Large Epidemiological Studies Research Articles

Correlation between Bronchopulmonary Dysplasia and Cerebral Palsy in Children: A Comprehensive Analysis Using the National Inpatient Sample Dataset

Background: The existing literature lacks conclusive evidence regarding the relationship between bronchopulmonary dysplasia (BPD) and cerebral palsy (CP). This large epidemiological study aimed to explore the co-occurrence of BPD and CP among children. Methods: This retrospective cohort analysis utilized the National Inpatient Sample (NIS) dataset from 2016 to 2019, investigating pediatric patients with BPD and CP diagnoses. Descriptive and inferential statistics, including univariate and multivariate regression analyses, were conducted to explore the association between BPD and CP. Results: Overall, 3,951,039 patients were analyzed. Among them, 28,880 patients had CP (n = 796 with BPD and n = 28,084 without BPD). The rates of intraventricular hemorrhage grade 3 and 4, central nervous system anomalies, chromosomal disorders, retinopathy of prematurity (≥grade 3), periventricular leukomalacia, prematurity, and low birth weight were significantly higher in the CP-with-BPD arm contrasted to the CP-without-BPD arm. Univariate regression demonstrated a significant BPD–CP association (odds ratio [OR] = 7.78, 95% confidence interval [CI]: 7.24–8.37, p < 0.0001). Multivariate analysis, adjusting for various confounders, reinforced this association (OR = 5.70, 95% CI: 5.17–6.28, p < 0.0001). We observed a significant association between increasing prematurity in neonates with BPD and an elevated risk of CP. Conclusions: This nationwide study identified a strong correlation between the co-occurrence of BPD and CP, though it does not establish causality. Rigorous adjustments revealed that patients with BPD appear to have a six-fold increased likelihood of being diagnosed with CP later on, compared to those without BPD. While aligned with the existing literature, this study represents the largest sample size with recommendations for targeted preventive strategies to mitigate the burden of CP.

A large epidemiological study on human papillomavirus vaccine post-vaccination symptoms and healthy vaccinee bias

Objective This study aimed to examine the existence of healthy vaccinee bias, a source of distortion in the evaluation of vaccine efficacy, through analysis without random assignment using real data on post-vaccination symptoms from the Nagoya Study, a large epidemiological study of human papillomavirus (HPV) vaccine post-vaccination symptoms.Methods For three school years of individuals born in 1997, 1998, and 1999, as the HPV vaccine had a 2-year target period, 3,246 were first vaccinated at age 14 years and 3,961 were unvaccinated. The proportion of symptom onset in these 7,207 individuals during the unvaccinated period at age 13 years was compared by birth year to examine the presence of a healthy vaccinee bias.Results Only four symptoms were significantly higher among unvaccinated participants, such as the proportion of "severe headache," which occurred in 2010 among those born in 1997, "hyperventilation," which occurred in 2011 among those born in 1998, "fatigue" and "sudden vision loss," which occurred in 2012 among those born in 1999. Healthy vaccinee biases are rarely observed.Conclusion Underestimation of the odds ratio of HPV vaccination due to healthy vaccinee bias is limited, and the claim that the supposedly high odds ratio in the Nagoya Study was masked by a healthy vaccinee bias is invalid.

Proportion of patients with prosthetic joint infection eligible for adjuvant phage therapy: a French single-centre retrospective study

BackgroundBone and joint infections represent a major public health issue due to their increasing prevalence, their functional prognosis and their cost to society. Phage therapy has valuable anti-biofilm properties against prosthetic joint infections (PJI). The aim of this study was to establish the proportion of patients eligible for phage therapy and to assess their clinical outcome judged against all patients presenting with PJI.Method. Patients admitted for periprosthetic joint infection (PJI) at a French general hospital between 2015 and 2019 were retrospectively included. Eligibility for phage therapy was determined based on French recommendations, with polymicrobial infections serving as exclusion criteria. Patients were categorized into two groups: those eligible and those ineligible for phage therapy. We analyzed their characteristics and outcomes, including severe adverse events, duration of intravenous antibiotic therapy, length of hospitalization, and relapse rates.Results. In this study, 96 patients with PJI were considered in multidisciplinary medical meetings. Of these, 44% patients (42/96) were eligible for additional phage therapy. This group of patients had a longer duration of intravenous therapy (17 days vs. 10 days, p = 0.02), more severe adverse events (11 vs. 3, p = 0.08) and had a longer hospital stay (43 days vs. 18 days, p < 0.01).Conclusion. A large number of patients met eligibility criteria for phage therapy and treatment and follow-up is more complex. A larger epidemiological study would more accurately describe the prognosis of eligible patients.

