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WMJ : Official Publication of the State... Jun 2018Relative bradycardia is a poorly understood paradoxical phenomenon that refers to a clinical sign whereby the pulse rate is lower than expected for a given body... (Review)
Review
INTRODUCTION
Relative bradycardia is a poorly understood paradoxical phenomenon that refers to a clinical sign whereby the pulse rate is lower than expected for a given body temperature.
OBJECTIVE
To provide an overview and describe infectious and noninfectious causes of relative bradycardia.
METHODS
PubMed and Medline databases were searched using individual and Medical Subject Headings terms including relative bradycardia, fever, pulse-temperature dissociation and pulsetemperature deficit in human studies published from inception to October 2, 2016. The causes and incidence of relative bradycardia were reviewed.
RESULTS
Relative bradycardia is found in a wide variety of infectious and noninfectious diseases. The pathogenesis remains poorly understood with proposed mechanisms including release of inflammatory cytokines, increased vagal tone, direct pathogenic effect on the myocardium, and electrolyte abnormalities. The incidence of this sign varies widely, which may be attributable to multiple factors, including population size, time course for measuring pulse and temperature, and lack of a consistent definition used. The fact that this sign is not consistently identified in case series suggests that relative bradycardia is caused by mechanisms presumably involving or influenced by pathogen and host factors.
CONCLUSIONS
Relative bradycardia is a sensitive but nonspecific clinical sign that may be an important bedside tool for narrowing the differential diagnosis of potential infectious and noninfectious etiologies. Recognizing this relationship may assist the clinician by providing bedside clinical clues into potential etiologies of disease, particularly in the setting of infectious diseases and in circumstances when other stigma of disease is absent.
Topics: Bradycardia; Diagnosis, Differential; Humans; Incidence; Risk Factors
PubMed: 30048576
DOI: No ID Found -
Annals of Clinical and Translational... Aug 2023The efficacy of perampanel (PER) in pediatric epilepsy with specific etiologies has not been well established. Here, we investigated outcome and predictors of PER...
OBJECTIVE
The efficacy of perampanel (PER) in pediatric epilepsy with specific etiologies has not been well established. Here, we investigated outcome and predictors of PER treatment in a pediatric cohort with known and presumed genetic etiology.
METHODS
We included pediatric patients with potential genetic epilepsy who received PER treatment and underwent whole-exome sequencing (WES) from January 2020 to September 2021. All patients were followed up for >12 months.
RESULTS
A total of 124 patients were included. Overall response rates were 51.6% and 49.6% at 6 months and 12 months, respectively. Pathogenic or likely pathogenic variants in 27 multiple genes were detected among 58 patients (46.8%) by WES. On performing multivariate logistic regression analysis, only developmental delay (OR = 0.406, P = 0.042) was a negative predictor of treatment response. However, the seizure onset age, positive WES results, and number of ASMs before PER administration were not significantly. Thirteen carriers with variants in the SCN1A gene showed a better response compared to eight patients with other sodium channels (P = 0.007), and to the other 45 patients with positive WES results (OR = 7.124, 95% CI = 1.306-38.860, P = 0.023). Adverse events were only reported in 23 patients, the most common being emotional problems.
INTERPRETATION
PER is safe and efficacious in pediatric patients with known and presumed genetic etiology. The response rate is comparable to that reported in other pediatric populations, and lower among those with developmental delay. A gene-specific response to PER is found along with better efficacy links to pathogenic variants in the SCN1A gene.
Topics: Humans; Child; Epilepsy; Seizures; Pyridones; Causality
PubMed: 37329172
DOI: 10.1002/acn3.51828 -
Clinical Interventions in Aging 2023Perivascular spaces are the fluid-filled areas surrounding small blood vessels in the brain, and they may play a role similar to lymphatic vessels in clearing metabolic... (Review)
Review
Perivascular spaces are the fluid-filled areas surrounding small blood vessels in the brain, and they may play a role similar to lymphatic vessels in clearing metabolic waste. When their diameters exceed 1 mm, as measured by structural magnetic resonance imaging, they are classified as enlarged perivascular spaces (EPVS). Previously, EPVS were considered to be benign, but increasing evidence suggests that their existence may be associated with various clinical diseases. Here, we review recent clinical studies to understand the potential clinical implications of EPVS. We also review the anatomy and imaging characteristics of EPVS and discuss four causal hypotheses for their formation and associated risk factors. Due to differences in research methods and concerns across studies, unified conclusions are difficult to achieve. Overall, more basic high-quality research is needed to clarify the subject and provide more concrete theoretical support.
