Case-control Comparison Research Articles

Analysis of the Methylation Level of the DAT1 Dopamine Transporter Gene in Patients Addicted to Stimulants, Taking into Account an Analysis of Personality Traits.

Drug addiction is a chronic biochemical drug use disorder that affects the human brain and behavior and leads to the uncontrolled use of legal or illicit drugs. It has been shown that three factors are involved in the development of addiction: genetic factors, a diverse environment, and the effect of medication on gene expression. The comprehensive approach and holistic analysis of the problem are due to the multigenic and multifactorial nature of addiction. Dopamine, one of the major neurotransmitters in the brain, is believed to be the "culprit" that leads to a drug abuse-induced "high". That is why, in our research, we focused mainly on the genes related to dopaminergic reuptake. In the present study, we chose methylation of the DAT1 dopamine transporter gene based on molecular reasons related to the dopaminergic theory of addiction. This study included two groups: 226 stimulant-dependent and 290 non-stimulant-dependent subjects. The analysis consisted of a case-control comparison of people addicted to psychostimulants compared to a control group of healthy and non-addicted people. There were differences in the levels of statistical significance between the groups. Our research shows lower methylation of islands 1, 9, and 14 in addicted people and greater methylation of islands 32 and 33. The difference in individual CpG methylation islands of the gene under study provides valuable information about the DNA methylation process in patients addicted to psychostimulants. Pearson's linear correlation analysis in stimulant dependence showed a negative correlation between total methylation island levels and the NEO-FFI Neuroticism scale. In subjects with neuroticism, the methylation level was statistically significantly lower. Pearson's linear correlation analysis of stimulant-dependent subjects showed a positive correlation between total methylation island levels and the NEO-FFI Openness scale and the NEO-FFI Conscientiousness scale.

Physeal Migration During Knee-guided Growth With Tension Band Plates: Influence of Implant Position.

Physeal migration during guided growth with tension band plates (TBPs) has been poorly described. The positioning factors associated with this phenomenon and its clinical implications are unknown. Our aim is to determine the influence of implant position on the risk of physeal migration during knee-guided growth with TBP. Retrospective study of 491 patients who underwent temporary hemi or epiphysiodesis with TBP around the knee between 2007 and 2019. We identified 29 patients who presented physeal migration during follow-up. Demographic and clinical data were collected, and the following measures were obtained from the immediate postoperative radiographs: epiphyseal screw base-physis distance/epiphyseal screw tip-physis distance, interscrew angle, epiphyseal screw-physis angle(ES-PHa)/metaphyseal screw-physis angle, plate-physis angle, epiphyseal screw-plate angle/metaphyseal screw-plate angle, and epiphyseal screw-physis length ratio. Using follow-up radiographs, the type of physeal migration of the epiphyseal screw (touch, occupy, or traverse) and the status of the physis after implant removal (unaltered, physeal bar, and skeletal maturity) were also recorded. A descriptive analysis of the cases and a case-control comparison of imaging studies were performed. The median patient age at intervention was 12.2 years (interquartile range: 11.3 to 14.1), and 76% were males. A statistically significant difference between cases and controls was obtained for epiphyseal screw base-physis distance (3.7 vs 6.3; P = 0.029), epiphyseal screw tip-physis distance (3.6 vs 7.85; P = 0.002), ES-PHa (-0.1 vs 7.45; P = 0.007), and plate-physis angle (85.45 vs 88.60; P = 0.012). In a categorical analysis, a significant difference was found for the ES-PHa categories ( P = 0.002) and for the ES-PHa/metaphyseal screw-physis angle categorical pair ( P = 0.018). In 16, 17, and 12 cases the physis was touched, occupied, or traversed, respectively, although we found no physeal alterations after plate removal. In our study, physeal migration of TBP is not an uncommon phenomenon, although no physeal abnormalities were detected. Convergent placement of the epiphyseal screw with the base or tip close to the physis should be avoided as this position is associated with a higher risk of physeal migration. Level III-case-control study.

