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PURPOSE: Previous studies assessed different components of telemedicine management pathway for OSA instead of the whole pathway. This randomized, controlled, and non-inferiority trial aimed to assess whether telemedicine management is clinically inferior to in-person care in China. METHODS: Adults suspected of OSA were randomized to telemedicine (web-based questionnaires, self-administered home sleep apnea test [HSAT], automatically adjusting positive airway pressure [APAP], and video-conference visits) or in-person management (paper questionnaires, in-person HSAT set-up, APAP, and face-to-face visits). Participants with an apnea-hypopnea index (AHI) ≥ 15 events/hour received APAP for 3 months. The non-inferiority analysis was based on the change in Functional Outcomes of Sleep Questionnaire (FOSQ) score and APAP adherence. Cost-effectiveness analysis was performed. RESULTS: In the modified intent-to-treat analysis set (n = 111 telemedicine, 111 in-person), FOSQ scores improved 1.73 (95% confidence interval [CI], 1.31-2.14) points with telemedicine and 2.05 (1.64-2.46) points with in-person care. The lower bound of the one-sided 95% non-inferiority CI for the difference in change between groups of - 0.812 was larger than the non-inferiority threshold of - 1. APAP adherence at 3 months was 243.3 (223.1-263.5) minutes/night for telemedicine and 241.6 (221.3-261.8) minutes/night for in-person care. The lower bound of the one-sided 95% non-inferiority CI of - 22.2 min/night was higher than the non-inferiority delta of - 45 min/night. Telemedicine had lower total costs than in-person management (CNY 1482.7 ± 377.2 vs. 1912.6 ± 681.3; p < 0.0001), driven by patient costs, but no significant difference in QALYs. CONCLUSIONS: Functional outcomes and adherence were not clinically inferior in patients managed by a comprehensive telemedicine approach compared to those receiving in-person care in China. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn , Registration number ChiCTR2000030546. Retrospectively registered on March 06, 2020.
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Apneia Obstrutiva do Sono , Telemedicina , Humanos , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/economia , Masculino , China , Feminino , Pessoa de Meia-Idade , Adulto , Pressão Positiva Contínua nas Vias Aéreas , Idoso , Análise Custo-BenefícioRESUMO
Cardiometabolic multimorbidity (CMM) is an increasingly significant global public health concern. It encompasses the coexistence of multiple cardiometabolic diseases, including hypertension, stroke, heart disease, atherosclerosis, and T2DM. A crucial component to the development of CMM is the disruption of endothelial homeostasis. Therefore, therapies targeting endothelial cells through multi-targeted and multi-pathway approaches hold promise for preventing and treatment of CMM. Curcumin, a widely used dietary supplement derived from the golden spice Carcuma longa, has demonstrated remarkable potential in treatment of CMM through its interaction with endothelial cells. Numerous studies have identified various molecular targets of curcumin (such as NF-κB/PI3K/AKT, MAPK/NF-κB/IL-1ß, HO-1, NOs, VEGF, ICAM-1 and ROS). These findings highlight the efficacy of curcumin as a therapeutic agent against CMM through the regulation of endothelial function. It is worth noting that there is a close relationship between the progression of CMM and endothelial damage, characterized by oxidative stress, inflammation, abnormal NO bioavailability and cell adhesion. This paper provides a comprehensive review of curcumin, including its availability, pharmacokinetics, pharmaceutics, and therapeutic application in treatment of CMM, as well as the challenges and future prospects for its clinical translation. In summary, curcumin shows promise as a potential treatment option for CMM, particularly due to its ability to target endothelial cells. It represents a novel and natural lead compound that may offer significant therapeutic benefits in the management of CMM.
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Aterosclerose , Curcumina , Humanos , Células Endoteliais , Curcumina/farmacologia , Curcumina/uso terapêutico , Multimorbidade , NF-kappa B , Fosfatidilinositol 3-Quinases , EspeciariasRESUMO
Obstructive Sleep Apnea (OSA) is a disorder that is characterized by obstructive apneas and hypopneas/respiratory effort-related arousals caused by upper airway collapse during sleep. Positive Airway Pressure (PAP) is the first-line treatment for moderate to severe OSA. However, the effectiveness of PAP therapies is contingent on treatment adherence. With the implementation of the wireless transmission for PAP treatment, it is possible to evaluate the objective adherence to PAP use. The purpose of this study is to assess the adherence to PAP therapy of Chinese OSA patients in a telemedicine management system which could fulfill automatic transmission of PAP treatment data. First, we use the telemedicine management system to extract PAP adherence information of OSA adult patients in one week, one month, three months, six months and 12 months. Second, we describe the general profile of PAP therapy adherence. Third, the latent class growth modeling and growth mixture modeling was conducted using Mplus 8.0 to identify the trajectories of adherence over time. Of all the 662 patients involved in our study, PAP adherence declined over time. After one year, the proportion of days compliant was 53.7%, the proportion of good compliance was 45.2%, the daily usage (all days) was 3.9 h/night, slightly lower than subjective adherence reported in the previous literatures. In addition, we identified three patterns of adherence over time: great users (39.9%; high mean value and level, negative slope, slow decline), good users (34.8%; moderate mean value and level, negative slope, rapid decline) and low users (25.3%; low mean value and level, negative slope, rapid decline). In brief, telemedicine management system provides a convenient platform for monitoring the treatment compliance of OSA patients powerfully and accurately. To improve the low PAP adherence in China, we should make good use of the PAP therapy telemedicine management platform to detect patients with poor adherence and provide timely intervention. Besides, our research provides a foundation for future studies to explore the determinants of observed trajectories of PAP adherence based on the telemedicine platforms.
