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1.
Anesth Analg ; 136(4): 814-824, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36745563

RESUMO

This article addresses the issue of patient sleep during hospitalization, which the Society of Anesthesia and Sleep Medicine believes merits wider consideration by health authorities than it has received to date. Adequate sleep is fundamental to health and well-being, and insufficiencies in its duration, quality, or timing have adverse effects that are acutely evident. These include cardiovascular dysfunction, impaired ventilatory function, cognitive impairment, increased pain perception, psychomotor disturbance (including increased fall risk), psychological disturbance (including anxiety and depression), metabolic dysfunction (including increased insulin resistance and catabolic propensity), and immune dysfunction and proinflammatory effects (increasing infection risk and pain generation). All these changes negatively impact health status and are counterproductive to recovery from illness and operation. Hospitalization challenges sleep in a variety of ways. These challenges include environmental factors such as noise, bright light, and overnight awakenings for observations, interventions, and transfers; physiological factors such as pain, dyspnea, bowel or urinary dysfunction, or discomfort from therapeutic devices; psychological factors such as stress and anxiety; care-related factors including medications or medication withdrawal; and preexisting sleep disorders that may not be recognized or adequately managed. Many of these challenges appear readily addressable. The key to doing so is to give sleep greater priority, with attention directed at ensuring that patients' sleep needs are recognized and met, both within the hospital and beyond. Requirements include staff education, creation of protocols to enhance the prospect of sleep needs being addressed, and improvement in hospital design to mitigate environmental disturbances. Hospitals and health care providers have a duty to provide, to the greatest extent possible, appropriate preconditions for healing. Accumulating evidence suggests that these preconditions include adequate patient sleep duration and quality. The Society of Anesthesia and Sleep Medicine calls for systematic changes in the approach of hospital leadership and staff to this issue. Measures required include incorporation of optimization of patient sleep into the objectives of perioperative and general patient care guidelines. These steps should be complemented by further research into the impact of hospitalization on sleep, the effects of poor sleep on health outcomes after hospitalization, and assessment of interventions to improve it.


Assuntos
Anestesia , Pacientes , Humanos , Anestesia/efeitos adversos , Hospitalização , Dor , Sono/fisiologia
2.
Am J Respir Crit Care Med ; 206(10): 1271-1280, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-35822943

RESUMO

Rationale: Obstructive sleep apnea (OSA) is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. There is strong clinical and epidemiologic evidence supporting the importance of genetic factors influencing OSA but limited data implicating specific genes. Objectives: To search for rare variants contributing to OSA severity. Methods: Leveraging high-depth genomic sequencing data from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and imputed genotype data from multiple population-based studies, we performed linkage analysis in the CFS (Cleveland Family Study), followed by multistage gene-based association analyses in independent cohorts for apnea-hypopnea index (AHI) in a total of 7,708 individuals of European ancestry. Measurements and Main Results: Linkage analysis in the CFS identified a suggestive linkage peak on chromosome 7q31 (LOD = 2.31). Gene-based analysis identified 21 noncoding rare variants in CAV1 (Caveolin-1) associated with lower AHI after accounting for multiple comparisons (P = 7.4 × 10-8). These noncoding variants together significantly contributed to the linkage evidence (P < 10-3). Follow-up analysis revealed significant associations between these variants and increased CAV1 expression, and increased CAV1 expression in peripheral monocytes was associated with lower AHI (P = 0.024) and higher minimum overnight oxygen saturation (P = 0.007). Conclusions: Rare variants in CAV1, a membrane-scaffolding protein essential in multiple cellular and metabolic functions, are associated with higher CAV1 gene expression and lower OSA severity, suggesting a novel target for modulating OSA severity.