#18 : Risk Factors for Placenta Accreta Spectrum in Pregnancies Conceived after Frozen-Thawed Embryo Transfer in a Hormone Replacement Cycle

Background and Aims: Assisted reproductive technology (ART), especially frozen–thawed embryo transfer (FET) in a hormone replacement cycle (HRC) is a risk factor for placenta accreta spectrum (PAS). This study aimed to clarify the risk factors for PAS related to the maternal background and ART techniques in pregnancies conceived after FET in an HRC. Method: We performed a case–control study in two tertiary perinatal centers in Japan. Among 14,028 patients who delivered at ≥24 weeks of gestation or were transferred after delivery to two tertiary perinatal centers between 2010 and 2021, 972 conceived with ART and 13,056 conceived without ART. PAS was diagnosed in patients 1) with histopathological findings of placenta increta/percreta, 2) those requiring manual evacuation of the placenta after delivery, or 3) those with retained placental tissue. Among women who conceived after FET in an HRC, 62 with PAS and 340 without PAS were included in this study. Multivariate logistic regression models were used for case–control comparisons, with adjustment for maternal age at delivery, parity, endometriosis or adenomyosis, the number of previous uterine surgeries of cesarean section, myomectomy, endometrial polypectomy or endometrial curettage, placenta previa, the stage of transferred embryos and endometrial thickness at the initiation of progestin administration. Results: PAS was associated with [Formula: see text]2 previous uterine surgeries (adjusted odds ratio [OR], 3.57; 95% confidence interval [CI], 1.60–7.97) and the number of blastocysts transferred (adjusted OR, 2.89; 95% CI, 1.15–7.26). In patients with <2 previous uterine surgeries, PAS was associated with an endometrial thickness of <7.0 mm (adjusted OR, 5.18; 95% CI, 1.10–24.44). Conclusion: A history of multiple previous uterine surgeries, the number of blastocysts transferred and a thin endometrium before ET are risk factors for PAS in pregnancies conceived after FET in an HRC.

Endophenotyping social cognition in the broader autism phenotype.

Relatives of individuals with autism spectrum disorder (ASD) may display milder social traits of the broader autism phenotype (BAP) providing potential endophenotypic markers of genetic risk for ASD. We performed a case-control comparison to quantify social cognition and pragmatic language difficulties in the BAP (n = 25 cases; n = 33 controls) using the Faux Pas test (FPT) and the Goldman-Eisler Cartoon task. Using deep phenotyping we then examined patterns of inheritance of social cognition in two large multiplex families and the spectrum of performance in 32 additional families (159 members; n = 51 ASD, n = 87 BAP, n = 21 unaffected). BAP individuals showed significantly poorer FPT performance and reduced verbal fluency with the absence of a compression effect in social discourse compared to controls. In multiplex families, we observed reduced FPT performance in 89% of autistic family members, 63% of BAP relatives and 50% of unaffected relatives. Across all affected families, there was a graded spectrum of difficulties, with ASD individuals showing the most severe FPT difficulties, followed by the BAP and unaffected relatives compared to community controls. We conclude that relatives of probands show an inherited pattern of graded difficulties in social cognition with atypical faux pas detection in social discourse providing a novel candidate endophenotype for ASD.

A case–control comparison of acute-phase peripheral blood gene expression in participants diagnosed with minor ischaemic stroke or stroke mimics

BackgroundPast studies suggest that there are changes in peripheral blood cell gene expression in response to ischaemic stroke; however, the specific changes which occur during the acute phase are poorly characterised. The current study aimed to identify peripheral blood cell genes specifically associated with the early response to ischaemic stroke using whole blood samples collected from participants diagnosed with ischaemic stroke (n = 29) or stroke mimics (n = 27) following emergency presentation to hospital. Long non-coding RNA (lncRNA), mRNA and micro-RNA (miRNA) abundance was measured by RNA-seq, and the consensusDE package was used to identify genes which were differentially expressed between groups. A sensitivity analysis excluding two participants with metastatic disease was also conducted.ResultsThe mean time from symptom onset to blood collection was 2.6 h. Most strokes were mild (median NIH stroke scale score 2.0). Ten mRNAs (all down-regulated in samples provided by patients experiencing ischaemic stroke) and 30 miRNAs (14 over-expressed and 16 under-expressed in participants with ischaemic stroke) were significantly different between groups in the whole cohort and sensitivity analyses. No significant over-representation of gene ontology categories by the differentially expressed genes was observed. Random forest analysis suggested a panel of differentially expressed genes (ADGRG7 and miRNAs 96, 532, 6766, 6798 and 6804) as potential ischaemic stroke biomarkers, although modelling analyses demonstrated that these genes had poor diagnostic performance.ConclusionsThis study provides evidence suggesting that the early response to minor ischaemic stroke is predominantly reflected by changes in the expression of miRNAs in peripheral blood cells. Further work in independent cohorts particularly in patients with more severe stroke is needed to validate these findings and investigate their clinical relevance.

