Awake at the wheel: how auto technology innovations present ongoing sleep challenges and new safety opportunities.

Individuals and society are dependent on transportation. Individuals move about their world for work, school, healthcare, social activities, religious and athletic events, and so much more. Society requires the movement of goods, food, medicine, etc. for basic needs, commerce, cultural and political exchanges, and all of its dynamic, complex elements. To meet these critical daily demands, the transportation system operates globally and around the clock. Regardless of their role, a basic requirement for the individuals operating the transportation system is that they are awake and at optimal alertness. This applies to individuals driving their own cars, riding a bike or motorcycle, as well as pilots of commercial aircraft, train engineers, long-haul truck drivers, and air traffic controllers. Alert operators are a basic requirement for a safe and effective transportation system. Decades of scientific and operational research have demonstrated that the 24/7 scheduling demands on operators and passengers of our transportation system create sleep and circadian disruptions that reduce alertness and performance and cause serious safety problems. These challenges underly the longstanding interest in transportation safety by the sleep and circadian scientific community. An area currently offering perhaps the most significant opportunities and challenges in transportation safety involves vehicle technology innovations. This paper provides an overview of these latest innovations with a focus on sleep-relevant issues and opportunities. Drowsy driving is discussed, along with fatigue management in round-the-clock transportation operations. Examples of cases where technology innovations could improve or complicate sleep issues are discussed, and ongoing sleep challenges and new safety opportunities are considered.

Effect of antifibrotic therapy in patients with idiopathic pulmonary fibrosis undergoing lung transplant in the peri and post-operative period.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive interstitial lung disease with high mortality. Lung transplant remains a cornerstone of treatment despite the advent of antifibrotic therapy. In light of the increasing number of patients on antifibrotic therapy prior to lung transplantation it is paramount to demonstrate these medications do not augment postoperative complications following transplant. RESEARCH QUESTION: Does antifibrotic therapy increase perioperative complications and mortality in lung transplant recipients? STUDY DESIGN AND METHODS: We conducted a retrospective chart review of all patients actively listed for lung transplant at Temple University Hospital from June 2014 to April 2017 with a listing diagnosis of IPF. Subjects who received treatment with antifibrotic therapy (either pirfenidone or nintedanib) up until the time of lung transplantation were compared to subjects not on therapy. Data was collected regarding baseline demographics, pulmonary function tests, IPF exacerbations, perioperative bleeding and cardiac events, and outcomes in the postoperative period. RESULTS: A total of 94 subjects were included in the study: 42 subjects on antifibrotic therapy (28 pirfenidone, 14 nintedanib) and 52 subjects not on therapy in the pre-transplant period. Baseline characteristics were similar between study groups. Subjects treated with antifibrotic therapy pre-transplant were noted to have less FVC decline, fewer hospitalizations, and greater weight loss while on the transplant waiting list. No difference in post-transplant airway anastomosis complications, bleeding or mortality was observed between study groups. INTERPRETATION: Subjects with IPF on antifibrotic therapy prior to lung transplantation had better preservation of lung function in the pre-transplant period, and similar outcomes in the postoperative period compared to those not on antifibrotic therapy before lung transplant.

Utility of the ROX Index in Predicting Intubation for Patients With COVID-19-Related Hypoxemic Respiratory Failure Receiving High-Flow Nasal Therapy: Retrospective Cohort Study.

