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Nevin Manimala Statistics

Shared genetics and causal relationships between migraine and thyroid function traits

Cephalalgia. 2023 Feb;43(2):3331024221139253. doi: 10.1177/03331024221139253.

ABSTRACT

BACKGROUND: Epidemiological studies have reported a comorbid relationship between migraine and thyroid dysfunction.

METHODS: We investigated the genetic relationship between migraine and thyroid function traits using genome-wide association study (GWAS) data.

RESULTS: We found a significant genetic correlation (rg) with migraine for hypothyroidism (rg = 0.0608), secondary hypothyroidism (rg = 0.195), free thyroxine (fT4) (rg = 0.0772), and hyperthyroidism (rg = -0.1046), but not thyroid stimulating hormone (TSH). Pairwise GWAS analysis revealed two shared loci with TSH and 11 shared loci with fT4. Cross-trait GWAS meta-analysis of migraine identified novel genome-wide significant loci: 17 with hypothyroidism, one with hyperthyroidism, five with secondary hypothyroidism, eight with TSH, and 15 with fT4. Of the genes at these loci, six (RERE, TGFB2, APLF, SLC9B1, SGTB, BTBD16; migraine + hypothyroidism), three (GADD45A, PFDN1, RSPH6A; migraine + TSH), and three (SSBP3, BRD3, TEF; migraine + fT4) were significant in our gene-based analysis (pFisher’s combined P-value < 2.04 × 10-6). In addition, causal analyses suggested a negative causal relationship between migraine and hyperthyroidism (p = 8.90 × 10-3) and a positive causal relationship between migraine and secondary hypothyroidism (p = 1.30 × 10-3).

CONCLUSION: These findings provide strong evidence for genetic correlation and suggest complex causal relationships between migraine and thyroid traits.

PMID:36739509 | DOI:10.1177/03331024221139253

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Nevin Manimala Statistics

Efficacy of bedside optic nerve sheath diameter measurement in differentiating provoked seizure from unprovoked seizure in the emergency department

Ann Saudi Med. 2023 Jan-Feb;43(1):42-49. doi: 10.5144/0256-4947.2023.42. Epub 2023 Feb 2.

ABSTRACT

BACKGROUND: Emergency departments (EDs) are typically the first medical contact for seizure patients, and early diagnosis and treatment is primarily the responsibility of emergency physicians.

OBJECTIVES: Demonstrate the efficacy of bedside ocular ultrasonography for optic nerve sheath diameter (ONSD) measurement in differentiating provoked seizure from unprovoked seizure in the ED.

DESIGN: Prospective observational study SETTINGS: Tertiary care hospital PATIENTS AND METHODS: Patients presenting to the ED with seizure were divided into two groups according to medical history, physical examination, laboratory results, cranial computed tomography findings and electroencephalography results. Patients with seizures that did not have a specific cause (unprovoked) were compared with patients who had seizures caused by underlying pathology (provoked). The measurement of the ONSD was taken at the bedside within 30 minutes of arrival. The study compared the ONSD values, age, sex, type of seizure, and Glasgow Coma Score between the two groups.

MAIN OUTCOME MEASURE: Efficacy of ONSD to distinguish between provoked and unprovoked seizures.

SAMPLE SIZE: 210 patients RESULTS: One hundred and fourteen (54.3%) patients were in the provoked seizure group and 96 (45.7%) were in the unprovoked seizure group. The ONSD measurements were significantly higher in the provoked seizure group compared with the unprovoked seizure group (median 6.1 mm vs. 5.2 mm, P<.001). The cut-off value of ONSD higher than 5.61 was significantly associated with the prediction of the provoked seizure (P<.001). The area under the curve value was 0.882 (95% CI: 0.830-0.922) with a sensitivity of 86.5 and specificity of 78.9%.

CONCLUSIONS: Bedside ONSD measurement by means of ocular ultrasound is an effective method for differentiating provoked seizure from unprovoked seizure.

LIMITATIONS: Statistical significance of age on ONSD and exclusion of pediatric patients.

CONFLICT OF INTEREST: None.

