-stage 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 PO1-28-01.

The state of cancer care in Russia: liver cancer – (C22). Age-related characteristics of morbidity and mortality, quality of registration, effectiveness of patient treatment. (clinical population study). Part 1

A clinical-population study was conducted to identify patterns in the dynamics of incidence, mortality, and patient accounting for liver cancer in Russia, as well as the specifics of changes in the structure of affected individuals by detailed localization and age. Over an 11-year period, the incidence of liver cancer in Russia increased by 24.4%, while mortality rose by 9.6%. Special attention was paid to the nature of changes in age-specific incidence and mortality rates for the population of Russia with liver cancer. The aim of the study was to investigate the dynamics of key parameters of incidence, mortality, and the quality of primary patient accounting for liver cancer at the population level in Russia and the Northwestern Federal District of the Russian Federation. The study results confirmed the severity of the problem of this pathology and the challenges associated with the timely detection and provision of adequate care to patients with liver cancer. In some territories, the mortality rate from liver cancer exceeded the number of newly diagnosed patients by 2–3 times. The impact of the coronavirus infection pandemic on the quality of registration of liver cancer patients was also assessed. The study also presented modern possibilities for early diagnosis and treatment of patients with liver cancer.

Exploring the Effectiveness of Pre-Exposure Prophylaxis (PrEP) Use for HIV Prevention among High-Risk Populations

Addressing the global burden of HIV requires effective preventative measures that have been shown to have high efficacy rates. PrEP is one of the preventative measures that is effective in preventing HIV. Different clinical trials and population studies have shown PrEPto have an efficacy rate of 40% to 90% when it comes to preventing HIV. Due to its high efficacy, PrEPcan reduce new HIV infections populations considered to be high risk. However, for efficacy to be high, there is a need to increase medication adherence and address the existing barriers that limit uptake. Some of these barriers are lack of knowledge, inadequate access, stigma,lack of trust in service providers, low perception of HIV risk, cost, and fear of side effects. Addressing these barriers can increase PrEP uptake and help in reducing HIV’s risk among high-risk populations. Some of the measures that can be put in place to address these barriers are providing education and training, allocating enough resources, leveraging technology, lowering PrEP costs, increasing insurance coverage, and improving communication among the targeted population.

Impact of the Covid pandemic on the mental health of children and young people with pre-existing mental health and neurodevelopmental conditions: a systematic review and meta-analysis

IntroductionExisting systematic reviews have suggested mixed effects of the Covid pandemic on the mental health of children and young people. Those with pre-existing mental health and neurodevelopmental conditions have been suggested to be disproportionately affected, but this has not been meta-analysed. Most reviews of studies in clinical populations to date only include cross-sectional studies during the first lockdown or longitudinal cohorts up to early 2021, which limits our understanding of causality and long-term effects. To our knowledge, this is the first systematic review and meta-analysis to examine the longitudinal impact of the pandemic on the mental health of children and young people with pre-existing mental health and neurodevelopmental conditions.ObjectivesTo compare 1) mental health pre versus during Covid, and 2) mental health during Covid.MethodsMedline, Embase, APA PsycInfo, and Global Health databases were searched up to August 2023. Longitudinal studies reporting mental health outcomes in children and young people (≤18 years old) with pre-Covid mental health and/or neurodevelopmental conditions were included. Cohorts were deemed eligible if children and young people were diagnosed using a diagnostic assessment, scored above clinical threshold on validated measures, or attended mental health services pre-Covid. Outcomes included internalising, externalising, and other symptoms. Studies were narratively synthesised by symptom category and meta-analyses performed where number of studies reporting the same outcomes were sufficient (≥5).Results6,083 records were identified and 21 studies (N=2,617) were included. These widely differed in country, setting, diagnosis, outcome, and timepoints under study. The narrative synthesis highlighted mixed findings in mental health changes during the pandemic for all three symptom categories showing increases, reductions, and no changes. Only studies reporting changes in internalising symptoms pre- versus during the pandemic were in sufficient number to be amenable to meta-analysis.ConclusionsOur findings suggest the pandemic’s impact on the mental health of children and young people with pre-existing mental health and neurodevelopmental conditions were complex and varied. We highlight an urgent need for longitudinal Covid research on long-term mental health outcomes in this vulnerable group. Understanding risk factors and longitudinal trajectories is warranted to guide clinical practice and policy.Disclosure of InterestNone Declared

Cortical white matter microstructural alterations underlying the impaired gamma-band auditory steady-state response in schizophrenia

