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1.
Circ Heart Fail ; 17(3): e010896, 2024 03.
Article En | MEDLINE | ID: mdl-38426319

BACKGROUND: Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults. METHODS: Untargeted metabolomic profiling was performed in Black and White adults from the ARIC study (Atherosclerosis Risk in Communities) visit 5 (n=3719; mean age, 75 years). We applied Cox regressions to identify metabolites associated with incident HF and its subtypes. The metabolite risk score (MRS) was constructed and examined for associations with HF, echocardiographic measures, and HF risk prediction. Independent samples from visit 3 (n=1929; mean age, 58 years) were used for replication. RESULTS: Sixty metabolites (hazard ratios range, 0.79-1.49; false discovery rate, <0.05) were associated with incident HF after adjusting for clinical risk factors, eGFR, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Mannonate, a hydroxy acid, was replicated (hazard ratio, 1.36 [95% CI, 1.19-1.56]) with full adjustments. MRS was associated with an 80% increased risk of HF per SD increment, and the highest MRS quartile had 8.7× the risk of developing HFpEF than the lowest quartile. High MRS was also associated with unfavorable values of cardiac structure and function. Adding MRS over clinical risk factors and NT-proBNP improved 5-year HF risk prediction C statistics from 0.817 to 0.850 (∆C, 0.033 [95% CI, 0.017-0.047]). The association between MRS and incident HF was replicated after accounting for clinical risk factors (P<0.05). CONCLUSIONS: Novel metabolites associated with HF risk were identified, elucidating disease pathways, specifically HFpEF. An MRS was associated with HF risk and improved 5-year risk prediction in older adults, which may assist at at-risk population identification.


Heart Failure , Humans , Aged , Middle Aged , Heart Failure/diagnosis , Heart Failure/epidemiology , Heart Failure/etiology , Stroke Volume , Prospective Studies , Biomarkers , Risk Factors , Peptide Fragments , Natriuretic Peptide, Brain , Prognosis
2.
Nat Commun ; 15(1): 528, 2024 Jan 15.
Article En | MEDLINE | ID: mdl-38225249

Heart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with diverse age, geography, and HF ascertainment to identify circulating proteins and protein networks associated with HF development. Parallel analyses in Atherosclerosis Risk in Communities study participants in mid-life and late-life and in Trøndelag Health Study participants identified 37 proteins consistently associated with incident HF independent of traditional risk factors. Mendelian randomization supported causal effects of 10 on HF, HF risk factors, or left ventricular size and function, including matricellular (e.g. SPON1, MFAP4), senescence-associated (FSTL3, IGFBP7), and inflammatory (SVEP1, CCL15, ITIH3) proteins. Protein co-regulation network analyses identified 5 modules associated with HF risk, two of which were influenced by genetic variants that implicated trans hotspots within the VTN and CFH genes.


Atherosclerosis , Heart Failure , Humans , Proteomics , Risk Factors , Phenotype , Carrier Proteins/genetics , Glycoproteins/genetics , Extracellular Matrix Proteins/genetics
3.
Appl Radiat Isot ; 205: 111175, 2024 Mar.
Article En | MEDLINE | ID: mdl-38194888

An intercomparison of neutron personal dose equivalent measured by the Harshaw thermoluminescence neutron dosimeters (TLDs) between the National Institute of Metrology of China (NIM) and the Institute for Nuclear Science and Technology of Vietnam (INST) was performed. Three sets of TLDs (each set consisting of five TLDs) were prepared for each laboratory. Each set was then irradiated to the corresponding same nominal standard value of neutron personal dose equivalent, Hp(10)n-stdi, of 1.0, 2.0, and 3.0 mSv, respectively at these two laboratories. The irradiated TLDs were then read-out at the INST using the Harshaw 4500-type TLD reader to obtain neutron personal dose equivalents at the NIM, Hp(10)n-NIMi and at the INST, Hp(10)n-INSTi, which are corresponding to different values of Hp(10)n-stdi. The TLDs' responses to different scattered components of neutrons in these two fields are also discussed. Comparisons between the corresponding pair values of Hp(10)n-NIMi and Hp(10)n-INSTi show good agreements within 10% with the standard uncertainty of 12.5% (k = 1). The measured values of Hp(10)n-NIMi and Hp(10)n-INSTi are satisfied the Trumpet curve criteria. This implies that the TLDs can be used for safety assessment of occupational neutron personal dose equivalents. This intercomparison result also confirms the capabilities of these two laboratories (i.e., NIM, INST) on deliveries of neutron personal dose equivalent standard values for calibrations.

