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Rationale: Sleep-disordered breathing (SDB) increases the risk of cardiac arrhythmias and sudden cardiac death.

Objectives: To characterize the associations between SDB, intermittent hypoxemia, and the beat-to-beat QT variability index (QTVI), a measure of ventricular repolarization lability associated with a higher risk for cardiac arrhythmias, sudden cardiac death, and mortality.

Methods: Three distinct cohorts were used for the current study. The first cohort, used for cross-sectional analysis, was a matched sample of 122 participants with and without severe SDB. The second cohort, used for longitudinal analysis, consisted of a matched sample of 52 participants with and without incident SDB. The cross-sectional and longitudinal cohorts were selected from the Sleep Heart Health Study participants. The third cohort comprised 19 healthy adults exposed to acute intermittent hypoxia and ambient air on two separate days. Electrocardiographic measures were calculated from one-lead electrocardiograms.

Results: Compared to those without SDB, participants with severe SDB had greater QTVI (-1.19 in participants with severe SDB vs. -1.43 in participants without SDB, P = 0.027), heart rate (68.34 vs. 64.92 beats/minute; P = 0.028), and hypoxemia burden during sleep as assessed by the total sleep time with oxygen saturation less than 90% (TST₉₀; 11.39% vs. 1.32%, P < 0.001). TST₉₀, but not the frequency of arousals, was a predictor of QTVI. QTVI during sleep was predictive of all-cause mortality. With incident SDB, mean QTVI increased from -1.23 to -0.86 over 5 years (P = 0.017). Finally, exposing healthy adults to acute intermittent hypoxia for four hours progressively increased QTVI (from -1.85 at baseline to -1.64 after four hours of intermittent hypoxia; P = 0.016).

Conclusions: Prevalent and incident SDB are associated with ventricular repolarization instability, which predisposes to ventricular arrhythmias and sudden cardiac death. Intermittent hypoxemia destabilizes ventricular repolarization and may contribute to increased mortality in SDB.

We investigate the causal relationship between educational attainment (EA) and mental health using two research designs. First, we compare the relationship between EA and 18 psychiatric diagnoses within sibship in Dutch national registry data (N=1.7 million), thereby controlling for unmeasured familial factors. Second, we apply two-sample Mendelian Randomization, which uses genetic variants related to EA or psychiatric diagnosis as instrumental variables, to test whether there is a causal relation in either direction. Our results suggest that lower levels of EA causally increase the risk of MDD, ADHD, alcohol dependence, GAD and PTSD diagnoses. We also find evidence of a causal effect of ADHD on EA. For schizophrenia, anorexia nervosa, OCD, and bipolar disorder, results were inconsistent across the different approaches, highlighting the importance of using multiple research designs to understand complex relationships such as between EA and mental health.

Studies have reported that prior-season influenza vaccination is associated with higher risk of clinical influenza infection among vaccinees. This effect might arise from incomplete consideration of within-season waning and recent infection. Using data from the US Flu Vaccine Effectiveness (VE) Network (2011-2012 to 2018-2019 seasons), we found that repeat vaccinees were vaccinated earlier in a season by one week. After accounting for waning VE, repeat vaccinees were still more likely to test positive for A(H3N2) (OR=1.11, 95%CI:1.02-1.21) but not for influenza B or A(H1N1). We found that clinical infection influenced individuals' decision to vaccinate in the following season while protecting against clinical infection of the same (sub)type. However, adjusting for recent clinical infections did not strongly influence the estimated effect of prior-season vaccination. In contrast, we found that adjusting for subclinical infection could theoretically attenuate this effect. Additional investigation is needed to determine the impact of subclinical infections on VE.

Background: Anxiety disorders are prevalent and anxiety symptoms co-occur with many psychiatric disorders. We aimed to identify genomic risk loci associated with anxiety, characterize its genetic architecture, and genetic overlap with psychiatric disorders.

Methods: We used the GWAS of anxiety symptoms, schizophrenia, bipolar disorder, major depression, and attention deficit hyperactivity disorder (ADHD). We employed MiXeR and LAVA to characterize the genetic architecture and genetic overlap between the phenotypes. Conditional and conjunctional false discovery rate analyses were performed to boost the identification of genomic loci associated with anxiety and those shared with psychiatric disorders. Gene annotation and gene set analyses were conducted using OpenTargets and FUMA, respectively.