The gamma-band auditory steady-state response (ASSR), primarily generated from the auditory cortex, has received substantial attention as a potential brain marker indicating the pathophysiology of schizophrenia. Previous studies have shown reduced gamma-band ASSR in patients with schizophrenia and demonstrated correlations with impaired neurocognition and psychosocial functioning. Recent studies in clinical and healthy populations have suggested that the neural substrates of reduced gamma-band ASSR may be distributed throughout the cortices surrounding the auditory cortex, especially in the right hemisphere. This study aimed to investigate associations between the gamma-band ASSR and white matter alterations in the bundles broadly connecting the right frontal, parietal and occipital cortices to clarify the networks underlying reduced gamma-band ASSR in patients with schizophrenia. We measured the 40 Hz ASSR using electroencephalography and diffusion tensor imaging in 42 patients with schizophrenia and 22 healthy comparison subjects. The results showed that the gamma-band ASSR was positively correlated with fractional anisotropy (an index of white matter integrity) in the regions connecting the right frontal, parietal and occipital cortices in healthy subjects (β = 0.41, corrected p = 0.075, uncorrected p = 0.038) but not in patients with schizophrenia (β = 0.17, corrected p = 0.46, uncorrected p = 0.23). These findings support our hypothesis that the generation of gamma-band ASSR is supported by white matter bundles that broadly connect the cortices and that these relationships may be disrupted in schizophrenia. Our study may help characterize and interpret reduced gamma-band ASSR as a useful brain marker of schizophrenia.

Incidence of immune-related adverse events in U.S. veterans treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) are associated with potentially severe immune-related adverse events (irAEs). Emerging clinical practice reports have suggested higher incidence of irAEs in real-world settings than initially observed in phase III clinical trials. Objectives were to determine the incidence of irAEs associated with ICIs in a clinical population, the Veterans Health Administration, characterize their time to onset, and explore potential risk factors. This retrospective observational study included patients from eight Midwest VA medical centers who initiated an ICI between January 1, 2014, and June 30, 2022. Courses of incident prednisone therapy lasting at least seven days at a dose ≥ 20 mg/day were used to identify irAEs, within two years following ICI initiation. A multivariate Cox proportional hazards regression model was used to explore potential irAE risk factors. Of 1314 patients, the incidence of irAEs was 19.8%, with most (86.5%) occurring within one year of ICI initiation. Monthly incidence rates peaked three months following ICI initiation at 3.0% and decreased thereafter. Female gender (hazard ratio [HR] = 2.01, 95% confidence interval [CI]: 1.01-4.00) and combination therapy with ipilimumab and nivolumab (HR = 2.46, 95% CI: 1.44-4.21) were significantly associated with irAE incidence. These findings are consistent with recent studies in clinical populations that demonstrate higher irAE incidence rates than originally reported in clinical trials. Our findings may enhance prompt recognition and treatment of irAEs for VA patients.

Diversity, equity, and inclusivity in observational ambulatory assessment: Recommendations from two decades of Electronically Activated Recorder (EAR) research.

Ambient audio sampling methods such as the Electronically Activated Recorder (EAR) have become increasingly prominent in clinical and social sciences research. These methods record snippets of naturalistically assessed audio from participants' daily lives, enabling novel observational research about the daily social interactions, identities, environments, behaviors, and speech of populations of interest. In practice, these scientific opportunities are equaled by methodological challenges: researchers' own cultural backgrounds and identities can easily and unknowingly permeate the collection, coding, analysis, and interpretation of social data from daily life. Ambient audio sampling poses unique and significant challenges to cultural humility, diversity, equity, and inclusivity (DEI) in scientific research that require systematized attention. Motivated by this observation, an international consortium of 21 researchers who have used ambient audio sampling methodologies created a workgroup with the aim of improving upon existing published guidelines. We pooled formally and informally documented challenges pertaining to DEI in ambient audio sampling from our collective experience on 40+ studies (most of which used the EAR app) in clinical and healthy populations ranging from children to older adults. This article presents our resultant recommendations and argues for the incorporation of community-engaged research methods in observational ambulatory assessment designs looking forward. We provide concrete recommendations across each stage typical of an ambient audio sampling study (recruiting and enrolling participants, developing coding systems, training coders, handling multi-linguistic participants, data analysis and interpretation, and dissemination of results) as well as guiding questions that can be used to adapt these recommendations to project-specific constraints and needs.

Is prevention of ADHD and comorbid conditions in adolescents possible?

