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Article ; Online: Three-Month FVC Change: A Trial Endpoint for Idiopathic Pulmonary Fibrosis Based on Individual Participant Data Meta-analysis.

Khan, Fasihul A / Stewart, Iain / Moss, Samuel / Fabbri, Laura / Robinson, Karen A / Johnson, Simon R / Jenkins, R Gisli

American journal of respiratory and critical care medicine

2022 Volume 205, Issue 8, Page(s) 936–948

Abstract: Rationale: ...

Abstract	Rationale:
MeSH term(s)	Disease Progression ; Humans ; Idiopathic Pulmonary Fibrosis/drug therapy ; Proportional Hazards Models ; Vital Capacity
Language	English
Publishing date	2022-05-12
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202109-2091OC
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Article ; Online: A systematic review of blood biomarkers with individual participant data meta-analysis of matrix metalloproteinase-7 in idiopathic pulmonary fibrosis.

Khan, Fasihul A / Stewart, Iain / Saini, Gauri / Robinson, Karen A / Jenkins, R Gisli

The European respiratory journal

2021 Volume 59, Issue 4

Abstract: Background: Blood-derived biomarkers have been described extensively as potential prognostic markers in idiopathic pulmonary fibrosis (IPF), but studies have been limited by analyses using data-dependent thresholds, inconsistent adjustment for ... ...

Abstract	Background: Blood-derived biomarkers have been described extensively as potential prognostic markers in idiopathic pulmonary fibrosis (IPF), but studies have been limited by analyses using data-dependent thresholds, inconsistent adjustment for confounders and an array of end-points, thus often yielding ungeneralisable results. Meta-analysis of individual participant data (IPD) is a powerful tool to overcome these limitations. Through systematic review of blood-derived biomarkers, sufficient studies with measurements of matrix metalloproteinase (MMP)-7 were identified to facilitate standardised analyses of the prognostic potential of this biomarker in IPF. Methods: Electronic databases were searched on 12 November 2020 to identify prospective studies reporting outcomes in patients with untreated IPF, stratified according to at least one pre-specified biomarker, measured at either baseline, or change over 3 months. IPD were sought for studies investigating MMP-7 as a prognostic factor. The primary outcome was overall mortality according to standardised MMP-7 z-scores, with a secondary outcome of disease progression in 12 months, all adjusted for age, gender, smoking and baseline forced vital capacity. Results: IPD was available for nine studies out of 12 identified, reporting outcomes from 1664 participants. Baseline MMP-7 levels were associated with increased mortality risk (adjusted hazard ratio 1.23, 95% CI 1.03-1.48; I Conclusion: IPD meta-analysis demonstrated that greater baseline MMP-7 levels were independently associated with an increased risk of poor outcomes in patients with untreated IPF, while short-term changes did not reflect disease progression.
MeSH term(s)	Biomarkers ; Disease Progression ; Humans ; Idiopathic Pulmonary Fibrosis ; Matrix Metalloproteinase 7/analysis ; Prospective Studies
Chemical Substances	Biomarkers ; MMP7 protein, human (EC 3.4.24.23) ; Matrix Metalloproteinase 7 (EC 3.4.24.23)
Language	English
Publishing date	2021-09-29
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.01612-2021
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Article ; Online: Parenchymal lung abnormalities following hospitalisation for COVID-19 and viral pneumonitis: a systematic review and meta-analysis.

Fabbri, Laura / Moss, Samuel / Khan, Fasihul A / Chi, Wenjie / Xia, Jun / Robinson, Karen / Smyth, Alan Robert / Jenkins, Gisli / Stewart, Iain

Thorax

2022 Volume 78, Issue 2, Page(s) 191–201

Abstract: Introduction: Persisting respiratory symptoms in COVID-19 survivors may be related to development of pulmonary fibrosis. We assessed the proportion of chest CT scans and pulmonary function tests consistent with parenchymal lung disease in the follow-up ... ...

