Cohort Of Individuals Research Articles

Theoretical Behavior Substitutions during the 24-Hour Day in Pregnancy and Infant Growth Outcomes.

To assess associations of theoretically reallocating time from sleep, sedentary behavior, or light intensity physical activity (LPA) to moderate/vigorous intensity physical activity (MVPA) during pregnancy with infant growth outcomes. We used data from a cohort of pregnant individuals with overweight or obesity (n = 116). At 9-15 and 30-36 weeks gestation, waking movement was measured using wrist-worn accelerometers and sleep duration was self-reported. Outcomes were obtained from delivery electronic health records (birth) and study visits (12 months). We used compositional isotemporal substitution models. In early pregnancy, reallocating 10 minutes of sleep, sedentary behavior, or LPA to MVPA was associated with 20% (RR = 0.80; 95%CI: 0.75,0.85), 21% (RR = 0.79; 95%CI: 0.75,0.84), and 25% (RR = 0.75; 95%CI: 0.70,0.81) lower risk of large-for-gestational age (LGA) birthweight, respectively, and 17% (RR = 0.83; 95%CI: 0.75,0.91), 18% (RR = 0.82; 95%CI: 0.75,0.91), and 22% (RR = 0.78; 95%CI: 0.70,0.88) lower risk of rapid infant growth (birth to 12 months), respectively. In late pregnancy, reallocating 10 minutes to MVPA was associated with 18% to 22% lower risk of LGA birthweight, but was not associated with rapid infant growth. Reallocating time to MVPA in early or late pregnancy was not associated with high newborn body fat percent. Our findings suggest beneficial associations of theoretically reallocating time from sleep, sedentary behavior, or LPA to MVPA, especially during early pregnancy, for reducing LGA birthweight and rapid infant growth.

Mortality and comorbidities in a Nationwide cohort of HIV-infected adults: comparison to a matched non-HIV adults' cohort, France, 2006-18.

Human immunodeficiency virus (HIV) remains a significant cause of morbidity and mortality worldwide. The aim of this study was to describe the mortality rate and associated comorbidities in a nationwide population-based cohort of persons living with HIV (PLWHIV) and to compare it with mortality in an age and gender-matched cohort of non-HIV individuals in France. Using data from the French national health data system, we identified and included 173712 PLWHIV (66.5% men) and 173712 non-HIV participants (66.5% men) matched for age and gender. PLHIV were identified based on ICD-10 HIV diagnoses, HIV-specific laboratory tests, and/or prescriptions for antiretroviral therapy specific to HIV. Hazard ratios (HRs) of mortality were assessed using multiple Cox regression models. During the 13 years of follow-up (2006-18), we observed 20018 deaths among PLWHIV compared with 6262 deaths among non-HIV participants (11.52% vs. 3.60%, P < 0.001). The over-mortality of PLWHIV was expressed by univariable HR = 2.135 (2.072-2.199), which remained significant after adjustment for region, Complementary Universal Health Insurance and AME, with multivariable HR = 2.182 (2.118-2.248). The results remained significant after adjusting for comorbidities, including infectious diseases [HR = 1.587 (1.538-1.638)]. Notably, PLWHIV were more importantly associated with mortality in women [HR = 2.966 (2.767-3.180)], compared in men [HR = 1.961 (1.898-2.027)]. Although the life expectancy of PLWHIV has globally increased, the causes of death should be prioritized in prevention policies and care management. Gender-specific policies should be highlighted, as we observed a higher impact of HIV mortality in women.

Clinical profile analysis of SARS-CoV-2 community infections during periods with omicron BA.2, BA.4/5, and XBB dominance in Hong Kong: a prospective cohort study