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Apneia Obstrutiva do Sono , Telemedicina , Adulto , Big Data , Pressão Positiva Contínua nas Vias Aéreas , Humanos , Cooperação do Paciente , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapiaRESUMO
Resorbable coatings are processed on flexible implants to facilitate penetrations. However, impacts of fabricating methods on implantation damage of coated probes are unclear. Herein, photosensitive polyimide (PSPI) based flexible neural implants are fabricated through clean-room technology. Polyethyleneglycol (PEG) - dexamethasone (DEX) coatings are processed through an improved micro moulding protocol in micro channels, fabricated by computer-numerical-controlled (CNC) micro milling, laser machining, and deep reactive ion etching (DRIE), respectively. An in vitro testing system is developed, using maximum insertion force [Formula: see text] and mean region-of-interest strain [Formula: see text] to accurately evaluate effects of the three fabricating methods on implantation damage at different insertion speed. Rat cerebrum, agarose gel, and silicone rubber are used as brain phantoms for tests. Results show that lower insertion speed, and micro channels fabricated by CNC micro milling or DRIE can minimize implantation damage. The decrease of insertion speed from 2.0 mm/s to 0.5 mm/s reduces [Formula: see text] by 76.2% ~85.1% and [Formula: see text] by 11.6% ~14.7%, respectively. Compared with laser machining, CNC micro milling and DRIE ensure dimensional accuracy of the PEG/DEX coating, reducing [Formula: see text] by 20.2% ~51.4% and [Formula: see text] by 8.0% ~11.6%, respectively. Compared with biological rat cerebrum, [Formula: see text] reduces by 5.8% ~25.1% in agarose gel phantom and increases by 7.7% ~21.0% in silicone rubber phantom, respectively. This study improves processing methods of polymer coatings and reveals mechanical difference between current used abiotic brain phantoms and biological brain tissues. Implantation tests establish quantitative relationship among insertion speed, fabricating methods, and implantation damage.
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Encéfalo , Polietilenoglicóis , Animais , Fenômenos Mecânicos , Imagens de Fantasmas , Polímeros , RatosRESUMO
Although mandibular advancement device (MAD) treatment of adults with obstructive sleep apnea (OSA) is generally less efficacious than positive airway pressure (PAP), the two treatments are associated, with similar clinical outcomes. As a sub-analysis of a randomized trial comparing the effect of MAD versus PAP on blood pressure, this study compared objectively measured adherence to MAD versus PAP treatment in adults with OSA. Adults with OSA (age 54.1 ± 11.2 [standard deviation] years, 71.1% male, apnea-hypopnea index 31.6 ± 22.7 events/h) were randomized to MAD (n = 89) or PAP (n = 91) treatment for 3-6 months. Objective adherence was assessed with a thermal sensor embedded in the MAD and a pressure sensor in the PAP unit. In a per protocol analysis, no difference was observed in average daily hours of use over all days in participants on MAD (n = 35, 4.4 ± 2.9 h) versus PAP (n = 51, 4.7 ± 1.6 h, p = .597) treatment when days with missing adherence data were included as no use. MAD was used on a lower percentage of days (62.5 ± 36.4% versus 79.9 ± 19.8%, p = .047), but with greater average daily hours of use on days used (6.4 ± 1.9 h versus 5.7 ± 1.2 h, p = .013). Average daily hours of use in the first week were associated with long-term adherence to MAD (p < .0001) and PAP (p = .0009) treatment. Similar results were obtained when excluding days with missing adherence data. In conclusion, no significant difference was observed in objectively measured average daily hours of MAD and PAP adherence in adults with OSA, despite differences in the patterns of use. MAD adherence in the first week predicted long-term use.
