Does tracheostomy predict outcome in severe COVID-19?

Introduction: The association of tracheostomy timing and clinical outcomes in ventilated COVID-19 patients remains controversial. Data from the pre-pandemic era has demonstrated the use of tracheostomy for ventilator weaning [1]. However, the use of tracheostomy in COVID- 19 patients was a subject of discussion [2]. Nevertheless, evidence of the impact of tracheostomy on the outcome in critically ill COVID patients is still lacking. This study aims to evaluate the impact on Intensive Care Unit (ICU) outcome (survival) of tracheostomy in COVID- 19 ventilated patients. Method(s): Monocentric descriptive observational study. Demographic and clinical data, timing of tracheostomy and outcome (ICU mortality) from 1st January to 31st December 2021 were registered. Analysis of descriptive statistics for continuous variables and survival analysis (log rank test). Result(s): 115 patients were included (72% males), all mechanically ventilated, 7 (6%) were subjected to tracheostomy. The mean age was 67.2 years (range 36-84 years). The ICU mortality was 62% (71). The group of patients not submitted to tracheostomy had a mean survival time of 24.4 days (SD +/- 1.5) and median survival time of 22 days (SD +/- 1.7). The group of patients that were subjected to tracheostomy, the mean survival time was 68.5 days (SD +/- 12.2) and median survival time was 50 days (SD +/- 2). This comparison is significative (Log Rank test, p = 0.0001). Conclusion(s): The present study demonstrates a better survival likelihood of the tracheostomized subpopulation. Tracheostomy was only done in 6% of patients, which elucidates a need to further prospective, randomized studies to assess the impact on the outcome of tracheostomy in ventilated COVID19 patients.

Neutrophil-to-lymphocyte ratio (NLR) as a predictor of survival in COVID-19-associated pneumonia patients (pts)

Prior studies have shown that increased NLR can be easily used as a rapid and available marker for COVID-19- associated pneumonia pts severity and survival. Aim(s): to determine the role in predicting the surviving in COVID-19-associated pneumonia pts. Material(s) and Method(s): we studied 105 hospitalized pts ((age - 58,4 +/- 1,4 yrs, male - 62 (59 %)) with severe, moderate and critical Covid-19 confirmed by RNA detection of the 2019-nCoV. Measurements included medical history, clinical status, hematological parameters with calculating of NLR. Patients were divided into three groups according to disease severity (1-Group - 37 critical pts (male - 21 (56,7 %)), 2-Group-44 severe (male-25 (26,8 %)), 3-Group-24 moderate (male-11 (45,8 %)). Result(s): research has shown that NLR level was the highest in critical pts 8,5 (6,2;10,1) (p=0,001). According to ROC curve analysis the cut off points of the NLR level was 5,65, and patients were divided into two groups according to NLR level-NLR>=5,65 (57 (53,7 % pts) and NLR<=5,65 (49 (46,3 % pts). We estimated the mean survival time according to NLR level. Estimated mean time until death was 9,7 days for NLR>=5.6 and 7,7 days for NLR<=5.6 (p<0.01) (figure 1). Conclusion(s): high NLR levels on admission were associated with severity of COVID-19. COVID-19-associated pneumonia pts with NLR>=5,6, were less likely to survive during observation period.

Comparison of abiraterone acetate and prednisolone (AAP) or combination enzalutamide (ENZ) + AAP for metastatic hormone sensitive prostate cancer (mHSPC) starting androgen deprivation therapy (ADT): Overall survival (OS) results of 2 randomised phase III trials from the STAMPEDE protocol