BACKGROUND: The use of high-flow nasal therapy (HFNT) to treat COVID-19 pneumonia has been greatly debated around the world due to concerns about increased health care worker transmission and delays in invasive mechanical ventilation (IMV). Herein, we analyzed the utility of the noninvasive ROX (ratio of oxygen saturation) index to predict the need for and timing of IMV. OBJECTIVE: This study aimed to assess whether the ROX index can be a useful score to predict intubation and IMV in patients receiving HFNT as treatment for COVID-19-related hypoxemic respiratory failure. METHODS: This is a retrospective cohort analysis of 129 consecutive patients with COVID-19 admitted to Temple University Hospital in Philadelphia, PA, from March 10, 2020, to May 17, 2020. This is a single-center study conducted in designated COVID-19 units (intensive care unit and other wards) at Temple University Hospital. Patients with moderate and severe hypoxemic respiratory failure treated with HFNT were included in the study. HFNT patients were divided into two groups: HFNT only and intubation (ie, patients who progressed from HFNT to IMV). The primary outcome was the value of the ROX index in predicting the need for IMV. Secondary outcomes were mortality, rate of intubation, length of stay, and rate of nosocomial infections in a cohort treated initially with HFNT. RESULTS: Of the 837 patients with COVID-19, 129 met the inclusion criteria. The mean age was 60.8 (SD 13.6) years, mean BMI was 32.6 (SD 8) kg/m², 58 (45%) were female, 72 (55.8%) were African American, 40 (31%) were Hispanic, and 48 (37.2%) were nonsmokers. The mean time to intubation was 2.5 (SD 3.3) days. An ROX index value of less than 5 at HFNT initiation was suggestive of progression to IMV (odds ratio [OR] 2.137, P=.052). Any further decrease in ROX index value after HFNT initiation was predictive of intubation (OR 14.67, P<.001). Mortality was 11.2% (n=10) in the HFNT-only group versus 47.5% (n=19) in the intubation group (P<.001). Mortality and need for pulmonary vasodilators were higher in the intubation group. CONCLUSIONS: The ROX index helps decide which patients need IMV and may limit eventual morbidity and mortality associated with the progression to IMV.

Tezepelumab as an Emerging Therapeutic Option for the Treatment of Severe Asthma: Evidence to Date.

Asthma is a complex heterogeneous disease defined by chronic inflammation of the airways. Patients present with wheezing, chest tightness, cough and shortness of breath. Bronchial hyperresponsiveness and variable expiratory airflow limitation are hallmark features. About 3.6-6.1% of patients, despite receiving high-dose inhaled corticosteroids (ICS) and a second controller medication, report persistent symptoms referred to as severe asthma. Uncontrolled severe asthma is associated with increased mortality, morbidity, diminished quality of life and increased health expenditures. The development of modern biological therapy has revolutionized severe asthma treatment. By targeting specific chemokines, asthma control has drastically improved, resulting in better quality of life, less emergency department visits and inpatient admissions, and decreased chronic systemic corticosteroid utilization. Despite these advances, there remains a subset of asthma patients who remain symptomatic with poor quality of life and heavy utilization of the healthcare system. Recently attention has been given to pharmaceutical therapy directed at receptors and cytokines on the epithelial layer of the lung referred to as "alarmins". Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like receptor family found on the epithelial layer of the lung that releases a cytokine cascade inducing eosinophilic inflammation, mucus production and airflow obstruction in asthmatics. Tezepelumab is the first investigational monoclonal antibody that inhibits TSLP. Proof of concept study and phase IIb studies demonstrated reduced asthma exacerbations, improvement in quality of life, less decline in FEV1 and decrease in biochemical inflammatory markers in comparison to placebo. It is presently undergoing three phase III studies and an additional phase II study.

Case series: Failure of imaging & biochemical markers to capture disease progression in COVID-19.

We report four individuals admitted for acute respiratory failure due to COVID-19 who demonstrated significant clinical improvement prior to discharge and subsequently were readmitted with worsening respiratory failure, elevated inflammatory markers and worsening chest imaging. We propose a multi-disciplinary discharge criterion to establish a safer discharge process including trending inflammatory markers, daily imaging and pursuing follow up CT chest, particularly in individuals with significant morbidities and health disparities.

Willingness to undergo a repeat liver biopsy among HIV/hepatitis C virus-coinfected and hepatitis C virus-monoinfected patients.

BACKGROUND: Guidelines for chronic hepatitis C virus (HCV) management have recommended that a liver biopsy be repeated at 3-year intervals for HIV/HCV-coinfected patients and 5-year intervals for those with HCV monoinfection to assess fibrosis progression. However, it is unclear if patients are willing to repeat this procedure. OBJECTIVE: To determine the prevalence and factors, particularly HIV coinfection, associated with willingness to repeat a liver biopsy. METHODS: A questionnaire was administered to 235 HCV-infected patients (113 with HIV coinfection) between January 2008 and June 2011 who previously underwent liver biopsy. The main outcome was self-reported willingness to repeat the biopsy. The questionnaire collected data on other hypothesized determinants of willingness to repeat the biopsy. These were evaluated by logistic regression. RESULTS: Among 235 subjects who completed the questionnaire, 32 (14%) reported unwillingness to repeat the biopsy, most commonly because of a perception that it was unimportant for care [13(41%)], concerns regarding pain [12(38%)], and a poor experience with the prior biopsy [7(21%)]. Considering biopsy to be safe [odds ratio (OR), 4.45; 95% CI, 1.50-13.27], important (OR, 4.87; 95% CI, 1.83-12.95), and knowing a person who underwent liver biopsy (OR, 3.45; 95% CI, 1.16-10.23) were associated with willingness to repeat the biopsy. HIV was not associated with willingness to repeat the biopsy (OR, 1.42; 95% CI, 0.67-3.03). CONCLUSIONS: Eighty-six percent of chronic HCV-infected patients were willing to repeat a liver biopsy. HIV was not associated with unwillingness. In patients in whom a repeat liver biopsy is indicated, education on the utility and safety of the biopsy is important to its acceptance.

