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Low- and middle-income countries (LMICs) bear most of the global burden of critical illness. Managing this burden requires improved understanding of epidemiology and outcomes in LMIC intensive care units (ICUs), including LMIC-specific mortality prediction scores. This study was a retrospective observational study at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia, examining all consecutive medical ICU admissions from June 2014 to April 2015. The primary outcome was ICU mortality; secondary outcomes were prolonged ICU stay and prolonged mechanical ventilation. ICU mortality prediction models were created using multivariable logistic regression and compared with the Mortality Probability Model-II (MPM-II). Associations with secondary outcomes were examined with multivariable logistic regression. There were 198 admissions during the study period; mortality was 35%. Age, shock on admission, mechanical ventilation, human immunodeficiency virus, and Glasgow Coma Scale ≤8 were associated with ICU mortality. The receiver operating characteristic curve for this 5-factor model had an AUC of 0.8205 versus 0.7468 for MPM-II, favoring the simplified new model. Mechanical ventilation and lack of shock were associated with prolonged ICU stays. Mortality in an LMIC medical ICU was high. This study examines an LMIC medical ICU population, showing a simplified prediction model may predict mortality as well as complex models. [ABSTRACT FROM AUTHOR]

Race‐inclusive estimated glomerular filtration rate (eGFR) could contribute to racial disparity in access to kidney transplantation. The Organ Procurement and Transplantation Network (OPTN) issued a policy allowing waiting time modification for candidates affected by race‐inclusive eGFR calculations. Implementation of the new OPTN policy at the kidney transplant program of the Mount Sinai Hospital involved review of 921 African American candidates, of whom 240 (26%) candidates gained a median of 1 year and 10 months. The duration of time candidates gained varied from a minimum of 5 days to a maximum of 12 years and 3 months; 45.4% gained at least 2 years, and 12% gained at least 4 years of wait time. Among those who gained wait time, 20 (8.3%) candidates received deceased donor kidney transplants. Candidates who gained wait time had similar sociodemographic characteristics as those who did not, except that the median age for the former was higher by 3 years (59 vs. 56). Our early data suggest that the current policy on waiting time modification for candidates affected by race‐inclusive estimation of GFR has the potential to improve racial disparity in access to kidney transplantation. However, the generalizability of our findings to other centers requires further study. [ABSTRACT FROM AUTHOR]

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and healthcare costs. Cigarette smoke is a causative factor; however, not all heavy smokers develop COPD. Microbial colonization and infections are contributing factors to disease progression in advanced stages. Objectives: We investigated whether lower airway dysbiosis occurs in mild-to-moderate COPD and analyzed possible mechanistic contributions to COPD pathogenesis. Methods: We recruited 57 patients with a >10 pack-year smoking history: 26 had physiological evidence of COPD, and 31 had normal lung function (smoker control subjects). Bronchoscopy sampled the upper airways, lower airways, and environmental background. Samples were analyzed by 16S rRNA gene sequencing, whole genome, RNA metatranscriptome, and host RNA transcriptome. A preclinical mouse model was used to evaluate the contributions of cigarette smoke and dysbiosis on lower airway inflammatory injury. Measurements and Main Results: Compared with smoker control subjects, microbiome analyses showed that the lower airways of subjects with COPD were enriched with common oral commensals. The lower airway host transcriptomics demonstrated differences in markers of inflammation and tumorigenesis, such as upregulation of IL-17, IL-6, ERK/MAPK, PI3K, MUC1, and MUC4 in mild-to-moderate COPD. Finally, in a preclinical murine model exposed to cigarette smoke, lower airway dysbiosis with common oral commensals augments the inflammatory injury, revealing transcriptomic signatures similar to those observed in human subjects with COPD. Conclusions: Lower airway dysbiosis in the setting of smoke exposure contributes to inflammatory injury early in COPD. Targeting the lower airway microbiome in combination with smoking cessation may be of potential therapeutic relevance. [ABSTRACT FROM AUTHOR]

Malignant pleural effusions (MPE) complicate malignancies and portend worse outcomes. MPE is comprised of various components, including immune cells, cancer cells, and cell-free DNA/RNA. There have been investigations into using these components to diagnose and prognosticate MPE. We hypothesize that the microbiome of MPE is unique and may be associated with diagnosis and prognosis. We compared the microbiota of MPE against microbiota of pleural effusions from non-malignant and paramalignant states. We collected a total of 165 pleural fluid samples from 165 subjects; Benign (n = 16), Paramalignant (n = 21), MPE-Lung (n = 57), MPE-Other (n = 22), and Mesothelioma (n = 49). We performed high throughput 16S rRNA gene sequencing on pleural fluid samples and controls. We showed that there are compositional differences among pleural effusions related to non-malignant, paramalignant, and malignant disease. Furthermore, we showed differential enrichment of bacterial taxa within MPE depending on the site of primary malignancy. Pleural fluid of MPE-Lung and Mesothelioma were associated with enrichment with oral and gut bacteria that are commonly thought to be commensals, including Rickettsiella, Ruminococcus, Enterococcus, and Lactobacillales. Mortality in MPE-Lung is associated with enrichment in Methylobacterium, Blattabacterium, and Deinococcus. These observations lay the groundwork for future studies that explore host-microbiome interactions and their influence on carcinogenesis. [ABSTRACT FROM AUTHOR]

