Background/objectives: Patients with obstructive sleep apnea (OSA) have an increased the risk of developing atrial fibrillation (AF). However, it remains unclear if patients with OSA carry a higher risk of recurrent AF after successful catheter ablation. This meta-analysis was conducted (1) to evaluate the association between OSA and recurrent AF after catheter ablation, and (2) to assess the effect of continuous positive airway pressure (CPAP) on the risk of recurrent AF in patients with OSA. Methods: A comprehensive literature review was conducted using MEDLINE, EMBASE, Cochrane databases from inception through July 2017 to identify studies that evaluated the risk of recurrent AF after successful catheter ablation in patients with OSA were included. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. Results: Seven observational studies with a total of 4572 patients AF after successful catheter ablation were enrolled. Compared to patients without OSA, the pooled OR of recurrent AF in patients with OSA was 1.70 (95% CI, 1.40-2.06, I2 = 0). Among OSA patients with AF after successful catheter ablation, the use of CPAP was significantly associated with decreased risk of recurrent AF with pooled OR of 0.28 (0.19-0.40, I2= 0). Egger's regression asymmetry test was performed and showed no publication bias for the associations of OSA and CPAP with recurrent AF. Conclusions: Our meta-analysis suggested a significant association between OSA and recurrent AF after catheter ablation. The use of CPAP in patients with OSA is associated with reduced risk of recurrent AF after catheter ablation.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19400号 / 医博第4051号 / 新制||医||1012(附属図書館) / 32425 / 京都大学大学院医学研究科医学専攻 / (主査)教授 横出 正之, 教授 福原 俊一, 教授 山下 潤 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20261号 / 医博第4220号 / 新制||医||1020(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 福田 和彦, 教授 木村 剛, 教授 大森 孝一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(人間健康科学) / 甲第23574号 / 人健博第94号 / 新制||人健||7(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 任 和子, 教授 木下 彩栄, 教授 平井 豊博 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

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Knowledge about biomechanical properties of veins is of importance for understanding the physiologyof the venous system. Specifically for this thesis there is a motivation based on an idea of how to usebiomechanics of the vein in the development of new non-invasive measurement techniques for assessingthe pressure in the brain. The cross sectional area of veins is known to depend on pressure changes insidethe vessel. There are many ways of provoking these pressure changes, like changing posture or creating apositive airway pressure. The hypothesis is that the positive airway pressure will increase the intrathoracic pressure and in turnincrease the pressure in the internal jugular veins by the same magnitude. The cross sectional area will from a pressure change subsequently change with respect to the biomechanical properties of the vessel walls. A first aim in this study was to determine how the cross sectional area of the internal jugular veins is altered due to changes in airway pressure. A second aim was to develop and evaluate a model where the biomechanical properties of the internal jugular veins is described, based on the relationship between pressure and area of the vein. Ultrasound measurements were performed on one healthy adult man to study the effect on the cross sectional area at different pressure provocations. Measurements on the subject was performed at four different head up tilt angles, causing a pressure decrease in the internal jugular vein. A controlled Valsalva method was performed to give the positive airway pressure giving corresponding pressure increases. With an increased airway pressure the effect on cross sectional area changes was about 23% of the effect dueto hydrostatic pressure changes, at a tilt angle from 0° to 8°. At a tilt angle from 8° to 16° the effect was about 35%. Thus the venous pressure seems to be increased due to an increased airway pressure, but not tothe same magnitude. The theoretical model was developed and subsequently evaluated using existing head down tilt magneticresonance imaging data on nine healthy volunteers. An expression for how radius of the vessel depends on pressure changes was derived and evaluated. This expression included individual biomechanical properties that were estimated on group level for the nine subjects. The resulting equation could beused to give an approximate prediction of the increase in radius to a change in venous pressure. In conclusion, the hypothesis suggesting that a positive airway