Existing studies on SARS-CoV-2 infection have mainly focused on severe clinical outcomes; understanding of the clinical severity profile of general community infections is poor. We aimed to assess and compare the clinical profiles of infections with SARS-CoV-2 omicron (B.1.1.529) subvariants in a representative community cohort in Hong Kong during periods of BA.2, BA.4/5, and XBB dominance. In this prospective cohort study in Hong Kong, a representative community cohort of individuals aged at least 5 years were recruited by random-digit dialling and underwent weekly rapid antigen testing for SARS-CoV-2, irrespective of symptoms, during three periods from March 1, 2022, to Oct 31, 2023, in which the BA.2, BA.4/5, or XBB subvariants were dominant. We analysed the likelihood of symptoms, as well as the patterns, severity, and duration of symptoms and their associations with participant demographics and vaccination and infection histories. 1126 (11·0%) of 10 279 participants in the BA.2 period, 830 (6·6%) of 12 588 in the BA.4/5 period, and 633 (11·1%) of 5690 during the XBB period tested positive for SARS-CoV-2 infection on rapid antigen tests. Community infections were generally mild, with asymptomatic infections comprising 22·0-25·0% of infections. No hospitalisations or deaths occurred as a direct result of SARS-CoV-2 infection during the study period. Compared with children aged 5-17 years, a higher likelihood of being symptomatic on infection was found for adults aged 18-59 years during the period of BA.2 dominance and adults aged 60 years or older during XBB dominance. Most (>90·0%) participants with symptomatic infections reported respiratory and systemic symptoms. Up-to-date vaccination with a regimen containing the BNT162b2 vaccine, compared with those without an up-to-date vaccine, was associated with a reduced likelihood of symptoms on infection during the period of BA.2 dominance and of severe symptoms causing substantial disturbance to daily life (grade 3 symptoms) during periods of BA.2 and BA.4/5 dominance, whereas no association was observed during the period of XBB dominance. Previous SARS-CoV-2 infection was associated with a reduced likelihood of symptoms on infection during BA.4/5 and XBB dominance and of severe symptoms during XBB dominance. Reports of severe symptoms increased over the three periods, from 236 (27·7%) of 852 symptomatic participants during BA.2 dominance to 176 (37·1%) of 475 during XBB dominance. The duration of symptoms was longest in the BA.2 period (median 10·0 days [95% CI 9·0-10·0]) and similar in the other two periods (8·0 [8·0-9·0] during BA.4/5 dominance and 8·0 [8·0-9·0] during XBB dominance). A symptom duration of 60 days or longer was reported only during the period of BA.2 dominance, in six (0·7%) of 824 infections. SARS-CoV-2 infections were generally mild, but not increasingly so, along the evolution of omicron subvariants in this highly vaccinated population. About a third of participants with symptomatic infections reported that the symptoms severely affected daily life even if they were not admitted to hospital, resulting in morbidity, absence from work or school due to illness, productivity loss, and increased medicoeconomic burden. A gradual reduction in the association of vaccines and increase in the association of previous infection with the symptom profile, possibly reflecting the effects of immune escape and waning, were observed over the study period. Henry Fok Foundation and Hong Kong Health Bureau.

Menstrual management using the etonogestrel implant in individuals with intellectual disabilities in Joinville, Brazil.

This study aimed to describe the use of etonogestrel (ENG) implants for menstrual management (i.e., management of bleeding and symptoms associated with menstruation) in individuals with intellectual disabilities. This study retrospectively analyzed a cohort of individuals with intellectual disabilities who began using ENG implants between 2003 and 2018, in Joinville, Brazil. We collected sociodemographic, clinical, and reproductive data from the medical records, along with information related to ENG implant use. In total, 369 implants were placed in 130 individuals with intellectual disabilities. The median age at the first implant was 20 (interquartile range [IQR], 17-26) years, and 43.8% of the patients were adolescents. By December 2018, 90 patients had received two or more subsequent implants. The median duration of current ENG implant use was 19 (IQR, 12.8-22) months. More than 40% of the patients had comorbidities, with epilepsy being the most common. During the use of the current implant, 80% of the patients had a favorable bleeding profile (no bleeding or ≤1 bleeding episode per month), and 53.8% (70/130) had no bleeding within 3 months before their last medical visit. Among patients experiencing dysmenorrhea and premenstrual syndrome (PMS), 79% (64/81) and 82% (54/66) reported complete improvement, respectively. The premature implant removal rate was 8.9% (33/369). Unfavorable bleeding was the main reason for premature implant removal (20 out 33 removals). ENG implants might be a suitable option for individuals with intellectual disabilities who require management of menstrual bleeding and symptoms associated with menstruation. Most patients had a favorable bleeding profile and experienced significant improvements in dysmenorrhea and PMS, contributing to the high continuation rates of ENG implants.

Clinical and Humanistic Burden of Non-inhibitor HaemophiliaA in Five European Countries: Insights from the CHESSII Study.