Abstract	Introduction: Persisting respiratory symptoms in COVID-19 survivors may be related to development of pulmonary fibrosis. We assessed the proportion of chest CT scans and pulmonary function tests consistent with parenchymal lung disease in the follow-up of people hospitalised with COVID-19 and viral pneumonitis. Methods: Systematic review and random effects meta-analysis of proportions using studies of adults hospitalised with SARS-CoV-2, SARS-CoV, MERS-CoV or influenza pneumonia and followed up within 12 months. Searches performed in MEDLINE and Embase. Primary outcomes were proportion of radiological sequelae on CT scans; restrictive impairment; impaired gas transfer. Heterogeneity was explored in meta-regression. Results: Ninety-five studies (98.9% observational) were included in qualitative synthesis, 70 were suitable for meta-analysis including 60 SARS-CoV-2 studies with a median follow-up of 3 months. In SARS-CoV-2, the overall estimated proportion of inflammatory sequelae was 50% during follow-up (0.50; 95% CI 0.41 to 0.58; I Discussion: Sequelae consistent with parenchymal lung disease were observed following COVID-19 and other viral pneumonitis. Estimates should be interpreted with caution due to high heterogeneity, differences in study casemix and initial severity. Prospero registration number: CRD42020183139.
MeSH term(s)	Adult ; Humans ; COVID-19/complications ; SARS-CoV-2 ; Pneumonia, Viral/complications ; Pneumonia, Viral/therapy ; Pneumonia, Viral/diagnosis ; Hospitalization ; Pulmonary Fibrosis/diagnostic imaging ; Pulmonary Fibrosis/etiology ; Lung/diagnostic imaging
Language	English
Publishing date	2022-03-25
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	204353-1
ISSN	1468-3296 ; 0040-6376
ISSN (online)	1468-3296
ISSN	0040-6376
DOI	10.1136/thoraxjnl-2021-218275
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Article ; Online: Systematic review and meta-analysis of anakinra, sarilumab, siltuximab and tocilizumab for COVID-19.

Khan, Fasihul A / Stewart, Iain / Fabbri, Laura / Moss, Samuel / Robinson, Karen / Smyth, Alan Robert / Jenkins, Gisli

Thorax

2021 Volume 76, Issue 9, Page(s) 907–919

Abstract: Background: There is accumulating evidence for an overly activated immune response in severe COVID-19, with several studies exploring the therapeutic role of immunomodulation. Through systematic review and meta-analysis, we assess the effectiveness of ... ...

Abstract	Background: There is accumulating evidence for an overly activated immune response in severe COVID-19, with several studies exploring the therapeutic role of immunomodulation. Through systematic review and meta-analysis, we assess the effectiveness of specific interleukin inhibitors for the treatment of COVID-19. Methods: Electronic databases were searched on 7 January 2021 to identify studies of immunomodulatory agents (anakinra, sarilumab, siltuximab and tocilizumab) for the treatment of COVID-19. The primary outcomes were severity on an Ordinal Scale measured at day 15 from intervention and days to hospital discharge. Key secondary endpoints included overall mortality. Results: 71 studies totalling 22 058 patients were included, 6 were randomised trials. Most studies explored outcomes in patients who received tocilizumab (60/71). In prospective studies, tocilizumab was associated with improved unadjusted survival (risk ratio 0.83, 95% CI 0.72 to 0.96, I Conclusion: Tocilizumab was associated with a lower relative risk of mortality in prospective studies, but effects were inconclusive for other outcomes. Current evidence for the efficacy of anakinra, siltuximab or sarilumab in COVID-19 is insufficient, with further studies urgently needed for conclusive findings. Prospero registration number: CRD42020176375.
MeSH term(s)	Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Agents/therapeutic use ; Antirheumatic Agents/therapeutic use ; COVID-19/mortality ; Humans ; Interleukin 1 Receptor Antagonist Protein/therapeutic use ; SARS-CoV-2 ; Survival Rate ; COVID-19 Drug Treatment
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; Antirheumatic Agents ; Interleukin 1 Receptor Antagonist Protein ; tocilizumab (I031V2H011) ; sarilumab (NU90V55F8I) ; siltuximab (T4H8FMA7IM)
Language	English
Publishing date	2021-02-12
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	204353-1
ISSN	1468-3296 ; 0040-6376
ISSN (online)	1468-3296
ISSN	0040-6376
DOI	10.1136/thoraxjnl-2020-215266
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Article ; Online: Post-viral parenchymal lung disease of COVID-19 and viral pneumonitis: A systematic review and meta-analysis.