4.
J Prof Nurs ; 48: 93-98, 2023.
Article En | MEDLINE | ID: mdl-37775247

Although the undermining of the nursing profession, time constraints, and the lack of inclusive teaching of evidence-based nursing (EBN) in the nursing school's curriculum have long been identified as being some of the main barriers to the adoption of evidence-based practice (EBP) by nurses, the specific role of nurse leaders in directly influencing and supporting evidence-based nursing is not well demonstrated. This opinion piece discusses potential factors that influence the implementation of EBP into clinical routine practice, as well as how nursing leadership styles can contribute to its promotion in contemporary healthcare settings.


Evidence-Based Nursing , Leadership , Humans , Evidence-Based Practice , Curriculum
5.
Front Immunol ; 14: 1209315, 2023.
Article En | MEDLINE | ID: mdl-37529038

Introduction: With increased diagnostic capabilities and treatment modalities in the field of primary immunodeficiencies (PID), many pediatric patients survive beyond childhood and experience a change of care to the adult-oriented healthcare system. Unfortunately, the transition pathways for PID are less clearly defined, resulting in deterioration of quality of care in adulthood. Hence, this is the first regional study to address PID clinicians' opinions on practices and challenges of transition care in 7 Southeast Asia (SEA) countries. Methods: We adopted a cross-sectional study design through an online survey platform to enquire opinions of transition practices from expert representatives in 7 SEA countries. Results: Regionally, 3 out 7 countries reported having no practice of transition care. Among cited challenges were reluctant adaptation by patients and caregivers to unfamiliarized adult healthcare systems, inadequate ratio of adult immunologists to patients and lack of facilities for transfer. Discussion and conclusion: Our study provides evidence to advocate policy makers on the importance of standardized integration of transition practice towards betterment of transiting PID patients into adulthood.


Primary Immunodeficiency Diseases , Adult , Child , Humans , Asia, Southeastern/epidemiology , Cross-Sectional Studies , Primary Immunodeficiency Diseases/diagnosis , Primary Immunodeficiency Diseases/epidemiology , Primary Immunodeficiency Diseases/therapy , Surveys and Questionnaires , Transition to Adult Care
6.
Front Immunol ; 14: 1134852, 2023.
Article En | MEDLINE | ID: mdl-37153592

Background: Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI) disorder that results from defects in the respiratory burst activity in phagocytes, leading to the inability to kill bacterial and fungal microorganisms. CGD patients usually have a high incidence of morbidity such as infections and autoinflammatory diseases and a high mortality rate. Allogeneic bone marrow transplantation (BMT) is the only definitive cure for patients who suffer from CGD. Case presentation: We report the first transplant case of chronic granulomatous disease in Vietnam. A 25-month-old boy with X-linked CGD underwent bone marrow transplantation from his 5-year-old, full-matched human leukocyte antigen (HLA)-carrier sibling after myeloablative conditioning regimen with busulfan 5.1 mg/kg/day for 4 days, fludarabine 30 mg/m2/day for 5 days, and rATG (Grafalon-Fresenius) 10 mg/kg/day for 4 days. Neutrophil was engrafted on day 13 posttransplant, donor chimerism was 100% on day 30 with the dihydrorhodamine-1,2,3 (DHR 123) flow cytometric assay test that reached 38% of the normal 45 days posttransplant. Five months after transplant, the patient was free of infection with stable DHR 123 assay at 37%, and donor chimerism remained 100%. No sign of a graft-versus-host disease had been observed posttransplant. Conclusion: We suggest that bone marrow transplantation is a safe and effectual cure for CGD patients, especially for patients with HLA-identical siblings.


