Pathogenesis of HIV-Related Lung Disease: Immunity, Infection, and Inflammation.

Despite anti-retroviral therapy (ART), human immunodeficiency virus-1 (HIV)-related pulmonary disease continues to be a major cause of morbidity and mortality for people living with HIV (PLWH). The spectrum of lung diseases has changed from acute opportunistic infections resulting in death to chronic lung diseases for those with access to ART. Chronic immune activation and suppression can result in impairment of innate immunity and progressive loss of T cell and B cell functionality with aberrant cytokine and chemokine responses systemically as well as in the lung. HIV can be detected in the lungs of PLWH and has profound effects on cellular immune functions. In addition, HIV-related lung injury and disease can occur secondary to a number of mechanisms including altered pulmonary and systemic inflammatory pathways, viral persistence in the lung, oxidative stress with additive effects of smoke exposure, microbial translocation, and alterations in the lung and gut microbiome. Although ART has had profound effects on systemic viral suppression in HIV, the impact of ART on lung immunology still needs to be fully elucidated. Understanding of the mechanisms by which HIV-related lung diseases continue to occur is critical to the development of new preventive and therapeutic strategies to improve lung health in PLWH.

"I Thought Cancer was a Tobacco Issue": Perspectives of Veterans with and without HIV on Cancer and Other Health Risks Associated with Alcohol and Tobacco/Nicotine Use.

U.S. Veterans and people living with HIV (PWH) experience higher rates of unhealthy alcohol and tobacco/nicotine use than non-Veterans and people without HIV (PWoH). Both groups are susceptible to adverse health outcomes associated with alcohol and tobacco/nicotine use. We explored awareness of alcohol- and tobacco/nicotine-related cancer and immune health risks among Veterans Health Administration (VA) patients with and without HIV. Among a sample of 41 (46% PWH; 73% male; 39% Black) purposively-selected VA patients receiving care 2020-2021 we conducted semi-structured interviews via telephone; interviews were recorded, transcribed and analyzed using a Rapid Assessment Process. Purposive selection was based on HIV status, alcohol and/or tobacco/nicotine use, and demographics. Among participants, 66% reported current smoking, and most screened positive for unhealthy alcohol use. Participants had high awareness of cancer and other health risks related to smoking but low awareness of synergistic risks and cancer risks associated with alcohol use despite awareness of a range of other alcohol-related risks. Awareness of alcohol and/or tobacco/nicotine's impacts on the immune system was variable. Findings did not distinctly differ between PWH and PWoH. Low awareness of alcohol-related cancer risk, risks of co-occurring use, and varying awareness of the impacts of alcohol and tobacco/nicotine on the immune system suggest a need for improved messaging regarding substance use-related cancer and immune risk. This may be especially important among PWH, for whom the prevalence and adverse effects of alcohol and tobacco use, and immune dysfunction are higher.

Trends Over Time in the Risk of Adverse Outcomes Among Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: We aimed to describe trends in adverse outcomes among patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between February and September 2020 within a national healthcare system. METHODS: We identified enrollees in the national United States Veterans Affairs healthcare system who tested positive for SARS-CoV-2 between 28 February 2020 and 30 September 2020 (n = 55 952), with follow-up extending to 19 November 2020. We determined trends over time in incidence of the following outcomes that occurred within 30 days of testing positive: hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death. RESULTS: Between February and July 2020, there were marked downward trends in the 30-day incidence of hospitalization (44.2% to 15.8%), ICU admission (20.3% to 5.3%), mechanical ventilation (12.7% to 2.2%), and death (12.5% to 4.4%), which subsequently plateaued between July and September 2020. These trends persisted after adjustment for sociodemographic characteristics, comorbid conditions, documented symptoms, and laboratory tests, including among subgroups of patients hospitalized, admitted to the ICU, or treated with mechanical ventilation. From February to September, there were decreases in the use of hydroxychloroquine (56.5% to 0%), azithromycin (48.3% to 16.6%), vasopressors (20.6% to 8.7%), and dialysis (11.6% to 3.8%) and increases in the use of dexamethasone (3.4% to 53.1%), other corticosteroids (4.9% to 29.0%), and remdesivir (1.7% to 45.4%) among hospitalized patients. CONCLUSIONS: The risk of adverse outcomes in SARS-CoV-2-positive patients decreased markedly between February and July, with subsequent stabilization from July to September. These trends were not explained by changes in measured baseline patient characteristics and may reflect changing treatment practices or viral pathogenicity.