Per-and polyfluoroalkyl substances and disrupted sleep: mediating roles of proteins

BackgroundPer-and polyfluoroalkyl substances (PFAS) contamination may disrupt sleep through disrupted metabolic and immune functions. The study aims to investigate the association and potential mechanism between PFAS and sleep. MethodsWe included 136 young adults recruited between 2014-2018 and 76 were re-assessed between 2020-2022. Additional 8 participants only had complete data between 2020-2022. Plasma PFAS (PFOS, PFOA, PFHxS, PFHpS, PFPeS, PFNA, PFDA) were measured at both visits using liquid-chromatography high-resolution mass spectrometry. Plasma proteins were measured by Olink® Explore 384 Cardiometabolic and Inflammation Panel I. Sleep duration was self-reported at both visits along with follow-up sleep disturbance and sleep-related impairment using validated instruments. We utilized multiple linear regression to explore the association between individual PFAS (in tertile) and these sleep outcomes. PFAS associated with sleep outcomes were subjected to computational toxicology analysis using the Comparative Toxicogenomics Database and Toxicology in the 21st Century database to identify potential genetic links between them. Mediation analysis using proteomic data was then performed to confirm the findings from computational toxicology analysis. ResultsAt baseline, one tertile increase in PFDA was associated with 0.39 (95% CI: 0.05, 0.73) hours of shorter nightly sleep duration, and, at follow-up, PFHxS and PFOA were associated with 0.39 (95% CI: 0.05, 0.72) and 0.32 (95% CI: 0.01, 0.63) hours shorter sleep duration, respectively. One tertile increase in PFOS exposure was associated with a 2.99-point increase in sleep disturbance scores (95% CI: 0.67, 5.31) and a 3.35-point increase in sleep-related impairment scores (95% CI: 0.51, 6.20). Computational toxicology and mediation analyses identified potential mediating roles for several proteins in the PFAS-sleep associations, including 11-beta-dehydrogenase isozyme 1 (HSD11B1), cathepsin B (CTSB) and several immune system-related proteins. ConclusionFuture large scale epidemiological and mechanistic studies should confirm our findings and test effect measure modification of the associations by age.

54098 Higher Incidence of Precocious Puberty in Pediatric Patients with Hidradenitis Suppurativa: A large database epidemiological study

54098 Higher Incidence of Precocious Puberty in Pediatric Patients with Hidradenitis Suppurativa: A large database epidemiological study

PREVALENCE OF LYMPHEDEMA USING LARGE DATA SETS; AN EPIDEMIOLOGICAL ANALYSIS IN THE UNITED STATES AND IN ITALY

There is a lack of large epidemiological studies focusing on the prevalence of lymphedema. Vital registration data from the United States (US) (1999-2020) and Veneto, Italy (2008-2021) were analyzed. Lymphedema-related deaths were identified using disease-specific ICD-10 codes and served to estimate the burden of disease in the general population. We studied (i) the lymphedema-specific proportionate mortality as a proxy of the disease-specific prevalence, (ii) the prevalence of lymphedema in key patient subgroups, and (iii) age and sex-specific mortality rates. The prevalence of lymphedema increased over the last two decades with marked sex-specific differences: in the US, the estimated prevalence of lymphedema was 2.7 per 10,000 deaths for women and 1.5 per 10,000 deaths for men. In Veneto, the prevalence was 3.0 per 10,000 deaths for women and 1.1 per 10,000 deaths for men. The prevalence of lymphedema was 2- to 20-times in specific subgroups of patients, including those with obesity, skin infections, hypertension, diabetes mellitus, breast/gynecological cancers, and venous thromboembolism. The estimated prevalence of lymphedema is 2- to 3- times higher than previously thought and has been increasing for the past two decades. These results will serve as a reference for future research in this field.