Granulomatous Disease, Chronic , Hematopoietic Stem Cell Transplantation , Male , Humans , Child, Preschool , Bone Marrow Transplantation , Granulomatous Disease, Chronic/therapy , Vietnam , Southeast Asian People , Hematopoietic Stem Cell Transplantation/methods
7.
Clin Exp Med ; 23(1): 157-161, 2023 Feb.
Article En | MEDLINE | ID: mdl-34842998

The X-linked hyper IgM syndrome is a primary immunodeficiency disorder (PID) due to mutations in the CD40LG gene. Hyper IgM syndrome is characterized by the absence or decreased levels of IgG and IgA and normal or elevated IgM levels in serum. Affected patients become susceptible to infections such as pneumonia, diarrhea, and skin ulcer types. Hematopoietic stem cell transplantation is the only treatment currently available and ideally performed before the age of 10 years. Early, accurate diagnosis will contribute to the effective treatment for patients with hyper IgM. The patients from different Vietnamese families who have been diagnosed with hyper IgM at The Allergy, Immunology and Rheumatology Department, Vietnam National Hospital Pediatrics, were performed a genetic analysis using whole exome sequencing. The mutations were confirmed by the Sanger sequencing method in patients and their families. The influence of the mutations was predicted with the in silico analysis tools: PROVEAN, SIFT, PolyPhen-2, and MutationTaster. In this study, two novel mutations (p.Thr254fs and p.Leu138Phe) in the CD40LG gene were found in Vietnamese patients with X-linked hyper IgM syndrome. Our results contribute to the general understanding of the etiology of the disease and can help diagnose the different forms of PID.


Hyper-IgM Immunodeficiency Syndrome, Type 1 , Child , Humans , Hyper-IgM Immunodeficiency Syndrome, Type 1/diagnosis , Hyper-IgM Immunodeficiency Syndrome, Type 1/genetics , Hyper-IgM Immunodeficiency Syndrome, Type 1/therapy , Southeast Asian People , Vietnam , CD40 Ligand/genetics , Mutation , Immunoglobulin M
8.
Pulm Ther ; 9(1): 127-137, 2023 Mar.
Article En | MEDLINE | ID: mdl-36459327

INTRODUCTION: Inhaled corticosteroid (ICS) is the most widely used and effective treatment of asthma. However, some patients do not respond to ICS, which might be due to various genetic factors. Hence, understanding the genetic factors involved in the ICS response could help physicians to individualize their treatment decision and action plans for given patients. This study aimed to analyze the characteristics of corticotropin-releasing hormone receptor 1 (CRHR1) genotypes in children with asthma and the correlation between rs242941 polymorphism of CRHR1 gene and ICS responsiveness. METHODS: This prospective study included children with uncontrolled asthma, assessing their eosinophil count, IgE concentration, lung function, and fractional concentration of nitric oxide in exhaled breath (FENO) and performing CRHR1 polymorphism sequencing. The level of asthma control was assessed by asthma control test (ACT); the responsiveness of asthma treatment with ICS was evaluated by measuring the change of ACT and forced expiratory volume in 1 s (FEV1) after treatment versus at inclusion. RESULTS: In total, 107 patients were analyzed for CRHR1 at rs242941. Among these, 86 (80.3%) had homozygous wild-type GG, 20 (18.7%) had heterozygous GT genotypes, and 1 (1.0%) had a homozygous variant for TT. Children with personal and family history of atopy were more likely to have GT and TT genotypes. The severity of asthma was similar between children with asthma in the three groups of GG, GT, and TT genotypes of CRHR1 at rs242941. FENO level, total IgE concentration, and eosinophilic count in children with asthma were not significantly different between GG and GT genotypes. The patient with a TT homozygous variant genotype had a higher level of FENO. There was no correlation between CRHR1 polymorphism at rs242941 and asthma control evaluated by asthma control test and lung function parameters. CONCLUSION: TT genotype of rs242941 in the CRHR1 gene is not frequent. Clinical and functional characteristics of children with asthma with rs242941 polymorphism of CRHR1 gene remain homogeneously similar. There is no correlation between rs242941 polymorphism and ACT or FEV1.

