Real world evidence of calcifediol or vitamin D prescription and mortality rate of COVID-19 in a retrospective cohort of hospitalized Andalusian patients

AbstractCOVID-19 is a major worldwide health problem because of acute respiratory distress syndrome, and mortality. Several lines of evidence have suggested a relationship between the vitamin D endocrine system and severity of COVID-19. We present a survival study on a retrospective cohort of 15,968 patients, comprising all COVID-19 patients hospitalized in Andalusia between January and November 2020. Based on a central registry of electronic health records (the Andalusian Population Health Database, BPS), prescription of vitamin D or its metabolites within 15–30 days before hospitalization were recorded. The effect of prescription of vitamin D (metabolites) for other indication previous to the hospitalization was studied with respect to patient survival. Kaplan–Meier survival curves and hazard ratios support an association between prescription of these metabolites and patient survival. Such association was stronger for calcifediol (Hazard Ratio, HR = 0.67, with 95% confidence interval, CI, of [0.50–0.91]) than for cholecalciferol (HR = 0.75, with 95% CI of [0.61–0.91]), when prescribed 15 days prior hospitalization. Although the relation is maintained, there is a general decrease of this effect when a longer period of 30 days prior hospitalization is considered (calcifediol HR = 0.73, with 95% CI [0.57–0.95] and cholecalciferol HR = 0.88, with 95% CI [0.75, 1.03]), suggesting that association was stronger when the prescription was closer to the hospitalization.

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Real world evidence of calcifediol use and mortality rate of COVID-19 hospitalized in a large cohort of 16,401 Andalusian patients

10.1101/2021.04.27.21255937 ◽

2021 ◽

Author(s):

Carlos Loucera ◽

María Peña-Chilet ◽

Marina Esteban-Medina ◽

Dolores Muñoyerro-Muñiz ◽

Román Villegas ◽

...

Keyword(s):

Vitamin D ◽

Real World ◽

Patient Survival ◽

Endocrine System ◽

Vitamin D Metabolites ◽

Survival Curves ◽

Hazard Ratios ◽

Real World Evidence ◽

Central Registry ◽

Health Database

AbstractBackgroundCOVID-19 is a major worldwide health problem because of acute respiratory distress syndrome, and mortality. Several lines of evidence have suggested a relationship between the vitamin D endocrine system and severity of COVID-19.MethodsWe present a retrospective survival study that includes all Andalusian patients hospitalized between January and November 2020 because of COVID-19 infection. Based on a central registry of electronic health records (the Andalusian Population Health Database, BPS), prescription of vitamin D or its metabolites within 15-30 days before hospitalization were recorded. The effect of treatment with vitamin D metabolites for other indication previous to the hospitalization was studied with respect to patient survival by means of Kaplan-Meyer survival curves and Log Hazard Ratios, using a propensity score to compensate the disbalance of compared classes and the confounding factors. The availability of detailed patient data in the BPS allowed to obtain Real-World Evidence (RWE) of the effects of prior use of vitamin D or its metabolites on the mortality due to COVID-19 infection.FindingsA retrospective cohort of 16.401patients was extracted from the BPS, which includes all the patients hospitalized with COVID-19 diagnosis between January and November 2020 in Andalusia, one of the largest regions in Europe with the size of an average median country. A total of 358 patients were found with cholecalciferol, and 193 with calcifediol, prescriptions 15 days before hospitalization. For a period extended to 30 days before hospitalization, the numbers increase to 416 and 210 and, respectively. Kaplan-Meyer survival curves and hazard ratios support an association between consumption of these metabolites and patient survival. Such association was stronger in calcifediol (Log Hazard Ratio, LHR = -1.27±0.32) than in cholecalciferol (LHR= -0.56±0.15), when prescribed 15 days before hospitalization This effect decreases when a larger 30 days period is considered (calcifediol LHR= -1.01±0.27 and cholecalciferol LHR= -0.27±0.12), suggesting that the closer was the treatment to the hospitalization the stronger the association.ConclusionsA significant reduction in mortality in patients hospitalized with COVID-19 is associated with the prescription of vitamin D, especially calcifediol, within 15-30 days prior to hospitalization.

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Project Switch: Docetaxel as a potential synthetic control in metastatic non-small cell lung cancer (mNSCLC) trials.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.9105 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 9105-9105 ◽

Cited By ~ 1

Author(s):

Michael E. Menefee ◽

Yutao Gong ◽

Pallavi Shruti Mishra-Kalyani ◽

Rajeshwari Sridhara ◽

Bindu Kanapuru ◽

...