HaemophiliaA (HA) is a congenital bleeding disorder caused by a deficiency/absence of factorVIII (FVIII) and characterised by frequent, acute and prolonged spontaneous or traumatic bleeding events, often leading to haemophilic arthropathy and progressive joint deterioration. HA severity is characterized by endogenous FVIII activity: mild (> 5-40%), moderate (1-5%), or severe (< 1%). HA poses a substantial clinical and socioeconomic burden on people with HA (PWHA), their caregivers, and society. This analysis evaluates clinical and patient-centric outcomes of a cohort of individuals with non-inhibitor HA sampled from France, Germany, Italy, Spain, and the UK in the 'Cost of Haemophilia in Europe: A Socioeconomic Survey II' (CHESSII) study. CHESSII was a cross-sectional burden-of-illness study collecting clinical and socioeconomic data on adult (≥ 18years) individuals with haemophiliaA or B of any severity with or without inhibitors from eight European countries. Descriptive analyses were conducted examining physician-reported demographics, clinical and health resource utilisation information. PWHA-reported health-related quality of life (HRQoL) using the EQ-5D-5L and Work Productivity and Activity Impairment (WPAI) were also examined. Outcomes were stratified by HA severity and reported at country level. Demographics and clinical characteristics of the cohort (N = 880) were generally consistent across countries. Individuals with severe HA experienced more frequent bleeding events and joint disease despite broad use of factor replacement therapy long-term prophylaxis. A minority of those with mild or moderate HA also experienced such challenges. HRQoL and workforce participation diminished, and chronic pain increased, with increasing HA severity. This analysis provides up-to-date insights on the impact of HA across five European countries. Increasing HA severity was generally associated with worse clinical outcomes, HRQoL and workforce participation. These findings suggest a place for continued evidence-based tailored treatment and clinical management approaches in addressing the residual burden of HA.

Hepatitis C Virus Infection in Pregnant Individuals with Opioid Use Disorder and Its Association with Preterm Birth.

Both hepatitis C virus (HCV) and opioid use disorder (OUD) have been associated with higher rates of preterm birth (PTB). It is unknown whether the higher prevalence of HCV in individuals with OUD may contribute to this association. The objective of this study is to evaluate the association between HCV and PTB in pregnant individuals with OUD. We conducted a retrospective cohort of pregnant individuals with OUD who participated in more than three visits in a co-located multidisciplinary program. Inclusion criteria were a diagnosis of OUD, participation in treatment/prenatal care program, and laboratory evaluation of HCV status. The primary exposure was the presence of HCV antibodies, and secondarily, a detectable viral load (viremia). The primary outcome was PTB, which was further classified as spontaneous or iatrogenic. Multivariable logistic regression was used to detect associations while adjusting for race, history of prior PTB, and tobacco use. A total of 941 individuals were included in the study, 404 with HCV and 537 without. Rates of PTB did not differ between those with compared to those without HCV (20.3 vs. 23.8%, adjusted odds ratio [aOR] = 0.75 [95% confidence interval (CI): 0.53-1.07]). There were similar rates of spontaneous PTB (13.1 vs. 16.2%, aOR = 0.79 [95% CI: 0.43-1.45]) and iatrogenic PTB (7.2 vs. 7.6%, aOR = 1.26 [95% CI: 0.69-2.30]). Comparing those with viremia to those without, there were also similar rates of overall PTB (21.6 vs. 17.9%, aOR = 0.86 [95% CI: 0.52-1.44]), spontaneous PTB (13.3 vs. 12.9%, aOR = 0.97 [95% CI: 0.52-1.87]), and iatrogenic PTB (8.3 vs. 5.0%, aOR = 1.83 [95% CI: 0.76-4.94]). HCV does not appear to be associated with spontaneous or iatrogenic PTB in pregnant persons with OUD who are engaged in treatment and prenatal care. The role of co-located multidisciplinary prenatal and addiction programs in the association between HCV and PTB warrants further investigation. · Hepatitis C antibodies are not associated with PTB in those with OUD.. · Hepatitis C viremia is not associated with PTB.. · Multidisciplinary treatment programs may contribute to these findings..

Multiple sclerosis and cancer: Navigating a dual diagnosis.

Healthcare breakthroughs are extending the lives of multiple sclerosis (MS) patients and cancer survivors, creating a growing cohort of individuals navigating a dual diagnosis. Determining the relationship between MS and cancer risk remains challenging, with inconclusive findings confounded by age, risk exposures, comorbidities, genetics and the ongoing introduction of new MS disease-modifying therapies (DMTs) across study periods.This research places significant emphasis on cancer survival, with less attention given to the impact on MS outcomes. Our review explores the existing literature on MS, cancer risk and the intersection of DMTs and cancer treatments. We aim to navigate the complexities of managing MS in cancer survivors to optimise outcomes for both conditions. Continuous research and the formulation of treatment guidelines are essential for guiding future care. Collaboration between neuro-immunology and oncology is crucial, with a need to establish databases for retrospective and ultimately prospective analysis of outcomes in these rapidly evolving fields.

