The Association of Sleep Apnea and Cardiorespiratory Fitness With Long-Term Major Cardiovascular Events

ObjectiveTo determine the risk of long-term major adverse cardiovascular events (MACE) when sleep-disordered breathing (SDB) and decreased cardiorespiratory fitness (CRF) co-occur.MethodsWe included consecutive patients who underwent symptom-limited cardiopulmonary exercise tests between January 1, 2005, and January 1, 2010, followed by first-time diagnostic polysomnography within 6 months. Patients were stratified based on the presence of moderate-to-severe SDB (apnea/hypopnea index ≥15 per hour) and decreased CRF defined as <70% predicted peak oxygen consumption (VO₂). Long-term MACE was a composite outcome of myocardial infarction (MI), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), stroke or transient ischemic attack (TIA), and death, assessed until May 21, 2018. Cox-proportional hazard models were adjusted for factors known to influence CRF and MACE.ResultsOf 498 included patients (60±13 years, 28.1% female), 175 (35%) had MACE (MI=17, PCI=14, CABG=13, stroke=20, TIA=12, deaths=99) at a median follow-up of 8.7 years (interquartile range=6.5 to 10.3 years). After adjusting for age, sex, beta blockers, systemic hypertension, diabetes mellitus, coronary artery disease, cardiac arrhythmia, chronic obstructive pulmonary disease, smoking, and use of positive airway pressure (PAP), decreased CRF alone (hazard ratio [HR]=1.91, 95% confidence interval [CI], 1.15 to 3.18; P=.01), but not SDB alone (HR=1.26, 95% CI, 0.75 to 2.13, P=.39) was associated with increased risk of MACE. Those with SDB and decreased CRF had greater risk of MACE compared with patients with decreased CRF alone (HR=1.85; 95% CI, 1.21 to 2.84; P<.005) after accounting for these confounders. The risk of MACE was attenuated in those with reduced CRF alone after additionally adjusting for adequate adherence to PAP (HR=1.59; 95% CI, 0.77 to 3.31; P=.21).ConclusionThe incidence of MACE, especially mortality, was high in this sample. Moderate-to-severe SDB with concurrent decreased CRF was associated with higher risk of MACE than decreased CRF alone. These results highlight the importance of possibly including CRF in the risk assessment of patients with SDB and, conversely, that of screening for SDB in patients with low peak VO₂.     

Azathioprine acts upon rat hepatocyte mitochondria and stress-activated protein kinases leading to necrosis: protective role of N-acetyl-L-cysteine

Azathioprine is an immunosuppressant drug widely used. Our purpose was to 1) determine whether its associated hepatotoxicity could be attributable to the induction of a necrotic or apoptotic effect in hepatocytes, and 2) elucidate the mechanism involved. To evaluate cellular responses to azathioprine, we used primary culture of isolated rat hepatocytes. Cell metabolic activity, reduced glutathione, cell proliferation, and lactate dehydrogenase release were assessed. Mitochondria were isolated from rat livers, and swelling and oxygen consumption were measured. Mitogen-activated protein kinase pathways and proteins implicated in cell death were analyzed. Azathioprine decreased the viability of hepatocytes and induced the following events: intracellular reduced glutathione (GSH) depletion, metabolic activity reduction, and lactate dehydrogenase release. However, the cell death was not accompanied by DNA laddering, procaspase-3 cleavage, and cytochrome c release. The negative effects of azathioprine on the viability of hepatocytes were prevented by cotreatment with N-acetyl-L-cysteine. In contrast, 6-mercaptopurine showed no effects on GSH content and metabolic activity. Azathioprine effect on hepatocytes was associated with swelling and increased oxygen consumption of intact isolated rat liver mitochondria. Both effects were cyclosporine A-sensitive, suggesting an involvement of the mitochondrial permeability transition pore in the response to azathioprine. In addition, the drug's effects on hepatocyte viability were partially abrogated by c-Jun N-terminal kinase and p38 kinase inhibitors. In conclusion, our findings suggest that azathioprine effects correlate to mitochondrial dysfunction and activation of stress-activated protein kinase pathways leading to necrotic cell death. These negative effects of the drug could be prevented by coincubation with N-acetyl-L-cysteine.     

Localization of realistic cortical activity in MEG using current multipoles

We present a novel approach to MEG source estimation based on a regularized first-order multipole solution. The Gaussian regularizing prior is obtained by calculation of the sample mean and covariance matrix for the equivalent moments of realistic simulated cortical activity. We compare the regularized multipole localization framework to the classical dipole and general multipole source estimation methods by evaluating the ability of all three solutions to localize the centroids of physiologically plausible patches of activity simulated on the surface of a human cerebral cortex. The results, obtained with a realistic sensor configuration, a spherical head model, and given in terms of field and localization error, depict the performance of the dipolar and multipolar models as a function of variable source surface area (50-500 mm(2)), noise conditions (20, 10, and 5 dB SNR), source orientation (0-90 degrees ), and source depth (3-11 cm). We show that as the sources increase in size, they become less accurately modeled as current dipoles. The regularized multipole systematically outperforms the single dipole model, increasingly so as the spatial extent of the sources increases. In addition, our simulations demonstrate that as the orientation of the sources becomes more radial, dipole localization accuracy decreases substantially, while the performance of the regularized multipole model is far less sensitive to orientation and even succeeds in localizing quasi-radial source configurations. Furthermore, our results show that the multipole model is able to localize superficial sources with higher accuracy than the current dipole. These results indicate that the regularized multipole solution may be an attractive alternative to current-dipole-based source estimation methods in MEG.     

