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Importance SARS-CoV-2 has infected over 200 million people worldwide, resulting in more than 4 million deaths. Randomized controlled trials are the single best tool to identify effective treatments against this novel pathogen. Objective To describe the characteristics of randomized controlled trials of treatments for COVID-19 in the United States launched in the first 9 months of the pandemic. Design, Setting, and Participants We conducted a cross-sectional study of all completed or actively enrolling randomized, interventional, clinical trials for the treatment of COVID-19 in the United States registered on www.clinicaltrials.gov as of August 10, 2020. We excluded trials of vaccines and other interventions intended to prevent COVID-19. Main Outcomes and Measures We used descriptive statistics to characterize the clinical trials and the statistical power for the available studies. For the late-phase trials (i.e., phase 3 and 2/3 studies), we compared the geographic distribution of the clinical trials with the geographic distribution of people diagnosed with COVID-19. Results We identified 200 randomized controlled trials of treatments for people with COVID-19. Across all trials, 87 (43.5%) were single-center, 64 (32.0%) were unblinded, and 80 (40.0%) were sponsored by industry. The most common treatments included monoclonal antibodies (N=46 trials), small molecule immunomodulators (N=28), antiviral medications (N=24 trials), and hydroxychloroquine (N=20 trials). Of the 9 trials completed by August 2020, the median sample size was 450 (IQR 67–1113); of the 191 ongoing trials, the median planned sample size was 150 (IQR 60–400). Of the late-phase trials (N=54), the most common primary outcome was a severity scale (N=23, 42.6%), followed by a composite of mortality and ventilation (N=10, 18.5%), and mortality alone (N=6, 11.1%). Among these late-phase trials, all trials of antivirals, monoclonal antibodies, or chloroquine/hydroxychloroquine had a power of less than 25% to detect a 20% relative risk reduction in mortality. Had the individual trials for a given class of treatments instead formed a single trial, the power to detect that same reduction in mortality would have been greater than 98%. There was large variability in access to trials with the highest number of trials per capita in the Northeast and the lowest in the Midwest. Conclusions and Relevance A large number of randomized trials were launched early in the pandemic to evaluate treatments for COVID-19. However, many trials were underpowered for important clinical endpoints and substantial geographic disparities were observed, highlighting the importance of improving national clinical trial infrastructure. Supplementary Information The online version contains supplementary material available at 10.1007/s11606-021-07167-9.

The impact of coronavirus disease 2019 vaccination on viral characteristics of breakthrough infections is unknown. In this prospective cohort study, incidence of severe acute respiratory syndrome coronavirus 2 infection decreased following vaccination. Although asymptomatic positive tests were observed following vaccination, the higher cycle thresholds, repeat negative tests, and inability to culture virus raise questions about their clinical significance.

BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR

Establishing equitable access to COVID-19 clinical trials is an important step in mitigating outcomes disparities. Historically, language has served as a barrier to equitable clinical trial participation.A centralized research infrastructure was established at our institution to screen potential trial participants and to promote efficient and equitable access to COVID-19 clinical trials. Rates of eligibility and enrollment in COVID-19 clinical trials by primary language between April 9 and July 31, 2020 (during the first regional COVID-19 surge) were evaluated using logistic regression. Estimates were adjusted for potential confounders including age, sex, and time.A total of 1245 patients were admitted to the hospital with COVID-19 during the study period and screened for clinical trial eligibility. Among all screened patients, 487 (39%) had a non-English primary language. After adjustment, patients with a non-English primary language had 1.98 times higher odds (CI 1.51 to 2.59) of being eligible for 1 or more COVID-19 clinical trials. Among eligible patients, those with a non-English primary language had 1.83 times higher odds (CI 1.36 to 2.47) of enrolling in COVID-19 clinical trials than patients with English as the primary language.These findings suggest that there are modifiable barriers that can be addressed to lessen the impact of language discordance on access to clinical trials and provide an opportunity to further investigate factors associated with clinical trial participation for patients whose primary language is not English.

BACKGROUND: The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear. METHODS: We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses. RESULTS: We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P = 0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P = 0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P = 0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo. CONCLUSIONS: Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937.).