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Pressão Positiva Contínua nas Vias Aéreas , Avanço Mandibular , Cooperação do Paciente , Apneia Obstrutiva do Sono/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placas Oclusais , Resultado do TratamentoRESUMO
BACKGROUND: Catathrenia is a rare sleep disorder characterized by repeated groaning in a protracted expiration preceded by a deep inspiration. This study aimed to explore whether anatomy is one of pathophysiology of catathrenia by investigating the anatomical features associated with catathrenia in the upper airway, craniofacial structures, and dental patterns. MATERIAL AND METHODS: Twenty-two patients with catathrenia (7 males, 15 females; age 22 to 69 years) were recruited as well as 66 patients matched by age and gender (matching proportion 1:3) with obstructive sleep apnea syndrome (OSAS). Both groups underwent cephalograms and dental casting, and cephalometric measurements and the Peer Assessment Rating (PAR) index was applied. Differences between the two groups were evaluated and cephalometric measurements in catathrenia group were compared with control values of Chinese patients from previous studies. RESULTS: As for airway-related measurements, increased PNS-R, PNS-UPW, and H-FH and decreased SPT and TGL were found in catathrenia group compared to normal values. Such trends were found even more evident when compared with the OSAS Group. As for craniofacial parameters, values of U1/NA and U1/SN were found increased in the catathrenia group compared with normal values and values of MP/FH and Y decreased. The differences were more distinct from the OSAS Group. Increased arch lengths and upper inter-first molar widths, and decreased overbite and PAR index, were found in catathrenia group compared with the OSAS Group. CONCLUSION: Catathrenia patients present with a broad upper airway, yet protrusive upper incisors and flat mandibular angles. Anatomical characteristics of catathrenia are different from those associated with OSAS, namely a wide airway, large skeleton, and good occlusion.
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Cefalometria , Técnica de Fundição Odontológica , Expiração/fisiologia , Sons Respiratórios/fisiologia , Apneia Obstrutiva do Sono/fisiopatologia , Transtornos do Sono-Vigília/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Masculino , Mandíbula/fisiopatologia , Pessoa de Meia-Idade , Dente Molar/fisiopatologia , Sobremordida/fisiopatologia , Palato/fisiopatologia , Valores de Referência , Adulto JovemRESUMO
Sepsis and septic shock are critical medical conditions characterized by a systemic inflammatory response to infection, significantly contributing to global mortality rates. The progression to multiple organ dysfunction syndrome (MODS) represents the most severe complication of sepsis and markedly increases clinical mortality. Central to the pathophysiology of sepsis, endothelial cells play a crucial role in regulating microcirculation and maintaining barrier integrity across various organs and tissues. Recent studies have underscored the pivotal role of endothelial function in the development of sepsis-induced MODS. This review aims to provide a comprehensive overview of the pathophysiology of sepsis-induced MODS, with a specific focus on endothelial dysfunction. It also compiles compelling evidence regarding potential small molecules that could attenuate sepsis and subsequent multi-organ damage by modulating endothelial function. Thus, this review serves as an essential resource for clinical practitioners involved in the diagnosing, managing, and providing intensive care for sepsis and associated multi-organ injuries, emphasizing the importance of targeting endothelial cells to enhance outcomes of the patients.
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Purpose: Catathrenia is a rare sleeping disorder characterized by repetitive nocturnal groaning during prolonged expirations. Patients with catathrenia had heterogeneous polysomnographic, comorbidity, craniofacial characteristics, and responses to treatment. Identifying phenotypes of catathrenia might benefit the exploration of etiology and personalized therapy. Patients and Methods: Sixty-six patients diagnosed with catathrenia by full-night audio/video polysomnography seeking treatment with mandibular advancement devices (MAD) or continuous positive airway pressure (CPAP) were included in the cohort. Polysomnographic characteristics including sleep architecture, respiratory, groaning, and arousal events were analyzed. Three-dimensional (3D) and 2D craniofacial hard tissue and upper airway structures were evaluated with cone-beam computed tomography and lateral cephalometry. Phenotypes of catathrenia were identified by K-mean cluster analysis, and inter-group comparisons were assessed. Results: Two distinct clusters of catathrenia were identified: cluster 1 (n=17) was characterized to have more males (71%), a longer average duration of groaning events (18.5±4.8 and 12.8±5.7s, p=0.005), and broader upper airway (volume 41,386±10,543 and 26,661±6700 mm3, p<0.001); cluster 2 (n=49) was characterized to have more females (73%), higher respiratory disturbance index (RDI) (median 1.0 [0.3, 2.0] and 5.2 [1.2, 13.3]/h, p=0.009), more respiratory effort-related arousals (RERA)(1 [1, 109] and 32 [13, 57)], p=0.005), smaller upper airway (cross-sectional area of velopharynx 512±87 and 339±84 mm2, p<0.001) and better response to treatment (41.2% and 82.6%, p=0.004). Conclusion: Two distinct phenotypes were identified in patients with catathrenia, primary catathrenia, and catathrenia associated with upper airway obstruction, suggesting respiratory events and upper airway structures might be related to the etiology of catathrenia, with implications for its treatment.