Keyword(s):

Randomized Trials ◽

Progression Free Survival ◽

Experimental Therapy ◽

Synthetic Control ◽

Small Cell Lung ◽

Free Survival ◽

Kaplan Meier ◽

Hazard Ratios ◽

Real World Evidence ◽

The Impact

9105 Background: Docetaxel is a common comparator arm to test novel therapies in post-platinum mNSCLC trials. The advent of Real World Evidence (RWE) has renewed interest in the use of synthetic control arms (control arms from previously conducted randomized trials) to improve accrual to trials and increase patient access of promising experimental agents. We reviewed legacy second-line (2L) mNSCLC trials to assess the impact of switching docetaxel control arms from one trial to another and compare to an experimental regimen. Methods: We identified 5 contemporary 2L trials that enrolled 2013 patients receiving an experimental therapy vs. docetaxel: 5 immunoncology head-to-head trials (one with 2 arms) and one anti-VEGF add-on trial. Kaplan-Meier curves of overall survival (OS) and progression-free survival (PFS) were produced for docetaxel controls. We calculated OS and PFS hazard ratios and 95% confidence intervals for each synthetic trial. A pooled doc arm was also compared with each experimental agent. Results: See Table. Conclusions: Both individual and pooled docetaxel switching of control arms approximated the original OS HR and 95% CI. Methods such as bootstrapped sampling and propensity score matching will be performed in an effort to more closely approximate the original trial characteristics. [Table: see text]

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Real-world evidence: Molecular subtype and its prognostic implications of Lung-molGPA in EGFR-mutated adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21621 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21621-e21621

Author(s):

Feng-Che Kuan ◽

Chung-Sheng Shi ◽

Wei-Hsun Yang ◽

Hung-Yi Lai ◽

Chun-Chieh Huang ◽

...

Keyword(s):

Brain Metastases ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Egfr Mutations ◽

Kaplan Meier ◽

Hazard Ratios ◽

Real World Evidence ◽

Prognostic Implications ◽

Egfr Mutated ◽

Exon 19

e21621 Background: EGFR mutations are heterogenous but all carry the same weight in the Lung-molGPA. The aim of this study was to elucidate the different prognostic implications of molecular subtypes and frontline TKIs in EGFR-mutated lung adenocarcinoma with synchronous brain metastases (BM) using the Lung-molGPA. Methods: Medical records were searched in hospital databases from 2011 to 2015. Patients with EGFR-mutated adenocarcinoma and brain metastases who received TKIs were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: A total of 256 patients were included with a median overall survival (OS) of 17.2months. Patients with Lung-molGPA scores of 1, 1.5-2.0, 2.5-3.0, and 3.5-4.0 had median OS of 5.9,11.5, 17.2, and 23.4months, respectively (p < 0.001). In multivariate analysis of OS, only age (³70 versus < 70 years, HR:1.71, 95% CI:1.25-2.35, p < 0.001), KPS ( < 70 versus ³70, HR:1.71, 95% CI:1.26-2.31, p < 0.001), and rare mutations (other versus exon 19 deletions, HR:1.78, 95% CI:1.04-3.05, p = 0.037) remained statistically significant. In patients with a Lung-molGPA score £2.5, EGFR molecular subtypes had different median OS (exon 19 deletions versus Leu858Arg versus other, 18.9vs 12.8vs 4.5months, p = 0.021) and prognostic implications (Leu858Arg versus exon 19 deletions, HR: 1.85, 95% CI: 1.20-2.84, p = 0.005; other versus exon 19 deletions, HR:2.18, 95% CI:1.11-4.26, p = 0.023). Conclusions: Different molecular subtypes treated with frontline TKIs have different prognostic implications in the Lung-molGPA. Further prospective studies are warranted to validate these findings.

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Real-world evidence: Adjuvant chemotherapy in colorectal cancer with liver metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16008 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16008-e16008

Author(s):

Feng-Che Kuan ◽

Gengping Lin ◽

Chih-Chien Chin ◽

Wen Shih Huang ◽

Chung-Wei Fan ◽

...

