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Find video protocols related to scientific articles indexed in Pubmed.
Quantifying the ventilatory control contribution to sleep apnoea using polysomnography.
Eur. Respir. J.
PUBLISHED: 10-18-2014
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Elevated loop gain, consequent to hypersensitive ventilatory control, is a primary nonanatomical cause of obstructive sleep apnoea (OSA) but it is not possible to quantify this in the clinic. Here we provide a novel method to estimate loop gain in OSA patients using routine clinical polysomnography alone. We use the concept that spontaneous ventilatory fluctuations due to apnoeas/hypopnoeas (disturbance) result in opposing changes in ventilatory drive (response) as determined by loop gain (response/disturbance). Fitting a simple ventilatory control model (including chemical and arousal contributions to ventilatory drive) to the ventilatory pattern of OSA reveals the underlying loop gain. Following mathematical-model validation, we critically tested our method in patients with OSA by comparison with a standard (continuous positive airway pressure (CPAP) drop method), and by assessing its ability to detect the known reduction in loop gain with oxygen and acetazolamide. Our method quantified loop gain from baseline polysomnography (correlation versus CPAP-estimated loop gain: n = 28; r = 0.63, p<0.001), detected the known reduction in loop gain with oxygen (n = 11; mean±sem change in loop gain (?LG) -0.23±0.08, p = 0.02) and acetazolamide (n = 11; ?LG -0.20±0.06, p = 0.005), and predicted the OSA response to loop gain-lowering therapy. We validated a means to quantify the ventilatory control contribution to OSA pathogenesis using clinical polysomnography, enabling identification of likely responders to therapies targeting ventilatory control.
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Clinical Predictors of the Respiratory Arousal Threshold in Patients with Obstructive Sleep Apnea.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 10-17-2014
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Rationale: A low respiratory arousal threshold (ArTH) is one of several traits involved in obstructive sleep apnea (OSA) pathogenesis and may be a therapeutic target; however, there is no simple way to identify patients without invasive measurements. Objectives: To determine the physiological determinates of the ArTH and develop a clinical tool that can identify patients with low ArTH. Methods: Anthropometric data were collected in 146 participants who underwent overnight polysomnography with an epiglottic catheter in order to measure the ArTH (nadir epiglottic pressure prior to arousal). The ArTH was measured from up to 20 NREM and REM respiratory events selected randomly. Multiple linear regression was used to determine the independent predictors of the ArTH. Logistic regression was used to develop a clinical scoring system. Measurements and Main Results: Nadir SpO2, apnea-hypopnea index and the fraction of events that were hypopneas (Fhypopneas) were independent predictors of the ArTH (r2=0.59, p<0.001). Using this information, we used ROC analysis and logistic regression to develop a clinical score to predict a low ArTH, which allocated a score of 1 to each criterion that was satisfied: (AHI<30 events/hr)+(nadir SpO2>82.5%)+(Fhypopneas>58.3%). A score of 2 or above correctly predicted a low arousal threshold in 84.1% of participants with a sensitivity of 80.4% and a specificity of 88.0%, a finding which was confirmed using leave-one-out cross validation analysis. Conclusions: Our results demonstrate that individuals with a low ArTH can be identified from standard, clinically available variables. This finding could facilitate larger interventional studies targeting the ArTH.
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Enhanced Upper-Airway Muscle Responsiveness Is a Distinct Feature of Overweight/Obese Individuals without Sleep Apnea.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 09-06-2014
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Body habitus is a major determinant of obstructive sleep apnea (OSA). However, many individuals do not have OSA despite being overweight/obese (body mass index > 25 kg/m(2)) for reasons that are not fully elucidated.
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Effects of aging on genioglossus motor units in humans.
PLoS ONE
PUBLISHED: 08-11-2014
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The genioglossus is a major upper airway dilator muscle thought to be important in obstructive sleep apnea pathogenesis. Aging is a risk factor for obstructive sleep apnea although the mechanisms are unclear and the effects of aging on motor unit remodeled in the genioglossus remains unknown. To assess possible changes associated with aging we compared quantitative parameters related to motor unit potential morphology derived from EMG signals in a sample of older (n?=?11; >55 years) versus younger (n?=?29; <55 years) adults. All data were recorded during quiet breathing with the subjects awake. Diagnostic sleep studies (Apnea Hypopnea Index) confirmed the presence or absence of obstructive sleep apnea. Genioglossus EMG signals were analyzed offline by automated software (DQEMG), which estimated a MUP template from each extracted motor unit potential train (MUPT) for both the selective concentric needle and concentric needle macro (CNMACRO) recorded EMG signals. 2074 MUPTs from 40 subjects (mean±95% CI; older AHI 19.6±9.9 events/hr versus younger AHI 30.1±6.1 events/hr) were extracted. MUPs detected in older adults were 32% longer in duration (14.7±0.5 ms versus 11.1±0.2 ms; P ?=? 0.05), with similar amplitudes (395.2±25.1 µV versus 394.6±13.7 µV). Amplitudes of CNMACRO MUPs detected in older adults were larger by 22% (62.7±6.5 µV versus 51.3±3.0 µV; P<0.05), with areas 24% larger (160.6±18.6 µV.ms versus 130.0±7.4 µV.ms; P<0.05) than those detected in younger adults. These results confirm that remodeled motor units are present in the genioglossus muscle of individuals above 55 years, which may have implications for OSA pathogenesis and aging related upper airway collapsibility.
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Effects of hyperoxia and hypoxia on the physiological traits responsible for obstructive sleep apnoea.
J. Physiol. (Lond.)
PUBLISHED: 08-01-2014
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Oxygen therapy is known to reduce loop gain (LG) in patients with obstructive sleep apnoea (OSA), yet its effects on the other traits responsible for OSA remain unknown. Therefore, we assessed how hyperoxia and hypoxia alter four physiological traits in OSA patients. Eleven OSA subjects underwent a night of polysomnography during which the physiological traits were measured using multiple 3-min 'drops' from therapeutic continuous positive airway pressure (CPAP) levels. LG was defined as the ratio of the ventilatory overshoot to the preceding reduction in ventilation. Pharyngeal collapsibility was quantified as the ventilation at CPAP of 0 cmH2O. Upper airway responsiveness was defined as the ratio of the increase in ventilation to the increase in ventilatory drive across the drop. Arousal threshold was estimated as the level of ventilatory drive associated with arousal. On separate nights, subjects were submitted to hyperoxia (n = 9; FiO2 ?0.5) or hypoxia (n = 10; FiO2 ?0.15) and the four traits were reassessed. Hyperoxia lowered LG from a median of 3.4 [interquartile range (IQR): 2.6-4.1] to 2.1 (IQR: 1.3-2.5) (P < 0.01), but did not alter the remaining traits. By contrast, hypoxia increased LG [median: 3.3 (IQR: 2.3-4.0) vs. 6.4 (IQR: 4.5-9.7); P < 0.005]. Hypoxia additionally increased the arousal threshold (mean ± s.d. 10.9 ± 2.1 l min(-1) vs. 13.3 ± 4.3 l min(-1); P < 0.05) and improved pharyngeal collapsibility (mean ± s.d. 3.4 ± 1.4 l min(-1) vs. 4.9 ± 1.3 l min(-1); P < 0.05), but did not alter upper airway responsiveness (P = 0.7). This study demonstrates that the beneficial effect of hyperoxia on the severity of OSA is primarily based on its ability to reduce LG. The effects of hypoxia described above may explain the disappearance of OSA and the emergence of central sleep apnoea in conditions such as high altitude.
