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Solomon, Joshua J.; Danoff, Sonye K.; Woodhead, Felix A.; Hurwitz, Shelley, Maurer, Rie, Glaspole, Ian, Dellaripa, Paul F.; Gooptu, Bibek, Vassallo, Robert, Cox, P. Gerard, Flaherty, Kevin R.; Adamali, Huzaifa I.; Gibbons, Michael A.; Troy, Lauren, Forrest, Ian A.; Lasky, Joseph A.; Spencer, Lisa G.; Golden, Jeffrey, Scholand, Mary Beth, Chaudhuri, Nazia, Perrella, Mark A.; Lynch, David A.; Chambers, Daniel C.; Kolb, Martin, Spino, Cathie, Raghu, Ganesh, Goldberg, Hilary J.; Rosas, Ivan O.; Haynes-Harp, Shana, Poli, Fernando, Vidya, Coimbatore Sree, Baron, Rebecca R.; Clouser, Timothy, Doyle, Tracy, Maeda, Anthony, Highland, Kristin B.; Albayda, Jemima F.; Collins, Sarah E.; Suresh, Karthik S.; Davis, John M.; Limper, Andrew H.; Amigues, Isabel, Eliopoulos, Kristina, Swigris, Jeffery J.; Humphries, Stephen, Huntwork, John C.; Glynn, Chris, Duncan, Steve R.; Danila, Maria I.; Glassberg, Marilyn K.; Oberstein, Elana M.; Belloli, Elizabeth A.; Briggs, Linda, Nagaraja, Vivek, Cholewa, Linda, DiFranco, Donna, Green, Edward, Liffick, Christie, Naik, Tanvi, Montas, Genevieve, Lebiedz-Odrobina, Dorota, Bissell, Reba, Wener, Mark, Lancaster, Lisa H.; Crawford, Leslie J.; Chan, Karmela, Kaner, Robert J.; Morris, Alicia, Wu, Xiaoping, Khalidi, Nader A.; Ryerson, Christopher J.; Wong, Alyson W.; Fell, Charlene D.; LeClercq, Sharon A.; Hyman, Mark, Shapera, Shane, Mittoo, Shikha, Shaffu, Shireen, Gaffney, Karl, Wilson, Andrew M.; Barratt, Shaney, Gunawardena, Harsha, Hoyles, Rachel K.; David, Joel, Kewalramani, Namrata, Maher, Toby M.; Molyneaux, Philip L.; Kokosi, Maria A.; Cates, Matthew J.; Mandizha, Mandizha, Ashish, Abdul, Chelliah, Gladstone, Parfrey, Helen, Thillai, Muhunthan, Vila, Josephine, Fletcher, Sophie V.; Beirne, Paul, Favager, Clair, Brown, Jo, Dawson, Julie K.; Ortega, Pilar Rivera, Haque, Sahena, Watson, Pippa, Khoo, Jun K.; Symons, Karen, Youssef, Peter, Mackintosh, John A..
The Lancet Respiratory Medicine ; 2022.
Article in English | ScienceDirect | ID: covidwho-2008216

ABSTRACT

Summary Background Interstitial lung disease is a known complication of rheumatoid arthritis, with a lifetime risk of developing the disease in any individual of 7·7%. We aimed to assess the safety, tolerability, and efficacy of pirfenidone for the treatment of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Methods TRAIL1 was a randomised, double-blind, placebo-controlled, phase 2 trial done in 34 academic centres specialising in interstitial lung disease in four countries (the UK, the USA, Australia, and Canada). Adults aged 18–85 years were eligible for inclusion if they met the 2010 American College of Rheumatology and European Alliance of Associations for Rheumatology criteria for rheumatoid arthritis and had interstitial lung disease on a high-resolution CT scan imaging and, when available, lung biopsy. Exclusion criteria include smoking, clinical history of other known causes of interstitial lung disease, and coexistant clinically significant COPD or asthma. Patients were randomly assigned (1:1) to receive 2403 mg oral pirfenidone (pirfenidone group) or placebo (placebo group) daily. The primary endpoint was the incidence of the composite endpoint of a decline from baseline in percent predicted forced vital capacity (FVC%) of 10% or more or death during the 52-week treatment period assessed in the intention-to-treat population. Key secondary endpoints included change in absolute and FVC% over 52 weeks, the proportion of patients with a decline in FVC% of 10% or more, and the frequency of progression as defined by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02808871. Findings From May 15, 2017, to March 31, 2020, 231 patients were assessed for inclusion, of whom 123 patients were randomly assigned (63 [51%] to the pirfenidone group and 60 [49%] to the placebo group). The trial was stopped early (March 31, 2020) due to slow recruitment and the COVID-19 pandemic. The difference in the proportion of patients who met the composite primary endpoint (decline in FVC% from baseline of 10% or more or death) between the two groups was not significant (seven [11%] of 63 patients in the pirfenidone group vs nine [15%] of 60 patients in the placebo group;OR 0·67 [95% CI 0·22 to 2·03];p=0·48). Compared with the placebo group, patients in the pirfenidone group had a slower rate of decline in lung function, measured by estimated annual change in absolute FVC (–66 vs –146;p=0·0082) and FVC% (–1·02 vs –3·21;p=0·0028). The groups were similar with regards to the decline in FVC% by 10% or more (five [8%] participants in the pirfenidone group vs seven [12%] in the placebo group;OR 0·52 [95% CI 0·14–1·90];p=0·32) and the frequency of progression as defined by OMERACT (16 [25%] in the pirfenidone group vs 19 [32%] in the placebo group;OR 0·68 [0·30–1·54];p=0·35). There was no significant difference in the rate of treatment-emergent serious adverse events between the two groups, and there were no treatment-related deaths. Interpretation Due to early termination of the study and underpowering, the results should be interpreted with caution. Despite not meeting the composite primary endpoint, pirfenidone slowed the rate of decline of FVC over time in patients with RA-ILD. Safety in patients with RA-ILD was similar to that seen in other pirfenidone trials. Funding Genentech.