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BACKGROUND: Septic shock, an extremely dangerous condition that causes impairment of organ function, always largely contributes to mortality in intensive care units. The impact of septic shock-induced organ damage on morbidity and mortality is substantially influenced by myocardial dysfunction. However, it remains unclear whether and in what manner anisodamine (654-1/654-2) ameliorates myocardial dysfunction caused by septic shock. PURPOSE: This study is the pioneering investigation and validation about the protective efficacy of anisodamine (654-1/654-2) against LPS-induced myocardial dysfunction in septic shock rats. It also aims to explore the differences in the underlying molecular mechanisms of both drugs. METHODS: A septic shock model was established in SD rats by after tail vein administration of LPS. 64 rats were distributed into eight groups, such as LPS group, control group, LPS+654-1 group (1.25, 2.5, and 5 mg/kg), and LPS+654-2 group (1.25, 2.5, and 5 mg/kg). The hemodynamics, echocardiography, immunohistochemical analysis, TEM, TUNEL assay, and H&E staining were utilized to assess the septic shock model and myocardial function. Lactic acid, inflammatory markers (IL-1ß, IL-6, and TNF-α), endothelial injure markers (SDC-1, HS and TM) and myocardial injury markers (CK, c-TNT and NT-pro BNP) were assessed using ELISA or biochemical kits. Additionally, the mechanisms of 654-1/654-2 were analyzed using RNA-seq and bioinformatics, and validated using western blotting and RT-PCR. RESULTS: Administration of 654-1/654-2 significantly restored hemodynamics and improved myocardial and endothelial glycocalyx injury in septic shock rats. Furthermore, 654-1/654-2 dose-dependently reduced plasma levels of lactic acid, inflammatory cytokines, and markers of endothelial and myocardial injury. Analyses using RNA-seq, WB and RT-PCR techniques indicated that 654-1/654-2 could mitigate myocardial and endothelial injury by inhibiting the NF-κB and NLRP-3 pathways, and activating the PI3K-AKT pathway. CONCLUSIONS: These findings demonstrated that 654-1/654-2 could alleviate myocardial damage in septic shock rats. Specifically, 654-1 inhibited the NF-κB/NLRP-3 pathway, whereas 654-2 promoted the PI3K-AKT pathway and inhibited the NF-κB pathway, effectively mitigating the inflammatory response and cell apoptosis.
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Cardiomiopatias , Choque Séptico , Alcaloides de Solanáceas , Ratos , Animais , NF-kappa B/metabolismo , Choque Séptico/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Lipopolissacarídeos/farmacologia , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Ácido Láctico/farmacologiaRESUMO
Non-communicable diseases (NCDs), including cardiovascular diseases, cancer, metabolic diseases, and skeletal diseases, pose significant challenges to public health worldwide. The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage. Nuclear factor erythroid 2-related factor 2 (Nrf2), a critical transcription factor, plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury. Therefore, Nrf2-targeting therapies hold promise for preventing and treating NCDs. Quercetin (Que) is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties. It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation. Que modulates mitochondrial function, apoptosis, autophagy, and cell damage biomarkers to regulate oxidative stress and inflammation, highlighting its efficacy as a therapeutic agent against NCDs. Here, we discussed, for the first time, the close association between NCD pathogenesis and the Nrf2 signaling pathway, involved in neurodegenerative diseases (NDDs), cardiovascular disease, cancers, organ damage, and bone damage. Furthermore, we reviewed the availability, pharmacokinetics, pharmaceutics, and therapeutic applications of Que in treating NCDs. In addition, we focused on the challenges and prospects for its clinical use. Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.