Circulating IL-17A and Executive Function in Middle-Aged Adults with and without Type 2 Diabetes

Abstract Background Midlife cardiovascular risk factors, such as Type 2 Diabetes Mellitus (T2DM) and obesity, are associated with a greater risk of cognitive impairment and dementia in later life, with altered peripheral inflammation postulated as a crucial mechanistic link. Yet there is a significant gap in knowledge regarding when pathogenic alterations to these systemic inflammatory responses change during the early stages of cognitive dysfunction prior to overt disease development. To assess the earliest possible signs of this link, we recruited a cohort of middle-aged cognitively-unimpaired individuals with and without uncomplicated T2DM. Methods A comprehensive neuropsychological assessment was performed at baseline and at 4-year follow-up. A panel of ten serum chemokines and cytokines were measured at both time-points using high-sensitivity assays (Eotaxin, MCP-1, MIP-1β, CXCL-10, IL-6, IL-10, IL12p70, IL-17A, IFN-γ and TNF-α). Results Overall, 136 individuals were recruited including 90 with uncomplicated midlife T2DM (age 52.6 ± 8.3; 47% female) and 46 without (age 52.9 ± 8.03; 61% female). Cognitive trajectories were stable over time and did not differ by T2DM status. Yet on cross-sectional analyses, we observed consistent evidence across timepoints between greater circulating IL-17A and poorer performance on tests of executive function/attention (β: -0.21; -0.40, -0.02, p = 0.03 at baseline; β: -0.26; -0.46, -0.05, p = 0.02 at follow-up) as well as poorer reaction time (β: 0.34; 0.12, 0.56, p = 0.003 at follow-up). These persisted on covariate adjustment and did not differ by T2DM status. Conclusion We provide exploratory evidence that greater serum IL-17A levels are associated with poorer executive function in midlife. Long-term follow-up of this and other cohorts will further elucidate this relationship to provide further mechanistic insights and potentially identify individuals at greatest risk for later cognitive decline.

Influence of Genetic Polymorphisms on the Age at Cancer Diagnosis in a Homogenous Lynch Syndrome Cohort of Individuals Carrying the MLH1:c.1528C>T South African Founder Variant.

Background: High variability in the age at cancer diagnosis in Lynch syndrome (LS) patients is widely observed, even among relatives with the same germline pathogenic variant (PV) in the mismatch repair (MMR) genes. Genetic polymorphisms and lifestyle factors are thought to contribute to this variability. We investigated the influence of previously reported genetic polymorphisms on the age at cancer diagnosis in a homogenous LS cohort with a South African founder germline PV c.1528C>T in the MLH1 gene. Methods: A total of 359 LS variant heterozygotes (LSVH) from 60 different families were genotyped for specific genetic polymorphisms in GSTM1, GSTT1, CYP1A1, CYP17, PPP2R2B, KIF20A, TGFB1, XRCC5, TNF, BCL2, CHFR, CDC25C, ATM, TTC28, CDC25C, HFE, and hTERT genes using Multiplex Polymerase Chain Reaction and MassArray methods. Kaplan-Meier survival analysis, univariate and multivariate Cox proportional hazards gamma shared frailty models adjusted for sex were used to estimate the association between age at cancer diagnosis and polymorphism genotypes. A p-value < 0.05 after correcting for multiple testing using the Benjamini-Hochberg method was considered significant at a 95% confidence interval. Results: We identified three genotypes in the cell-cycle regulation, DNA repair, and xenobiotic-metabolism genes significantly associated with age at cancer diagnosis in this cohort. The CYP1A1 rs4646903 risk (GG) and CDC25C rs3734166 polymorphic (GA+AA) genotypes were significantly associated with an increased risk of a younger age at cancer diagnosis (Adj HR: 2.03 [1.01-4.08], p = 0.034 and Adj HR: 1.53 [1.09-2.14], p = 0.015, respectively). LSVH who were heterozygous for the XRCC5 rs1051685 SNP showed significant protection against younger age at cancer diagnosis (Adj HR: 0.69 [CI, 0.48-0.99], p = 0.043). The risk of a younger age at any cancer diagnosis was significantly high in LS carriers of one to two risk genotypes (Adj HR: 1.49 [CI: 1.06-2.09], corrected p = 0.030), while having one to two protective genotypes significantly reduced the risk of developing any cancer and CRC at a younger age (Adj HR: 0.52 [CI: 0.37-0.73], and Adj HR: 0.51 [CI: 0.36-0.74], both corrected p < 0.001). Conclusions: Polymorphism genotypes in the cell-cycle regulation, DNA repair, and xenobiotic metabolizing genes may influence the age at cancer diagnosis in a homogenous LS cohort with a South African founder germline PV c.1528C>T in the MLH1 gene.