Applying Artificial Intelligence to Identify Common Targets for Treatment of Asthma, Eczema, and Food Allergy

Introduction: Allergic disorders are common diseases marked by the abnormal immune response toward foreign antigens that are not pathogens. Often patients with food allergy also suffer from asthma and eczema. Given the similarities of these diseases and a shortage of effective treatments, developing novel therapeutics against common targets of multiple allergies would offer an efficient and cost-effective treatment for patients. Methods: We employed the artificial intelligence-driven target discovery platform, PandaOmics, to identify common targets for treating asthma, eczema, and food allergy. Thirty-two case-control comparisons were generated from 15, 11, and 6 transcriptomics datasets related to asthma (558 cases, 315 controls), eczema (441 cases, 371 controls), and food allergy (208 cases, 106 controls), respectively, and allocated into three meta-analyses for target identification. Top-100 high-confidence targets and Top-100 novel targets were prioritized by PandaOmics for each allergic disease. Results: Six common high-confidence targets (i.e., IL4R, IL5, JAK1, JAK2, JAK3, and NR3C1) across all three allergic diseases have approved drugs for treating asthma and eczema. Based on the targets’ dysregulated expression profiles and their mechanism of action in allergic diseases, three potential therapeutic targets were proposed. IL5 was selected as a high-confidence target due to its strong involvement in allergies. PTAFR was identified for drug repurposing, while RNF19B was selected as a novel target for therapeutic innovation. Analysis of the dysregulated pathways commonly identified across asthma, eczema, and food allergy revealed the well-characterized disease signature and novel biological processes that may underlie the pathophysiology of allergies. Conclusion: Altogether, our study dissects the shared pathophysiology of allergic disorders and reveals the power of artificial intelligence in the exploration of novel therapeutic targets.

The impact of quality control on cortical morphometry comparisons in autism.

Structural magnetic resonance imaging (MRI) quality is known to impact and bias neuroanatomical estimates and downstream analysis, including case-control comparisons, and a growing body of work has demonstrated the importance of careful quality control (QC) and evaluated the impact of image and image-processing quality. However, the growing size of typical neuroimaging datasets presents an additional challenge to QC, which is typically extremely time and labour intensive. One of the most important aspects of MRI quality is the accuracy of processed outputs, which have been shown to impact estimated neurodevelopmental trajectories. Here, we evaluate whether the quality of surface reconstructions by FreeSurfer (one of the most widely used MRI processing pipelines) interacts with clinical and demographic factors. We present a tool, FSQC, that enables quick and efficient yet thorough assessment of outputs of the FreeSurfer processing pipeline. We validate our method against other existing QC metrics, including the automated FreeSurfer Euler number, two other manual ratings of raw image quality, and two popular automated QC methods. We show strikingly similar spatial patterns in the relationship between each QC measure and cortical thickness; relationships for cortical volume and surface area are largely consistent across metrics, though with some notable differences. We next demonstrate that thresholding by QC score attenuates but does not eliminate the impact of quality on cortical estimates. Finally, we explore different ways of controlling for quality when examining differences between autistic individuals and neurotypical controls in the Autism Brain Imaging Data Exchange (ABIDE) dataset, demonstrating that inadequate control for quality can alter results of case-control comparisons.

Hyperbaric oxygen therapy: a possible choice for patients with resistant thin endometrium during frozen embryo transfer treatments

BackgroundThin endometrium is considered suboptimal for embryo implantation, leading to compromised pregnancy rates without effective therapies. While some studies have reported promoted endometrial growth after a period of hyperbaric oxygen therapy (HBOT) in patients with intrauterine adhesion, there have been no reports in patients with resistant thin endometrium. The purpose of this study was to investigate the impact of HBOT on endometrium growth and pregnancy outcomes in patients with resistant thin endometrium during frozen embryo transfer (FET) treatments.MethodsThis prospective pre-post cohort study was conducted at a university-affiliated assisted reproductive medical center between October 2021 and December 2022. Patients who had experienced at least one canceled transfer cycle due to a thin endometrium(< 7 mm) on the endometrium transformation day, despite the use of standard therapies as well as adjuvant therapies, were enrolled in the study. Patients were assigned voluntarily to either the HBOT group or the concurrent control group. The HBOT group received daily HBOT for at least 10 days during the proliferative phase, in addition to the routine endometrium preparation methods and the concurrent control group underwent cycles without HBOT. Propensity score matching (PSM) was used to ensure comparability between the groups. Both self-control and case-control comparisons were conducted. The primary outcome measured was endometrial thickness (ET) on the day of endometrium transformation. Secondary outcomes included intrauterine pregnancy rate (IPR), embryo implantation rate (IR), miscarriage rate, and others.ResultsPatients in the HBOT group demonstrated a significantly thicker endometrial thickness on the day of endometrium transformation after undergoing therapy (5.76 ± 1.66 vs. 6.57 ± 1.23, P = 0.002). This improvement was accompanied by a decreased rate of cycle cancellations. Baseline parameters and endometrial thickness were comparable between the HBOT group and the concurrent control group during the cycle. The IPR was similar in patients who received cleavage-stage embryos (0.0% vs. 6.7%, P = 1.00), but significantly higher in patients in the HBOT group who received blastocysts (53.8% vs. 18.2%, P = 0.017).ConclusionsA period of HBOT prior to endometrium transformation contributes to increased endometrial thickness and facilitates blastocyst implantation in patients with resistant thin endometrium during FET treatments.Trial registrationThe trial was registered on the Chinese Clinical Trial Registry (registration no. ChiCTR2300072831, retrospectively registered).