Assuntos
Apneia Obstrutiva do Sono , Humanos , Caveolina 1/genética , Apneia Obstrutiva do Sono/genética , Análise de Sequência de DNA , Sequenciamento de Nucleotídeos em Larga Escala
3.
Am J Hum Genet ; 105(5): 1057-1068, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31668705

RESUMO

Average arterial oxyhemoglobin saturation during sleep (AvSpO2S) is a clinically relevant measure of physiological stress associated with sleep-disordered breathing, and this measure predicts incident cardiovascular disease and mortality. Using high-depth whole-genome sequencing data from the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) project and focusing on genes with linkage evidence on chromosome 8p23,1,2 we observed that six coding and 51 noncoding variants in a gene that encodes the GTPase-activating protein (DLC1) are significantly associated with AvSpO2S and replicated in independent subjects. The combined DLC1 association evidence of discovery and replication cohorts reaches genome-wide significance in European Americans (p = 7.9 × 10-7). A risk score for these variants, built on an independent dataset, explains 0.97% of the AvSpO2S variation and contributes to the linkage evidence. The 51 noncoding variants are enriched in regulatory features in a human lung fibroblast cell line and contribute to DLC1 expression variation. Mendelian randomization analysis using these variants indicates a significant causal effect of DLC1 expression in fibroblasts on AvSpO2S. Multiple sources of information, including genetic variants, gene expression, and methylation, consistently suggest that DLC1 is a gene associated with AvSpO2S.


Assuntos
Cromossomos Humanos Par 8/genética , Proteínas Ativadoras de GTPase/genética , Oxiemoglobinas/genética , Sono/genética , Proteínas Supressoras de Tumor/genética , Ligação Genética/genética , Estudo de Associação Genômica Ampla , Humanos , Sequenciamento Completo do Genoma/métodos
4.
PLoS Genet ; 15(4): e1007739, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30990817

RESUMO

Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.


Assuntos
Hexoquinase/genética , Subunidade alfa de Receptor de Interleucina-18/genética , Oxiemoglobinas/metabolismo , Sono/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Moléculas de Adesão Celular Neuronais/genética , Biologia Computacional , Proteínas da Matriz Extracelular/genética , Feminino , Redes Reguladoras de Genes , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Hipóxia/sangue , Hipóxia/genética , Masculino , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas do Tecido Nervoso/genética , Oxigênio/sangue , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Proteína Reelina , Serina Endopeptidases/genética , Síndromes da Apneia do Sono/sangue , Síndromes da Apneia do Sono/genética , Adulto Jovem
5.
Anesth Analg ; 132(5): 1314-1320, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33857973

RESUMO

Adequate sleep is essential to health and well-being. Adverse effects of sleep loss are evident acutely and are cumulative in their effect. These include impairment of cognition, psychomotor function, and mood, as well as cardiovascular, metabolic, and immune dysfunction including proinflammatory effects and increased catabolic propensity. Such effects are counterproductive to recovery from illness and operation, yet hospitalization challenges sleep through the anxieties, discomforts, and sleep environmental challenges faced by patients, the inadequate attention given to the needs of patients with preexisting sleep disorders, and the lack of priority these issues receive from hospital staff and their leaders. Mitigation of the adverse effects of noise, light, uncomfortable bedding, intrusive observations, anxiety, and pain together with attention to specific sleep needs and monitoring of sleep quality are steps that would help address the issue and potentially improve patient outcomes.


Assuntos
Hospitalização , Transtornos do Sono-Vigília/complicações , Sono , Procedimentos Cirúrgicos Operatórios , Humanos , Pacientes Internados , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Recuperação de Função Fisiológica , Medição de Risco , Fatores de Risco , Transtornos do Sono-Vigília/fisiopatologia , Transtornos do Sono-Vigília/terapia , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Resultado do Tratamento
6.
BMC Public Health ; 21(1): 1539, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380465

