The Effect of Chronic Altitude Exposure on COPD Outcomes in the SPIROMICS Cohort.

RATIONALE: Individuals with COPD have airflow obstruction and maldistribution of ventilation. For those living at high altitude, any gas exchange abnormality is compounded by reduced partial pressures of inspired oxygen. OBJECTIVES: Does residence at higher-altitude exposure affect COPD outcomes, including lung function, imaging characteristics, symptoms, health status, functional exercise capacity, exacerbations, or mortality? METHODS: From the SPIROMICS cohort, we identified individuals with COPD living below 1,000 ft (305 m) elevation (n= 1,367) versus above 4,000 ft (1,219 m) elevation (n= 288). Multivariable regression models were used to evaluate associations of exposure to high altitude with COPD-related outcomes. MEASUREMENTS AND MAIN RESULTS: Living at higher altitude was associated with reduced functional exercise capacity as defined by 6MWD (-32.3 m, (-55.7 to -28.6)). There were no differences in patient-reported outcomes as defined by symptoms (CAT, mMRC), or health status (SGRQ). Higher altitude was not associated with a different rate of FEV1 decline. Higher altitude was associated with lower odds of severe exacerbations (IRR 0.65, (0.46 to 0.90)). There were no differences in small airway disease, air trapping, or emphysema. In longitudinal analyses, higher altitude was associated with increased mortality (HR 1.25, (1.0 to 1.55)); however, this association was no longer significant when accounting for air pollution. CONCLUSIONS: Chronic altitude exposure is associated with reduced functional exercise capacity in individuals with COPD, but this did not translate into differences in symptoms or health status. Additionally, chronic high-altitude exposure did not affect progression of disease as defined by longitudinal changes in spirometry.

Return to work after critical illness: a systematic review and meta-analysis.

BACKGROUND: Survivors of critical illness often experience poor outcomes after hospitalisation, including delayed return to work, which carries substantial economic consequences. OBJECTIVE: To conduct a systematic review and meta-analysis of return to work after critical illness. METHODS: We searched PubMed, Embase, PsycINFO, CINAHL and Cochrane Library from 1970 to February 2018. Data were extracted, in duplicate, and random-effects meta-regression used to obtain pooled estimates. RESULTS: Fifty-two studies evaluated return to work in 10 015 previously employed survivors of critical illness, over a median (IQR) follow-up of 12 (6.25-38.5) months. By 1-3, 12 and 42-60 months' follow-up, pooled return to work prevalence (95% CI) was 36% (23% to 49%), 60% (50% to 69%) and 68% (51% to 85%), respectively (τ2=0.55, I2=87%, p=0.03). No significant difference was observed based on diagnosis (acute respiratory distress syndrome (ARDS) vs non-ARDS) or region (Europe vs North America vs Australia/New Zealand), but was observed when comparing mode of employment evaluation (in-person vs telephone vs mail). Following return to work, 20%-36% of survivors experienced job loss, 17%-66% occupation change and 5%-84% worsening employment status (eg, fewer work hours). Potential risk factors for delayed return to work include pre-existing comorbidities and post-hospital impairments (eg, mental health). CONCLUSION: Approximately two-thirds, two-fifths and one-third of previously employed intensive care unit survivors are jobless up to 3, 12 and 60 months following hospital discharge. Survivors returning to work often experience job loss, occupation change or worse employment status. Interventions should be designed and evaluated to reduce the burden of this common and important problem for survivors of critical illness. TRIAL REGISTRATION NUMBER: PROSPERO CRD42018093135.

Chitosan films: crosslinking with EDTA modifies physicochemical and mechanical properties.

The present study was aimed to develop chitosan-EDTA films and evaluate their physico-chemical and mechanical properties. The physical properties suggested lowest swelling, volume and volume index of films prepared by employing equal weight of chitosan (CH) and EDTA (1.5% w/v). The CH:EDTA film (1:l, on weight basis) showed minimum contact angle, work of adhesion and high negative spreading coefficient indicating lipophilic behavior of film. Further, the FTIR and DSC analysis suggested maximum crosslinking density in film prepared with equal proportion of CH and EDTA. The mechanical properties explored using texture analyzer revealed increasing the proportions of EDTA rendered the films more flexible and decreased their hardness. Furthermore, in vitro permeation of 5-FU and mesalamine with different solubilities showed minimum permeation across CH­EDTA (1:1) film, indicating high crosslinking density that decreased void space inside the film. Hence, the CH­EDTA conjugate could be considered to be possess great potential for various pharmaceutical applications such as film based delivery systems, controlled and sustained delivery systems etc.