A 25-year-old man with cerebral palsy, scoliosis, and ventilator dependence since SARS-CoV-2 infection 11 months earlier presented with a 2-week history of chest redness and swelling. The area of erythema and edema was located on the left side of the anterior chest and had grown to approximately 9 cm in diameter over the 2 weeks. It was tender to palpation. There was no history of trauma, injury, or bug bites at that site. He had not had a rash or similar lesions elsewhere on his body and had not taken any new medications. He did have increased, thick, yellow secretions from his tracheostomy, but no fevers. He was born in the Dominican Republic and moved to the United States as a child. He had not traveled anywhere outside the United States in more than a decade. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is a leading complication after both liver and kidney transplantation. Factors associated with and rates of cardiovascular events (CVEs) after simultaneous liver-kidney transplant (SLKT) are unknown. This was a retrospective cohort study of adult SLKT recipients between 2002 and 2017 at six centers in six United Network for Organ Sharing regions in the US Multicenter SLKT Consortium. The primary outcome was a CVE defined as hospitalization due to acute coronary syndrome, arrhythmia, congestive heart failure, or other CV causes (stroke or peripheral vascular disease) within 1 year of SLKT. Among 515 SLKT subjects (mean age ± SD, 55.4 ± 10.6 years; 35.5% women; 68.1% White), 8.7% had a CVE within 1 year of SLKT. The prevalence of a CVE increased from 3.3% in 2002-2008 to 8.9% in 2009-2011 to 14.0% in 2012-2017 (p = 0.0005). SLKT recipients with a CVE were older (59.9 vs. 54.9 years, p < 0.0001) and more likely to have coronary artery disease (CAD) (37.8% vs. 18.4%, p = 0.002) and atrial fibrillation (AF) (27.7% vs. 7.9%, p = 0.003) than those without a CVE. There was a trend toward older age by era of SLKT (p = 0.054). In multivariate analysis adjusted for cardiac risk factors at transplant, age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02, 1.11), CAD (OR, 3.62; 95% CI, 1.60, 8.18), and AF (OR, 2.36; 95% CI, 1.14, 4.89) were associated with a 1-year CVE after SLKT. Conclusion: Among SLKT recipients, we observed a 4-fold increase in the prevalence of 1-year CVEs over time. Increasing age, CAD, and AF were the main potential explanatory factors for this trend independent of other risk factors. These findings suggest that CV risk protocols may need to be tailored to this high-risk population. [ABSTRACT FROM AUTHOR]

Background: Various reports suggested that pre-existing medical illnesses, including hypertension and other demographic, clinical, and laboratory factors, could pose an increased risk of disease severity and mortality among COVID-19 patients. This study aimed to assess the relation of hypertension and other factors to the severity of COVID-19 pneumonia in patients discharged from Eka Kotebe Hospital in June-September, 2020. Methods: This is a single-center case-control study of 265 adult patients discharged alive or dead, 75 with a course of severe COVID-19 for the cases arm and 190 with the non-severe disease for the control arm. Three age and sex-matched controls were selected randomly for each patient on the case arm. Chi-square, multivariable binary logistic regression, and odds ratio (OR) with a 95% confidence interval was used to assess the association between the various factors and the severity of the disease. A p-value of <0.05 is considered statistically significant. Results: Of the 265 study participants, 80% were male. The median age was 43 IQR(36–60) years. Both arms had similar demographic characteristics. Hypertension was strongly associated with the severity of COVID-19 pneumonia based on effect outcome adjustment (AOR = 2.93, 95% CI 1.489, 5.783, p-value = 0.002), similarly, having diabetes mellitus (AOR = 3.17, 95% CI 1.374, 7.313, p-value<0.007), chronic cardiac disease (AOR = 4.803, 95% CI 1.238–18.636, p<0.023), and an increase in a pulse rate (AOR = 1.041, 95% CI 1.017, 1.066, p-value = 0.001) were found to have a significant association with the severity of COVID-19 pneumonia. Conclusions: Hypertension was associated with the severity of COVID-19 pneumonia, and so were diabetes mellitus, chronic cardiac disease, and an increase in pulse rate. [ABSTRACT FROM AUTHOR]