Saliva-derived DNA is suitable for the detection of clonal haematopoiesis of indeterminate potential

Clonal haematopoiesis of indeterminate potential (CHIP) has been associated with many adverse health outcomes. However, further research is required to understand the critical genes and pathways relevant to CHIP subtypes, evaluate how CHIP clones evolve with time, and further advance functional characterisation and therapeutic studies. Large epidemiological studies are well placed to address these questions but often collect saliva rather than blood from participants. Paired saliva- and blood-derived DNA samples from 94 study participants were sequenced using a targeted CHIP-gene panel. The ten genes most frequently identified to carry CHIP-associated variants were analysed. Fourteen unique variants associated with CHIP, ten in DNMT3A, two in TP53 and two in TET2, were identified with a variant allele fraction (VAF) between 0.02 and 0.2 and variant depth ≥ 5 reads. Eleven of these CHIP-associated variants were detected in both the blood- and saliva-derived DNA sample. Three variants were detected in blood with a VAF > 0.02 but fell below this threshold in the paired saliva sample (VAF 0.008—0.013). Saliva-derived DNA is suitable for detecting CHIP-associated variants. Saliva can offer a cost-effective biospecimen that could both advance CHIP research and facilitate clinical translation into settings such as risk prediction, precision prevention, and treatment monitoring.

53 Associations between body composition, ClearCode34, and clinical outcomes in localized clear cell renal cell carcinoma

Abstract Background Emerging evidence suggests that pre-surgical body composition is a prognostic factor for cancer outcomes. Lower skeletal muscle quantity and radiodensity have been associated with renal cell carcinoma (RCC) outcomes in other studies, while reports of the relationship between visceral adipose tissue and RCC outcomes have been inconsistent. Mechanisms underlying these associations are unclear but may relate to tumor biology. We leveraged a large molecular epidemiology study of localized clear cell renal cell carcinoma (ccRCC) patients to examine how pre-surgical body composition features were associated with survival post-nephrectomy as well as ClearCode34 status, a previously validated prognostic gene expression signature. Methods The RESOLVE study at Memorial Sloan Kettering Cancer Center is a retrospective study of 1,239 patients with stage I-III ccRCC undergoing nephrectomy without systemic therapy. Pre-surgical CT scans at the third lumbar vertebrae were segmented for the cross-sectional areas and radiodensities of skeletal muscle, subcutaneous adipose and visceral adipose tissues using Automatica software. Formalin-fixed, paraffin-embedded tumor tissue samples were available for 929 patients, which were sent to the University of North Carolina at Chapel Hill and assayed for gene expression. RNA was extracted from these samples and analyzed using the Nanostring nCounter system on a custom panel of 356 genes, including the 34 genes used in the ClearCode34 assay. Of the 929 patients with tumor tissue available, gene expression data from 837 patients (90.1%) passed RNA extraction and data QC. Samples were classified into either ccA or ccB ClearCode34 classes using a reference data set and PAM (prediction analysis of microarrays) centroid-based classification. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) within five years of diagnosis using Cox proportional hazards models for both body composition variables and ClearCode34 subtype. We also estimated odds ratios (ORs) and 95% CIs for associations between ClearCode34 subtype and body composition with logistic regression. All multivariable models were adjusted for age, sex, and all body composition variables. Results Of the 837 patients in our analytic sample, 219 (26%) had ccB tumors. Men, patients with high stage or grade tumors, and patients with chronic kidney disease prior to nephrectomy were more likely to present with ccB tumors. Lower skeletal muscle density (SMD) was significantly associated with lower five-year DFS [HR (95% CI) per 10 HU decrease in SMD: 1.7 (1.2, 2.3)]. While no other body composition features were significantly associated, we also observed non-significantly increased HRs for VATI and VATD [HR (95% CIs): 1.3 (0.8, 2.0) and 1.5 (0.9, 2.7), respectively]. ClearCode34 subtype was significantly associated with five-year DFS, where patients with ccB tumors had poorer DFS [HR (95% CI): 1.7 (1.1, 2.5)] compared to patients with ccA tumors. Notably, we observed no significant associations between any body composition feature and ClearCode34 in univariable analyses. However, in multivariable models that accounted for all body composition variables simultaneously as well as age and sex, lower SMD emerged as significantly associated with ccB subtype [OR (95% CI) per 10 HU decrease in SMD: 1.3 (1.0, 1.7)]. Conclusions Our findings suggest that the associations observed between body composition features and clinical outcomes in ccRCC may be related to tumor biology. Lower pre-surgical SMD, which may represent myosteatosis and metabolic dysregulation in ccRCC patients, was associated with both decreased five-year DFS and an increased likelihood of presenting with a more aggressive ccB tumor. Future studies should investigate body composition features related to ccRCC prognosis and additional markers of tumor biology, such as immune-related gene expression patterns, to extend these findings.