Ocular Surface Evaluation in Immunoglobulin G4–Related Ophthalmic Disease

To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients. Cross-sectional, matched case-control comparison study. This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.4 ± 12.2 years, 39 male) and 64 sex- and age-matched healthy controls. Patients were managed by hospitals covering the publicly funded ophthalmology service in Hong Kong. Outcome measures included anterior segment examination and keratographic and meibographic imagings. A total of 64 worst-affected eyes of the 64 IgG4-ROD patients were analyzed. Corneal fluorescein staining (P=.0187), lid margin telangiectasia (P=.0360), lid-parallel conjunctival folds (P=.0112), papillae (P=.0393), meibomian gland plugging (P=.0001), meibomian gland expressibility (P=.0001), and meibum quality (P=.0001) were more significant in IgG4-ROD patients compared with healthy controls. Both upper and lower meibomian gland dropouts (P=.001 and .0003), and tear meniscus height (P=.0001) were higher in IgG4-ROD patients. Non-invasive tear break-up time (NITBUT) (P=.0166) and Schirmer test results (P=.0243) were lower in IgG4-ROD patients. Upper (r=0.336, P=.0140) meibomian gland dropouts and NITBUT (r=-0.293, P=.0497) were positively and negatively correlated with the IgG4-ROD onset age, respectively. The number of extraocular organ involvement was negatively correlated with the Schirmer test(r=-0.341, P=.0167). Lower NITBUT was found in IgG4-ROD eyes with lacrimal gland enlargement than in IgG4-ROD eyes without lacrimal gland enlargement radiologically (P < .0001). IgG4-ROD patients showed features of both aqueous tear deficiency and evaporative dry eye disease. We recommend ocular surface evaluation to all patients newly diagnosed with IgG4-ROD. Further studies are warranted to clarify the mechanism of IgG4-related dry eye disease.

A Wearable Artificial Intelligence Feedback Tool (Wrist Angel) for Treatment and Research of Obsessive Compulsive Disorder: Protocol for a Nonrandomized Pilot Study.

Obsessive compulsive disorder (OCD) in youth is characterized by behaviors, emotions, physiological reactions, and family interaction patterns. An essential component of therapy involves increasing awareness of the links among thoughts, emotions, behaviors, bodily sensations, and family interactions. An automatic assessment tool using physiological signals from a wearable biosensor may enable continuous symptom monitoring inside and outside of the clinic and support cognitive behavioral therapy for OCD. The primary aim of this study is to evaluate the feasibility and acceptability of using a wearable biosensor to monitor OCD symptoms. The secondary aim is to explore the feasibility of developing clinical and research tools that can detect and predict OCD-relevant internal states and interpersonal processes with the use of speech and behavioral signals. Eligibility criteria for the study include children and adolescents between 8 and 17 years of age diagnosed with OCD, controls with no psychiatric diagnoses, and one parent of the participating youths. Youths and parents wear biosensors on their wrists that measure pulse, electrodermal activity, skin temperature, and acceleration. Patients and their parents mark OCD episodes, while control youths and their parents mark youth fear episodes. Continuous, in-the-wild data collection will last for 8 weeks. Controlled experiments designed to link physiological, speech, behavioral, and biochemical signals to mental states are performed at baseline and after 8 weeks. Interpersonal interactions in the experiments are filmed and coded for behavior. The films are also processed with computer vision and for speech signals. Participants complete clinical interviews and questionnaires at baseline, and at weeks 4, 7, and 8. Feasibility criteria were set for recruitment, retention, biosensor functionality and acceptability, adherence to wearing the biosensor, and safety related to the biosensor. As a first step in learning the associations between signals and OCD-related parameters, we will use paired t tests and mixed effects models with repeated measures to assess associations between oxytocin, individual biosignal features, and outcomes such as stress-rest and case-control comparisons. The first participant was enrolled on December 3, 2021, and recruitment closed on December 31, 2022. Nine patient dyads and nine control dyads were recruited. Sixteen participating dyads completed follow-up assessments. The results of this study will provide preliminary evidence for the extent to which a wearable biosensor that collects physiological signals can be used to monitor OCD severity and events in youths. If we find the study to be feasible, further studies will be conducted to integrate biosensor signals output into machine learning algorithms that can provide patients, parents, and therapists with actionable insights into OCD symptoms and treatment progress. Future definitive studies will be tasked with testing the accuracy of machine learning models to detect and predict OCD episodes and classify clinical severity. ClinicalTrials.gov NCT05064527; https://clinicaltrials.gov/ct2/show/NCT05064527. DERR1-10.2196/45123.

