Epidemiology and Outcomes of Critical Illness and Novel Predictors of Mortality in an Ethiopian Medical Intensive Care Unit.

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.

Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19.

BACKGROUND: Hydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use. METHODS: We examined the association between hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding consecutive patients hospitalized with Covid-19, excluding those who were intubated, died, or discharged within 24 hours after presentation to the emergency department (study baseline). The primary end point was a composite of intubation or death in a time-to-event analysis. We compared outcomes in patients who received hydroxychloroquine with those in patients who did not, using a multivariable Cox model with inverse probability weighting according to the propensity score. RESULTS: Of 1446 consecutive patients, 70 patients were intubated, died, or discharged within 24 hours after presentation and were excluded from the analysis. Of the remaining 1376 patients, during a median follow-up of 22.5 days, 811 (58.9%) received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days); 45.8% of the patients were treated within 24 hours after presentation to the emergency department, and 85.9% within 48 hours. Hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive hydroxychloroquine (median ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs. 360). Overall, 346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation). In the main analysis, there was no significant association between hydroxychloroquine use and intubation or death (hazard ratio, 1.04, 95% confidence interval, 0.82 to 1.32). Results were similar in multiple sensitivity analyses. CONCLUSIONS: In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed. (Funded by the National Institutes of Health.).

The Role of Chest Imaging in Patient Management during the COVID-19 Pandemic: A Multinational Consensus Statement from the Fleischner Society.

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.

Advances in the diagnosis and treatment of latent tuberculosis infection.

PURPOSE OF REVIEW: This review describes the major developments in the rationale for treating latent tuberculosis infection; new approaches to identifying persons with latent infection who are most likely to progress to active disease; and the development of novel short-course regimens for treatment of latent tuberculosis. RECENT FINDINGS: As many as one-third of the world's population has latent infection with Mycobacterium tuberculosis. Models demonstrate that tuberculosis will not be eliminated without large-scale treatment of persons with latent TB. Current tools for identifying persons at risk for active tuberculosis disease include TST and IGRA, which have poor positive predictive values. Newer approaches using gene expression profiling show promise and are being studied in the ongoing trials. Development of short-course regimens are a major advance in treatment of latent TB. Three months of rifapentine with isoniazid, 4 months of rifampin, and 1 month of rifapentine with isoniazid have been found to be noninferior to the standard 9 months of isoniazid. SUMMARY: Progress towards TB elimination can be accelerated by instituting public health measures that take into account new developments in identifying and treating persons with latent tuberculosis infection who are most likely to progress to active disease.

Precision Surveillance for Viral Respiratory Pathogens: Virome Capture Sequencing for the Detection and Genomic Characterization of Severe Acute Respiratory Infection in Uganda.

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.

Perception of asthma control among asthmatics seen inChest Clinic at Tertiary Hospital, Addis Ababa, Ethiopia.

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.

National trends in emergency room diagnosis of pulmonary embolism, 2001-2010: a cross-sectional study.

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.

SEQUELAE OF PATIENTS TREATED FOR PULMONARY TUBERCULOSIS IN CHEST CLINIC, TIKUR ANBESSA SPECIALIZED HOSPITAL (TASH), ADDIS ABABA, ETHIOPIA.

BACKGROUND: Pulmonary tuberculosis (PTB) is one of the most common infectious diseases worldwide, and contributes significantly to morbidity and mortality in developing countries. Despite availability of effective treatment, a significant number of patients suffer from permanent lung damage, which predisposes patients to numerous pulmonary complications. OBJECTIVE: To assess chronic sequelae of patients treated for PTB in a chest clinic at Tikur Anbessa Hospital. METHODS: This was a retrospective, cross-sectional analysis of patients registered in a clinical database at the chest clinic of Tikur Anbessa specialized Hospital between January and December 2013. Patients with a history of pulmonary tuberculosis treatment were identified and included in the analysis. RESULTS: Among all patients having follow-up at the chest clinic of TASH during the study period, 134 (18.5%) presented with chronic pulmonary complications of TB. Seventy two patients (54%) were male, and the mean and median ages were 40 and 37 years, respectively. Of the study population, 83 (61.9%) patients had clinically significant parenchymal scarring and fibrosis, 40 (29.9%) had bronchiectasis, 5(3.7%) had Aspergilloma, 4(3%) had granuloma/calcification, one patient (0.7%) had pleural thickening, and one patient (0.7%) underwent pneumonectomy during the study period. CONCLUSIONS: Fibrosis and bronchiectasis were the most common pulmonary complications of tuberculosis among patients encountered at the TASH chest clinic during the study period. This demonstrates the impact of pulmonary tuberculosis is beyond management of active disease.

QT Prolongation Associated with Administration of Bedaquiline, a Novel Anti-Tuberculosis Drug.

Bedaquiline is a diarylquinoline compound that has recently been introduced and approved for use in the treatment of multidrug-resistant tuberculosis (MDR-TB). Its mechanism of action is inhibition of adenosine triphosphate-synthase. In combination with other antibiotics, bedaquiline-containing regimens administered for 6 months achieve cure rates of roughly 90%, in contrast to the previously used, 24-month-long WHO-recommended regimens for the treatment of MDR-TB. However, since its introduction, concerns have been raised about its effects on QT prolongation and its safety in routine clinical use. We reviewed the published experience regarding bedaquiline use, QT prolongation, and adverse cardiac events when the drug was used alone or in combination. Overall, data are reassuring that bedaquiline use in clinical practice is not associated with an excess of cardiac deaths or other clinically meaningful cardiac events. This review provides reassurance and support for the continued use of bedaquiline in the treatment of MDR-TB.

Advances in the diagnosis of latent tuberculosis infection.

Accurate diagnosis of tuberculosis (TB) infection is an important component of tuberculosis control programs in many countries. Identification of persons with asymptomatic, or latent, tuberculosis infection allows for treatment of individuals at high risk for progressing to active disease so that the overall burden of tuberculosis disease is diminished. In the United States, targeted testing and treatment of latent tuberculosis infection (LTI) are major components of the Centers for Disease Control and Prevention's efforts at TB elimination. This review focuses on the comparative utility of tuberculin skin testing and interferon-gamma release assays (IGRAs) to diagnose LTI. Commercially available IGRAs have superior sensitivity and specificity compared with conventional tuberculin skin testingin some settings (particularly bacille-Calmette Guérin-vaccinated individuals). Also discussed are the performance characteristics of these tests in specific populations, including foreign-born persons from high-prevalence countries, close contacts of actively infected patients, immunocompromised populations, and health care workers.