Dexamethasone in hospitalised COVID-19 patients not on intensive respiratory support.

BACKGROUND: Dexamethasone decreases mortality in coronavirus disease 2019 (COVID-19) patients on intensive respiratory support (IRS) but is of uncertain benefit if less severely ill. We determined whether early (within 48 h) dexamethasone was associated with mortality in patients hospitalised with COVID-19 not on IRS. METHODS: We included patients admitted to US Veterans Affairs hospitals between 7 June 2020 and 31 May 2021 within 14 days after a positive test for severe acute respiratory syndrome coronavirus 2. Exclusions included recent prior corticosteroids and IRS within 48 h. We used inverse probability of treatment weighting (IPTW) to balance exposed and unexposed groups, and Cox proportional hazards models to determine 90-day all-cause mortality. RESULTS: Of 19 973 total patients (95% men, median age 71 years, 27% black), 15 404 (77%) were without IRS within 48 h. Of these, 3514 out of 9450 (34%) patients on no oxygen received dexamethasone and 1042 (11%) died; 4472 out of 5954 (75%) patients on low-flow nasal cannula (NC) only received dexamethasone and 857 (14%) died. In IPTW stratified models, patients on no oxygen who received dexamethasone experienced 76% increased risk for 90-day mortality (hazard ratio (HR) 1.76, 95% CI 1.47-2.12); there was no association with mortality among patients on NC only (HR 1.08, 95% CI 0.86-1.36). CONCLUSIONS: In patients hospitalised with COVID-19, early initiation of dexamethasone was common and was associated with no mortality benefit among those on no oxygen or NC only in the first 48 h; instead, we found evidence of potential harm. These real-world findings do not support the use of early dexamethasone in hospitalised COVID-19 patients without IRS.

Wellness and Coping of Physicians Who Worked in ICUs During the Pandemic: A Multicenter Cross-Sectional North American Survey.

OBJECTIVES: Few surveys have focused on physician moral distress, burnout, and professional fulfilment. We assessed physician wellness and coping during the COVID-19 pandemic. DESIGN: Cross-sectional survey using four validated instruments. SETTING: Sixty-two sites in Canada and the United States. SUBJECTS: Attending physicians (adult, pediatric; intensivist, nonintensivist) who worked in North American ICUs. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We analysed 431 questionnaires (43.3% response rate) from 25 states and eight provinces. Respondents were predominantly male (229 [55.6%]) and in practice for 11.8 ± 9.8 years. Compared with prepandemic, respondents reported significant intrapandemic increases in days worked/mo, ICU bed occupancy, and self-reported moral distress (240 [56.9%]) and burnout (259 [63.8%]). Of the 10 top-ranked items that incited moral distress, most pertained to regulatory/organizational ( n = 6) or local/institutional ( n = 2) issues or both ( n = 2). Average moral distress (95.6 ± 66.9), professional fulfilment (6.5 ± 2.1), and burnout scores (3.6 ± 2.0) were moderate with 227 physicians (54.6%) meeting burnout criteria. A significant dose-response existed between COVID-19 patient volume and moral distress scores. Physicians who worked more days/mo and more scheduled in-house nightshifts, especially combined with more unscheduled in-house nightshifts, experienced significantly more moral distress. One in five physicians used at least one maladaptive coping strategy. We identified four coping profiles (active/social, avoidant, mixed/ambivalent, infrequent) that were associated with significant differences across all wellness measures. CONCLUSIONS: Despite moderate intrapandemic moral distress and burnout, physicians experienced moderate professional fulfilment. However, one in five physicians used at least one maladaptive coping strategy. We highlight potentially modifiable factors at individual, institutional, and regulatory levels to enhance physician wellness.