9.
Nat Commun ; 13(1): 5350, 2022 09 12.
Article En | MEDLINE | ID: mdl-36097025

Age-related changes to the genome-wide DNA methylation (DNAm) pattern observed in blood are well-documented. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the age-related acquisition and expansion of leukemogenic mutations in hematopoietic stem cells (HSCs), is associated with blood cancer and coronary artery disease (CAD). Epigenetic regulators DNMT3A and TET2 are the two most frequently mutated CHIP genes. Here, we present results from an epigenome-wide association study for CHIP in 582 Cardiovascular Health Study (CHS) participants, with replication in 2655 Atherosclerosis Risk in Communities (ARIC) Study participants. We show that DNMT3A and TET2 CHIP have distinct and directionally opposing genome-wide DNAm association patterns consistent with their regulatory roles, albeit both promoting self-renewal of HSCs. Mendelian randomization analyses indicate that a subset of DNAm alterations associated with these two leading CHIP genes may promote the risk for CAD.


Clonal Hematopoiesis , Coronary Artery Disease , Clonal Hematopoiesis/genetics , Coronary Artery Disease/genetics , DNA Methylation/genetics , Hematopoiesis/genetics , Hematopoietic Stem Cells , Humans
10.
Front Pediatr ; 10: 834037, 2022.
Article En | MEDLINE | ID: mdl-35498784

Background: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare and life-threatening disease of the skin and mucosal surfaces. Although gastrointestinal manifestations in adults are potential prognostic factors for disease severity, there are limited data on such cases and their standard management in the pediatric population. Case Presentation: We herein report the case of an 8-year-old girl with a 1-year history of epilepsy, who presented with bilateral conjunctivitis and progressively widespread bullous, and pruritic eruption based on erythematous skin after administration of carbamazepine. A diagnosis of carbamazepine-induced TEN was made, and the drug was immediately discontinued. The result of genetic screening showed that the patient was positive for the HLA-B*15:02 allele. Then, her condition got worse by developing gastrointestinal involvement, including hematemesis and severe watery bloody diarrhea. A combination of the intravenous immunoglobulin and the appropriate dose of systemic steroids have contributed to a favorable outcome in this case. Multidisciplinary care of mucocutaneous involvement, supplemental nutrition, and fluid replacement was also critically warranted. This report aims to contribute to the current literature on TEN-related gastrointestinal manifestations in pediatrics and highlights the need for further investigations in determining the optimal treatment in such cases. Conclusion: In conclusion, we reported the successful treatment of TEN-related gastrointestinal manifestations in a pediatric patient, which should be critically considered in patients with SJS/TEN. Since it may significantly contribute to the poor prognosis of the illness, further investigations in determining standard management in such cases are necessary.

11.
Resour Policy ; 77: 102721, 2022 Aug.
Article En | MEDLINE | ID: mdl-35431399

COVID-19 pandemic caused havoc around the globe in both economic and non-economic sectors. This paper, unlike previous studies, evaluates the role of COVID-19 on the volatility in natural resources. The volatility of natural resources commodity prices has been the center of discussion, especially during the pandemic. Unlike previous studies, this study aims to evaluate the role of the pandemic, i.e., Covid-19 and its possible impact on volatility in natural resources commodity prices for China. China has been the center of this epidemic disease and is considered one of the major economies affected by the Covid-19; therefore, it is better to conduct this study for China. This study uses data from January 2020 till September 2021 to capture the peak time of Covid-19. Moreover, this study employs the novel wavelet power spectrum and wavelet coherence approach to better capture volatility within commodity prices volatility and Covid-19 and evaluate the association between both variables. The empirical results reveal that only natural resources commodity prices are volatile and only short. While Covid-19 positive cases and Covid-19 deaths are not vulnerable during the study period. Moreover, the wavelet coherence conforms that both Covid-19 positive cases and Covid-19 deaths significantly cause volatility in natural resources commodity prices. Although, volatility is found at different periods; still, volatility is observed only in the short-run. The study also provides relevant policy implications to ensure a relevant and timely solution for the existing issue. Moreover, future research guidelines and the study's limitations are also provided.