Background: AAP or ENZ added to ADT improves outcomes for mHSPC. Any benefit of combining ENZ & AAP in this disease setting is uncertain. Methods: STAMPEDE is a multi-arm, multi-stage (MAMS), platform protocol conducted at 117 sites in the UK & Switzerland. 2 trials with no overlapping controls randomised mHSPC patients (pts) 1:1 to ADT +/- AAP (1000mg od AA + 5mg od P) or AAP + ENZ (160mg od). Treatment was continued to progression. From Jan 2016 docetaxel 75mg/m2 3-weekly with P 10mg od was permitted + ADT. Using meta-analysis methods, we tested for evidence of a difference in OS and secondary outcomes (as described previously: failure-free, metastatic progression-free, progression-free & prostate cancer specific survival) across the 2 trials using data frozen 3 Jul 2022. All confidence intervals (CI) 95%. Restricted mean survival times (RMST) restricted to 84 months (m). Results: Between Nov 2011 & Jan 2014, 1003 pts were randomised ADT +/- AAP & between Jul 2014 & Mar 2016, 916 pts were randomised ADT +/- AAP + ENZ. Randomised groups were well balanced across both trials. Pt cohort: age, median 68 years (yr), IQR 63, 72;PSA prior to ADT, median 95.7 ng/ml, IQR 26.5, 346;de novo 94%, relapsed after radical treatment, 6%. In AAP + ENZ trial, 9% had docetaxel + ADT. OS benefit in AAP + ENZ trial, HR 0.65 (CI 0.55‒0.77) p = 1.4×10-6;in AAP trial, HR 0.62 (0.53, 0.73) p = 1.6×10-9. No evidence of a difference in treatment effect (interaction HR 1.05 CI 0.83‒1.32, p = 0.71) or between-trial heterogeneity (I2 p = 0.70). Same for secondary end-points. % (CI) of pts reporting grade 3-5 toxicity in 1st 5 yr: AAP trial, ADT: 38.5 (34.2-42.8), + AAP: 54.4 (50.0-58.8);AAP + ENZ trial, ADT: 45.2 (40.6 – 49.8), + AAP + ENZ: 67.9 (63.5 – 72.2);most frequently increased with AAP or AAP + ENZ = liver derangement, hypertension. At 7 yr in AAP trial (median follow-up: 95.8m), % (CI) pts alive with ADT: 30 (26, 34) versus with ADT + AAP: 48 (43, 52);RMST: ADT: 50.4m, ADT + AAP: 60.6m, p = 6.6 x 10-9. Conclusions: ENZ + AAP need not be combined for mHSPC. Clinically important improvements in OS when adding AAP to ADT are maintained at 7 yr. Clinical trial identification: NCT00268476. Legal entity responsible for the study: Medical Research Council Clinical Trials Unit at University College London. Funding: Cancer Research UK, Medical Research Council, Janssen, Astellas. Disclosure: G. Attard: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, AstraZeneca;Financial Interests, Personal, Advisory Board: Janssen, Astellas, Novartis, Bayer, AstraZeneca, Pfizer, Sanofi, Sapience, Orion;Financial Interests, Personal, Royalties, Included in list of rewards to discoverers of abiraterone: Institute of Cancer Research;Financial Interests, Institutional, Research Grant: Janssen, Astellas;Non-Financial Interests, Principal Investigator: Janssen, Astellas;Non-Financial Interests, Advisory Role: Janssen, AstraZeneca. W.R. Cross: Financial Interests, Personal, Invited Speaker, Speaker fee: Myriad Genetics, Janssen, Astellas;Financial Interests, Personal, Advisory Board, Advisory Board fee: Bayer;Financial Interests, Institutional, Research Grant, Research grant: Myriad Genetics. S. Gillessen: Financial Interests, Personal, Advisory Board, 2018: Sanofi, Roche;Financial Interests, Personal, Advisory Board, 2018, 2019: Orion;Financial Interests, Personal, Invited Speaker, 2019 Speaker's Bureau: Janssen Cilag;Financial Interests, Personal, Advisory Board, 2020: Amgen;Financial Interests, Personal, Invited Speaker, 2020: ESMO;Financial Interests, Personal, Other, Travel Grant 2020: ProteoMEdiX;Financial Interests, Institutional, Advisory Board, 2018, 2019, 2022: Bayer;Financial Interests, Institutional, Advisory Board, 2020: Janssen Cilag, Roche, MSD Merck Sharp & Dohme, Pfizer;Financial Interests, Institutional, Advisory Board, 2018: AAA International, Menarini Silicon Biosystems;Financial Interests, Institutional, Advisory Board, 2019, 2020: Astellas Pharma;Financial Interests, Institutional, Advisory B ard, 2019: Tolero Pharmaceuticals;Financial Interests, Personal, Invited Speaker, 2021, 2022: SAKK, DESO;Financial Interests, Institutional, Advisory Board, 2021: Telixpharma, BMS, AAA International, Novartis, Modra Pharmaceuticas Holding B.V.;Financial Interests, Institutional, Other, Steering Committee 2021: Amgen;Financial Interests, Institutional, Advisory Board, 2021, 2022: Orion, Bayer;Financial Interests, Personal, Invited Speaker, 2021: SAKK, SAKK, SAMO - IBCSG (Swiss Academy of Multidisciplinary oncology);Financial Interests, Personal, Advisory Board, 2021: MSD Merck Sharp & Dhome;Financial Interests, Personal, 2021: RSI (Televisione Svizzera Italiana);Financial Interests, Institutional, Invited Speaker, 2021: Silvio Grasso Consulting;Financial Interests, Institutional, Other, Faculty activity 2022: WebMD-Medscape;Financial Interests, Institutional, Advisory Board, 2022: Myriad genetics, AstraZeneca;Financial Interests, Institutional, Invited Speaker, 2022: TOLREMO;Financial Interests, Personal, Other, Travel support 2022: AstraZeneca;Financial Interests, Institutional, Funding, 2021, Unrestricted grant for a Covid related study as co-investigator: Astellas;Non-Financial Interests, Advisory Role, 2019: Menarini Silicon Biosystems, Aranda;Non-Financial Interests, Advisory Role, Continuing: ProteoMediX. C. Pezaro: Financial Interests, Personal, Advisory Board, Ad board Dec 2020: Advanced Accelerator Applications;Financial Interests, Personal, Advisory Board, Aug 2021: Astellas;Financial Interests, Personal, Advisory Board, Oct 2021: Bayer;Financial Interests, Personal, Invited Speaker, Sept-Oct 2020: AstraZeneca;Financial Interests, Personal, Invited Speaker, Oct 2020: Janssen;Financial Interests, Personal, Advisory Board, July-Sept 2022: Pfizer. Z. Malik: Financial Interests, Personal, Advisory Board, advisry board for new hormonal therapy for breast cancer: sanofi;Financial Interests, Institutional, Invited Speaker, research grant for CHROME study: sanofi;Other, Other, support to attend meetings or advisory boards in the past: Astellas,Jaansen,Bayer;Other, Other, Sponsorship to attend ASCO meeting 2022: Bayer. M.R. Sydes: Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training sessions for clinicians (no discussion of particular drugs): Janssen;Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training session for clinicians (no discussion of particular drugs): Eli Lilly;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Astellas, Janssen, Novartis, Pfizer, Sanofi;Financial Interests, Institutional, Research Grant, Educational grant and biomarker costs for STAMPEDE trial: Clovis Oncology. L.C. brown: Financial Interests, Institutional, Research Grant, £170k educational grant for the FOCUS4-C Trial from June 2017 to Dec 2021: AstraZeneca;Financial Interests, Institutional, Funding, Various grants awarded to my institution for work undertaken as part of the STAMPEDE Trial: janssen pharmaceuticals;Non-Financial Interests, Other, I am a member of the CRUK CERP funding advisory panel and my Institution also receive grant funding from CRUK for the STAMPEDE and FOCUS4 trials: Cancer Research UK. M.K. Parmar: Financial Interests, Institutional, Full or part-time Employment, Director at MRC Clinical Trials Unit at UCL: Medical Research Council Clinical Trials Unit at UCL;Financial Interests, Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Clovis;Non-Financial Interests, Advisory Role, Euro Ewing Consortium: University College London;Non-Financial Interests, Advisory Role, rEECur: University of Birmingham;Non-Financial Interests, Advisory Role, CompARE Trial: University of Birmingham. N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen, Clovis, Novartis;Financial Interests, Institutional, Expert Testimony, Assisted with submissions regarding licencing for abiraterone: Janssen;Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi;Financial Interests, Institutional, Expert Testimony, Providing STAMPEDE trial data to facilitate licence extensions internationally for docetaxel: Sanofi;Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck;Financial Interests, Personal, Advisory Board, Advice around novel hormone therapies for prostate cancer: Bayer;Financial Interests, Personal, Invited Speaker, Lecture tour in Brazil August 2022 - speaking on therapy for advanced prostate cancer: Merck Sharp & Dohme (UK) Limited;Financial Interests, Institutional, Invited Speaker, Funding for STAMPEDE trial: Janssen, Astellas;Financial Interests, Institutional, Invited Speaker, Funding for RADIO trial bladder cancer: AstraZeneca. All other authors have declared no conflicts of interest.

