Age differences in the association of comorbid burden with adverse outcomes in SARS-CoV-2

Abstract Background Older age and comorbid burden are both associated with adverse outcomes in SARS-CoV-2, but it is not known whether the association between comorbid burden and adverse outcomes differs in older and younger adults. Objective To compare the relationship between comorbid burden and adverse outcomes in adults with SARS-CoV-2 of different ages (18–64, 65–79 and ≥ 80 years). Design, setting, and participants Observational longitudinal cohort study of 170,528 patients who tested positive for SARS-CoV-2 in the US Department of Veterans Affairs (VA) Health Care System between 2/28/20 and 12/31/2020 who were followed through 01/31/2021. Measurements Charlson Comorbidity Index (CCI); Incidence of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death within 30 days of a positive SARS-CoV-2 test. Results The cumulative 30-day incidence of death was 0.8% in cohort members < 65 years, 7.1% in those aged 65–79 years and 20.6% in those aged ≥80 years. The respective 30-day incidences of hospitalization were 8.2, 21.7 and 29.5%, of ICU admission were 2.7, 8.6, and 11% and of mechanical ventilation were 1, 3.9 and 3.2%. Median CCI (interquartile range) ranged from 0.0 (0.0, 2.0) in the youngest, to 4 (2.0, 7.0) in the oldest age group. The adjusted association of CCI with all outcomes was attenuated at older ages such that the threshold level of CCI above which the risk for each outcome exceeded the reference group (1st quartile) was lower in younger than in older cohort members (p < 0.001 for all age group interactions). Limitations The CCI is calculated based on diagnostic codes, which may not provide an accurate assessment of comorbid burden. Conclusions Age differences in the distribution and prognostic significance of overall comorbid burden could inform clinical management, vaccination prioritization and population health during the pandemic and argue for more work to understand the role of age and comorbidity in shaping the care of hospitalized patients with SARS-CoV-2.

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Prognostic Significance Of NPM1 mutations In The Absence Of FLT3-ITD in Older Patients With AML: A SWOG Report

Blood ◽

10.1182/blood.v122.21.1315.1315 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1315-1315 ◽

Cited By ~ 4

Author(s):

Fabiana Ostronoff ◽

Megan Othus ◽

Soheil Meshinchi ◽

John E. Godwin ◽

Kenneth J. Kopecky ◽

...

Keyword(s):