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STUDY OBJECTIVES: This study assessed the current state of sleep medicine accreditation and training in Asia by conducting a comprehensive survey across 29 Asian countries and regions facilitated by the Asian Society of Sleep Medicine (ASSM) to identify existing gaps and provide recommendations for future enhancements. METHODS: The ASSM Education Task Force Committee designed a survey to gather data on accreditation, education, and training standards in sleep medicine, including information on challenges in enhancing education in the field. RESULTS: With an 86% (25 countries/regions) response rate, the survey showed that sleep medicine is recognized as an independent specialty in just nine countries/regions (36% of the countries/regions surveyed). Ten countries/regions have established sleep medicine training programs, with Japan and Saudi Arabia offering it as a distinct specialty. Significant disparities in training and accreditation standards were identified, with many countries/regions lacking formalized training and practice guidelines. The survey also revealed that most local sleep societies across Asia support the development of an Asian Sleep Medicine Training Curriculum led by the ASSM. However, several barriers significantly impede the establishment and development of sleep medicine training programs, including the scarcity of trained specialists and technologists and the absence of national accreditation for sleep medicine. CONCLUSIONS: The survey highlights the need for standardized sleep medicine training and accreditation across Asia. Developing an Asian Sleep Medicine Training Curriculum and promoting ASSM accreditation guidelines are key recommendations. Implementing these strategies is essential for advancing sleep medicine as a widely recognized discipline throughout Asia.
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STUDY OBJECTIVES: To systemically describe the clinical features, polysomnography (PSG) finding, laboratory tests and single-nucleotide polymorphisms (SNPs) in a clinic based Chinese primary restless legs syndrome (RLS) population. METHODS: This observational study, conducted from January 2020 to October 2021 across 22 sleep labs in China, recruited 771 patients diagnosed with RLS following the 2014 RLSSG criteria. Clinical data, PSG testing, and laboratory examination and SNPs of patients with RLS were collected. A total of 32 SNPs in 24 loci were replicated using the Asian Screening Array chip, employing data from the Han Chinese Genomes Initiative as controls. RESULTS: In this study with 771 RLS patients, 645 had primary RLS, and 617 has DNA available for SNP study. Among the 645 primary RLS, 59.7% were women. 33% had a family history of RLS, with stronger familial influence in early-onset cases. Clinical evaluations showed 10.4% had discomfort in body parts other than legs. PSG showed that 57.1% of RLS patients had periodic leg movement index (PLMI) of >5/h and 39.1% had PLMI >15/h, respectively; 73.8% of RLS patients had an Apnea-Hypopnea Index (AHI) > 5/h, and 45.3% had an AHI >15/h. The laboratory examinations revealed serum ferritin levels <75 ng/ml in 31.6%, and transferrin saturation (TSAT) of <45% in 88.7% of RLS patients. Seven new SNPs in 5 genes showed a significant allelic association with Chinese primary RLS, with one previously reported (BTBD9) and four new findings (TOX3, PRMT6, DCDC2C, NOS1). CONCLUSIONS: Chinese RLS patients has specific characters in many aspects. A high family history with RLS not only indicates strong genetic influence, but also reminds us to consider the familial effect in the epidemiological study. Newly developed sequencing technique with large samples remains to be done.
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Síndrome das Pernas Inquietas , Humanos , Feminino , Masculino , Polissonografia , Síndrome das Pernas Inquietas/epidemiologia , Sono , Perna (Membro) , China , Proteínas Nucleares , Proteína-Arginina N-MetiltransferasesRESUMO
OBJECTIVE: To investigate the impact of hip fracture on coagulation function in elderly patients. METHODS: In our study, 127 elderly patients with hip fracture were diagnosed and admitted to Peking University People's Hospital from January 2011 to March 2012. Specimens of their venous blood were obtained before and after the surgery, and measured for fibrinogen (FIB) and D-dimer. Also, we analyzed their age, type of fracture, fracture time, and concomitant diseases. RESULTS: The FIB level of the patients (127 cases) before surgery was (3.91 ± 1.06) g/L, and 42.52% (54/127) patients' FIB was higher than normal. After the surgery, 28 patients underwent FIB test [(4.21 ± 1.24) g/L], which was higher than the FIB value before surgery, but was not statistically significant. Before surgery, 15 patients underwent D-dimer test [(2 059.5 ± 1 948.0) µg/L]. After the surgery, 26 patients underwent D-dimer test [(2 574.9 ± 1 702.4) µg/L].The two values were significantly higher than normal (P<0.05). The elevated value of FIB had no relationship with age, diabetes, cardiovascular or cerebrovascular diseases. Before surgery, 45.83% (22/48) of the intertrochanteric fracture patients had abnormal FIB, and 40.50% (32/79) of the patients with femoral neck fracture had abnormal FIB, but they were not statistically significant. Grouped according to the fracture time, when fracture time was longer than 96 h, the ratio of abnormal FIB was 26.7%, lower than those of other groups, and the difference was statistically significant (P<0.05). CONCLUSION: The hip fracture in elderly patients has a direct impact on coagulation system, and FIB and D-dimer have significantly changed. According to the variation of FIB after fracture,we speculate that fracture surgery after 96 h may affect the coagulation system at the lowest level.