Isolation guidelines for SARS-CoV-2 are largely derived from data collected prior to emergence of the delta variant. We followed a cohort of ambulatory patients with post-vaccination breakthrough SARS-CoV-2 infections with longitudinal collection of nasal swabs for SARS-CoV-2 viral load quantification, whole genome sequencing, and viral culture. All delta variant infections (8/8, 100%) in our cohort were symptomatic, compared with 64% (9/14) of non-delta variant infections. Delta variant breakthrough infections were characterized by higher initial viral load, longer duration of virologic shedding by PCR (median 13.5 vs 4 days, hazard ratio [HR] 0.45, 95%CI 0.17-1.17), greater likelihood of replication-competent virus at early stages of infection (6/8 [75%] vs 3/14 [23%], P=0.03), and longer duration of culturable virus (median 7 vs 3 days, HR 0.38, 95%CI 0.14-1.02) compared to non-delta variants. Nonetheless, no individuals with delta variant infections had replication-competent virus by day 10 after symptom onset or 24 hours after resolution of symptoms. These data support current US Center for Disease Control isolation guidelines and reinforce the importance of prompt testing and isolation among symptomatic individuals with delta variant breakthrough infections. Additional data are needed to evaluate these relationships among asymptomatic and more severe delta variant breakthrough infections.

Rationale: Clinical and research training opportunities in global health are of increasing interest to medical trainees, but little is known about such opportunities in U.S.-based pulmonary and pulmonary/critical care medicine (PCCM) fellowship programs. Objectives: Summarize currently available global health–related training opportunities and identify potential barriers to implementing global health curricula among U.S.-based PCCM fellowship programs. Methods: We sent a confidential, online, targeted needs assessment to PCCM fellowship program directors and associate program directors. Data collected included program demographics, currently available global health–related clinical and research training opportunities, potential barriers to the implementation of global health–related programmatic content, and perceived interest in global health–related training opportunities by current and/or prospective trainees. To evaluate for nonresponse bias, we performed an online search to identify global health–related training opportunities offered by nonresponding programs. Results: Out of 171 surveyed programs, 63 PCCM fellowship programs (37%) provided survey responses. Most responses (n = 56, 89%) were from combined PCCM training programs; 66% (n = 40) of programs offered at least one component of global health–related clinical or research training. Overall, 27% (n = 17) had a Ruth L. Kirschstein National Research Service Award Institutional Research Training Grant (National Institutes of Health T32), 73% (n = 46) had fewer than 35 faculty members, and 51% (n = 32) had at least one faculty member conducting global health–focused research. Most responding programs (66%, n = 40) offered at least one global health–related educational component. Among programs that would like to offer global health–related training components, the most common barriers included competing priorities for lecture content and a lack of in-division mentors with global health experience, a champion for global health–related activities, and established partnerships outside the United States. Conclusions: PCCM program leaders are interested in offering global health–related training opportunities, but important barriers include lack of mentorship, dedicated fellowship time, and established global partnerships. Future research is needed to better understand global health–related interests and training needs of incoming fellows and to design creative solutions for providing global health–related training across academic institutions with variable global health–related training capacities.

Background Although ≈70% of the world's population of people living with HIV reside in sub‐Saharan Africa, there are minimal prospective data on the contributions of HIV infection to atherosclerosis in the region. Methods and Results We conducted a prospective observational cohort study of people living with HIV on antiretroviral therapy >40 years of age in rural Uganda, along with population‐based comparators not infected with HIV. We collected data on cardiovascular disease risk factors and carotid ultrasound measurements annually. We fitted linear mixed effects models, adjusted for cardiovascular disease risk factors, to estimate the association between HIV serostatus and progression of carotid intima media thickness (cIMT). We enrolled 155 people living with HIV and 154 individuals not infected with HIV and collected cIMT images at 1045 visits during a median of 4 annual visits per participant (interquartile range 3–4, range 1–5). Age (median 50.9 years) and sex (49% female) were similar by HIV serostatus. At enrollment, there was no difference in mean cIMT by HIV serostatus (0.665 versus 0.680 mm, P =0.15). In multivariable models, increasing age, blood pressure, and non–high‐density lipoprotein cholesterol were associated with greater cIMT ( P P =0.25). Conclusions In rural Uganda, treated HIV infection was not associated with faster cIMT progression. These results do not support classification of treated HIV infection as a risk factor for subclinical atherosclerosis progression in rural sub‐Saharan Africa. Registration URL: https://www.ClinicalTrials.gov ; Unique identifier: NCT02445079.