Risk Factor ◽

Relapse Rate ◽

Conflicts Of Interest ◽

Performance Status ◽

Prognostic Significance ◽

Age Groups ◽

Adverse Outcomes ◽

Prognostic Impact ◽

Age Group ◽

Npm1 Mutation

Abstract Introduction Younger acute myeloid leukemia (AML) patients with a NPM1 mutation but without FLT3-ITD (NPM1+/FLT3-ITD-) have favorable prognosis, but the prognostic significance of these mutations in patients older than 55 years is less clear. Therefore, we evaluated the prognostic impact of the NPM1+/FLT3-ITD- in older AML patients. Methods Samples were obtained from AML patients enrolled onto SWOG trials S9333, S9031, S9500 and S0106 who were ³55 years and received “7+3 like” induction regimens. Cytarabine/daunorubicin (S9031 and S9033) or HiDAC (9500 and S0106) were used for consolidation. Gemtuzumab ozogamicin, either during induction, consolidation, and/or post-consolidation, was administered to some patients enrolled onto S0106. Samples were examined for FLT3, NPM1, DNMT3A, IDH1/2 mutations using previously reported techniques. Results A total of 1,239 patients enrolled in these trials, and pre-treatment samples were available for 156 patients who were older than 55 years (median age of 60 years, range 55-83). NPM1 and FLT3-ITD mutations were present in 33% and 24% of the patients, respectively. The complete remission (CR) rate, 2-year overall survival (OS) and relapse-free survival (RFS) for the entire cohort were 62%, 31% and 32%, respectively. Increased age, unfavorable cytogenetics and FLT3-ITD were associated with a worse OS and RFS. NPM1 mutations were not significantly associated with OS or RFS. Patients were then divided into two age groups, 55-65 and >65 years, based on previous data that favorable prognostic factors such as good-risk cytogenetics have not been shown to be associated with favorable outcomes for AML patients age >65. Both age groups displayed similar patient characteristics (in regards to white blood cell count, bone marrow blast %, cytogenetics, secondary AML, sex and ECOG performance status), with the exception that >65 years group did not include any patients from S0106 or S9500 due to age restrictions for these trials. Patients >65 had a higher relapse rate (P =0.001) and significantly worse OS (P<0.001) and RFS (P=0.007) than those aged 55-65. FLT3-ITD retained its unfavorable prognostic significance for patients age 55-65, while patients >65 years had such a uniformly poor prognosis that this mutation lost much of its prognostic significance. NPM1 mutations were not significantly associated with either OS or RFS in either age group. We then examined the most favorable NPM1+/FLT3-ITD- genotype, which is currently being used to risk-stratify AML patients. NPM1+/FLT3-ITD- was associated with an improved OS in the 55-65 age group (P<0.001), which was similar to previously described results in younger patients (Figure 1A). Additional analyses showed that the favorable impact of this genotype was not due to the inclusion of patients enrolled onto S0106 and S9500 (Figure 1B). In contrast, patients >65 years with the NPM1+/FLT3-ITD- had a low CR rate and high 1-year relapse rate, which translated into a relatively poor 5-year OS (<30%, Figure 1C) that was not significantly different from patients >65 without this genotype (P=0.33). Since mutations in DNMT3A, IDH1/2 have been associated with adverse outcomes for patients with NPM1 mutations, samples with the NPM1+/FLT3-ITD- genotype were examined for these mutations. The frequencies for DNMT3A, IDH1/2 mutations were similar in both age groups, indicating that these mutations were not responsible for the age-dependent findings. Furthermore, multivariate models adjusting for known prognostic covariates showed that the NPM1+/FLT3-ITD- remained independently associated with improved OS for patients age 55-65 but not those >65. Conclusions This study represents one of the largest investigations on the prognostic significance of NPM1+/FLT3-ITD- in older AML patients. The NPM1+/FLT3-ITD- genotype remains a favorable-risk factor for AML patients age 55-65 years but may not be a favorable-risk factor for patients >65 years, at least not for those treated with standard induction followed by conventional consolidation. Disclosures: No relevant conflicts of interest to declare.

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Trends over time in the risk of adverse outcomes among patients with SARS-CoV-2 infection

10.1101/2021.03.08.21253090 ◽

2021 ◽

Author(s):

George N. Ioannou ◽

Ann M. O’Hare ◽

Kristin Berry ◽

Vincent S Fan ◽

Kristina Crothers ◽

...

Keyword(s):

Mechanical Ventilation ◽

Healthcare System ◽

Hospitalized Patients ◽

Adverse Outcomes ◽

Interrupted Time Series Analysis ◽

Icu Admission ◽

National Healthcare ◽

Laboratory Test Results ◽

National Healthcare System ◽

Subsequent Stabilization

AbstractObjectivesWe aimed to describe trends in the incidence of adverse outcomes among patients who tested positive for SARS-CoV-2 between February and September 2020 within a national healthcare system.SettingUS Veterans Affairs national healthcare system.ParticipantsEnrollees in the VA healthcare system who tested positive for SARS-CoV-2 between 2/28/2020 and 9/30/2020 (n=55,952).OutcomesDeath, hospitalization, intensive care unit (ICU) admission and mechanical ventilation within 30 days of testing positive.The incidence of these outcomes was examined among patients infected each month and trends were evaluated using an interrupted time-series analysis.ResultsBetween February and July 2020, during the first wave of the US pandemic, 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%), with subsequent stabilization between July and September 2020. These trends persisted after adjustment for sociodemographic characteristics, comorbid conditions, and documented symptoms and after additional adjustment for laboratory test results among hospitalized patients, including among subgroups admitted to the ICU and treated with mechanical ventilation. Among hospitalized patients, 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%) decreased while use of dexamethasone (3.4% to 53.1%), other corticosteroids (4.9% to 29.0%) and remdesivir (1.7% to 45.4%) increased from February to September.ConclusionsAmong patients who tested positive for SARS-CoV-2 in a large national US healthcare system, risk for a range of adverse outcomes 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.