Fabbri, Laura / Moss, Samuel / Khan, Fasihul / Chi, Wenjie / Xia, Jun / Robinson, Karen / Smyth, Alan / Jenkins, Gisli / Stewart, Iain

medRxiv

Abstract: Background: Approximately half of patients discharged following COVID-19 related hospitalisation are reported to suffer from persisting respiratory symptoms. We assess the prevalence of long term radiological and functional pulmonary sequelae in ... ...

Abstract	Background: Approximately half of patients discharged following COVID-19 related hospitalisation are reported to suffer from persisting respiratory symptoms. We assess the prevalence of long term radiological and functional pulmonary sequelae in survivors from COVID-19 and other viral pneumonia in published literature. Methods: We performed systematic review and meta-analysis of all original studies in adults admitted to hospital with SARS-CoV-2, SARS-CoV, MERS-CoV, or Influenza pneumonia and followed within 12 months from discharge. Searches were run on MEDLINE and Embase, with the last update on 1st March 2021. Primary outcomes were presence of 1) radiologic sequelae at CT scans; 2) restrictive impairment; 3) reduced diffusing capacity for carbon monoxide (DLCO). This review is registered on PROSPERO, CRD42020183139. Results: Sixty studies were included for qualitative synthesis, of which 41 were suitable for meta-analysis. On follow up CT scans, the overall estimated proportion was 0.56 (95%CI 0.44 to 0.66, I2= 94.44%) for inflammatory changes, and 0.40 (95%CI 0.29 to 0.52, I2=95.19%) for fibrotic findings. In SARS-CoV-2 specifically, proportions were estimated at 0.43 (95%CI 0.32 to 0.56, I2=94.60%) and 0.30 (95%CI 0.19 to 0.43, I2=94.89%) for inflammatory and fibrotic findings, respectively. Overall proportion for restrictive impairment was 0.19 (95%CI 0.12 to 0.27, I2=94.46%), DLCO reduction was estimated at 0.45 (95%CI 0.38 to 0.52, I2=90.10). Elevated radiological and functional estimates persisted across follow-up times. Confidence in the estimates was deemed very low as studies were largely observational without control groups, heterogeneity in estimates was high but was not clearly attributable to between-study differences of severity or design. Conclusion: Although estimates of prevalence are likely limited by differences in case mix and initial severity, a substantial proportion of radiological and functional sequelae are observed following viral pneumonitis, including COVID-19. This highlights the importance of vigilant radiological and functional follow up.
Keywords	covid19
Language	English
Publishing date	2021-03-17
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.03.15.21253593
Database	COVID19

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Article: Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK.

Dixon, Giles / Hague, Samuel / Mulholland, Sarah / Adamali, Huzaifa / Khin, Aye Myat Noe / Thould, Hannah / Connon, Roisin / Minnis, Paul / Murtagh, Eoin / Khan, Fasihul / Toor, Sameen / Lawrence, Alexandra / Naqvi, Marium / West, Alex / Coker, Robina K / Ward, Katie / Yazbeck, Leda / Hart, Simon / Garfoot, Theresa /