BackgroundObjective and early identification of hospitalized patients, and particularly those with novel coronavirus disease 2019 (COVID-19), who may require mechanical ventilation (MV) may aid in delivering timely treatment.Research questionCan a transparent deep learning (DL) model predict the need for MV in hospitalized patients and those with COVID-19 up to 24h in advance?Study design and methodsWe trained and externally validated a transparent DL algorithm to predict the future need for MV in hospitalized patients, including those with COVID-19, using commonly available data in electronic health records. Additionally, commonly used clinical criteria (heart rate, oxygen saturation, respiratory rate, Fio2, and pH) were used to assess future need for MV. Performance of the algorithm was evaluated using the area under receiver operating characteristic curve (AUC), sensitivity, specificity, and positive predictive value.ResultsWe obtained data from more than 30,000 ICU patients (including more than 700 patients with COVID-19) from two academic medical centers. The performance of the model with a 24-h prediction horizon at the development and validation sites was comparable (AUC, 0.895 vs0.882, respectively), providing significant improvement over traditional clinical criteria (P< .001). Prospective validation of the algorithm among patients with COVID-19 yielded AUCs in the range of 0.918 to 0.943.InterpretationA transparent deep learning algorithm improves on traditional clinical criteria to predict the need for MV in hospitalized patients, including in those with COVID-19. Such an algorithm may help clinicians to optimize timing of tracheal intubation, to allocate resources and staff better, and to improve patient care.

Background Hydroxychloroquine (HCQ) poisoning is a life-threatening but treatable toxic ingestion. The scale of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) and the controversial suggestion that HCQ is a treatment option have led to a significant increase in HCQ use.1 Hence, HCQ poisoning should be at the top-of-mind for emergency providers in cases of toxic ingestion. Treatment for HCQ poisoning includes sodium bicarbonate, epinephrine, and aggressive electrolyte repletion.2–5 Here, we highlight the use of hypertonic saline and diazepam. Case Report We describe the case of a 37-year-old man who presented to the emergency department (ED) after the ingestion of approximately 16 grams of HCQ tablets (initial serum concentration 4,270 ng/mL). He was treated with an epinephrine infusion, hypertonic sodium chloride, high-dose diazepam, sodium bicarbonate, and aggressive potassium repletion. Persistent altered mental status necessitated intubation, and he was managed in the medical intensive care unit until his QRS widening and QTc prolongation resolved. After his mental status improved and it was confirmed that his ingestion was not with the intent to self-harm, he was discharged home with outpatient follow-up. Why should an emergency physician be aware of this? For patients presenting with HCQ overdose and an unknown initial serum potassium level, high-dose diazepam and hypertonic sodium chloride should be started immediately for the patient with widened QRS. The choice of hypertonic sodium chloride instead of sodium bicarbonate is to avoid exacerbating underlying hypokalemia which may in turn potentiate unstable dysrhythmia. In addition, early intubation should be a priority in vomiting patients as both HCQ toxicity and high-dose diazepam cause profound sedation.

Women with HIV (WWH) transitioning through menopause have heightened cardiovascular disease (CVD) risk. In the general population, hot flash burden relates to CVD risk indices. We found higher hot flash burden among women with vs without HIV. Further, among WWH, hot flash burden related to select CVD risk indices.ClinicalTrials.gov RegistrationNCT02874703.

Background Patients with severe coronavirus disease 2019 (COVID-19) have respiratory failure with hypoxemia and acute bilateral pulmonary infiltrates, consistent with ARDS. Respiratory failure in COVID-19 might represent a novel pathologic entity. Research Question How does the lung histopathology described in COVID-19 compare with the lung histopathology described in SARS and H1N1 influenza? Study Design and Methods We conducted a systematic review to characterize the lung histopathologic features of COVID-19 and compare them against findings of other recent viral pandemics, H1N1 influenza and SARS. We systematically searched MEDLINE and PubMed for studies published up to June 24, 2020, using search terms for COVID-19, H1N1 influenza, and SARS with keywords for pathology, biopsy, and autopsy. Using PRISMA-Individual Participant Data guidelines, our systematic review analysis included 26 articles representing 171 COVID-19 patients; 20 articles representing 287 H1N1 patients; and eight articles representing 64 SARS patients. Results In COVID-19, acute-phase diffuse alveolar damage (DAD) was reported in 88% of patients, which was similar to the proportion of cases with DAD in both H1N1 (90%) and SARS (98%). Pulmonary microthrombi were reported in 57% of COVID-19 and 58% of SARS patients, as compared with 24% of H1N1 influenza patients. Interpretation DAD, the histologic correlate of ARDS, is the predominant histopathologic pattern identified in lung pathology from patients with COVID-19, H1N1 influenza, and SARS. Microthrombi were reported more frequently in both patients with COVID-19 and SARS as compared with H1N1 influenza. Future work is needed to validate this histopathologic finding and, if confirmed, elucidate the mechanistic underpinnings and characterize any associations with clinically important outcomes.