The Relationship Between Insurance Status and the Affordable Care Act on Asthma Outcomes Among Low-Income US Adults.

BACKGROUND: Asthma disproportionately affects individuals with lower income. High uninsured rates are a potential driver for this disparity. Previous studies have not examined the effect of the Affordable Care Act (ACA) on asthma-related outcomes for individuals with low income. RESEARCH QUESTION: What is the impact of insurance status and the ACA on asthma outcomes for adults 18 to 64 years of age in households with low-income status? STUDY DESIGN AND METHODS: This study was a pooled cross-sectional observational study using National Health Interview Survey data from 2011 through 2013 and 2016 through 2018. Individuals 18 to 64 years of age with a history of asthma and low income were included. Survey-weighted regression modeling and mediation analysis was used to explore the relationship of insurance status and asthma control. Univariate and multivariate survey-weighted regression modeling then was used to evaluate the correlation of the ACA and asthma outcomes. RESULTS: We identified 4,043 individual observations. Having health insurance was correlated with improved asthma outcomes (OR, 1.25). This relationship was completely mediated by cost barriers to medications and physician visits. Although the ACA resulted in significant changes in insurance status (OR, 2.4), no statistically significant change was found in asthma outcomes. Furthermore, cost barriers to both medications and physician visits persisted in the insured population, 20.7% and 30.0%, respectively. INTERPRETATION: Insurance coverage is associated with improved asthma control for adults 18 to 64 years from households with low socioeconomic status. The ACA reduced the rates of uninsured, but did not have the same magnitude of effect on reducing cost barriers. The persistence of cost barriers may explain in part the lack of population-level improvement in asthma control.

Increasing cervical cancer screening at a non-government medical center in Lilongwe, Malawi.

Malawi has the highest incidence of and mortality rate due to cervical cancer in the world. This is largely because of inadequate screening and high rates of human immunodeficiency virus (HIV) infection, which greatly increases cervical cancer risk. We describe the implementation of a quality improvement program to increase use of cervical cancer screening at a non-government medical center in Lilongwe, Malawi. The intervention, developed and launched from March to August 2017, aimed to promote education among patients and clinicians about the importance of cervical cancer screening and improve accessibility of screening information within medical records. Visual inspection with acetic acid (VIA) was used to screen for cervical cancer. Women with a positive VIA were offered treatment using thermocoagulation. The number of VIA screenings conducted in 2016 (pre-intervention), 2017 (intervention), and 2018 (post-intervention) was 125, 234 and 456, respectively. Of the 815 women screened during this period, 36 (4.4%) had a VIA-positive result and 12 (1.5%) had suspect cancer. Of the VIA-positive women, 13 (36.1%) received same-day treatment with thermocoagulation. An interrupted time series regression revealed that there was a sustained increase in monthly screenings between the pre- and post-intervention period (ß = 30.84; p = 0.006; 95% CI 9.72-51.97), suggesting that the intervention likely was effective in increasing cervical cancer screening. Our results demonstrate that focusing on developing sustainable solutions and improving system processes, without additional equipment or funding, significantly increased the number of women screened and should be considered in other settings to enhance cervical cancer prevention services.

Obesity and smoking as risk factors for invasive mechanical ventilation in COVID-19: A retrospective, observational cohort study.

PURPOSE: To describe the trajectory of respiratory failure in COVID-19 and explore factors associated with risk of invasive mechanical ventilation (IMV). MATERIALS AND METHODS: A retrospective, observational cohort study of 112 inpatient adults diagnosed with COVID-19 between March 12 and April 16, 2020. Data were manually extracted from electronic medical records. Multivariable and Univariable regression were used to evaluate association between baseline characteristics, initial serum markers and the outcome of IMV. RESULTS: Our cohort had median age of 61 (IQR 45-74) and was 66% male. In-hospital mortality was 6% (7/112). ICU mortality was 12.8% (6/47), and 18% (5/28) for those requiring IMV. Obesity (OR 5.82, CI 1.74-19.48), former (OR 8.06, CI 1.51-43.06) and current smoking status (OR 10.33, CI 1.43-74.67) were associated with IMV after adjusting for age, sex, and high prevalence comorbidities by multivariable analysis. Initial absolute lymphocyte count (OR 0.33, CI 0.11-0.96), procalcitonin (OR 1.27, CI 1.02-1.57), IL-6 (OR 1.17, CI 1.03-1.33), ferritin (OR 1.05, CI 1.005-1.11), LDH (OR 1.57, 95% CI 1.13-2.17) and CRP (OR 1.13, CI 1.06-1.21), were associated with IMV by univariate analysis. CONCLUSIONS: Obesity, smoking history, and elevated inflammatory markers were associated with increased need for IMV in patients with COVID-19.