Low prevalence of necrolytic acral erythema in patients with chronic hepatitis C virus infection.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with necrolytic acral erythema (NAE). However, the prevalence of NAE among patients with HCV is unknown, and the clinical and histologic features have not been well defined. OBJECTIVE: We sought to determine the prevalence, overall clinical features, and cutaneous histopathological characteristics of patients with NAE. METHODS: A cross-sectional study was performed among patients with chronic HCV infection cared for at 3 Philadelphia hospitals. Patients completed a questionnaire and underwent a dermatologic examination. All undiagnosed skin lesions with clinical features of NAE as described in the literature underwent skin biopsy. RESULTS: Among 300 patients with chronic HCV infection (median age 55 years; 73% male; 70% HCV genotype 1), 5 of them (prevalence 1.7%; 95% confidence interval 0.5%-3.8%) had skin lesions consistent with NAE clinically, which were analyzed and confirmed with skin biopsy specimen. All 5 skin biopsy specimens demonstrated variable psoriasiform hyperplasia, mild papillomatosis, parakeratosis, and necrotic keratinocytes in the superficial epidermis. All 5 patients were older than 40 years, were African American men, were infected with HCV genotype 1, and had a high viral load (>200,000 IU/mL). LIMITATIONS: Previous descriptions of NAE were used to guide the evaluation and need for a biopsy; however, other unknown clinical characteristics of the disease may exist. The senior author was the sole interpreter of the biopsy specimens. Only 300 of the 2500 eligible patients enrolled in the study. CONCLUSION: The prevalence of NAE among patients with chronic HCV in this sample was very low. Further research is needed to determine the origin and appropriate therapies of NAE.

Validity of diagnostic codes and liver-related laboratory abnormalities to identify hepatic decompensation events in the Veterans Aging Cohort Study.

PURPOSE: The absence of validated methods to identify hepatic decompensation in cohort studies has prevented a full understanding of the natural history of chronic liver diseases and impact of medications on this outcome. We determined the ability of diagnostic codes and liver-related laboratory abnormalities to identify hepatic decompensation events within the Veterans Aging Cohort Study (VACS). METHODS: Medical records of patients with hepatic decompensation codes and/or laboratory abnormalities of liver dysfunction (total bilirubin ≥ 5.0 g/dL, albumin ≤ 2.0 g/dL, INR ≥ 1.7) recorded 1 year before through 6 months after VACS entry were reviewed to identify decompensation events (i.e., ascites, spontaneous bacterial peritonitis, variceal hemorrhage, hepatic encephalopathy, hepatocellular carcinoma) at VACS enrollment. Positive predictive values (PPVs) of diagnostic codes, laboratory abnormalities, and their combinations for confirmed outcomes were determined. RESULTS: Among 137 patients with a hepatic decompensation code and 197 with a laboratory abnormality, the diagnosis was confirmed in 57 (PPV, 42%; 95%CI, 33%-50%) and 56 (PPV, 28%; 95%CI, 22%-35%) patients, respectively. The combination of any code plus laboratory abnormality increased PPV (64%; 95%CI, 47%-79%). One inpatient or ≥2 outpatient diagnostic codes for ascites, spontaneous bacterial peritonitis, or variceal hemorrhage had high PPV (91%; 95%CI, 77%-98%) for confirmed hepatic decompensation events. CONCLUSION: An algorithm of 1 inpatient or ≥ 2 outpatient codes for ascites, peritonitis, or variceal hemorrhage has sufficiently high PPV for hepatic decompensation to enable its use for epidemiologic research in VACS. This algorithm may be applicable to other cohorts.

The Yale cTAKES extensions for document classification: architecture and application.