Objectives: To examine how the concept of prevention is applicable to adolescent ADHD, which preventive interventions may be feasible, and which methods can be used to evaluate effectiveness. Method: Following a literature search for prevention clinical trials relevant to adolescent ADHD, selected studies are critically reviewed to identify suitable targets and promising interventions. Results: There is some evidence from controlled studies that interventions delivered to prepubertal children at high risk for ADHD or diagnosed with ADHD may decrease the incidence or persistence of ADHD in adolescence. Uncontrolled follow-up of clinical samples and population studies suggest that treatment of adolescents with ADHD can decrease the risk for several negative functional outcomes in youth. A controlled trial found a specific cognitive training intervention to decrease risky driving. Conclusions: Prevention of ADHD and associated negative outcomes is possible and of high clinical relevance. Assessing prevention effects is methodologically challenging, but feasible.

CE Workshop 10: Advances in Event-Related Potential Methods for Assessing Clinical Populations

Abstract &amp; Learning Objectives:Event-related potentials (ERPs) have been used to examine perceptual, cognitive, motor, and affective processes for over 50 years. Although newer techniques provide greater neuroanatomical specificity, the excellent temporal resolution and ease of acquisition of ERPs continue to be highly valuable. In addition, continued methodological refinements have made it possible to answer progressively more sophisticated questions using ERPs. In this presentation, I will describe several key methodological improvements that are now in widespread use or are on the verge of becoming widely used. This will include improved recording methods, such as innovations in electrodes that allow both fast and low-noise EEG acquisition. It will also include EEG preprocessing methods that minimize artifacts and increase the signal-to-noise ratio of the ERPs. Finally, it will include multivariate pattern analysis methods that can be used to "decode" what a participant perceives and stores in working memory. Together, these new methods have dramatically increased the information that can be obtained about dysfunctional brain activity in clinical populations.Upon conclusion of this course, learners will be able to: 1.Evaluate and critically assess ERP studies of clinical populations that were published over the last decade, making use of advanced recording and analysis methods that are now widely used2.Evaluate and critically assess ERP studies of clinical populations that have been published recently or will be published in the near future that take advantage of state-of-the-art recording and analysis methods, such as dry electrodes and multivariate pattern analysis3.Integrate recent and emerging research findings into your research or clinical practice

State of cancer care in Russia: Age and cancer. Features of localization structure, quality of recording, and survival of middle-aged patients with CNS tumors (a clinical-population study). Part 3.

According to the World Health Organization (WHO) standard, the middle age refers to the population between 45 and 59 years old. In the previous two studies, we examined the specific characteristics of the detailed localization structure of morbidity, mortality, and survival of children, adolescents, and young adults. This analysis of these characteristics for individuals belonging to the middle age group is conducted for the first time. The population belonging to this age group is most actively involved in public life, has a stable financial status, and often finds themselves at the peak of their professional and personal maturity. The concept of "middle age" encompasses three components. According to the WHO standards, the first component represents the total population aged 45 to 49 years. In the previous two studies, we examined the characteristics of the detailed localization structure of morbidity, mortality, and survival of children, adolescents, and young adults. The analysis of these characteristics for individuals belonging to the middle age group is conducted for the first time. The population that falls within this age group is most actively involved in public life, has a stable socioeconomic status, and often reaches the pinnacle of their professional and personal maturity. The concept of "middle age" encompasses three components. According to the standards of the World Health Organization (WHO), the first component represents the aggregate population aged 45 to 49 years.

State of oncological care in Russia: age and cancer. Features of the localization structure, quality of recording, and survival of young adults with malignant neoplasms (clinical-population study). Part 2.

In the first part of our clinical-population study, we present the results of assessing the effectiveness of anti-cancer measures conducted in Russia among children and adolescents. In this study, we focus on the prevalence and structure of oncological diseases, the quality of accounting, and the survival of primary patients in the "young adults" age group. To address the set tasks, we selected two groups for research: the entire Russia for calculating the incidence, mortality, and quality of accounting for patients, as well as the entire Northwest Federal District for calculating the survival of cancer patients. According to the WHO classification, young population is considered to be the age group from 18 to 44 years, i.e. after the adolescent period and up to 45 years. The main goal of our study is to investigate the specifics of the localization structure of oncological diseases for different age groups of the population, and the main reports present data for five-year age groups. In the future, we will analyze the features of the localization structure of oncopathology by five-year age intervals, starting from the age group of 20-24 years. This is of particular importance, as our previous study of the adolescent group (15-19 years old) did not reveal significant differences in the structure and survival of patients aged 15-17 years.

Brief Form of the Affective Neuroscience Personality Scales: Preliminary Psychometric Properties in a European Portuguese Community Sample.