RESUMO

BACKGROUND AND OBJECTIVE: Chronic medical conditions accumulate within individuals with age. However, knowledge concerning the trends, patterns and determinants of multimorbidity remains limited. This study assessed the prevalence and patterns of multimorbidity using extensive individual phenotyping in a general population of Australian middle-aged adults. METHODS: Participants (n = 5029, 55% female), born between 1946 and 1964 and attending the cross-sectional phase of the Busselton Healthy Ageing Study (BHAS) between 2010 and 2015, were studied. Prevalence of 21 chronic conditions was estimated using clinical measurement, validated instrument scores and/or self-reported doctor-diagnosis. Non-random patterns of multimorbidity were explored using observed/expected (O/E) prevalence ratios and latent class analysis (LCA). Variables associated with numbers of conditions and class of multimorbidity were investigated. RESULTS: The individual prevalence of 21 chronic conditions ranged from 2 to 54% and multimorbidity was common with 73% of the cohort having 2 or more chronic conditions. (mean ± SD 2.75 ± 1.84, median = 2.00, range 0-13). The prevalence of multimorbidity increased with age, obesity, physical inactivity, tobacco smoking and family history of asthma, diabetes, myocardial infarct or cancer. There were 13 pairs and 27 triplets of conditions identified with a prevalence > 1.5% and O/E > 1.5. Of the triplets, arthritis (> 50%), bowel disease (> 33%) and depression-anxiety (> 33%) were observed most commonly. LCA modelling identified 4 statistically and clinically distinct classes of multimorbidity labelled as: 1) "Healthy" (70%) with average of 1.95 conditions; 2) "Respiratory and Atopy" (11%, 3.65 conditions); 3) "Non-cardiometabolic" (14%, 4.77 conditions), and 4) "Cardiometabolic" (5%, 6.32 conditions). Predictors of multimorbidity class membership differed between classes and differed from predictors of number of co-occurring conditions. CONCLUSION: Multimorbidity is common among middle-aged adults from a general population. Some conditions associated with ageing such as arthritis, bowel disease and depression-anxiety co-occur in clinically distinct patterns and at higher prevalence than expected by chance. These findings may inform further studies into shared biological and environmental causes of co-occurring conditions of ageing. Recognition of distinct patterns of multimorbidity may aid in a holistic approach to care management in individuals presenting with multiple chronic conditions, while also guiding health resource allocation in ageing populations.


Assuntos
Envelhecimento Saudável , Multimorbidade , Adulto , Austrália/epidemiologia , Doença Crônica , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
7.
Eur Respir J ; 55(1)2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31601716

RESUMO

BACKGROUND AND AIM: Hypoglossal nerve stimulation (HNS) decreases obstructive sleep apnoea (OSA) severity via genioglossus muscle activation and decreased upper airway collapsibility. This study assessed the safety and effectiveness at 6 months post-implantation of a novel device delivering bilateral HNS via a small implanted electrode activated by a unit worn externally, to treat OSA: the Genio™ system. METHODS: This prospective, open-label, non-randomised, single-arm treatment study was conducted at eight centres in three countries (Australia, France and the UK). Primary outcomes were incidence of device-related serious adverse events and change in the apnoea-hypopnoea index (AHI). The secondary outcome was the change in the 4% oxygen desaturation index (ODI). Additional outcomes included measures of sleepiness, quality of life, snoring and device use. This trial was registered with ClinicalTrials.gov, number NCT03048604. RESULTS: 22 out of 27 implanted participants (63% male, aged 55.9±12.0 years, body mass index (BMI) 27.4±3.0 kg·m-2) completed the protocol. At 6 months BMI was unchanged (p=0.85); AHI decreased from 23.7±12.2 to 12.9±10.1 events·h-1, a mean change of 10.8 events·h-1 (p<0.001); and ODI decreased from 19.1±11.2 to 9.8±6.9 events·h-1, a mean change of 9.3 events·h-1 (p<0.001). Daytime sleepiness (Epworth Sleepiness Scale; p=0.01) and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire-10; p=0.02) both improved significantly. The number of bed partners reporting loud, very intense snoring, or leaving the bedroom due to participant snoring decreased from 96% to 35%. 91% of participants reported device use >5 days per week, and 77% reported use for >5 h per night. No device-related serious adverse events occurred during the 6-month post-implantation period. CONCLUSIONS: Bilateral HNS using the Genio™ system reduces OSA severity and improves quality of life without device-related complications. The results are comparable with previously published HNS systems despite minimal implanted components and a simple stimulation algorithm.