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Coagulação Sanguínea , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Fraturas do Quadril/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Colo Femoral/sangue , Fraturas do Colo Femoral/cirurgia , Fraturas do Quadril/cirurgia , Humanos , Masculino , Estudos RetrospectivosRESUMO
Introduction: Pfeiffer syndrome is a rare genetic disorder characterized by craniosynostosis, broad thumbs and big toes, and partial syndactyly of the hands and feet. This case report presents the case of a girl diagnosed with type 2 Pfeiffer syndrome who experienced severe obstructive sleep apnea (OSA). Case report: The patient had been using an oropharyngeal airway since the age of 4 months due to snoring and witnessed apnea during sleep. At 11 months old, she was referred to our sleep clinic because of growth limitation and gross motor ability issues. Polysomnography (PSG) showed severe obstructive hypopnea before any treatment, and revealed severe central sleep apnea with the oropharyngeal airway in place. Positive airway pressure (PAP) therapy was initiated, which improved both her sleep and gross motor ability. Conclusion: This case report emphasizes the importance of thorough sleep studies for diagnosing sleep and breathing disorders in Pfeiffer syndrome patients and highlights the effectiveness of PAP therapy in managing these conditions.
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This study was aimed to investigate the therapeutic effect and mechanism of AKHO on 5-fluorouracil (5-FU)-induced intestinal mucositis in mice. Mouse body weight, diarrhea score, and H&E staining were applied to judge the therapeutic effect of AKHO. 16S rDNA and nontargeted metabolomics have been used to study the mechanism. WB, ELISA, and immunohistochemistry were adopted to validate possible mechanisms. The results demonstrated that AKHO significantly reduced diarrhea scores and intestinal damage induced by 5-FU in mice. AKHO lowered the serum levels of LD and DAO, and upregulated the expressions of ZO-1 and occludin in the ileum. Also, AKHO upregulated the abundance of Lactobacillus in the gut and suppressed KEGG pathways such as cortisol synthesis and secretion and arachidonic acid metabolism. Further validation studies indicated that AKHO downregulated the expressions of prostaglandin E2 (PGE2), microsomal prostaglandin E synthase-1 (mPGES-1), and PGE2 receptor EP4, as well as upregulated the expression of glucocorticoid (GC) receptor (GR), leading to improved intestinal epithelial barrier function. Taken together, AKHO elicited protective effects against 5-FU-induced mucositis by regulating the expressions of tight junction proteins via modulation of GC/GR and mPGES-1/PGE2/EP4 pathway, providing novel insights into the utilization and development of this pharmaceutical/food resource.
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Alpinia , Microbioma Gastrointestinal , Mucosite , Óleos Voláteis , Camundongos , Animais , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Dinoprostona , Prostaglandina-E Sintases/genética , Prostaglandina-E Sintases/metabolismo , Óleos Voláteis/farmacologia , Fluoruracila/efeitos adversos , DiarreiaRESUMO
STUDY OBJECTIVES: To determine if a home sleep apnea test (HSAT) using a type III portable monitor (PM), Nox-T3 (Nox Medical, Inc., Reykjavik, Iceland), detects obstructive sleep apnea in pregnant women. METHODS: Ninety-two pregnant women (34.5 ± 4.3 years; gestational age 25.4 ± 8.9 weeks; body mass index 29.9 ± 4.7 kg/m2) with suspected obstructive sleep apnea underwent HSAT with the Nox-T3 PM followed by overnight polysomnography (PSG) and PM recording simultaneously in the laboratory within 1 week. PMs were scored automatically and manually using a 3% criteria and compared with PSGs scored by following guidelines. RESULTS: Apnea-hypopnea indexes were 8.56 ± 10.42, 8.19 ± 13.79, and 8.71 ± 14.19 events/h on HSAT, in-laboratory PM recording, and PSG (P = .955), respectively. Bland-Altman analysis of the apnea-hypopnea index on PSG vs HSAT showed a mean difference (95% confidence interval) of -0.15 (-1.83, 1.53); limits of agreement (± 2 SD) were -16.26 to 16.56 events/h. Based on a threshold apnea-hypopnea index ≥ 5 events/h, HSAT had 91% sensitivity, 85% specificity, 84% positive-predictive value, and 92% negative-predictive value compared with PSG. When comparing the simultaneous recordings, closer agreement was observed. Automated vs manual analysis of PM showed no significant difference. CONCLUSIONS: A type III PM had an acceptable failure rate and high diagnostic performance operating as a reasonable alternative for in-laboratory PSG in pregnant women. CITATION: Wang J, Zhang C, Xu L, et al. Home monitoring for clinically suspected obstructive sleep apnea in pregnancy. J Clin Sleep Med. 2023;19(11):1951-1960.
