Household Air Pollution Interventions to Improve Health in Low- and Middle-Income Countries: An Official American Thoracic Society Research Statement.

Background: An estimated 3 billion people, largely in low- and middle-income countries, rely on unclean fuels for cooking, heating, and lighting to meet household energy needs. The resulting exposure to household air pollution (HAP) is a leading cause of pneumonia, chronic lung disease, and other adverse health effects. In the last decade, randomized controlled trials of clean cooking interventions to reduce HAP have been conducted. We aim to provide guidance on how to interpret the findings of these trials and how they should inform policy makers and practitioners.Methods: We assembled a multidisciplinary working group of international researchers, public health practitioners, and policymakers with expertise in household air pollution from within academia, the American Thoracic Society, funders, nongovernmental organizations, and global organizations, including the World Bank and the World Health Organization. We performed a literature search, convened four sessions via web conference, and developed consensus conclusions and recommendations via the Delphi method.Results: The committee reached consensus on 14 conclusions and recommendations. Although some trials using cleaner-burning biomass stoves or cleaner-cooking fuels have reduced HAP exposure, the committee was divided (with 55% saying no and 45% saying yes) on whether the studied interventions improved measured health outcomes.Conclusions: HAP is associated with adverse health effects in observational studies. However, it remains unclear which household energy interventions reduce exposure, improve health, can be scaled, and are sustainable. Researchers should engage with policy makers and practitioners working to scale cleaner energy solutions to understand and address their information needs.

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.

Clinical characteristics, imaging, and lung function among patients with persistent dyspnea of COVID-19: a retrospective observational cohort study.

The available medical literature on lung function and corresponding clinical characteristics among symptomatic survivors of Corona Virus Disease 2019 (long COVID) is sparse. Primary physicians referred patients who manifested persistent dyspnea months after their index case of infection to a designated clinic. Patients underwent symptom-driven, quality-of-life, physical, and focused respiratory [pulmonary function tests and computed tomography (CT) of the chest] evaluations and were followed over time. In this paper, we present our findings. Patients with abnormal CT imaging were more likely to be of advanced age and to have been hospitalized during their COVID-19 infection. Forced exhaled volume in the first second, forced vital capacity (FVC), total lung capacity, and diffusion capacity of carbon monoxide measurements were found to be significantly lower in patients with abnormal CT imaging. Multivariate regression of clinical characteristics uncovered a significant association between FVC, body mass index, history of hospitalization, and diabetes mellitus. In conclusion, longer-term studies will help further our understanding of the risk factors, disease course, and prognosis of long COVID patients.

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.).

Hospital Readmissions After Implementation of a Discharge Care Program for Patients with COVID-19 Illness.

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.

A Spatiotemporal Tool to Project Hospital Critical Care Capacity and Mortality From COVID-19 in US Counties.

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.

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.

Predictive value of TNF-α, IFN-γ, and IL-10 for tuberculosis among recently exposed contacts in the United States and Canada.

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.

Knowledge and attitudes towards ambulatory treatment of tuberculоsis in Kazakhstan.

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.

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.

Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial.

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).