Let's talk about radiation dose and radiation protection in children.

Children are more sensitive to ionizing radiation than adults. Even though the risk is very low, exposure from radiological examinations can possibly cause them long-term side effects. Recent large epidemiological studies involving children and young adults have added evidence suggesting that even small doses of radiation, such as those from computed tomography scans, might slightly increase the risk of developing cancer later in life. Therefore, even though radiologic studies are essential for an accurate diagnosis and management of various conditions, it is crucial to minimize radiation exposure. This article addresses radiation protection for children in the medical use of ionizing radiation and it is set in the context of the European legislative framework regarding radiation protection. It advocates for a holistic approach to paediatric radiological tests. This approach includes the key principles of radiation protection, such as the justification of imaging procedures supported by referral guidelines, as well as the optimization of techniques (according to the ALARA principle) and effective communication with parents about the benefits and the risks of radiologic procedures. Protecting children from unnecessary radiation is not only a technical challenge, but also a moral obligation and a legal requirement.

Differences in self-reported disruptions in mental health treatment during COVID-19 in a national household sample: impact of severity of functional impairment.

This report uses data from Mental Disorders Prevalence Study (MDPS), a large epidemiologic study that provided national prevalence estimates of seven mental disorders based on the Structured Clinical Interview for DSM-5 (SCID), to assess the odds of treatment disruption during COVID for SMI and non-SMI groups. This cross-sectional study conducted from 2020 to 2022 included 2,810 household participants with any lifetime mental health treatment. Weighted logistic regressions estimated the odds of reporting disruptions in access to mental health care or psychotropic prescriptions due to COVID. SMI was broadly defined as having an MDP diagnosis and serious functional impairment (GAF ≤50, a validated and widely used cutoff). Non-SMI groups were a mental diagnosis without serious impairment (MDPS diagnosis, GAF >50) and any lifetime treatment and no serious impairment (no MDPS diagnosis, GAF >50). The SMI and mental disorder without serious impairment groups had approximately 6.4- and 2.4-greater odds, respectively, of reporting inability to access mental health care and 4- and 3- greater odds, respectively, of having prescriptions delayed, relative to the group with any lifetime treatment. Among those with serious mental illness, having Medicare insurance increased the odds of reporting inability to access mental health care. Individuals with SMI were much more likely to experience treatment disruptions throughout the pandemic than non-SMI groups.

Mitochondrial DNA abundance in blood is associated with Alzheimer's disease- and dementia-risk.

The mitochondrial cascade hypothesis of Alzheimer's disease (AD) has been portrayed through molecular, cellular, and animal studies; however large epidemiological studies are lacking. This study aimed to explore the association of mitochondrial DNA copy number (mtDNAcn), a marker representative of mtDNA abundance per cell, with risk of incident all-cause dementia, AD, and vascular dementia diagnosis within 17 years and dementia-related blood biomarkers (P-tau181, GFAP, and NfL). Additionally, sex-stratified analyses were completed. In this German population-based cohort study (ESTHER), 9940 participants aged 50-75 years were enrolled by general practitioners and followed for 17 years. Participants were included in this study if information on dementia status and blood-based mtDNAcn measured via real-time polymerase chain reaction were available. In a nested case-control approach, a subsample of participants additionally had measurements of P-tau181, GFAP, and NfL in blood samples taken at baseline. Of 4913 participants eligible for analyses, 386 were diagnosed with incident all-cause dementia, including 130 AD and 143 vascular dementia cases, while 4527 participants remained without dementia diagnosis within 17 years. Participants with low mtDNAcn (lowest 10%) experienced 45% and 65% percent increased risk of incident all-cause dementia and AD after adjusting for age and sex (all-cause dementia: HRadj, 95%CI:1.45, 1.08-1.94; AD: HRadj, 95%CI: 1.65, 1.01-2.68). MtDNAcn was not associated to vascular dementia diagnosis and was more strongly associated with all-cause dementia among women. In the nested case-control study (n = 790), mtDNAcn was not significantly associated with the dementia-related blood biomarkers (P-tau181, GFAP, and NfL) levels in blood from baseline before dementia diagnosis. This study provides novel epidemiological evidence connecting mtDNA abundance, measured via mtDNAcn, to incident dementia and AD at the population-based level. Reduced mitochondrial abundance may play a role in pathogenesis, especially among women.