Personality theory based on affective neuroscience research suggests the presence of seven affective neurobiological systems. These dimensions have been identified using psychometric instruments such as the Affective Neuroscience Personality Scales (ANPS) and its brief version known as the Brief Affective Neuroscience Personality Scales (BANPS). Despite being a psychometric valid instrument, the BANPS was not adapted to European Portuguese. This study describes a psychometric analysis of the BANPS in a Portuguese population sample. A European Portuguese-speaking sample was recruited (N = 355, Mage = 27.31, DP = 12.75). Confirmatory factor analysis (CFA) was used to confirm the BANPS factorial structure. Pearson correlations were used to explore convergent validity with self-reports for psychological distress and psychopathology. Six factor model was confirmed with adequate goodness-of-fit indices (χ2(449) = 808,9841, TLI = .90, CFI = .92, RMSEA = .048 (.042-.053). Non-agreeable affective systems (anger, fear, distress), correlated positively with psychological distress and symptomology, while play and care systems correlated negatively. Seek and care subscales showed the weakest psychometric properties. The original factor structure was confirmed, suggesting the BANPS may be a valid measure to assess affective behavioral traits in the Portuguese population. Further studies in clinical populations may improve the psychometric data of the BANPS.

Metabolic systems approaches update molecular insights of clinical phenotypes and cardiovascular risk in patients with homozygous familial hypercholesterolemia

BackgroundHomozygous familial hypercholesterolemia (HoFH) is an orphan metabolic disease characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C), xanthomas, aortic stenosis, and premature atherosclerotic cardiovascular disease (ASCVD). In addition to LDL-C, studies in experimental models and small clinical populations have suggested that other types of metabolic molecules might also be risk factors responsible for cardiovascular complications in HoFH, but definitive evidence from large-scale human studies is still lacking. Herein, we aimed to comprehensively characterize the metabolic features and risk factors of human HoFH by using metabolic systems strategies.MethodsTwo independent multi-center cohorts with a total of 868 individuals were included in the cross-sectional study. First, comprehensive serum metabolome/lipidome-wide analyses were employed to identify the metabolomic patterns for differentiating HoFH patients (n = 184) from heterozygous FH (HeFH, n = 376) and non-FH (n = 100) subjects in the discovery cohort. Then, the metabolomic patterns were verified in the validation cohort with 48 HoFH patients, 110 HeFH patients, and 50 non-FH individuals. Subsequently, correlation/regression analyses were performed to investigate the associations of clinical/metabolic alterations with typical phenotypes of HoFH. In the prospective study, a total of 84 HoFH patients with available follow-up were enrolled from the discovery cohort. Targeted metabolomics, deep proteomics, and random forest approaches were performed to investigate the ASCVD-associated biomarkers in HoFH patients.ResultsBeyond LDL-C, various bioactive metabolites in multiple pathways were discovered and validated for differentiating HoFH from HoFH and non-FH. Our results demonstrated that the inflammation and oxidative stress-related metabolites in the pathways of arachidonic acid and lipoprotein(a) metabolism were independently associated with the prevalence of corneal arcus, xanthomas, and supravalvular/valvular aortic stenosis in HoFH patients. Our results also identified a small marker panel consisting of high-density lipoprotein cholesterol, lipoprotein(a), apolipoprotein A1, and eight proinflammatory and proatherogenic metabolites in the pathways of arachidonic acid, phospholipid, carnitine, and sphingolipid metabolism that exhibited significant performances on predicting first ASCVD events in HoFH patients.ConclusionsOur findings demonstrate that human HoFH is associated with a variety of metabolic abnormalities and is more complex than previously known. Furthermore, this study provides additional metabolic alterations that hold promise as residual risk factors in HoFH population.

Profiling of plasma biomarkers in the context of memory assessment in a tertiary memory clinic

