Impact of obstructive sleep apnoea/hypopnoea and its treatment with continuous positive airway pressure on the outcome of stroke

BACKGROUND: The prevalence of sleep-disordered breathing (SDB) in stroke is high. One study showed SDB had a negative impact on the functional capacity of stroke patients on discharge and another that SDB was associated with a higher mortality rate. However, these findings are disputed. The impact of SDB in stroke patients on cognition and health-related quality of life is also not clear. The one randomized controlled trial of nasal continuous positive airway pressure (CPAP) in stroke patients with SDB showed CPAP improved wellbeing but not other outcomes. I hypothesised that: (1) SDB is related to stroke outcome and (2) treatment of SDB in stroke patients with CPAP would improve functional outcome.METHODS: There are three parts of the thesis: (1) a study of the prevalence of SDB after stroke; (2) a randomized controlled trial (RCT) of CPAP after stroke and (3) a longitudinal cohort study to investigate the impact of SDB on outcome after stroke. On day 14-19 after stroke, recruited patients underwent a limited sleep study using a validated system (Embletta PDS, Medcare Flaga, Iceland). Baseline assessments were performed on the morning following the sleep study. On day 21-25 following stroke, patients who had (A+H)-h⁻¹ ≥ 30 with < 30% of central events were randomized to 8 weeks of CPAP treatment with Autoset T (ResMed, SanDiego USA) or conservative treatment for SDB. All outcomes were recorded in the 8th week after randomization or 3 months after stroke for non-randomized patients. All recruited patients received follow-up at six months after stroke. If available, patients also received 12 months and 18 months follow-up until the last recruited patient had had his 6 months follow-up. The Nottingham Extended ADL Index (EADL) was chosen as the primary outcome measure. Secondary outcome measures included: Subscales of EADL, NIH Stroke Scale (NIHSS), Barthel Index (BI), Stanford Sleepiness Scale (SSS), Addenbrooke's Cognitive Examination (ACE) and Mini- Mental State Examination (MMSE), Hospital Anxiety and Depression Scale (HADS), MOS Short Form 36 Health Survey (SF-36) and ambulatory blood pressure - measured with Spacelabs 90207 (Spacelabs, Redmond, USA).RESULTS: We screened 658 patients with recent strokes and excluded those with dementia, confusion, severe dysphasia or insufficient hand function to use CPAP. Only 96 of 658 patients remained eligible of whom 25 declined to give informed consent. 71 patients were thus successfully recruited for overnight limited sleep study 14-19 days following stroke. Sixty-six patients with adequate recording were included in the study: 45 men and 21 women, median age 74yrs. The sleep study showed 50% of patients had more than 30 apnoeas + hypopnoeas per hour in bed [expressed as (A+H)-h⁻¹]. Pulse oximetry alone had lower sensitivity (70%) but high specificity (90%) to predict (A+H)-h⁻¹ ≥ 30. A combination of age, body mass index, snoring and excessive daytime sleepiness based on logistic regression model is useful as a screening tool at the bedside (sensitivity = 85%, specificity = 70%) to predict (A+H)-h⁻¹ ≥ 30 in stroke before referring patients for overnight sleep study. Interaction of lowest oxygen saturation and lowest heart rate is independently associated with stroke during sleep in patients with (A+H)-h⁻¹ < 30 (p = 0.023). Patients with (A+H)-h⁻¹ ≥ 30 more often had their stroke during daytime than patients with (A+H)-h⁻¹ < 30 (p = 0.006). Thirty patients who had (A+H)-h⁻¹ ≥ 30, with < 30% central apnoea or Cheyne-Stokes respiration, proceeded to a randomized controlled trial starting from the 4th week after stroke with 15 patients randomized to CPAP and 15 to conservative treatment for SDB. Conventional stroke treatment was maintained in all patients. Duration of treatment was 8 weeks and blind outcome assessment was performed at 3 months and 6 month after stroke. The result showed compliance with CPAP was poor with mean 1.40 hours and median 0.16 hours per night. There was no statistically significant difference in the outcomes, sleepiness and ambulatory blood pressure with CPAP therapy. Increased length of keeping CPAP was correlated with higher score of language subscale in the Addenbrooke's Cognitive Examination (Spearman's rho = 0.544, p = 0.036) and lower score in the depression subscale of the Hospital Anxiety and Depression Scale (HADS, Spearman's rho = -0.538, p = 0.039). All 66 patients with adequate sleep studies received longitudinal follow-up at 3, 6 12 and 18 months following stroke. The patients with (A+H)-h⁻¹ ≥ 30 had a trend to worse functional capacity in both Barthel Index and Nottingham Extended ADL Index (EADL) than patients with (A+H)-h⁻¹ < 30 but there was only a statistically significant difference in the mobility subscale of EADL. The negative influence of (A+H)-h⁻¹ ≥ 30 on functional capacity and health-related quality of life following stroke was only statistically significant in patients with mild stroke (NIH Stroke Scale, NIHSS < 7) at both 3 and 6 months, lesser emotional distress (HADS < 8) at both 3 and 6 months and lesser cognitive impairment (Mini Mental State Examination ≥ 28) at 6 months after stroke in subgroup analysis. The difference of Modified Rankin Scale between groups was significant at 6 months after stroke (p = 0.026). There was no difference in cognitive or emotional outcome. No significant difference of mortality rate was noted.CONCLUSIONS: We focused on a group of patients with mild to moderate stroke (median NIHSS = 6) within a narrow time span (14-19 days) and confirmed a high prevalence of SDB in stroke. CPAP compliance was a major problem but might be enhanced by selecting patients with higher functional capacity, higher cognitive function especially language and less depression in the acute or subacute phase of stroke. We also found that sleep-disordered breathing had little or no effect on cognitive and emotional outcomes, health-related quality of life and mortality in stroke patients. Many other factors resulting from brain damage or complications of stroke have stronger influences on stroke outcome than SDB