Topics: Humans; Magnetic Resonance Imaging; Brain; Risk Factors; Causality
PubMed: 37274869
DOI: 10.2147/CIA.S404908 -
International Journal of Environmental... Feb 2024Autism Spectrum Disorder (ASD) belongs to the group of neurodevelopmental disorders, and has a high prevalence, affecting 1 in 100 children according to data from the... (Review)
Review
Autism Spectrum Disorder (ASD) belongs to the group of neurodevelopmental disorders, and has a high prevalence, affecting 1 in 100 children according to data from the World Health Organization (WHO). To be diagnosed with ASD, the child must have persistent deficits in communication and social interactions, and restricted and repetitive patterns of behavior, interests, or activities. Despite its prevalence, the etiology of ASD is still uncertain, with multifactorial characteristics, including those associated with the gestational period, where maternal exposure to biological, chemical, or physical hazards occurs, some of which have already been proposed as causes of ASD outcomes. Since pregnancy requires a balance between the maternal-fetal binomial, the breakdown of this balance caused by such environmental hazards can lead to altered fetal neurodevelopment, including ASD. With this firmly in mind, this review aims to compile the most recent data on the gestational causes that may be associated with the development of ASD to help health professionals identify risk factors and act for the prevention and management of ASD.
Topics: Child; Pregnancy; Female; Humans; Autism Spectrum Disorder; Risk Factors; Maternal Exposure; Causality; Neurodevelopmental Disorders
PubMed: 38541246
DOI: 10.3390/ijerph21030244 -
Cold Spring Harbor Perspectives in... Aug 2021Much research effort is invested in attempting to determine causal influences on disease onset and progression to inform prevention and treatment efforts. However, this... (Review)
Review
Much research effort is invested in attempting to determine causal influences on disease onset and progression to inform prevention and treatment efforts. However, this is often dependent on observational data that are prone to well-known limitations, particularly residual confounding and reverse causality. Several statistical methods have been developed to support stronger causal inference. However, a complementary approach is to use design-based methods for causal inference, which acknowledge sources of bias and attempt to mitigate these through the design of the study rather than solely through statistical adjustment. Genetically informed methods provide a novel and potentially powerful extension to this approach, accounting by design for unobserved genetic and environmental confounding. No single approach will be absent from bias. Instead, we should seek and combine evidence from multiple methodologies that each bring different (and ideally uncorrelated) sources of bias. If the results of these different methodologies align-or triangulate-then we can be more confident in our causal inference. To be truly effective, this should ideally be done prospectively, with the sources of evidence specified in advance, to protect against one final source of bias-our own cognitions, expectations, and fondly held beliefs.
Topics: Causality; Disease; Genetics; Research Design
PubMed: 33355252
DOI: 10.1101/cshperspect.a040659 -
Frontiers in Endocrinology 2022Previous observational studies have revealed the association between serum uric acid and 25-hydroxyvitamin D. However, the causality and the direction of the...
BACKGROUND
Previous observational studies have revealed the association between serum uric acid and 25-hydroxyvitamin D. However, the causality and the direction of the associations remain unknown. Thus, we performed a two-sample bidirectional Mendelian Randomization (MR) analysis to investigate the causal association between uric acid and 25-hydroxyvitamin D and to determine the direction of the association.
METHOD
Based on the summary-level GWAS data from large genome-wide association studies, several steps were taken in our analysis to select eligible single-nucleotide polymorphisms (SNPs), which were strongly related to exposure as the instrumental variables. We used different analytical methods, such as inverse-variance weighting (IVW) method, weighted median, MR-Egger regression, and weighted mode method, to make our result more robust and reliable. The IVW method was used as the primary analysis. The Cochran's Q test, MR-Egger intercept test, MR-PRESSO method, and "leave-one-out" sensitivity analysis was performed to evaluate the heterogeneities, horizontal pleiotropy, and robustness of the results. MR analyses were also conducted using genetic risk scores (GRS) as instrumental variables in both directions by using the same summary-level GWAS data.
RESULTS
Our two-sample MR analysis suggested a causal association of genetically predicted uric acid on 25-hydroxyvitamin D [IVW method: β(SE), -0.0352(0.0149); = 0.0178], which suggested that a per mg/dl increase in uric acid was associated with a decrease of 0.74 nmol/L of 25-hydroxyvitamin D, and the above results remained stable in the sensitivity analysis. By contrast, four MR methods suggested no causal relationship of 25-hydroxyvitamin D on serum uric acid [IVW β(SE), 0.0139 (0.0635); = 0.826; MR-Egger β(SE), 0.0671 (0.108); = 0.537; weighted median β(SE), 0.0933 (0.0495); = 0.0598; weighted mode β(SE), 0.0562 (0.0463); = 0.228, respectively]. After excluding the SNPs, which were associated with confounding factors and outlier SNPs, the IVW method suggested that there was still no causal association of 25-hydroxyvitamin D on serum uric acid. The GRS approach showed similar results.