Plasma biomarkers have shown promising performance in research cohorts in discriminating between different stages of Alzheimer’s disease (AD). Studies in clinical populations are necessary to provide insights on the clinical utility of plasma biomarkers before their implementation in real-world settings. Here we investigated plasma biomarkers (glial fibrillary acidic protein (GFAP), tau phosphorylated at 181 and 231 (pTau181, pTau231), amyloid β (Aβ) 42/40 ratio, neurofilament light) in 126 patients (age = 65 ± 8) who were admitted to the Clinic for Cognitive Disorders, at Karolinska University Hospital. After extensive clinical assessment (including CSF analysis), patients were classified as: mild cognitive impairment (MCI) (n = 75), AD (n = 25), non-AD dementia (n = 16), no dementia (n = 9). To refine the diagnosis, patients were examined with [18F]flutemetamol PET (Aβ-PET). Aβ-PET images were visually rated for positivity/negativity and quantified in Centiloid. Accordingly, 68 Aβ+ and 54 Aβ– patients were identified. Plasma biomarkers were measured using single molecule arrays (SIMOA). Receiver-operated curve (ROC) analyses were performed to detect Aβ-PET+ using the different biomarkers. In the whole cohort, the Aβ-PET centiloid values correlated positively with plasma GFAP, pTau231, pTau181, and negatively with Aβ42/40 ratio. While in the whole MCI group, only GFAP was associated with Aβ PET centiloid. In ROC analyses, among the standalone biomarkers, GFAP showed the highest area under the curve discriminating Aβ+ and Aβ– compared to other plasma biomarkers. The combination of plasma biomarkers via regression was the most predictive of Aβ-PET, especially in the MCI group (prior to PET, n = 75) (sensitivity = 100%, specificity = 82%, negative predictive value = 100%). In our cohort of memory clinic patients (mainly MCI), the combination of plasma biomarkers was sensitive in ruling out Aβ-PET negative individuals, thus suggesting a potential role as rule-out tool in clinical practice.

Emotional and behavioral outcomes among youths with mental disorders during the first Covid lockdown and school closures in England: a large clinical population study using health care record integrated surveys

PurposeEmotional and behavioral problems in children and young people (CYP) have increased over the pandemic. Those with pre-existing mental disorders are more vulnerable but have been understudied. We investigated emotional and behavioral outcomes in this population; differences across diagnostic groups; and social, educational, and clinical determinants.MethodsWe invited 5386 caregivers and CYP (aged 5–17) under child mental health services pre-pandemic to complete an online survey on CYP’s emotional/behavioral symptoms and pandemic-related circumstances, and integrated responses with clinicodemographic information extracted from electronic health records. We compared four parent-rated outcomes (total emotional/behavioral scores and emotional/behavioral changes as compared to before the pandemic) across the three most common diagnostic groups in our population (Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD) and emotional disorders (EmD)). We then estimated the association of clinicodemographic and pandemic-related characteristics with emotional/behavioral outcomes.ResultsA total of 1741 parents (32.3%) completed the survey. Parents of CYP with ADHD or ASD reported more behavioral difficulties (t(591) = 5.618 (0.001); t(663) = 6.527 (0.001)); greater emotional deterioration (t(591) = 2.592 (0.009); t(664) = 4.670 (< 0.001); and greater behavioral deterioration (t(594) = 4.529 (< 0.001); t(664) = 5.082 (< 0.001)) as compared to the EmD group. Those with ASD and EmD showed more emotional difficulties than ADHD (t(891) = − 4.431 (< 0.001); t(590) = − 3.254 (0.001)). Across diagnoses, poor parental mental health and challenges with education were most strongly associated with worse outcomes.ConclusionsWithin our clinical population, CYP with ADHD/ASD were the most adversely affected during lockdown. Enhancing clinical service provision that tackles parental stress and supports education may help mitigate the impact of future restrictions.

An exploratory structural equation modelling (ESEM) of the Eating Disorders Examination Questionnaire (EDE-Q) in bariatric patients.

Several studies in clinical and non-clinical populations indicate differences between rationally and empirically derived subscales for the Eating Disorder Examination Questionnaire (EDE-Q), including samples of patients seeking bariatric surgery. This study aimed to use exploratory structural equation modelling (ESEM) to estimate the factor structure of the EDE-Q and assess for the additive value of alternative measurement of eating disorder symptoms. Adolescents and adults completed the EDE-Q and a psychiatric evaluation prior to bariatric surgery. Data from 330 participants were analysed using the original four-factor and modified three-factor structure of the EDE-Q using both confirmatory factor analysis (CFA) and exploratory structural equation modelling (ESEM). Age, ethnicity, and body mass index were examined as covariates in the best fitting model, and model subscales used to generate a predictive model of clinician screened DSM-5 eating disorder diagnoses for criterion validity. A CFA of the four-factor EDE-Q provided poor model fit for a pre-surgical bariatric population, but the three-factor EDE-Q and an ESEM of the four-factor EDE-Q provided excellent model fit. The Eating Concern subscale of the four-factor ESEM model significantly predicted eating disorder diagnosis and was positively correlated with age. Our results suggest the ESEM derived factors of the EDE-Q offered some improvements to the original empirically derived factor structure, as subscale scores based on the original items and cross-loading items yielded an adequate prediction of clinician diagnoses.