Newman, Kate / Rivera-Ortega, Pilar / Stranks, Lachlan / Beirne, Paul / Bradley, Jessica / Rowan, Catherine / Agnew, Sarah / Ahmad, Mahin / Spencer, Lisa G / Aigbirior, Joshua / Fahim, Ahmed / Wilson, Andrew M / Butcher, Elizabeth / Chong, Sy Giin / Saini, Gauri / Zulfikar, Sabrina / Chua, Felix / George, Peter M / Kokosi, Maria / Kouranos, Vasileios / Molyneaux, Philip / Renzoni, Elisabetta / Vitri, Benedetta / Wells, Athol U / Nicol, Lisa M / Bianchi, Stephen / Kular, Raman / Liu, HuaJian / John, Alexander / Barth, Sarah / Wickremasinghe, Melissa / Forrest, Ian A / Grimes, Ian / Simpson, A John / Fletcher, Sophie V / Jones, Mark G / Kinsella, Emma / Naftel, Jennifer / Wood, Nicola / Chalmers, Jodie / Crawshaw, Anjali / Crowley, Louise E / Dosanjh, Davinder / Huntley, Christopher C / Walters, Gareth I / Gatheral, Timothy / Plum, Catherine / Bikmalla, Shiva / Muthusami, Raja / Stone, Helen / Rodrigues, Jonathan C L / Tsaneva-Atanasova, Krasimira / Scotton, Chris J / Gibbons, Michael A / Barratt, Shaney L

ERJ open research

2024 Volume 10, Issue 1

Abstract: Background: Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in ... ...

Abstract	Background: Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting. Methods: 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected Results: 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD. Conclusion: We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting.
Language	English
Publishing date	2024-01-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2827830-6
ISSN	2312-0541
ISSN	2312-0541
DOI	10.1183/23120541.00529-2023
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Article: Innovative solutions to medical workforce challenges.

Khan, Fasihul

Future healthcare journal

2019 Volume 6, Issue Suppl 1, Page(s) 48

Language	English
Publishing date	2019-07-30
Publishing country	England
Document type	Journal Article
ZDB-ID	3016427-8
ISSN	2514-6653 ; 2514-6645
ISSN (online)	2514-6653
ISSN	2514-6645
DOI	10.7861/futurehosp.6-1-s48
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Article: Educating and engaging junior doctors.

Khan, Fasihul

Future healthcare journal

2019 Volume 6, Issue Suppl 1, Page(s) 189

Language	English
Publishing date	2019-07-30
Publishing country	England
Document type	Journal Article
ZDB-ID	3016427-8
ISSN	2514-6653 ; 2514-6645
ISSN (online)	2514-6653
ISSN	2514-6645
DOI	10.7861/futurehosp.6-1-s189
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Article ; Online: Understanding the burden of interstitial lung disease post-COVID-19: the UK Interstitial Lung Disease-Long COVID Study (UKILD-Long COVID).

Wild, Jim M / Porter, Joanna C / Molyneaux, Philip L / George, Peter M / Stewart, Iain / Allen, Richard James / Aul, Raminder / Baillie, John Kenneth / Barratt, Shaney L / Beirne, Paul / Bianchi, Stephen M / Blaikley, John F / Brooke, Jonathan / Chaudhuri, Nazia / Collier, Guilhem / Denneny, Emma K / Docherty, Annemarie / Fabbri, Laura / Gibbons, Michael A /

Gleeson, Fergus V / Gooptu, Bibek / Hall, Ian P / Hanley, Neil A / Heightman, Melissa / Hillman, Toby E / Johnson, Simon R / Jones, Mark G / Khan, Fasihul / Lawson, Rod / Mehta, Puja / Mitchell, Jane A / Platé, Manuela / Poinasamy, Krisnah / Quint, Jennifer K / Rivera-Ortega, Pilar / Semple, Malcolm / Simpson, A John / Smith, Djf / Spears, Mark / Spencer, LIsa G / Stanel, Stefan C / Thickett, David R / Thompson, A A Roger / Walsh, Simon Lf / Weatherley, Nicholas D / Weeks, Mark Everard / Wootton, Dan G / Brightling, Chris E / Chambers, Rachel C / Ho, Ling-Pei / Jacob, Joseph / Piper Hanley, Karen / Wain, Louise V / Jenkins, R Gisli

BMJ open respiratory research

2022 Volume 8, Issue 1

Abstract: Introduction: The COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and ...

