Cardiopulmonary Sleep Spectrograms Open a Novel Window Into Sleep Biology-Implications for Health and Disease.

The interactions of heart rate variability and respiratory rate and tidal volume fluctuations provide key information about normal and abnormal sleep. A set of metrics can be computed by analysis of coupling and coherence of these signals, cardiopulmonary coupling (CPC). There are several forms of CPC, which may provide information about normal sleep physiology, and pathological sleep states ranging from insomnia to sleep apnea and hypertension. As CPC may be computed from reduced or limited signals such as the electrocardiogram or photoplethysmogram (PPG) vs. full polysomnography, wide application including in wearable and non-contact devices is possible. When computed from PPG, which may be acquired from oximetry alone, an automated apnea hypopnea index derived from CPC-oximetry can be calculated. Sleep profiling using CPC demonstrates the impact of stable and unstable sleep on insomnia (exaggerated variability), hypertension (unstable sleep as risk factor), improved glucose handling (associated with stable sleep), drug effects (benzodiazepines increase sleep stability), sleep apnea phenotypes (obstructive vs. central sleep apnea), sleep fragmentations due to psychiatric disorders (increased unstable sleep in depression).

Automated Apnea-Hypopnea Index from Oximetry and Spectral Analysis of Cardiopulmonary Coupling.

Rationale: The increased prevalence of obstructive sleep apnea (OSA) coincides with a severe shortage of sleep physicians. There is a need for widescale home-sleep-testing devices with accurate automated scoring to accelerate access to treatment.Objectives: To examine the accuracy of an automated apnea-index (AHI) derived from spectral analysis of cardiopulmonary coupling (CPC) extracted from electrocardiograms, combined with oximetry signals, in relation to polysomnograms (PSGs).Methods: Electrocardiograms and pulse-oximeter tracings on PSGs from APPLES (Apnea Positive Pressure Long-term Efficacy Study) were analyzed. Distinct CPC spectral bands were combined with the oxygen desaturation index to create a derived AHI (DAHI). Correlation statistics between the DAHI and the conventionally scored AHI, in which hypopneas required ≥50% airflow reduction alone or a lesser airflow reduction associated with ≥3% desaturation or arousal, using PSGs from APPLES were calculated.Results: A total of 833 adult subjects were included. The DAHI has excellent and strong correlation with the conventionally scored AHI on PSGs, with Pearson coefficients of 0.972 and receiver operating characteristic curves demonstrating strong agreement in all OSA categories: 98.5% in mild OSA (95% confidence interval [CI], 97.6-99.3%), 96.4% in moderate OSA (95% CI, 95.3-97.5%), and 98.5% in severe OSA (95% CI, 97.8-99.2%).Conclusions: An accurate automated AHI can be derived from oximetry and CPC.

The Implications of the Current Visa System for Foreign Medical Graduates During and After Graduate Medical Education Training.

The current and projected deficit in the physician workforce in the US is a challenge for primary care and specialty medical settings. Foreign medical graduates (FMGs) represent an important component of the US graduate medical education (GME) training pathway and can help to address the US physician workforce deficit. Availability of FMGs is particularly important to the internal medicine community, as recent data demonstrate that internal medicine is the specialty with the highest number of FMGs. System-based and logistical inefficiencies in the current US visa system represent significant obstacles to FMG trainees and have important psychological, emotional, and logistical consequences to FMG engagement and participation in US GME training and in the post-training workforce. In this article, we review the contemporary structure, process, and challenges of obtaining a visa for GME training. The H1B and J1 visa programs are compared and contrasted, with an emphasis on logistical specifics for FMG GME trainees and training programs. The process of and options for J1 visa waivers are reviewed. These considerations are specifically reviewed in the context of recent policy decisions by the Trump administration, with emphasis on the effects of these decisions on FMGs in medical training and practice.

Sequencing Alpha-1 MZ Individuals Shows Frequent Biallelic Mutations.