Assuntos
Nervo Hipoglosso , Apneia Obstrutiva do Sono , Adulto , Austrália , Feminino , França , Humanos , Masculino , Estudos Prospectivos , Qualidade de Vida , Apneia Obstrutiva do Sono/terapia , Resultado do Tratamento
8.
Anesth Analg ; 130(4): 1008-1017, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-30896596

RESUMO

BACKGROUND: The propensities for the upper airway to collapse during anesthesia and sleep are related, although much of our understanding of this relationship has been inferred from clinical observation and indirect measures such as the apnea-hypopnea index. The aim of this study was to use an identical, rigorous, direct measure of upper airway collapsibility (critical closing pressure of the upper airway) under both conditions to allow the magnitude of upper airway collapsibility in each state to be precisely compared. METHODS: Ten subjects (8 men and 2 women; mean ± SD: age, 40.4 ± 12.1 years; body mass index, 28.5 ± 4.0 kg/m) were studied. Critical closing pressure of the upper airway was measured in each subject on separate days during (1) propofol anesthesia and (2) sleep. RESULTS: Critical closing pressure of the upper airway measurements were obtained in all 10 subjects during nonrapid eye movement sleep and, in 4 of these 10 subjects, also during rapid eye movement sleep. Critical closing pressure of the upper airway during anesthesia was linearly related to critical closing pressure of the upper airway during nonrapid eye movement sleep (r = 0.64 [95% CI, 0.02-0.91]; n = 10; P = .046) with a similar tendency in rapid eye movement sleep (r = 0.80 [95% CI, -0.70 to 0.99]; n = 4; P = .200). However, critical closing pressure of the upper airway during anesthesia was systematically greater (indicating increased collapsibility) than during nonrapid eye movement sleep (2.1 ± 2.2 vs -2.0 ± 3.2 cm H2O, respectively, n = 10; within-subject mean difference, 4.1 cm H2O [95% CI, 2.32-5.87]; P < .001) with a similar tendency during rapid eye movement sleep (1.6 ± 2.4 vs -1.9 ± 4.3 cm H2O, respectively, n = 4; unadjusted difference, 3.5 cm H2O [95% CI, -0.95 to 7.96]; P = .087). CONCLUSIONS: These results demonstrate that the magnitude of upper airway collapsibility during anesthesia and sleep is directly related. However, the upper airway is systematically more collapsible during anesthesia than sleep, suggesting greater vulnerability to upper airway obstruction in the anesthetized state.


Assuntos
Manuseio das Vias Aéreas/métodos , Anestesia , Sistema Respiratório/efeitos dos fármacos , Sono/fisiologia , Adulto , Obstrução das Vias Respiratórias , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Sistema Respiratório/fisiopatologia , Sono REM/fisiologia
9.
Anesthesiology ; 131(5): 962-973, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31403974

RESUMO

BACKGROUND: Dexmedetomidine is a sedative promoted as having minimal impact on ventilatory drive or upper airway muscle activity. However, a trial recently demonstrated impaired ventilatory drive and induction of apneas in sedated volunteers. The present study measured upper airway collapsibility during dexmedetomidine sedation and related it to propofol. METHODS: Twelve volunteers (seven female) entered this nonblinded, randomized crossover study. Upper airway collapsibility (pharyngeal critical pressure) was measured during low and moderate infusion rates of propofol or dexmedetomidine. A bolus dose was followed by low (0.5 µg · kg · h or 42 µg · kg · min) and moderate (1.5 µg · kg · h or 83 µg · kg · min) rates of infusion of dexmedetomidine and propofol, respectively. RESULTS: Complete data sets were obtained from nine volunteers (median age [range], 46 [23 to 66] yr; body mass index, 25.4 [20.3 to 32.4] kg/m). The Bispectral Index score at time of pharyngeal critical pressure measurements was 74 ± 10 and 65 ± 13 (mean difference, 9; 95% CI, 3 to 16; P = 0.011) during low infusion rates versus 57 ± 16 and 39 ± 12 (mean difference, 18; 95% CI, 8 to 28; P = 0.003) during moderate infusion rates of dexmedetomidine and propofol, respectively. A difference in pharyngeal critical pressure during sedation with dexmedetomidine or propofol could not be shown at either the low or moderate infusion rate. Median (interquartile range) pharyngeal critical pressure was -2.0 (less than -15 to 2.3) and 0.9 (less than -15 to 1.5) cm H2O (mean difference, 0.9; 95% CI, -4.7 to 3.1) during low infusion rates (P = 0. 595) versus 0.3 (-9.2 to 1.4) and -0.6 (-7.7 to 1.3) cm H2O (mean difference, 0.0; 95% CI, -2.1 to 2.1; P = 0.980) during moderate infusion of dexmedetomidine and propofol, respectively. A strong linear relationship between pharyngeal critical pressure during dexmedetomidine and propofol sedation was evident at low (r = 0.82; P = 0.007) and moderate (r = 0.90; P < 0.001) infusion rates. CONCLUSIONS: These observations suggest that dexmedetomidine sedation does not inherently protect against upper airway obstruction.