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Risk factors for adverse outcomes among 35 879 veterans with and without diabetes after diagnosis with COVID-19

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2021-002252 ◽

2021 ◽

Vol 9 (1) ◽

pp. e002252

Author(s):

Pandora L Wander ◽

Elliott Lowy ◽

Lauren A Beste ◽

Luis Tulloch-Palomino ◽

Anna Korpak ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Adverse Outcomes ◽

Cardiac Biomarkers ◽

Department Of Veterans Affairs ◽

Related Factors ◽

Icu Admission ◽

Patients With Diabetes ◽

Design And Methods ◽

Insulin Use

IntroductionRisk factors and mediators of associations of diabetes with COVID-19 outcomes are unclear.Research design and methodsWe identified all veterans receiving Department of Veterans Affairs healthcare with ≥1 positive nasal swab for SARS-CoV-2 (28 February–31 July 2020; n=35 879). We assessed associations of diabetes (with and without insulin use) with hospitalization, intensive care unit (ICU) admission, or death at 30 days, and with hazard of death until the censoring date. Among participants with diabetes (n=13 863), we examined associations of hemoglobin A1c and antihyperglycemic medication use with COVID-19 outcomes. We estimated mediation between diabetes and outcomes by comorbidities (cardiovascular disease, heart failure, and chronic kidney disease), statin or ACE inhibitor/angiotensin receptor blocker (ARB) use, and cardiac biomarkers (brain natriuretic peptide and troponin).ResultsDiabetes with and without insulin use was associated with greater odds of hospitalization, ICU admission, and death at 30 days, and with greater hazard of death compared with no diabetes (OR 1.73, 1.76 and 1.63, and HR 1.61; and OR 1.39, 1.49 and 1.33, and HR 1.37, respectively, all p<0.0001). Prior sulfonylurea use was associated with greater odds of hospitalization and prior insulin use with hospitalization and death among patients with diabetes; among all participants, statin use was associated with lower mortality and ARB use with lower odds of hospitalization. Cardiovascular disease-related factors mediated <20% of associations between diabetes and outcomes.ConclusionsDiabetes is independently associated with adverse outcomes from COVID-19. Associations are only partially mediated by common comorbidities.

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Exploring the link between Vitamin D and clinical outcomes in COVID-19.

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00517.2020 ◽

2021 ◽

Author(s):

Prateek Lohia ◽

Paul Nguyen ◽

Neel Patel ◽

Shweta Kapur

Keyword(s):

Vitamin D ◽

Mechanical Ventilation ◽

Pulmonary Embolism ◽

Cohort Study ◽

Clinical Outcomes ◽

Retrospective Cohort ◽

Age Group ◽

Icu Admission ◽

Vitamin D Levels

Background The immunomodulating role of vitamin D might play a role in COVID-19 disease. Objective To study the association between vitamin D and clinical outcomes in COVID-19 patients. Methods Retrospective cohort study on COVID-19 patients with documented vitamin D levels within the last year. Vitamin D levels were grouped as ≥ 20 ng/mL or <20 ng/mL. Main outcomes were mortality, need for mechanical ventilation, new DVT or pulmonary embolism, and ICU admission. Results A total of 270 patients (mean (SD) age, 63.81 (14.69) years); 117 (43.3%) males; 216 (80%) African Americans; 139 (51.5%) in 65 and older age group were included. Vitamin D levels were less than 20 ng/ml in 95 (35.2%) patients. During admission, 72 patients (26.7%) died, 59 (21.9%) needed mechanical ventilation, and 87 (32.2%) required ICU. Vitamin D levels showed no significant association with mortality (OR=0.69; 95% CI, 0.39 - 1.24; p=0.21), need for mechanical ventilation (OR=1.23; 95% CI, 0.68 - 2.24; p=0.49), new DVT or PE(OR= 0.92; 95% CI, 0.16- 5.11; p=1.00) or ICU admission (OR=1.38; 95% CI, 0.81 - 2.34; p=0.23). Conclusion We did not find any significant association of vitamin D levels with mortality, the need for mechanical ventilation, ICU admission and the development of thromboembolism in COVID-19 patients.

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Fever Patterns, Cytokine Profiles, and Outcomes in COVID-19

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa375 ◽

2020 ◽

Vol 7 (9) ◽

Author(s):

Deborah H L Ng ◽

Chiaw Yee Choy ◽

Yi-Hao Chan ◽

Barnaby E Young ◽

Siew-Wai Fong ◽

...