How pre-analytical conditions impact glucose measurement and (gestational) diabetes diagnosis: A real-world stability study and a call for harmonization

Background and aimsSince 2023, guidelines of the AACC/ADA recommend the use of citrate buffer-containing tubes as a first option for glucose measurement. This study aims to assess the pre-analytical stability of glucose under various conditions (room temperature (RT) or at 4 °C) and the potential real-world impact of introducing these tubes on (gestational) diabetes and IFG prevalence. Materials and Methods25 healthy volunteers were sampled to assess glucose stability across time, at 4 °C and at RT, before and following centrifugation. 701 patients undergoing fasting plasma glucose analysis and 109 women having OGTT were collected according to current procedures (NaFl K2C2O4 (NaFl) tubes) as well as with citrate-containing tubes (FC Mix). ResultsThe mean glucose concentration bias between FC Mix and NaFl tubes when centrifugation occurred within 5 min was 0.53 % and this difference raised slowly to reach 2.3 %, six-hours post-centrifugation. When centrifugation was delayed, a rapid decrease in glucose concentrations was observed for NaFl tubes (4.9 % at 30 min) and this trend was only partially reduced by placing samples at 4 °C (3.1 %). The decrease reached 10.8 % (RT) and 7.8 % (4 °C) at 2 h, before reaching a plateau. Samples collected on citrate remained stable during 24 h. In real-life conditions, the mean bias between FC Mix and NaFl tubes increased progressively over time and reached 8.59 % for samples centrifuged between two- and four-hours following sampling. Compared to widespread practices, the use of citrate-containing tubes increased IFG, DM and GDM prevalences by 84.0 %, 36.7 % and 150 %, respectively. ConclusionsGlucose concentrations rapidly decrease in NaFl tubes following collection and placing samples at 4 °C reduces only marginally the decay. Citrate-containing tubes offer a valuable solution for direct and long-lasting glucose stabilization but, before wider adoption, large epidemiologic studies should confirm or redefine current diabetes diagnostic thresholds.

Epidemiology of childhood interstitial lung disease in France: the RespiRare cohort

IntroductionInterstitial lung disease in children (chILD) are rare and mostly severe lung diseases. Very few epidemiological data are available in limited series of patients. The aim of this study was...

Prospective “common arm” comparison of US SWOG S0424 and Japanese JME studies in early-stage non-small cell lung cancer (NSCLC): Survival differences in the context of race, gender and smoking.

8036 Background: In NSCLC, overall frequencies and subtype distribution of EGFR and KRAS mutations differ significantly between Japanese and US patients. In many NSCLC clinical trials, Japanese patient outcomes appear superior to those in western populations. Since 2009, SWOG and Japanese investigators have used the “Common Arm” analytic method to interpret globally-conducted lung cancer clinical trials, providing a mechanism for direct patient-level comparisons in matching trials performed in the US and Japan. S0424 and the Japanese Molecular Epidemiology Study (JME) are large prospective molecular epidemiology studies conducted by SWOG and Japanese investigators and prospectively planned for “Common Arm” analysis. We investigated the effects of mutation distribution on overall survival in early stage NSCLC using data from JME and S0424. Methods: Both studies were designed to accrue representative proportions of ever-smokers (ES) versus never-smokers (NS) in male and female cohorts. Accrual to S0424 was completed in 2011 with 981 pts enrolled (Cheng et al JNCI 2018); JME was completed in 2012 with 957 pts (Kawaguchi et al JCO 2016). A comprehensive questionnaire was used to capture lifestyle, carcinogenic exposures, demographic and clinical data. Five years of follow-up was completed for each study. The association between baseline characteristics and mutation types were analyzed using multivariate logistic regression. The product-limit method was used to estimate overall survival and Cox regression models were fit to estimate hazard ratios. p-values were two-sided and p-values &lt; 0.05 were considered significant. Results: Evaluable pts: 876 for JME; 957 for S0424. Demographic distribution: S0424: 87% Caucasian, 5% Asian, 4% Black; JME: 100% Japanese. As expected, multivariate logistic models adjusting for age, smoking status, gender and BMI showed JME were more likely to have EGFR mutations (p &lt; 0.0001) and less likely to have KRAS mutations (p = 0.02). EGFR mutations were associated with never-smoking (p &lt; 0.0001) and female sex (p &lt; 0.0001); KRAS was associated with smoking (p &lt; 0.0001). Adjusting for age, smoking status and gender, overall survival was greater in JME patients (p &lt; 0.0001,HR = 0.49 (95% CI: 0.40-0.60)). In the subset of pts without an EGFR mutation, survival still favored the JME cohort (p &lt; 0.001, HR = 0.68 (0.53-0.86). Conclusions: Patient level comparison of US (SWOG) and Japanese (JME) patients with early stage NSCLC demonstrated longer survival in Japanese patients even after adjusting for EGFR mutation frequency. Identification of factors that contribute to this finding are under investigation. Female sex remained a risk factor for EGFR mutation-driven disease in both populations. This analysis forms the basis for applying this population-related model in other clinical settings.