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Obstructive sleep apnea in older adults is a distinctly different physiological phenotype.
Sleep
PUBLISHED: 07-26-2014
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Current evidence suggests that the pathological mechanisms underlying obstructive sleep apnea (OSA) are altered with age. However, previous studies examining individual physiological traits known to contribute to OSA pathogenesis have been assessed in isolation, primarily in healthy individuals.
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A Physiological Time Series Dynamics-Based Approach toPatient Monitoring and Outcome Prediction.
IEEE J Biomed Health Inform
PUBLISHED: 07-12-2014
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Cardiovascular variables such as heart rate (HR) and blood pressure (BP) are regulated by an underlying control system, and therefore the time series of these vital signs exhibit rich dynamical patterns of interaction in response to external perturbations (e.g., drug administration) as well as pathological states (e.g., onset of sepsis and hypotension). A question of interest is whether "similar" dynamical patterns can be identified across a heterogeneous patient cohort, and be used for prognosis of patients' health and progress. In this work, we used a switching vector autoregressive (SVAR) framework to systematically learn and identify a collection of vital sign time series dynamics, which are possibly recurrent within the same patient and may be shared across the entire cohort. We show that these dynamical behaviors can be used to characterize the physiological "state" of a patient. We validate our technique using simulated time series of the cardiovascular system, and human recordings of HR and BP time series from an orthostatic stress study with known postural states. Using the HR and BP dynamics of an intensive care unit (ICU) cohort of over 450 patients from the MIMIC II database, we demonstrate that the discovered cardiovascular dynamics are significantly associated with hospital mortality (dynamic modes 3 and 9, p = 0:001, p = 0:006 from logistic regression after adjusting for the APACHE scores). Combining the dynamics of BP time series and SAPS-I or APACHE-III provided a more accurate assessment of patient survival/mortality in the hospital than using SAPS-I and APACHE-III alone (p = 0:005 and p = 0:045). Our results suggest that the discovered dynamics of vital sign time series may contain additional prognostic value beyond that of the baseline acuity measures, and can potentially be used as an independent predictor of outcomes in the ICU.
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High flow nasal cannula for continuous positive airway pressure weaning in preterm neonates: A single-centre experience.
J Paediatr Child Health
PUBLISHED: 06-16-2014
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High flow nasal cannula therapy (HFNC) is an emerging method of non-invasive respiratory support therapy for premature infants. Recent evidence around its safety and efficacy for post-extubation respiratory support is encouraging. However, its effect on long-term respiratory outcomes is not known. The aim of this study is to determine the effect of HFNC on respiratory outcomes (chronic lung disease (CLD), need for home oxygen) when used to wean babies from continuous positive airway pressure (CPAP).
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Model-based estimation of loop gain using spontaneous breathing: a validation study.
Respir Physiol Neurobiol
PUBLISHED: 06-16-2014
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Non-invasive assessment of ventilatory control stability or loop gain (which is a key contributor in a number of sleep-related breathing disorders) has proven to be cumbersome. We present a novel multivariate autoregressive model that we hypothesize will enable us to make time-varying measurements of loop gain using nothing more than spontaneous fluctuations in ventilation and CO2. The model is adaptive to changes in the feedback control loop and therefore can account for system non-stationarities (e.g. changes in sleep state) and it is resistant to artifacts by using a signal quality measure. We tested this method by assessing its ability to detect a known increase in loop gain induced by proportional assist ventilation (PAV). Subjects were studied during sleep while breathing on continuous positive airway pressure (CPAP) alone (to stabilize the airway) or on CPAP+PAV. We show that the method tracked the PAV-induced increase in loop gain, demonstrating its time-varying capabilities, and it remained accurate in the face of measurement related artifacts. The model was able to detect a statistically significant increase in loop gain from 0.14±10 on CPAP alone to 0.21±0.13 on CPAP+PAV (p<0.05). Furthermore, our method correctly detected that the PAV-induced increase in loop gain was predominantly driven by an increase in controller gain. Taken together, these data provide compelling evidence for the validity of this technique.
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Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold.
Sleep
PUBLISHED: 06-06-2014
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The effect of common sedatives on upper airway physiology and breathing during sleep in obstructive sleep apnea (OSA) has been minimally studied. Conceptually, certain sedatives may worsen OSA in some patients. However, sleep and breathing could improve with certain sedatives in patients with OSA with a low respiratory arousal threshold. This study aimed to test the hypothesis that trazodone increases the respiratory arousal threshold in patients with OSA and a low arousal threshold. Secondary aims were to examine the effects of trazodone on upper airway dilator muscle activity, upper airway collapsibility, and breathing during sleep.
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Association of sleep habits with accidents and near misses in United States transportation operators.
J. Occup. Environ. Med.
PUBLISHED: 05-09-2014
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To explore sleep risk factors and their association with adverse events in transportation operators.
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New frontiers in obstructive sleep apnoea.
Clin. Sci.
PUBLISHED: 05-01-2014
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OSA (obstructive sleep apnoea), the most common respiratory disorder of sleep, is caused by the loss of upper airway dilating muscle activity during sleep superimposed on a narrow upper airway. This results in recurrent nocturnal asphyxia. Termination of these events usually requires arousal from sleep and results in sleep fragmentation and hypoxaemia, which leads to poor quality sleep, excessive daytime sleepiness, reduced quality of life and numerous other serious health consequences. Furthermore, patients with untreated sleep apnoea are at an increased risk of hypertension, stroke, heart failure and atrial fibrillation. Although there are many predisposing risk factors for OSA, including male gender, endocrine disorders, use of muscle relaxants, smoking, fluid retention and increased age, the strongest risk factor is obesity. The aim of the present review is to focus on three cutting-edge topics with respect to OSA. The section on animal models covers various strategies used to simulate the physiology or the effects of OSA in animals, and how these have helped to understand some of the underlying mechanisms of OSA. The section on diabetes discusses current evidence in both humans and animal models demonstrating that intermittent hypoxia and sleep fragmentation has a negative impact on glucose tolerance. Finally, the section on cardiovascular biomarkers reviews the evidence supporting the use of these biomarkers to both measure some of the negative consequences of OSA, as well as the potential benefits of OSA therapies.
