RESUMO
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with an abnormal accumulation of fibrotic tissue in the lung parenchyma and elevated glycolysis level in associated cells without effective therapy options. Lactate accumulation in pulmonary fibrotic tissue is a significant factor aggravating IPF development, but the main mechanism regulating glycolysis needs further investigation. In this study, lung fibrosis model was induced by bleomycin (BLM) intratracheally in female C57BL/6 mice. The changes of lactate level and fibrotic markers were detected. For in vitro studies, cell lines of alveolar epithelial cell and lung fibroblast cell were stimulated with TGF-ß1 and BLM respectively, to detect changes in their fibrotic properties. The function of lactate accumulation on facilitating fibrosis was verified. We demonstrated that BLM-induced pulmonary fibrosis is accompanied by lactate accumulation owing to glycolysis upregulation. Significantly high PDK1 expression in lung fibrotic tissue promotes glycolysis. Moreover, PDK1 stimulated trans-differentiation of lung fibroblasts and epithelial-mesenchymal transition (EMT) of alveolar epithelial cells. Furthermore, phosphorylated Akt2 activated PDK1 to cause pulmonary fibrosis and inhibitors of Akt2 and PDK1 could suppress fibrotic process. This study is the first to consider PDK1 facilitated lactate accumulation through glycolysis as a vital factor in pulmonary fibrosis and could be initiated by Akt2. We concluded that the pro-fibrotic properties of PDK1 are associated with Akt2 phosphorylation and thus provide new potential therapeutic targets for pulmonary fibrosis.
Assuntos
Fibrose Pulmonar Idiopática , Ácido Láctico , Feminino , Camundongos , Animais , Camundongos Endogâmicos C57BL , Transdução de Sinais , Fibrose Pulmonar Idiopática/induzido quimicamente , Células Epiteliais Alveolares , Bleomicina/toxicidade , Proteínas Proto-Oncogênicas c-aktRESUMO
Mutations in IBA57 disrupt iron-sulfur clusters maturation, causing a rare mitochondrial disease. Clinical manifestations vary from neonatal lethality to childhood-onset spastic paraparesis, yet the ethnic heterogeneity and natural history remain unclear, necessitating further exploration. This study aimed to delineate the genotype-phenotype correlation of IBA57 mutations by analyzing diverse clinical presentations. We report 11 Chinese patients and include literature-reported cases, totaling 61 patients enrolled for analysis. Clinical, neuroimaging, genetic, and disease progression information were collected. Among these, 46 presented as multiple mitochondrial dysfunctions syndrome 3 (MMDS3), with 58.7% originating from Chinese population. Based on disease course, we propose three clinical subtypes: neonatal, infant and childhood subtypes. Neonatal cases universally displayed hypotonia and respiratory distress at presentation, deceased within three months. Most infancy and childhood cases exhibited developmental regression and impaired motor function. Cavitating leukoencephalopathy was a typical neuroimaging finding in MMDS3 patients. The c.286 T > C mutation was reported in 85.2% of Chinese patients. A significantly lower mortality rate was observed compared to the non-Chinese group (P = 0.002), with a survival rate exceeding 90% at 5 years, indicating a relatively stable disease progression. Fifteen cases from three families manifested the spastic paraplegia 74 phenotype, demonstrating normal development before onset, with common clinical manifestations including spastic paraplegia (14/15), visual impairment (10/13), and peripheral neuropathy (9/13). In conclusion, this study indicates a hotspot mutation in Chinese and analyses the disease progression with different clinical subtypes.
RESUMO
Genome sequencing (GS) has been used in the diagnosis of global developmental delay (GDD)/intellectual disability (ID). However, the performance of GS in patients with inconclusive results from chromosomal microarray analysis (CMA) and exome sequencing (ES) is unknown. We recruited 100 pediatric GDD/ID patients from multiple sites in China from February 2018 to August 2020 for GS. Patients have received at least one genomic diagnostic test before enrollment. Reanalysis of their CMA/ES data was performed. The yield of GS was calculated and explanations for missed diagnoses by CMA/ES were investigated. Clinical utility was assessed by interviewing the parents by phone. The overall diagnostic yield of GS was 21%. Seven cases could have been solved with reanalysis of ES data. Thirteen families were missed by previous CMA/ES due to improper methodology. Two remained unsolved after ES reanalysis due to complex variants missed by ES, and a CNV in untranslated regions. Follow-up of the diagnosed families revealed that nine families experienced changes in clinical management, including identification of targeted treatments, cessation of unnecessary treatment, and considerations for family planning. GS demonstrated high diagnostic yield and clinical utility in this undiagnosed GDD/ID cohort, detecting a wide range of variant types of different sizes in a single workflow.