Prescription Patterns of Chinese Herbal Products for Osteoporosis in Taiwan: A Population-Based Study

Background. Traditional Chinese medicine (TCM) includes Chinese herbal products (CHPs), acupuncture, and traumatology manipulative therapies. TCM physicians often prescribe CHP to treat patients with osteoporosis; however, the drugs used and their patterns of prescriptions have yet to be characterized. This study, therefore, aimed to evaluate the CHP used for the treatment of osteoporosis in Taiwan and their prescription patterns. Methods. A cohort of one million randomly sampled cases from the National Health Insurance Research Database (NHIRD) was analyzed to evaluate the frequencies and percentages of herbal formula and single herb prescriptions for osteoporosis. Association rules were then applied to evaluate the CHP coprescription patterns and the prevalence of osteoporosis. Results. The osteoporosis cohort included 16 544 patients, of whom more than 70% had used TCM on one or more occasion. Of these patients, 4 292 (25.9%) had been hospitalized at least once because of fracture. Du-Huo-Ji-Sheng-Tang and Du Zhong (Cortex Eucommiae) were the most frequently prescribed herbal formula and single herb, respectively, for the treatment of osteoporosis. Conclusion. This study identified patterns of CHP use for the treatment of osteoporosis. However, further research is required to fully elucidate the efficacy and safety of these CHP

Orthodontically Induced Changes to the Genetic Profile in Periodontal Ligament Tissue and Cytokine Release in Gingival Crevicular Fluid - a Pilot Investigation

BACKGROUND/PURPOSE: It has been known that genetic factors influence orthodontic tooth movement, however, scientific research on humans is lacking. Therefore, this study aimed to investigate dynamic changes to the genetic profile in human periodontal ligament (PDL) tissue and cytokine release in gingival crevicular fluid (GCF) during the first 28 days of orthodontic treatment. MATERIALS AND METHODS: Fifteen teeth from three patients were recruited. Full-mouth fixed appliances with extraction of four premolars and one maxillary third molar was planned for orthodontic treatment. GCF collection and tooth extraction were performed following force application for 0, 1, 3, 7, and 28 days. GCF was analyzed using multiplex immunoassay for 27 cytokines. PDL tissue was collected after extraction and submitted for RNA exome-sequencing using Illumina sequencing platform. Further analysis of differentially expressed genes (DEGs), gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and heatmaps were conducted. RESULTS: GCF cytokine levels varied among three patients; some patients exhibited a peak cytokine level on Day 0 whereas others did so on Days 1-3. In RNA exome sequencing data, GO and KEGG analyses showed that genes associated with sensory receptors were upregulated on Day 1, genes involved in bone remodeling were upregulated on Days 3 and 28, and genes related to osteoclast differentiation were upregulated on Day 7. CONCLUSION: RNA sequencing data demonstrate that the specific types of genes are expressed at different time points, whereas the data on cytokine changes show a large variation in concentration levels and dynamic change patterns among the patients