Improving Clinical Trial Enrollment Despite formidable barriers to designing, implementing, and completing clinical trials in the midst of a pandemic, there are ways to ensure that the selected tri...

IMPORTANCEObjective and early identification of hospitalized patients, and particularly those with novel coronavirus disease 2019 (COVID-19), who may require mechanical ventilation is of great importance and may aid in delivering timely treatment.OBJECTIVETo develop, externally validate and prospectively test a transparent deep learning algorithm for predicting 24 hours in advance the need for mechanical ventilation in hospitalized patients and those with COVID-19.DESIGNObservational cohort studySETTINGTwo academic medical centers from January 01, 2016 to December 31, 2019 (Retrospective cohorts) and February 10, 2020 to May 4, 2020 (Prospective cohorts).PARTICIPANTSOver 31,000 admissions to the intensive care units (ICUs) at two hospitals. Additionally, 777 patients with COVID-19 patients were used for prospective validation. Patients who were placed on mechanical ventilation within four hours of their admission were excluded.MAIN OUTCOME(S) and MEASURE(S)Electronic health record (EHR) data were extracted on an hourly basis, and a set of 40 features were calculated and passed to an interpretable deep-learning algorithm to predict the future need for mechanical ventilation 24 hours in advance. Additionally, commonly used clinical criteria (based on heart rate, oxygen saturation, respiratory rate, FiO2and pH) was used to assess future need for mechanical ventilation. Performance of the algorithms were evaluated using the area under receiver-operating characteristic curve (AUC), sensitivity, specificity and positive predictive value.RESULTSAfter applying exclusion criteria, the external validation cohort included 3,888 general ICU and 402 COVID-19 patients. The performance of the model (AUC) with a 24-hour prediction horizon at the validation site was 0.882 for the general ICU population and 0.918 for patients with COVID-19. In comparison, commonly used clinical criteria and the ROX score achieved AUCs in the range of 0.773 – 0.782 and 0.768 – 0.810 for the general ICU population and patients with COVID-19, respectively.CONCLUSIONS and RELEVANCEA generalizable and transparent deep-learning algorithm improves on traditional clinical criteria to predict the need for mechanical ventilation in hospitalized patients, including those with COVID-19. Such an algorithm may help clinicians with optimizing timing of tracheal intubation, better allocation of mechanical ventilation resources and staff, and improve patient care.

OBJECTIVES: Atrial fibrillation (AF) is a major risk factor for stroke, which is the leading cause of cardiovascular mortality in sub-Saharan Africa. However, there is limited population-based epidemiological data on AF in sub-Saharan Africa. We sought to estimate the prevalence and correlates of AF in rural Uganda. METHODS: We conducted a cross-sectional study using community health fairs in 2015 targeting eight villages in rural Uganda. Study participants completed a medical history, a clinical exam, blood collection, and 12-lead electrocardiographic (ECG) screening. Of 1,814 participants enrolled in a parent cohort study that includes 98% of adults residing in the geographic area, 856 attended a health fair and were included in this study. Our primary outcome was AF or atrial flutter. We modelled population prevalence of the outcome with inverse probability of treatment weighting using data collected from the full population. RESULTS: 856 (47.2%) adults in the area attended a health fair and were included in the analysis. Health fair attendees were older (42 vs 34 years, p