Assuntos
Obstrução das Vias Respiratórias/diagnóstico , Dexmedetomidina/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Faringe/efeitos dos fármacos , Propofol/administração & dosagem , Adulto , Idoso , Obstrução das Vias Respiratórias/induzido quimicamente , Obstrução das Vias Respiratórias/fisiopatologia , Estudos Cross-Over , Dexmedetomidina/efeitos adversos , Feminino , Voluntários Saudáveis , Humanos , Hipnóticos e Sedativos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Faringe/fisiologia , Propofol/efeitos adversos , Adulto Jovem
10.
Lung ; 197(3): 315-319, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30982940

RESUMO

This multi-centred, randomised controlled trial explored the effects of adding ongoing feedback to a 12-month unsupervised maintenance walking program, on daily physical activity (PA) in people with chronic obstructive pulmonary disease. Participants were randomised to either an intervention group (IG) or a usual care group (UCG). During the maintenance program, the IG received ongoing feedback (telephone calls, biofeedback provided via pedometer and progressive goal setting) and the UCG received no feedback. The SenseWear® Pro3 Armband was used to measure PA. Of the 86 participants {IG = 42, (mean [SD]: age 70 [7] years; FEV1 43 [16] % predicted); UCG = 44, (age 69 [9] years; FEV1 44 [15] % predicted)} included at baseline, 43 had sufficient data to be included in the final analysis. There were no between-group differences in any of the PA variables from baseline to completion of the program (all p > 0.05). Ongoing feedback was no more effective than no feedback in improving PA during a 12-month unsupervised walking program.Trial Registration: The trial was registered in the Australia and New Zealand Clinical Trials Registry (ACTRN12609000472279).


Assuntos
Terapia por Exercício , Exercício Físico , Retroalimentação Psicológica , Doença Pulmonar Obstrutiva Crônica/reabilitação , Caminhada , Acelerometria , Idoso , Feminino , Monitores de Aptidão Física , Volume Expiratório Forçado , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
11.
Sleep Breath ; 23(1): 49-56, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29556920

RESUMO

PURPOSE: To determine the effect of temazepam on assessment of the severity of obstructive sleep apnea (OSA) by polysomnography (PSG). METHODS: Analysis of diagnostic laboratory-PSG studies was performed in OSA patients who were administered temazepam (10 mg) to facilitate sleep ("temazepam group", n = 73) and in OSA patients (matched for age, gender, body mass index and study date) in whom temazepam was not administered ("control group", n = 73). Sleep- and respiratory-related variables were compared between the groups for the (i) first 3 h of study following temazepam in the temazepam group (when peak blood concentration is expected) or following lights out in the control group, and (ii) entire study duration. RESULTS: Within the first 3 h, no differences in sleep-related variables were observed between the groups. Over the entire study duration, the temazepam group had a reduced total sleep time compared to the control group, likely due to the overnight sleep difficulties that led to its use. Whether measured during the first 3 h of study or over the entire study duration, no significant differences were detected between the groups for any respiratory-related variable, including apnea hypopnea index, arousal index, oxygen desaturation, apnea index, hypopnea index, and event duration. When patients were considered in terms of OSA severity, decreased arousal index was noted in the temazepam group over the entire study duration, but only in those with severe OSA. CONCLUSION: Oral administration of 10 mg of temazepam during the course of PSG does not systematically affect assessment of the severity of OSA by PSG.