PMID:36739503 | DOI:10.5144/0256-4947.2023.42

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Nevin Manimala Statistics

The combined impact of hyponatremia and hematocrit on the risk for 90-day readmission and death in patients with heart failure: dilutional hyponatremia versus depletional hyponatremia

Ann Saudi Med. 2023 Jan-Feb;43(1):17-24. doi: 10.5144/0256-4947.2023.17. Epub 2023 Feb 2.

ABSTRACT

BACKGROUND: Hyponatremia is common in hospitalized patients with heart failure (HF) and predicts a poor prognosis after discharge. In general, hyponatremia can be divided into two types: dilutional or depletional.

OBJECTIVE: Assess the impact of hyponatremia type on short-term outcomes.

DESIGN: Retrospective cohort SETTINGS: Single center in China PATIENTS AND METHODS: We sorted patients by hyponatremia into two types: dilutional hyponatremia (DiH, with hematocrit <35%) and depletional hyponatremia (DeH, with hematocrit ≥35%). The Kaplan-Meier method and Cox regression analysis were used to identify the impact of hyponatremia types on the risk for 90-day readmission and death.

MAIN OUTCOME MEASURES: 90-day readmission and death combined.

SAMPLE SIZE: 1770 patients.

RESULTS: Hyponatremia was present in 324/1770 patients with 182 cases classified as DiH versus 142 as DeH. Kaplan-Meier analyses showed a higher incidence of poor short-term outcomes in hyponatremia compared with normonatremia (log-rank P<.001), and the risk was higher in DiH than DeH although the difference was not statistically significant (log-rank P=.656). Multivariate Cox regression analyses showed that only DiH was independently associated with short-term outcomes (HR=1.34, 95%CI: 1.02-1.77, P=.038), but not DeH (HR=1.32, 95%CI: 0.97-1.80, P=.081). Analysis of the secondary endpoints showed that DiH increased the risk of readmission but not death (HR=1.36, P=.035 for readmission; HR=1.13, P=.831 for all-cause death).

CONCLUSIONS: Low hematocrit, rather than high hematocrit, with hyponatremia was associated with a risk of 90-day readmission in patients with HF.

LIMITATIONS: Single center, nonrandomized.

CONFLICT OF INTEREST: None.

PMID:36739500 | DOI:10.5144/0256-4947.2023.17

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Nevin Manimala Statistics

Dependence of clinical outcomes on time of hospital admission in patients with ST-segment elevation myocardial infarction

Ann Saudi Med. 2023 Jan-Feb;43(1):25-34. doi: 10.5144/0256-4947.2023.25. Epub 2023 Feb 2.

ABSTRACT

BACKGROUND: There are conflicting results in studies investigating the effects of percutaneous coronary intervention (PCI) on the prognosis of patients with ST-segment elevation myocardial infarction (STEMI) during or outside of usual hospital working hours. While some researchers have reported higher mortality rates in STEMI patients admitted outside of working hours, others did not find a statistically significant difference.

OBJECTIVES: Investigate the short-term endpoints and long-term outcomes of STEMI patients by time of admission.

DESIGN: Retrospective SETTING: Tertiary percutaneous coronary intervention center.

PATIENTS AND METHODS: Patients were grouped by admission, which consisted of four intervals: 06:00 to <12:00, 12:00 to <18:00, 18:00 to <24:00, and 24:00 to <06:00. We analyzed demographic, clinical and mortality by admission time interval and mortality by multivariate analyses, including the time intervals.

MAIN OUTCOME MEASURES: Clinical data and mortality SAMPLE SIZE: 735 patients; median (IQR) age 62 (22) years; 215 (29.3%) women.

RESULTS: Patients admitted at night were 1.37 times more likely to experience pulmonary edema than patients whose symptoms started in the daytime (P=.012); 32.9% of the patients whose symptoms started at night presented with Killip class II-IV, while during the daytime, 21.4% presented with Killip class II-IV (P=.001). Among the patients, the most common was inferior STEMI (38.6%). However, no-reflow was significantly higher during the daytime compared to the nighttime (P=.12). The risk of the cardiac arrest on admission was 1.2 times higher in patients admitted at night (P=.034). Neither time interval of admission nor several other variables had an effect on clinical outcome or mortality.