Results: Anxiety was polygenic with 12.9k estimated genetic risk variants and overlapped extensively with psychiatric disorders (4.1-11.4k variants). MiXeR and LAVA revealed predominantly positive genetic correlations between anxiety and psychiatric disorders. We identified 114 novel loci for anxiety by conditioning on the psychiatric disorders. We also identified loci shared between anxiety and major depression (n = 47), bipolar disorder (n = 33), schizophrenia (n = 71), and ADHD (n = 20). Genes annotated to anxiety loci exhibit enrichment for a broader range of biological pathways and differential tissue expression in more diverse tissues than those annotated to the shared loci.

Conclusions: Anxiety is a highly polygenic phenotype with extensive genetic overlap with psychiatric disorders. These genetic overlaps enabled the identification of novel loci for anxiety. The shared genetic architecture may underlie the extensive cross-disorder comorbidity of anxiety, and the identified genetic loci implicate molecular pathways that may lead to potential drug targets.

Objective: Limited research links hospital-based experiences of skin-to-skin (STS) care to longer-term neurodevelopmental outcomes in preterm children. The present study examined relations between inpatient STS and neurodevelopmental scores measured at 12 months in a sample of very preterm (VPT) infants.

Study design and methods: From a retrospective study review of medical records of 181 VPT infants (<32 weeks gestational age (GA)) we derived the STS rate, i.e., the total minutes of STS each infant received/day of hospital stay. We used scores on the Capute Scales from routine follow-up care at 12 months as the measure of neurodevelopmental outcome (n=181).

Results: Families averaged approximately 17 minutes/day of STS care (2 days/week, 70 minutes/session), although there was substantial variability. Variation in STS rate was positively associated with outcomes at 12 months corrected age ( r = 0.25, p < .001). STS rate significantly predicted 6.2% unique variance in 12-month neurodevelopmental outcomes, after controlling for GA, socioeconomic status (SES), health acuity, and visitation frequency. A 20-minute increase in STS per day was associated with a 10-point increase (.67 SDs) in neurodevelopmental outcomes at 12 months. SES, GA, and infant health acuity did not moderate these relations.

Conclusion: VPT infants who experienced more STS during hospitalization demonstrated higher scores on 12-month assessments of neurodevelopment. Results provide evidence that STS care may confer extended neuroprotection on VPT infants through the first year of life.

The standard of care for brain tumors is maximal safe surgical resection. Neuronavigation augments the surgeon's ability to achieve this but loses validity as surgery progresses due to brain shift. Moreover, gliomas are often indistinguishable from surrounding healthy brain tissue. Intraoperative magnetic resonance imaging (iMRI) and ultrasound (iUS) help visualize the tumor and brain shift. iUS is faster and easier to incorporate into surgical workflows but offers a lower contrast between tumorous and healthy tissues than iMRI. With the success of data-hungry Artificial Intelligence algorithms in medical image analysis, the benefits of sharing well-curated data cannot be overstated. To this end, we provide the largest publicly available MRI and iUS database of surgically treated brain tumors, including gliomas (n=92), metastases (n=11), and others (n=11). This collection contains 369 preoperative MRI series, 320 3D iUS series, 301 iMRI series, and 356 segmentations collected from 114 consecutive patients at a single institution. This database is expected to help brain shift and image analysis research and neurosurgical training in interpreting iUS and iMRI.

Objective: In the chronic phase after a stroke, limitations in activities of daily living (ADLs) and instrumental ADL (IADLs) initially plateau before steadily increasing. The benefits of pre-stroke physical activity on these limitations remain unclear. To clarify this relationship, we examined the effect of physical activity on the long-term evolution of functional limitations in a cohort of stroke survivors and compared it to a cohort of matched stroke-free adults.

Methods: Longitudinal data from 2,143 stroke survivors and 10,717 stroke-free adults aged 50 years and older were drawn from a prospective cohort study based on the Survey of Health, Ageing and Retirement in Europe (2004-2022; 8 data collection waves). Physical activity was assessed in the pre-stroke wave. Functional limitations were assessed in the post-stroke waves. Each stroke survivor was matched with 5 stroke-free adults who had similar propensity scores computed on the basis of key covariates, including baseline age, sex, body mass index, limitations in ADL and IADL, chronic conditions and country of residence, before any of the participants from either cohort had experienced a stroke.