CONCLUSIONS
Serum uric acid may causally affect the 25-hydroxyvitamin D levels, whereas the causal role of 25-hydroxyvitamin D on uric acid was not supported in our MR analysis. Our findings suggest that increased levels of uric acid should prompt investigation for vitamin D deficiency.
Topics: Calcifediol; Genome-Wide Association Study; Risk Factors; Uric Acid; Vitamin D; Mendelian Randomization Analysis; Causality
PubMed: 36583002
DOI: 10.3389/fendo.2022.1024675 -
Osteoarthritis and Cartilage Nov 2022
Topics: Causality; Observational Studies as Topic
PubMed: 36063988
DOI: 10.1016/j.joca.2022.08.010 -
Prediction or causality? A scoping review of their conflation within current observational research.European Journal of Epidemiology Sep 2021Etiological research aims to uncover causal effects, whilst prediction research aims to forecast an outcome with the best accuracy. Causal and prediction research... (Review)
Review
Etiological research aims to uncover causal effects, whilst prediction research aims to forecast an outcome with the best accuracy. Causal and prediction research usually require different methods, and yet their findings may get conflated when reported and interpreted. The aim of the current study is to quantify the frequency of conflation between etiological and prediction research, to discuss common underlying mistakes and provide recommendations on how to avoid these. Observational cohort studies published in January 2018 in the top-ranked journals of six distinct medical fields (Cardiology, Clinical Epidemiology, Clinical Neurology, General and Internal Medicine, Nephrology and Surgery) were included for the current scoping review. Data on conflation was extracted through signaling questions. In total, 180 studies were included. Overall, 26% (n = 46) contained conflation between etiology and prediction. The frequency of conflation varied across medical field and journal impact factor. From the causal studies 22% was conflated, mainly due to the selection of covariates based on their ability to predict without taking the causal structure into account. Within prediction studies 38% was conflated, the most frequent reason was a causal interpretation of covariates included in a prediction model. Conflation of etiology and prediction is a common methodological error in observational medical research and more frequent in prediction studies. As this may lead to biased estimations and erroneous conclusions, researchers must be careful when designing, interpreting and disseminating their research to ensure this conflation is avoided.
Topics: Biomedical Research; Causality; Epidemiologic Studies; Forecasting; Humans; Research Design
PubMed: 34392488
DOI: 10.1007/s10654-021-00794-w -
PloS One 2023Observational studies suggest physical activity (PA) enhances intelligence, while sedentary behavior (SB) poses a risk. However, causality remains unclear.
BACKGROUND
Observational studies suggest physical activity (PA) enhances intelligence, while sedentary behavior (SB) poses a risk. However, causality remains unclear.
METHODS
We extracted genetic instruments from large genome-wide association studies summary data and employed an inverse-variance weighted (IVW) approach within a random-effects model as the primary method of Mendelian randomization (MR) analysis to estimate the overall effect of various physical activity statuses on intelligence. To assess IVW stability and MR sensitivity, we also utilized supplementary methods including weighted median, MR-Egger, and MR-PRESSO. Furthermore, multivariable MR analysis was conducted to examine the independent effects of each physical activity trait on intelligence.
RESULTS
The MR primary results indicated that LST was negatively associated with intelligence (β = -0.133, 95%CI: -0.177 to -0.090, p = 1.34×10-9), while SBW (β = 0.261, 95% CI: 0.059 to 0.463, p = 0.011) may have a positive effect on intelligence; however, MVPA and SC did not show significant effects on intelligence. Inverse causality analyses demonstrated intelligence significantly influenced all physical activity states.
CONCLUSIONS
Our study highlights a bidirectional causal relationship between physical activity states and intelligence.
Topics: Genome-Wide Association Study; Mendelian Randomization Analysis; Causality; Exercise; Intelligence
PubMed: 37527259
DOI: 10.1371/journal.pone.0289252 -
Frontiers in Endocrinology 2022
Topics: Addison Disease; Adrenal Insufficiency; Causality; Humans
PubMed: 36105391
DOI: 10.3389/fendo.2022.995151