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2.
EBioMedicine ; 83: 104208, 2022 Aug 08.
Article in English | MEDLINE | ID: covidwho-2035962

ABSTRACT

BACKGROUND: Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. METHODS: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed. FINDINGS: The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC. INTERPRETATION: Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. FUNDING: NIH.

4.
Transport Problems ; 17(2):189-197, 2022.
Article in English | Scopus | ID: covidwho-2026060

ABSTRACT

The COVID-19 pandemic has caused the reduction of services, including transport services. Companies operating in public water passenger transport were not prepared for the implementation of restrictions because, in some countries, the general procedures for the safe operation of regular public water passenger transport were not known. The main contribution of this paper is to discuss the implementation of the current system of safe operation of regular public water transport services in the Netherlands and Spain to a generally applicable model for transport companies. This article links these measures with the general plan for the release and tightening of measures of the Ministry of Health of the Slovak Republic known as COVID-AUTOMAT. © 2022 Silesian University of Technology. All rights reserved.

5.
Pharmacy (Basel) ; 10(4)2022 Jul 27.
Article in English | MEDLINE | ID: covidwho-2024000

ABSTRACT

Providing patient-centered care to manage chronic pain and opioid use disorder (OUD) is associated with improved health outcomes. However, adopting a holistic approach to providing care is often challenging in rural communities. This study aims to identify and contrast challenges to providing patient-centered care from the perspective of patients and providers. A participatory design approach was adopted to elicit the perceptions of providers and patients with lived experiences of chronic pain and/or OUD in Jefferson County, Wisconsin. Two focus groups were conducted with each stakeholder group to identify problems that participants face with respect to chronic pain management and OUD and possible solutions. Four interviews were conducted with providers experienced in chronic pain management. Analysis of focus group sessions and interviews show consensus among patients and providers that lack of behavioral health and recovery resources create barriers to effectively manage OUD and chronic pain. However, there was discordance among the two groups about other barriers such as patient and provider attitudes, tapering approach, and access to medications for OUD. This tension among patients and providers can influence patients' retention in therapy. More efforts are needed to mitigate stigma among providers in rural communities and support psychosocial needs of patients.

6.
JMIR Med Inform ; 2022 Jul 26.
Article in English | MEDLINE | ID: covidwho-2022413

ABSTRACT

BACKGROUND: The adverse impact of COVID-19 on marginalized and under-resourced communities of color has highlighted the need for accurate, comprehensive race and ethnicity data. However, a significant technical challenge related to integrating race and ethnicity data in large, consolidated databases is the lack of consistency in how data about race and ethnicity is collected and structured by healthcare organizations. OBJECTIVE: To evaluate and describe variations in how healthcare systems collect and report information about the race and ethnicity of their patients, and to assess how well these data are integrated when aggregated into a large clinical database. METHODS: At the time of our analysis, the National COVID Cohort Collaborative (N3C) Data Enclave contained records from 6.5 million patients contributed by 56 healthcare institutions. We quantified the variability in the harmonized race and ethnicity data in the N3C Enclave by analyzing its conformance to healthcare standards for such data. We conducted a descriptive analysis by comparing the harmonized data available for research purposes in the database to the original source data contributed by healthcare institutions. To make the comparison, we tabulated the original source codes, enumerating how many patients had been reported with each encoded value and how many distinct ways each category was reported. The non-conforming data was also cross-tabulated by three factors: patient ethnicity, the number of data partners using each code, and which data models utilized those particular encodings. For the non-conforming data, we used an inductive approach to sort the source encodings into categories. For example, values such as "Declined" were grouped with "Refused"; "Multiple Race" was grouped with "Two or more races" and "Multiracial", etc. RESULTS: "No matching concept" was the second largest harmonized concept used by the N3C to describe the race of patients in their database. 20.7% of the race data did not conform to the standard; the largest category was data that were missing. Hispanic or Latino patients were over-represented in the non-conforming racial data, and data from American Indian or Alaska Native patients were obscured. Although only a small proportion of the source data had not been mapped to the correct concepts (0.6%), Black or African-American and Hispanic/Latino patients were over-represented in this category. CONCLUSIONS: Differences in how race and ethnicity data is conceptualized and encoded by healthcare institutions can affect the quality of the data in aggregated clinical databases. The impact of data quality issues in the N3C Data Enclave was not equal across all races and ethnicities, which has the potential to introduce bias in analyses and conclusions drawn from these data. Transparency about how data has been transformed can help users make accurate analyses and inferences, and eventually better guide clinical care and public policy.