Physical activity levels are associated with depressive symptoms: A cross-sectional study of 58,445 adults

IntroductionDepression is the leading cause of mental health-related illnesses and disabilities. Physical activity (PA) has been included as part of therapeutic approaches for patients with depression. This study aimed to investigate the associations between depressive symptoms and PA levels in a large representative cohort of Brazilian adults and older individuals. MethodsData from 58,445 Brazilian adults (68.6 % males and 31.4 % females) aged 18 years or older (42.2 ± 10 years) who participated in health screening initiatives between 2008 and 2022 at the Center for Preventive Medicine at a quaternary hospital in Sao Paulo, Brazil were analyzed. Standardized health data (anthropometric, laboratory, clinical, and behavioral) were collected. A hierarchical regression model was used to examine the associations based on the presence and absence of depressive symptoms. ResultsIn the final model, age, gender (female), body mass index (BMI) (each kg/m2), presence of hypertension, presence of diabetes mellitus, risk of alcohol consumption, smoking status, and perceived stress were associated with higher odds of depressive symptoms. However, PA levels were associated with lower odds of depressive symptoms. ConclusionThe findings revealed that any level of PA was independently and significantly associated reduced risk of depressive symptoms.

Unveiling the role of IGF1R in autism spectrum disorder: a multi-omics approach to decipher common pathogenic mechanisms in the IGF signaling pathway.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by impairments in social interaction, communication, and repetitive behaviors. Emerging evidence suggests that the insulin-like growth factor (IGF) signaling pathway plays a critical role in ASD pathogenesis; however, the precise pathogenic mechanisms remain elusive. This study utilizes multi-omics approaches to investigate the pathogenic mechanisms of ASD susceptibility genes within the IGF pathway. Whole-exome sequencing (WES) revealed a significant enrichment of rare variants in key IGF signaling components, particularly the IGF receptor 1 (IGF1R), in a cohort of Chinese Han individuals diagnosed with ASD, as well as in ASD patients from the SFARI SPARK WES database. Subsequent single-cell RNA sequencing (scRNA-seq) of cortical tissues from children with ASD demonstrated elevated expression of IGF receptors in parvalbumin (PV) interneurons, suggesting a substantial impact on their development. Notably, IGF1R appears to mediate the effects of IGF2R on these neurons. Additionally, transcriptomic analysis of brain organoids derived from ASD patients indicated a significant association between IGF1R and ASD. Protein-protein interaction (PPI) and gene regulatory network (GRN) analyses further identified ASD susceptibility genes that interact with and regulate IGF1R expression. In conclusion, IGF1R emerges as a central node within the IGF signaling pathway, representing a potential common pathogenic mechanism and therapeutic target for ASD. These findings highlight the need for further investigation into the modulation of this pathway as a strategy for ASD intervention.

Navigating Market Movements: The Role of Herd Behaviour in Indian Stocks

When an individual elects to allocate their financial resources towards the stock market for the initial occasion or on a consistent basis, yet possesses insufficient knowledge pertaining to market analysis and investment strategies, the primary issue or inquiry that emerges is the appropriate allocation of capital. In more straightforward terms, this involves determining whether to invest in equity shares, preference shares, debentures, or to allocate resources to mutual funds, and if so, in which specific equity/preference shares, debentures, or mutual funds the investment should be made. Individuals may either engage the services of a stock broker to manage their investments on their behalf or choose to undertake the investment process independently. In both scenarios, their decision-making processes are likely to be influenced, either wholly or partially, by herd behaviour, commonly referred to as the bandwagon effect. Individuals tend to adhere to prevailing trends. When a substantial cohort of individuals engages in investment in a particular stock, there exists a propensity among others to similarly invest in that stock, often without conducting thorough independent analysis. They possess a belief that a significant collective cannot err. The bandwagon effect is an inherent phenomenon that is relatively innocuous to a certain degree; however, it can occasionally be strategically manipulated to influence market movements in a preferred direction, an action that may constitute unfair trade practices and is frequently observed within the stock market. While herd behaviour in everyday situations may be benign, it can prove detrimental when related to investment decisions.