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Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Gravidez , Humanos , Feminino , Lactente , Monitorização Ambulatorial , Apneia Obstrutiva do Sono/diagnóstico , Síndromes da Apneia do Sono/diagnóstico , Sono , PolissonografiaRESUMO
Rationale: Craniofacial and pharyngeal morphology influences risk for obstructive sleep apnea (OSA). Quantitative photography provides phenotypic information about these anatomical factors and is feasible in large samples. However, whether associations between morphology and OSA severity differ among populations is unknown. Objectives: The aim of this study was to examine this question in a large sample encompassing people from different ancestral backgrounds. Methods: Participants in SAGIC (Sleep Apnea Global Interdisciplinary Consortium) with genotyping data were included (N = 2,393). Associations between photography-based measures and OSA severity were assessed using linear regression, controlling for age, sex, body mass index, and genetic ancestry. Subgroups (on the basis of 1000 Genomes reference populations) were identified: European (EUR), East Asian, American, South Asian, and African (AFR). Interaction tests were used to assess if genetically determined ancestry group modified these relationships. Results: Cluster analysis of genetic ancestry proportions identified four ancestrally defined groups: East Asia (48.3%), EUR (33.6%), admixed (11.7%; 46% EUR, 27% Americas, and 22% AFR), and AFR (6.4%). Multiple anatomical traits were associated with more severe OSA independent of ancestry, including larger cervicomental angle (standardized ß [95% confidence interval (CI)] = 0.11 [0.06-0.16]; P < 0.001), mandibular width (standardized ß [95% CI] = 0.15 [0.10-0.20]; P < 0.001), and tongue thickness (standardized ß [95% CI] = 0.06 [0.02-0.10]; P = 0.001) and smaller airway width (standardized ß [95% CI] = -0.08 [-0.15 to -0.002]; P = 0.043). Other traits, including maxillary and mandibular depth angles and lower face height, demonstrated different associations with OSA severity on the basis of ancestrally defined subgroups. Conclusions: We confirm that multiple facial and intraoral photographic measurements are associated with OSA severity independent of ancestral background, whereas others differ in their associations among the ancestrally defined subgroups.
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Face , Apneia Obstrutiva do Sono , Humanos , Cefalometria , Face/anatomia & histologia , Apneia Obstrutiva do Sono/genética , Índice de Massa Corporal , FaringeRESUMO
In this study, we aim to identify the distinct subtypes of continuous positive airway pressure (CPAP) user profiles based on the telemedicine management platform and to determine clinical and psychological predictors of various patterns of adherence. A total of 301 patients used auto-CPAP (Autoset 10, Resmed Inc.) during the treatment period. Four categories of potential predictors for CPAP adherence were examined: (1) demographic and clinical characteristics, (2) disease severity and comorbidities, (3) sleep-related health issues, and (4) psychological evaluation. Then, growth mixture modeling was conducted using Mplus 8.0 to identify the unique trajectories of adherence over time. Adherence data were collected from the telemedicine management platform (Airview, Resmed Inc.) during the treatment. Three novel subgroups were identified and labeled "adherers" (53.8% of samples, intercept = 385, slope = -51, high mean value, negative slope and moderate decline), "Improvers" (18.6%, intercept = 256, slope = 50, moderate mean value, positive slope and moderate growth) and "non-adherers" (27.6%, intercept = 176, slope = -31, low mean value, negative slope and slight decline). The comorbidities associated with OSA and the apnea-hypopnea index (AHI), which reflects the objective severity of the disease, did not differ significantly among the subgroups. However, "improvers" showed higher levels of daytime sleepiness (8.1 ± 6.0 vs. 12.1 ± 7.0 vs. 8.0 ± 6.1 in SWIFT, p = 0.01), reduced daytime function (4.6 ± 1.6 vs. 3.8 ± 1.6 vs. 4.2 ± 1.8 in QSQ daytime symptoms, p = 0.02), and characteristics of positive coping style (1.8 ± 0.5 vs. 1.9 ± 0.5 vs. 1.7 ± 0.5 in SCSQ positive coping index, p = 0.02). Negative emotion was more pronounced in patients with "non-adherers" (12.9 ± 3.8 vs. 13.7 ± 3.3 vs. 14.6 ± 3.5, p = 0.02 in the HADS depression dimension; 9.0 ± 6.1 vs. 9.8 ± 5.1 vs. 11.5 ± 6.3, p = 0.01 with Negative Affectivity in DS14, and 9.3 ± 6.1 vs. 10.3 ± 5.1 vs. 11.7 ± 6.5, p = 0.01 with Social Inhibition in DS14). Overall, our study demonstrated that CPAP therapy may present distinct trajectories of adherence over time in addition to the traditional binary classification. Self-reported sleep health issues (diurnal sleepiness and daytime dysfunction) as well as psychological characteristics (negative emotions and coping style) were predictors of different adherence subtypes in patients with OSA. Understanding CPAP use profiles and their predictors enable the identification of those who may require additional intervention to improve adherence and further enhance the therapeutic effect in OSA patients.