Lung Cancer Resection During the Covid-19 Pandemic: A Single Centre Study

Introduction: During the Covid-19 pandemic, less invasive alternatives to surgery were recommended to minimise the risk of patient exposure to the virus. Therefore, this study aimed to assess the impact of covid-19 on lung cancer resections. Methods: We retrospectively analysed lung resections between March 2019 and May 2021. Eligibility criteria included patients with confirmed non-small cell lung cancer. We divided the patients into Group A (lung cancer resection between March 2019 and February 2020 and Group B (lung cancer resection between March 2020 and May 2021. The WHO declared Covid-19 a pandemic on 11th March 2020. The outcome measures were (1) the number of lung resections, (2) the completed waiting period and (3) Survival between the two groups Results: In Group A, 192 (78.7%) were for primary lung cancer, while in Group B, 133 (71%) were for primary lung cancer (p<0.05). The mean completed waiting period for Group A patients was 71.85±60 days (median 58 days;R 5-449 days), while the mean completed waiting period in Group B patients was 45.2±34 days (median 38 days;R 4-213 days) (p<0.0001). The mean survival times for Group A & B were 17.8 and 18.7 months, respectively (Logrank = 0.015). In Group A, survival at 30-days, 90 days and 1-year was 99.48%, 98% and 91.67%) respectively. In Group B, survival was 100%, 99.25%, and 97.1% at 30-days, 90 days, and 1-year Conclusions: We found a 30.7% decrease in the lung cancer resection volume. Also, the completed waiting times for lung cancer resection decreased by 26.51 days during the study period. Early survival was better in Group B patients than Group A. Recoded staging figures reflected higher pathological stages in the latter group (p=0.04). Additionally, subgroup analysis showed that we operated on more stage-1 lung cancers in Group B vs Group A (63.4% vs 54.2%). [Formula presented] [Formula presented] Keywords: Lung cancer resection, Covid-19, Survival

Survival Analysis Based on the Siddha Body Constitution of Asymptomatic SARS-CoV-2 Patients Under Integrative Management of Hydroxychloroquine (HCQ) and Kaba Sura Kudineer (KSK): A Retrospective Cross-sectional Case Series from Tirupati