A family information brochure and dedicated website to improve the ICU experience for patients’ relatives: an Italian multicenter before-and-after study

Purpose

Good communication between ICU staff and patients’ relatives may reduce the occurrence of post-traumatic stress disorder, anxiety or depression, and dissatisfaction with clinicians. An information brochure and website to meet relatives’ needs were designed to explain in technical yet simple terms what happens during and after an ICU stay, to legitimize emotions such as fear, apprehension, and suffering, and to improve cooperation with relatives without increasing staff workload. The main outcomes were improved understanding of prognosis and procedures, and decrease of relatives’ anxiety, depression, and stress symptoms.

Methods

In this prospective multicenter before-and-after study, a self-administered questionnaire was used to investigate relatives’ understanding of prognosis, treatments, and organ dysfunction, families’ satisfaction, and symptoms of anxiety, depression, and post-traumatic stress.

Results

A total of 551 relatives received questionnaires in nine Italian ICUs; 332 (60%) responded, 144 before and 179 after implementation of the brochure and website. Of the 179 relatives who responded after, 131 (73%) stated they had read the brochure and 34 (19%) reported viewing the website. The intervention was associated with increased correct understanding of the prognosis (from 69 to 84%, p = 0.04) and the therapeutic procedures (from 17 to 28%, p = 0.03). Multivariable analysis, together with non-modifiable factors (relative’s gender, education level, relationship to patient, and patient status at ICU discharge), showed the intervention to be significantly associated with a lower incidence of post-traumatic stress symptoms (Poisson coefficient = ?0.29, 95% CI ?0.52/?0.07). The intervention had no effect on the prevalence of symptoms of anxiety and depression.

Conclusion

An information brochure and website designed to meet relatives’ needs improved family members’ comprehension and reduced their prevalence of stress symptoms.

     

Assessing the quality of nursing work life

Traditionally, nursing has measured job satisfaction by focusing on employees' likes and dislikes. However, job satisfaction is an unsatisfactory construct to assess either the jobs themselves or employees' feelings about work sinceas much as 30% of the variance explained in job satisfaction surveys is a function of personality, something employers can do little to change. Based on socio-technical systems theory, quality of nursing work life (QNWL) assessments focus on identifying opportunities for nurses to improve their work and work environment while achieving the organization's goals. Moreover, some evidence suggests that improvements in work life are needed to improve productivity. Therefore, assessing QNWL reveals areas for improvement where the needs of both the employees and the organization converge. The purpose of this article was to assess the QNWL of staff nurses using Brooks' Quality of Nursing Work Life Survey.     

Resting fluctuations in arterial carbon dioxide induce significant low frequency variations in BOLD signal

Carbon dioxide is a potent cerebral vasodilator. We have identified a significant source of low-frequency variation in blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) signal at 3 T arising from spontaneous fluctuations in arterial carbon dioxide level in volunteers at rest. Fluctuations in the partial pressure of end-tidal carbon dioxide (Pet(CO(2))) of +/-1.1 mm Hg in the frequency range 0-0.05 Hz were observed in a cohort of nine volunteers. Correlating with these fluctuations were significant generalized grey and white matter BOLD signal fluctuations. We observed a mean (+/-standard error) regression coefficient across the group of 0.110 +/- 0.033% BOLD signal change per mm Hg CO(2) for grey matter and 0.049 +/- 0.022% per mm Hg in white matter. Pet(CO(2))-related BOLD signal fluctuations showed regional differences across the grey matter, suggesting variability of the responsiveness to carbon dioxide at rest. Functional magnetic resonance imaging (fMRI) results were corroborated by transcranial Doppler (TCD) ultrasound measurements of the middle cerebral artery (MCA) blood velocity in a cohort of four volunteers. Significant Pet(CO(2))-correlated fluctuations in MCA blood velocity were observed with a lag of 6.3 +/- 1.2 s (mean +/- standard error) with respect to Pet(CO(2)) changes. This haemodynamic lag was adopted in the analysis of the BOLD signal. Doppler ultrasound suggests that a component of low-frequency BOLD signal fluctuations is mediated by CO(2)-induced changes in cerebral blood flow (CBF). These fluctuations are a source of physiological noise and a potentially important confounding factor in fMRI paradigms that modify breathing. However, they can also be used for mapping regional vascular responsiveness to CO(2).     

Using action research to construct national evidence-based nursing care guidance for gerontological nursing

Aim. This paper explores the development of a low‐cost, involving methodology for constructing nursing‐focused evidence‐based national care guidance, known as Best Practice Statements, the intended users of which are gerontological nurses practising throughout Scotland. Design. The Best Practice Statement construction methodology forms one cycle in a five‐year longitudinal action research study that aims to achieve evidence‐based nursing, facilitate professional networking to support practice development and promote the principles and practice of gerontological nursing. Achieving these aims involved designing a virtual Practice Development College. Methods. A Community of Practice comprising practising gerontological nurses, expert advisors, academic teaching and research nurses collaborated in face‐to‐face meetings and in the virtual Practice Development College to delineate and refine the procedural model for Best Practice Statement construction. Focus groups, telephone interviews, analysis of on‐line archives and documentary outputs formed the analytic dataset. Results. Qualitative analysis indicated that, from the perspective of the community of practice, the emerging methodology facilitated the melding of knowledge sources reflecting the dominant evidence hierarchy with other forms of evidence valued by gerontological nurses, in the Best Practice Statement. Relevance to clinical practice. Current methods of care guidance construction rarely address the concerns of nurses and the evidence from which guidelines are developed is narrowly defined with regard to inclusion and acceptability. In contrast this model focuses on nursing issues, embraces a wider definition of evidence and ensures that the published Best Practice Statements are credible and achievable in gerontological practice, where they are tested and refined as an inherent aspect of the development process.