Assuntos
Deficiência Intelectual , Criança , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/genética , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Análise em Microsséries/métodos , Estudos Prospectivos , Sequenciamento do ExomaRESUMO
OBJECTIVE: To explore the clinical and genetic characteristics of three children with 22q13 deletion syndrome. METHODS: Clinical data were collected and copy number variations in the patients and their parents were detected by using array-based comparative genomic hybridization (aCGH) and copy number variation sequencing (CNV-seq). The DECIPHER, ClinGen, OMIM, PubMed and Gene Review databases were retrieved for pathogenicity analysis. RESULTS: The common phenotypes of the three children have included variable global developmental delay, among which speech delay was the most obvious. Patient 1 had abnormalities of corpus callosum shown by magnetic resonance imaging. Patient 2 had dental crowding, pale skin, thick palms, hypotonia, and other facial features. Patient 3 had the mildest symptoms including language dysfunction, which has caught up with the development and improved significantly. All of the three children had harbored de novo deletions of 22q13.33q13.33 region, which spanned 0.84 Mb, 8.70 Mb and 0.90 Mb and involved 37, 126, and 34 genes, respectively. CONCLUSION: Above finding has enriched the clinical and genetic characteristics of 22q13 deletion syndrome and laid a foundation for genetic counseling and prenatal diagnosis.
Assuntos
Transtornos Cromossômicos , Variações do Número de Cópias de DNA , Deleção Cromossômica , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 22/genética , Hibridização Genômica Comparativa/métodos , HumanosRESUMO
Hypomyelinating leukodystrophies (HLDs) are a rare group of disorders characterized by myelin deficit of the brain-based on MRI. Here, we studied 20 patients with unexplained HLD to uncover their genetic etiology through whole-exome sequencing (WES). Trio-based WES was performed for 20 unresolved HLDs families after genetic tests for the PLP1 duplication and a panel of 115 known leukodystrophy-related genes. Variants in both known genes that related to HLDs and promising candidate genes were analyzed. Minigene splicing assay was conducted to confirm the effect of splice region variant. All 20 patients were diagnosed with HLDs clinically based on myelin deficit on MRI and impaired motor ability. Through WES, in 11 of 20 trios, 15 causative variants were detected in seven genes TUBB4A, POLR1C, POLR3A, SOX10, TMEM106B, DEGS1, and TMEM63A. The last three genes have just been discovered. Of 15 variants, six were novel. Using minigene splicing assay, splice variant POLR3A c.1770 + 5 G > C was proved to disrupt the normal splicing of intron 13 and led to a premature stop codon at position 618 (p.(P591Vfs*28)). Our analysis determined the molecular diagnosis of 11 HLDs patients. It emphasizes the heterogenicity of HLDs, the diagnostic power of trio-based WES for HLDs. Comprehensive analysis including a focus on candidate genes helps to discover novel disease-causing genes, determine the diagnosis for the first time, and improve the yield of WES. Moreover, novel mutations identified in TUBB4A, POLR3A, and POLR1C expand the mutation spectrum of these genes.