Objectives Donor-derived malignancy of the liver allograft is a rare but serious condition in the setting of necessary immunosuppression. Retransplantation after abrupt immunosuppression cessation has been performed with durable cancer-free survival. Methods We present 2 cases of patients with donor-derived malignancy who were treated with complete immunosuppression cessation, which induced rapidly progressive liver allograft rejection and failure, with a need for subsequent retransplantation. We reviewed all serial liver biopsies and explants from both patients and performed C4d immunostaining. Results Initial explants of both patients showed severe allograft rejection, with unusual features of sinusoidal obstruction syndrome and C4d positivity. Malignant tumors in the explants were necrotic, related to rejection of donor-derived cancer cells and tissue. Follow-up of both patients has shown long-term cancer-free survival but issues with recurrent allograft failure requiring a third transplant. The reasons for retransplantation in both cases were related to allograft failure from antibody-mediated rejection. Conclusions Clinicians should be aware of a potentially increased risk of rejection and recurrent allograft failure when strategizing treatment of donor-derived malignancy with immunosuppression cessation and retransplantation. [ABSTRACT FROM AUTHOR]

The article discusses the race adjustment in pulmonary function testing, one of few physiologic determinations in which self-reported race or ethnicity is used to establish a normal range for measurement. Topics include determinants of pulmonary function, impact of race adjustment of PFTs pulmonary function tests (PFTs) on clinical outcomes, and indication of overestimation of pulmonary function by race-adjusted prediction equations.

Efforts to end the HIV and hepatitis C virus (HCV) epidemics begin with ascertainment of a person's infection status through screening. Despite its importance as a site of testing, missed opportunities for screening in the Emergency Department (ED) are common. We describe the impact of implementing an individualized provider feedback intervention on HIV and HCV testing in a quaternary ED. We conducted an interrupted time series analysis to evaluate the impact of the intervention on weekly HIV and HCV screening in an observational cohort of patients seeking care in the ED. The intervention included a physician champion individualized feedback with peer comparisons to all providers in the ED and an existing HIV/HCV testing and response team. Data were abstracted from the electronic medical record (EMR) for 30 weeks before, during, and after implementing the intervention. We used Poisson regression analysis to estimate changes in the weekly counts and rates of HIV and HCV testing. The incidence rate ratios (IRRs) of HIV testing were 1.94 [95% confidence interval (CI) 1.85–2.04] and 1.38 (95% CI 1.31–1.45) times higher for the intervention and post-intervention period compared with the pre-intervention period. The IRRs of HCV testing was 6.96 (95% CI 6.40–7.58) and 4.70 (95% CI 4.31–5.13) for the intervention and post-intervention periods. There were no meaningful differences in demographic characteristics during the observation period. The intervention meaningfully increased HIV and HCV testing volume and positive case detection, including testing in high-risk groups like young adults and individuals without prior testing. Although diminished, the intervention effect sustained in the 30-week period following implementation. [ABSTRACT FROM AUTHOR]

Background: We examined cytokine immune response profiles among contacts to tuberculosis patients to identify immunologic and epidemiologic correlates of tuberculosis.Methods: We prospectively enrolled 1272 contacts of culture-confirmed pulmonary tuberculosis patients at 9 United States and Canadian sites. Epidemiologic characteristics were recorded. Blood was collected and stimulated with Mycobacterium tuberculosis culture filtrate protein, and tumor necrosis factor (TNF-α), interferon gamma (IFN-γ), and interleukin 10 (IL-10) concentrations were determined using immunoassays.Results: Of 1272 contacts, 41 (3.2%) were diagnosed with tuberculosis before or < 30 days after blood collection (co-prevalent tuberculosis) and 19 (1.5%) during subsequent four-year follow-up (incident tuberculosis). Compared with contacts without tuberculosis, those with co-prevalent tuberculosis had higher median baseline TNF-α and IFN-γ concentrations (in pg/mL, TNF-α 129 versus 71, P < .01; IFN-γ 231 versus 27, P < .001), and those who subsequently developed incident tuberculosis had higher median baseline TNF-α concentrations (in pg/mL, 257 vs. 71, P < .05). In multivariate analysis, contact age < 15 years, US/Canadian birth, and IFN or TNF concentrations > the median were associated with co-prevalent tuberculosis (P < .01 for each); female sex (P = .03) and smoking (P < .01) were associated with incident tuberculosis. In algorithms combining young age, positive skin test results, and elevated CFPS TNF-α, IFN-γ, and IL-10 responses, the positive predictive values for co-prevalent and incident tuberculosis were 40 and 25%, respectively.Conclusions: Cytokine concentrations and epidemiologic factors at the time of contact investigation may predict co-prevalent and incident tuberculosis. [ABSTRACT FROM AUTHOR]