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Detecting brain injury in neonatal hypoxic ischemic encephalopathy: Closing the gap between experimental and clinical research.
Exp. Neurol.
PUBLISHED: 04-22-2014
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Moderate to severe neonatal hypoxic ischemic encephalopathy remains an important cause of infant death and childhood disability. Early and accurate diagnosis of encephalopathy is difficult but critical for timely intervention. Thus, we have utilized a clinically relevant large animal model of asphyxia in-utero, followed by immediate lamb delivery, resuscitation and clinical care over the next 72h for assessment of potential biomarkers of brain injury. In-utero asphyxia was induced in twelve near-term lambs and outcomes compared with seven controls. Asphyxia resulted in bradycardia (97±12beats/min), hypotension (12.1±1mm Hg) and metabolic acidosis (pH6.9±0.02; base-excess -13.8±0.8mmol/l). 72h following asphyxia, cerebrospinal concentrations of malondialdehyde and S100B were elevated 2-fold and 5-fold, respectively, in asphyxic lambs compared to control lambs. Magnetic resonance spectroscopy (MRS) at 72h showed a significant decrease in n-acetyl aspartate: choline ratio in asphyxia lambs compared to that observed at 12h (0.56±0.23 vs. 0.82±0.15, respectively); lactate:choline ratio was not changed over this time. Marked neuropathology was observed in asphyxia lambs with neuronal degeneration in the hippocampus, thalamus, striatum and cortex. Astrogliosis was observed in the hippocampus and thalamus. Early blood markers of metabolic state showed limited predictive value of histological damage at 72h. MRS outcomes at 72h showed a modest but significant correlation with histological evidence of neuronal brain injury (lactate:N-acetyl aspartate ratio in the thalamus r(2)=0.2, p<0.01). MRS at 72h was best able to detect established brain injury, but a combination of biomarkers over multiple phases of injury may be able to assess the evolution of neonatal brain injury.
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Blood pressure improvement with continuous positive airway pressure is independent of obstructive sleep apnea severity.
J Clin Sleep Med
PUBLISHED: 04-16-2014
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We sought to perform a patient-level meta-analysis using the individual patient data of the trials identified in our previous study-level meta-analysis investigating the effect of positive airway pressure (PAP) treatment for obstructive sleep apnea (OSA) on blood pressure (BP).
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Obstructive Sleep Apnea Is Associated with Impaired Exercise Capacity: A Cross-Sectional Study.
J Clin Sleep Med
PUBLISHED: 04-09-2014
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Obstructive sleep apnea (OSA) is associated with increased risk of adverse cardiovascular events. Because cardiopulmonary exercise testing (CPET) aids in prognostic assessment of heart disease, there is rising interest in its utility for cardiovascular risk stratification of patients with OSA. However, the relationship between OSA and exercise capacity is unclear. This study was conducted to test the hypothesis that OSA is associated with impaired exercise capacity.
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Upper Airway Collapsibility is Associated with Obesity and Hyoid Position.
Sleep
PUBLISHED: 04-05-2014
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Upper airway anatomy plays a major role in obstructive sleep apnea (OSA) pathogenesis. An inferiorly displaced hyoid as measured by the mandibular plane to hyoid distance (MPH) has been consistently associated with OSA. The hyoid is also a common landmark for pharyngeal length, upper airway volume, and tongue base. Tongue dimensions, pharyngeal length, and obesity are associated with OSA severity, although the link between these anatomical variables and pharyngeal collapsibility is less well known. We hypothesized that obesity as measured by body mass index (BMI), neck and waist circumferences, and variables associated with hyoid position (pharyngeal length, upper airway volume, and tongue dimensions) would be associated with passive pharyngeal critical closing pressure (Pcrit).
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Influence of pharyngeal muscle activity on inspiratory negative effort dependence in the human upper airway.
Respir Physiol Neurobiol
PUBLISHED: 03-31-2014
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The upper airway is often modeled as a Starling resistor, which predicts that flow is independent of inspiratory effort during flow limitation. However, while some obstructive sleep apnea (OSA) patients exhibit flat, Starling resistor-like flow limitation, others demonstrate considerable negative effort dependence (NED), defined as the percent reduction in flow from peak to mid-inspiration. We hypothesized that the variability in NED could be due to differences in phasic pharyngeal muscle activation between individuals. Therefore, we induced topical pharyngeal anesthesia to reduce phasic pharyngeal muscle activation to see if it increased NED. Twelve subjects aged 50±10 years with a BMI of 35±6 kg/m(2) and severe OSA (apnea-hypopnea index=52±28 events/h) were studied. NED and phasic genioglossus muscle activity (EMG(GG)) of flow limited breaths were determined before and after pharyngeal anesthesia with lidocaine. Pharyngeal anesthesia led to a 33% reduction in EMG(GG) activity (p<0.001), but NED worsened only by 3.6±5.8% (p=0.056). In conclusion, phasic EMG(GG) had little effect on NED. This finding suggests that individual differences in phasic EMG(GG) activation do not likely explain the variability in NED found among OSA patients.
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Spousal involvement and CPAP adherence: A dyadic perspective.
Sleep Med Rev
PUBLISHED: 03-21-2014
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Poor adherence to continuous positive airway pressure (CPAP) treatment is associated with substantial health care costs, morbidity and mortality, and has been a leading obstacle in the effective management of obstructive sleep apnea (OSA). Successful interventions to improve CPAP adherence may ultimately include a variety of components. For patients living with spouses (refers to all domestic partners), the spouse will likely be an integral component to any successful intervention. Developing understanding of the role of spouses in adherence to CPAP has been identified to be a critical research need. This review expands the investigation of CPAP adherence to a broader context, from an exclusive focus on individual patients to a dyadic perspective encompassing both patients and their spouses. A conceptual framework based on social support and social control theories is proposed to understand spousal involvement in CPAP adherence. Methodologies for future investigations are discussed, along with implications for developing interventions that engage both patients and their spouses to improve CPAP use.
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Restless legs syndrome status as a predictor for lower physical function.
Neurology
PUBLISHED: 03-05-2014
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To examine the potential long-term impact of restless legs syndrome (RLS) and other common sleep complaints on subsequent physical function (PF), we conducted a longitudinal analysis of 12,556 men in the Health Professionals Follow-up Study.
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Physiological mechanisms of upper airway hypotonia during REM sleep.
Sleep
PUBLISHED: 03-04-2014
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Rapid eye movement (REM)-induced hypotonia of the major upper airway dilating muscle (genioglossus) potentially contributes to the worsening of obstructive sleep apnea that occurs during this stage. No prior human single motor unit (SMU) study of genioglossus has examined this possibility to our knowledge. We hypothesized that genioglossus SMUs would reduce their activity during stable breathing in both tonic and phasic REM compared to stage N2 sleep. Further, we hypothesized that hypopneas occurring in REM would be associated with coincident reductions in genioglossus SMU activity.