Validity of Measured vs. Self-Reported Weight and Height and Practical Considerations for Enhancing Reliability in Clinical and Epidemiological Studies: A Systematic Review.

Self-reported measures of height and weight are often used in large epidemiological studies. However, concerns remain regarding the validity and reliability of these self-reported measures. The aim of this systematic review was to summarise and evaluate the comparative validity of measured and self-reported weight and height data and to recommend strategies to improve the reliability of self-reported-data collection across studies. This systematic review adopted the PRISMA guidelines. Four online sources, including PubMed, Medline, Google Scholar, and CINAHL, were utilised. A total of 17,800 articles were screened, and 10 studies were eligible to be included in the SLR based on the defined inclusion and exclusion criteria. The findings from the studies revealed good agreement between measured and self-reported weight and height based on intra-class correlation coefficient and Bland-Altman plots. Overall, measured weight and height had higher validity and reliability (ICC > 0.9; LOA < 1 SD). However, due to biases such as social pressure and self-esteem issues, women underreported their weight, while men overreported their height. In essence, self-reported measures remain valuable indicators to supplement the restricted direct anthropometric data, particularly in large-scale surveys. However, it is essential to address potential sources of bias.

Quantification of 25-hydroxyvitamin D3 in dried blood spots as compared to plasma among Indian adults

Background Vitamin D may play an important role in later-life physical and cognitive health. Vitamin D status is standardly assessed in serum and plasma; however, collection, transport, and storage costs make large epidemiologic studies challenging. We assessed the agreement of 25-hydroxyvitamin D3 (25(OH)D3) quantification from dried blood spots (DBS) as compared to standard plasma assessment among older Indian adults. Methods A total of 58 adults over 45 years of age who resided in Pune, India were enrolled in the study from July 2020 to June 2021. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to assess 25(OH)D3 concentrations in paired plasma and DBS samples. Results Plasma and DBS 25(OH)D3 concentrations were highly correlated (Pearson’s correlation = 0.976). The median 25(OH)D3 concentration of the study population assessed by plasma was 14.6 ng/mL (Q1=12.0, Q3= 18.1) while the median concentration assessed in DBS was 12.8 ng/mL (Q1=11.0, Q3= 16.6). 25(OH)D3 concentrations measured from DBS were on average 6% (95% CI: 2-13%) lower than concentrations assessed by plasma across the observed 25(OH)D3 distribution. Conclusions We found good agreement between 25(OH)D3 quantification between DBS and plasma and our findings indicate that DBS can be used in epidemiologic studies of vitamin D among Indian adults.

Preconception depression reduces fertility: a couple-based prospective preconception cohort.

