The purpose of this review was to summarize what is currently known regarding two important questions facing the field of sleep medicine today: (1) How many hours of CPAP use per night are necessary ...to improve daytime symptoms and reduce cardiovascular risk associated with OSA?; and (2) What strategies could be implemented to optimize adherence in clinical settings? Despite the widespread adoption of a threshold approach to CPAP management, the literature to date suggests a dose-response relationship between CPAP usage and a range of outcomes, including sleepiness, functional status, and BP; the data also suggest that the optimal adherence level differs depending on the outcome in question. Over the years, psychological measures of behavior change constructs have been increasingly recognized as the most consistent predictors of CPAP adherence, and, as such, the most successful interventions for optimizing adherence have been behavioral in nature. Unfortunately, behavioral therapies have not been translated from highly controlled research settings to comparative-effectiveness studies and finally into routine care, mainly due to feasibility and cost issues. More recently, theory-driven telemedicine adherence interventions have emerged, which take advantage of the framework that already exists in the United States and elsewhere for real-time remote-monitoring of CPAP. Combining theory-driven behavioral approaches with telemedicine technology could hold the answer to increasing real-world CPAP adherence rates, although randomized studies are still required, and socioeconomic barriers to telemedicine will need to be addressed to promote health equity.
We sought to provide an updated systematic review and meta-analysis of studies investigating the effect of positive airway pressure (PAP) treatment for obstructive sleep apnea (OSA) on systolic and ...diastolic blood pressure (SBP, DBP).
Two independent investigators undertook a systematic search of the PubMed database (1980-2012) to identify randomized controlled trials comparing therapeutic PAP to sham-PAP, pill placebo, or standard care over at least one week in adult OSA patients without major comorbidities. The mean, variance, and sample size for diurnal and nocturnal SBP and DBP data were also extracted independently from each study. Random effects meta-analyses were conducted, followed by pre-specified subgroup and meta-regression analyses.
32 studies were identified, with data available from 28 studies representing n = 1,948 patients. The weighted mean difference in diurnal SBP (-2.58 mm Hg, 95% CI -3.57 to -1.59 mm Hg) and DBP (-2.01 mm Hg, 95% CI -2.84 to -1.18 mm Hg) both significantly favored PAP treatment over control arms, with similar results seen in nocturnal readings. Statistically significant reductions in BP were seen in studies whose patients were younger, sleepier, had more severe OSA, and exhibited greater PAP adherence. Meta-regression indicated that the reductions in DBP with PAP were predicted by mean baseline BP (β = -0.22, p = 0.02) and Epworth Sleepiness Scale scores (β = -0.27, p = 0.04).
PAP treatment for OSA is associated with modest but significant reductions in diurnal and nocturnal SBP and DBP. Future research should be directed towards identifying subgroups likely to reap greater treatment benefits as well as other therapeutic benefits provided by PAP therapy.
Digital medicine is an interdisciplinary field, drawing together stakeholders with expertize in engineering, manufacturing, clinical science, data science, biostatistics, regulatory science, ethics, ...patient advocacy, and healthcare policy, to name a few. Although this diversity is undoubtedly valuable, it can lead to confusion regarding terminology and best practices. There are many instances, as we detail in this paper, where a single term is used by different groups to mean different things, as well as cases where multiple terms are used to describe essentially the same concept. Our intent is to clarify core terminology and best practices for the evaluation of Biometric Monitoring Technologies (BioMeTs), without unnecessarily introducing new terms. We focus on the evaluation of BioMeTs as fit-for-purpose for use in clinical trials. However, our intent is for this framework to be instructional to all users of digital measurement tools, regardless of setting or intended use. We propose and describe a three-component framework intended to provide a foundational evaluation framework for BioMeTs. This framework includes (1) verification, (2) analytical validation, and (3) clinical validation. We aim for this common vocabulary to enable more effective communication and collaboration, generate a common and meaningful evidence base for BioMeTs, and improve the accessibility of the digital medicine field.
No data exist as to the role of ethnicity in the associations between obstructive sleep apnea (OSA), sleep duration, and metabolic dysfunction.