CONCLUSIONS: While patients admitted at night presented with pulmonary edema and cardiogenic shock more frequently, no reflow was observed during the day after the procedure. Although patients admitted at night with STEMI presented with worse clinical conditions, similar results were observed between the groups in clinical outcomes.

LIMITATIONS: More “real world” results might have been obtained if the study had replicated more typical referral conditions for PCI.

CONFLICT OF INTEREST: None.

PMID:36739499 | DOI:10.5144/0256-4947.2023.25

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Nevin Manimala Statistics

The relationship between degree of coronary artery stenosis detected by coronary computed tomography angiography and ACEF risk score in patients with chronic coronary syndrome

Ann Saudi Med. 2023 Jan-Feb;43(1):35-41. doi: 10.5144/0256-4947.2023.35. Epub 2023 Feb 2.

ABSTRACT

BACKGROUND: The ACEF risk score (age, creatinine, and ejection fraction) has been associated with satisfactory predictive values not only for short-term and long-term mortality but also for major adverse cardiovascular events.

OBJECTIVES: Investigate the relationship between ACEF risk score and degree of coronary artery stenosis.

DESIGN: Retrospective, observational study.

SETTING: Tertiary percutaneous coronary intervention center.

PATIENTS AND METHODS: In patients with coronary coronary artery stenosis <70% were compared with patients with stenosis ≥70%. All were diagnosed with chronic coronary syndrome (CCS) and had undergone coronary computed tomography angiography (CTA). Receiver operating characteristic analysis was performed for the cut-off value of the ACEF risk score. Univariable and multivariable regression analyses were performed for significant parameters related to degree of coronary artery stenosis in coronary CTA.

MAIN OUTCOME MEASURES: Relationship between ACEF risk score and degree of coronary artery stenosis in coronary CTA.

SAMPLE SIZE: 148 patients.

RESULTS: In the multivariable regression analysis; left ventricular ejection fraction (OR: 0.94; 95%CI: 0.89-0.99, P=.015) and ACEF risk score (OR: 5.63; 95% CI: 1.62-19.57, P=.007) were independent predictors for degree of coronary artery stenosis. The ACEF risk score was statistically significantly higher in with patients with stenosis ≥70% (1.43 [0.59]) than in patients with stenosis <70% (0.98 [0.35]), P<.001). An ACEF risk score value >1.04 was a predictor of the presence of severe coronary artery stenosis detected by coronary CTA in patients with CCS, with 66% sensitivity and 69% specificity.

CONCLUSIONS: A high ACEF risk score (age, creatinine, ejection fraction) in patients with CCS is associated with the presence of severe coronary artery stenosis detected by coronary CTA, and was useful as an assessment tool for coronary angiography in patients with CCS.

LIMITATIONS: Since we do not have long-term follow-up results, we do not know the prognostic value of the ACEF risk score in the long-term follow-up of patients with CCS.

CONFLICT OF INTEREST: None.

PMID:36739497 | DOI:10.5144/0256-4947.2023.35

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Nevin Manimala Statistics

Carotid Intima-media Thickness in Hemodialysis Patients and Related Biochemical and Clinical Factors

Iran J Kidney Dis. 2023 Jan;1(1):28-36.

ABSTRACT

INTRODUCTION: Cardiovascular complications are the most frequent cause of death in chronic kidney disease that happens due to both general and uremic risk factors. Recently, the medical literature has declared the carotid artery intima-media thickness to be an indicator for predicting cardiovascular diseases.

METHODS: This paper is an attempt to introduce an analytical cross-sectional study of 128 hemodialysis patients. The researchers collected the data by reviewing medical records, interviewing the patients, chemical analysis of the patient’s serum and carotid artery Doppler ultrasound, and providing the relevant questionnaire. We performed descriptive statistics, bivariate correlation, and general linear model (GLM) analysis. And, the significance level of hypothesis tests was .05.