Background: The present study analysed the impact of the integrated medical care of Hydroxychloroquine (HCQ) and Siddha herbal preparation KSK on asymptomatic COVID-19 patients based on their body constitution. Objective: The present study aimed to analyse the duration of the hospital stay of asymptomatic COVID-19 patients treated with the integrated medical care of hydroxychloroquine (HCQ) and herbal decoction of Kaba Sura Kudineer (KSK). Design: The study included a retrospective case series of 19 asymptomatic confirmed SARS-Cov-2 patients from District COVID Care Centre, Tirupati, India, between 23rd May to 7th June 2020. Methods: Clinical data were collected using a standardised case report form containing demographic information, length of hospital stays, and Siddha Yakkai Ilakkanam (body constitution) from the records. The association between the length of hospital stay, age, gender, and Siddha YI for the confirmed patients after admission was analysed by the Kaplan Meier survival analysis method. Results: Patients belonging to the Aiyam group stayed for at least nine days in the hospital, and 80% took ten or more days to cure the disease. About 71.4% took more than four days and three days of hospital stay in the Azhal and Vali groups, respectively. It was observed that 75% of females and 73.3% of males took nine days or more of hospital stay, respectively. The range of hospital stay was between 2-15 days for patients aged between 19 – 40 years. Conclusion: The present study explored the significance of integrating Siddha medicine with Western medicine in the management of SARS Cov-2 infection. An overall median of 9 days in the length of stay and 8.5 days in the overall mean survival time was documented. The patients of the present study on integrative treatment recovered about nine days earlier in comparison to the patients studied in Vietnam and China.

Cardiac injury and mortality among covid-19 patients in a predominantly black community of east flatbush brooklyn

Introduction: Black/African-American (AA) populations have been previously shown to have increased disease burden of COVID-19 and related deaths. However, not many studies have examined cardiovascular comorbidities and associated cardiac injury contributions to morbidity and mortality of COVID-19 in this population. In this study, we investigate the contributions of cardiac injury to mortality of COVID-19 in a predominantly AA population. Study Design: This is a retrospective cohort study of 572 laboratory confirmed COVID-19 patients admitted to SUNY Downstate HSC in East Flatbush, Brooklyn between March 12 and May 12, 2020. Patients with a documented troponin level above 0.15 μg/L were denoted as having cardiac injury. Of this group, 110 patients were in the cardiac injury group and 462 patients were in the no cardiac injury group. Statistical significance was designated at the p=0.05 level. Outcome: The primary outcome is 60-day mortality. Secondary outcomes included length of stay, non-invasive and invasive ventilation requirement, requirement of intensive care unit admission. Results: The median age was 69 years. 303 (52.97%) were males, and 515 (90.03%) were AA. When compared to patient's non-cardiac injury group, the cardiac injury group tended to be older, and more likely to have comorbidities such as CHF, COPD, and ESRD. Patients with cardiac injury were also more likely to be smokers. In the cardiac injury group, laboratory data showed a higher white blood cell count, blood urea nitrogen, creatinine, and procalcitonin. Patients with cardiac injury had higher proportion of renal failure, were more likely to require intubation, and were more likely to be transferred to ICU. Notably in comparison to the non-cardiac injury group, patients with cardiac injury found to have a statistically significant two-fold increase in 60-day mortality (62.73% vs 32.90%), reduced mean survival time (33.57 vs 52.70) and a hazard ratio of 1.53 after controlling for confounders using the multiple adjusted Cox proportional hazard regression model. Conclusions and Relevance: The study results exhibit a statistically significant association between cardiac injury and mortality among COVID-19 positive individuals from a predominantly AA population.

Communicating About Mortality in Health Decision Support: 'What and Why and When, and How and Where and Who'.

The Covid-19 pandemic has only accelerated the need and desire to deal more openly with mortality, because the effect on survival is central to the comprehensive assessment of harms and benefits needed to meet a 'reasonable patient' legal standard. Taking the view that this requirement is best met through a multi-criterial decision support tool, we offer our preferred answers to the questions of What should be communicated about mortality in the tool, and How, given preferred answers to Who for, Who by, Why, When, and Where. Summary measures, including unrestricted Life Expectancy and Restricted Mean Survival Time are found to be reductionist and relative, and not as easy to understand and communicate as often asserted. Full lifetime absolute survival curves should be presented, even if they cannot be 'evidence-based' beyond trial follow-up limits, along with equivalent measures for other criteria in the (necessarily) multi-criterial decision. A decision support tool should relieve the reasonable person of the resulting calculation burden.