7.
PLoS One ; 17(6): e0267392, 2022.
Article in English | MEDLINE | ID: covidwho-2021694

ABSTRACT

INTRODUCTION: There have been more than 425 million COVID-19 infections worldwide. Post-COVID illness has become a common, disabling complication of this infection. Therefore, it presents a significant challenge to global public health and economic activity. METHODS: Comprehensive clinical assessment (symptoms, WHO performance status, cognitive testing, CPET, lung function, high-resolution CT chest, CT pulmonary angiogram and cardiac MRI) of previously well, working-age adults in full-time employment was conducted to identify physical and neurocognitive deficits in those with severe or prolonged COVID-19 illness. RESULTS: 205 consecutive patients, age 39 (IQR30.0-46.7) years, 84% male, were assessed 24 (IQR17.1-34.0) weeks after acute illness. 69% reported ≥3 ongoing symptoms. Shortness of breath (61%), fatigue (54%) and cognitive problems (47%) were the most frequent symptoms, 17% met criteria for anxiety and 24% depression. 67% remained below pre-COVID performance status at 24 weeks. One third of lung function tests were abnormal, (reduced lung volume and transfer factor, and obstructive spirometry). HRCT lung was clinically indicated in <50% of patients, with COVID-associated pathology found in 25% of these. In all but three HRCTs, changes were graded 'mild'. There was an extremely low incidence of pulmonary thromboembolic disease or significant cardiac pathology. A specific, focal cognitive deficit was identified in those with ongoing symptoms of fatigue, poor concentration, poor memory, low mood, and anxiety. This was notably more common in patients managed in the community during their acute illness. CONCLUSION: Despite low rates of residual cardiopulmonary pathology, in this cohort, with low rates of premorbid illness, there is a high burden of symptoms and failure to regain pre-COVID performance 6-months after acute illness. Cognitive assessment identified a specific deficit of the same magnitude as intoxication at the UK drink driving limit or the deterioration expected with 10 years ageing, which appears to contribute significantly to the symptomatology of long-COVID.


Subject(s)
COVID-19 , Acute Disease , Adult , COVID-19/complications , Fatigue/etiology , Female , Humans , Lung , Male
8.
Biomedicines ; 10(8):1959, 2022.
Article in English | ProQuest Central | ID: covidwho-2023147

ABSTRACT

Cannabinoid receptor 2 (CB2) is of interest as a much-needed target for the treatment or prevention of several neurogenerative diseases. However, CB2 agonists, particularly phytocannabinoids, have been ascribed antimicrobial properties and are associated with the induction of microbiome compositional fluxes. When developing novel CB2 therapeutics, CB2 engagement and antimicrobial functions should both be considered. This review summarizes those cannabinoids and cannabis-informed molecules and preparations (CIMPs) that show promise as microbicidal agents, with a particular focus on the most recent developments. CIMP–microbe interactions and anti-microbial mechanisms are discussed, while the major knowledge gaps and barriers to translation are presented. Further research into CIMPs may proffer novel direct or adjunctive strategies to augment the currently available antimicrobial armory. The clinical promise of CIMPs as antimicrobials, however, remains unrealized. Nevertheless, the microbicidal effects ascribed to several CB2 receptor-agonists should be considered when designing therapeutic approaches for neurocognitive and other disorders, particularly in cases where such regimens are to be long-term. To this end, the potential development of CB2 agonists lacking antimicrobial properties is also discussed.

9.
Preprint in English | bioRxiv | ID: ppbiorxiv-508614

ABSTRACT

SARS-CoV-2 primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe COVID-19. To elucidate molecular mechanisms in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type II (AT2) epithelial cell and cardiac cultures infected with SARS-CoV-2. With CRISPR- Cas9 mediated knock-out of ACE2, we demonstrated that angiotensin converting enzyme 2 (ACE2) was essential for SARS-CoV-2 infection of both cell types but further processing in lung cells required TMPRSS2 while cardiac cells required the endosomal pathway. Host responses were significantly different; transcriptome profiling and phosphoproteomics responses depended strongly on the cell type. We identified several antiviral compounds with distinct antiviral and toxicity profiles in lung AT2 and cardiac cells, highlighting the importance of using several relevant cell types for evaluation of antiviral drugs. Our data provide new insights into rational drug combinations for effective treatment of a virus that affects multiple organ systems. One-sentence summaryRational treatment strategies for SARS-CoV-2 derived from human PSC models