Abstract B012: Prioritization of ancestry-specific variations in disease data helps to alleviate bias in genomic data

Abstract 95% of sequencing data is from individuals of European descent. Underrepresentation of non- European individuals in genomic resources has limited our understanding of the effects of population-specific variants on complex traits and disease. Human populations have undergone selection for variants beneficial to survival in their environment, resulting in individuals with genetic variants unique to their ancestral populations. While these variants can impact disease occurrence and treatment outcome, genetic ancestry is often unaccounted for in disease modeling. Lack of ancestral population representation in data has led to disparate disease outcomes and treatment. While the primary proposed solution to this problem is more diverse sequencing of patients, these efforts will take years of effort and continual work to maintain the diversity balance. Additionally, they will not solve the issue; clinical trials cannot expect to capture human global diversity at every stage. Here we show we can mitigate data bias by utilizing readily available genomic population databases to target genes with ancestrally relevant variations. Our AI model, PhyloFrame, creates equitable gene signatures from transcriptomic input data. PhyloFrame corrects for ancestral bias in data by utilizing genomic population databases and functional interaction networks to identify genes both relevant to disease and associated with a variant unique to a single ancestry. PhyloFrame uses gnomAD data to quantify genome-wide ancestry-specific allele frequencies from a large cohort of healthy individuals, which PhyloFrame uses to create ancestry-agnostic signatures when modeling disease data. Our model demonstrates the utility of including readily available population-level data from healthy individuals in AI methods to overcome existing genomic data bias. PhyloFrame serves also as a demonstration of how equitable AI methods create gene signatures applicable across ancestries without requiring sample-specific ancestry information. Our model demonstrates how AI can be used to help mitigate ancestral bias in genomic data using preexisting data and contribute to equitable representation in medical research. Citation Format: Leslie A. Smith, Kiley Graim, James A. Cahill. Prioritization of ancestry-specific variations in disease data helps to alleviate bias in genomic data [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B012.

Interpretation of Sydney Swallow Questionnaire results using the oropharyngeal dysphagia risk matrix.

Oropharyngeal dysphagia (OD) commonly occurs in neuromuscular diseases (NMD). Appropriate management involves early detection, clinical evaluation, and tailored follow-up to minimize complications. Various assessment tools exist, including the Sydney Swallow Questionnaire (SSQ), a patient-reported outcome measure for assessing OD severity in adult patients. This paper proposes utilizing an innovative risk matrix (OD-Risk-Matrix) to enhance SSQ interpretation. This matrix categorizes OD risk for each SSQ question, offering valuable assistance to clinicians. This study analyzes SSQ results from a cohort of individuals with NMD (n = 57). Patients filled in the SSQ during outpatient visits at our neuromuscular center. Subsequently, SSQ scores were grouped by NMD conditions and interpreted using the OD-Risk-Matrix categorizing each question's risk as low, moderate, or high. This matrix is based on the SSQ results by categorizing the risk of OD for each question, as well as the likelihood of occurrence of OD. In light of the OD-Risk-Matrix, the interpretation of SSQ scores revealed various risk categories associated with each question, while also highlighting distinct OD characteristics and discrepancies among the different NMDs. In conclusion, the OD-Risk-Matrix offers a framework for interpreting the SSQ, revealing variations in the risks of OD among different questions in patients with NMD. This novel approach could be a valuable tool in SSQ interpretation to identify specific fields of OD and could lead to a tailored management plan, prioritizing interventions aimed at reducing the risk of aspiration, ensuring proper nutrition, and enhancing swallowing safety and efficiency.

The impact of genotype on age at loss of ambulation in individuals with Duchenne muscular dystrophy treated with corticosteroids: A single-center study of 555 patients.