Keyword(s):

Colorectal Cancer ◽

Survival Rate ◽

Adjuvant Chemotherapy ◽

Neoadjuvant Chemotherapy ◽

Liver Metastases ◽

Research Database ◽

Biologic Drugs ◽

Kaplan Meier ◽

Hazard Ratios ◽

Real World Evidence

e16008 Background: Systematic chemotherapy with biologics improves survival in metastatic colorectal cancer (mCRC). Oxaliplatin-based adjuvant chemotherapy is suggested in stage III and high-risk stage II CRC. However, whether adjuvant oxaliplatin-based chemotherapy remains standard treatment in CRC with liver metastases after hepatectomy is not elucidated. Methods: Medical records were searched in Chang-Gung Research Database from 2004 to 2017. Patients with CRC and liver metastases who received systematic therapies and salvage hepatectomy were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Total 454 patients received upfront hepatectomy (cohort 1) and 232 patients received neoadjuvant chemotherapy +/- biologics and salvage hepatectomy (cohort 2) were included in this study. In cohort 1 or cohort 2, the baseline characteristics of those received either postoperative oxaliplatin-containing regimen or other systematic regimens were not statistically different in gender, age, primary site, and biologic drugs. In cohort 1, overall survival (OS) in those received postoperative oxaliplatin-containing chemotherapy was significantly better than that of those received non-oxaliplatin-containing chemotherapy (median OS: 6.6 vs. 4.5 years, Log-rank p = 0.032; 5-year survival rate: 57.5 vs. 47.0%). In cohort 2, OS in those received postoperative oxaliplatin-containing chemotherapy was similar with that of those received irinotecan or biologics-containing chemotherapy (median OS: 3.1 vs. 3.5 vs. 3.8 years, Log-rank p = 0.472; 5-year survival rate: 30.9 vs. 33.3 vs. 37.0%). Conclusions: Oxaliplatin-containing chemotherapy provides better OS and remains standard adjuvant treatment in CRC with liver metastases after upfront hepatectomy. However, adjuvant chemotherapy in those received neoadjuvant chemotherapy +/- biologics and salvage hepatectomy should be individualized. Further prospective studies are warranted to validate these findings.

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Serum ANCA and Overall Mortality: A 10-Year Retrospective Cohort Study on 1,024 Italian Subjects

Frontiers in Immunology ◽

10.3389/fimmu.2021.714174 ◽

2021 ◽

Vol 12 ◽

Author(s):

Enrico Brunetta ◽

Giacomo Ramponi ◽

Marco Folci ◽

Maria De Santis ◽

Emanuela Morenghi ◽

...

Keyword(s):

Overall Survival ◽

Cohort Study ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Cox Regression ◽

Antineutrophil Cytoplasmic Antibodies ◽

Kaplan Meier ◽

Hazard Ratios ◽

Perinuclear Anca ◽

Worse Prognosis

BackgroundAntineutrophil cytoplasmic antibodies (ANCA) are primarily involved in the pathogenesis of ANCA-associated vasculitides (AAV). However, ANCA may also be present in healthy subjects and in patients with autoimmune disorders different from AAV. We hypothesized that serum ANCA are associated with a worse prognosis in disorders other than AAV.ObjectiveWe investigated the association between the overall survival and the presence of serum ANCA in 1,024 Italian subjects with various testing indications in a 10-year interval.MethodsIn this retrospective cohort study, a population of 6,285 patients (many of whom were subsequently excluded due to our criteria) who tested for ANCA at a single center in 10 years was considered, and life status and comorbidities of subjects were collected. We compared the overall survival of ANCA-positive and ANCA-negative patients by means of Kaplan-Meier curves, while a multivariable adjusted Cox regression was used to evaluate the association between the ANCA status and the outcome (death) in terms of hazard ratios (HR) with 95% confidence intervals (CI).ResultsThe positivity of perinuclear ANCA (pANCA) increased significantly mortality (HR, 1.60; 95% CI, 1.10–2.32), while cytoplasmic ANCA (cANCA) positivity failed to show a significant association (HR, 1.43; 95% CI, 0.77–2.68). The increased mortality rate was observed for both pANCA and cANCA in patients suffering from rheumatic disorders. No association was found between mortality and anti-MPO (HR, 0.63; 95% CI, 0.20–2.00) or anti-PR3 (HR, 0.98; 95% CI, 0.24–3.96) after adjusting for confounders.ConclusionsSerum pANCA and cANCA are independent negative prognostic factors in patients with concurrent autoimmune diseases.

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