The impact of treatment for obstructive sleep apnoea (OSA) on reduction of cardiovascular risk is unclear. This study aimed to examine the effect of continuous positive airway pressure (CPAP) on ...ambulatory blood pressure (BP) and subclinical myocardial injury in subjects with OSA and hypertension.
This was a parallel-group randomised controlled trial. Subjects with hypertension requiring at least three antihypertensive medications and moderate-to-severe OSA were enrolled. Eligible subjects were randomised (1:1) to receive either CPAP treatment or control (no CPAP) for 8 weeks. Changes in ambulatory BP and serum biomarkers were compared. Stratified analysis according to circadian BP pattern was performed.
92 subjects (75% male; mean±sd age 51±8 years and apnoea-hypopnoea index 40±8 events·h
, taking an average of 3.4 (range 3-6) antihypertensive drugs) were randomised. The group on CPAP treatment, compared with the control group, demonstrated a significant reduction in 24-h systolic BP (-4.4 (95% CI -8.7- -0.1) mmHg; p=0.046), 24-h diastolic BP (-2.9 (95% CI -5.5- -0.2) mmHg; p=0.032), daytime systolic BP (-5.4 (95% CI -9.7- -1.0) mmHg; p=0.016) and daytime diastolic BP (-3.4 (95% CI -6.1- -0.8) mmHg; p=0.012). CPAP treatment was associated with significant BP lowering only in nondippers, but not in dippers. Serum troponin I (mean difference -1.74 (95% CI -2.97- -0.50) pg·mL
; p=0.006) and brain natriuretic peptide (-9.1 (95% CI -17.6- -0.6) pg·mL
; p=0.036) were significantly reduced in CPAP compared with the control group.
In a cohort with OSA and multiple cardiovascular risk factors including difficult-to-control hypertension, short-term CPAP treatment improved ambulatory BP, and alleviated subclinical myocardial injury and strain.
The availability of efficacious anti‐cancer treatments, including oral targeted therapy, do not obviate the need of definitive measures for MPE in newly diagnosed lung cancer. Both early MPE control ...measures and cancer treatments are warranted to minimize the need of pleural re‐interventions in the course of malignancy.
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ABSTRACT
Background and objective
The advent of effective anti‐cancer therapy has brought about uncertainty on the benefit of early definitive measures for newly diagnosed MPE from lung cancer. This study aims to investigate the outcomes of MPE in this setting.
Methods
Lung cancer patients with MPE at first presentation to a tertiary care hospital were followed up till death or censored from 2011 to 2018. Early MPE control measures included chemical pleurodesis or IPC before or shortly after oncological treatment. Predictors of time to MPE re‐intervention were identified with Cox proportional hazard analyses.
Results
Of the 509 records screened, 233 subjects were eligible. One hundred and twenty‐seven subjects received oral targeted therapy as first‐line treatment and 34 (26.8%) underwent early definitive MPE control measures. Early MPE control measures in addition to targeted therapy, as compared to targeted therapy alone, significantly reduced the subsequent need of MPE re‐intervention (23.5% vs 53.8%, P = 0.002). Similar benefits from MPE control measures were found in groups receiving systemic anti‐cancer therapy or best supportive care (0% vs 52%, P = 0.003; 18% vs 56.7%, P = 0.024, respectively). In the group with targetable mutations, both early MPE control measures (HR: 0.25, 95% CI: 0.12–0.53, P < 0.001) and the use of targeted therapy (HR: 0.22, 95% CI: 0.10–0.46, P < 0.001) were independently associated with longer time to MPE re‐interventions.
Conclusion
Early MPE control measures in lung cancer has additional benefits on reducing the need and prolonging the time to MPE re‐intervention, independent of anti‐cancer therapies.
Background: Obstructive sleep apnea (OSA) is associated with adverse cardiovascular outcomes. C-reactive protein (CRP) predicts atherosclerotic
complications. Our study evaluates whether OSA is ...associated with an elevated CRP level, after elimination of known confounders
including visceral obesity.
Methods: Men without significant chronic medical illness, regular medications, or illness in the preceding 4 weeks were enrolled.
Subjects with morbid obesity, newly detected high BP, or fasting glucose were excluded. They underwent polysomnography and
MRI of abdomen to quantify visceral fat volume. High-sensitivity CRP levels were measured.
Results: 111 men with mean body mass index (BMI) 26.3 ± 3.8 kg/m 2 were evaluated. After adjustment for age, smoking, BMI, waist circumference, and sleep efficiency, CRP correlated positively
with the apnea-hypopnea index (AHI) r = 0.35, p < 0.001, duration of O 2 saturation < 90% ( r = 0.29, p = 0.002), and arousal index ( r = 0.32, p = 0.001), and it correlated negatively with minimal O 2 saturation ( r = â0.29, p = 0.002). These correlations were consistent when adjustment was made for MRI visceral fat volume instead of waist
circumference. In the regression model, significant predictors of CRP included AHI, waist circumference, and triglycerides
(adjusted R 2 , 0.33, p = 0.001, p = 0.002, p = 0.018, respectively). Among the 111 subjects, 32 subjects with no or mild OSA (AHI < 15
events/h) were matched with 32 subjects with moderate-to-severe OSA (AHI ⥠15 events/h) in MRI visceral fat volume. CRP was
higher in subjects with moderate-to-severe OSA (median, 1.32; 0.45 to 2.34 mg/L) when compared to subjects with no or mild
OSA (median, 0.54; 0.25 to 0.89 mg/L; p = 0.001).