To examine links between OSA, objectively measured ...habitual sleep duration, and fasting glucose in U.S. ethnic groups.
The Multi-Ethnic Study of Atherosclerosis is a multisite community-based study that conducted polysomnography and wrist actigraphy. In 2,151 subjects (1,839 in fully adjusted models), the apnea-hypopnea index was used to classify OSA as none (0-4.9/h), mild (5-14.9/h), or moderate to severe (≥15/h). Actigraphic sleep duration was classified as short (≤5 h/night), intermediate (>5 and <8 h/night), or long (≥8 h/night). Subjects were classified as having normal fasting glucose (<100 mg/dl and no hypoglycemic medication use) or abnormal fasting glucose (≥100 mg/dl and/or hypoglycemic medication use).
The sample was 45.8% male, age 68.5 ± 9.2 (mean ± SD) years, and 27.3% African American, 37.2% white, 11.8% Chinese, and 23.8% Hispanic. The prevalence of abnormal fasting glucose was 40.2%. Relative to subjects without apnea, moderate-to-severe OSA was significantly associated with abnormal fasting glucose in African Americans (odds ratio, 2.14; 95% confidence interval, 1.12-4.08) and white participants (odds ratio, 2.85; 95% confidence interval, 1.20-6.75), but not among Chinese or Hispanic subjects, after adjusting for site, age, sex, waist circumference, and sleep duration (P = 0.06 for ethnicity-by-OSA severity interaction). In contrast, sleep duration was not significantly associated with abnormal fasting glucose after considering the influence of OSA.
This large multiethnic study confirmed previous reports of an independent association between OSA and metabolic dysfunction, and suggested that this association may vary by ethnicity.
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-1α?? 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-1α expression in HMVEC, while increased A20, VCAM-1 and HIF-1αexpression 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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
CPAP effectiveness is limited by suboptimal adherence. Prior studies of adherence have focused on middle-aged men.
Does CPAP adherence vary by age and sex?
Telemonitoring data from a CPAP ...manufacturer database were used to assess adherence in patients initiating CPAP therapy between November 2015 and October 2018. Analyses were restricted to patients in the United States aged 18 to 90 years.
Across 789,260 patients initiated on CPAP (mean age, 55 ± 14 years; 58.2% male), overall adherence by US Centers of Medicare & Medicaid Services criteria was 72.6%, but it varied dramatically by age and sex, ranging from 51.3% in 18- to 30-year-old women to 80.6% in 71- to 80-year-old men. Patterns of use over the first 90 days demonstrated that younger age groups had peak CPAP use by the 2nd night, with a subsequent decay in use, including abandonment of CPAP, which was greatest among 18- to 30-year-old women. In contrast, older patients steadily increase use, taking more than a week to maximize usage, and then they have much slower decays in use over time. Younger, but not older, patients have lower use of CPAP on weekends compared with weekday nights.
CPAP adherence rates vary substantially by demographics, with 18- to 30-year-old women having the lowest adherence. The pattern of use over the first 90 days also varies substantially by age and sex. Further research to understand and address the causes of disparities will be crucial to maximizing the benefits of CPAP therapy.
A low respiratory arousal threshold (ArTH) is one of several traits involved in obstructive sleep apnea pathogenesis and may be a therapeutic target; however, there is no simple way to identify ...patients without invasive measurements.
To determine the physiologic determinates of the ArTH and develop a clinical tool that can identify patients with low ArTH.
Anthropometric data were collected in 146 participants who underwent overnight polysomnography with an epiglottic catheter to measure the ArTH (nadir epiglottic pressure before arousal). The ArTH was measured from up to 20 non-REM 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.
Nadir oxygen saturation as measured by pulse oximetry, apnea-hypopnea index, and the fraction of events that were hypopneas (Fhypopneas) were independent predictors of the ArTH (r(2) = 0.59; P < 0.001). Using this information, we used receiver operating characteristic 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: (apnea-hypopnea index, <30 events per hour) + (nadir oxygen saturation as measured by pulse oximetry >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 that was confirmed using leave-one-out cross-validation analysis.
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.