12.
JCI Insight ; 7(10)2022 05 23.
Article En | MEDLINE | ID: mdl-35446786

Uromodulin (UMOD) is a major risk gene for monogenic and complex forms of kidney disease. The encoded kidney-specific protein uromodulin is highly abundant in urine and related to chronic kidney disease, hypertension, and pathogen defense. To gain insights into potential systemic roles, we performed genome-wide screens of circulating uromodulin using complementary antibody-based and aptamer-based assays. We detected 3 and 10 distinct significant loci, respectively. Integration of antibody-based results at the UMOD locus with functional genomics data (RNA-Seq, ATAC-Seq, Hi-C) of primary human kidney tissue highlighted an upstream variant with differential accessibility and transcription in uromodulin-synthesizing kidney cells as underlying the observed cis effect. Shared association patterns with complex traits, including chronic kidney disease and blood pressure, placed the PRKAG2 locus in the same pathway as UMOD. Experimental validation of the third antibody-based locus, B4GALNT2, showed that the p.Cys466Arg variant of the encoded N-acetylgalactosaminyltransferase had a loss-of-function effect leading to higher serum uromodulin levels. Aptamer-based results pointed to enzymes writing glycan marks present on uromodulin and to their receptors in the circulation, suggesting that this assay permits investigating uromodulin's complex glycosylation rather than its quantitative levels. Overall, our study provides insights into circulating uromodulin and its emerging functions.


Hypertension , Renal Insufficiency, Chronic , Blood Pressure , Genome-Wide Association Study , Humans , Hypertension/genetics , Renal Insufficiency, Chronic/genetics , Uromodulin/genetics
13.
Gut ; 71(6): 1095-1105, 2022 06.
Article En | MEDLINE | ID: mdl-34127525

OBJECTIVE: Tryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota. METHOD: We analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites. RESULTS: Tryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with T2D risk. We identified multiple host genetic variants, dietary factors, gut bacteria and their potential interplay associated with these T2D-relaetd metabolites. Intakes of fibre-rich foods, but not protein/tryptophan-rich foods, were the dietary factors most strongly associated with tryptophan metabolites. The fibre-indolepropionate association was partially explained by indolepropionate-associated gut bacteria, mostly fibre-using Firmicutes. We identified a novel association between a host functional LCT variant (determining lactase persistence) and serum indolepropionate, which might be related to a host gene-diet interaction on gut Bifidobacterium, a probiotic bacterium significantly associated with indolepropionate independent of other fibre-related bacteria. Higher milk intake was associated with higher levels of gut Bifidobacterium and serum indolepropionate only among genetically lactase non-persistent individuals. CONCLUSION: Higher milk intake among lactase non-persistent individuals, and higher fibre intake were associated with a favourable profile of circulating tryptophan metabolites for T2D, potentially through the host-microbial cross-talk shifting tryptophan metabolism toward gut microbial indolepropionate production.


Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Bacteria/genetics , Bacteria/metabolism , Cohort Studies , Diabetes Mellitus, Type 2/genetics , Diet , Gastrointestinal Microbiome/genetics , Humans , Kynurenine/metabolism , Lactase/metabolism , Tryptophan/metabolism
14.
Front Neurol ; 13: 1065038, 2022.
Article En | MEDLINE | ID: mdl-36686503

Background: Obstructive sleep apnea (OSA) is the most common form of respiratory disorders during sleep in children, especially those with severe asthma. However, optimal treatment of asthma might significantly improve OSA severity. Methods: It was a cohort study including children aged >5 years old and diagnosed with asthma according to GINA (Global Initiative for Asthma). The data related to age, gender, height, weight, body mass index (BMI), clinical symptoms and medical history of asthma, spirometry (FEV1: forced expiratory in 1 s), and exhaled nitric oxide (FENO) were recorded for analysis. Respiratory polygraphy (RPG) was done for each study subject to diagnose OSA and its severity. Results: Among 139 asthmatic children, 99 patients with OSA (71.2%) were included in the present study (9.3 ± 0.2 years): 58.6% with uncontrolled asthma and 32.3% with partial controlled asthma. The mean ACT (asthma control testing) score was 19.0 ± 3.4. The most frequent night-time symptoms were restless sleep (76.8%), snoring (61.6%), sweating (52.5%), and trouble breathing during sleep (48.5%). The common daytime symptoms were irritable status (46.5%) and abnormal behavior (30.3%). The mean AHI (apnea-hypopnea index) was 3.5 ± 4.0 events/h. There was a significant correlation between BMI and snoring index (R = 0.189 and P = 0.027), bronchial and nasal FENO with AHI (R = 0.046 and P < 0.001; R = 0.037 and P < 0.001; respectively). There was no significant correlation between asthma level, FEV1 and AHI. The severity of asthma and respiratory function were improved significantly after 3 months and 6 months of asthma treatment in combination with leukotriene receptor antagonist (LRA) treatment. The symptoms related to OSA were significantly improved after treatment with LRA. The severity of OSA was decreased significantly after 3 months and 6 months of treatment. Conclusion: The treatment of asthmatic children with comorbid OSA by LRA in combination with standard therapy for asthma could improve the control of asthma and the symptoms and severity of OSA.