RATIONALE: Individuals with a single Z mutation in the SERPINA1 gene that codes for alpha-1 antitrypsin (AAT) are at increased risk for COPD if they have ever-smoked. Whether additional variants alter the risk for COPD in this population remains unknown. OBJECTIVES: To determine whether additional SERPINA1 variants impact COPD development in a previously identified MZ (carrier) cohort. METHODS: Individuals with prior MZ results and AAT serum level <16uM were recruited from the Alpha-1 Coded Testing study and Alpha-1 Foundation Research Registry. Participants completed smoking history, demographics, and COPD Severity Score (Range 0-33) using REDCap data capture. At-home finger-stick tests were performed for next generation sequencing (NGS) at the Biocerna LLC laboratory. A genetic counselor reviewed records and interviewed participants with additional variants by NGS. A Wilcoxon Rank Sum test was used to assess correlation between variants and the COPD severity score. RESULTS: A second SERPINA1 variant of known or possible significance was identified in 6 (5.8%) participants. One each of ZZ, SZ, FZ, ZSmunich, ZM2obernburg, and Z/c.922G>T genotypes were identified. ZZ, SZ, and FZ are known pathogenic genotypes. Smunich is a likely pathogenic variant. M2obernburg and c.922G>T are variants of uncertain significance. The ZZ individual was on augmentation therapy when determined MZ by protease inhibitor (Pi) phenotyping; the others had limited targeted genotyping with MZ results. These six participants with biallelic variants had positive COPD severity scores >1. Presence of additional variants was not significantly associated with COPD symptoms in this small sample size. CONCLUSIONS: Some diagnosed MZ individuals instead have biallelic variants. Larger studies are needed to determine COPD-risk liability of variants. Accurate diagnosis impacts medical management and familial risk assessment. Pi phenotyping can be confounded by augmentation therapy and liver transplantation. Because a normal M allele may be reported in the absence of tested mutation(s) in AATD genotyping, clinicians should consider clinical circumstances and laboratory methods when selecting and interpreting AATD tests. Advanced testing, including NGS, may be beneficial for select individuals with prior MZ results. CLINICAL TRIAL REGISTRATION: This study was registered with clinicaltrials.gov (NCT NCT02810327).

Oxygen Therapy in Patients with Acute Myocardial Infarction: A Systemic Review and Meta-Analysis.

OBJECTIVE: Oxygen therapy is frequently used for patients with acute myocardial infarction. The aim of this study is to perform a systematic review and meta-analysis to compare the outcomes of oxygen therapy versus no oxygen therapy in post-acute myocardial infarction settings. METHODS: A systematic search of electronic databases was conducted for randomized studies, which reported cardiovascular events in oxygen versus no oxygen therapy. The evaluated outcomes were all-cause mortality, recurrent coronary events (ischemia or myocardial infarction), heart failure, and arrhythmias. Summary-adjusted risk ratios (RRs) were calculated by the random effects DerSimonian and Laird model. The risk of bias of the included studies was assessed by Cochrane scale. RESULTS: Our meta-analysis included a total of 7 studies with 3842 patients who received oxygen therapy and 3860 patients without oxygen therapy. Oxygen therapy did not decrease the risk of all-cause mortality (pooled RR, 0.99; 95% confidence interval [CI], 0.81-1.21; P = .43), recurrent ischemia or myocardial infarction (pooled RR, 1.19; 95% CI, 0.95-1.48; P = .75), heart failure (pooled RR, 0.94; 95% CI, 0.61-1.45; P = .348), and occurrence of arrhythmia events (pooled RR, 1.01; 95% CI, 0.85-1.2; P = .233) compared with the no oxygen arm. CONCLUSIONS: This meta-analysis confirms the lack of benefit of routine oxygen therapy in patients with acute myocardial infarction with normal oxygen saturation levels.

Emergency Department Blood Gas Utilization and Changes in Ventilator Settings.

BACKGROUND: Mechanically ventilated patients increasingly spend hours in emergency department beds before ICU admission. This study evaluated the performance of blood gases in mechanically ventilated subjects in the emergency department and subsequent changes to mechanical ventilation settings. METHODS: This was a multi-center, prospective, observational study of subjects ventilated in the emergency department, conducted at 3 academic emergency departments from July 2011 to March 2013. We measured the rate of arterial blood gas (ABG) and venous blood gas (VBG) analysis, and we assessed the associations between the conditions of hypoxemia, hyperoxia, hypercapnia, or acidemia and changes to mechanical ventilator settings. RESULTS: Of 292 ventilated subjects, 17.1% did not have a blood gas sent in the emergency department. Ventilator changes were made significantly more frequently for subjects who had an ABG as the initial blood gas sent in the emergency department (odds ratio 2.70, 95% CI 1.46-4.99, P = .002). However, findings of hypoxemia, hyperoxia, hypercapnia, or acidemia were not correlated with ventilator adjustments. CONCLUSIONS: In this prospective observational study of subjects mechanically ventilated in the emergency department, the majority had a blood gas checked while in the emergency department. While ABGs were associated with having changes made to ventilator settings in the emergency department, clinical findings of hypoxemia, hyperoxia, hypercapnia, and acidemia were not. Inattention to blood gas results may lead to missed opportunities in guiding ventilator changes in the emergency department.