RESULTS: Seventy-three patients (57%) were male, and 55 (43%) were female. The mean and standard deviation of the age was 58.66 ± 15.54 years. Nearly 42% of patients affected by diabetes, 95.3% were hypertensive and 28.1% had a history of cardiovascular disease. In the bivariate analysis, age, serum albumin, serum magnesium, hypertension, and history of cardiovascular disease showed a statistically significant relationship with carotid intima-media thickness (CIMT). In GLM, we observed a statistically significant relationship between CIMT, age and magnesium.

CONCLUSION: Increased CIMT is observed in a considerable percentage of hemodialysis patients. Age and serum magnesium concentration demonstrate a statistically significant association with CIMT. We recommend more precise long-term longitudinal follow-up studies to investigate the relationship between biochemical risk factors and CIMT. Therefore, multivariate analysis is necessary to assess the simultaneous effects of independent variables and manage influences of confounding factors. We also recommend developing a practical guideline for periodic determination of CIMT in hemodialysis patients to implement convenient preventive or therapeutic measures. DOI: 10.52547/ijkd.7303.

PMID:36739488

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Nevin Manimala Statistics

Acute Kidney Injury in Pediatric Patients with COVID-19; Clinical Features and Outcome

Iran J Kidney Dis. 2023 Jan;1(1):20-27.

ABSTRACT

INTRODUCTION: Renal disorders have been reported as the underlying cause as well as complications of critical COVID-19 in pediatric patients. The purpose of this study was to investigate the pattern of kidney involvement, particularly acute kidney injury (AKI), among pediatric patients with COVID-19.

METHODS: In this prospective study, hospitalized pediatric patients with a clinical diagnosis of COVID-19 were enrolled. Demographic, clinical, and laboratory findings were collected and analyzed using a mixed method of qualitative and quantitative approaches and descriptive statistics.

RESULTS: One hundred and eighty-seven patients, including 120 (64.2%) males and 67 (35.8%) females with COVID-19 with a median age (interquartile range) of 60 (24 to 114) months were enrolled in this study. Most patients (n = 108, 58.1%) had one or two underlying comorbidities, mainly malnutrition (77.4%), neurologic/learning disorders (21.4%), and malignancy (10.2%). According to the Kidney Disease Improving Global Outcomes (KDIGO) classification, AKI was detected in 38.5% of patients (stage 1: 55.6%, stage 2: 36.1%, and stage 3: 8.3%) at presentation or during hospitalization. Nine patients (4.8%) required hemodialysis and 16 (8.6%) eventually died. There was no significant association between AKI and admission to the pediatric intensive care unit (PICU) (P > .05), a multisystem inflammatory syndrome in children (MIS-C) (P > .05), comorbidities (P > .05), and mortality rate (P > .05).

CONCLUSION: Kidneys are among the major organs affected by COVID-19. Although kidney abnormalities resolve in the majority of pediatric COVID-19 infections, particular attention should be paid to serum creatinine and electrolyte levels in patients affected by COVID-19, particularly children with a history of malnutrition and kidney disorders. DOI: 10.52547/ijkd.7151.

PMID:36739487

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Nevin Manimala Statistics

Vast heterogeneity in cytoplasmic diffusion rates revealed by nanorheology and Doppelgänger simulations

Biophys J. 2023 Feb 3:S0006-3495(23)00089-9. doi: 10.1016/j.bpj.2023.01.040. Online ahead of print.

ABSTRACT

The cytoplasm is a complex, crowded, actively-driven environment whose biophysical characteristics modulate critical cellular processes such as cytoskeletal dynamics, phase separation, and stem-cell fate. Little is known about the variance in these cytoplasmic properties. Here, we employed particle-tracking nanorheology on genetically encoded multimeric 40-nm nanoparticles (GEMs) to measure diffusion within the cytoplasm of the fission yeast Schizosaccharomyces pombe. We found that the apparent diffusion coefficients of individual GEM particles varied over a 400-fold range, while the differences in average particle diffusivity among individual cells spanned a 10-fold range. To determine the origin of this heterogeneity, we developed a Doppelgänger Simulation approach that uses stochastic simulations of GEM diffusion that replicate the experimental statistics on a particle-by-particle basis, such that each experimental track and cell had a one-to-one correspondence with their simulated counterpart. These simulations showed that the large intra- and inter-cellular variations in diffusivity could not be explained by experimental variability but could only be reproduced with stochastic models that assume a wide intra- and inter-cellular variation in cytoplasmic viscosity. The simulation combining intra- and inter-cellular variation in viscosity also predicted weak non-ergodicity in GEM diffusion, consistent with the experimental data. To probe the origin of this variation, we found that the variance in GEM diffusivity was largely independent of factors such as temperature, cytoskeletal effects, cell cycle stage and spatial locations, but was magnified by hyperosmotic shocks. Taken together, our results provide a striking demonstration that the cytoplasm is not “well-mixed” but represents a highly heterogeneous environment in which subcellular components at the 40-nm size- scale experience dramatically different effective viscosities within an individual cell, as well as in different cells in a genetically identical population. These findings carry significant implications for the origins and regulation of biological noise at cellular and subcellular levels.