15.
Front Neurol ; 13: 1097202, 2022.
Article En | MEDLINE | ID: mdl-36698884

Background: Asthma and obstructive sleep apnea (OSA) are common chronic respiratory disorders in children. The relationship between asthma and OSA is bidirectional; these conditions share multiple epidemiological risk factors. Untreated OSA may cause attention deficit hyperactivity disorder (ADHD) symptoms. This study aimed to assess the prevalence of ADHD in asthmatic children with OSA and the link between asthma control and lung function of children with asthma and OSA. Methods: A total of 96 children aged 6-15 years diagnosed with asthma, according to the Global Initiative for Asthma (GINA) 2020, were enrolled in this study. All demographic data, including age, gender, body mass index, asthma control status, therapy, the Vanderbilt ADHD Diagnostic Parent Rating Scale, lung function, and exhaled nitric oxide, were collected. In addition, home respiratory polygraphy was used to identify OSA in study subjects. Results: A total of 96 patients (8.4 ± 2.4 years) were included in the present study. OSA was identified in 60.4% of asthmatic children with a mean apnea-hypopnea index (AHI) of 3.5 ± 3.0 event/h. The inattentive ADHD subtype was significantly lower in the non-OSA asthmatic group than in the OSA asthmatic group (7.9 vs. 34.5%, p < 0.05). ADHD had a higher probability of presence (OR: 3.355; 95% CI: 1.271-8.859; p < 0.05) in the OSA group (AHI >1 event/h). Children with poorly controlled asthma had a significantly high risk of OSA (83.0 vs. 17.0%, p < 0.001) than children with well-controlled asthma. Allergic rhinitis increased the odds of having OSA in patients with asthma [OR: 8.217 (95% CI: 3.216-20.996); p < 0.05]. Conclusion: The prevalence of OSA is increased among poorly controlled asthma. ADHD may have a higher prevalence in children with OSA. Therefore, prompt diagnosis of OSA will lead to an accurate asthma control strategy in patients with asthma.

16.
J Am Coll Cardiol ; 78(1): 42-52, 2021 07 06.
Article En | MEDLINE | ID: mdl-34210413

BACKGROUND: Age-related clonal hematopoiesis of indeterminate potential (CHIP), defined as clonally expanded leukemogenic sequence variations (particularly in DNMT3A, TET2, ASXL1, and JAK2) in asymptomatic individuals, is associated with cardiovascular events, including recurrent heart failure (HF). OBJECTIVES: This study sought to evaluate whether CHIP is associated with incident HF. METHODS: CHIP status was obtained from whole exome or genome sequencing of blood DNA in participants without prevalent HF or hematological malignancy from 5 cohorts. Cox proportional hazards models were performed within each cohort, adjusting for demographic and clinical risk factors, followed by fixed-effect meta-analyses. Large CHIP clones (defined as variant allele frequency >10%), HF with or without baseline coronary heart disease, and left ventricular ejection fraction were evaluated in secondary analyses. RESULTS: Of 56,597 individuals (59% women, mean age 58 years at baseline), 3,406 (6%) had CHIP, and 4,694 developed HF (8.3%) over up to 20 years of follow-up. CHIP was prospectively associated with a 25% increased risk of HF in meta-analysis (hazard ratio: 1.25; 95% confidence interval: 1.13-1.38) with consistent associations across cohorts. ASXL1, TET2, and JAK2 sequence variations were each associated with an increased risk of HF, whereas DNMT3A sequence variations were not associated with HF. Secondary analyses suggested large CHIP was associated with a greater risk of HF (hazard ratio: 1.29; 95% confidence interval: 1.15-1.44), and the associations for CHIP on HF with and without prior coronary heart disease were homogenous. ASXL1 sequence variations were associated with reduced left ventricular ejection fraction. CONCLUSIONS: CHIP, particularly sequence variations in ASXL1, TET2, and JAK2, represents a new risk factor for HF.