A disfiguring neglected tropical disease sweeps war-torn Yemen: a community-based study of prevalence and risk factors of cutaneous leishmaniasis among rural communities in the western highlands.

Cutaneous leishmaniasis (CL) is a major health problem in Yemen and is endemic in many rural areas across the country. A community-based cross-sectional survey followed by unmatched case-control comparisons was conducted among 612 participants in Utmah district, western Yemen. A total of 223 participants were included in the case-control analysis to identify the significant risk factors. Skin scrapping samples were examined by microscopy and internal transcribed spacer 1 nested polymerase chain reaction. Overall, 33% (202/612) of the participants had active skin lesions and/or scars that met the clinical criteria for CL. A total of 90 (14.7%) participants had suspected active CL lesions; however, a prevalence of 8.7% (53/612) was obtained based on molecular and parasitological examination, with Leishmania tropica being the only causative agent identified. Multivariable logistic regression analyses showed that being ≤10y old, being female, living in houses with cracked walls, living in the presence of other family members with typical ulcerating skin diseases and sleeping outside were factors significantly associated with an increased likelihood of having CL. Moreover, keeping livestock on the ground floor of the house was significantly associated with a decreased likelihood of having CL. The study reveals an alarmingly high prevalence of CL among the studied population. Therefore there is an urgent need for effective control measures and improved treatment efforts against this devastating disease.

Profile of patients with a positive HCV viral load in a large French psychiatric hospital (2019-2021): A case-control study.

Hepatitis C virus (HCV) is highly prevalent in people with mental disorders (PWMDs). However, in the international context of HCV elimination, no previous study has explored the features of seropositive PWMDs with vs. without a positive viral load (VL). We retrospectively retrieved all HCV serology results of patients hospitalized in 2019, 2020 and 2021 in the second-largest psychiatric hospital of France. Using the medical records of all patients found seropositive for HCV, the following data were collected: sex (male, female), age (in years), previous history of illicit drug use except cannabis (yes or no) and previous history of incarceration (yes or no). We conducted a case-control comparison of these variables between the PWMDs who had and did not have a positive VL, thus providing odds ratios and 95% confidence intervals (ORs [95% CI]). In a total of 13,276 inpatients, 2540 (19.1%) underwent at least one HCV serology; 55 of them (2.16%) were found positive. A VL count was performed for 48 of them, finding 15 (31.3%) individuals with active HCV. Compared with those with a negative VL, these 15 individuals were less likely to have previous documented illicit drug use (OR = 0.18; 95% CI [0.05-0.68]) and to have been previously incarcerated (OR = 0.23; 95% CI [0.06-0.99]); age and sex did not statistically differ. In the context of HCV elimination, PWMDs yet to be treated for HCV are more likely to be those with no identified risk factor for HCV, which supports a strategy of systematic screening for HCV among PWMDs.

Improve the model of disease subtype heterogeneity by leveraging external summary data.

Researchers are often interested in understanding the disease subtype heterogeneity by testing whether a risk exposure has the same level of effect on different disease subtypes. The polytomous logistic regression (PLR) model provides a flexible tool for such an evaluation. Disease subtype heterogeneity can also be investigated with a case-only study that uses a case-case comparison procedure to directly assess the difference between risk effects on two disease subtypes. Motivated by a large consortium project on the genetic basis of non-Hodgkin lymphoma (NHL) subtypes, we develop PolyGIM, a procedure to fit the PLR model by integrating individual-level data with summary data extracted from multiple studies under different designs. The summary data consist of coefficient estimates from working logistic regression models established by external studies. Examples of the working model include the case-case comparison model and the case-control comparison model, which compares the control group with a subtype group or a broad disease group formed by merging several subtypes. PolyGIM efficiently evaluates risk effects and provides a powerful test for disease subtype heterogeneity in situations when only summary data, instead of individual-level data, is available from external studies due to various informatics and privacy constraints. We investigate the theoretic properties of PolyGIM and use simulation studies to demonstrate its advantages. Using data from eight genome-wide association studies within the NHL consortium, we apply it to study the effect of the polygenic risk score defined by a lymphoid malignancy on the risks of four NHL subtypes. These results show that PolyGIM can be a valuable tool for pooling data from multiple sources for a more coherent evaluation of disease subtype heterogeneity.