Studies have demonstrated that certain genotypes in Duchenne muscular dystrophy (DMD) have milder or more severe phenotypes. These studies included individuals treated and not treated with corticosteroids and multiple sites with potentially varying standards of care. We aimed to assess genotype-phenotype correlations for age at loss of ambulation (LoA) in a large cohort of individuals with DMD treated with corticosteroids at one center. In this retrospective review of medical records, encounters were included for individuals diagnosed with DMD if prescribed corticosteroids, defined as daily deflazacort or prednisone or high-dose weekend prednisone, for 12 consecutive months. Encounters were excluded if the participants were taking disease-modifying therapy. Data were analyzed using survival analysis for LoA and Fisher's exact tests to assess the percentage of late ambulatory (>14 years old) individuals for selected genotypes. Overall, 3948 encounters from 555 individuals were included. Survival analysis showed later age at LoA for exon 44 skip amenable (p = .004), deletion exons 3-7 (p < .001) and duplication exon 2 (p = .043) cohorts and earlier age at LoA for the exon 51 skip amenable cohort (p < .001) when compared with the rest of the cohort. Individuals with deletions of exons 3-7 had significantly more late ambulatory individuals than other cohorts (75%), while those with exon 51 skip amenable deletions had significantly fewer (11.9%) compared with other cohorts. This confirms previous observations of genotype-phenotype correlations in DMD and enhances information for trial design and clinical management.

Adynamic spoken language in corpus callosum dysgenesis

Corpus callosum dysgenesis (CCD) is a congenital brain malformation that occurs when the development of the corpus callosum is disrupted, either partially or completely. The cognitive outcomes in individuals with CCD vary greatly, but generally the neuropsychological profile is characterised by slow processing speed, poor transfer of interhemispheric sensory-motor information, and impaired complex problem solving. Core language skills are often preserved in CCD, but there is some evidence that complex language may be impaired. Thus, the current study sought to examine whether spontaneous speech output was reduced in a cohort of individuals with CCD compared to age-matched controls. We further explored a series of factors that may be contributing to poor spontaneous speech in CCD, such as difficulties generating, selecting, and sequencing ideas for expression, as well as apathy and slowed processing speed. A cohort of 25 individuals with CCD and 39 neurotypical controls were enrolled in this study. Participants completed a picture description task to measure spontaneous speech output, alongside a series of cognitive and language baseline tests. Verbal and nonverbal fluency tasks gauged idea generation and sequencing, and sentence-level selection tasks measured idea selection. We found that, despite having largely intact core language skills, individuals with CCD produced significantly less spontaneous speech on the picture description task than controls. This language profile may be described as “adynamic”. Further, we found that poor spontaneous speech output in CCD was related to problems generating ideas for expression, as individuals with CCD performed below controls on the verbal and nonverbal fluency tasks. Exploratory analyses revealed that apathy and slowed processing speed may be contributing factors. Adynamia in CCD is a novel finding that may be an intervention target for improving communication skills in this population.

Circulating Interleukin-17A is associated with executive function in middle aged adults with and without type 2 diabetes

Midlife cardiovascular risk factors such as Type 2 Diabetes (T2DM) and obesity are associated with the later development of cognitive impairment and dementia. Systemic inflammation is postulated as a crucial mechanism, yet there are few studies examining this at the earliest stages prior to overt cognitive impairment. To assess this, we recruited a cohort of middle-aged cognitively-unimpaired individuals with and without uncomplicated T2DM. Comprehensive neuropsychological assessment was performed at baseline and at 4-year follow-up. Ten serum chemokines and cytokines (Eotaxin, MCP-1, MIP-1β, CXCL10, IL-6, IL-10, IL12p70, IL-17A, IFN-γ and TNF-α) were measured at both baseline and follow-up using high-sensitivity assays. Overall, 136 participants were recruited including 90 with uncomplicated midlife T2DM (age 52.6 ± 8.3; 47% female) and 46 without (age 52.9 ± 8.03; 61% female). Cognitive trajectories were stable over time and did not differ with T2DM. Yet on cross-sectional analyses at both baseline and follow-up, greater circulating IL-17A was consistently associated with poorer performance on tests of executive function/attention (β: 0.21; −0.40, −0.02, p = 0.03 at baseline; β: 0.26; −0.46, −0.05, p = 0.02 at follow-up). Associations persisted on covariate adjustment and did not differ by T2DM status. In summary, we provide evidence that greater circulating IL-17A levels were associated with poorer executive function in midlife, independent of T2DM. Long-term follow-up of this and other cohorts will further elucidate the earliest stages in the relationship between systemic inflammation and cognitive decline to provide further mechanistic insights and potentially identify those at greatest risk for later cognitive decline.