10.
Journal of Sleep Research ; : 1, 2022.
Article in English | Academic Search Complete | ID: covidwho-2019522

ABSTRACT

Summary The COVID‐19 pandemic is a rare stressor that has precipitated an accompanying mental health crisis. Prospective studies traversing the pandemic's onset can elucidate how pre‐existing disease vulnerabilities augured risk for later stress‐related morbidity. We examined how pre‐pandemic sleep reactivity predicted maladaptive stress reactions and depressive symptoms in response to, and during, the pandemic. This study is a secondary analysis of a randomised controlled trial from 2016 to 2017 comparing digital cognitive behavioural therapy for insomnia (dCBT‐I) against sleep education (N = 208). Thus, we also assessed whether dCBT‐I moderated the association between pre‐pandemic sleep reactivity and pandemic‐related distress. Pre‐pandemic sleep reactivity was measured at baseline using the Ford Insomnia Response to Stress Test. In April 2020, participants were recontacted to report pandemic‐related distress (stress reactions and depression). Controlling for the treatment condition and the degree of COVID‐19 impact, higher pre‐pandemic sleep reactivity predicted more stress reactions (β = 0.13, ± 0.07 SE, p = 0.045) and depression (β = 0.22, ± 0.07 SE, p = 0.001) during the pandemic. Further, the odds of reporting clinically significant stress reactions and depression during the pandemic were over twice as high in those with high pre‐pandemic sleep reactivity. Notably, receiving dCBT‐I in 2016–2017 mitigated the relationship between pre‐pandemic sleep reactivity and later stress reactions (but not depression). Pre‐pandemic sleep reactivity predicted psychological distress 3–4 years later during the COVID‐19 pandemic, and dCBT‐I attenuated its association with stress reactions, specifically. Sleep reactivity may inform prevention and treatment efforts by identifying individuals at risk of impairment following stressful events. [ FROM AUTHOR] Copyright of Journal of Sleep Research is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

11.
ACR Open Rheumatol ; 2022 Jun 24.
Article in English | MEDLINE | ID: covidwho-2013314

ABSTRACT

Clinical trials of novel therapeutics in the United States have not been adequately representative of diverse populations, particularly racial and ethnic minorities. The challenges and consequences of underrepresentation in clinical trial recruitment are exemplified by the case of belimumab, a biologic treatment for systemic lupus erythematosus (SLE), a disease that is more prevalent in patients of Black African ancestry and of Hispanic/Latino ethnicity than in other patient populations. Although belimumab was found to be effective in phase 2 and 3 clinical trials in the general population, post hoc analyses of efficacy data in patients of Black African ancestry showed inconsistent results. Consequently, a cautionary statement regarding belimumab use in this population was added to the product label. To alleviate concerns that belimumab may not be safe and effective for patients of Black African ancestry, the Efficacy and Safety of Belimumab in Black Race Patients with SLE (EMBRACE) study was conducted in a post-marketing commitment to the Food and Drug Administration. The study recruited only patients who self-identified as being of Black race; its findings led to the removal of the cautionary labeling of belimumab use in patients of Black African ancestry. Our manuscript highlights the critical lessons learned from the successes and failures of the EMBRACE study. It also provides suggestions for overcoming health disparities, highlighting strategies for conducting well-designed clinical trials to overcome systematic barriers to diversity in recruitment, with a focus on enacting long-term support to ensure equity in the process, products, and benefits from drug development and clinical trials.

12.
Clin Infect Dis ; 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-2017765

ABSTRACT

BACKGROUND: Remdesivir (RDV) improved clinical outcomes among hospitalized COVID-19 patients in randomized trials, but data from clinical practice are limited. METHODS: We examined survival outcomes for US patients hospitalized with COVID-19 between Aug-Nov 2020 and treated with RDV within two-days of hospitalization vs. those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges (NSO), low-flow oxygen (LFO), high-flow oxygen/non-invasive ventilation (HFO/NIV) and invasive mechanical ventilation/ECMO (IMV/ECMO) and two-month admission window and excluded if discharged within 3-days of admission (to exclude anticipated discharges/transfers within 72-hrs consistent with ACTT-1 study). Cox Proportional Hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV and IMV/ECMO. RESULTS: 28,855 RDV patients were matched to 16,687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14- and 28-days, respectively compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14-days (HR[95% CI]: 0.76[0.70-0.83]) and 28-days (0.89[0.82-0.96]). This mortality benefit was also seen for NSO, LFO and IMV/ECMO at 14-days (NSO:0.69[0.57-0.83], LFO:0.68[0.80-0.77], IMV/ECMO:0.70[0.58-0.84]) and 28-days (NSO:0.80[0.68-0.94], LFO:0.77[0.68-0.86], IMV/ECMO:0.81[0.69-0.94]). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14-days (0.81[0.70-0.93]) but no statistical significance at 28-days. CONCLUSIONS: RDV initiated upon hospital admission was associated with improved survival among COVID-19 patients. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.