Порівняльний аналіз поширеності та структури порушень нічного сну в дітей з розладами нейророзвитку під час воєнного і мирного часу

The problem of sleep disorders in children is one of the most urgent in the practice of a pediatrician and has become especially acute during wartime, given the chronic effects of a significant number of stressors. The need to develop practical recommendations for improving the quality of sleep in children during wartime necessitated a comparative study of the frequency and structure of sleep disorders in children during wartime and peacetime. Purpose - to determine the frequency and structure of nighttime sleep disorders in children with neurodevelopmental disorders and healthy children in wartime and peacetime. Materials and methods. An online survey of parents of 529 children aged 1-7 years (26.8% of healthy children and 73.2% of children with neurodevelopmental disorders) was conducted in 2022 during wartime. A survey of parents of 1352 children under the age of 7 was conducted in 2002 in peacetime (as part of the Family and Children of Ukraine project), with a case-control comparison. Results. The overall prevalence of nighttime sleep disorders among all children in wartime was 93.6% in healthy children and 94.8% in children with neurodevelopmental disorders. Difficulties falling asleep were noted in 51.4% of healthy children and 56.8% of children with neurodevelopmental disorders; frequent nighttime awakenings - in 35.9% and 39.0% of children, respectively. Sleep disorders: snoring - in 16.2% and 18.9% of children; apnoea - in 9.9% and 14.9% of children. Parasomnias: night terrors - in 19.7% and 18.6% of children; sleepwalking - in 2.8% and 4.4% of children. Comparison of the frequency of nighttime sleep disorders in healthy children in peacetime (2002) and wartime (2022): half of healthy children had difficulty going to bed (51.4% vs. 47.2%); early waking (49.8% vs. 12.7%); frequent waking at night (47.3% vs. 35.9%); snoring (33.6% vs. 16.2%); increased daytime sleepiness - 5 times more often in 2002 (30.3% vs. 6.3%); every fourth child has nightmares (25.6% vs. 26.8%); prolonged falling asleep (23.5% vs. 51.4% in 2022). Conclusions. The overall prevalence of nighttime sleep disorders among all children in wartime was 94.5%. In children with neurodevelopmental disorders, early awakenings (29.2% vs. 12.7%), sleep apnoea (14.9% vs. 9.9%), increased daytime sleepiness (14.9% vs. 6.3%), and catalepsy (8.3% vs. 4.2%) were more common compared to healthy children. In wartime, the incidence of early wake-ups (49.8% vs. 12.7% in 2022), snoring (33.6% vs. 16.2% in 2022), and increased daytime sleepiness (30.3% vs. 6.3% in 2022) decreased among healthy children, but the incidence of falling asleep problems increased by 2 times (51.4% vs. 23.5% in the 2002). Children with neurodevelopmental disorders are a more vulnerable group that reacts negatively to the stressful conditions of martial law by increasing the frequency of nighttime sleep disorders. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies.

Psychological Impacts of the COVID-19 Pandemic on Canadian Healthcare Workers: A Case Control Comparison From Three Cross Sectional Surveys.

The aim of the study is to describe mental health impacts of the COVID-19 pandemic and identify roles that predict distress among Canadian healthcare workers (HCWs). Using data from three cross-sectional Canadian surveys, we compared 799 HCWs to demographically matched controls and compared HCWs with and without COVID-19 patient contact. Participants completed validated measures of depression, anxiety, trauma-related stress, alcohol problems, coping self-efficacy, and sleep quality. Non-HCWs reported more depression and anxiety in Fall 2020 and more alcohol problems in Fall/Winter 2021 than HCWs. In Winter 2020-2021, HCWs reported more trauma-related stress than non-HCWs. As of early 2021, HCWs with direct patient contact reported worse symptoms across nearly all measures than HCWs without. Although Canadian HCWs did not report worse mental health than demographically similar peers, mental health supports are needed for HCWs providing direct patient care.

Breast cancer risk associated with missense variants in BRCA2.