Assuntos
Predisposição Genética para Doença , Variação Genética , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Canais de Cálcio/genética , Criança , Pré-Escolar , RNA Polimerases Dirigidas por DNA/genética , Ácidos Graxos Dessaturases/genética , Feminino , Testes Genéticos , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/diagnóstico , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Proteínas de Membrana/genética , Mutação , Bainha de Mielina/metabolismo , Proteínas do Tecido Nervoso/genética , RNA Polimerase III/genética , Splicing de RNA , Fatores de Transcrição SOXE/genética , Tubulina (Proteína)/genética , Sequenciamento do ExomaRESUMO
BACKGROUND: Intellectual disability/developmental delay is a complex condition with extraordinary heterogeneity. A large proportion of patients lacks a specific diagnosis. Next generation sequencing, enabling identification of genetic variations in multiple genes, has become an efficient strategy for genetic analysis in intellectual disability/developmental delay. METHODS: Clinical data of 112 Chinese families with unexplained intellectual disability/developmental delay was collected. Targeted next generation sequencing of 454 genes related to intellectual disability/developmental delay was performed for all 112 index patients. Patients with promising variants and their other family members underwent Sanger sequencing to validate the authenticity and segregation of the variants. RESULTS: Fourteen promising variants in genes EFNB1, MECP2, ATRX, NAA10, ANKRD11, DHCR7, LAMA1, NFIX, UBE3A, ARID1B and PTPRD were identified in 11 of 112 patients (11/112, 9.82%). Of 14 variants, eight arose de novo, and 13 are novel. Nine patients (9/112, 8.03%) got definite molecular diagnoses. It is the first time to report variants in EFNB1, NAA10, DHCR7, LAMA1 and NFIX in Chinese intellectual disability/developmental delay patients and first report about variants in NAA10 and LAMA1 in affected individuals of Asian ancestry. CONCLUSIONS: Targeted next generation sequencing of 454 genes is an effective test strategy for patients with unexplained intellectual disability/developmental delay. Genetic heterogenicity is significant in this Chinese cohort and de novo variants play an important role in the diagnosis. Findings of this study further delineate the corresponding phenotypes, expand the mutation spectrum and support the involvement of PTPRD in the disease.
Assuntos
Deficiências do Desenvolvimento/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Deficiência Intelectual/genética , Mutação , Adolescente , Criança , Pré-Escolar , China , Cromossomos Humanos X , Feminino , Genes Dominantes , Genes Recessivos , Heterogeneidade Genética , Humanos , Lactente , Masculino , Linhagem , FenótipoRESUMO
BACKGROUND: Atrial fibrillation (AF) significantly increases the risk of ischemic stroke depending on various risk factors. The CHA2DS2-VASc score is used widely to improve stratification of AF-related stroke to identify for whom anticoagulation could be safely withheld. As upstream therapy, the management of lifestyle for AF and related stroke prevention has been ongoing for past decades. CASE PRESENTATION: A 56-year-old male was taken to our hospital because of acute ischemic stroke. Without intracranial vascular malformation and angiostenosis, two small emboli were successfully taken out from the left middle cerebral artery by mechanical thrombectomy. During the hospitalisation, no apparent abnormalities were found in various laboratory tests, echocardiogram or the coronary computed tomography angiography. However, asymptomatic paroxysmal AF was first diagnosed and was presumed to be responsible for his stroke. Noticeable, he was always in good fitness benefiting from the formed good habits of no smoking and drinking. With a CHA2DS2-VASc score of 0, he had no history of any known diseases or risk factors associated with AF and related stroke. Instead of lacking exercise, he persisted in playing table tennis faithfully 3-4 times a week and 2-3 h each time over the past 30 years, and, in fact, has won several amateur table tennis championships. CONCLUSION: In view of the possible pathophysiological mechanisms resulting from the long-term vigorous endurance exercise, it may be a potential risk factor for developing AF and even for subsequent stroke. Not merely should strengthen the screening for AF in specific individuals as sports enthusiasts, but the necessity of oral anticoagulant for those with a CHA2DS2-VASc score of 0 might deserve the further investigation.