Abstract	Introduction: The COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and fatigue whether hospitalised or not. Early data suggest potentially severe long-term consequence of COVID-19 is development of long COVID-19-related interstitial lung disease (LC-ILD). Methods and analysis: The UK Interstitial Lung Disease Consortium (UKILD) will undertake longitudinal observational studies of patients with suspected ILD following COVID-19. The primary objective is to determine ILD prevalence at 12 months following infection and whether clinically severe infection correlates with severity of ILD. Secondary objectives will determine the clinical, genetic, epigenetic and biochemical factors that determine the trajectory of recovery or progression of ILD. Data will be obtained through linkage to the Post-Hospitalisation COVID platform study and community studies. Additional substudies will conduct deep phenotyping. The Xenon MRI investigation of Alveolar dysfunction Substudy will conduct longitudinal xenon alveolar gas transfer and proton perfusion MRI. The POST COVID-19 interstitial lung DiseasE substudy will conduct clinically indicated bronchoalveolar lavage with matched whole blood sampling. Assessments include exploratory single cell RNA and lung microbiomics analysis, gene expression and epigenetic assessment. Ethics and dissemination: All contributing studies have been granted appropriate ethical approvals. Results from this study will be disseminated through peer-reviewed journals. Conclusion: This study will ensure the extent and consequences of LC-ILD are established and enable strategies to mitigate progression of LC-ILD.
MeSH term(s)	COVID-19/complications ; Humans ; Longitudinal Studies ; Lung Diseases, Interstitial/epidemiology ; Observational Studies as Topic ; Pandemics ; Prospective Studies ; United Kingdom/epidemiology ; Post-Acute COVID-19 Syndrome
Language	English
Publishing date	2022-03-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2736454-9
ISSN	2052-4439 ; 2052-4439
ISSN (online)	2052-4439
ISSN	2052-4439
DOI	10.1136/bmjresp-2021-001049
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Article ; Online: Residual Lung Abnormalities after COVID-19 Hospitalization: Interim Analysis of the UKILD Post-COVID-19 Study.

Stewart, Iain / Jacob, Joseph / George, Peter M / Molyneaux, Philip L / Porter, Joanna C / Allen, Richard J / Aslani, Shahab / Baillie, J Kenneth / Barratt, Shaney L / Beirne, Paul / Bianchi, Stephen M / Blaikley, John F / Chalmers, James D / Chambers, Rachel C / Chadhuri, Nazia / Coleman, Christopher / Collier, Guilhem / Denneny, Emma K / Docherty, Annemarie /

Elneima, Omer / Evans, Rachael A / Fabbri, Laura / Gibbons, Michael A / Gleeson, Fergus V / Gooptu, Bibek / Greening, Neil J / Guio, Beatriz Guillen / Hall, Ian P / Hanley, Neil A / Harris, Victoria / Harrison, Ewen M / Heightman, Melissa / Hillman, Toby E / Horsley, Alex / Houchen-Wolloff, Linzy / Jarrold, Ian / Johnson, Simon R / Jones, Mark G / Khan, Fasihul / Lawson, Rod / Leavy, Olivia / Lone, Nazir / Marks, Michael / McAuley, Hamish / Mehta, Puja / Parekh, Dhruv / Hanley, Karen Piper / Platé, Manuela / Pearl, John / Poinasamy, Krisnah / Quint, Jennifer K / Raman, Betty / Richardson, Matthew / Rivera-Ortega, Pilar / Saunders, Laura / Saunders, Ruth / Semple, Malcolm G / Sereno, Marco / Shikotra, Aarti / Simpson, A John / Singapuri, Amisha / Smith, David J F / Spears, Mark / Spencer, Lisa G / Stanel, Stefan / Thickett, David R / Thompson, A A Roger / Thorpe, Mathew / Walsh, Simon L F / Walker, Samantha / Weatherley, Nicholas David / Weeks, Mark E / Wild, Jim M / Wootton, Dan G / Brightling, Chris E / Ho, Ling-Pei / Wain, Louise V / Jenkins, Gisli R

American journal of respiratory and critical care medicine

2022 Volume 207, Issue 6, Page(s) 693–703

Abstract: Rationale: ...

Abstract	Rationale:
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19/epidemiology ; Bayes Theorem ; Lung/diagnostic imaging ; Hospitalization ; Lung Diseases, Interstitial
Language	English
Publishing date	2022-12-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202203-0564OC
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