PMID:36739478 | DOI:10.1016/j.bpj.2023.01.040

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Nevin Manimala Statistics

On multistability and constitutive relations of cell motion on Fibronectin lanes

Biophys J. 2023 Feb 3:S0006-3495(23)00093-0. doi: 10.1016/j.bpj.2023.02.001. Online ahead of print.

ABSTRACT

Cell motility on flat substrates exhibits coexisting steady and oscillatory morphodynamics, the biphasic adhesion-velocity relation, and the universal correlation between speed and persistence (UCSP) as simultaneous observations common to many cell types. Their universality and concurrency suggest a unifying mechanism causing all three of them. Stick-slip models for cells on 1dimensional lanes suggest multistability to arise from the non-linear friction of retrograde flow. This study suggests a mechanical mechanism controlled by integrin signalling on the basis of a biophysical model and analysis of trajectories of MDA-MB-231 cells on Fibronectin lanes which additionally explains the constitutive relations. The experiments exhibit cells with steady or oscillatory morphodynamics and either spread or moving with spontaneous transitions between the dynamic regimes, spread and moving and spontaneous direction reversals. Our biophysical model is based on the force balance at the protrusion edge, the noisy clutch of retrograde flow and a response function of friction and membrane drag to integrin signaling. The theory reproduces the experimentally observed cell states, characteristics of oscillations and state probabilities. Analysis of experiments with the biophysical model establishes a stick-slip oscillation mechanism, explains multistability of cell states and the statistics of state transitions. It suggests protrusion competition to cause direction reversal events, the statistics of which explain the UCSP. The effect of integrin signalling on drag and friction explains the adhesion-velocity relation and cell behavior at Fibronectin density steps. The dynamics of our mechanism are non-linear flow mechanics driven by F-actin polymerization and shaped by the noisy clutch of retrograde flow friction, protrusion competition via membrane tension and drag forces. Integrin signalling controls the parameters of the mechanical system.

PMID:36739476 | DOI:10.1016/j.bpj.2023.02.001

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Nevin Manimala Statistics

Database of daily Lagrangian Arctic sea ice parcel drift tracks with coincident ice and atmospheric conditions

Sci Data. 2023 Feb 4;10(1):73. doi: 10.1038/s41597-023-01987-6.

ABSTRACT

Since the early 2000s, sea ice has experienced an increased rate of decline in thickness, extent and age. This new regime, coined the ‘New Arctic’, is accompanied by a reshuffling of energy flows at the surface. Understanding of the magnitude and nature of this reshuffling and the feedbacks therein remains limited. A novel database is presented that combines satellite observations, model output, and reanalysis data with sea ice parcel drift tracks in a Lagrangian framework. This dataset consists of daily time series of sea ice parcel locations, sea ice and snow conditions, and atmospheric states, including remotely sensed surface energy budget terms. Additionally, flags indicate when sea ice parcels travel within cyclones, recording cyclone intensity and distance from the cyclone center. The quality of the ice parcel database was evaluated by comparison with sea ice mass balance buoys and correlations are high, which highlights the reliability of this database in capturing the seasonal changes and evolution of sea ice. This database has multiple applications for the scientific community; it can be used to study the processes that influence individual sea ice parcel time series, or to explore generalized summary statistics and trends across the Arctic.

PMID:36739456 | DOI:10.1038/s41597-023-01987-6