10501 Background: Greater than 90% of missense variants in BRCA2 are classified as variants of uncertain significance (VUS). In addition, among the few known missense pathogenic variants (PVs) in BRCA2, breast cancer risk has been reported to be lower compared to pathogenic truncating variants (PTVs) (Li et al., 2022) . Herein, we aim to reclassify several missense variants in BRCA2 and investigate the associated breast cancer risk. Methods: A total of 450 BRCA2 missense variants in the C-terminal DNA binding domain (DBD) were evaluated for functional effect utilizing a previously validated homology-directed DNA double-strand repair (HDR) assay. The results of the functional evaluation along with clinical, structural, and in-silico data were applied to the rules-based ACMG/AMP criteria for variant classification to identify pathogenic/likely pathogenic (P/LP) variants and benign/likely benign (B/LB) variants. A pooled case-control analysis was performed comparing the frequency of reclassified P/LP missense variants among 82,372 women with breast cancer within the Ambry Genetics database as cases and 174,167 unaffected women within gnomAD, CARRIERS, and BRIDGES datasets as controls to evaluate associated breast cancer risk. Separate case-control analysis and comparisons with BRCA2 DBD PTVs, exon 11 PTVs, and known missense PV standards in ENIGMA were also performed. Results: From the 450 missense variants in the DBD, 137 (30.4%) were noted to be functionally deleterious and 313 (69.6%) were functionally neutral by the HDR assay. Incorporation of the functional and other data into an ACMG/AMP model led to the reclassification of 439 (97.6%) variants, with 131 as P/LP and 308 as B/LB variants. In a pooled case-control analysis, reclassified BRCA2 missense P/LP variants were associated with clinically significant increased risks of breast cancer (Odds Ratio (OR):5.6, 95%CI:3.9–8.0), whereas B/LB missense variants were not (OR:1.1, 95%CI:1.1–1.2). Similarly elevated risks of breast cancer were observed for BRCA2 PTVs in the DBD (OR:6.8, 95%CI:5.1–9.0) and missense PV standards in ENIGMA (OR:7.8, 95%CI:4.1–14.7). However, PTVs in exon 11 of BRCA2 were associated with a lower risk of breast cancer (OR:4.4, 95%CI:3.8–4.9) compared to PTVs in DBD, confirming the ovarian cancer cluster region effect in BRCA2. Conclusions: The study demonstrates that the HDR functional assay in conjunction with other clinical and genomic data can be a powerful tool that can aid in the reclassification of &gt; 95% of missense variants in BRCA2. In addition, missense PVs in DBD were noted to have a similarly elevated risk of breast cancer as PTVs. The reclassification of the BRCA2 missense VUS and identification of associated breast cancer risk in this study will significantly influence breast cancer risk assessment and management strategies among carriers of these missense variants.

Biologic Therapies Decrease Disease Severity and Improve Depression and Anxiety Symptoms in Psoriasis Patients.

Psoriasis is an immune-mediated chronic skin disease that is associated with a significant psychological burden. A newer line of therapy is represented by biologic agents. Our study aimed to evaluate the effect of biologic therapies in the treatment of psoriasis concerning both disease severity and psychological comorbidity. We performed a prospective case-control comparison to evaluate the prevalence of depression and anxiety in psoriasis patients and unaffected individuals. All patients were recruited between October 2017 and February 2021. Baseline depression (PHQ-9), anxiety (GAD-7), PASI, and DLQI scores were noted. Then, we evaluated the efficacy of biologic treatment in reducing these scores at 6 months of therapy. Patients were treated with either ixekizumab, secukinumab, guselkumab, certolizumab, ustekinumab, risankizumab, or adalimumab. 106 bio-naïve patients with psoriasis and 106 controls without the disease were included in this study. Depression and anxiety were significantly more common among psoriasis patients than in unaffected individuals (p < 0.0001). Female patients presented both depression and anxiety more frequently than men in both case and control groups. Disease severity was significantly associated with worsened depression and anxiety symptoms. Biologic therapy resulted in a significant decrease in all four scores at the 6-month mark for each patient (p < 0.0001). Only an improved PASI correlated significantly with lower depression and anxiety scores (p < 0.005), whereas a decreased DLQI did not (p > 0.955). None of the seven biologic agents used was discovered to be superior. biologic therapies are effective in decreasing both disease severity and alleviating depression and anxiety symptoms in psoriasis.