Prostate Cancer Screening and Incidence among Aging Persons Living with HIV.

PURPOSE: The risk of prostate cancer among persons living with human immunodeficiency virus (PWH) is not well understood and may be obscured by different opportunities for detection. MATERIALS AND METHODS: We identified 123,472 (37,819 PWH and 85,653 comparators) men enrolled in the Veterans Aging Cohort Study, a prospective national cohort of PWH and demographically matched, uninfected comparators in 2000-2015. We calculated rates of prostate specific antigen (PSA) testing by human immunodeficiency virus (HIV) status and fit multivariable Poisson models comparing the rates of PSA testing, prostate biopsy, and cancer incidence. RESULTS: The mean age at enrollment was 52 years. Rates of PSA testing were lower in PWH versus uninfected comparators (0.58 versus 0.63 tests per person-year). Adjusted rates of PSA screening and prostate biopsy were lower among PWH (incidence rate ratio [IRR] 0.87, 95% CI 0.75-0.84 and IRR 0.79 95% CI 0.74-0.83, respectively). The crude IRR for prostate cancer was lower in PWH versus controls (IRR 0.90, 95% CI 0.83-0.97). However, in a multivariable model adjusting for PSA testing, cancer incidence was similar by HIV status (IRR=0.93, 95% CI 0.86-1.01, p=0.08). Among patients who received a prostate biopsy, incidence of prostate cancer did not differ significantly by HIV status (IRR 1.06, 95% CI 0.98-1.15, p=0.15). Among incident cancers, there were significant differences in the distributions of Gleason grade (p=0.05), but not cancer stage (p=0.14) by HIV status. CONCLUSIONS: When accounting for less PSA testing among PWH, the incidence of prostate cancer was similar by HIV status. These findings suggest that less screening contributed to lower observed incidence of prostate cancer in PWH.

Tobacco smoking and binge alcohol use are associated with incident venous thromboembolism in an HIV cohort.

BACKGROUND: People with HIV (PWH) are at increased risk of cardiovascular comorbidities and substance use is a potential predisposing factor. We evaluated associations of tobacco smoking and alcohol use with venous thromboembolism (VTE) in PWH. METHODS: We assessed incident, centrally adjudicated VTE among 12 957 PWH within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort between January 2009 and December 2018. Using separate Cox proportional hazards models, we evaluated associations of time-updated alcohol and cigarette use with VTE, adjusting for demographic and clinical characteristics. Smoking was evaluated as pack-years and never, former, or current use with current cigarettes per day. Alcohol use was parameterized using categorical and continuous alcohol use score, frequency of use, and binge frequency. RESULTS: During a median of 3.6 years of follow-up, 213 PWH developed a VTE. One-third of PWH reported binge drinking and 40% reported currently smoking. In adjusted analyses, risk of VTE was increased among both current (HR: 1.44, 95% CI: 1.02-2.03) and former (HR: 1.44, 95% CI: 0.99-2.07) smokers compared to PWH who never smoked. Additionally, total pack-years among ever-smokers (HR: 1.10 per 5 pack-years; 95% CI: 1.03-1.18) was associated with incident VTE in a dose-dependent manner. Frequency of binge drinking was associated with incident VTE (HR: 1.30 per 7 days/month, 95% CI: 1.11-1.52); however, alcohol use frequency was not. Severity of alcohol use was not significantly associated with VTE. CONCLUSIONS: Current smoking and pack-year smoking history were dose-dependently associated with incident VTE among PWH in CNICS. Binge drinking was also associated with VTE. Interventions for smoking and binge drinking may decrease VTE risk among PWH.

Cirrhosis and Severe Acute Respiratory Syndrome Coronavirus 2 Infection in US Veterans: Risk of Infection, Hospitalization, Ventilation, and Mortality.

