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Background: The main approach to preventing stroke in patients with atrial fibrillation (AF) is anticoagulation (AC), but only about 60% of at-risk individuals are on AC. Patient-facing electronic health record–based interventions have produced mixed results. Little is known about the impact of health portal–based messaging on AC use. Objective: The purpose of this study was describe a protocol we will use to measure the association between AC use and patient portal message opening. We also will measure patient attitudes toward education materials housed on a professional society Web site. Methods: We will send portal messages to patients aged ≥18 years with AF 1 week before an office/teleconference visit with a primary care or cardiology provider. The message will be customized for 3 groups of patients: those on AC; those at elevated risk but off AC; and those not currently at risk but may be at risk in the future. Within the message, we will embed a link to UpBeat.org, a Web site of the Heart Rhythm Society containing patient educational materials. We also will embed a link to a survey. Among other things, the survey will request patients to rate their attitude toward the Heart Rhythm Society Web pages. To measure the effectiveness of the intervention, we will track AC use and its association with message opening, adjusting for potential confounders. Conclusion: If we detect an increase in AC use correlates with message opening, we will be well positioned to conduct a future comparative effectiveness trial. If patients rate the UpBeat.org materials highly, patients from other institutions also may benefit from receiving these materials.

IMPORTANCE:. Kidney and lung injury are closely inter-related during acute respiratory illness, but the molecular risk factors that these organ injuries share are not well defined. OBJECTIVES:. We identified plasma biomarkers associated with severe acute kidney injury (AKI) during acute respiratory illness, and compared them to biomarkers associated with severe acute respiratory failure (ARF). DESIGN, SETTINGS, AND PARTICIPANTS:. Prospective observational cohort study enrolling March 2020 through May 2021, at three hospitals in a large academic health system. We analyzed 301 patients admitted to an ICU with acute respiratory illness. MAIN OUTCOMES AND MEASURES:. Outcomes were ascertained between ICU admission and day 14, and included: 1) severe AKI, defined as doubling of serum creatinine or new dialysis and 2) severe ARF, which included new or persistent need for high-flow oxygen or mechanical ventilation. We measured biomarkers of immune response and endothelial function, pathways related to adverse kidney and lung outcomes, in plasma collected within 24 hours of ICU admission. Severe AKI occurred in 48 (16%), severe ARF occurred in 147 (49%), and 40 (13%) patients experienced both. Two-fold higher concentrations of soluble tumor necrosis factor receptor-1 (sTNFR-1) (adjusted relative risk [aRR], 1.56; 95% CI, 1.24–1.96) and soluble triggering receptor on myeloid cells-1 (sTREM-1) (aRR, 1.85; 95% CI, 1.42–2.41), biomarkers of innate immune activation, were associated with higher risk for severe AKI after adjustment for age, sex, COVID-19, and Acute Physiology and Chronic Health Evaluation-III. These biomarkers were not significantly associated with severe ARF. Soluble programmed cell death receptor-1 (sPDL-1), a checkpoint pathway molecule, as well as soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), molecules involved with endothelial-vascular leukocyte adhesion, were associated with both severe AKI and ARF. CONCLUSIONS AND RELEVANCE:. sTNFR-1 and sTREM-1 were linked strongly to severe AKI during respiratory illness, while sPDL-1, sICAM-1 and sVCAM-1 were associated with both severe AKI and ARF. These biomarker signatures may shed light on pathophysiology of lung-kidney interactions, and inform precision medicine strategies for identifying patients at high risk for these organ injuries.

Coeliac disease (CeD) is a T-cell mediated enteropathy triggered by dietary gluten which remains substantially under-diagnosed around the world. The diagnostic gold-standard requires histological assessment of intestinal biopsies taken at endoscopy while consuming a gluten-containing diet. However, there is a lack of concordance between pathologists in histological assessment, and both endoscopy and gluten challenge are burdensome and unpleasant for patients. Identification of gluten-specific T-cell receptors (TCRs) in the TCR repertoire could provide a less subjective diagnostic test, and potentially remove the need to consume gluten. We review published gluten-specific TCR sequences, and develop an interpretable machine learning model to investigate their diagnostic potential. To investigate this, we sequenced the TCR repertoires of mucosal CD4+ T cells from 20 patients with and without CeD. These data were used as a training dataset to develop the model, then an independently published dataset of 20 patients was used as the testing dataset. We determined that this model has a training accuracy of 100% and testing accuracy of 80% for the diagnosis of CeD, including in patients on a gluten-free diet (GFD). We identified 20 CD4+ TCR sequences with the highest diagnostic potential for CeD. The sequences identified here have the potential to provide an objective diagnostic test for CeD, which does not require the consumption of gluten.