Assuntos
Fibrilação Atrial/complicações , Isquemia Encefálica/etiologia , Exercício Físico , Embolia Intracraniana/etiologia , Acidente Vascular Cerebral/etiologia , Administração Oral , Anticoagulantes/administração & dosagem , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/terapia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/terapia , Tomada de Decisão Clínica , Humanos , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/fisiopatologia , Embolia Intracraniana/terapia , Masculino , Pessoa de Meia-Idade , Resistência Física , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Trombectomia , Resultado do TratamentoRESUMO
Oleogels are innovative structured fat systems that can replace detrimental lipids and saturated fats. Among the various gelators used to construct oleogels, phytosterols are regarded as potential oleogelators due to ability to lower blood cholesterol levels and protect patients from cardiovascular illnesses, although little research has been conducted on phytosterols. This article examines the formation, characterization, and application of phytosterol-based oleogels in detail. The oleogelation behaviors of phytosterol-based oleogels are affected by their formulation, which includes phytosterol type, combined oleogelator, proportion, concentration and oil type. These oleogels exhibit potential applications as solid fat substitutes without affecting the texture or sensory properties of food products or as effective delivery vehicles. To encourage the research and implementation of phytosterol-based oleogels, we will ultimately not only highlight problems related to their use in food processing, but also provide a few viewpoints, with the goal of providing fresh insights for advancing trends.
Assuntos
Compostos Orgânicos , Fitosteróis , Fitosteróis/química , Compostos Orgânicos/química , Humanos , Substitutos da Gordura/químicaRESUMO
Thiamine pyrophosphokinase (TPK) deficiency, is a rare autosomal recessive disorder of congenital metabolic dysfunction caused by variants in the TPK1 gene. TPK1 variants can lead to thiamine metabolic pathway obstacles, and its clinical manifestations are highly variable. We describe two cases of TPK deficiency with completely different phenotypes and different therapeutic effects, and 26 cases of previously reported were retrospectively reviewed to improve our understanding of the clinical and genetic features of the disease. Patients with TPK deficiency present with ataxia, dysarthria, dystonia, disturbance of consciousness, seizures, and other nervous system dysfunction. Different gene variant sites may lead to different clinical features and therapeutic effects. Gene analysis is important for the diagnosis of TPK deficiency caused by TPK1 variants, and thiamine supplementation has been the mainstay of treatment for TPK deficiency to date.
RESUMO
Hypomyelination leukodystrophies constitute a group of heritable white matter disorders exhibiting defective myelin development. Initially identified as a lysosomal protein, the TMEM106B D252N mutant has recently been associated with hypomyelination. However, how lysosomal TMEM106B facilitates myelination and how the D252N mutation disrupts that process are poorly understood. We used superresolution Hessian structured illumination microscopy (Hessian-SIM) and spinning disc-confocal structured illumination microscopy (SD-SIM) to find that the wild-type TMEM106B protein is targeted to the plasma membrane, filopodia, and lysosomes in human oligodendrocytes. The D252N mutation reduces the size of lysosomes in oligodendrocytes and compromises lysosome changes upon starvation stress. Most importantly, we detected reductions in the length and number of filopodia in cells expressing the D252N mutant. PLP1 is the most abundant myelin protein that almost entirely colocalizes with TMEM106B, and coexpressing PLP1 with the D252N mutant readily rescues the lysosome and filopodia phenotypes of cells. Therefore, interactions between TMEM106B and PLP1 on the plasma membrane are essential for filopodia formation and myelination in oligodendrocytes, which may be sustained by the delivery of these proteins from lysosomes via exocytosis.
Assuntos
Proteínas do Tecido Nervoso , Pseudópodes , Humanos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Pseudópodes/metabolismo , Oligodendroglia/metabolismo , Bainha de Mielina/metabolismo , Mutação , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismoRESUMO
Biotransformation is an effective technique to modify the structure and physicochemical properties of carbohydrates. In this work, Chinese yam (Dioscorea opposita Thunb.) starch was fermented by lactobacteria. The effect of fermentation time (6, 12, 30, 42 and 72 h) on structure and physicochemical properties of Chinese yam starch were investigated. The microstructure was destroyed after lactobacteria fermentation for 42 and 72 h. The X-ray diffraction pattern of Chinese yam starch indicated a transformed A to A + V crystalline type. â 4)-α-d-glucose-(1 â from backbone and unreduced terminal α-d-glucose-(1 â 4 from branch were identified by NMR spectra, and free glucose was only detected in fermented starch at 72 h. With the extension of fermentation time, the crystallinity and thermal parameters increased within 42 h and thereafter decreased. Mw, Mw/Mn, long chains of DP25-36 and DP ≥ 37, peak viscosity, trough viscosity, finally viscosity and setback presented a reverse trend.