Objectives. To create a tool to rapidly determine where pandemic demand for critical care overwhelms county-level surge capacity and to compare public health and medical responses. Methods. In March 2020, COVID-19 cases requiring critical care were estimated using an adaptive metapopulation SEIR (susceptible-exposed-infectious-recovered) model for all 3142 US counties for future 21-day and 42-day periods from April 2, 2020, to May 13, 2020, in 4 reactive patterns of contact reduction--0%, 20%, 30%, and 40%--and 4 surge response scenarios--very low, low, medium, and high. Results. In areas with increased demand, surge response measures could avert 104 120 additional deaths--55% through high clearance of critical care beds and 45% through measures such as greater ventilator access. The percentages of lives saved from high levels of contact reduction were 1.9 to 4.2 times greater than high levels of hospital surge response. Differences in projected versus actual COVID-19 demands were reasonably small over time. Conclusions. Nonpharmaceutical public health interventions had greater impact in minimizing preventable deaths during the pandemic than did hospital critical care surge response. Ready-to-go spatiotemporal supply and demand data visualization and analytics tools should be advanced for future preparedness and all-hazards disaster response. [ABSTRACT FROM AUTHOR]

Background: The surge of coronavirus 2019 (COVID-19) hospitalizations in New York City required rapid discharges to maintain hospital capacity. Objective: To determine whether lenient provisional discharge guidelines with remote monitoring after discharge resulted in safe discharges home for patients hospitalized with COVID-19 illness. Design: Retrospective case series Setting: Tertiary care medical center Patients: Consecutive adult patients hospitalized with COVID-19 illness between March 26, 2020, and April 8, 2020, with a subset discharged home Interventions: COVID-19 Discharge Care Program consisting of lenient provisional inpatient discharge criteria and option for daily telephone monitoring for up to 14 days after discharge Measurements: Fourteen-day emergency department (ED) visits and hospital readmissions Results: Among 812 patients with COVID-19 illness hospitalized during the study time period, 15.5% died prior to discharge, 24.1% remained hospitalized, 10.0% were discharged to another facility, and 50.4% were discharged home. Characteristics of the 409 patients discharged home were mean (SD) age 57.3 (16.6) years; 245 (59.9%) male; 27 (6.6%) with temperature ≥ 100.4 °F; and 154 (37.7%) with oxygen saturation < 95% on day of discharge. Over 14 days of follow-up, 45 patients (11.0%) returned to the ED, of whom 31 patients (7.6%) were readmitted. Compared to patients not referred, patients referred for remote monitoring had fewer ED visits (8.3% vs 14.1%; OR 0.60, 95% CI 0.31–1.15, p = 0.12) and readmissions (6.9% vs 8.3%; OR 1.15, 95% CI 0.52–2.52, p = 0.73). Limitations: Single-center study; assignment to remote monitoring was not randomized. Conclusions: During the COVID-19 surge in New York City, lenient discharge criteria in conjunction with remote monitoring after discharge were associated with a rate of early readmissions after COVID-related hospitalizations that was comparable to the rate of readmissions after other reasons for hospitalization before the COVID pandemic. [ABSTRACT FROM AUTHOR]

The author comments on a research paper on the use of race adjustment in predicting clinical events related to lung health, which references a study by A. Elmaleh-Sachs et al., published within the issue. Topics discussed include the use of pulmonary function testing by physicians, the methods used in the study, and the accuracy of using race-adjusted prediction equations derived from the Global Lung Function Initiative in predicting lower respiratory disease-related deaths or hospitalizations.

Background: New York City (NYC) reported a higher pneumonia and influenza death rate than the rest of New York State during 2010–2014. Most NYC pneumonia and influenza deaths are attributed to pneumonia caused by infection acquired in the community, and these deaths typically occur in hospitals. Methods: We identified hospitalizations of New York State residents aged ≥20 years discharged from New York State hospitals during 2010–2014 with a principal diagnosis of community-setting pneumonia or a secondary diagnosis of community-setting pneumonia if the principal diagnosis was respiratory failure or sepsis. We examined mean annual age-adjusted community-setting pneumonia-associated hospitalization (CSPAH) rates and proportion of CSPAH with in-hospital death, overall and by sociodemographic group, and produced a multivariable negative binomial model to assess hospitalization rate ratios. Results: Compared with non-NYC urban, suburban, and rural areas of New York State, NYC had the highest mean annual age-adjusted CSPAH rate at 475.3 per 100,000 population and the highest percentage of CSPAH with in-hospital death at 13.7%. NYC also had the highest proportion of CSPAH patients residing in higher-poverty-level areas. Adjusting for age, sex, and area-based poverty, NYC residents experienced 1.3 (95% confidence interval [CI], 1.2–1.4), non-NYC urban residents 1.4 (95% CI, 1.3–1.6), and suburban residents 1.2 (95% CI, 1.1–1.3) times the rate of CSPAH than rural residents. Conclusions: In New York State, NYC as well as other urban areas and suburban areas had higher rates of CSPAH than rural areas. Further research is needed into drivers of CSPAH deaths, which may be associated with poverty. [ABSTRACT FROM AUTHOR]