pressure would give an equally increased venous pressure could not be confirmed, and this knowledge should be considered when trying to assess thepressure in the brain with this technique. The derived biomechanical model was promising for predictionof cross sectional area with respect to a change in venous pressure. / Att ha kännedom om biomekaniska egenskaper hos vener är viktigt för att kunna förstå fysiologin hos vensystemet. I den här rapporten finns det i synnerhet ett intresse av detta baserat på en idé för hur veners biomekanik kan användas för att utveckla en ny icke-invasiv mätteknik för att uppskatta trycket i hjärnan. Det är känt att tvärsnittsnittarean av vener beror på tryckförändringar inne i kärlet. Att provocera fram dessatryckförändringar går att göra på många sätt, till exempel genom en förändrad kroppsposition eller genomatt sätta ett positivt tryck på luftvägarna. Hypotesen är att ett positivt luftvägstryck kommer att höja det intratorakala trycket, vilket i sin turkommer att höja trycket inne i de interna jugularvenerna lika mycket. Tvärsnittsarean kommer därmed att ändras enligt biomekaniska egenkaper hos kärlväggen. Ett första syftet i det här arbetet var att bestämma hur tvärsnittsarean av de internal jugularvenerna varierar enligt förändringar i luftvägstryck. Det andra syftet var att utveckla en modell som beskriver de biomekaniska egenskaperna hos de interna jugularvenerna. Detta baserat på relationen mellan tryck och area hos venen. För att studera effekten på tvärsnittsarea för olika tryckprovokationer, genomfördes ultraljudsmätningar på en frisk och vuxen man. Mätningarna på subjektet genomfördes med överkroppen positionerad i fyra olika positiva vinklar relativt horisontalplanet, vilket leder till ett minskat tryck i jugularvenerna. En kontrollerad Valsalvametod användes för att skapa det positiva luftvägstrycket som då ska ge en motsvarande tryckökning. Vid en tiltvinkel på 8° var effekten på areaförändringarna som en följd av ökat luftvägstryck ca 23% av effekten som en följd av de hydrostatiska tryckförändringarna. Vid en tiltvinkel på 16° var effekten ca 35%. Det verkar som att ventrycket ökar med ökat luftvägstryck, men inte med samma storleksordning som det pålagda trycket. Den teoretiska modellen utvecklades och utvärderades sedemera med hjälp av befintligt MRI-data för nio friska och frivilliga subjekt, där överkropparna var positionerade i nedåt tilt. Modellen bestod av ettuttryck för hur radien av ett kärl beror på tryckförändringar inne i det. Modellen innehåller individspecifika egenskaper men utvärderingen gjordes på gruppnivå för de nio subjekten. Det resulterande uttrycket kunde användas för att ge en approximativ förutsägelse om hur radie förändras till följd av en variation i ventryck. Som slutsats så kunde hypotesen som föreslog att ett positivt luftvägstryck skulle ge en lika stor ökning av ventryck inte bekräftas. Om denna teknik ska användas för att försöka bestämma trycket i hjärna så måste hänsyn tas till dessa resultat. Den utvecklade biomekaniska modellen verkar lovande för att kunna förutsäga tvärsnittsarea utifrån ventrycksförändringar.

Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is characterised by repeated cycles of upper airway obstruction during sleep, leading to diurnal symptoms. Individuals with Down syndrome (DS) are predisposed to this as the DS phenotype overlaps with OSAHS risk factors. Around 2-4% of the general adult population and 55% of children with DS have OSAHS but, to date, no large-scale study has assessed OSAHS prevalence or efficacy of treatment in DS adults. This study aimed to: 1) Systematically assess subjective and objective OSAHS prevalence; 2) Assess the effectiveness of continuous positive airway pressure (CPAP) in an adult DS population. Standard questionnaires including pictorial Epworth Sleepiness Scale (pESS) and Developmental Behaviour Checklist for Adults (DBC-A) were sent to UK adults aged ≥16yr with DS and their caregivers. All questionnaire responders were invited to undergo home polygraphy. Symptomatic adults with DS with ≥10 apnoeas/hypopnoeas per hour in bed (AH) on home polygraphy were invited to participate in a prospective randomised controlled trial (RCT) of CPAP v. lifestyle advice, with review at 1, 3, 6 and 12m. Participants in the lifestyle arm were offered CPAP at 1m. Standard measurements of sleepiness, behaviour, cognitive function and general health were undertaken. Standard statistical analyses were conducted, with significance set at p < 0.001 to control for multiple testing. Of 5270 questionnaires sent, 1105 responses were valid (21%). Responders (55% males) were overweight/obese young adults: mean BMI 