Synthetic control of living cells by intracellular polymerization

An emerging cellular engineering method creates synthetic polymer matrices inside cells. By contrast with classical genetic, enzymatic, or radioactive techniques, this materials-based approach introduces non-natural polymers inside cells, thus modifying cellular states and functionalities. Here, we cover various materials and chemistries that have been exploited to create intracellular polymer matrices. In addition, we discuss emergent cellular properties due to the intracellular polymerization, including nonreplicating but active metabolism, maintenance of membrane integrity, and resistance to environmental stressors. We also discuss past work and future opportunities for developing and applying synthetic cells that contain intracellular polymers. The materials-based approach will usher in new applications of synthetic cells for broad biotechnological applications

Left ventricular mass and hemodynamic overload in normotensive hemodialysis patients

Left ventricular mass and hemodynamic overload in normotensive hemodialysis patients.BackgroundIt remains uncertain whether the hemodynamic parameters are important determinants of left ventricular mass (LVM) in normotensive chronic hemodialysis (NTHD) patients, as has been found in their hypertensive counterparts.MethodsForty NTHD patients (mean age, 53.7 ± 14.4 years; male/female, 18/22) without the requirement of antihypertensive drugs for at least six months were studied. Controls were 41 hypertensive hemodialysis patients (HTHD) and 46 normotensive subjects with normal renal function (NTNR). The influence of anthropometrics, cardiovascular structure and function, and volume status on LVM (by two-dimensional echocardiography) was analyzed by steps of multiple linear regression.ResultsAs compared with the NTNR and NTHD group, the HTHD group had obvious pressure and volume/flow overload, and greater LV wall thickness, chamber size and mass. In contrast, NTHD subjects had similar blood pressure, large artery function, LV chamber size and stroke volume as the NTNR subjects. However, the NTHD patients still had greater wall thickness and LVM, along with greater cardiac output, lower total peripheral resistance and lower end-systolic meridional stress to volume ratio (ESSV) than the NTNR group. LVM in the NTHD group was significantly positively related to averaged systolic blood pressure (SBPavg), body surface area, extracellular fluid (ECF), carotid intima-media thickness (IMT), aortic pulse wave velocity (PWV), and negatively related to ESSV and Kt/V. The independent significant noncardiac structural determinants of LVM in NTHD subjects were ESSV, SBPavg, PWV and SV (model r2 = 0.617, P < 0.001).ConclusionsThe NTHD patients, without significant pressure and volume overload, still had increased LVM that was partially explained by the persistent flow overload and subclinical LV dysfunction

Triptolide Transcriptionally Represses HER2 in Ovarian Cancer Cells by Targeting NF- κ

Triptolide (TPL) inhibits the proliferation of a variety of cancer cells and has been proposed as an effective anticancer agent. In this study, we demonstrate that TPL downregulates HER2 protein expression in oral, ovarian, and breast cancer cells. It suppresses HER2 protein expression in a dose- and time-dependent manner. Transrepression of HER2 promoter activity by TPL is also observed. The interacting site of TPL on the HER2 promoter region is located between −207 and −103 bps, which includes a putative binding site for the transcription factor NF-κB. Previous reports demonstrated that TPL suppresses NF-κB expression. We demonstrate that overexpression of NF-κB rescues TPL-mediated suppression of HER2 promoter activity and protein expression in NIH3T3 cells and ovarian cancer cells, respectively. In addition, TPL downregulates the activated (phosphorylated) forms of HER2, phosphoinositide-3 kinase (PI3K), and serine/threonine-specific protein kinase (Akt). TPL also inhibits tumor growth in a mouse model. Furthermore, TPL suppresses HER2 and Ki-67 expression in xenografted tumors based on an immunohistochemistry (IHC) assay. These findings suggest that TPL transrepresses HER2 and suppresses the downstream PI3K/Akt-signaling pathway. Our study reveals that TPL can inhibit tumor growth and thereby may serve as a potential chemotherapeutic agent