Background Guidelines recommend adding intravenous (IV) metronidazole to oral vancomycin for fulminant Clostridioides difficile infection (CDI). In this study, we compared dual therapy with IV metronidazole and vancomycin vs vancomycin monotherapy. We assessed prevalence of use and effectiveness of dual therapy in nonfulminant and fulminant CDI. Methods This was a 2-center retrospective study conducted from 2010 to 2018. Adult inpatients were included if they had a positive C. difficile polymerase chain reaction (PCR) performed on an unformed stool and received vancomycin within 2 days of testing. Patients were classified as having received dual therapy if IV metronidazole was given within the same time window, and otherwise classified as vancomycin monotherapy. The primary outcome was death or colectomy within 90 days after the index test. Logistic regression modeling was used to adjust for CDI severity and other established predictors of CDI outcomes. CDI recurrence was examined as a secondary outcome, adjusting for death as a competing risk. Results The study included 2114 patients (dual therapy, 993; monotherapy, 1121); 23% met the primary outcome. There was no association between dual therapy and the primary outcome (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI],.79–1.45), which remained true when the analysis was restricted to patients with fulminant CDI (aOR, 1.17; 95% CI,.65–2.10). There was also no association between dual therapy and CDI recurrence. Conclusions Dual therapy with IV metronidazole and vancomycin was common for nonfulminant and fulminant CDI but was not associated with improved outcomes compared with vancomycin alone. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Isoniazid or isonicotinic acid hydrazide (INH) becoming the earliest antibiotics introduced for the treatment of tuberculosis (TB). Topics include enzyme being critical to the synthesis of mycolic acids which being a vital component of the mycobacterial cell wall; and technologies such as nucleic acid amplification and whole genome sequencing transforming the ability for rapidly diagnosing TB.

With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first 3 months of 2020, the coronavirus disease 2019 (COVID-19) pandemic has emerged as an unprecedented health care crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, health care delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and health care workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. Although mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography and CT are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pretest probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing patients with COVID-19 across a spectrum of health care environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based on the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of chest radiography and CT in the management of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Ambulatory based treatment of tuberculosis has been recently introduced in Kazakhstan. We sought to assess the attitudes of the general population, TB patients and their household members towards ambulatory TB treatment and identify how knowledge of TB is associated with these attitudes.Methods: New pulmonary TB cases and their household and community controls were recruited from three regions of Kazakhstan in 2012-2014. 1083 participants completed audio computer-assisted self interviews to assess their knowledge of TB and attitudes towards ambulatory care. Mixed effects logistic regression models were used to identify factors associated with attitudes toward ambulatory TB treatment.Results: The proportion of people who considered ambulatory TB treatment as appropriate was very low (24.9%). Positive attitudes towards ambulatory TB treatment were significantly associated with region of residence, higher level of education, family support and experience with TB. The association between sufficient tuberculosis knowledge and favorable attitude toward ambulatory treatment was stronger among community controls compared to TB patients and their family members.Conclusions: This study provides insight into attitudes toward ambulatory TB treatment among different groups and the specific influence of TB knowledge on these attitudes. Our findings can inform the process of integration of new TB treatment strategies and the development of appropriate education and advocacy programs in the general population. [ABSTRACT FROM AUTHOR]