29.0±6.8kg/m2; mean age 28±9 years. Women had a higher BMI (p < 0.0001), but collar size was greater in men (p < 0.0001). Mean pESS scores were broadly within the normal range (7±5/24). No significant gender differences in OSAHS symptoms were noted. Individuals with probable OSAHS had higher pESS and DBC-A scores, and significantly more symptoms of OSAHS. Subjective OSAHS prevalence was estimated at 35%. Of the 790 individuals invited, 149 underwent polygraphy, with 134 valid studies obtained: mean AH 21.8(10.9-42.7); mean oximetry desaturation index (ODI) 6.6(2.3-20.0). No significant gender differences were observed. Forty-two percent of participants met standard clinical diagnostic criteria for OSAHS. Twenty-eight eligible adults with DS (19 male) were randomised: age 28±9yr; BMI 31.5±7.9kg/m2; AH 28.6(14.8-47.9); ODI 7.3(1.8-21.9); pESS 11±6/24. Groups did not differ significantly at baseline. By 12m, 4 participants had withdrawn (all remaining participants on CPAP). The pESS (p=0.001), DBC-A Disruptive (p < 0.0001) and Kaufmann Brief Intelligence Test verbal subscale (p=0.001) scores improved significantly. This first large study of OSAHS prevalence in the adult DS population estimates a prevalence of 35-42% - around 10 times higher than in the general adult population. Sustained, significant improvements in sleepiness, cognitive function and behavioural/emotional outcomes with CPAP use over a 12m period were demonstrated during this first RCT of CPAP in adults with DS. A larger trial of CPAP in this population is warranted.

A pressão positiva contínua nas vias aéreas(CPAP) é a forma mais simples de ventilação não invasiva. O objetivo deste estudo é comparar o desempenho de dois modelos de gerador de fluxo com um ventilador projetado especificamente para ventilação não invasiva no modo CPAP, através de um modelo mecânico de pulmão e em voluntários sadios, em três diferentes alimentações de pressão e em CPAP de 5, 10 e 15 cm H2O. Conclui-se que os geradores de fluxo têm capacidade similar ao ventilador específico para manter o nível de CPAP, se ajustados para sua melhor pressão de alimentação, que foi ao redor de 100 L/min / Continuous positive airway pressure (CPAP) is the simplest form of noninvasive ventilation. Mechanical ventilators designed to invasive ventilation, ventilators specifically designed to noninvasive ventilation (NIV-Ventilator) and continuous flow generators can provide CPAP. The objectives of this study is compare the performance of two continuous flow generators with a ventilator designed to NIV to deliver continuous positive airway pressure (CPAP) and compare flow generators using different oxygen pressure supplies in lung model and healthy subjects, in CPAP of 5, 10 and 15 cm H2O. It was observed that flow generators had similar performance to noninvasive ventilator if they were adjust in their best output flow, that was around 100 L/min

Introduction: Obstructive sleep apnoea (OSA) is common and is caused by repetitive obstruction of the upper airway during sleep. OSA is associated with increased cardiovascular morbidity and mortality and is an independent risk factor for hypertension. The immediate physiological effects of OSA include intermittent hypoxia, repeated arousal from sleep and intra-thoracic pressure swings. The resulting activation of the sympathetic nervous system, systemic inflammation and oxidative stress may result in increased arterial stiffness and endothelial dysfunction, potentially explaining any causal link between OSA and cardiovascular disease (CVD). Continuous positive airway pressure (CPAP) therapy improves excessive daytime sleepiness (EDS) and in non-randomised studies, reduces cardiovascular mortality. Prior to starting this study, there was a limited amount of evidence suggesting that CPAP therapy improved arterial stiffness and endothelial function, but the effects in subjects without pre-existing CVD were unclear. Aims: i) to determine whether CPAP therapy has an effect upon measures of arterial stiffness and endothelial function in patients with OSA, in the absence of known CVD. ii) To compare arterial stiffness and endothelial function in a subset of patients with OSAHS (defined as OSA and EDS), with a group of well-matched control subjects. Methods: Fifty three patients with OSA, defined as an apnoea/hypopnoea index of ≥15, and without known CVD, entered a double-blind placebo-controlled crossover trial of 12 weeks CPAP therapy, of whom forty three completed the study protocol. Sham CPAP was used in the placebo arm of the study and vascular assessments were made at baseline and after each arm of the study. Arterial stiffness was determined by measuring aortic distensibility