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A pilot study investigating the effects of continuous positive airway pressure treatment and weight-loss surgery on autonomic activity in obese obstructive sleep apnea patients.
J Electrocardiol
PUBLISHED: 02-27-2014
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We have previously demonstrated that severity of obstructive sleep apnea (OSA) as measured by the apnea-hypopnea index (AHI) is a significant independent predictor of readily-computed time-domain metrics of short-term heart rate variability (HRV).
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Effects of inhaled fluticasone on upper airway during sleep and wakefulness in asthma: a pilot study.
J Clin Sleep Med
PUBLISHED: 02-18-2014
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Obstructive sleep apnea is prevalent among people with asthma, but underlying mechanisms remain unknown. Inhaled corticosteroids may contribute. We tested the effects of orally inhaled fluticasone propionate (FP) on upper airway (UAW) during sleep and wakefulness.
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The classical Starling resistor model often does not predict inspiratory airflow patterns in the human upper airway.
J. Appl. Physiol.
PUBLISHED: 01-23-2014
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The upper airway is often modeled as a classical Starling resistor, featuring a constant inspiratory airflow, or plateau, over a range of downstream pressures. However, airflow tracings from clinical sleep studies often show an initial peak before the plateau. To conform to the Starling model, the initial peak must be of small magnitude or dismissed as a transient. We developed a method to simulate fast or slow inspirations through the human upper airway, to test the hypothesis that this initial peak is a transient. Eight subjects [4 obstructive sleep apnea (OSA), 4 controls] slept in an "iron lung" and wore a nasal mask connected to a continuous/bilevel positive airway pressure machine. Downstream pressure was measured using an epiglottic catheter. During non-rapid eye movement (NREM) sleep, subjects were hyperventilated to produce a central apnea, then extrathoracic pressure was decreased slowly (?2-4 s) or abruptly (<0.5 s) to lower downstream pressure and create inspiratory airflow. Pressure-flow curves were constructed for flow-limited breaths, and slow vs. fast reductions in downstream pressure were compared. All subjects exhibited an initial peak and then a decrease in flow with more negative pressures, demonstrating negative effort dependence (NED). The rate of change in downstream pressure did not affect the peak to plateau airflow ratio: %NED 22 ± 13% (slow) vs. 20 ± 5% (fast), P = not significant. We conclude that the initial peak in inspiratory airflow is not a transient but rather a distinct mechanical property of the upper airway. In contrast to the classical Starling resistor model, the upper airway exhibits marked NED in some subjects.
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Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis.
Intensive Care Med
PUBLISHED: 01-17-2014
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Prone positioning for ARDS has been performed for decades without definitive evidence of clinical benefit. A recent multicenter trial demonstrated for the first time significantly reduced mortality with prone positioning. This meta-analysis was performed to integrate these findings with existing literature and test whether differences in tidal volume explain conflicting results among randomized trials.
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Obesity and sleep apnea are independently associated with adverse left ventricular remodeling and clinical outcome in patients with atrial fibrillation and preserved ventricular function.
Am. Heart J.
PUBLISHED: 01-06-2014
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Obesity is associated with the development of atrial fibrillation (AF), and both obesity and AF are independently associated with the development of heart failure with preserved ejection fraction. We tested the hypothesis that sleep apnea (SA) would have a body mass index (BMI) independent association with adverse left ventricular (LV) remodeling and clinical outcomes in patients with AF and preserved LV function.
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The Efficacy of Surfactant Replacement Therapy in the Growth-Restricted Preterm Infant: What is the Evidence?
Front Pediatr
PUBLISHED: 01-01-2014
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Surfactant replacement therapy (SRT) is an integral part of management of preterm surfactant deficiency respiratory distress syndrome (RDS). Its role in the management of RDS has been extensively studied. However, its efficacy in the management of lung disease in preterm infants born with intrauterine growth restriction (IUGR) has not been systematically studied.
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Obstructive sleep apnea and psychomotor vigilance task performance.
Nat Sci Sleep
PUBLISHED: 01-01-2014
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Obstructive sleep apnea (OSA) is a highly prevalent disorder with considerable morbidity and mortality. Vigilance and attentiveness are often impaired in OSA patients. In occupational medicine settings, subjective reports of sleepiness are notoriously inaccurate, making the identification of objective measures of vigilance potentially important for risk assessments of fitness for duty. In order to evaluate the effects of OSA on attentiveness and vigilance, we conducted a cross-sectional study to examine the association between OSA and psychomotor vigilance task (PVT) performance.
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Untreated sleep-disordered breathing: links to aging-related decline in sleep-dependent memory consolidation.
PLoS ONE
PUBLISHED: 01-01-2014
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Increasing age is associated with a decline in cognition and motor skills, while at the same time exacerbating one's risk of developing obstructive sleep apnea (OSA). OSA-related cognitive deficits are highly prevalent and can affect various memory systems including overnight memory consolidation on a motor sequence task. Thus, the aim of our study was to examine the effect of aging on sleep-dependent motor memory consolidation in patients with and without OSA.
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The impact of circadian misalignment on athletic performance in professional football players.
Sleep
PUBLISHED: 12-03-2013
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We hypothesized that professional football teams would perform better than anticipated during games occurring close to their circadian peak in performance.
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Effect of sleep apnea and continuous positive airway pressure on cardiac structure and recurrence of atrial fibrillation.
J Am Heart Assoc
PUBLISHED: 11-27-2013
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Sleep apnea (SA) is associated with an increased risk of atrial fibrillation (AF). We sought to determine the effect of SA on cardiac structure in patients with AF, whether therapy for SA was associated with beneficial cardiac structural remodelling, and whether beneficial cardiac structural remodelling translated into a reduced risk of recurrence of AF after pulmonary venous isolation (PVI).
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Air leak during CPAP titration as a risk factor for central apnea.
J Clin Sleep Med
PUBLISHED: 11-16-2013
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Emergence of central sleep apnea has been described in the setting of continuous positive airway pressure (CPAP) initiation. The underlying mechanism is unclear; however, we postulate that air leak washing out anatomical dead space is a contributing factor.
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Acoustic pharyngometry measurement of minimal cross-sectional airway area is a significant independent predictor of moderate-to-severe obstructive sleep apnea.
J Clin Sleep Med
PUBLISHED: 11-16-2013
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The current gold-standard method of diagnosing obstructive sleep apnea (OSA) is polysomnography, which can be inefficient. We therefore sought to determine a method to triage patients at risk of OSA, without using subjective data, which are prone to mis-reporting. We hypothesized that acoustic pharyngometry in combination with age, gender, and neck circumference would predict the presence of moderate-to-severe OSA.