Background: Patient awareness of asthma severity is important for optimal asthma management. However, there is often a discrepancy between physician assessment of asthma control based on guidelines and patient discernment of control. We compared physician and patient perception of asthma control in a clinic population seen at a tertiary hospital in Addis Ababa, Ethiopia.Methods: In this cross-sectional study, 182 consecutive patients with a physician diagnosis of asthma seen in Chest Clinic at Tikur Anbessa Specialized Hospital (TASH) between July and December 2015 were studied. Demographics, asthma symptoms, medication use in the past month, and self-perception of asthma control in the past 7 days were obtained from the clinic records. Physician assessed asthma control was based on the GINA asthma symptom control assessment tool. Lung function was measured using a Diagnostic EasyOne Plus model 2001 SN spirometer. The institutional review board approved the study protocol.Results: Of the 182 subjects, 68.1% were female. The mean age was 52 ± 12 years, and the mean (SD) duration of asthma was 19.4 ± 12.7 years. Forty-four (24.2%) patients had physician determined well-controlled asthma and 138 (75.8%) patients had physician determined partly controlled/uncontrolled asthma. One hundred and fifty-one (83%) patients thought their asthma control was good. However, the degree of concordance between physician evaluation and patient perception of asthma control was low (kappa index = 0.09). On multivariate analysis, self-perceived poor asthma control was associated with any activity limitation due to asthma and inconsistent inhaled corticosteroid use.Conclusion: In our study, the first of its kind in Ethiopia, a high percent of patients with physician determined well-controlled asthma has appropriate perception of their disease state. However, those patients with partly controlled/uncontrolled asthma had poor self-perception of their disease, emphasizing the need for further patient education. These conclusions may be especially useful in the care of asthmatics from other low-income countries. [ABSTRACT FROM AUTHOR]

The article offers updates in lung infections and tuberclosis from 2018. Topics discussed include role of the microbiome in lung inflammation continues to gain attention in clinical and experimental studies; humans and mice, microbiota-depleting antibiotic treatment resulted in reduced levels of a proliferation; and role in propagating pseudomonal and other infections, and its therapeutic implications.

Acute aortic occlusion is a very rare but devastating occurrence in diabetic ketoacidosis (DKA). We report a unique presentation of DKA with aortic thrombi and distal arterial emboli. A 53-year-old woman, type 2 diabetes presented due to 7 days of abdominal complaint and DKA. She developed gangrene of her right leg. Contrast-enhanced CT revealed extensive thrombus formation in the aorta, and filling defects in other major arteries. The arterial occlusions most likely resulted from a hypercoagulable state associated with her DKA. Clinicians should maintain a high index of suspicion for arterial thrombosis in patients presenting with DKA. [ABSTRACT FROM AUTHOR]

Background Precision public health is a novel set of methods to target disease prevention and mitigation interventions to high-risk subpopulations. We applied a precision public health strategy to syndromic surveillance for severe acute respiratory infection (SARI) in Uganda by combining spatiotemporal analytics with genomic sequencing to detect and characterize viral respiratory pathogens with epidemic potential. Methods Using a national surveillance network we identified patients with unexplained, influenza-negative SARI from 2010 to 2015. Spatiotemporal analyses were performed retrospectively to identify clusters of unexplained SARI. Within clusters, respiratory viruses were detected and characterized in naso- and oropharyngeal swab samples using a novel oligonucleotide probe capture (VirCapSeq-VERT) and high-throughput sequencing platform. Linkage to conventional epidemiologic strategies further characterized transmission dynamics of identified pathogens. Results Among 2901 unexplained SARI cases, 9 clusters were detected, accounting for 301 (10.4%) cases. Clusters were more likely to occur in urban areas and during biannual rainy seasons. Within detected clusters, we identified an unrecognized outbreak of measles-associated SARI; sequence analysis implicated cocirculation of endemic genotype B3 and genotype D4 likely imported from England. We also detected a likely nosocomial SARI cluster associated with a novel picobirnavirus most closely related to swine and dromedary viruses. Conclusions Using a precision approach to public health surveillance, we detected and characterized the genomics of vaccine-preventable and zoonotic respiratory viruses associated with clusters of severe respiratory infections in Uganda. Future studies are needed to assess the feasibility, scalability, and impact of applying similar approaches during real-time public health surveillance in low-income settings. [ABSTRACT FROM AUTHOR]

Introduction: Asthma is significant in Ethiopia and appropriate treatment has been inconsistent. We evaluated lung function and medication use among asthmatics seen in the outpatient chest clinic of Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. Methods: A cross-sectional study was conducted from July 1 to December 30, 2015. Chart review was used to obtain clinical information and spirometric values on those with physician-diagnosed asthma. Airflow obstruction was defined as a FEV1/FVC < 70% and an FEV1< 80% predicted. Results: 96 study subjects were identified. The mean age was 53 ± 12 years; 64.6% (n=62) were female. Twenty-five percent (n=24) had normal spirometry and 75% (n=72) had airflow obstruction. In multivariate analysis, impaired lung function was associated with longer duration of asthma (adjusted OR 3.89, 95% CI 1.24- 12.24) and an asthma exacerbation in the last 12 months (adjusted OR 3.38, 95% CI 1.11-10.30). Of those 72 asthmatics with impaired lung function, 94.4% (n=68) were using SABA but only 56% (n=40) were on ICS. Conclusion: Most study asthmatics had impaired lung function and were not on appropriate asthma treatment. These findings suggest a need for more readily available and inexpensive asthma medications as well as qualified physicians to guide asthma management in Ethiopia. [ABSTRACT FROM AUTHOR]