Keyword(s):

Intensive Care Unit ◽

Mechanical Ventilation ◽

Intensive Care ◽

Case Control Study ◽

Case Control ◽

Adverse Outcomes ◽

Icu Admission ◽

Prolonged Fever ◽

Interleukin 1Α ◽

Control Study

Abstract Background Prolonged fever is associated with adverse outcomes in dengue viral infection. Similar fever patterns are observed in COVID-19 with unclear significance. Methods We conducted a hospital-based case–control study of patients admitted for COVID-19 with prolonged fever (fever >7 days) and saddleback fever (recurrence of fever, lasting <24 hours, after defervescence beyond day 7 of illness). Fever was defined as a temperature of ≥38.0°C. Cytokines were determined with multiplex microbead-based immunoassay for a subgroup of patients. Adverse outcomes were hypoxia, intensive care unit (ICU) admission, mechanical ventilation, and mortality. Results A total of 142 patients were included in the study; 12.7% (18/142) of cases had prolonged fever, and 9.9% (14/142) had saddleback fever. Those with prolonged fever had a median duration of fever (interquartile range [IQR]) of 10 (9–11) days for prolonged fever cases, while fever recurred at a median (IQR) of 10 (8–12) days for those with saddleback fever. Both prolonged (27.8% vs 0.9%; P < .01) and saddleback fever (14.3% vs 0.9%; P = .03) were associated with hypoxia compared with controls. Cases with prolonged fever were also more likely to require ICU admission compared with controls (11.1% vs 0.9%; P = .05). Patients with prolonged fever had higher induced protein–10 and lower interleukin-1α levels compared with those with saddleback fever at the early acute phase of disease. Conclusions Prolonged fever beyond 7 days from onset of illness can identify patients who may be at risk of adverse outcomes from COVID-19. Patients with saddleback fever appeared to have good outcomes regardless of the fever.

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Adverse Outcomes and Mortality in Users of Non-Steroidal Anti-Inflammatory Drugs tested positive for SARS-CoV-2: A Danish Nationwide Cohort Study

10.1101/2020.06.08.20115683 ◽

2020 ◽

Author(s):

Lars Christian Lund ◽

Kasper Bruun Kristensen ◽

Mette Reilev ◽

Steffen Christensen ◽

Reimar W. Thomsen ◽

...

Keyword(s):

Mechanical Ventilation ◽

Cohort Study ◽

Renal Replacement Therapy ◽

Replacement Therapy ◽

Population Based ◽

Adverse Outcomes ◽

The European Union ◽

Icu Admission ◽

Increased Risk ◽

Anti Inflammatory

Background Concerns over the safety of non-steroidal anti-inflammatory drug (NSAID) use during SARS-CoV-2 infection have been raised. Objectives To study whether use of NSAIDs is associated with adverse outcomes and mortality during SARS-CoV-2 infection. Design Population based cohort study Setting Danish administrative and health registries. Participants Individuals tested positive for SARS-CoV-2 during Feb 27, 2020 to Apr 29, 2020. Treated individuals (defined as a filled NSAID prescription up to 30 days before the SARS-CoV-2 test) were matched to up to 4 non-treated individuals on propensity scores based on age, sex, relevant comorbidities and prescription fills. Outcome measures The main outcome was 30-day mortality and treated individuals were compared to untreated individuals using risk ratios (RR) and risk differences (RD). Secondary outcomes included hospitalisation, intensive care unit (ICU) admission, mechanical ventilation and acute renal replacement therapy. Results A total of 9236 SARS-CoV-2 PCR positive individuals were eligible for inclusion. Of these, 248 (2.7%) had filled a prescription for NSAIDs and 535 (5.8%) died within 30 days. In the matched analyses, treatment with NSAIDs was not associated with 30-day mortality (RR 1.02, 95% CI 0.57 to 1.82; RD 0.1%, -3.5% to 3.7%), increased risk of hospitalisation (RR 1.16, 0.87 to 1.53; RD 3.3%, -3.4% to 10%), ICU-admission (RR 1.04, 0.54 to 2.02; RD 0.2%, -3.0% to 3.4%), mechanical ventilation (RR 1.14, 0.56 to 2.30; RD 0.5%, -2.5% to 3.6%), or renal replacement therapy (RR 0.86, 0.24 to 3.09; RD -0.2%, -2.0% to 1.6%). Conclusion Use of NSAIDs was not associated with 30-day mortality, hospitalisation, ICU-admission, mechanical ventilation or renal replacement therapy in Danish individuals tested positive for SARS-CoV-2. Registration: The European Union electronic Register of Post-Authorisation Studies, EUPAS-34734 (http://www.encepp.eu/encepp/viewResource.htm?id=34735)

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The association between immunosuppressants use and COVID-19 adverse outcome: National COVID-19 cohort in South Korea

10.1101/2021.08.17.21262183 ◽

2021 ◽

Author(s):

Hyun Joon Shin ◽

Ronald Chow ◽

Hyerim Noh ◽

Jongseong Lee ◽

Jihui Lee ◽

...