BACKGROUND: Open-source clinical natural-language-processing (NLP) systems have lowered the barrier to the development of effective clinical document classification systems. Clinical natural-language-processing systems annotate the syntax and semantics of clinical text; however, feature extraction and representation for document classification pose technical challenges. METHODS: The authors developed extensions to the clinical Text Analysis and Knowledge Extraction System (cTAKES) that simplify feature extraction, experimentation with various feature representations, and the development of both rule and machine-learning based document classifiers. The authors describe and evaluate their system, the Yale cTAKES Extensions (YTEX), on the classification of radiology reports that contain findings suggestive of hepatic decompensation. RESULTS AND DISCUSSION: The F(1)-Score of the system for the retrieval of abdominal radiology reports was 96%, and was 79%, 91%, and 95% for the presence of liver masses, ascites, and varices, respectively. The authors released YTEX as open source, available at http://code.google.com/p/ytex.

The influence of abacavir and other antiretroviral agents on virological response to HCV therapy among antiretroviral-treated HIV-infected patients.

BACKGROUND: It remains unclear if certain antiretroviral medications, particularly abacavir, compromise response to HCV therapy. Such data could inform the selection of appropriate antiretrovirals in HIV/HCV-coinfected patients. The aim of this study was to determine if use of abacavir, as well as other antiretrovirals, was associated with reduced response to pegylated interferon (PEG-IFN) plus ribavirin. METHODS: A cohort study was performed among antiretroviral-treated HIV/HCV-coinfected patients initiating PEG-IFN plus ribavirin between January 2001 and June 2007 at six sites in the United States. Abacavir and other antiretrovirals represented exposures of interest. Study outcomes included an early virological response (> or =2 log IU/ml decrease in HCV viral load at 12 weeks) and sustained virological response (undetectable HCV viral load 24 weeks after treatment discontinuation). RESULTS: Among 212 patients, 74 (35%) received abacavir. For patients infected with HCV genotype 1 or 4, no differences were observed between abacavir users and non-users in early virological response (26 [40%] versus 53 [44%]; adjusted odds ratio [OR] 1.00; 95% confidence interval [CI] 0.50-2.00) or sustained virological response (8 [13%] versus 13 [12%]; adjusted OR 1.34; 95% CI 0.50-3.62). Among genotype 2 and 3 patients, rates of early virological response (7 [78%] versus 16 [89%]; OR 0.44; 95% CI 0.05-3.76) and sustained virological response (3 [33%] versus 8 [44%]; OR 0.63; 95% CI 0.12-3.32) were also similar between abacavir users and non-users. No association was found between other antiretrovirals and a lack of early or sustained response. CONCLUSIONS: Use of abacavir or other antiretroviral medications was not associated with reduced early or sustained virological response rates.

Rates of HCV treatment eligibility among HCV-monoinfected and HCV/HIV-coinfected patients in tertiary care referral centers.

BACKGROUND: Treatment eligibility rates in patients with HCV monoinfection have not been directly compared with patients with HCV/HIV coinfection. These data are important for planning interventions to optimize HCV management. METHOD: We enrolled consecutive HCV-monoinfected and HCV/HIV-coinfected subjects presenting to hepatology and HIV clinics at three academic medical centers. Data were obtained through structured subject and provider interviews and a review of medical records. RESULTS: Of the 399 subjects enrolled, 241 (60%) were HCV monoinfected and 158 (40%) were HCV/HIV coinfected. HCV/HIV-coinfected subjects were less likely to have indications for treatment based on HCV RNA positivity (70.9% vs. 81.3%, p = .04) but were more likely to have at least one contraindication to treatment (81.6% vs. 64.9%, p < .004). Depression and ongoing alcohol and injection drug abuse were more common in the HCV/HIV-coinfected persons. HCV/HIV-coinfected persons were less likely to undergo liver biopsy or to ever get treatment for HCV. CONCLUSIONS: HCV/HIV-coinfected persons are less likely to undergo a liver biopsy or be eligible for HCV therapy and are more likely to have treatment contraindications compared with HCV-monoinfected subjects. Strategies to address modifiable factors (e.g., depression, substance abuse) may enhance treatment eligibility in HCV-infected populations.

Effect of race and HIV co-infection upon treatment prescription for hepatitis C virus.