Clonal Hematopoiesis/genetics , DNA-Binding Proteins/genetics , Heart Failure , Janus Kinase 2/genetics , Proto-Oncogene Proteins/genetics , Repressor Proteins/genetics , Ventricular Dysfunction, Left , Aged , Correlation of Data , Demography , Dioxygenases , Female , Heart Failure/diagnosis , Heart Failure/epidemiology , Heart Failure/physiopathology , Humans , Male , Middle Aged , Mutation , Proportional Hazards Models , Risk Factors , Stroke Volume , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/genetics , Exome Sequencing/methods
17.
BMC Anesthesiol ; 21(1): 95, 2021 03 30.
Article En | MEDLINE | ID: mdl-33784987

BACKGROUND: Pneumoperitoneum and Trendelenburg position in laparoscopic surgeries could contribute to postoperative pulmonary dysfunction. In recent years, intraoperative lung-protective mechanical ventilation (LPV) has been reportedly able to attenuate ventilator-induced lung injuries (VILI). Our objectives were to test the hypothesis that LPV could improve intraoperative oxygenation function, pulmonary mechanics and early postoperative atelectasis in laparoscopic surgeries. METHODS: In this randomized controlled clinical trial, 62 patients indicated for elective abdominal laparoscopic surgeries with an expected duration of greater than 2 h were randomly assigned to receive either lung-protective ventilation (LPV) with a tidal volume (Vt) of 7 ml kg- 1 ideal body weight (IBW), 10 cmH2O positive end-expiratory pressure (PEEP) combined with regular recruitment maneuvers (RMs) or conventional ventilation (CV) with a Vt of 10 ml kg- 1 IBW, 0 cmH2O in PEEP and no RMs. The primary endpoints were the changes in the ratio of PaO2 to FiO2 (P/F). The secondary endpoints were the differences between the two groups in PaO2, alveolar-arterial oxygen gradient (A-aO2), intraoperative pulmonary mechanics and the incidence of atelectasis detected on chest x-ray on the first postoperative day. RESULTS: In comparison to CV group, the intraoperative P/F and PaO2 in LPV group were significantly higher while the intraoperative A-aO2 was clearly lower. Cdyn and Cstat at all the intraoperative time points in LPV group were significantly higher compared to CV group (p < 0.05). There were no differences in the incidence of atelectasis on day one after surgery between the two groups. CONCLUSIONS: Lung protective mechanical ventilation significantly improved intraoperative pulmonary oxygenation function and pulmonary compliance in patients experiencing various abdominal laparoscopic surgeries, but it could not ameliorate early postoperative atelectasis and oxygenation function on the first day after surgery. TRIAL REGISTRATION: https://www.clinicaltrials.gov/identifier: NCT04546932 (09/05/2020).


Abdomen/surgery , Positive-Pressure Respiration/methods , Ventilator-Induced Lung Injury/prevention & control , Adult , Aged , Elective Surgical Procedures , Female , Humans , Laparoscopy , Male , Middle Aged , Oxygen/blood , Postoperative Complications/epidemiology , Pulmonary Atelectasis/epidemiology , Tidal Volume
18.
Front Immunol ; 11: 1605, 2020.
Article En | MEDLINE | ID: mdl-32903579

Background: The Asia Pacific Society for Immunodeficiencies (APSID) conducted nine primary immunodeficiency (PID) Schools in 5 years since inauguration to provide PID care training for early career physicians in Asia Pacific, a region with divergent needs in PID resources and training. Objective: To identify differences in PID patient care resource and training needs across Asia Pacific and propose a corresponding action plan. Methods: The Human Development Index (HDI) indicates the degree of socio-economic development in each country/region. Information related to investigations and learning issues were extracted from the abstracts and personal statements from all Schools and mapped onto resource and training needs. Correlations between HDI and country/region-specific parameters were tested by two-tailed Pearson correlation. Results: A total of 427 abstracts were received in nine Schools between 2015 and 2020, predominantly on immunodeficiencies affecting cellular and humoral immunity. Genetic confirmation was described in 61.8% of abstracts, and its absence negatively correlated with HDI (r = -0.696, p = 0.004). Essential immunologic and genetic tests were not available in 25.4 and 29.5% of abstracts, respectively, and their absence negatively correlated with HDI (r = -0.788, p < 0.001; r = -0.739, p = 0.002). HDI positively correlated with average testing level (r = 0.742, p = 0.002). Cases from medium-HDI countries/regions focused on learning how to investigate a patient for PIDs in cases of severe or atypical infections, whereas those from very-high-HDI countries/regions, from which most faculty members originated, listed hematopoietic stem cell transplantation and gene therapy, newborn screening, and research as learning issues more frequently. Conclusion: There are unique HDI-related PID resource and training needs in each country/region. APSID proposes HDI group-specific strategies to improve PID care and education in her member countries/regions. Further quantitative analysis of needs in PID care in Asia Pacific is needed for lobbying governments to increase their support for PID care and research.