COPD in individuals with the PiMZ alpha-1 antitrypsin genotype.

Since the discovery of severe alpha-1 antitrypsin deficiency as a genetic risk factor for emphysema, there has been ongoing debate over whether individuals with intermediate deficiency with one protease inhibitor Z allele (PiMZ, or MZ) are at some risk for emphysema. This is important, because MZ individuals comprise 2-5% of the general population. In this review we summarise the evidence about the risks of the MZ population to develop emphysema or asthma. We discuss the different study designs that have tried to answer this question. The risk of emphysema is more pronounced in case-control than in population-based studies, perhaps due to inadequate power. Carefully designed family studies show an increased risk of emphysema in MZ smokers. This is supported by the rapid decline in lung function of MZ individuals when compared to the general population after massive environmental exposures. The risk of asthma in MZ subjects is less studied, and more literature is needed before firm conclusions can be made. Augmentation therapy in MZ individuals is not supported by any objective studies. MZ smokers are at increased risk for emphysema that is more pronounced when other environmental challenges are present.

Duration of Mechanical Ventilation in the Emergency Department.

INTRODUCTION: Due to hospital crowding, mechanically ventilated patients are increasingly spending hours boarding in emergency departments (ED) before intensive care unit (ICU) admission. This study aims to evaluate the association between time ventilated in the ED and in-hospital mortality, duration of mechanical ventilation, ICU and hospital length of stay (LOS). METHODS: This was a multi-center, prospective, observational study of patients ventilated in the ED, conducted at three academic Level I Trauma Centers from July 2011 to March 2013. All consecutive adult patients on invasive mechanical ventilation were eligible for enrollment. We performed a Cox regression to assess for a mortality effect for mechanically ventilated patients with each hour of increasing LOS in the ED and multivariable regression analyses to assess for independently significant contributors to in-hospital mortality. Our primary outcome was in-hospital mortality, with secondary outcomes of ventilator days, ICU LOS and hospital LOS. We further commented on use of lung protective ventilation and frequency of ventilator changes made in this cohort. RESULTS: We enrolled 535 patients, of whom 525 met all inclusion criteria. Altered mental status without respiratory pathology was the most common reason for intubation, followed by trauma and respiratory failure. Using iterated Cox regression, a mortality effect occurred at ED time of mechanical ventilation > 7 hours, and the longer ED stay was also associated with a longer total duration of intubation. However, adjusted multivariable regression analysis demonstrated only older age and admission to the neurosciences ICU as independently associated with increased mortality. Of interest, only 23.8% of patients ventilated in the ED for over seven hours had changes made to their ventilator. CONCLUSION: In a prospective observational study of patients mechanically ventilated in the ED, there was a significant mortality benefit to expedited transfer of patients into an appropriate ICU setting.

Meta-Analysis of Cardiovascular Outcomes With Continuous Positive Airway Pressure Therapy in Patients With Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Continuous positive airway pressure (CPAP) is the main treatment of OSA. The present study explores the impact of CPAP on cardiovascular outcomes. A systematic search of electronic databases for randomized controlled trials comparing CPAP with medical therapy alone in patients with OSA who reported cardiovascular outcomes of interest was performed. The main outcome was major adverse cardiac events. Other outcomes included cardiac mortality, myocardial infarction, angina pectoris, stroke, and transient ischemic attack. Fixed effect model was used in all analyses except for subgroup analysis in which the random effect DerSimonian and Laird's model was used. Four randomized controlled trials with a total of 3,780 patients were included. Compared with medical therapy alone, CPAP use was not associated with reduced risk of major adverse cardiac events (relative risk [RR] 0.94, 95% confidence interval [CI] 0.78 to 1.15, p = 0.93, I2 = 0%) except in the subgroup that wore CPAP >4 hours (RR 0.70, 95% CI 0.52 to 0.94, p = 0.02, I2 = 0%). Furthermore, no reduction in the risk of cardiac mortality (RR 1.14, 95% CI 0.66 to 1.97, p <0.36, I2 = 2%), myocardial infarction (RR 0.96, 95% CI 0.64 to 1.44, p <0.15, I2 = 47%), angina pectoris (RR 1.16, 95% CI 0.9 to 1.50, p <0.51, I2 = 0%), stroke (RR 1.01, 95% CI 0.73 to 1.38, p <0.0.86, I2 = 0%), and transient ischemic attack (RR 1.36, 95% CI 00.69 to 2.68, p <0.24, I2 = 30%) was observed. Subgroup analysis of CPAP adherence in regards to cardiac outcomes showed that CPAP use is not associated with decreased risk of heart failure (RR 0.91, 95% CI 0.50 to 1.66, p <0.55, I2 = 0%). In conclusion, compared with medical therapy alone, utilization of CPAP in patients with OSA is not associated with improved cardiac outcomes except in patients who wore it for >4 hours.