Assuntos
Dioscorea , Dioscorea/química , Fermentação , Glucose , Amido/química , ViscosidadeRESUMO
BACKGROUND: The natural history and genotype-phenotype correlation of Pelizaeus-Merzbacher disease (PMD) of Chinese patients has been rarely reported. METHOD: Patients who met the criteria for PMD were enrolled in our study. Genomic analysis was conducted by multiplex ligation probe amplification (MLPA) and Sanger or whole-exome sequencing (WES). Natural history differences and genotype-phenotype correlations were analyzed. RESULT: A total of 111 patients were enrolled in our follow-up study. The median follow-up interval was 53 m (1185). Among PMD patients, developmental delay was the most common sign, and nystagmus and hypotonia were the most common initial symptoms observed. A total of 78.4% of the patients were able to control their head, and 72.1% could speak words. However, few of the patients could stand (9.0%) or walk (4.5%) by themselves. Nystagmus improved in more than half of the patients, and hypotonia sometimes deteriorated to movement disorders. More PLP1 point mutations patients were categorized into severe group, while more patients with PLP1 duplications were categorized into mild group (p < 0.001). Compared to patients in mild groups, those in the severe group had earlier disease onset and had acquired fewer skills at a later age. CONCLUSION: PMD patients have early disease onset with nystagmus and hypotonia followed by decreased nystagmus and movement disorders, such as spasticit. Patients with PLP1 duplication were more likely to be categorized into the mild group, whereas patients with point mutations were more likely to be categorized into the severe group.
Assuntos
Doença de Pelizaeus-Merzbacher , China , Seguimentos , Estudos de Associação Genética , Humanos , Proteína Proteolipídica de Mielina/genética , Doença de Pelizaeus-Merzbacher/diagnóstico , Doença de Pelizaeus-Merzbacher/genéticaRESUMO
Objective: To study the burden of neurodevelopmental diseases (NDDs) via cost-of-illness analysis of Chinese patients with genetic diagnosis. Methods: We recruited NDD patients (0-18 years old) with genetic diagnosis (GD) from September 1, 2020 to January 30, 2021. We gathered basic information on the details of diagnosis, as well as the direct medical cost, direct non-healthcare cost and indirect cost before and after receiving GD. We corrected the cost for time biases by calculating the cost per day for each patient. Results: For the 502 patients with NDDs, the mean age was 4.08 ± 3.47. The household income was 0.6 (0.4, 1.0) 10,000 CNY per-month on average. The direct medical cost, direct non-healthcare cost and indirect cost were 12.27 (7.36, 22.23) 10,000 CNY, 1.45 (0.73, 2.69)10,000 CNY and 14.14(4.80, 28.25) 10,000 CNY per patient, respectively. Every patient received 1.20 (0.34, 3.60) 10,000 CNY on average (15.91%) from insurance. The daily total cost after receiving GD were ~62.48% lower than those before GD (191.59 CNY vs. 71.45 CNY). The descend range of lab cost (95.77%, P < 0.05) was the largest, followed by drugs (91.39%, P < 0.05), hospitalization (90.85%, P < 0.05), and consultation (57.41%, P < 0.05). The cost of rehabilitation kept slightly increasing but there were no significant differences (P > 0.05). The daily direct medical cost of each patient fell by 75.26% (P < 0.05) from 311.79 CNY to 77.14 CNY when the diagnostic age was younger than 1, and declined by 49.30% (P < 0.05) and 8.97% (P > 0.05) when the diagnostic age was 1-3 and older than 3, respectively. Conclusions: Early genetic diagnosis is crucial for to reducing the burden of disease because of the amount of money spent was lower when they are diagnosed at younger age. Patients with NDDs can incur a heavy economic burden, especially in rehabilitation cost and indirect cost, because the insurance coverage for patients is low, so it is urgent for governments to pay more attention to these issues.