Understanding the relationship between cerebellar structure and social abilities

BackgroundThe cerebellum contains more than 50% of all neurons in the brain and is involved in a broad range of cognitive functions, including social communication and social cognition. Inconsistent atypicalities in the cerebellum have been reported in individuals with autism compared to controls suggesting the limits of categorical case control comparisons. Alternatively, investigating how clinical dimensions are related to neuroanatomical features, in line with the Research Domain Criteria approach, might be more relevant. We hypothesized that the volume of the “cognitive” lobules of the cerebellum would be associated with social difficulties.MethodsWe analyzed structural MRI data from a large pediatric and transdiagnostic sample (Healthy Brain Network). We performed cerebellar parcellation with a well-validated automated segmentation pipeline (CERES). We studied how social communication abilities—assessed with the social component of the Social Responsiveness Scale (SRS)—were associated with the cerebellar structure, using linear mixed models and canonical correlation analysis.ResultsIn 850 children and teenagers (mean age 10.8 ± 3 years; range 5–18 years), we found a significant association between the cerebellum, IQ and social communication performance in our canonical correlation model.LimitationsCerebellar parcellation relies on anatomical boundaries, which does not overlap with functional anatomy. The SRS was originally designed to identify social impairments associated with autism spectrum disorders.ConclusionOur results unravel a complex relationship between cerebellar structure, social performance and IQ and provide support for the involvement of the cerebellum in social and cognitive processes.

Drug-drug interactions of protein kinase inhibitors in chronic myeloid leukaemia patients: a study using the French health insurance database.

The introduction of protein kinase inhibitors (PKIs) for chronic myeloid leukaemia (CML) has considerably improved prognosis of the disease but has also demonstrated a great potential for drug-drug interactions. Using the French health insurance databases, we aim to investigate the frequency, identify the associated factors, and describe the potential consequences of potential drug-drug interactions (pPKI-DIs) between PKIs and concurrent medications in CML. A retrospective cohort study has been performed among patients with CML identified in the French healthcare database from 2011 to 2014. A pPKI-DI is defined as the presence of drugs listed as "interacting" on the same day as PKI dispensing (co-dispensing), or in its coverage period (co-medication) during the first year of follow-up. The list of interacting drugs is based on the summary of products characteristics (SPC) and Thesaurus of interactions. We performed specific nested case-control comparisons to investigate the association between PKI-DI and each of the three potential outcomes (death, hospitalisation for adverse drug reactions and switch to another PKI). We included 3,480 patients; 1,429 (41%) had a co-dispensing pPKI-DI and 2,153 (62%) had a co-medication pPKI-DI. 50% of the pPKI-DIs were "to be taken into account" and 17% were "not recommended". The PKI with the most interactions was imatinib, and additional common drug classes included statins, benzodiazepines and proton pump inhibitors. Multivariate analysis demonstrated that the use of a higher number of additional drugs, comorbidities at baseline, high number of prescribers and higher ages were potential risk factors. Nilotinib and dasatinib showed a tendency towards a higher risk of pPKI-DI compared to imatinib. Despite the fact that some PKI-DIs were potentially clinically relevant, we did not find any significant association with death, hospitalisation for adverse drug reactions and switching. These findings should increase awareness to help reduce the prevalence of PKI-drug interactions, and thereby ensure better management of CML patients.

58 Utilizing VA Data to Define Long COVID and Identify Patients at Risk

OBJECTIVES/GOALS: To determine the signs, symptoms, and diagnoses that are significantly upregulated in cases of long COVID while identifying risk factors and demographics that increase one’s likelihood of developing long COVID. METHODS/STUDY POPULATION: This is a retrospective, big data science study. Data from Veterans Affairs (VA) medical centers across the United States between the start of 2020 and the end of 2022 were utilized. Our cohort consists of 316,782 individuals with positive COVID-19 tests recorded in the VA EHR with a history of ICD10-CM diagnosis codes in the record for case-control comparison. We looked at all new diagnoses that were not present in the six months before COVID diagnosis but were present in the time period from one month after COVID through seven months after. We determined which were significantly enriched and calculated odds ratios for each, organized by long COVID subtypes by medical specialty / affected organ system. Demographic analyses were also performed for long COVID patients and patients without any new long COVID ICD10-CM codes. RESULTS/ANTICIPATED RESULTS: This profile shows disorders that are highly upregulated in the post-COVID population and provides strong evidence for a broad definition of long COVID. By breaking this into subtypes by medical specialty, we define cardiac long COVID, neurological long COVID, pulmonary long COVID, and eight others. The long COVID cohort was older with more comorbidities than their non-long COVID counterparts. We also noted any differences regarding sex, race, ethnicity, severity of acute COVID-19 symptoms, vaccination status, as well as some analysis regarding medications taken. DISCUSSION/SIGNIFICANCE: This profile can be utilized to decisively define long COVID as a clinical diagnosis and will lead to consistence in future research. Elucidating an actionable model for long COVID will help clinicians identify those in their care that may be experiencing long COVID, allowing them to be admitted into more intensive monitoring and treatment programs.