Conclusions: In healthy middle-aged men, elevated CRP level is associated with OSA independent of visceral obesity.
ABSTRACT
The endothelium functions not only as a semi‐selective barrier between body tissue and circulation; it also plays an active role in the maintenance of a healthy vasculature. Endothelial ...dysfunction is increasingly found to play a pivotal role in the pathogenesis of atherosclerosis. Impaired endothelium‐dependent vasodilation, as a marker of endothelial dysfunction, predates and predicts cardiovascular disease. Endothelial dysfunction is thought to result from oxidative stress, inflammatory gene activation and cytokine cascade, as well as impairment of endothelial repair mechanisms. In the context of sleep‐related breathing disorders, obstructive sleep apnoea (OSA) is postulated to contribute independently to cardiovascular morbidity and mortality. Thus, endothelial dysfunction is an important target of research in vascular pathogenesis and also serves as an intermediary outcome indicator in clinical trials evaluating cardiovascular sequelae in OSA. Basic or translational studies have identified cellular and molecular mechanisms of potential relevance to endothelial dysfunction in OSA, while epidemiological or clinical studies have shown endothelial dysfunction attributable to sleep‐disordered breathing, which could improve with effective treatment of OSA. Endothelial dysfunction is poised to serve as a call for timely intervention with possibility of halting or even reverting vascular injury in sleep‐related breathing disorders. Much remains to be explored about the complex pathways of endothelial dysfunction and its clinical manifestations in subjects with OSA, which are likely to involve multiple contributing factors. Evidence‐based information will allow us to construct the framework for guiding individualized clinical management and public health strategies for OSA, as well as cardiometabolic diseases.
Nicotine and its derivatives, by binding to nicotinic acetylcholine receptors (nAChRs) on bronchial epithelial cells, can regulate cellular signaling and inflammatory processes. Delineation of nAChR ...subtypes and their responses to nicotine stimulation in bronchial epithelium may provide information for therapeutic targeting in smoking-related inflammation in the airway. Expression of nAChR subunit genes in 60 bronchial epithelial biopsies and immunohistochemical staining for the subcellular locations of nAChR subunit expression were evaluated. Seven human bronchial epithelial cell lines (HBECs) were exposed to nicotine in vitro for their response in nAChR subunit gene expression to nicotine exposure and removal. The relative normalized amount of expression of nAChR α4, α5, and α7 and immunohistochemical staining intensity of nAChR α4, α5, and β3 expression showed significant correlation with lung function parameters. Nicotine stimulation in HBECs resulted in transient increase in the levels of nAChR α5 and α6 but more sustained increase in nAChR α7 expression. nAChR expression in bronchial epithelium was found to correlate with lung function. Nicotine exposure in HBECs resulted in both short and longer term responses in nAChR subunit gene expression. These results gave insight into the potential of targeting nAChRs for therapy in smoking-related inflammation in the airway.
•Developed two simple-to-use nomograms to identify COVID-19-positive patients•Probabilities are provided to allow healthcare leaders to decide suitable cut-offs•Variables are age, white cell count, ...chest X-ray appearances, and contact history•Model variables are easily available in the general hospital setting
To develop: (1) two validated risk prediction models for coronavirus disease-2019 (COVID-19) positivity using readily available parameters in a general hospital setting; (2) nomograms and probabilities to allow clinical utilisation.
Patients with and without COVID-19 were included from 4 Hong Kong hospitals. The database was randomly split into 2:1: for model development database (n = 895) and validation database (n = 435). Multivariable logistic regression was utilised for model creation and validated with the Hosmer–Lemeshow (H–L) test and calibration plot. Nomograms and probabilities set at 0.1, 0.2, 0.4 and 0.6 were calculated to determine sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).
A total of 1330 patients (mean age 58.2 ± 24.5 years; 50.7% males; 296 COVID-19 positive) were recruited. The first prediction model developed had age, total white blood cell count, chest x-ray appearances and contact history as significant predictors (AUC = 0.911 CI = 0.880−0.941). The second model developed has the same variables except contact history (AUC = 0.880 CI = 0.844−0.916). Both were externally validated on the H–L test (p = 0.781 and 0.155, respectively) and calibration plot. Models were converted to nomograms. Lower probabilities give higher sensitivity and NPV; higher probabilities give higher specificity and PPV.
Two simple-to-use validated nomograms were developed with excellent AUCs based on readily available parameters and can be considered for clinical utilisation.
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