13.
Clin Infect Dis ; 2021 Sep 21.
Article in English | MEDLINE | ID: covidwho-2017763

ABSTRACT

BACKGROUND: The public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

14.
Journal of Wildlife Management ; 86(7):1-21, 2022.
Article in English | Academic Search Complete | ID: covidwho-2013666

ABSTRACT

Negative interactions between waterbirds and people are increasing. Waterbirds feeding on agricultural crops cause significant losses to farmers worldwide, but so far most research to address these conflicts has been conducted on migratory species in the temperate northern hemisphere. We investigated the space use and habitat selection of the magpie goose (Anseranas semipalmata), a taxonomically distinct waterbird endemic to Australia and southern Papua New Guinea. In tropical northern Australia, magpie geese are protected but are increasingly persecuted by farmers to protect crops during the late dry–early wet season (~Sep–Jan), a bottleneck of natural resources for waterbirds in the monsoonal tropics. Using satellite telemetry of 38 geese spread across 3 seasons (2016–2017, 2017–2018, 2018–2019), we evaluated daily and seasonal space use, individual site fidelity, and habitat selection to determine the extent of use of agricultural fields by geese, and the spatiotemporal scales at which management should be undertaken. Geese used relatively small daily areas (x̄ = 8.2 km2) consistently throughout the late dry–early wet season, and repeatedly used agricultural fields, forested bushlands, and local wetlands. Geese used comparatively large seasonal areas (x̄ = 219.5 km2) encompassing several agricultural areas, and had a low mean overlap between successive weekly core activity areas, indicating that site fidelity rapidly weakened over time. These results suggest that farm‐scale (<30 ha) management of geese is unlikely to be effective because hazed individuals are likely to be replaced soon afterwards. Instead, our findings suggest that goose management should be coordinated strategically at the local (~1,000 ha), or regional (~100,000 ha) scale. Farm‐level management would likely be more effective if implemented in conjunction with the creation of regional sanctuaries where geese could rest and potentially feed undisturbed away from farms. Our findings can be used by wildlife managers for optimizing the location of such sanctuaries and highlight the necessity for management to be adaptive given the opportunistic nature of the species. [ FROM AUTHOR] Copyright of Journal of Wildlife Management is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

15.
European journal of public health ; 32(Suppl 2), 2022.
Article in English | EuropePMC | ID: covidwho-2012869

ABSTRACT

Background Regular physical activity is known to reduce premature mortality, and help prevent and manage chronic diseases. Despite this, older people are not sufficiently active. Playing golf is associated with better aerobic fitness and mental wellbeing but evidence of a relationship with strength and balance is lacking. If the physical demands of golf are sufficient to meet the World Health Organisation recommendations for strength and balance, golf may qualify for exercise on prescription/social prescribing for people with long-term conditions. The hypothesis of this ongoing study is that playing recreational golf will be associated with better strength and balance in older people. Data are presented for grip strength and dynamic balance in golfers and sedentary older adults, tested using simple techniques suitable in community settings. Methods Seventy nine healthy older participants (aged 65-79 years) have been studied: 62 golfers (n = 31 females, 31 males) and 17 sedentary non golfers (9 males, 8 females). Difficulties in recruiting sedentary participants and then the outbreak of Covid-19 explain the discrepancy between group sizes. Golfers played 18 holes at least once a week for minimum of two years. Grip strength was tested for the right hand using the MIE hand-grip dynamometer, with results normalized to body weight. Dynamic balance was assessed using the Y-balance test, with reaching distance normalized to lower-limb length. Non-parametric statistics were used due to unequal group sizes. Results Grip strength was significantly greater in golfers than non-golfers (median and interquartile range);males and females combined;golfers 4.3±1.2;non-golfers 3.3±1.9 (p=0.039*;Mann-Whitney). The Y-balance performance was also significantly better in golfers than non-golfers (p=0.002*: Mann-Whitney). Normalised composite reach distance data (3 directions) for the right side were greater in golfers (81.7±13.3) than non-golfers (74.2±17.2). Conclusions These preliminary data indicate that playing recreational golf at least once a week is associated with greater grip strength and better dynamic balance in older golfers compared to sedentary non-golfers. These findings support further data collection (when permitted) to produce reference data. This will allow parametric statistical analysis to determine whether conclusive evidence will support the hypothesis, forming the basis of a randomised controlled trial.