Transplantation in potential candidates who have recently recovered from COVID‐19 is a challenge with uncertainties regarding the diagnosis, multi‐organ systemic involvement, prolonged viral shedding in immunocompromised patients, and optimal immunosuppression. A 42 year male with alcoholic hepatitis underwent a successful deceased donor liver transplantation 71 days after the initial diagnosis of COVID‐19. At the time of transplant, he was SARS‐CoV‐2 PCR negative for 24 days and had a MELD score of 33. His post‐operative course was complicated by acute rejection which responded to intense immune‐suppression using T‐cell depletion and steroids. He was discharged with normal end‐organ function and no evidence of any active infection including COVID‐19. Prospective organ transplant recipients who have recovered from COVID‐19 can be considered for transplantation after careful pre‐transplant evaluation, donor selection, and individualized risk‐benefit analysis. [ABSTRACT FROM AUTHOR]

Rationale: Data are limited regarding the safety of 12-dose once-weekly isoniazid (H, 900 mg) plus rifapentine (P, 900 mg) (3HP) for latent infection treatment during pregnancy.Objectives: To assess safety and pregnancy outcomes among pregnant women who were inadvertently exposed to study medications in two latent tuberculosis infection trials (PREVENT TB or iAdhere) evaluating 3HP and 9 months of daily isoniazid (H, 300 mg) (9H).Methods: Data from reproductive-age (15-51 yr) women who received one or more study dose of 3HP or 9H in either trial were analyzed. Drug exposure during pregnancy occurred if the estimated date of conception was on or before the last dose date.Results: Of 126 pregnancies (125 participants) that occurred during treatment or follow-up, 87 were exposed to study drugs. Among these, fetal loss was reported for 4/31 (13%) and 8/56 (14%), 3HP and 9H, respectively (difference, 13% - 14% = -1%; 95% confidence interval = -17% to +18%) and congenital anomalies in 0/20 and 2/41 (5%) live births, 3HP and 9H, respectively (difference, 0% - 5% = -5%; 95% confidence interval = -18% to +16%). All fetal losses occurred in pregnancies of less than 20 weeks. Of the total 126 pregnancies, fetal loss was reported in 8/54 (15%) and 9/72 (13%), 3HP and 9H, respectively; and congenital anomalies in 1/37 (3%) and 2/56 (4%) live births, 3HP and 9H, respectively. The overall proportion of fetal loss (17/126 [13%]) and anomalies (3/93 [3%]) were similar to those estimated for the United States, 17% and 3%, respectively.Conclusions: Among reported pregnancies in these two latent tuberculosis infection trials, there was no unexpected fetal loss or congenital anomalies. These data offer some preliminary reassurance to clinicians and patients in circumstances when these drugs and regimens are the best option in pregnancy or in women of child-bearing potential. This work used the identifying trial registration numbers NCT00023452 and NCT01582711, corresponding to the primary clinical trials PREVENT TB and iAdhere (Tuberculosis Trials Consortium Study 26 and 33). [ABSTRACT FROM AUTHOR]

Objective: Uncontrolled asthma negatively impacts patients, families, and the community. The level of symptom control among asthmatics in Ethiopia has not been well studied. We investigated the level of asthma control and risk factors for poor asthma control in clinic patients seen in the largest public hospital in Ethiopia. Results: In this cross-sectional study, we studied all 182 consecutive subjects with a physician diagnosis of asthma who were seen in chest clinic at Tikur Anbessa Specialized Hospital between July and December 2015. Of the 182 subjects, 68.1% were female. The mean age was 52 ± 12 years and the median duration of asthma was 20 ± 12.7 years. One hundred and seventeen subjects (64.3%) had nighttime awakening due to asthma. Fifty-eight (31%) were not using controller medications and 62 (34.6%) had improper inhaler technique. Only 44 (24.2%) subjects had well-controlled asthma. On multivariate analysis, variables associated with uncontrolled asthma included: use of biomass fuel for cooking, longer duration of asthma (> 30 year), incorrect inhalation technique, and asthma exacerbation in the last 12 months. Most asthmatics attending in the largest public hospital in Ethiopia, had uncontrolled asthma. Several risk factors for poor asthma control were identified. Improved asthma control is possible through directed interventions. [ABSTRACT FROM AUTHOR]