Obesity and Smoking as Risk Factors for Invasive Mechanical Ventilation in COVID-19: a Retrospective, Observational Cohort Study.

PURPOSE: To describe the trajectory of respiratory failure in COVID-19 and explore factors associated with risk of invasive mechanical ventilation (IMV). MATERIALS AND METHODS: A retrospective, observational cohort study of 112 inpatient adults diagnosed with COVID-19 between March 12 and April 16, 2020. Data were manually extracted from electronic medical records. Multivariable and Univariable regression were used to evaluate association between baseline characteristics, initial serum markers and the outcome of IMV. RESULTS: Our cohort had median age of 61 (IQR 45-74) and was 66% male. In-hospital mortality was 6% (7/112). ICU mortality was 12.8% (6/47), and 18% (5/28) for those requiring IMV. Obesity (OR 5.82, CI 1.74-19.48), former (OR 8.06, CI 1.51-43.06) and current smoking status (OR 10.33, CI 1.43-74.67) were associated with IMV after adjusting for age, sex, and high prevalence comorbidities by multivariable analysis. Initial absolute lymphocyte count (OR 0.33, CI 0.11-0.96), procalcitonin (OR 1.27, CI 1.02-1.57), IL-6 (OR 1.17, CI 1.03-1.33), ferritin (OR 1.05, CI 1.005-1.11), LDH (OR 1.57, 95% CI 1.13-2.17) and CRP (OR 1.13, CI 1.06-1.21), were associated with IMV by univariate analysis. CONCLUSIONS: Obesity, smoking history, and elevated inflammatory markers were associated with increased need for IMV in patients with COVID-19.

Spelunking Meckel Cave: A 31-Year-Old With Diplopia and Loss of Taste and Smell.

CASE PRESENTATION: A 31-year-old woman presented to the ED with a loss of taste and smell of 2 months' duration and a frontal headache, bilateral facial numbness, photophobia, and horizontal diplopia that was worse with far vision of 2 weeks' duration. A review of systems revealed mild nausea and decreased appetite without weight loss. She denied any cardiopulmonary symptoms, specifically no cough or shortness of breath. Her medical history was notable for arthralgias. The patient was diagnosed with ankylosing spondylitis, for which she had been taking etanercept for several months. She consumed minimal alcohol and had no history of tobacco or drug use or recent travel. Her family history was unremarkable.

Exploiting the synergistic effect of chitosan-EDTA conjugate with MSA for the early recovery from colitis.

The present study was aimed to exploit the antibacterial/antifungal and film coating potential of Chitosan-EDTA (CH-EDTA) conjugate in combination with mesalamine (anti-inflammatory agent) for the early recovery from TNBS induced coilitis. The results suggested CH:EDTA (1:1) spray coated mesalamine tablets has an ability to transport drug in buffer pH 6.8 with rat caecal content condition. The CH-EDTA shows high level of adhesiveness of coat with core tablet. Further, FTIR, DSC and SEM analysis suggested spray coating of CH-EDTA on tablets was beneficial as compared to ladling method as it enhances interaction density and showed resistance from pH (1.2, 6.8 and 7.4). The pharmacokinetic parameters, AUC and AUMC of spray coated tablets were respectively, 4.70 fold and 2.10 fold increased. A synergistic therapeutic effect with CH-EDTA spray coated mesalamine was observed as evaluated by colon/body weight ratio, clinical activity score and damage score. X ray image study supported that CH-EDTA conjugate successfully delivered MSA tablets to large intestine. Histopathology of colon tissues showed rapid recovery from TNBS induced colitis in rats within 4 days. The findings revealed decreased recovery period was due to combined effect of both CH-EDTA and MSA to treat TNBS induced colitis.