BACKGROUND AND AIMS: Whether patients with cirrhosis have increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the extent to which infection and cirrhosis increase the risk of adverse patient outcomes remain unclear. APPROACH AND RESULTS: We identified 88,747 patients tested for SARS-CoV-2 between March 1, 2020, and May 14, 2020, in the Veterans Affairs (VA) national health care system, including 75,315 with no cirrhosis-SARS-CoV-2-negative (C0-S0), 9,826 with no cirrhosis-SARS-CoV-2-positive (C0-S1), 3,301 with cirrhosis-SARS-CoV-2-negative (C1-S0), and 305 with cirrhosis-SARS-CoV-2-positive (C1-S1). Patients were followed through June 22, 2020. Hospitalization, mechanical ventilation, and death were modeled in time-to-event analyses using Cox proportional hazards regression. Patients with cirrhosis were less likely to test positive than patients without cirrhosis (8.5% vs. 11.5%; adjusted odds ratio, 0.83; 95% CI, 0.69-0.99). Thirty-day mortality and ventilation rates increased progressively from C0-S0 (2.3% and 1.6%) to C1-S0 (5.2% and 3.6%) to C0-S1 (10.6% and 6.5%) and to C1-S1 (17.1% and 13.0%). Among patients with cirrhosis, those who tested positive for SARS-CoV-2 were 4.1 times more likely to undergo mechanical ventilation (adjusted hazard ratio [aHR], 4.12; 95% CI, 2.79-6.10) and 3.5 times more likely to die (aHR, 3.54; 95% CI, 2.55-4.90) than those who tested negative. Among patients with SARS-CoV-2 infection, those with cirrhosis were more likely to be hospitalized (aHR, 1.37; 95% CI, 1.12-1.66), undergo ventilation (aHR, 1.61; 95% CI, 1.05-2.46) or die (aHR, 1.65; 95% CI, 1.18-2.30) than patients without cirrhosis. Among patients with cirrhosis and SARS-CoV-2 infection, the most important predictors of mortality were advanced age, cirrhosis decompensation, and high Model for End-Stage Liver Disease score. CONCLUSIONS: SARS-CoV-2 infection was associated with a 3.5-fold increase in mortality in patients with cirrhosis. Cirrhosis was associated with a 1.7-fold increase in mortality in patients with SARS-CoV-2 infection.

Nucleic Acid-based Testing for Noninfluenza Viral Pathogens in Adults with Suspected Community-acquired Pneumonia. An Official American Thoracic Society Clinical Practice Guideline.

Background: This document provides evidence-based clinical practice guidelines on the diagnostic utility of nucleic acid-based testing of respiratory samples for viral pathogens other than influenza in adults with suspected community-acquired pneumonia (CAP).Methods: A multidisciplinary panel developed a Population-Intervention-Comparison-Outcome question, conducted a pragmatic systematic review, and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: The panel evaluated the literature to develop recommendations regarding whether routine diagnostics should include nucleic acid-based testing of respiratory samples for viral pathogens other than influenza in suspected CAP. The evidence addressing this topic was generally adjudicated to be of very low quality because of risk of bias and imprecision. Furthermore, there was little direct evidence supporting a role for routine nucleic acid-based testing of respiratory samples in improving critical outcomes such as overall survival or antibiotic use patterns. However, on the basis of direct and indirect evidence, recommendations were made for both outpatient and hospitalized patients with suspected CAP. Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was not addressed in the literature at the time of the evidence review.Conclusions: The panel formulated and provided their rationale for recommendations on nucleic acid-based diagnostics for viral pathogens other than influenza for patients with suspected CAP.

Risk Factors for Testing Positive for Severe Acute Respiratory Syndrome Coronavirus 2 in a National United States Healthcare System.