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An official American Thoracic Society research statement: comparative effectiveness research in pulmonary, critical care, and sleep medicine.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 10-29-2013
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Comparative effectiveness research (CER) is intended to inform decision making in clinical practice, and is central to patient-centered outcomes research (PCOR).
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Tracking progression of patient state of health in critical care using inferred shared dynamics in physiological time series.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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Physiologic systems generate complex dynamics in their output signals that reflect the changing state of the underlying control systems. In this work, we used a switching vector autoregressive (switching VAR) framework to systematically learn and identify a collection of vital sign dynamics, which can possibly be recurrent within the same patient and shared across the entire cohort. We show that these dynamical behaviors can be used to characterize and elucidate the progression of patients states of health over time. Using the mean arterial blood pressure time series of 337 ICU patients during the first 24 hours of their ICU stays, we demonstrated that the learned dynamics from as early as the first 8 hours of patients ICU stays can achieve similar hospital mortality prediction performance as the well-known SAPS-I acuity scores, suggesting that the discovered latent dynamics structure may yield more timely insights into the progression of a patients state of health than the traditional snapshot-based acuity scores.
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An official American Thoracic Society statement: continuous positive airway pressure adherence tracking systems. The optimal monitoring strategies and outcome measures in adults.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 09-03-2013
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Continuous positive airway pressure (CPAP) is considered the treatment of choice for obstructive sleep apnea (OSA), and studies have shown that there is a correlation between patient adherence and treatment outcomes. Newer CPAP machines can track adherence, hours of use, mask leak, and residual apnea-hypopnea index (AHI). Such data provide a strong platform to examine OSA outcomes in a chronic disease management model. However, there are no standards for capturing CPAP adherence data, scoring flow signals, or measuring mask leak, or for how clinicians should use these data.
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State-Dependent and Reflex Drives to the Upper Airway: Basic Physiology with Clinical Implication.
J. Appl. Physiol.
PUBLISHED: 08-22-2013
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The root cause of the most common and serious of the sleep disorders is impairment of breathing, and a number of factors predispose a particular individual to hypoventilation during sleep. In turn, obstructive hypopneas and apneas are the most common of the sleep-related respiratory problems, and are caused by dysfunction of the upper airway as a conduit for airflow. The overarching principle that underpins the full spectrum of clinical sleep-related breathing disorders is that the sleeping brain modifies respiratory muscle activity and control mechanisms, and diminishes the ability to respond to respiratory distress. Depression of upper airway muscle activity and reflex responses, and suppression of arousal (i.e., waking-up) responses to respiratory disturbance, can also occur with commonly used sedating agents (e.g., hypnotics and anesthetics). Growing evidence indicates that the sometimes-critical problems of sleep and sedation-induced depression of breathing and arousal responses may be working through common brain pathways acting on common cellular mechanisms. To identify these state-dependent pathways and reflex mechanisms, as they affect the upper airway, is the focus of this paper. Major emphasis is on the synthesis of established and recent findings. In particular, we specifically focus on: (I) The recently defined mechanism of genioglossus muscle inhibition in rapid-eye-movement sleep; (II) Convergence of diverse neurotransmitters and signaling pathways onto one root mechanism that may explain pharyngeal motor suppression in sleep and drug-induced brain sedation. (III) The lateral reticular formation as a key hub of respiratory and reflex drives to the upper airway.
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Obstructive sleep apnea (OSA) in preadolescent girls is associated with delayed breast development compared to girls without OSA.
J Clin Sleep Med
PUBLISHED: 08-16-2013
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Adults with obstructive sleep apnea (OSA) have lower sex steroid levels than controls. We sought to determine whether OSA also interferes with reproductive hormones in adolescence by tracking the pace of pubertal development.
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Impact of CPAP use and age on mortality in patients with combined COPD and obstructive sleep apnea: the overlap syndrome.
J Clin Sleep Med
PUBLISHED: 08-16-2013
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The overlap syndrome, defined by concurrent existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), is associated with poor outcomes. From a large outpatient cohort we aimed to define better the risk factors for increased mortality in the overlap syndrome and hypothesized that CPAP adherence would be associated with improved survival in patients with overlap syndrome.
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Congenital chylothorax: Associations and neonatal outcomes.
J Paediatr Child Health
PUBLISHED: 08-12-2013
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Congenital chylothorax is a rare but significant neonatal entity with major morbidity and mortality. The study aims to describe the related associations, management and outcomes of this condition in neonates.
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Adult obstructive sleep apnoea.
Lancet
PUBLISHED: 08-02-2013
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Obstructive sleep apnoea is an increasingly common disorder of repeated upper airway collapse during sleep, leading to oxygen desaturation and disrupted sleep. Features include snoring, witnessed apnoeas, and sleepiness. Pathogenesis varies; predisposing factors include small upper airway lumen, unstable respiratory control, low arousal threshold, small lung volume, and dysfunctional upper airway dilator muscles. Risk factors include obesity, male sex, age, menopause, fluid retention, adenotonsillar hypertrophy, and smoking. Obstructive sleep apnoea causes sleepiness, road traffic accidents, and probably systemic hypertension. It has also been linked to myocardial infarction, congestive heart failure, stroke, and diabetes mellitus though not definitively. Continuous positive airway pressure is the treatment of choice, with adherence of 60-70%. Bi-level positive airway pressure or adaptive servo-ventilation can be used for patients who are intolerant to continuous positive airway pressure. Other treatments include dental devices, surgery, and weight loss.
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Contemporary ventilator management in patients with and at risk of ALI/ARDS.
Respir Care
PUBLISHED: 07-03-2013
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Ventilator practices in patients at risk for acute lung injury (ALI) and ARDS are unclear. We examined factors associated with choice of set tidal volumes (VT), and whether VT < 8 mL/kg predicted body weight (PBW) relates to the development of ALI/ARDS.
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High altitude, continuous positive airway pressure, and obstructive sleep apnea: subjective observations and objective data.
High Alt. Med. Biol.
PUBLISHED: 06-26-2013
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We report observations made by one of the authors who ascended to the Thorang La pass (5416?m) in the Nepal Himalaya in October 2010, despite moderate-severe obstructive sleep apnea. We report the first recorded use of nasal CPAP to treat high altitude pulmonary edema (progressively severe dyspnea at rest and severe orthopnea, with tachycardia and tachypnea) that occurred at 4400 meters, when snow and darkness made safe evacuation difficult. We also present objective longitudinal data of the effects of altitude on auto-adjusting CPAP delivered via a portable nasal CPAP device, and on the apnea hypopnea index measured during sleep while using the device. OSA may be a risk factor for the development of high altitude pulmonary edema and we suggest that a nasal CPAP device located in high altitude trekking stations may provide an additional or alternative treatment option for managing high altitude pulmonary edema until evacuation is possible.