17.
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.

18.
JTCVS Open ; 2022.
Article in English | ScienceDirect | ID: covidwho-2008183

ABSTRACT

Objective The COVID -19 pandemic presents a high mortality rate amongst patients who develop severe acute respiratory distress syndrome (ARDS). The purpose of this study was to evaluate the outcomes of venovenous ECMO in COVID-19-related ARDS and identify the patients that benefit the most from this procedure. Methods Adult COVID-19 patients with severe ARDS requiring VV-ECMO support at four academic insititutions between March and October 2020 were included. Data were collected through retrospective chart reviews. Bivariate and multivariable analysis were performed with the primary outcome of in-hospital mortality. Results Fifty-one consecutive patients underwent VV-ECMO with a mean age of 50.4 years;64.7% were male. Survival to hospital discharge was 62.8%. Median ICU and hospitalization duration were 27.4 (IQR:17-37) and 34.5 days (IQR:23-43), respectively. Survivors and non-survivors had a median ECMO cannulation time of 11 days (IQR 8-18) and 17 days (IQR: 12-25). The average post decannulation length of stay was 17.5 days (IQR: 12.4-25) for survivors and 0 days for non-survivors (IQR 0-6 days). Only one non-survivor was able to be decannulated. Clinical characteristics associated with mortality between non-surviors and survivors included increasing age (p=0.0048), hemorrhagic stroke (p=0.0014), and post operative dialysis (p=0.0013)were associated with mortality in a bivariate model and retained statistical significance in a multivariable model. Conclusion This multicenter study confirms the effectiveness of VV-ECMO in selected critically ill patients with COVID-19-related severe ARDS. The survival of these patients is comparable to non-COVID-19-related ARDS.

19.
Cell Reports Medicine ; : 100750, 2022.
Article in English | ScienceDirect | ID: covidwho-2008181

ABSTRACT

Summary As COVID-19 cases exceed hundreds of millions globally, many survivors face cognitive challenges and prolonged symptoms. However, important questions about the cognitive impacts of COVID-19 remain unresolved. In this cross-sectional online study, 478 adult volunteers who self-reported a positive test for COVID-19 (M=30 days since most recent test) perform significantly worse than pre-pandemic norms on cognitive measures of processing speed, reasoning, verbal, and overall performance, but not short-term memory – suggesting domain-specific deficits. Cognitive differences are even observed in participants that did not require hospitalisation. Factor analysis of health- and COVID-related questionnaires reveals two clusters of symptoms: one that varies mostly with physical symptoms and illness severity, and one with mental health. Cognitive performance is positively correlated with the global measure encompassing physical symptoms, but not the one that broadly described mental health, suggesting that the subjective experience of “long COVID” relates to physical symptoms and cognitive deficits, especially executive dysfunction.

20.
International Journal of Environmental Research and Public Health ; 19(17):10635, 2022.
Article in English | MDPI | ID: covidwho-2006007

ABSTRACT

Exercise during pregnancy presents many benefits for the mother and baby. Yet, pregnancy is characterised by a decrease in exercise. Studies have reported barriers to antenatal exercise. The coronavirus (COVID-19) pandemic may have further exacerbated barriers to antenatal exercise as pregnant females faced many challenges. Rich, in-depth exploration into pregnant female's perceived barriers to antenatal exercise during COVID-19 is imperative. Questionnaires reporting physical activity levels were completed by all participants (n = 14). Semi-structured interviews were conducted between November 2020 and May 2021 in the UK. Interviews were analysed using thematic analysis and revealed four main themes: 'Perceptions of being an active person shaping activity levels in pregnancy', 'How do I know what is right? Uncertainty, seeking validation and feeling informed', 'Motivators to antenatal exercise' and 'A process of adaptations and adjustment'. Findings indicate that the COVID-19 pandemic exacerbated barriers to antenatal exercise and highlight the importance of direct psychosocial support and clear, trustworthy information. Findings also support the fundamental need for better education amongst healthcare professionals regarding antenatal exercise.

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