Is preconception depression associated with time to pregnancy (TTP) and infertility? Couples with preconception depression needed a longer time to become pregnant and exhibited an increased risk of infertility. Preconception depression in women contributes to impaired fertility in clinical populations. However, evidence from the general population-especially based on couples-is relatively scant. A couple-based prospective preconception cohort study was performed in 16 premarital examination centers between April 2019 and June 2021. The final analysis included 16521 couples who tried to conceive for ≤6 months at enrollment. Patients with infertility were defined as those with a TTP ≥12 months and those who conceived through ART. Couples' depression was assessed using the Patient Health Questionnaire-9 at baseline. Reproductive outcomes were obtained via telephone at 6 and 12 months after enrollment. Fertility odds ratios (FORs) and infertility risk ratios (RRs) in different preconception depression groups were analyzed using the Cox proportional-hazard models and logistic regression, respectively. Of the 16 521 couples analyzed, 10834 (65.6%) and 746 (4.5%) couples achieved pregnancy within the first 6 months and between the 6th and 12th months, respectively. The median (P25, P75) TTP was 3.0 (2.0, 6.0) months. The infertility rate was 13.01%. After adjusting for potential confounders, in the individual-specific analyses, we found that preconception depression in women was significantly related to reduced odds of fertility (FOR = 0.947, 95% CI: 0.908-0.988), and preconception depression in either men or women was associated with an increased risk of infertility (women: RR = 1.212, 95% CI: 1.076-1.366; men: RR = 1.214, 95% CI: 1.068-1.381); in the couple-based analyses, we found that-compared to couples where neither partner had depression-the couples where both partners had depression exhibited reduced fertility (adjusted FOR = 0.904, 95% CI: 0.838-0.975). The risk of infertility in the group where only the woman had depression and both partners had depression increased by 17.8% (RR = 1.178, 95% CI: 1.026-1.353) and 46.9% (RR = 1.469, 95% CI: 1.203-1.793), respectively. Reporting and recall bias were unavoidable in this large epidemiological study. Some residual confounding factors-such as the use of anti-depressants and other medications, sexual habits, and prior depressive and anxiety symptoms-remain unaddressed. We used a cut-off score of 5 to define depression, which is lower than prior studies. Finally, we assessed depression only at baseline, therefore we could not detect effects of temporal changes in depression on fertility. This couple-based study indicated that preconception depression in individuals and couples negatively impacts couples' fertility. Early detection and intervention of depression to improve fertility should focus on both sexes. This work was supported by grants from the National Natural Science Foundation of China (No. 82273638) and the National Key Research and Development Program of China (No. 2018YFC1004201). All authors declare no conflicts of interest. N/A.

Diabetes mellitus, metabolic syndrome, and sleep disorders: An underestimated relationship

Abstract Diabetes mellitus (DM) is the most prevalent endocrine disorder globally. DM is under-evaluated and less efficiently managed in terms of ruling out comorbid conditions associated with it and predisposing factors resulting in poor outcomes. Sleep disorders are more common than usually diagnosed due to less awareness in the community regarding the importance of timely diagnosis and the impact of interventions related to proper sleep hygiene and sleep structure. Obstructive sleep apnea (OSA) is independently associated with cardiovascular and cardiometabolic risk in several large epidemiological studies. OSA leads to several physiological disturbances, such as intermittent hypoxia, sleep fragmentation, and an increase in autonomic tone. Metabolic syndrome (MS) is an adverse outcome that is typically associated with obesity. It is a cluster of metabolic risk factors for type 2 DM (T2DM) and cardiovascular diseases (CVDs), including central obesity, hypertension, hyperglycemia, insulin resistance, and dyslipidemia. T2DM is often associated with OSA, and a bidirectional relationship may exist between the two diseases, mediated by both weight- and physiology-dependent mechanisms. OSA is highly associated with T2DM, and treatment of OSA may have a positive impact on the cardiometabolic profile. In this review, we have attempted to summarize the impact of sleep disorders on MS and DM, and vice versa, with special emphasis on newer medical options in the management of DM and cardiometabolic syndrome.

Young Trauma-Exposed Women with Low Sleep Effciency have Blunted Sympathetic Baroreflex Sensitivity and Higher Muscle Sympathetic Nerve Activity