Keyword(s):

Mechanical Ventilation ◽

South Korea ◽

Primary Outcome ◽

Composite Endpoint ◽

Population Based ◽

Adverse Outcomes ◽

Added Value ◽

Icu Admission ◽

Outpatient Prescription ◽

Exposure Variable

SummaryBackgroundThere is uncertainty of the effect of immunosuppression, including corticosteroids, before COVID-19 infection on COVID-19 outcomes. The aim of this study was to investigate the relationship between prehospitalization immunosuppressants use (exposure), and COVID-19 patient outcomes.MethodsWe conducted a population-based retrospective cohort study using a nationwide healthcare claims database of South Korea as of May 15, 2020. Confirmed COVID-19 infection in hospitalized individuals aged 40 years or older were included for analysis. We defined exposure variable by using inpatient and outpatient prescription records of immunosuppressants from the database. Our primary outcome was a composite endpoint of all-cause death, intensive care unit (ICU) admission, and mechanical ventilation use. Inverse probability of treatment weighting (IPTW)-adjusted logistic regression analyses were used, to estimate odds ratio (OR) and 95% confidence intervals, comparing immunosuppressants users and non-users.FindingsWe identified 4,349 patients, for which 1,356 were immunosuppressants users and 2,903 were non-users. Patients who used immunosuppressants were at increased odds of the primary outcome of all-cause death, ICU admission and mechanical ventilation use (IPTW OR 1.32; 95% CI: 1.06 – 1.63). Patients who used corticosteroids were at increased odds of the primary outcome (IPTW OR 1.33; 95% CI: 1.07 – 1.64).InterpretationWe support the latest guidelines from the CDC, that people on immunosuppressants are at high risk of severe COVID-19 and immunocompromised people may need booster COVID-19 vaccinations.FundingYGC’s work was partially supported by 2020R1G1A1A01006229 awarded by the National Research Foundation of Korea.Research in contextEvidence before this studyIt is currently unclear whether immunosuppressants use before COVID-19 is associated with adverse outcomes.Added value of this studyImmunosuppressants in patients with COVID-19 were at increased odds of the primary outcome of all-cause death, ICU admission and mechanical ventilation use.Implications of all the available evidenceImmunosuppressant use before COVID-19 is associated with adverse outcomes and immunocompromised people may need booster COVID-19 vaccination.

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Breast carcinoma in young females below the age of 35 years - histopathological and prognostic significance

Journal of Pathology of Nepal ◽

10.3126/jpn.v2i3.6021 ◽

1970 ◽

Vol 2 (3) ◽

pp. 198-202

Author(s):

D Ghartimagar ◽

A Ghosh ◽

OP Talwar ◽

R Narasimhan

Keyword(s):

Breast Carcinoma ◽

Young Women ◽

Early Stage ◽

Prognostic Significance ◽

Age Group ◽

Breast Cancers ◽

Young Females ◽

Younger Age ◽

Grade 3 ◽

Group Grade

Background: Breast cancers rarely occur in young women but are known to have more aggressive behaviors and poorer outcome. We here compare the significance of breast carcinoma in female below the age of 35 to the age over 35 whose specimens were submitted to Manipal teaching hospital, Pokhara. Materials and Methods: All cases of mastectomy with carcinoma from January 2000 to September 2011 were included in the study. Clinical and histopathological datas of all cases were reviewed and collated. Results: A total of 148 mastectomy specimens were received, among which, 23 cases (16%) were below 35 years; whereas 125 cases (84%) were above 35 years of age. In both groups, Stage II was the commonest stage but stage III was much more common in older group (33% versus 9%) and stage I was more common in younger age group (39% versus 27%). Bloom Richardson grading showed that in the older age group, grade 1 is the commonest grade (50%) while in the younger group; grade 3 is the commonest (39%). Patients were followed for a varying period of 6 months to 5 years. Two cases (2% of followed up cases) in older group and 3 cases (15% of followed up cases) in the younger group showed recurrence. Conclusion: Breast carcinoma in the patients younger than 35 years though presented at an early stage has higher grade tumor and poorer outcome. DOI: http://dx.doi.org/10.3126/jpn.v2i3.6021 JPN 2012; 2(3): 198-202

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Cross-sectional observational study of epidemiology of COVID-19 and clinical outcomes of hospitalised patients in North West London during March and April 2020

BMJ Open ◽

10.1136/bmjopen-2020-044384 ◽

2021 ◽

Vol 11 (2) ◽

pp. e044384

Author(s):

Guduru Gopal Rao ◽

Alexander Allen ◽

Padmasayee Papineni ◽

Liyang Wang ◽

Charlotte Anderson ◽

...