Background: Women with HIV (WWH) (vs. women without HIV) have an increased risk of cardiovascular disease (CVD) in relation to heightened systemic immune activation/inflammation. Moreover, WWH show evidence of advanced reproductive aging and unique patterns of hot flash symptomatology. General population studies have revealed that hot flashes may relate to surrogate markers of CVD risk. The relationship between hot flashes and immune activation as well as subclinical cardiac pathology among WWH has not been previously investigated. Methods: In a prospective, cross-sectional study, 23 WWH on anti-retroviral therapy and 19 women without HIV (ages 40–75), group-matched on age and BMI, were enrolled and completed reproductive health assessments, immune phenotyping and cardiovascular MRI. Women without prior CVD or diabetes were eligible. Results: Women were similar in age and BMI (WWH vs. women without HIV: 51 ± 5 vs. 52 ± 6 years, P=0.79 and 32 ± 8 vs. 31 ± 7 kg/m2, P=0.71). There was no significant between-group difference in the percentage of women without menses in the past year (p=0.52) or in the percentage of women with undetectable levels of anti-mullerian hormone (p=0.71). No women in either group were on estrogen and/or progesterone for treatment of menopausal symptoms. Hot flash frequency (days per week with hot flashes) was higher among WWH versus women without HIV (median [IQR], 7.0 [1.3, 7.0] vs. 0.8 [0.0, 2.1], p=0.01). In sensitivity analyses excluding either women with menses in the past year or with detectable AMH, WWH still reported a significantly higher number of days per week with hot flashes (7.0 [6.3, 7.0] vs. 0.4 [0.0, 2.3], p=0.007, and 7.0 [2.4, 7.0] vs. 0.8 [0.0, 2.1], p=0.01, respectively). Among WWH experiencing (vs. not experiencing) hot flashes in the past year, longer duration of ART use was noted (21.2 [16.0, 22.7] vs. 9.3 [3.3, 16.0] years, p=0.03). Among the entire cohort and among WWH, women with more than one hot flash per day had higher levels of soluble CD14, a marker of monocyte activation, compared to women with one or fewer hot flash per day (p=0.004 and p=0.02, respectively). Among WWH and a history of hot flashes, years since onset of hot flashes related to cardiovascular MRI-derived measures of subclinical pathology. Specifically, years since onset of hot flashes related directly to myocardial steatosis (intramyocardial triglyceride content; ρ=0.80, p=0.02) and inversely to diastolic function (left atrial passive ejection fraction; ρ=─0.70, p=0.03). Conclusions: WWH experienced a higher frequency of hot flashes compared to women without HIV. Among WWH, hot flash symptomatology related to systemic immune activation and to cardiovascular MRI-derived measures of CVD risk. Additional research is required to improve understanding of mechanisms underlying these relationships and determine if hot flashes are a sex-specific risk factor for CVD in WWH.

Background Most of the global burden of pollution-related morbidity and mortality is believed to occur in resource-limited settings, where HIV serostatus and sex may influence the relationship between air pollution exposure and respiratory morbidity. The lack of air quality monitoring networks in these settings limits progress in measuring global disparities in pollution-related health. Personal carbon monoxide monitoring may identify sub-populations at heightened risk for air pollution-associated respiratory morbidity in regions of the world where the financial cost of air quality monitoring networks is prohibitive. Methods From September 2015 through May 2017, we measured 48-h ambulatory carbon monoxide (CO) exposure in a longitudinal cohort of HIV-infected and uninfected adults in rural southwestern Uganda. We fit generalized mixed effects models to identify correlates of CO exposure exceeding international air quality thresholds, quantify the relationship between CO exposure and respiratory symptoms, and explore potential effect modification by sex and HIV serostatus. Results Two hundred and sixty study participants completed 419 sampling periods. Personal CO exposure exceeded international thresholds for 50 (19%) participants. In covariate-adjusted models, living in a home where charcoal was the main cooking fuel was associated with CO exposure exceeding international thresholds (adjusted odds ratio [AOR] 11.3, 95% confidence interval [95%CI] 4.7–27.4). In sex-stratified models, higher CO exposure was associated with increased odds of respiratory symptoms among women (AOR 3.3, 95%CI 1.1–10.0) but not men (AOR 1.3, 95%CI 0.4–4.4). In HIV-stratified models, higher CO exposure was associated with increased odds of respiratory symptoms among HIV-infected (AOR 2.5, 95%CI 1.01–6.0) but not HIV-uninfected (AOR 1.4, 95%CI 0.1–14.4) participants. Conclusions In a cohort in rural Uganda, personal CO exposure frequently exceeded international thresholds, correlated with biomass exposure, and was associated with respiratory symptoms among women and people living with HIV. Our results provide support for the use of ambulatory CO monitoring as a low-cost, feasible method to identify subgroups with heightened vulnerability to pollution-related respiratory morbidity in resource-limited settings and identify subgroups that may have increased susceptibility to pollution-associated respiratory morbidity. Electronic supplementary material The online version of this article (10.1186/s12940-019-0517-z) contains supplementary material, which is available to authorized users.