BACKGROUND: Treatment rates for hepatitis C virus (HCV) have not been compared directly between HCV mono-infected and HCV-HIV co-infected patients in academic center settings. METHODS: We prospectively enrolled consecutive mono-infected and co-infected subjects at three academic centers in the USA. Clinical and laboratory data were gathered through interviews and medical records. Logistic regression analysis was used to determine the factors associated with treatment prescription for HCV. RESULTS: The 241 HCV mono-infected and 158 HCV-HIV co-infected subjects were similar in age, but there were more blacks (58.9% vs. 30.7%, p < 0.001) and males (81.6% vs. 58.5%, p < 0.001) in the latter group. The co-infected subjects were less likely to have a liver biopsy (43.7% vs. 71.4%, p < 0.001) or ever receive treatment for HCV (32.3% vs. 62.2%, p < 0.001). In bivariate analysis, subjects not prescribed treatment for HCV were more likely to be black, have HIV co-infection, and have ongoing alcohol abuse. In multivariate analysis, black race (odds ratio (OR) 0.44, 95% confidence interval (CI) 0.28-0.70) and HIV co-infection (OR 0.33, 95% CI 0.21-0.53) were independently associated with non-prescription of treatment. CONCLUSIONS: Black race and HIV co-infection are associated with a lower likelihood of treatment for HCV. Addressing comorbidities in these populations may help to reduce such treatment disparities.

Adherence to hepatitis C virus therapy and early virologic outcomes.

BACKGROUND: Suboptimal drug exposure attributable to physician-directed dosage reductions of pegylated interferon and/or ribavirin are associated with decreased sustained virologic response rates. However, data are limited with regard to suboptimal drug exposure that is attributable to missed doses by patients with chronic hepatitis C virus (HCV) infection. We examined the relationship between adherence to pegylated interferon and ribavirin therapy, measured by pharmacy refill, and HCV suppression during the initial 12 weeks of therapy. METHODS: We conducted a cohort study involving 188 patients with chronic HCV infection who were treated with pegylated interferon plus ribavirin. Adherence was calculated using pharmacy refill data and could exceed 100%. The primary outcome was decrease in HCV load at 12 weeks; early virologic response was a secondary outcome. Mixed-effects regression models estimated the association between adherence and HCV suppression during the initial 12 weeks. Subanalyses were performed among patients who received optimal weight-based dosages. RESULTS: The mean decrease in HCV load at 12 weeks was 0.66 log IU/mL greater for patients with > or =85% adherence than for those with <85% adherence (3.23 vs. 2.57 log IU/mL; P = .04). When patients who received a suboptimal ribavirin dosage were excluded, the decrease in viral load was 1.00 log IU/mL greater for persons with > or =85% adherence (3.32 vs. 2.32 log IU/mL; P = .01). Early virologic response was more common among patients with > or =85% adherence than it was among those with <85% adherence to treatment with pegylated interferon (73% vs. 29%; P = .02) and ribavirin (73% vs. 55%; P = .08). CONCLUSIONS: Adherence of > or =85% to pegylated interferon and ribavirin treatment was associated with increased HCV suppression. Decreases in HCV load became greater when patients with > or =85% adherence to their regimen continued to receive their recommended weight-based ribavirin dosage.

Incidence of transaminitis among HIV-infected patients with occult hepatitis B.

BACKGROUND: The clinical significance of occult hepatitis B virus (HBV) infection, defined as the presence of HBV DNA in individuals with HBV core antibodies (anti-HBc) in the absence of HBV surface antigen (HBsAg), is unclear in HIV-infected patients. This information is needed to determine the importance of detecting and treating occult HBV in this population. OBJECTIVE: To determine if HIV-infected patients with occult HBV infection have an increased incidence of transaminitis. STUDY DESIGN: We performed a cohort study among randomly selected HBsAg-/anti-HBc+ HIV-infected patients in the Penn CFAR Database and Specimen Repository. HBV DNA was qualitatively detected using a transcription-mediated amplification assay. Hepatic transaminase levels, the main study outcome, were collected at 6-month intervals from the time of occult HBV determination. RESULTS: Among 97 randomly selected subjects without baseline transaminitis, 13 (13%) had occult HBV. These subjects more frequently had detectable HIV RNA. The 2-year incidence of transaminitis among HIV-infected subjects with occult HBV (50 events/100 person-years) was not significantly different from those without occult HBV (38 events/100 person-years; adjusted incidence rate ratio=1.36 [95% CI, 0.72-2.59]). CONCLUSIONS: Occult HBV did not increase the incidence of hepatic transaminitis over 2 years. Future studies should determine whether occult HBV is associated with other clinically important outcomes, particularly hepatocellular carcinoma.