Introduction: Poor sleep, a known risk factor for cardiovascular disease (CVD) and one of the American Heart Association’s essential 8th, is common after trauma-exposure. Although premenopausal women are thought to be protected from CVD, trauma exposure might increase their CVD risk. In a recent large epidemiological study examining sleep-related CVD comorbidities, the empirical cut off point for optimal sleep effciency (SE) was set at 83%, distinguishing between good and poor sleep effciency. Studies have suggested an overactive sympathetic nervous system and an impaired baroreflex sensitivity (BRS) as potential mechanisms of increased CVD risk. However, the impact of poor sleep effciency on muscle sympathetic nerve activity (MSNA) and BRS in young trauma-exposed women is unknown. We hypothesized that young trauma-exposed women with poor sleep effciency will present with impaired BRS and increased MSNA at rest. Methods: We collected data on 30 women (18 – 40 years) from diverse backgrounds who had been exposed to trauma. Sleep data was acquired via ActiWatch for 7 days and used to categorize our participants into two groups: good effciency (SE &gt; 83%, n=17) and poor effciency (SE &lt; 83%, n=13), with SE calculated as the percentage of time spent asleep while in bed. Additionally, we collected continuous noninvasive blood pressure (BP), heart rate (HR), and MSNA (burst frequency, incidence, and total activity) during 10 minutes of quiet rest. Sympathetic BRS was determined as the slope of the regression between individual sympathetic bursts and diastolic BP bins (3 mmHg), weighted against the number of cardiac cycles, utilizing an automated program (Ensemble, NZ). Results: There were no significant differences in trauma symptom severity, resting BP and HR between the two groups (p&gt;0.05 for all). However, resting sympathetic BRS was blunted in the poor SE (-0.10±0.88 bursts/100hb/mmHg) compared to the good SE (-1.44±1.58 bursts/100hb/mmHg, p=0.006) group, even after adjusting for age (p=0.009). Likewise, resting total MSNA was higher in the poor SE compared to the good SE after adjusting for age (p=0.028). MSNA burst frequency and burst incidence were comparable between the groups (p&gt;0.05). Conclusion: Our analyses revealed that poor sleep effciency is associated with decreased sympathetic baroreflex sensitivity and higher total muscle sympathetic activity at rest, regardless of age. Blunted sympathetic BRS may contribute to increased sympathetic activity in young women with poor sleep effciency. Future studies testing strategies to improve sleep effciency in this population could provide potential long-term cardiovascular benefits. UL1TR002494 and NIH K01HL161027 No disclosure. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Objective Sleep Effciency Is Negatively Associated with Resting Heart Rate in Young Trauma-Exposed Women with Poor Sleep

Introduction: Women are twice as likely as men to develop post-traumatic stress disorder (PTSD), a debilitating mental health disorder caused by a traumatic event that can lead to a higher risk of developing cardiovascular disease (CVD). Sleep is currently recognized as an essential component of cardiovascular health by the American Heart Association. Further, a large epidemiological study empirically set the cut-off point for normal sleep effciency (SE) at 83%, differentiating good sleep from poor sleep. Trauma-provoked sleep disturbances such as disruptive nocturnal behaviors and nightmares are a hallmark of PTSD. Yet, the impact of sleep disturbances on cardiovascular biomarkers such as blood pressure (BP) and heart rate (HR) in young trauma-exposed women is unknown. Therefore, the aim of our study was to investigate how objectively recorded sleep measures are associated with HR and BP in these young trauma-exposed women. We hypothesized that sleep quality will predict HR and/or BP, independently of the severity of trauma symptoms. Methods: We recruited 93 trauma-exposed young women (18-40 years). During the in-person visit, we measured BP and HR using an automated vital signs monitor. Additionally, we assessed trauma symptom severity using the PTSD checklist for DSM-5 (PCL5). After the laboratory visit, we sent participants home with a sleep watch (Philips Respironics) for 7 consecutive days, to quantify the percentage of time spent asleep while in bed. Given that a minimum of 83% SE is considered effcient sleep, we separated our data into two groups based on SE [good effciency (SE &gt;83%, n= 42) and poor effciency (SE &lt;83%, n= 51)]. Results: Participants’ mean age and body mass index were 26 ± 7 years and 25.7 ± 6.6 kg/m2 respectively. Pearson correlations revealed a negative correlation between resting HR and SE (r= -0.486, p&lt; 0.001) and HR and age (r= -0.246, p= 0.085) in the SE &lt;83% group. In contrast, there was no correlation between resting HR and SE (r= 0.025, p= 0.861) in the SE &gt;83% group. Therefore, we conducted further analysis in the SE &gt;83% group only. We observed a negative correlation between HR and the trauma symptoms subcluster of hyperarousal (r= -0.285, p= 0.045) in this poor SE group. Next, we ran a multiple linear regression predicting HR with SE, age, and the subclusters of hyperarousal and intrusion (affected by disruptive nocturnal behaviors and nightmares) as predictors. The model predicting HR was significant (R2= 0.366, p&lt; 0.001) and SE remained the strongest predictor (β= -0.458, p= 0.001) even when controlling for age, and trauma symptom subclusters, followed by age (β= -0.263, p= 0.037). Conclusion: Our analyses reveal that sleep effciency in trauma-exposed women is a strong predictor of resting HR, even when controlling for age and trauma symptoms subclusters of intrusion and hyperarousal. These findings suggest that in the context of trauma, it is the reduction in sleep effciency that has the greatest impact on resting heart rate, and ultimately mental health-associated CVD. K01HL161027 and UMN CTSI UL1TR002494 No Disclosure. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.