using cardiovascular magnetic resonance imaging and by measuring the augmentation index (AIx) and aortic pulse wave velocity (PWV) by applanation tonometry. Endothelial function was assessed non-invasively by measuring vascular reactivity after administration of salbutamol and glyceryl trinitrate. In a subset of twenty patients with OSAHS, arterial stiffness and endothelial function at baseline were compared to readings obtained from healthy control subjects, matched on a one-to-one basis for age, sex and BMI. Results: Patients with OSAHS (n=20) had increased arterial stiffness [AIx 19.3(10.9) vs. 12.6(10.2) %; p=0.017] and impaired endothelial function, measured as the change in AIx following salbutamol [-4.3(3.2) vs. -8.0(4.9) %; p=0.02] compared to controls. Twelve weeks of CPAP therapy had no significant effect upon any measure of arterial stiffness or endothelial function in patients with OSA (n=43). A trend towards a reduction in AIx following CPAP therapy was seen, but this was non-significant. There was a reduction in systolic blood pressure following CPAP therapy [126(12) vs. 129(14) mmHg]. Sub group analysis showed CPAP to have no effect on arterial stiffness or endothelial function in patients with EDS or in patients using CPAP for ≥4 hours per night. Conclusions: This study demonstrates that even in the absence of known CVD, patients with OSAHS have evidence of increased arterial stiffness and impaired endothelial function. However, in patients with OSA, free from CVD, CPAP therapy did not lead to an improvement in any measure of arterial stiffness or endothelial function after 12 weeks.

Objetivos: Determinar o tempo de espera para o diagnóstico e início do tratamento da síndrome da apneia obstrutiva do sono (SAOS) em hospital público brasileiro. Desenho do estudo: Estudo transversal. Métodos: Foi avaliada, com um questionário específico, uma amostra de conveniência composta por 68 pacientes com síndrome da apneia obstrutiva do sono (SAOS), com indicação de tratamento com pressão positiva em vias aéreas (PAP) e que utilizaram o aparelho durante acompanhamento ambulatorial, no período de janeiro de 2005 a dezembro de 2009. Foram excluídos os pacientes menores de 18 anos, incapazes de responder ao questionário ou que se negaram a participar. Resultados: Dos pacientes avaliados, a maioria era de homens (62%), com média de idade de 54,4 (+ 10,7) anos e obesos (IMC médio 33,7 + 7,1 Kg/m2); 76% eram hipertensos, 22% portadores de diabete melito e igual número de doença arterial coronariana; 10% destes apresentavam hipoventilação associada. A mediana do tempo entre a primeira consulta médica e a realização da PSG diagnóstica foi de 8,3 (intervalos interquartis [IQ] 3,3-14,3) meses e a mediana do tempo da indicação da PAP até a aquisição do aparelho foi de 10,5 (IQ 3,1-16,7) meses. Sessenta e quatro pacientes (94%) eram usuários de CPAP e 4 usuários de bilevel (6%). A maioria dos aparelhos (57%) foi obtida de forma gratuita por meio da rede pública de saúde. Conclusão: O presente estudo evidenciou a demora excessiva para diagnóstico e tratamento dos pacientes portadores de SAOS em atendimento em um hospital público de referência no Brasil. / Objectives: To determine the waiting time for the diagnosis and beginning of treatment of syndrome of obstructive sleep apnea (OSA) in Brazilian public hospital. Study design: cross-sectional study Methods: A convenience sample composed of 68 patients with syndrome of obstructive sleep apnea (OSA) was assessed through a specific questionnaire. All patients were indicated a treatment with positive airway pressure (PAP) and that used the unit during de period between January 2005 and December 2009. Patients who were under 18 years old, who were uncapable of answering the questionnaire or who refused to answer were excluded. Results: Among the patients, the majority were men (62%), with an average age of 54.4 (+10.7) years and obese (mean BMI 33.7 + 7.1 kg/m2); 76% were hypertensive, 22% diabetes mellitus patients and an equal number with coronary artery disease, 10% of them had associated hypoventilation. The average time between the first medical consultation and the implementation of diagnostic PSG was 8.3 (interquartile range [IQ] 3.3 to 14.3) months and the average time indication of the PAP until the purchase of the equipment was 10,5 (CI 3.1 to 16.7) months. Sixty-four patients (94%) were users of CPAP and 4 were users of bilevel (6%). Most appliances (57%) were obtained free of charge through the public health system. Conclusion: The present study demonstrated the excessive delay to diagnosis and treatment of patients with OSAS in attendance at a public hospital of reference in Brazil.