Background The global burden of chronic obstructive pulmonary disease (COPD) disproportionately affects resource-limited settings such as sub-Saharan Africa (SSA), but population-based prevalence estimates in SSA are rare. We aimed to estimate the population prevalence of COPD and chronic respiratory symptoms in rural southwestern Uganda. Methods Adults at least 18 years of age who participated in a population-wide census in rural southwestern Uganda completed respiratory questionnaires and lung function testing with bronchodilator challenge at health screening events in June 2015. We defined COPD as post-bronchodilator forced expiratory volume in one second to forced vital capacity ratio less than the lower limit of normal. We fit multivariable linear and log binomial regression models to estimate correlates of abnormal lung function and respiratory symptoms, respectively. We included inverse probability of sampling weights in models to facilitate population-level estimates. Results Forty-six percent of census participants (843/1814) completed respiratory questionnaires and spirometry, of which 565 (67%) met acceptability standards. COPD and respiratory symptom population prevalence were 2% (95% confidence interval (CI) = 1%-3%) and 30% (95% CI = 25%-36%), respectively. Respiratory symptoms were more prevalent and lung function was lower among women and ever-smokers (P

Background Sex-based differences in cardiovascular disease (CVD) burden are widely acknowledged, with male sex considered a risk factor in high-income settings. However, these relationships have not been examined in sub-Saharan Africa (SSA). We aimed to apply the American Heart Association (AHA) ideal cardiovascular health (CVH) tool modified by the addition of C-reactive protein (CRP) to examine potential sex-based differences in the prevalence of CVD risk in rural Uganda. Methods In a cross-sectional study nested within a population-wide census, 857 community-living adults completed physical and laboratory-based assessments to calculate individual ideal CVH metrics including an eight category for CRP levels. We summarized sex-specific ideal CVH indices, fitting ordinal logistic regression models to identify correlates of improving CVH. As secondary outcomes, we assessed subscales of ideal CVH behaviours and factors. Models included inverse probability of sampling weights to determine population-level estimates. Results The weighted-population mean age was 39.2 (1.2) years with 52.0 (3.7) % females. Women had ideal scores in smoking (80.4% vs. 68.0%; p

A republication, with permission, of 'Air Pollution in the Asia‐Pacific Region. A Joint Asian Pacific Society of Respirology/American Thoracic Society Perspective'. Am. J. Respir. Crit. Care Med. 2019; 199: 693–700. doi: 10.1164/rccm.201804‐0673PP

A growing number of pulmonary and critical care medicine fellowship programs in the United States offer global health training opportunities. Formal, integrated global health programs within pulmonary and critical care fellowships are relatively new but are built on principles and ideals of global health that focus on the mutually beneficial exchange of knowledge and social justice. Although core competencies consistent with these overarching themes in global health education have not been formalized for pulmonary and critical care trainees, relevant competency areas include clinical knowledge, international research training, cultural competency, and clinical and research capacity building. Existing global health education in U.S. pulmonary and critical care medicine training programs can generally be classified as one of three different models: integrated global health tracks, global health electives, and additional research years. Successful global health education programs foster partnerships and collaborations with international sites that emphasize bidirectional exchange. This bidirectional exchange includes ongoing, equitable commitments to mutual opportunities for training and professional development, including a focus on the particular knowledge and skill sets critical for addressing the unique priorities of individual countries. However, barriers related to the availability of mentorship, funding, and dedicated time exist to expanding global health education in pulmonary and critical care medicine. The implementation of global health training within pulmonary and critical care medicine programs requires continued optimization, but this training is essential to prepare the next generation of physicians to address the global aspects of respiratory disease and critical illness.