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Prospective study of restless legs syndrome and mortality among men.
Neurology
PUBLISHED: 06-12-2013
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To prospectively examine whether men with restless legs syndrome (RLS) had an increased risk of mortality.
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An official American Thoracic Society Clinical Practice Guideline: sleep apnea, sleepiness, and driving risk in noncommercial drivers. An update of a 1994 Statement.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 06-04-2013
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Sleepiness may account for up to 20% of crashes on monotonous roads, especially highways. Obstructive sleep apnea (OSA) is the most common medical disorder that causes excessive daytime sleepiness, increasing the risk for drowsy driving two to three times. The purpose of these guidelines is to update the 1994 American Thoracic Society Statement that described the relationships among sleepiness, sleep apnea, and driving risk.
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Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 06-01-2013
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The pathophysiologic causes of obstructive sleep apnea (OSA) likely vary among patients but have not been well characterized.
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Hypoglossal nerve stimulation improves obstructive sleep apnoea: 12-month outcomes.
J Sleep Res
PUBLISHED: 05-23-2013
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Reduced upper airway muscle activity during sleep is a key contributor to obstructive sleep apnoea pathogenesis. Hypoglossal nerve stimulation activates upper airway dilator muscles, including the genioglossus, and has the potential to reduce obstructive sleep apnoea severity. The objective of this study was to examine the safety, feasibility and efficacy of a novel hypoglossal nerve stimulation system (HGNS(®) ; Apnex Medical, St Paul, MN, USA) in treating obstructive sleep apnoea at 12 months following implantation. Thirty-one subjects (35% female, age 52.4 ± 9.4 years) with moderate to severe obstructive sleep apnoea and unable to tolerate positive airway pressure underwent surgical implantation and activation of the hypoglossal nerve stimulation system in a prospective single-arm interventional trial. Primary outcomes were changes in obstructive sleep apnoea severity (apnoea-hypopnoea index, from in-laboratory polysomnogram) and sleep-related quality of life [Functional Outcomes of Sleep Questionnaire (FOSQ)]. Hypoglossal nerve stimulation was used on 86 ± 16% of nights for 5.4 ± 1.4 h per night. There was a significant improvement (P < 0.001) from baseline to 12 months in apnoea-hypopnoea index (45.4 ± 17.5 to 25.3 ± 20.6 events h(-1) ) and Functional Outcomes of Sleep Questionnaire score (14.2 ± 2.0 to 17.0 ± 2.4), as well as other polysomnogram and symptom measures. Outcomes were stable compared with 6 months following implantation. Three serious device-related adverse events occurred: an infection requiring device removal; and two stimulation lead cuff dislodgements requiring replacement. There were no significant adverse events with onset later than 6 months following implantation. Hypoglossal nerve stimulation demonstrated favourable safety, feasibility and efficacy.
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Characteristics of infants at risk of hypoglycaemia secondary to being infant of a diabetic mother.
J. Pediatr. Endocrinol. Metab.
PUBLISHED: 04-15-2013
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Abstract Background: Infants of diabetic mothers (IDMs) are at risk of hypoglycaemia in the neonatal period. The prediction of which of these infants are at higher risk of developing hypoglycaemia is complex. Aims: To determine the characteristics of infants of diabetic mothers who are more likely to need an admission to the neonatal intensive care unit to manage their hypoglycaemia. Methods: Retrospective chart review of maternal and infant characteristics of at-risk infants. Electronic patient records and neonatal and obstetric database accessed to obtain data. Results: A total of 326 infants were identified in a study period accessible to electronic patient records. Macrosomia was present in 15% of the infants. Hypoglycaemic episodes occurred in 109 (33.4%) infants. Maternal diabetes type, HbA1c, prematurity, macrosomia, and temperature instability were identified as risk factors most commonly associated in infants who actually went on to develop hypoglycaemia. Conclusions: A weighted risk score to predict hypoglycaemia in this at-risk population may serve to rationalise admission to the neonatal unit and management of IDMs.
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Agreement in computer-assisted manual scoring of polysomnograms across sleep centers.
Sleep
PUBLISHED: 04-09-2013
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To determine intersite agreement in respiratory event scoring of polysomnograms (PSGs) using different hypopnea definitions.
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Performance of an automated polysomnography scoring system versus computer-assisted manual scoring.
Sleep
PUBLISHED: 04-09-2013
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Manual scoring of polysomnograms (PSG) is labor intensive and has considerable variance between scorers. Automation of scoring could reduce cost and improve reproducibility. The purpose of this study was to compare a new automated scoring system (YST-Limited, Winnipeg, Canada) with computer-assisted manual scoring.
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A mechanism for upper airway stability during slow wave sleep.
Sleep
PUBLISHED: 04-09-2013
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The severity of obstructive sleep apnea is diminished (sometimes markedly) during slow wave sleep (SWS). We sought to understand why SWS stabilizes the upper airway. Increased single motor unit (SMU) activity of the major upper airway dilating muscle (genioglossus) should improve upper airway stability. Therefore, we hypothesized that genioglossus SMUs would increase their activity during SWS in comparison with Stage N2 sleep.
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Patent foramen ovale in severe obstructive sleep apnea: clinical features and effects of closure.
Chest
PUBLISHED: 04-03-2013
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Patent foramen ovale (PFO) may contribute to nocturnal desaturation in patients with obstructive sleep apnea (OSA), and the effect of PFO closure in OSA is unknown. Our study tested the hypotheses that: (1) patients with severe OSA have a higher prevalence of PFO compared with healthy control subjects, (2) patients with severe OSA with clinically significant PFO experience more nocturnal desaturation than those without, and (3) PFO closure reduces nocturnal desaturation.
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Neonatal presentation of chromosome 9q33.2-q34.3 duplication.
Gene
PUBLISHED: 03-28-2013
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Partial terminal duplication of chromosome 9 is a rare anomaly that is known to be associated with specific dysmorphic features. While having common characteristics, these patients also have inconsistent phenotypic features. These inconsistent features may be attributed to the length and the region of the duplicated segment of chromosome 9. We discuss a case of an infant with similar physical features to those previously reported including dysmorphology of the craniofacial region, hands and feet. However we also describe findings of malrotation and renal anomalies. Microarray demonstrated duplication of 9q33.2-q34.3 with normal parental karyotyping. This is the first reported case of duplication of this specific region of chromosome 9q and the phenotypic presentation represents a new constellation of clinical findings.
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Respiration and heart rate complexity: effects of age and gender assessed by band-limited transfer entropy.