Background: Intrinsic resistance to androgen receptor signalling inhibitors (ARSI) occurs in 20–30% of men with metastatic castration-resistant prostate cancer (mCRPC). Ceramide metabolism may have a role in ARSI resistance. Our study's aim is to investigate the association of the ceramide-sphingosine-1-phosphate (ceramide-S1P) signalling axis with ARSI resistance in mCRPC. Methods: Lipidomic analysis (∼700 lipids) was performed on plasma collected from 132 men with mCRPC, before commencing enzalutamide or abiraterone. AR gene aberrations in 77 of these men were identified by deep sequencing of circulating tumour DNA. Associations between circulating lipids, radiological progression-free survival (rPFS) and overall survival (OS) were examined by Cox regression. Inhibition of ceramide-S1P signalling with sphingosine kinase (SPHK) inhibitors (PF-543 and ABC294640) on enzalutamide efficacy was investigated with in vitro assays, and transcriptomic and lipidomic analyses of prostate cancer (PC) cell lines (LNCaP, C42B, 22Rv1). Findings: Men with elevated circulating ceramide levels had shorter rPFS (HR=2·3, 95% CI=1·5–3·6, p = 0·0004) and shorter OS (HR=2·3, 95% CI=1·4–36, p = 0·0005). The combined presence of an AR aberration with elevated ceramide levels conferred a worse prognosis than the presence of only one or none of these characteristics (median rPFS time = 3·9 vs 8·3 vs 17·7 months; median OS time = 8·9 vs 19·8 vs 34·4 months). SPHK inhibitors enhanced enzalutamide efficacy in PC cell lines. Transcriptomic and lipidomic analyses indicated that enzalutamide combined with SPHK inhibition enhanced PC cell death by SREBP-induced lipotoxicity. Interpretation: Ceramide-S1P signalling promotes ARSI resistance, which can be reversed with SPHK inhibitors. Funding: None.

ABSTRACT Objective: Impaired respiratory mechanics and gas exchange may contribute to sleep disturbance in patients with COPD. We aimed to assess putative associations of different domains of lung function (airflow limitation, lung volumes, and gas exchange efficiency) with polysomnography (PSG)-derived parameters of sleep quality and architecture in COPD. Methods: We retrospectively assessed data from COPD 181 patients ≥ 40 years of age who underwent spirometry, plethysmography, and overnight PSG. Univariate and multivariate linear regression models predicted sleep efficiency (total sleep time/total recording time) and other PSG-derived parameters that reflect sleep quality. Results: The severity of COPD was widely distributed in the sample (post-bronchodilator FEV1 ranging from 25% to 128% of predicted): mild COPD (40.3%), moderate COPD (43.1%), and severe-very severe COPD (16.6%). PSG unveiled a high proportion of obstructive sleep apnea (64.1%) and significant nocturnal desaturation (mean pulse oximetry nadir = 82.2% ± 6.9%). After controlling for age, sex, BMI, apnea-hypopnea index, nocturnal desaturation, comorbidities, and psychotropic drug prescription, FEV1/FVC was associated with sleep efficiency (β = 25.366; R2 = 14%; p < 0.001), whereas DLCO predicted sleep onset latency (β = −0.314; R2 = 13%; p < 0.001) and rapid eye movement sleep time/total sleep time in % (β = 0.085; R2 = 15%; p = 0.001). Conclusions: Pulmonary function variables reflecting severity of airflow and gas exchange impairment, adjusted for some potential confounders, were weakly related to PSG outcomes in COPD patients. The direct contribution of the pathophysiological hallmarks of COPD to objectively measured parameters of sleep quality seems to be less important than it was previously assumed.

This paper presents a review of Environmental Niche Modeling and a methodology for isolating the environmental niche of an aquatic species, given that prior information is available for characterising the physical tolerances for that species. To test and demonstrate our methodology, the environmental niche of the kelp bass has been isolated within Big Fisherman's Cove, Santa Catalina Island, CA, at specific confidence intervals. The motivation for this examination is to demonstrate the utility of ecological analysis in Robotics. Specifically, the utilisation of physical water properties to provide relative navigation and localisation for an aquatic robot. The environmental niches act as navigational landmarks in the seemingly featureless underwater environment. As water patches tend to stick together, this provides persistent landmarks for use in aquatic navigation problems. We provide the background and development of Environmental Niche Models, and present results from field trials for solving the navigation and localisation problem for underwater vehicles. Specifically, we provide results from a technique developed by the authors that utilises physical water parameters, e.g., temperature, salinity, chlorophyll, etc., to localise an underwater vehicle in a given region. The presented method leverages the concept of Environmental Niche Models to provide accurate position estimation that rivals GPS accuracy.