Background: Sputum smear-positive tuberculosis (TB) patients have a high risk of transmission and are of great epidemiological and infection control significance. Little is known about the smear-positive populations in high TB burden regions, such as Kazakhstan. The objective of this study is to characterize the smear-positive population in Kazakhstan and identify associated modifiable risk factors. Methods: Data on incident TB cases’ (identified between April 2012 and March 2014) socio-demographic, risk behavior, and comorbidity characteristics were collected in four regions of Kazakhstan through structured survey and medical record review. We used multivariable logistic regression to determine factors associated with smear positivity. Results: Of the total sample, 193 (34.3%) of the 562 study participants tested smear-positive. In the final adjusted multivariable logistic regression model, sex (adjusted odds ratio (aOR) = 2.0, 95% CI:1.3–3.1, p < 0.01), incarceration (aOR = 3.6, 95% CI:1.2–11.1, p = 0.03), alcohol dependence (aOR = 2.6, 95% CI:1.2–5.7, p = 0.02), diabetes (aOR = 5.0, 95% CI:2.4–10.7, p < 0.01), and physician access (aOR = 2.7, 95% CI:1.3–5.5p < 0.01) were associated with smear-positivity. Conclusions: Incarceration, alcohol dependence, diabetes, and physician access are associated with smear positivity among incident TB cases in Kazakhstan. To stem the TB epidemic, screening, treatment and prevention policies should address these factors. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Grosset murine model of treatment for latent tuberculosis infection (LTBI). Topics include inbred mice being immunized with an aerosol challenge with bacillus Calmette-Guerin (BCG) and infected with virulent Mycobacterium tuberculosis; and creative combinations using mixtures of drugs, doses, and routes of administration.

Despite an extensive burden of lung disease in East Africa, there are remarkably few pulmonary physicians in the region and no pulmonary subspecialty training programs. We developed a unique training program for pulmonary medicine in Ethiopia. The East African Training Initiative (EATI) is a 2-year fellowship program at Tikur Anbessa (Black Lion) Specialized Teaching Hospital, the largest public hospital in Ethiopia and the teaching hospital for the Addis Ababa University School of Medicine. The first year is devoted to clinical care and procedural skills. Lectures, conferences, daily inpatient and outpatient rounds, and procedure supervision by visiting faculty provide the clinical knowledge foundation. In the second year, training in clinical research is added to ongoing clinical training. Before graduation, fellows must pass rigorous written and oral examinations and achieve high marks on faculty evaluations. Funding derives from several sources. Ethiopian trainees are paid by the Ethiopian Ministry of Health and the Addis Ababa University School of Medicine. The World Lung Foundation and the Swiss Lung Foundation supply travel and housing costs for visiting faculty, who receive no other stipend. The first two trainees graduated in January 2015, and a second class of three fellows completed training in January 2016. All five presented research abstracts at the annual meetings of the International Union Against Tuberculosis and Lung Disease in 2014 and 2015. The EATI has successfully provided pulmonary medicine training in Ethiopia and has capacity for local leadership. We believe that EATI could be a model for other resource-limited countries. [ABSTRACT FROM AUTHOR]

Background: Little is known about the United States diagnosis and burden of pulmonary embolism (PE) in the emergency department (ED), and their evolution over the past decade. We examined nationally representative data to evaluate factors associated with and trends in ED diagnosis of PE. Methods: We conducted a cross-sectional study using National Hospital Ambulatory Medical Care Survey (NHAMCS) data from January 1, 2001 to December 31, 2010. We identified all ED patient visits where PE was diagnosed and corresponding demographic, hemodynamic, testing and disposition data. Analyses were performed using descriptive statistics and multivariable logistic regression. Results: During the study period 988,000 weighted patient visits with diagnosis of PE were identified. Among patients with an ED visit, the likelihood of having a diagnosis of PE per year increased significantly from 2001 to 2010 (odds ratio [OR] 1.091, 95% confidence interval [CI] 1.034-1.152, P = 0.002 for trend) when adjusted for demographic and hospital information. In contrast, when further adjusted for the use of computed tomography (CT) among patients in the ED, the likelihood of having a diagnosis of PE per year did not change (OR 1.041, 95% CI 0.987-1.097, P = 0.14). Overall, 75.1% of patients seen with a diagnosis of PE were hemodynamically stable; 86% were admitted with an in-hospital death rate under 3%. Conclusions: The proportion of ED visits with a diagnosis of PE increased significantly from 2001 to 2010 and this rise can be attributed in large part to the increased availability and use of CT. Most of these patients were admitted with low in-hospital mortality. [ABSTRACT FROM AUTHOR]

Rationale: Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown.Objectives: We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment.Methods: Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase.Measurements and Main Results: A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration-time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively).Conclusions: Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629). [ABSTRACT FROM AUTHOR]