Respir Physiol Neurobiol
PUBLISHED: 03-15-2013
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Aging and disease are accompanied with a reduction of complex variability in the temporal patterns of heart rate. This reduction has been attributed to a break down of the underlying regulatory feedback mechanisms that maintain a homeodynamic state. Previous work has established the utility of entropy as an index of disorder, for quantification of changes in heart rate complexity. However, questions remain regarding the origin of heart rate complexity and the mechanisms involved in its reduction with aging and disease. In this work we use a newly developed technique based on the concept of band-limited transfer entropy to assess the aging-related changes in contribution of respiration and blood pressure to entropy of heart rate at different frequency bands. Noninvasive measurements of heart beat interval, respiration, and systolic blood pressure were recorded from 20 young (21-34 years) and 20 older (68-85 years) healthy adults. Band-limited transfer entropy analysis revealed a reduction in high-frequency contribution of respiration to heart rate complexity (p<0.001) with normal aging, particularly in men. These results have the potential for dissecting the relative contributions of respiration and blood pressure-related reflexes to heart rate complexity and their degeneration with normal aging.
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A multicenter evaluation of oral pressure therapy for the treatment of obstructive sleep apnea.
Sleep Med.
PUBLISHED: 03-14-2013
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We aimed to evaluate the impact of a novel noninvasive oral pressure therapy (OPT) (Winx®, ApniCure) system on polysomnographic measures of sleep-disordered breathing, sleep architecture, and sleep stability in obstructive sleep apnea (OSA).
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Methods of blood pressure measurement in the ICU.
Crit. Care Med.
PUBLISHED: 03-05-2013
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Minimal clinical research has investigated the significance of different blood pressure monitoring techniques in the ICU and whether systolic vs. mean blood pressures should be targeted in therapeutic protocols and in defining clinical study cohorts. The objectives of this study are to compare real-world invasive arterial blood pressure with noninvasive blood pressure, and to determine if differences between the two techniques have clinical implications.
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Clinical consequences of altered chemoreflex control.
Respir Physiol Neurobiol
PUBLISHED: 02-14-2013
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Control of ventilation dictates various breathing patterns. The respiratory control system consists of a central pattern generator and several feedback mechanisms that act to maintain ventilation at optimal levels. The concept of loop gain has been employed to describe its stability and variability. Synthesizing all interactions under a general model that could account for every behavior has been challenging. Recent insight into the importance of these feedback systems may unveil therapeutic strategies for common ventilatory disturbances. In this review we will address the major mechanisms that have been proposed as mediators of some of the breathing patterns in health and disease that have raised controversies and discussion on ventilatory control over the years.
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Acetazolamide attenuates the ventilatory response to arousal in patients with obstructive sleep apnea.
Sleep
PUBLISHED: 02-02-2013
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The magnitude of the post-apnea/hypopnea ventilatory overshoot following arousal may perpetuate subsequent respiratory events in obstructive sleep apnea (OSA) patients, potentially contributing to the disorders severity. As acetazolamide can reduce apnea severity in some patients, we examined the effect of acetazolamide on the ventilatory response to spontaneous arousals in CPAP-treated OSA patients.
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A simplified method for determining phenotypic traits in patients with obstructive sleep apnea.
J. Appl. Physiol.
PUBLISHED: 01-24-2013
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We previously published a method for measuring several physiological traits causing obstructive sleep apnea (OSA). The method, however, had a relatively low success rate (76%) and required mathematical modeling, potentially limiting its application. This paper presents a substantial revision of that technique. To make the measurements, continuous positive airway pressure (CPAP) was manipulated during sleep to quantify 1) eupneic ventilatory demand, 2) the level of ventilation at which arousals begin to occur, 3) ventilation off CPAP (nasal pressure = 0 cmH(2)O) when the pharyngeal muscles are activated during sleep, and 4) ventilation off CPAP when the pharyngeal muscles are relatively passive. These traits could be determined in all 13 participants (100% success rate). There was substantial intersubject variability in the reduction in ventilation that individuals could tolerate before having arousals (difference between ventilations #1 and #2 ranged from 0.7 to 2.9 liters/min) and in the amount of ventilatory compensation that individuals could generate (difference between ventilations #3 and #4 ranged from -0.5 to 5.5 liters/min). Importantly, the measurements accurately reflected clinical metrics; the difference between ventilations #2 and #3, a measure of the gap that must be overcome to achieve stable breathing during sleep, correlated with the apnea-hypopnea index (r = 0.9, P < 0.001). An additional procedure was added to the technique to measure loop gain (sensitivity of the ventilatory control system), which allowed arousal threshold and upper airway gain (response of the upper airway to increasing ventilatory drive) to be quantified as well. Of note, the traits were generally repeatable when measured on a second night in 5 individuals. This technique is a relatively simple way of defining mechanisms underlying OSA and could potentially be used in a clinical setting to individualize therapy.
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Characteristics of infants admitted with hypoglycemia to a neonatal unit.
J. Pediatr. Endocrinol. Metab.
PUBLISHED: 01-18-2013
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Neonatal hypoglycemia is a common symptom in early infant life. The currently available literature identifies the risk factors but not the degree to which each factor lends itself to the development or severity of an ensuing hypoglycemia.
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Molecular biomarkers of vascular dysfunction in obstructive sleep apnea.
PLoS ONE
PUBLISHED: 01-01-2013
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Untreated and long-lasting obstructive sleep apnea (OSA) may lead to important vascular abnormalities, including endothelial cell (EC) dysfunction, hypertension, and atherosclerosis. We observed a correlation between microcirculatory reactivity and endothelium-dependent release of nitric oxide in OSA patients. Therefore, we hypothesized that OSA affects (micro)vasculature and we aimed to identify vascular gene targets of OSA that could possibly serve as reliable biomarkers of severity of the disease and possibly of vascular risk. Using quantitative RT-PCR, we evaluated gene expression in skin biopsies of OSA patients, mouse aortas from animals exposed to 4-week intermittent hypoxia (IH; rapid oscillations in oxygen desaturation and reoxygenation), and human dermal microvascular (HMVEC) and coronary artery endothelial cells (HCAEC) cultured under IH. We demonstrate a significant upregulation of endothelial nitric oxide synthase (eNOS), tumor necrosis factor-alpha-induced protein 3 (TNFAIP3; A20), hypoxia-inducible factor 1 alpha (HIF-1??? and vascular endothelial growth factor (VEGF) expression in skin biopsies obtained from OSA patients with severe nocturnal hypoxemia (nadir saturated oxygen levels [SaO2]<75%) compared to mildly hypoxemic OSA patients (SaO2 75%-90%) and a significant upregulation of vascular cell adhesion molecule 1 (VCAM-1) expression compared to control subjects. Gene expression profile in aortas of mice exposed to IH demonstrated a significant upregulation of eNOS and VEGF. In an in vitro model of OSA, IH increased expression of A20 and decreased eNOS and HIF-1? expression in HMVEC, while increased A20, VCAM-1 and HIF-1?expression in HCAEC, indicating that EC in culture originating from distinct vascular beds respond differently to IH stress. We conclude that gene expression profiles in skin of OSA patients may correlate with disease severity and, if validated by further studies, could possibly predict vascular risk in OSA patients.