ObjectivesTo determine the incidence of venous thromboembolism (VTE) and the incidence of hospital-acquired VTE (HA-VTE) arising within the population served by the Ireland East Hospital Group (IEHG).Design/home/user/Documents/Sathish Kumar G/RFO/June/21-06-2019/bmjopen_iss_9_7_20190621_1/ A retrospective observational study was conducted using hospital discharge data obtained from the hospital inpatient enquiry data reporting system. In this system, VTE events recorded as ‘primary diagnosis’ represented the reason for initial hospital admission, whereas VTE recorded as a ‘secondary diagnosis’ occurred following admission and were therefore used as an approximation of HA-VTE. These data were used to estimate the overall incidence of VTE and the proportion of these events which were hospital-acquired.SettingThe IEHG is the largest hospital group in the Irish healthcare system and serves a population of over 1 million individuals.ParticipantsData were generated from records pertaining to the 2727 patient admission episodes where a diagnosis of VTE was made during the 22-month study period.ResultsDuring the study period, 2727 VTE events were recorded within the IEHG (which serves a population of 1 036 279) corresponding to an incidence of 1.44 (95% CI 1.36 to 1.51) per 1000 per annum. 1273 (47%) of VTE events were recorded as secondary VTE. The incidence of VTE was highest among individuals over 85 years of age (16.03 per 1000;95% CI 12.81 to 19.26) and was more common following emergency hospital admission.ConclusionThese data suggest that HA-VTE accounts for at least 47% of all VTE events arising within a hospital group serving a population of over 1 million individuals within the Ireland. Given that HA-VTE is a well-recognised source of (potentially preventable) hospital deaths, these findings provide a compelling argument for prioritising strategies directed at reducing the risk of VTE among hospital patients served by the IEHG and within the Ireland as a whole.

Individuals with obstructive sleep apnea (OSA) experience sleep fragmentation and poor sleep quality that results in daytime sleepiness, which impairs performance during driving and leads to an increased risk for collisions. Not surprisingly, observational studies have shown that patients with OSA experience a two- to 10-fold higher risk for collision compared with healthy controls. Although treatment would clearly mitigate these risks, there is no current Canadian position on driving and OSA. This article, the first Canadian position statement addressing the issue, provides an overview of provincial regulations and proposes recommendations with regard to driving in patients with OSA.

Case 1: Mr. P was a 75 year old gentleman with a history of splenic marginal zone lymphoma. His cancer was complicated by development of a pleural effusion and ascites. He was admitted to hospital due to abdominal discomfort but following discharge developed dyspnea. He was referred to the Pleural Space Clinic by his oncologist for worsening dyspnea and consideration of thoracentesis.

The Canadian Thoracic Society (CTS) published an executive summary of guidelines for the diagnosis and treatment of sleep disordered breathing in 2006/2007. These guidelines were developed during several meetings by a group of experts with evidence grading based on committee consensus. These guidelines were well received and the majority of the recommendations remain unchanged. The CTS embarked on a more rigorous process for the 2011 guideline update, and addressed eight areas that were believed to be controversial or in which new data emerged. The CTS Sleep Disordered Breathing Committee posed specific questions for each area. The recommendations regarding maximum assessment wait times, portable monitoring, treatment of asymptomatic adult obstructive sleep apnea patients, treatment with conventional continuous positive airway pressure compared with automatic continuous positive airway pressure, and treatment of central sleep apnea syndrome in heart failure patients replace the recommendations in the 2006/2007 guidelines. The recommendations on bariatric surgery, complex sleep apnea and optimum positive airway pressure technologies are new topics, which were not covered in the 2006/2007 guidelines.

BACKGROUND: Obstructive sleep apnea (OSA) is a common disorder that affects both quality of life and cardiovascular health. The causal link between OSA and cardiovascular morbidity/mortality remains elusive. One possible explanation is that repeated episodes of nocturnal hypoxia lead to a hypercoagulable state that predisposes patients to thrombotic events. There is evidence supporting a wide array of hematological changes that affect hemostasis (eg, increased hematocrit, blood viscosity, platelet activation, clotting factors and decreased fibrinolytic activity).

The present position paper on the use of portable monitoring (PM) as a diagnostic tool for obstructive sleep apnea/hypopnea (OSAH) in adults was based on consensus and expert opinion regarding best practice standards from stakeholders across Canada. These recommendations were prepared to guide appropriate clinical use of this new technology and to ensure that quality assurance standards are adhered to. Clinical guidelines for the use of PM for the diagnosis and management of OSAH as an alternative to in-laboratory polysomnography published by the American Academy of Sleep Medicine Portable Monitoring Task Force were used to tailor our recommendations to address the following: indications; methodology including physician involvement, physician and technical staff qualifications, and follow-up requirements; technical considerations; quality assurance; and conflict of interest guidelines. When used appropriately under the supervision of a physician with training in sleep medicine, and in conjunction with a comprehensive sleep evaluation, PM may expedite treatment when there is a high clinical suspicion of OSAH.

Polysomnography remains the gold standard for diagnosis of Sleep Apnea (SA) and evaluation of the apnea/hypopnea index (AHI) which is used as the primary index of SA severity. The electrocardiogram (typically a single lead) obtained during the polysomnographic study is usually used to report the association between SA and cardiac rhythm disturbances. These findings help in guiding medical decisions but they could also represent a source for confusion. Electrophysiologists are frequently consulted to determine whether interventions need to be taken. We present 2 cases where the ECG during a polysomnography study required the intervention of an electrophysiologist to help with management.