RESUMO
OBJECTIVE: To investigate the prevalence of core attention-deficit/hyperactivity disorder (ADHD) symptoms in Chinese narcolepsy type 1 (NT1) patients and to explore mood, quality of life, and executive function in narcolepsy patients with or without ADHD and the response to Methylphenidate Hydrochloride Extended-release tablets (ER-MPH) treatment. METHOD: A total of 267 pediatric NT1 patients (194 males and 73 females, 5-17 years old) were evaluated for ADHD symptoms by a psychiatrist using the DSM-IV diagnostic criteria of the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI Kid) from February 2011 to July 2013 at Peking University People's Hospital. All patients underwent Stanford Sleep Inventory (SSI) evaluation and polysomnography followed by multiple sleep latency tests (MSLT) before ER-MPH treatment. Neuropsychological evaluations, including the Inventory of Subjective Life Quality (ISLQ), Depression Self-resting Scale for Children (DSRS-C), Screening for Child Anxiety-related Emotional Disorders (SCARED) and Barratt Impulsiveness Scale (BIS), were performed before and after 16 weeks of ER-MPH treatment. Executive abilities were assessed by the Behavior Rating Inventory of Executive Function-parent version (BRIEF-P). The narcolepsy symptoms, evaluated by the Pediatric Sleep Questionnaire (PSQ), and ADHD symptoms were assessed before and after treatment in NT1 patients with ADHD. RESULT: Seventy-seven of 267 (28.8%) NT1 patients had ADHD symptoms, with 73 patients being inattentive type (ADHD-I) and 4 patients being combined type (ADHD-C). Despite similar objective sleep parameters, NT1 patients with ADHD symptoms experienced higher anxiety levels, more impulsive behaviors, lower health-related quality of life and worse executive functions than those without ADHD (p<0.05). Methylphenidate treatment was effective in improving daytime sleepiness in NT1 patients with ADHD (PSQ, 16.7 ± 2.1 vs 13.5 ± 1.9, p<0.05) but was ineffective on ADHD symptoms (ADHD-RS, 25.3 ± 9.1 vs 26.4 ± 8.9, p>0.05). CONCLUSION: A high prevalence of ADHD (28.8%) was identified in children and adolescents with NT1. Comorbid ADHD symptoms were associated with increased levels of mood disorders and lower quality of life. ER-MPH treatment could reduce daytime sleepiness but not ADHD symptoms in narcolepsy patients with ADHD, suggesting that new treatment strategies are needed for this group of patients.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Narcolepsia , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Pré-Escolar , Função Executiva , Feminino , Humanos , Masculino , Metilfenidato/uso terapêutico , Narcolepsia/complicações , Narcolepsia/tratamento farmacológico , Narcolepsia/epidemiologia , Qualidade de VidaRESUMO
STUDY OBJECTIVES: We assessed the yearly seasonal, environmental effects on birth pattern in Chinese patients later diagnosed with narcolepsy and cataplexy and explored if this effect persisted in patients with symptoms onset date before, following, and after the 2009 H1N1 pandemic. METHODS: A total of 1,942 patients with birth data information and diagnosed narcolepsy with cataplexy were included in this study. The birth month and seasonal effect of 1,064 patients born from 1970 to 2000 were compared to controls (n = 2,028,714) from the general population. Furthermore, birth season effect in 1,373 patients with definite disease onset month were compared among patients with onset date before (n = 595), following (from January 2010 to December 2010) (n = 325), and after (n = 453) the H1N1 pandemic. RESULTS: Patients with narcolepsy and cataplexy had a significantly different seasonality from the general population (P = .027). The monthly distribution of birth month yielded a peak in November (odds ratio = 1.23 [95% confidence interval, 1.01-1.49], P = .042) and a trough in April (odds ratio = 0.68 [95% confidence interval, 0.52-0.88], P = .004). No significant difference was observed in the birth month across patients with symptom onset dates before, following, and after the 2009 H1N1 pandemic (P = .603). CONCLUSIONS: This finding across many years of seasonal effect in Chinese narcolepsy cataplexy supports a role for early-life environmental influences on disease development. CITATION: Guo J, Xu L, Wang J, et al. The month of birth has a seasonal effect in Chinese patients with narcolepsy and cataplexy. J Clin Sleep Med. 2022;18(2):461-467.