People living with HIV (PLWH) are more likely to smoke compared to HIV-uninfected counterparts, but little is known about smoking behaviors in sub-Saharan Africa. To address this gap in knowledge, we characterized smoking cessation patterns among people living with HIV (PLWH) compared to HIV-uninfected individuals in rural Uganda. PLWH were at least 40 years of age and on antiretroviral therapy for at least three years, and HIV-uninfected individuals were recruited from the clinical catchment area. Our primary outcome of interest was smoking cessation, which was assessed using an adapted WHO STEPS smoking questionnaire. We fit Cox proportional hazards models to compare time to smoking cessation between PLWH pre-care, PLWH in care, and HIV-uninfected individuals. We found that, compared to HIV-uninfected individuals, PLWH in care were less likely to have ever smoked (40% vs. 49%, p = 0.04). The combined sample of 267 ever-smokers had a median age of 56 (IQR 49-68), 56% (n = 150) were male, and 26% (n = 70) were current smokers. In time-to-event analyses, HIV-uninfected individuals and PLWH prior to clinic enrollment ceased smoking at similar rates (HR 0.8, 95% CI 0.5-1.2). However, after enrolling in HIV care, PLWH had a hazard of smoking cessation over twice that of HIV-uninfected individuals and three times that of PLWH prior to enrollment (HR 2.4, 95% CI 1.3-4.6, p = 0.005 and HR 3.0, 95% CI 1.6-5.5, p = 0.001, respectively). In summary, we observed high rates of smoking cessation among PLWH after engagement in HIV care in rural Uganda. While we hypothesize that greater access to primary care services and health counseling might contribute, future studies should better investigate the mechanism of this association.

This chapter describes the clinical presentation of commonly-encountered occupational and environmental respiratory disorders, including principles regarding disease recognition and prevention. Where appropriate, clinical cases are included to illustrate specific diseases. The chapter begins with a general introduction to the evaluation of individuals and populations, including important considerations from the history and physical examination as well as common findings on typical diagnostic tests such as chest X-rays and other imaging studies, and pulmonary function testing. Specific disease topics covered include (a) disorders due to irritant exposures (high-, moderate-, and low-solubility irritants); (b) disorders due to nonirritant exposures (carbon monoxide and indoor and ambient air pollution); (c) occupational airways diseases (work-related asthma and occupational chronic obstructive pulmonary disease); (d) hypersensitivity pneumonitis, byssinosis, and other diseases due to organic dust exposure; and (e) pneumoconiosis (including asbestosis, silicosis, and coal workers’ pneuconiosis). Childhood asthma is discussed as a risk factor for occupationally-related lung disease.

HIV is associated with chronic obstructive pulmonary disease (COPD) in high resource settings. Similar relationships are less understood in low resource settings. We aimed to estimate the association between HIV infection, tuberculosis, and COPD in rural Uganda. The Uganda Non-communicable Diseases and Aging Cohort study observes people 40 years and older living with HIV (PLWH) on antiretroviral therapy, and population-based HIV-uninfected controls in rural Uganda. Participants completed respiratory questionnaires and post-bronchodilator spirometry. Among 269 participants with spirometry, median age was 52 (IQR 48–55), 48% (n = 130) were ever-smokers, and few (3%, n = 9) reported a history of COPD or asthma. All participants with prior tuberculosis (7%, n = 18) were PLWH. Among 143 (53%) PLWH, median CD4 count was 477 cells/mm3 and 131 (92%) were virologically suppressed. FEV1 was lower among older individuals (− 0.5%pred/year, 95% CI 0.2–0.8, p

Household air pollution (HAP) and chronic HIV infection are each associated with significant respiratory morbidity. Little is known about relationships between HAP and respiratory symptoms among people living with HIV. The objective of this study was to investigate the relationship between cooking fuel type and chronic respiratory symptoms in study participants from the Uganda AIDS Rural Treatment Outcomes Study. Study participants were enrolled at the time of antiretroviral therapy initiation and seen quarterly from 2005 to 2014 for health-focused questionnaires, CD4 count and HIV viral load. We used multivariable logistic regression and generalised estimating equations, with each study visit as a unit of observation, to investigate relationships between cooking fuel type and chronic respiratory symptoms. We observed an association between cooking with firewood (versus charcoal) and chronic cough among HIV-infected females in rural Uganda (adjusted OR 1.41, 95% CI 1.00–1.99; p=0.047). We did not observe an association between cooking fuel type and respiratory symptoms among males (adjusted OR 0.88, 95% CI 0.47–1.63; p=0.658). Associations between cooking fuel and chronic cough in this HIV-infected cohort may be influenced by sex-based roles in meal preparation. This study raises important questions about relationships between household air pollution, HIV infection and respiratory morbidity., This study raises important questions about relationships between air pollution, HIV and respiratory morbidity http://ow.ly/zjsJ30arkI0