Assuntos
Hipnóticos e Sedativos/administração & dosagem , Polissonografia/métodos , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/diagnóstico , Temazepam/administração & dosagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia/efeitos dos fármacos , Respiração/efeitos dos fármacos , Sono/efeitos dos fármacos
12.
Am J Respir Cell Mol Biol ; 58(3): 391-401, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29077507

RESUMO

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10-8) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.


Assuntos
Estudo de Associação Genômica Ampla , Locos de Características Quantitativas/genética , Apneia Obstrutiva do Sono/genética , Sono REM/fisiologia , Fatores de Transcrição/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidiletanolamina N-Metiltransferase/genética , Caracteres Sexuais , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Transativadores , Proteínas ras/genética
14.
Respirology ; 22(2): 230-239, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27988979

RESUMO

Anaesthesia and sleep are different states of unconsciousness with considerable physiological common ground. Because of their shared depressant effects on muscle activation and ventilatory drive, patients with anatomically compromised airways will tend to obstruct in either state and those with impaired ventilatory capacity will tend to hypoventilate. Breathing behaviour in one state is predictive of that in the other. An essential difference is that while arousal responses are preserved during sleep, they are depressed during sedation and abolished by anaesthesia. This renders patients with sleep-related breathing disorders vulnerable to hypoventilation and asphyxia when deeply sedated. Addressing this vulnerability requires a systematic approach to identification of patients and circumstances that magnify this risk, and methods of managing it that seek to reconcile the need for safety with cost-effective use of resources.


Assuntos
Anestesia/efeitos adversos , Anestesia/métodos , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/fisiopatologia , Sono/fisiologia , Adulto , Nível de Alerta , Asfixia/etiologia , Humanos , Hipoventilação/etiologia , Fatores de Risco
16.
Chron Respir Dis ; 14(3): 256-269, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28774199

RESUMO

We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV1], 49% predicted) were studied cross-sectionally. Demographics, anthropometrics, lung function and clinical data were assessed. Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband. Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters. Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns. Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data. Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV1, worse dyspnoea and higher ADO index compared to other clusters ( p < 0.05 for all). Daily physical activity measures and hourly patterns are heterogeneous in COPD. Clusters of patients were identified solely based on physical activity data. These findings may be useful to develop interventions aiming to promote physical activity in COPD.


Assuntos
Exercício Físico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Actigrafia , Fatores Etários , Idoso , Agnosia , Índice de Massa Corporal , Análise por Conglomerados , Estudos Transversais , Dispneia/etiologia , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Doença Pulmonar Obstrutiva Crônica/complicações , Comportamento Sedentário , Índice de Gravidade de Doença
18.
Anesth Analg ; 123(2): 452-73, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27442772

RESUMO

The purpose of the Society of Anesthesia and Sleep Medicine guideline on preoperative screening and assessment of adult patients with obstructive sleep apnea (OSA) is to present recommendations based on the available clinical evidence on the topic where possible. As very few well-performed randomized studies in this field of perioperative care are available, most of the recommendations were developed by experts in the field through consensus processes involving utilization of evidence grading to indicate the level of evidence upon which recommendations were based. This guideline may not be appropriate for all clinical situations and all patients. The decision whether to follow these recommendations must be made by a responsible physician on an individual basis. Protocols should be developed by individual institutions taking into account the patients' conditions, extent of interventions and available resources. This practice guideline is not intended to define standards of care or represent absolute requirements for patient care. The adherence to these guidelines cannot in any way guarantee successful outcomes and is rather meant to help individuals and institutions formulate plans to better deal with the challenges posed by perioperative patients with OSA. These recommendations reflect the current state of knowledge and its interpretation by a group of experts in the field at the time of publication. While these guidelines will be periodically updated, new information that becomes available between updates should be taken into account. Deviations in practice from guidelines may be justifiable and such deviations should not be interpreted as a basis for claims of negligence.