Survival Analysis of Treatment Efficacy in Comparative Coronavirus Disease 2019 Studies.

For survival analysis in comparative coronavirus disease 2019 trials, the routinely used hazard ratio may not provide a meaningful summary of the treatment effect. The mean survival time difference/ratio is an intuitive, assumption-free alternative. However, for short-term studies, landmark mortality rate differences/ratios are more clinically relevant and should be formally analyzed and reported.

Patients With Lung Cancer Have High Susceptibility of COVID-19: A Retrospective Study in Wuhan, China.

Patients with lung cancer are presumed to be at high risk from COVID-19 infection due to underlying malignancy. A total of 31 COVID-19 patients with pre-diagnosed lung cancer and 186 age and sex matched COVID-19 patients without cancer in 6 hospitals in Wuhan, China were identified in our study. There was a significantly higher level of IL-6 in lung cancer group showed by multifactorial analysis. The restricted mean survival time in 10, 20, and 53 days in COVID-19 patients with lung cancer were ealier than non-cancer COVID-19 patients in the same observation time (all P values < 0.05). Our results indicated that pre-diagnosed lung cancer was associated with higher morbidity and mortality in COVID-19 patients.

Statistical Issues and Lessons Learned From COVID-19 Clinical Trials With Lopinavir-Ritonavir and Remdesivir.

BACKGROUND: Recently, three randomized clinical trials on coronavirus disease (COVID-19) treatments were completed: one for lopinavir-ritonavir and two for remdesivir. One trial reported that remdesivir was superior to placebo in shortening the time to recovery, while the other two showed no benefit of the treatment under investigation. OBJECTIVE: The aim of this paper is to, from a statistical perspective, identify several key issues in the design and analysis of three COVID-19 trials and reanalyze the data from the cumulative incidence curves in the three trials using more appropriate statistical methods. METHODS: The lopinavir-ritonavir trial enrolled 39 additional patients due to insignificant results after the sample size reached the planned number, which led to inflation of the type I error rate. The remdesivir trial of Wang et al failed to reach the planned sample size due to a lack of eligible patients, and the bootstrap method was used to predict the quantity of clinical interest conditionally and unconditionally if the trial had continued to reach the originally planned sample size. Moreover, we used a terminal (or cure) rate model and a model-free metric known as the restricted mean survival time or the restricted mean time to improvement (RMTI) to analyze the reconstructed data. The remdesivir trial of Beigel et al reported the median recovery time of the remdesivir and placebo groups, and the rate ratio for recovery, while both quantities depend on a particular time point representing local information. We use the restricted mean time to recovery (RMTR) as a global and robust measure for efficacy. RESULTS: For the lopinavir-ritonavir trial, with the increase of sample size from 160 to 199, the type I error rate was inflated from 0.05 to 0.071. The difference of RMTIs between the two groups evaluated at day 28 was -1.67 days (95% CI -3.62 to 0.28; P=.09) in favor of lopinavir-ritonavir but not statistically significant. For the remdesivir trial of Wang et al, the difference of RMTIs at day 28 was -0.89 days (95% CI -2.84 to 1.06; P=.37). The planned sample size was 453, yet only 236 patients were enrolled. The conditional prediction shows that the hazard ratio estimates would reach statistical significance if the target sample size had been maintained. For the remdesivir trial of Beigel et al, the difference of RMTRs between the remdesivir and placebo groups at day 30 was -2.7 days (95% CI -4.0 to -1.2; P<.001), confirming the superiority of remdesivir. The difference in the recovery time at the 25th percentile (95% CI -3 to 0; P=.65) was insignificant, while the differences became more statistically significant at larger percentiles. CONCLUSIONS: Based on the statistical issues and lessons learned from the recent three clinical trials on COVID-19 treatments, we suggest more appropriate approaches for the design and analysis of ongoing and future COVID-19 trials.