Objectives: We aimed to estimate the prevalence and correlates of QT interval prolongation in rural Uganda.Background: Major electrocardiographic abnormalities, including prolonged QT interval, have been shown to be independently predictive of adverse cardiovascular events among Western populations. Cardiovascular diseases are on the rise in sub-Saharan Africa with poorly characterized context-specific risk factors. An important question is whether ECG screening might have value in cardiovascular disease risk stratification in SSA.Methods: We conducted a cross-sectional survey in a sample of adults participating in an ongoing whole-population cohort in Mbarara, Uganda, in 2015. Of 1,814 subjects enrolled in the parent whole-population cohort, 856 (47%) participated in the study. Participants completed 12-lead electrocardiography and cardiovascular disease risk factors assessment. We summarized sex-specific, heart rate variationeadjusted QT (QTa) defining prolonged QTa as >460 ms in women and >450 ms in men. We fit linear and logistic regression models to estimate correlates of (continuous) QTa interval length and (dichotomous) prolonged QTa. Models included inverse probability of sampling weights to generate population-level estimates accounting for study nonparticipation.Results: We assessed data from 828 participants with electrocardiograms. The weighted population mean age was 38.4 years (95% confidence interval: 36.3–40.4). The weighted population was 50.4% female, 11.5% had elevated blood pressure, and 57.6% had a high-sensitivity C-reactive protein >1 mg/dl. The population mean QTa was 409.1 ms (95% confidence interval: 405.1–413.1), and 10.3% (95% confidence interval: 7.8–13.5) met criteria for prolonged QTa. Women had a higher mean QTa (421.6 ms vs. 396.3 ms; p < 0.001), and a higher proportion of women had a prolonged QTa (14.0% vs. 9.3%; p = 0.122) than did men. In multivariable-adjusted regression models, female sex and hypertension correlated with higher mean QTa and meeting criteria for prolonged QTa, respectively.Conclusions: QT interval prolongation is highly prevalent in rural Uganda and may be more common than in high-income settings. Female sex, age, and high blood pressure correlated with QT interval prolongation. Future work should assess whether genetic predisposition or environmental factors in sub-Saharan African populations contribute to prolonged QT and clarify consequences.HighlightsProlongation of QT interval is known to be associated with incident major adverse cardiovascular events and death in populations in high-income settings.QT interval prolongation is highly prevalent in rural Uganda and may be more common than in high-income settings.In rural Uganda, female sex, age, and high blood pressure are correlated with QT interval prolongation.Additional data are needed to understand context-specific QT interval norms, and how, if, they contribute to major adverse cardiovascular events or death in this setting.

Introduction Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for influenza-related morbidity and mortality. Influenza vaccination is known to decrease influenza incidence, severity, hospitalizations, and mortality. Identification of barriers to influenza vaccination among patients with COPD may aid in efforts to increase vaccination rates. This study aims to identify predictors of influenza vaccination in COPD patients. Methods This study used data from the 2012 Behavioral Risk Factor Surveillance System (BRFSS). Participants with self-reported COPD and receiving an influenza vaccination in the prior 12 months were identified. Independent predictors of the exposure were identified by estimating a parsimonious logistic regression model of influenza vaccination. All analyses were performed using weighted data. Results The final study sample consisted of 36,811 COPD participants, with 48.5% of COPD patients reporting having been vaccinated and 51.5% reporting being unvaccinated. A total of 15 independent predictors of influenza vaccination in COPD patients were identified. Negative predictors included predisposing factors (younger age, male gender, household children, black or non-white/non-Hispanic/non-black race/ethnicity, lower education level, heavy alcohol use, current tobacco use) and enabling factors that reflect access to medical care (insurance status, ability to afford care, having a recent check-up). Positive predictors of influenza vaccination included need factors (chronic comorbidities), being a military veteran, or being a former smoker. Conclusions This analysis identifies multiple predictors of influenza vaccination in persons with COPD. Identification of at risk-groups provides the foundation for development of focused efforts to improve influenza vaccination rates in patients with COPD.

In the last 20 years, there has been an increased focus on gender differences in health and disease. The earliest studies of lung cancer enrolled mainly men, as the incidence of lung cancer among women was exceedingly low. As social patterns changed around World War II and women began to smoke more, the epidemiology of lung cancer has changed. The higher percentage of lung cancer in nonsmoking women as compared with nonsmoking men suggests that lung cancer behaves differently in women. Studies of lung cancer in women indicate that there are differences in risk factors, histology, pathophysiology, treatment outcomes, and prognosis as compared with men. The purpose of this review is to provide a concise summary of the literature on lung cancer as it pertains to women, with an emphasis on new areas of research and treatment options.