BACKGROUND: Identifying risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could help health systems improve testing and screening strategies. The aim of this study was to identify demographic factors, comorbid conditions, and symptoms independently associated with testing positive for SARS-CoV-2. METHODS: This was an observational cross-sectional study at the Veterans Health Administration, including persons tested for SARS-CoV-2 nucleic acid by polymerase chain reaction (PCR) between 28 February and 14 May 2020. Associations between demographic characteristics, diagnosed comorbid conditions, and documented symptoms with testing positive for SARS-CoV-2 were measured. RESULTS: Of 88 747 persons tested, 10 131 (11.4%) were SARS-CoV-2 PCR positive. Positivity was associated with older age (≥80 vs <50 years: adjusted odds ratio [aOR], 2.16 [95% confidence interval {CI}, 1.97-2.37]), male sex (aOR, 1.45 [95% CI, 1.34-1.57]), regional SARS-CoV-2 burden (≥2000 vs <400 cases/million: aOR, 5.43 [95% CI, 4.97-5.93]), urban residence (aOR, 1.78 [95% CI, 1.70-1.87]), black (aOR, 2.15 [95% CI, 2.05-2.26]) or American Indian/Alaska Native Hawaiian/Pacific Islander (aOR, 1.26 [95% CI, 1.05-1.52]) vs white race, and Hispanic ethnicity (aOR, 1.52 [95% CI, 1.40-1.65]). Obesity and diabetes were the only 2 medical conditions associated with testing positive. Documented fevers, chills, cough, and diarrhea were also associated with testing positive. The population attributable fraction of positive tests was highest for geographic location (35.3%), followed by demographic variables (27.1%), symptoms (12.0%), obesity (10.5%), and diabetes (0.4%). CONCLUSIONS: The majority of positive SARS-CoV-2 tests were attributed to geographic location, demographic characteristics, and obesity, with a minor contribution of chronic comorbid conditions.

Community-acquired Pneumonia Guideline Recommendations-Impact of a Consensus-based Process versus Systematic Reviews.

BACKGROUND: The American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) Community-acquired Pneumonia (CAP) guidelines were developed using systematic reviews to inform every recommendation, as suggested by the Institute of Medicine Standards for Trustworthy Guidelines. Recent studies suggest that an expert consensus-based approach, called the Convergence of Opinion on Recommendations and Evidence (CORE) process, can produce recommendations that are concordant with recommendations informed by systematic reviews. PURPOSE: The goal of the study was to evaluate the efficacy of the CORE process had it been used to develop the ATS/IDSA CAP guidelines. METHODS: Experts in CAP who were not on the guideline panel and had no knowledge of the guideline's systematic reviews or recommendations were recruited to participate in the CORE process, addressing the same questions asked by the guideline panel. Recommendations derived from the CORE process were compared to the guideline recommendations. Concordance of the course of action, strength of recommendation, and quality of evidence were determined. RESULTS: Using a threshold of 70% of experts selecting the same course of action to make a recommendation, the CORE process yielded a recommendation for 20 of 31 (65%) questions. Among the 20 CORE-derived recommendations, 19 (95%) were concordant with the guideline recommendations (kappa agreement 0.88, 95% CI .64-1.00). There was less agreement among the strength of recommendations (58%) and quality of evidence (42%). CONCLUSIONS: If the CORE process had been used, 11 systematic reviews would have been necessary rather than 31, with minimal impact on the recommended courses of action.

Does pulmonary subspecialty referral from primary care affect the adherence to vaccination recommendations in COPD patients?

The importance of vaccinations for COPD patients has been previously described. However, there is still a gap between guideline recommendations and the implementation of preventive care delivery for these patients. Specially, the rise of SARS-CoV-2 pandemic has made the significance of vaccination adherence more critical to address. Our study showed that referral to pulmonary clinic is associated with increased odds of receiving influenza (OR = 1.97, [95% CI 1.07, 3.65]) and pneumococcal vaccinations (PCV13 OR = 3.55, [1.47, 8.54]; PPSV23 OR = 4.92, [1.51, 16.02]). These data suggest that partnerships between primary care physicians and pulmonologists can potentially improve the vaccination rates for patients with COPD.

Association of Syndemic Unhealthy Alcohol Use, Smoking, and Depressive Symptoms on Incident Cardiovascular Disease among Veterans With and Without HIV-Infection.