Delivery of Health Care , Health Services Needs and Demand , Immunologic Deficiency Syndromes/epidemiology , Primary Health Care , Asia/epidemiology , Disease Management , Disease Susceptibility , Genetic Testing , Geography, Medical , Health Resources , Humans , Immunologic Deficiency Syndromes/diagnosis , Immunologic Deficiency Syndromes/etiology , Immunologic Deficiency Syndromes/therapy , Public Health Surveillance
19.
J Clin Med ; 8(1)2019 Jan 17.
Article En | MEDLINE | ID: mdl-30658424

Protecting the rights of the lesbians, gays, bisexuals, transgender, intersex, and queers (LGBTIQ) population requires, first and foremost, a proper understanding of their sexual orientation and gender identity. This study highlights a severe misunderstanding and lack of knowledge among health professionals in Vietnam with regard to the men who have sex with men (MSM) and transgenders. This study uses (i) a survey based on the convenience sampling method among 150 health workers that covered 61 questions and (ii) 12 in-depth interviews in two metropolitan centres in Vietnam, Hanoi and Ho Chi Minh city. Three main topics are explored: (i) the general knowledge of healthcare workers about MSM and transgenders; (ii) their knowledge about the sexual reproductive health and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) risks of MSM and transgenders; and (iii) their attitudes and behaviors towards MSM and transgenders. One of the notable findings is how prevalent the misperceptions are across the board, namely, in staff of both sexes, in both cities, at various kinds of medical facilities, at different work positions and educational levels. Half of the respondents consider transgenders to have a curable mental problem while 45% say MSM only have sex with males. Most remarkably, 12.7% state if they have any choice, they want nothing to do with MSM and transgenders. The study finds there is a considerable percentage of health professionals who lack knowledge about the diversity of sexual orientation, gender identity, and health issues related to the sexual minorities and gender non-conforming population. To improve the clinical process for serving these at-risk groups, the study suggests the continual education for the health workers needs to be added to their formal as well as in-job training.

20.
Am J Alzheimers Dis Other Demen ; 33(7): 423-432, 2018 11.
Article En | MEDLINE | ID: mdl-29642720

This study examined the use of potentially inappropriate medicines that may affect cognition (PIMcog) in people with dementia and its associated factors. Medical records of all outpatients with dementia attending a tertiary hospital in Vietnam between January 1, 2015, and December 31, 2016, were examined. Medicine use was assessed against a list of PIMcog. Variables associated with having a PIMcog were assessed using a multiple logistic regression. Of the 128 patients, 41% used a PIMcog, 39.1% used cholinesterase inhibitors (CEIs) concomitantly with anticholinergics, and 18% used antipsychotics. The number of hospital visits (adjusted odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.02-1.16) and number of treating specialists (adjusted OR: 0.61; 95% CI: 0.45-0.83) were associated with PIMcog use. This study highlights a high-level use of medicines that can further impair cognition or reduce the effectiveness of CEIs in people with dementia. Efforts to improve quality use of medicines for this population are warranted.


Antipsychotic Agents/administration & dosage , Cholinergic Antagonists/administration & dosage , Cholinesterase Inhibitors/administration & dosage , Dementia/epidemiology , Potentially Inappropriate Medication List/standards , Aged , Aged, 80 and over , Antipsychotic Agents/adverse effects , Cholinergic Antagonists/adverse effects , Cholinesterase Inhibitors/adverse effects , Cognition/drug effects , Female , Humans , Male , Vietnam/epidemiology
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