Assuntos
Estresse Financeiro , Hospitalização , Adolescente , Criança , Pré-Escolar , Custos e Análise de Custo , Humanos , Lactente , Recém-NascidoRESUMO
Hypomyelinating leukodystrophies (HLDs) are a rare group of heterogeneously genetic disorders characterized by persistent deficit of myelin observed on magnetic resonance imaging (MRI). To identify a new disease-associated gene of HLD, trio-based whole exome sequencing was performed for unexplained patients with HLD. Functional studies were performed to confirm the phenotypic effect of candidate protein variants. Two de novo heterozygous variants, c.227T>G p.(L76R) or c.227T>C p.(L76P) in TMEM163 were identified in two unrelated HLD patients. TMEM163 protein is a zinc efflux transporter localized within the plasma membrane, lysosomes, early endosomes, and other vesicular compartments. It has not been associated with hypomyelination. Functional zinc flux assays in HeLa cells stably-expressing TMEM163 protein variants, L76R and L76P, revealed distinct attenuation or enhancement of zinc efflux, respectively. Experiments using a zebrafish model with knockdown of tmem163a and tmem163b (morphants) showed that loss of tmem163 causes dysplasia of the larvae, locomotor disability and myelin deficit. Expression of human wild type TMEM163 mRNAs in morphants rescues the phenotype, while the TMEM163 L76P and L76R mutants aggravated the condition. Moreover, poor proliferation, elevated apoptosis of oligodendrocytes, and reduced oligodendrocytes and neurons were also observed in zebrafish morphants. Our findings suggest an unappreciated role for TMEM163 protein in myelin development and add TMEM163 to a growing list of genes associated with hypomyelination leukodystrophy.
Assuntos
Doenças Desmielinizantes , Doenças por Armazenamento dos Lisossomos , Proteínas de Membrana , Doenças Neurodegenerativas , Animais , Doenças Desmielinizantes/metabolismo , Células HeLa , Humanos , Doenças por Armazenamento dos Lisossomos/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Bainha de Mielina/genética , Bainha de Mielina/metabolismo , Doenças Neurodegenerativas/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Zinco/metabolismoRESUMO
Among the hypomyelinating leukodystrophies, Pelizaeus-Merzbacher disease (PMD) is a representative disorder. The disease is caused by different types of PLP1 mutations, among which PLP1 duplication accounts for â¼70% of the mutations. Previous studies have shown that PLP1 duplications lead to PLP1 retention in the endoplasmic reticulum (ER); in parallel, recent studies have demonstrated that PLP1 duplication can also lead to mitochondrial dysfunction. As such, the respective roles and interactions of the ER and mitochondria in the pathogenesis of PLP1 duplication are not clear. In both PLP1 patients' and healthy fibroblasts, we measured mitochondrial respiration with a Seahorse XF Extracellular Analyzer and examined the interactions between the ER and mitochondria with super-resolution microscopy (spinning-disc pinhole-based structured illumination microscopy, SD-SIM). For the first time, we demonstrated that PLP1 duplication mutants had closer ER-mitochondrion interfaces mediated through structural and morphological changes in both the ER and mitochondria-associated membranes (MAMs). These changes in both the ER and mitochondria then led to mitochondrial dysfunction, as reported previously. This work highlights the roles of MAMs in bridging PLP1 expression in the ER and pathogenic dysfunction in mitochondria, providing novel insight into the pathogenicity of mitochondrial dysfunction resulting from PLP1 duplication. These findings suggest that interactions between the ER and mitochondria may underlie pathogenic mechanisms of hypomyelinating leukodystrophies diseases at the organelle level.