Unhealthy alcohol use, smoking, and depressive symptoms are risk factors for cardiovascular disease (CVD). Little is known about their co-occurrence - termed a syndemic, defined as the synergistic effect of two or more conditions-on CVD risk in people with HIV (PWH). We used data from 5621 CVD-free participants (51% PWH) in the Veteran's Aging Cohort Study-8, a prospective, observational study of veterans followed from 2002 to 2014 to assess the association between this syndemic and incident CVD by HIV status. Diagnostic codes identified cases of CVD (acute myocardial infarction, stroke, heart failure, peripheral artery disease, and coronary revascularization). Validated measures of alcohol use, smoking, and depressive symptoms were used. Baseline number of syndemic conditions was categorized (0, 1, ≥ 2 conditions). Multivariable Cox Proportional Hazards regressions estimated risk of the syndemic (≥ 2 conditions) on incident CVD by HIV-status. There were 1149 cases of incident CVD (52% PWH) during the follow-up (median 10.1 years). Of the total sample, 64% met our syndemic definition. The syndemic was associated with greater risk for incident CVD among PWH (Hazard Ratio [HR] 1.87 [1.47-2.38], p < 0.001) and HIV-negative veterans (HR 1.70 [1.35-2.13], p < 0.001), compared to HIV-negative with zero conditions. Among those with the syndemic, CVD risk was not statistically significantly higher among PWH vs. HIV-negative (HR 1.10 [0.89, 1.37], p = .38). Given the high prevalence of this syndemic combined with excess risk of CVD, these findings support linked-screening and treatment efforts.

The United States National Cancer Institute's Coordinated Research Effort on Tobacco Use as a Major Cause of Morbidity and Mortality among People with HIV.

The use of antiretroviral therapy for people with HIV (PWH) has improved life expectancy. However, PWH now lose more life-years to tobacco use than to HIV infection. Unfortunately, PWH smoke at higher rates and have more difficulty maintaining abstinence than the general population, compounding their risk for chronic disease. In this Commentary, we describe a United States National Cancer Institute-led initiative to address the relative lack of research focused on developing, testing, and implementing smoking cessation interventions for PWH. This initiative supports seven clinical trials designed to systematically test and/or develop and test adaptations of evidence-based smoking cessation interventions for PWH (eg, combination of behavioral and pharmacological). We summarize each project, including setting/recruitment sites, inclusion/exclusion criteria, interventions being tested, and outcomes. This initiative provides critical opportunities for collaboration and data harmonization across projects. The knowledge gained will inform strategies to assist PWH to promote and maintain abstinence, and ensure that these efforts are adaptable and scalable, thereby addressing one of the major threats to the health of PWH. Reducing smoking behavior may be particularly important during the COVID-19 pandemic given that smokers who become infected with SARS-CoV-2 may be at risk for more severe disease. IMPLICATIONS: This Commentary describes a National Cancer Institute-led initiative to advance the science and practice of treating tobacco use among PWH, which is now responsible for more life years lost than HIV. We describe the scope of the problem, the objectives of the initiative, and a summary of the seven funded studies. Harmonization of data across projects will provide information related to treatment mediators and moderators that was not previously possible. Stakeholders interested in tobacco cessation, including researchers, clinicians and public health officials, should be aware of this initiative and the evidence-base it will generate to advance tobacco treatment among this high-risk population.

Addressing Disparities in Lung Cancer Screening Eligibility and Healthcare Access. An Official American Thoracic Society Statement.

Background: There are well-documented disparities in lung cancer outcomes across populations. Lung cancer screening (LCS) has the potential to reduce lung cancer mortality, but for this benefit to be realized by all high-risk groups, there must be careful attention to ensuring equitable access to this lifesaving preventive health measure.Objectives: To outline current knowledge on disparities in eligibility criteria for, access to, and implementation of LCS, and to develop an official American Thoracic Society statement to propose strategies to optimize current screening guidelines and resource allocation for equitable LCS implementation and dissemination.Methods: A multidisciplinary panel with expertise in LCS, implementation science, primary care, pulmonology, health behavior, smoking cessation, epidemiology, and disparities research was convened. Participants reviewed available literature on historical disparities in cancer screening and emerging evidence of disparities in LCS.Results: Existing LCS guidelines do not consider racial, ethnic, socioeconomic, and sex-based differences in smoking behaviors or lung cancer risk. Multiple barriers, including access to screening and cost, further contribute to the inequities in implementation and dissemination of LCS.Conclusions: This statement identifies the impact of LCS eligibility criteria on vulnerable populations who are at increased risk of lung cancer but do not meet eligibility criteria for screening, as well as multiple barriers that contribute to disparities in LCS implementation. Strategies to improve the selection and dissemination of LCS in vulnerable groups are described.

Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study.

BACKGROUND: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19). We investigated racial and ethnic disparities in patterns of COVID-19 testing (i.e., who received testing and who tested positive) and subsequent mortality in the largest integrated healthcare system in the United States. METHODS AND FINDINGS: This retrospective cohort study included 5,834,543 individuals receiving care in the US Department of Veterans Affairs; most (91%) were men, 74% were non-Hispanic White (White), 19% were non-Hispanic Black (Black), and 7% were Hispanic. We evaluated associations between race/ethnicity and receipt of COVID-19 testing, a positive test result, and 30-day mortality, with multivariable adjustment for a wide range of demographic and clinical characteristics including comorbid conditions, health behaviors, medication history, site of care, and urban versus rural residence. Between February 8 and July 22, 2020, 254,595 individuals were tested for COVID-19, of whom 16,317 tested positive and 1,057 died. Black individuals were more likely to be tested (rate per 1,000 individuals: 60.0, 95% CI 59.6-60.5) than Hispanic (52.7, 95% CI 52.1-53.4) and White individuals (38.6, 95% CI 38.4-38.7). While individuals from minority backgrounds were more likely to test positive (Black versus White: odds ratio [OR] 1.93, 95% CI 1.85-2.01, p < 0.001; Hispanic versus White: OR 1.84, 95% CI 1.74-1.94, p < 0.001), 30-day mortality did not differ by race/ethnicity (Black versus White: OR 0.97, 95% CI 0.80-1.17, p = 0.74; Hispanic versus White: OR 0.99, 95% CI 0.73-1.34, p = 0.94). The disparity between Black and White individuals in testing positive for COVID-19 was stronger in the Midwest (OR 2.66, 95% CI 2.41-2.95, p < 0.001) than the West (OR 1.24, 95% CI 1.11-1.39, p < 0.001). The disparity in testing positive for COVID-19 between Hispanic and White individuals was consistent across region, calendar time, and outbreak pattern. Study limitations include underrepresentation of women and a lack of detailed information on social determinants of health. CONCLUSIONS: In this nationwide study, we found that Black and Hispanic individuals are experiencing an excess burden of SARS-CoV-2 infection not entirely explained by underlying medical conditions or where they live or receive care. There is an urgent need to proactively tailor strategies to contain and prevent further outbreaks in racial and ethnic minority communities.

Incidence, Risk Factors, and Outcomes of Idiopathic Pneumonia Syndrome after Allogeneic Hematopoietic Cell Transplantation.

Our current knowledge of idiopathic pneumonia syndrome (IPS) predates improved specificity in the diagnosis of IPS and advances in hematopoietic cell transplantation (HCT) and critical care practices. In this study, we describe and update the incidence, risk factors, and outcomes of IPS. We performed a retrospective cohort study of all adults who underwent allogeneic HCT at the Fred Hutchinson Cancer Research Center between 2006 and 2013 (n = 1829). IPS was defined using the National Heart, Lung, and Blood Institute consensus definition: multilobar airspace opacities on chest imaging, absence of lower respiratory tract infection, and hypoxemia. We described IPS incidence and mortality within 120 and 365 days after HCT. We examined conditioning intensity (nonmyeloablative versus myeloablative with high-dose total body irradiation [TBI] versus myeloablative with low-dose TBI) as an IPS risk factor in a time-to-event analysis using Cox models, controlled for age at transplant, HLA matching, stem cell source, and pretransplant Lung function Score (a combined measure of impairment in Forced Expiratory Volume in the first second (FEV1) and Diffusion capacity for carbon monoxide (DLCO)). Among 1829 HCT recipients, 67 fulfilled IPS criteria within 120 days (3.7%). Individuals who developed IPS were more likely to be black/non-Hispanic versus other racial groups and have severe pulmonary impairment but were otherwise similar to participants without IPS. In adjusted models, myeloablative conditioning with high-dose TBI was associated with increased risk of IPS (hazard ratio, 2.5; 95% confidence interval, 1.2 to 5.2). Thirty-one patients (46.3%) with IPS died within the first 120 days of HCT and 47 patients (70.1%) died within 365 days of HCT. In contrast, among the 1762 patients who did not acquire IPS in the first 120 days, 204 (11.6%) died within 120 days of HCT and 510 (29.9%) died within 365 days of HCT. Our findings suggest that although the incidence of IPS may be declining, it remains associated with post-transplant mortality. Future study should focus on early detection and identifying pathologic mediators of IPS to facilitate timely, targeted therapies for those most susceptible to lung injury post-HCT.