Cannabis expectancies and associations with cannabis use and health functioning among adults with chronic pain

IntroductionCannabis is increasingly available to individuals in the United States, with the majority of states legalizing medical or recreational cannabis use. Cannabis expectancies (e.g., positive expectations from cannabis use) are related to more frequent cannabis use and associated with greater odds of lapse following a cessation attempt. MethodsTo evaluate the relationship between expectancies and cannabis- and health-related outcomes, we surveyed adults who used medical cannabis for chronic pain (n = 633; 52.2 % female; 82.1 % white) over a two-year period. Then, we performed a principal components analysis (PCA) on the Cannabis Expectancies Questionnaire to derive components of cannabis expectancies. We performed k-means clustering to identify subgroups with similar expectancies. The relationship between subgroup assignment and cannabis use outcomes (frequency, quantity), and physical and mental health functioning were evaluated. ResultsThe PCA identified a three-component solution and k-means clustering identified four subgroups: low expectancies, negative expectancies, amotivation expectancies, and positive expectancies. Participants’ cannabis expectancies were dynamic over time. After adjusting for demographics, expectancy subgroup was able to predict six-month cannabis use frequency (χ2(3) = 11.244; p = 0.010) and mental health functioning (χ2(3) = 24.926; p < 0.001), but not quantity (χ2(3) = 2.741, p = 0.433) or physical health functioning (χ2(3) = 5.110, p = 0.164). ConclusionIn a large cohort of individuals who use medical cannabis, four subgroups with differing cannabis expectancies emerged: low expectancies, negative expectancies, amotivation expectancies, and positive expectancies. These subgroups predicted subsequent outcomes and may be important for targeted intervention approaches to reduce cannabis use and improve functioning.

The Impact of Unrelated Future Medical Costs on Economic Evaluation Outcomes for Different Models of Diabetes.

This study leveraged data from 11 independent international diabetes models to evaluate the impact of unrelated future medical costs on the outcomes of health economic evaluations in diabetes mellitus. Eleven models simulated the progression of diabetes and occurrence of its complications in hypothetical cohorts of individuals with type 1 (T1D) or type 2 (T2D) diabetes over the remaining lifetime of the patients to evaluate the cost effectiveness of three hypothetical glucose improvement interventions versus a hypothetical control intervention. All models used the same set of costs associated with diabetes complications and interventions, using a United Kingdom healthcare system perspective. Standard utility/disutility values associated with diabetes-related complications were used. Unrelated future medical costs were assumed equal for all interventions and control arms. The statistical significance of changes on the total lifetime costs, incremental costs and incremental cost-effectiveness ratios (ICERs) before and after adding the unrelated future medical costs were analysed using t-test and summarized in incremental cost-effectiveness diagrams by type of diabetes. The inclusion of unrelated costs increased mean total lifetime costs substantially. However, there were no significant differences between the mean incremental costs and ICERs before and after adding unrelated future medical costs. Unrelated future medical cost inclusion did not alter the original conclusions of the diabetes modelling evaluations. For diabetes, with many costly noncommunicable diseases already explicitly modelled as complications, and with many interventions having predominantly an effect on the improvement of quality of life, unrelated future medical costs have a small impact on the outcomes of health economic evaluations.

Establishment of tumor marker reference intervals for different age and gender groups in the healthy population of South China

To establish age- and sex-specific reference intervals (RIs) for serum tumor markers (AFP, CEA, CA125, CA199, CA153, HE4, CA724, CYFRA21-1, PSA, and NSE) among a cohort of healthy individuals in South China, a retrospective analysis was conducted on 51,353 samples collected from 2015 to 2020, during health assessments at Guangdong Provincial People’s Hospital. The influence of age and gender on serum tumor markers was investigated. New RIs were determined using non-parametric rank-based methods per CLSI EP28-A3C guidelines. Significant differences were detected across age groups for AFP, CEA, CA125, CA199, HE4, CYFRA21-1, PSA, and NSE (p < 0.05). The upper reference limits (URLs) for CA153 and HE4 are significantly lower compared to our current laboratory standards. The URL for CA125 exceeds these limits in individuals under 50 but decreases in those aged 50 and above. For CA199, CEA, and PSA, the URLs are below current standards in individuals younger than 60 but exceed them in those aged 60 and older. Noteworthy elevations were observed in CA724, CYFRA21-1, and NSE levels. Our study establishes age- and sex-specific RIs for ten serum tumor markers among healthy individuals from South China, providing a fundamental resource for the prevention, early detection, and management of tumor-related disorders.