Assuntos
Anestesia/normas , Anestesiologia/normas , Cuidados Pré-Operatórios/normas , Apneia Obstrutiva do Sono/diagnóstico , Adulto , Anestesia/efeitos adversos , Anestesia/métodos , Anestesiologia/métodos , Consenso , Procedimentos Cirúrgicos Eletivos , Medicina Baseada em Evidências/normas , Humanos , Seleção de Pacientes , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Medição de Risco , Fatores de Risco , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/terapia , Resultado do Tratamento
19.
J Sleep Res ; 24(1): 92-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25131139

RESUMO

Catheters that traverse the pharynx are often in place during clinical or research evaluations of upper airway function. The purpose of this study was to determine whether the presence of such catheters affects measures of upper airway collapsibility itself. To do so, pharyngeal critical closing pressure (Pcrit) and resistance upstream of the site of collapse Rus) were assessed in 24 propofol-anaesthetized subjects (14 men) with and without a multi-sensor oesophageal catheter (external diameter 2.7 mm) in place. Anaesthetic depth and posture were maintained constant throughout each study. Six subjects had polysomnography(PSG)-defined obstructive sleep apnea (OSA) and 18 either did not have or were at low risk of OSA. Airway patency was maintained with positive airway pressure. At intervals, pressure was reduced by varying amounts to induce varying degrees of inspiratory flow limitation. The slope of the pressure flow relationship for flow-limited breaths defined Rus. Pcrit was similar with the catheter in and out (-1.5 ± 5.4 cmH2 O and -2.1 ± 5.6 cmH2O, respectively, P = 0.14, n = 24). This remained the case both for those with PSG-defined OSA (3.9 ± 2.2 cmH2O and 2.6 ± 1.4 cmH2O, n = 6) and those at low risk/without OSA (-3.3 ± 4.9 cmH2O and -3.7 ± 5.6 cmH2O, respectively, n = 18). Rus was similar with the catheter in and out (20.0 ± 12.3 cmH2O mL(-1) s(-1) and 16.8 ± 10.1 cmH2O mL(-1) s(-1), P = 0.22, n = 24). In conclusion, the presence of a small catheter traversing the pharynx had no significant effect on upper airway collapsibility in these anaesthestized subjects, providing reassurance that such measures can be made reliably in their presence.


Assuntos
Obstrução das Vias Respiratórias/fisiopatologia , Catéteres , Faringe/fisiopatologia , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Obstrução das Vias Respiratórias/etiologia , Anestesiologia/instrumentação , Índice de Massa Corporal , Catéteres/efeitos adversos , Feminino , Humanos , Masculino , Faringe/anatomia & histologia , Polissonografia , Propofol/administração & dosagem , Propofol/farmacologia , Respiração
20.
Eur Respir J ; 44(4): 885-94, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25142484

RESUMO

This study was designed to determine the effect of ground-based walking training on health-related quality of life and exercise capacity in people with chronic obstructive pulmonary disease (COPD). People with COPD were randomised to either a walking group that received supervised, ground-based walking training two to three times a week for 8-10 weeks, or a control group that received usual medical care and did not participate in exercise training. 130 out of 143 participants (mean±sd age 69±8 years, forced expiratory volume in 1 s 43±15% predicted) completed the study. Compared to the control group, the walking group demonstrated greater improvements in the St George's Respiratory Questionnaire total score (mean difference -6 points (95% CI -10- -2), p<0.003), Chronic Respiratory Disease Questionnaire total score (mean difference 7 points (95% CI 2-11), p<0.01) and endurance shuttle walk test time (mean difference 208 s (95% CI 104-313), p<0.001). This study shows that ground-based walking training is an effective training modality that improves quality of life and endurance exercise capacity in people with COPD.


Assuntos
Terapia por Exercício , Tolerância ao Exercício , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/reabilitação , Qualidade de Vida , Caminhada , Idoso , Método Duplo-Cego , Humanos , Estudos Prospectivos
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