2.
Mayo Clin Proc ; 96(10): 2528-2539, 2021 10.
Article in English | MEDLINE | ID: covidwho-1294052

ABSTRACT

OBJECTIVE: To identify risk factors associated with severe COVID-19 infection in a defined Midwestern US population overall and within different age groups. PATIENTS AND METHODS: We used the Rochester Epidemiology Project research infrastructure to identify persons residing in a defined 27-county Midwestern region who had positive results on polymerase chain reaction tests for COVID-19 between March 1, 2020, and September 30, 2020 (N=9928). Age, sex, race, ethnicity, body mass index, smoking status, and 44 chronic disease categories were considered as possible risk factors for severe infection. Severe infection was defined as hospitalization or death caused by COVID-19. Associations between risk factors and severe infection were estimated using Cox proportional hazard models overall and within 3 age groups (0 to 44, 45 to 64, and 65+ years). RESULTS: Overall, 474 (4.8%) persons developed severe COVID-19 infection. Older age, male sex, non-White race, Hispanic ethnicity, obesity, and a higher number of chronic conditions were associated with increased risk of severe infection. After adjustment, 36 chronic disease categories were significantly associated with severe infection. The risk of severe infection varied significantly across age groups. In particular, persons 0 to 44 years of age with cancer, chronic neurologic disorders, hematologic disorders, ischemic heart disease, and other endocrine disorders had a greater than 3-fold increased risk of severe infection compared with persons of the same age without those conditions. Associations were attenuated in older age groups. CONCLUSION: Older persons are more likely to experience severe infections; however, severe cases occur in younger persons as well. Our data provide insight regarding younger persons at especially high risk of severe COVID-19 infection.


Subject(s)
COVID-19/epidemiology , Health Status Disparities , Severity of Illness Index , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Chronic Disease/epidemiology , Comorbidity , Humans , Infant , Male , Middle Aged , Midwestern United States , Risk Factors , Young Adult
3.
Mayo Clin Proc ; 96(7): 1890-1895, 2021 07.
Article in English | MEDLINE | ID: covidwho-1202099

ABSTRACT

Predictive models have played a critical role in local, national, and international response to the COVID-19 pandemic. In the United States, health care systems and governmental agencies have relied on several models, such as the Institute for Health Metrics and Evaluation, Youyang Gu (YYG), Massachusetts Institute of Technology, and Centers for Disease Control and Prevention ensemble, to predict short- and long-term trends in disease activity. The Mayo Clinic Bayesian SIR model, recently made publicly available, has informed Mayo Clinic practice leadership at all sites across the United States and has been shared with Minnesota governmental leadership to help inform critical decisions during the past year. One key to the accuracy of the Mayo Clinic model is its ability to adapt to the constantly changing dynamics of the pandemic and uncertainties of human behavior, such as changes in the rate of contact among the population over time and by geographic location and now new virus variants. The Mayo Clinic model can also be used to forecast COVID-19 trends in different hypothetical worlds in which no vaccine is available, vaccinations are no longer being accepted from this point forward, and 75% of the population is already vaccinated. Surveys indicate that half of American adults are hesitant to receive a COVID-19 vaccine, and lack of understanding of the benefits of vaccination is an important barrier to use. The focus of this paper is to illustrate the stark contrast between these 3 scenarios and to demonstrate, mathematically, the benefit of high vaccine uptake on the future course of the pandemic.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , COVID-19/epidemiology , Forecasting , Hospitalization/statistics & numerical data , Hospitalization/trends , Humans , United States/epidemiology
5.
BMJ Open ; 11(3): e044010, 2021 03 17.
Article in English | MEDLINE | ID: covidwho-1140334