Keyword(s):

Mechanical Ventilation ◽

Clinical Outcomes ◽

Severe Infection ◽

Older Age ◽

Cross Sectional ◽

North West ◽

Icu Admission ◽

Risk Of Death ◽

Hospitalised Patients ◽

Increased Risk

ObjectiveThe aim of this paper is to describe evolution, epidemiology and clinical outcomes of COVID-19 in subjects tested at or admitted to hospitals in North West London.DesignObservational cohort study.SettingLondon North West Healthcare NHS Trust (LNWH).ParticipantsPatients tested and/or admitted for COVID-19 at LNWH during March and April 2020Main outcome measuresDescriptive and analytical epidemiology of demographic and clinical outcomes (intensive care unit (ICU) admission, mechanical ventilation and mortality) of those who tested positive for COVID-19.ResultsThe outbreak began in the first week of March 2020 and reached a peak by the end of March and first week of April. In the study period, 6183 tests were performed in on 4981 people. Of the 2086 laboratory confirmed COVID-19 cases, 1901 were admitted to hospital. Older age group, men and those of black or Asian minority ethnic (BAME) group were predominantly affected (p<0.05). These groups also had more severe infection resulting in ICU admission and need for mechanical ventilation (p<0.05). However, in a multivariate analysis, only increasing age was independently associated with increased risk of death (p<0.05). Mortality rate was 26.9% in hospitalised patients.ConclusionThe findings confirm that men, BAME and older population were most commonly and severely affected groups. Only older age was independently associated with mortality.

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Effect of timing of intubation on clinical outcomes of critically ill patients with COVID-19: a systematic review and meta-analysis of non-randomized cohort studies

Critical Care ◽

10.1186/s13054-021-03540-6 ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Eleni Papoutsi ◽

Vassilis G. Giannakoulis ◽

Eleni Xourgia ◽

Christina Routsi ◽

Anastasia Kotanidou ◽

...

Keyword(s):

Systematic Review ◽

Mechanical Ventilation ◽

Clinical Outcomes ◽

Critically Ill ◽

Critically Ill Patients ◽

Meta Analysis ◽

Mortality And Morbidity ◽

Icu Admission ◽

All Cause Mortality ◽

Detectable Difference

Abstract Background Although several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis. Methods PubMed and Scopus were systematically searched, while references and preprint servers were explored, for relevant articles up to December 26, 2020, to identify studies which reported on mortality and/or morbidity of patients with COVID-19 undergoing early versus late intubation. “Early” was defined as intubation within 24 h from intensive care unit (ICU) admission, while “late” as intubation at any time after 24 h of ICU admission. All-cause mortality and duration of mechanical ventilation (MV) were the primary outcomes of the meta-analysis. Pooled risk ratio (RR), pooled mean difference (MD) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42020222147). Results A total of 12 studies, involving 8944 critically ill patients with COVID-19, were included. There was no statistically detectable difference on all-cause mortality between patients undergoing early versus late intubation (3981 deaths; 45.4% versus 39.1%; RR 1.07, 95% CI 0.99–1.15, p = 0.08). This was also the case for duration of MV (1892 patients; MD − 0.58 days, 95% CI − 3.06 to 1.89 days, p = 0.65). In a sensitivity analysis using an alternate definition of early/late intubation, intubation without versus with a prior trial of high-flow nasal cannula or noninvasive mechanical ventilation was still not associated with a statistically detectable difference on all-cause mortality (1128 deaths; 48.9% versus 42.5%; RR 1.11, 95% CI 0.99–1.25, p = 0.08). Conclusions The synthesized evidence suggests that timing of intubation may have no effect on mortality and morbidity of critically ill patients with COVID-19. These results might justify a wait-and-see approach, which may lead to fewer intubations. Relevant guidelines may therefore need to be updated.

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