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Subgaleal hemorrhage: risk factors and outcomes.
Acta Obstet Gynecol Scand
PUBLISHED: 12-16-2011
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Subgaleal hemorrhage in the newborn is a serious adverse event that is often unrecognized and under-appreciated. This retrospective case series aimed to determine perinatal factors associated with subgaleal hemorrhage and subsequent neonatal outcomes. Obstetric and neonatal details of 21 infants with subgaleal hemorrhage over a 10-year period were collected. The mother was primiparous in 95% cases, 48% had a prolonged second stage (>120 minutes) and 43% had prolonged rupture of membranes (>12 hours). Thirteen infants (62%) were born by instrumental vaginal delivery. Ten infants (48%) required resuscitation at delivery. The severity of subgaleal hemorrhage was mild in four infants (19%), moderate in 10 (48%) and severe in seven (33%). Hypovolemic shock developed in 10 infants (48%), encephalopathy in 13 (62%) and coagulopathy was present in five infants (24%). There were three (14%) deaths. Long-term outcomes were good in the surviving infants.
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Congenital hypothyroidism in association with chromosome 3p25.3-pter deletion.
J. Pediatr. Endocrinol. Metab.
PUBLISHED: 12-08-2011
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This report describes a case of a neonate presenting with many of the typical phenotypic characteristics of chromosome 3p deletion including hypertelorism, flat nasal bridge, flat philtrum, thin lips and low-set ears. The hands and feet showed post axial polydactyly, single palmar creases and rocker bottom feet. A karyotype confirmed chromosome 3p25.3-pter deletion with normal parental karyotypes. A high TSH was noted on newborn screening and congenital hypothyroidism was confirmed on thyroid function tests. Thyroid nuclear imaging was suggestive of dyshormonogenesis. This is the first reported case of congenital hypothyroidism in an infant with chromosome 3p deletion.
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Acute upper airway responses to hypoglossal nerve stimulation during sleep in obstructive sleep apnea.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 12-01-2011
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Hypoglossal nerve stimulation (HGNS) recruits lingual muscles, reduces pharyngeal collapsibility, and treats sleep apnea.
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Phasic respiratory modulation of pharyngeal collapsibility via neuromuscular mechanisms in rats.
J. Appl. Physiol.
PUBLISHED: 11-03-2011
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Obstructive sleep apnea patients experience recurrent upper airway (UA) collapse due to decreases in the UA dilator muscle activity during sleep. In contrast, activation of UA dilators reduces pharyngeal critical pressure (Pcrit, an index of pharyngeal collapsibility), suggesting an inverse relationship between pharyngeal collapsibility and dilator activity. Since most UA muscles display phasic respiratory activity, we hypothesized that pharyngeal collapsibility is modulated by respiratory drive via neuromuscular mechanisms. Adult male Sprague-Dawley rats were anesthetized, vagotomized, and ventilated (normocapnia). In one group, integrated genioglossal activity, Pcrit, and maximal airflow (V(max)) were measured at three expiration and five inspiration time points within the breathing cycle. Pcrit was closely and inversely related to phasic genioglossal activity, with the value measured at peak inspiration being the lowest. In other groups, the variables were measured during expiration and peak inspiration, before and after each of five manipulations. Pcrit was 26% more negative (-15.0 ± 1.0 cmH(2)O, -18.9 ± 1.2 cmH(2)O; n = 23), V(max) was 7% larger (31.0 ± 1.0 ml/s, 33.2 ± 1.1 ml/s), nasal resistance was 12% bigger [0.49 ± 0.05 cmH(2)O/(ml/s), 0.59 ± 0.05 cmH(2)O/(ml/s)], and latency to induced UA closure was 14% longer (55 ± 4 ms, 63 ± 5 ms) during peak inspiration vs. expiration (all P < 0.005). The expiration-inspiration difference in Pcrit was abolished with neuromuscular blockade, hypocapnic apnea, or death but was not reduced by the superior laryngeal nerve transection or altered by tracheal displacement. Collectively, these results suggest that pharyngeal collapsibility is moment-by-moment modulated by respiratory drive and this phasic modulation requires neuromuscular mechanisms, but not the UA negative pressure reflex or tracheal displacement by phasic lung inflation.
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Treating obstructive sleep apnea with hypoglossal nerve stimulation.
Sleep
PUBLISHED: 11-02-2011
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Reduced upper airway muscle activity during sleep is fundamental to obstructive sleep apnea (OSA) pathogenesis. Hypoglossal nerve stimulation (HGNS) counteracts this problem, with potential to reduce OSA severity.
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A review of genetic association studies of obstructive sleep apnea: field synopsis and meta-analysis.
Sleep
PUBLISHED: 11-02-2011
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Obstructive sleep apnea (OSA) is a multifactorial disorder with a heritable component. We performed a field synopsis of genetic association studies of OSA to synthesize the available evidence.
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Neurogenic changes in the upper airway of patients with obstructive sleep apnea.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 10-20-2011
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Controversy persists regarding the presence and importance of hypoglossal nerve dysfunction in obstructive sleep apnea (OSA).
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Restless legs syndrome and hypertension in middle-aged women.
Hypertension
PUBLISHED: 10-10-2011
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Limited research suggests a relationship between restless legs syndrome and hypertension. We, therefore, assessed the relationship between restless legs syndrome and hypertension among middle-aged women. This is a cross-sectional study including 65 544 women (aged 41-58 years) participating in Nurses Health Study II. The participants with diabetes mellitus and arthritis were excluded, because these conditions can mimic restless legs syndrome. Restless legs syndrome was assessed by a self-administered questionnaire based on the International Restless Legs Study Group criteria. Information on diagnosis of hypertension and blood pressure values were collected via questionnaires. Multivariable logistic regression models were used to analyze the relation between restless legs syndrome and hypertension, with adjustment for age, race, body mass index, physical activity, menopausal status, smoking, use of analgesics, and intake of alcohol, caffeine, folate, and iron. Compared with women with no restless legs symptoms, the multiple adjusted odds of having hypertension were 1.20 times (95% CI: 1.10-1.30; P<0.0001) higher among women with restless legs symptoms. The adjusted odds ratios for women who reported restless legs symptoms 5 to 14 times per month and ?15 times per month were 1.06 (95% CI: 0.94-1.18) and 1.41 (95% CI: 1.24-1.61) respectively, compared with those without the symptoms (P trend: <0.0001). Greater frequency of restless legs symptoms was associated with higher concurrent systolic and diastolic blood pressures (P trend: <0.0001 for both). Women with restless legs syndrome have a higher prevalence of hypertension, and this prevalence increases with more frequent restless legs symptoms.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.