Abstract
Study Objectives
To quantify the amount of sleep stage ambiguity across expert scorers and to validate a new auto-scoring platform against sleep staging performed by multiple scorers.
...Methods
We applied a new auto-scoring system to three datasets containing 95 PSGs scored by 6–12 scorers, to compare sleep stage probabilities (hypnodensity; i.e. the probability of each sleep stage being assigned to a given epoch) as the primary output, as well as a single sleep stage per epoch assigned by hierarchical majority rule.
Results
The percentage of epochs with 100% agreement across scorers was 46 ± 9%, 38 ± 10% and 32 ± 9% for the datasets with 6, 9, and 12 scorers, respectively. The mean intra-class correlation coefficient between sleep stage probabilities from auto- and manual-scoring was 0.91, representing excellent reliability. Within each dataset, agreement between auto-scoring and consensus manual-scoring was significantly higher than agreement between manual-scoring and consensus manual-scoring (0.78 vs. 0.69; 0.74 vs. 0.67; and 0.75 vs. 0.67; all p < 0.01).
Conclusions
Analysis of scoring performed by multiple scorers reveals that sleep stage ambiguity is the rule rather than the exception. Probabilities of the sleep stages determined by artificial intelligence auto-scoring provide an excellent estimate of this ambiguity. Compared to consensus manual-scoring, sleep staging derived from auto-scoring is for each individual PSG noninferior to manual-scoring meaning that auto-scoring output is ready for interpretation without the need for manual adjustment.
Adaptive servoventilation (ASV) has demonstrated efficacy in treating sleep-disordered breathing (SDB) in patients with heart failure (HF), but large randomized trials are lacking. We, therefore, ...sought to perform a systematic review and meta-analysis of existing data.
A systematic search of the PubMed database was undertaken in March 2012. Publications were independently assessed by two investigators to identify studies of ≥ 1-week duration that compared ASV to a control condition (ie, subtherapeutic ASV, continuous or bilevel pressure ventilation, oxygen therapy, or no treatment) in adult patients with SDB and HF. Mean, variability,and sample size data were extracted independently for the following outcomes: apneahypopnea index (AHI), left ventricular ejection fraction (LVEF), quality of life (SF-36 Health Survey; Medical Outcomes Trust), 6-min walk distance, peak oxygen consumption ( VO 2 ) % predicted, and ventilatory equivalent ratio for CO 2 ( VE / Vco 2 ) slope measured during exercise. Random effects meta-analysis models were applied.
Fourteen studies were identified (N = 538). Comparing ASV to control conditions, the weighted mean difference in AHI ( -14.64 events/h; 95% CI, -21.03 to - 8.25) and LVEF (0.40;95% CI, 0.08-0.71) both significantly favored ASV. ASV also improved the 6-min walk distance,but not peak O 2 % predicted, VE / VCO 2 slope, or quality of life, compared with control conditions.
In patients with HF and SDB, ASV was more effective than control conditions in reducing the AHI and improving cardiac function and exercise capacity. These data provide a compelling rationale for large-scale randomized controlled trials to assess the clinical impact of ASV on hard outcomes in these patients.
Whereas traditional oncology clinical trial endpoints remain key for assessing novel treatments, capturing patients' functional status is increasingly recognized as an important aspect for supporting ...clinical decisions and assessing outcomes in clinical trials. Existing functional status assessments suffer from various limitations, some of which may be addressed by adopting digital health technologies (DHTs) as a means of collecting both objective and self‐reported outcomes. In this mini‐review, we propose a device‐agnostic multi‐domain model for oncology capturing functional status, which includes physical activity data, vital signs, sleep variables, and measures related to health‐related quality of life enabled by connected digital tools. By using DHTs for all aspects of data collection, our proposed model allows for high‐resolution measurement of objective data as patients navigate their daily lives outside of the hospital setting. This is complemented by electronic questionnaires administered at intervals appropriate for each instrument. Preliminary testing and practical considerations to address before adoption are also discussed. Finally, we highlight multi‐institutional pre‐competitive collaborations as a means of successfully transitioning the proposed digitally enabled data collection model from feasibility studies to interventional trials and care management.
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