Incidence of ventilator associated pneumonia in burn patients with inhalation injury treated with high frequency percussive ventilation versus volume control ventilation: A systematic review.

BACKGROUND: Pneumonia increases mortality in burn patients with inhalation injuries. We evaluated whether the use of High Frequency Percussive Ventilation (HFPV) in burn patients with inhalation injuries can decrease rates of Ventilator Associated Pneumonia (VAP) compared to Volume Control Ventilation (VCV). METHODS: Data were gathered from PubMed, EMBASE, Web of Science, reference lists, and hand search. For unpublished data we searched ClinicalTrials.gov and RePORTER. We included observational and Randomized Controlled Trials (RCTs) that compared rates of VAP with the use of HFPV and VCV in adult burn patients with inhalation injury. Two reviewers independently extracted data from the retrieved studies and assessed them for eligibility, methodology, and quality. RESULTS: 281 abstracts were reviewed, of which 4 studies (540 patients) were included. Two were observational and two were RCTs. All studies had moderate risk of bias. One study had low external validity while others had moderate external validity. The two observational studies found non-concordant results. One study found a 24% statistically significant reduction in the rates of VAP while the other found no difference. The two RCTs had small sample sizes. There was no significant difference in VAP rates between HFPV and VCV. The VCV arms of the four studies were heterogeneous. Only one study used low tidal volumes, whereas the rest used high tidal volumes in the VCV arm. CONCLUSION: Evidence about decreased incidence of VAP in burn patients with inhalation injuries who are on HFPV compared to those on VCV is inconclusive. Although enhanced airway clearance by HFPV was thought to play a role in decreasing VAP in this population, high tidal volume in the VCV arms could be a confounding factor that should be eliminated in future studies before a firm conclusion can be reached. More RCTs comparing HFPV to low tidal volume VCV are needed.

Effect of Compliance With a Nurse-Led Intensive Care Unit Checklist on Clinical Outcomes in Mechanically and Nonmechanically Ventilated Patients.

BACKGROUND: Use of checklists brings about improvements in a variety of patient outcomes. Nevertheless, whether compliance with a nurse-led intensive care unit (ICU) checklist produces the same effect is currently unknown. METHODS: This is a retrospective analysis of data obtained during the implementation of a quality improvement project consisting of the utilization of a nurse-led ICU checklist. A consecutive series of checklists obtained from patients admitted in our ICU during 7 consecutive months were included. The ICU stay, hospital stay, and ventilator stay were compared between patients whose practitioners completed or did not complete the checklist. Variables were analyzed using Mann-Whitney U tests for continuous variables and Fisher exact tests for categorical variables. A 2-tailed P < .05 was considered statistically significant. RESULTS: One thousand checklists, corresponding to 346 eligible patients, were collected over 7 months. Mechanical ventilation was used in 203 (59%) patients. Completed checklists were observed for 37.6% (n = 130) of all patients and 38.9% (n = 79) of mechanically ventilated patients. After adjusting for age, Acute Physiology and Chronic Health Evaluation II (APACHE II), body mass index, reason for admission, and type of ICU, completion of the checklist was associated with a 20% increase in the number of days in the ICU compared with the group with incomplete lists. In mechanically ventilated patients, completion of the checklist was associated with a 31% increase in hospital length of stay, a 34% increase in the number of ICU days, and a 32% increase in mechanical ventilation days. CONCLUSION: Compliance with completion of a nurse-led ICU checklist was associated with prolonged ICU stay, hospital stay, and ventilator stay.

Humidification during mechanical ventilation in the adult patient.

Humidification of inhaled gases has been standard of care in mechanical ventilation for a long period of time. More than a century ago, a variety of reports described important airway damage by applying dry gases during artificial ventilation. Consequently, respiratory care providers have been utilizing external humidifiers to compensate for the lack of natural humidification mechanisms when the upper airway is bypassed. Particularly, active and passive humidification devices have rapidly evolved. Sophisticated systems composed of reservoirs, wires, heating devices, and other elements have become part of our usual armamentarium in the intensive care unit. Therefore, basic knowledge of the mechanisms of action of each of these devices, as well as their advantages and disadvantages, becomes a necessity for the respiratory care and intensive care practitioner. In this paper, we review current methods of airway humidification during invasive mechanical ventilation of adult patients. We describe a variety of devices and describe the eventual applications according to specific clinical conditions.