ABSTRACT

OBJECTIVES: Evaluate associations between ACE inhibitors (ACEis) and angiotensin receptor blockers (ARBs) and clinical outcomes in acute viral respiratory illness (AVRI). DESIGN: Retrospective cohort analysis of claims data. SETTING: The USA; 2018-2019 influenza season. PARTICIPANTS: Main cohort: people with hypertension (HTN) taking an ACEi, ARB or other HTN medications, and experiencing AVRI. Falsification cohort: parallel cohort receiving elective knee or hip replacement. MAIN OUTCOME MEASURES: Main cohort: hospital admission, intensive care unit, acute respiratory distress (ARD), ARD syndrome and all-cause mortality. Falsification cohort: complications after surgery and all-cause mortality. RESULTS: The main cohort included 236 843 episodes of AVRI contributed by 202 629 unique individuals. Most episodes were in women (58.9%), 81.4% in people with Medicare Advantage and 40.3% in people aged 75+ years. Odds of mortality were lower in the ACEi (0.78 (0.74 to 0.83)) and ARB (0.64 (0.61 to 0.68)) cohorts compared with other HTN medications. On all other outcomes, people taking ARBs (but not ACEis) had a >10% reduction in odds of inpatient stays compared with other HTN medications.In the falsification analysis (N=103 353), both ACEis (0.89 (0.80 to 0.98)) and ARBs (0.82 (0.74 to 0.91)) were associated with decreased odds of complications compared with other HTN medications; ARBs (0.64 (0.47 to 0.87)) but not ACEis (0.79 (0.60 to 1.05)) were associated with lower odds of death compared with other HTN medications. CONCLUSIONS: Outpatient use of ARBs was associated with better outcomes with AVRI compared with other medications for HTN. ACEis were associated with reduced risk of death, but with minimal or no reduction in risk of other complications. A falsification analysis conducted to provide context on the possible causal implications of these findings did not provide a clear answer. Further analysis using observational data will benefit from additional approaches to assess causal relationships between these drugs and outcomes in AVRI.


Subject(s)
Angiotensin Receptor Antagonists , Hypertension , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Cohort Studies , Female , Humans , Hypertension/drug therapy , Hypertension/epidemiology , Medicare , Outpatients , Retrospective Studies , United States/epidemiology
6.
Mayo Clin Proc ; 96(3): 690-698, 2021 03.
Article in English | MEDLINE | ID: covidwho-1002862

ABSTRACT

In March 2020, our institution developed an interdisciplinary predictive analytics task force to provide coronavirus disease 2019 (COVID-19) hospital census forecasting to help clinical leaders understand the potential impacts on hospital operations. As the situation unfolded into a pandemic, our task force provided predictive insights through a structured set of visualizations and key messages that have helped the practice to anticipate and react to changing operational needs and opportunities. The framework shared here for the deployment of a COVID-19 predictive analytics task force could be adapted for effective implementation at other institutions to provide evidence-based messaging for operational decision-making. For hospitals without such a structure, immediate consideration may be warranted in light of the devastating COVID-19 third-wave which has arrived for winter 2020-2021.


Subject(s)
COVID-19/therapy , Decision Making , Disease Management , Hospitals/statistics & numerical data , Intensive Care Units/statistics & numerical data , Pandemics , SARS-CoV-2 , COVID-19/epidemiology , Forecasting , Humans
7.
Sci Immunol ; 5(53)2020 11 06.
Article in English | MEDLINE | ID: covidwho-999190

ABSTRACT

Lower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome coronavirus 2 infections, often cause severe viral pneumonia in aged individuals. Here, we report that influenza viral pneumonia leads to chronic nonresolving lung pathology and exacerbated accumulation of CD8+ tissue-resident memory T cells (TRM) in the respiratory tract of aged hosts. TRM cell accumulation relies on elevated TGF-ß present in aged tissues. Further, we show that TRM cells isolated from aged lungs lack a subpopulation characterized by expression of molecules involved in TCR signaling and effector function. Consequently, TRM cells from aged lungs were insufficient to provide heterologous protective immunity. The depletion of CD8+ TRM cells dampens persistent chronic lung inflammation and ameliorates tissue fibrosis in aged, but not young, animals. Collectively, our data demonstrate that age-associated TRM cell malfunction supports chronic lung inflammatory and fibrotic sequelae after viral pneumonia.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Immunologic Memory/immunology , Lung/immunology , Pneumonia, Viral/immunology , SARS-CoV-2/immunology , Age Factors , Animals , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/virology , COVID-19/metabolism , COVID-19/virology , Host-Pathogen Interactions/immunology , Humans , Influenza, Human/immunology , Influenza, Human/metabolism , Influenza, Human/virology , Lung/metabolism , Lung/virology , Mice, Inbred C57BL , Orthomyxoviridae/immunology , Orthomyxoviridae/physiology , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/metabolism , Orthomyxoviridae Infections/virology , Pandemics , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , SARS-CoV-2/physiology , Transforming Growth Factor beta/immunology , Transforming Growth Factor beta/metabolism
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