Major interventions are associated with survival of out of hospital cardiac arrest patients - a population based survey

Background. The overall survival rate of out-of-hospital cardiac arrest (OHCA) in Taiwan or even in the whole of Asia is relatively low. Major interventions, such as target temperature management (TTM), coronary artery angiography, and extracorporeal membrane oxygenation (ECMO), have been associated with better patient outcome. However, studies in Taiwan revealing evidence of the benefits of these interventions are limited. Methods. A population-based study used an 8-year database to analyze overall survival and risk factors ˝among OHCA patients. All adult non-trauma OHCA patients were identified through diagnostic and procedure codes. Hospital survival and return of spontaneous circulation (ROSC) were primary and secondary outcomes. Logistic regression and Cox regression analyses were conducted. Results. There was a relationship between major interventions (including TTM, coronary artery angiography, and ECMO) and better hospital survival. Age, income, major interventions, and acute myocardial infarction history were associated with hospital survival. The adjusted hazard ratios (HRs) were 0.406 (95% CI, 0.295 to 0.558), 1.109 (95% CI, 1.027 to 1.197), 1.075 (95% CI, 1.002 to 1.154), 1.097 (95% CI, 1.02 to 1.181) and 0.799(95% CI, 0.677 to 0.942) for patients with major interventions, age≥50, medium low and low income, middle income, and acute myocardial infarction history, respectively. Conclusion. This population-based study in Taiwan revealed that older age (≥50), medium low and low income were associated with a lower rate of survival. Major interventions, including TTM, coronary angiography, and ECMO, were related to better survival

The Inhibitory Effect of Ellagic Acid on Cell Growth of Ovarian Carcinoma Cells

Ellagic acid (EA) is able to inhibit the growth of several cancer cells; however, its effect on human ovarian carcinoma cells has not yet been investigated. Ovarian carcinoma ES-2 and PA-1 cells were treated with EA (10~100 μM) and assessed for viability, cell cycle, apoptosis, anoikis, autophagy, and chemosensitivity to doxorubicin and their molecular mechanisms. EA inhibited cell proliferation in a dose- and time-dependent manner by arresting both cell lines at the G1 phase of the cell cycle, which were from elevating p53 and Cip1/p21 and decreasing cyclin D1 and E levels. EA also induced caspase-3-mediated apoptosis by increasing the Bax : Bcl-2 ratio and restored anoikis in both cell lines. The enhancement of apoptosis and/or inhibition of autophagy in these cells by EA assisted the chemotherapy efficacy. The results indicated that EA is a potential novel chemoprevention and treatment assistant agent for human ovarian carcinoma

Outcome of lung cancer patients with acute respiratory failure requiring mechanical ventilation

AbstractTo assess the weaning outcome of lung cancer patients with acute respiratory failure (ARF) requiring mechanical ventilation, we retrospectively analyzed the database of the respiratory intensive care unit at a university-affiliated tertiary care hospital.Charts were reviewed for cancer status, biochemistries before respiratory failure, causes of respiratory failure, acute physiology and chronic health evaluation (APACHE) III score, ventilatory settings, data recorded during spontaneous breathing, duration of ventilator days, and weaning outcome. Ninety-five consecutive respiratory failure events in 81 patients were recorded from January 1, 1995 through June 30, 1999.Twenty-six episodes ended with successful weaning (27.4%). Age, gender, and cancer status did not affect the weaning outcome. Serum albumin level, APACHE III score, highest fractional inspired O2 (FiO2) and highest positive end-expiratory pressure, organ failure, ability to shift to partial ventilatory support, and duration of mechanical ventilation could significantly influence the weaning outcome statistically. The overall hospital mortality rate was 85.2%.Our results suggested that lung cancer patients with ARF will have a better chance to wean if the initial APACHE III score was less than 70, use of FiO2 never exceeded 0.6, or less than 2 additional organ systems failed during the treatment course