Assuntos
Proteína Proteolipídica de Mielina , Doença de Pelizaeus-Merzbacher , Retículo Endoplasmático , Humanos , Mitocôndrias , Mutação , Proteína Proteolipídica de Mielina/genética , Doença de Pelizaeus-Merzbacher/genética , VirulênciaRESUMO
BACKGROUND: The potential effectiveness of integrated management in further improving the prognosis of patients with atrial fibrillation has been demonstrated; however, the best strategy for implementation remains to be discovered. OBJECTIVE: The aim of this study was to ascertain the feasibility of implementing integrated atrial fibrillation care via the Hospital-Community-Family-Based Telemedicine (HCFT-AF) program. METHODS: In this single-arm, pre-post design pilot study, a multidisciplinary teamwork, supported by efficient infrastructures, provided patients with integrated atrial fibrillation care following the Atrial fibrillation Better Care (ABC) pathway. Eligible patients were continuously recruited and followed up for at least 4 months. The patients' drug adherence, and atrial fibrillation-relevant lifestyles and behaviors were assessed at baseline and at 4 months. The acceptability, feasibility, and usability of the HCFT-AF technology devices and engagement with the HCFT-AF program were assessed at 4 months. RESULTS: A total of 73 patients (mean age, 68.42 years; 52% male) were enrolled in November 2019 with a median follow up of 132 days (IQR 125-138 days). The patients' drug adherence significantly improved after the 4-month intervention (P<.001). The vast majority (94%, 64/68) of indicated patients received anticoagulant therapy at 4 months, and none of them received antiplatelet therapy unless there was an additional indication. The atrial fibrillation-relevant lifestyles and behaviors ameliorated to varying degrees at the end of the study. In general, the majority of patients provided good feedback on the HCFT-AF intervention. More than three-quarters (76%, 54/71) of patients used the software or website more than once a week and accomplished clinic visits as scheduled. CONCLUSIONS: The atrial fibrillation-integrated care model described in this study is associated with improved drug adherence, standardized therapy rate, and lifestyles of patients, which highlights the possibility to better deliver integrated atrial fibrillation management. TRIAL REGISTRATION: Clinicaltrials.gov NCT04127799; https://clinicaltrials.gov/ct2/show/NCT04127799.
Assuntos
Fibrilação Atrial , Telemedicina , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Estudos de Viabilidade , Feminino , Humanos , Masculino , Projetos PilotoRESUMO
BACKGROUND: An increasing number of patients with chronic heart failure (CHF) are demanding more convenient and efficient modern health care systems, especially in remote areas away from central cities. Telehealth is receiving increasing attention, which may be useful to patients with CHF. OBJECTIVE: This study aimed to evaluate the feasibility of a hospital-community-family (HCF)-based telehealth program, which was designed to implement remote hierarchical management in patients with CHF. METHODS: This was a single-arm prospective study in which 70 patients with CHF participated in the HCF-based telehealth program for remote intervention for at least 4 months. The participants were recruited from the clinic and educated on the use of smart health tracking devices and mobile apps to collect and manually upload comprehensive data elements related to the risk of CHF self-care management. They were also instructed on how to use the remote platform and mobile app to send text messages, check notifications, and open video channels. The general practitioners viewed the index of each participant on the mobile app and provided primary care periodically, and cardiologists in the regional central hospital offered remote guidance, if necessary. The assessed outcomes included accomplishments of the program, usability and satisfaction, engagement with the intervention, and changes of heart failure-related health behaviors. RESULTS: As of February 2018, a total of 66 individuals, aged 40-79 years, completed the 4-month study. Throughout the study period, 294 electronic medical records were formed on the remote monitoring service platform. In addition, a total of 89 remote consultations and 196 remote ward rounds were conducted. Participants indicated that they were generally satisfied with the intervention for its ease of use and usefulness. More than 91% (21/23) of physicians believed the program was effective, and 87% (20/23) of physicians stated that their professional knowledge could always be refreshed and enhanced through a library hosted on the platform and remote consultation. More than 60% (40/66) of participants showed good adherence to the care plan in the study period, and 79% (52/66) of patients maintained a consistent pattern of reporting and viewing their data over the course of the 4-month follow-up period. The program showed a positive effect on self-management for patients (healthy diet: P=.046, more fruit and vegetable intake: P=.02, weight monitoring: P=.002, blood pressure: P<.001, correct time: P=.049, and daily dosages of medicine taken: P=.006). CONCLUSIONS: The HCF-based telehealth program is feasible and provided researchers with evidence of remote hierarchical management for patients with CHF, which can enhance participants' and their families' access and motivation to engage in self-management. Further prospective studies with a larger sample size are necessary to confirm the program's effectiveness.