Pulmonary infections in the hematopoietic cell transplant patient.

PURPOSE OF REVIEW: Despite progress in the management of pulmonary infections in the hematopoietic cell transplant (HCT) population, substantial diagnostic, and therapeutic uncertainty remains. RECENT FINDINGS: A growing HCT population reflects more transplants and improved long-term survival. We continue to learn about the epidemiologic and prognostic significance of posttransplant pulmonary infections. Mold-active triazoles have removed invasive fungal pneumonia as a barrier to transplant eligibility. Ibrutinib and respiratory viruses are newly recognized risk factors for invasive fungal disease. Prophylaxis has elevated concerns of resistance in invasive fungal species and late onset Cytomegalovirus. The impact of human herpesviruses, community-associated respiratory viruses, and the microbiome is increasingly appreciated. Multiple antiviral therapies are currently in clinical trials and novel molecular diagnostics may improve the performance of bronchoscopy for infectious causes. SUMMARY: Fungal and viral pneumonias remain an important cause of morbidity and mortality in the HCT population. Despite our increased understanding of the epidemiology and outcomes of species-specific diagnoses, the utility of invasive diagnostic testing continues to be debated and effective therapies for many clinically relevant pathogens remain limited. Pulmonary infections are a priority for research efforts in this immunocompromised population.

What Exactly Is Shared Decision-Making? A Qualitative Study of Shared Decision-Making in Lung Cancer Screening.

BACKGROUND: Shared decision-making (SDM) is widely recommended and required by the Centers for Medicare and Medicaid for patients considering lung cancer screening (LCS). OBJECTIVE: We examined clinicians' communication practices and perceived barriers of SDM for LCS at three medical centers with established screening programs. DESIGN: Multicenter qualitative study of clinicians participating in LCS. APPROACH: We performed semi-structured interviews, which were transcribed and analyzed using directed content analysis, guided by a theoretical model of patient-clinician communication. PARTICIPANTS: We interviewed 24 clinicians including LCS coordinators (2), pulmonologists (3), and primary care providers (17), 4 of whom worked for the LCS program, a thoracic surgeon, and a radiologist. RESULTS: All clinicians agreed with the goal of SDM, to ensure the screening decision was congruent with the patient's values. The depth and type of information presented by each clinician role varied considerably. LCS coordinators presented detailed information including numeric estimates of benefit and harm. Most PCPs explained the process more generally, focusing on logistics and the high rate of nodule detection. No clinician explicitly elicited values or communication preferences. Many PCPs tailored the conversation based on their implicit understanding of patients' values and preferences, gained from past experiences. PCPs reported that time, lack of detailed personal knowledge of LCS, and patient preferences were barriers to SDM. Many clinicians perceived that a significant proportion of patients were not interested in specific percentages and preferred to receive a clinician recommendation. CONCLUSIONS: Our results suggest that clinicians support the goal of SDM for LCS decisions but PCPs may not perform some of its elements. The lack of completion of some elements, such as PCPs' lack of in-depth information exchange, may reflect perceived patient preferences for communication. As LCS is implemented, further research is needed to support a personalized, patient-centered approach to produce better outcomes.

Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America.

Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.