Results: Results showed an interaction between stroke status and physical activity on ADL limitations (b = -0.076; 95% CI = -0.142 to -0.011), with the effect of physical activity being stronger in stroke survivors (b = -0.345, 95% CI = -0.438 to -0.252) than in stroke-free adults (b = -0.269, 95% CI = -0.269 to -0.241).

Conclusion: The beneficial effect of pre-stroke physical activity on ADL limitations after stroke is stronger than its effect in matched stroke-free adults followed for a similar number of years.

Impact: Physical activity, an intervention within the physical therapist's scope of practice, is effective in reducing the risk of functional dependence after stroke. Moreover, pre-stroke levels of physical activity can inform the prognosis of functional dependence in stroke survivors.

Publicly available audio data presents a unique opportunity for the development of digital health technologies with large language models (LLMs). In this study, YouTube was mined to collect audio data from individuals with self-declared positive COVID-19 tests as well as those with other upper respiratory infections (URI) and healthy subjects discussing a diverse range of topics. The resulting dataset was transcribed with the Whisper model and used to assess the capacity of LLMs for detecting self-reported COVID-19 cases and performing variant classification. Following prompt optimization, LLMs achieved accuracies of 0.89, 0.97, respectively, in the tasks of identifying self-reported COVID-19 cases and other respiratory illnesses. The model also obtained a mean accuracy of 0.77 at identifying the variant of self-reported COVID-19 cases using only symptoms and other health-related factors described in the YouTube videos. In comparison with past studies, which used scripted, standardized voice samples to capture biomarkers, this study focused on extracting meaningful information from public online audio data. This work introduced novel design paradigms for pandemic management tools, showing the potential of audio data in clinical and public health applications.

Background: Bipolar disorder (BD) presents with a wide range of symptoms that vary among relatives, casting doubt on categorical illness models. To address this uncertainly, we investigated the heritability and genetic relationships between categorical and dimensional models of BD in a family sample.

Methods: Participants in the Amish-Mennonite Bipolar Genetics (AMBiGen) study were assigned categorical mood disorder diagnoses by structured psychiatric interview and completed the Mood Disorder Questionnaire (MDQ), which assesses lifetime history of manic symptoms and associated impairment. Major MDQ dimensions were analyzed by Principal Component Analysis (PCA) in 726 participants. Heritability and genetic overlaps between categorical diagnoses and MDQ-derived dimensions were estimated with SOLAR-ECLIPSE within 432 genotyped participants.

Results: MDQ scores were significantly higher among individuals diagnosed with BD and related disorders, as expected, but varied widely among relatives. PCA suggested a three-component model for the MDQ. Heritability of the MDQ score was 30% (p<0.001), evenly distributed across its three principal components. Strong and significant genetic correlations were found between categorical diagnoses and most MDQ measures.

Limitations: Recruitment through probands with BD resulted in increased prevalence of BD in this sample, limiting generalizability. Unavailable genetic data reduced sample size for some analyses.

Conclusion: heritability and high genetic correlations between categorical diagnoses and MDQ measures support a genetic continuity between dimensional and categorical models of BD.

Little is known regarding the relationship between common comorbidities in persons with tuberculosis (TB) (including human immunodeficiency virus [HIV], diabetes, and hepatitis C virus [HCV]) with post-TB mortality. We conducted a retrospective cohort study among persons who initiated treatment for rifampicin-resistant and multi/extensively drug-resistant (RR and M/XDR) TB reported to the country of Georgia's TB surveillance during 2009-2017. Exposures included HIV serologic status, diabetes, and HCV status. Our outcome was all-cause post-TB mortality determined by cross-validating vital status with Georgia's death registry through November 2019. We estimated adjusted hazard rate ratios (aHR) and 95% confidence intervals (CI) of post-TB mortality among participants with and without comorbidities using cause-specific hazard regressions. Among 1032 eligible participants, 34 (3.3%) died during treatment and 87 (8.7%) died post-TB treatment. Among those who died post-TB treatment, the median time to death was 21 months (interquartile range 7-39) post-TB treatment. After adjusting for confounders, the hazard rates of post-TB mortality were higher among participants with HIV co-infection (aHR=3.74, 95%CI 1.77-7.91) compared to those without HIV co-infection. In our cohort, post-TB mortality occurred most commonly in the first three years post-TB treatment. Linkage to care for common TB comorbidities post-treatment may reduce post-TB mortality rates.