Observational Study of Chlorpromazine in Hospitalized Patients with Covid-19

On the grounds of its anti-inflammatory and potential antiviral effects, chlorpromazine has been suggested to be effective treatment for Covid-19. We examined the association between chlorpromazine use and respiratory failure among all hospitalized adults with Covid-19 at the 39 Greater Paris University hospitals since the beginning of the epidemic. Study baseline was defined as the date of hospital admission. The primary endpoint was a composite of intubation or death in a time-to-event analysis adjusting for numerous potential confounders. We used a multivariable Cox model with inverse probability weighting according to the propensity score. Of the 12,217 adult inpatients with a positive Covid-19 RT-PCR test included in the analyses, 57 (0.47%) received chlorpromazine. Over a mean follow-up of 20.8 days, the primary endpoint occurred in 29 patients (50.9%) exposed to chlorpromazine and 1,899 patients (15.6%) who were not. In the main analysis, there was a positive significant association between chlorpromazine use and the outcome (HR, 1.67; 95% CI, 1.09 to 2.56, p=0.019), while a Cox regression in a matched analytic sample yielded non-significant association (1.38; 95% CI, 0.91 to 2.09, p=0.123). These findings suggest that chlorpromazine is unlikely to have a clinical efficacy for Covid-19.

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From positive to negative: a time to event analysis in Regione Lombardia.

10.21203/rs.3.rs-97923/v2 ◽

2020 ◽

Author(s):

Gabriele Del Castillo ◽

Ambra Castrofino ◽

Francesca Grosso ◽

Giuseppe Marano ◽

Patrizia Boracchi ◽

...

Keyword(s):

Time Span ◽

Positive Patient ◽

Event Analysis ◽

Time To Event ◽

Rt Pcr ◽

Rna Detection ◽

Time To Death ◽

Cumulative Probabilities

Abstract Objectives. To assess the time span from positive to negative SARS-CoV-2 RNA detection by RT-PCR, and to evaluate the reliability of the test-based criteria as the required condition for the reintroduction of the asymptomatic SARS-CoV-2 positive patient in the community. Methods. We used information concerning negativization and the respective times. Cumulative probabilities of negativization during the follow-up were evaluated by Crude Cumulative Incidences (CCIs). Non-parametric estimates of CCIs and respective 95% C.I.s were obtained.Results. We report only the results for 52,186 individuals. 33486 subjects resulted negative or potentially negative with a CCI of 75.2% at 70 days from the first swab (95% CI: 74.8% to 75.7%). 11,000 subjects deceased before 14/05/2020 without diagnosis of negative status (CCI 21.9%; 95% CI: 21.5% to 22.3%), at 56 days from the first swab (maximum observed time to death).Conclusions. SARS-CoV-2 positivity is a condition that frequently lasts more than 30 days. Since the determination of isolation based only on a status of positivity could be excessive, more solid studies are required to determinate the significance of a prolonged state of positivity and the consequences on the policies of dismission of quarantine and isolation.

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From positive to negative: a time to event analysis in Regione Lombardia.

10.21203/rs.3.rs-97923/v1 ◽

2020 ◽

Author(s):

Gabriele Del Castillo ◽

Ambra Castrofino ◽

Francesca Grosso ◽

Giuseppe Marano ◽

Patrizia Boracchi ◽

...

Keyword(s):

Time Span ◽

Positive Patient ◽

Event Analysis ◽

Time To Event ◽

Rt Pcr ◽

Rna Detection ◽

Time To Death ◽

Cumulative Probabilities ◽

Non Parametric

Abstract Objectives. To assess the time span from positive to negative SARS-CoV-2 RNA detection by RT-PCR, and to evaluate the reliability of the test-based criteria as the required condition for the reintroduction of the asymptomatic SARS-CoV-2 positive patient in the community. Methods. We used information concerning negativization and the respective times. Cumulative probabilities of negativization during the follow-up were evaluated by through Crude Cumulative Incidences (CCIs). Non-parametric estimates of CCIs and respective 95% C.I.s were obtained.Results. We report only the results for 52,186 individuals. 33486 subjects resulted negative or potentially negative with a CCI of 75.2% at 70 days from the first swab (95% CI: 74.8% to 75.7%). 11,000 subjects deceased before 14/05/2020 without diagnosis of negative status (CCI 21.9%; 95% CI: 21.5% to 22.3%) at 56 days from the first swab (maximum observed time to death).Conclusions. SARS-CoV-2 positivity is a condition that frequently lasts more than 30 days. Since isolation based only on positivity status could be excessive, more solid studies are required to determine a single internationally accepted policy regarding the dismission of quarantine and isolation.

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Association between Functional Inhibitors of Acid Sphingomyelinase and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID-19: results from an observational multicenter study

10.1101/2021.02.22.21252209 ◽

2021 ◽

Author(s):

Nicolas Hoertel ◽

Marina Sánchez-Rico ◽

Erich Gulbins ◽

Johannes Kornhuber ◽

Alexander Carpinteiro ◽

...

Keyword(s):

Primary Endpoint ◽

Randomized Clinical Trials ◽

Cox Regression ◽

Acid Sphingomyelinase ◽

Sensitivity Analyses ◽

University Hospitals ◽

Primary Analysis ◽

Double Blind ◽

Treatment Target

ABSTRACTSeveral medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the (ASM)/ceramide system may be central to SARS-CoV-2 infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe COVID-19 in an observational multicenter retrospective study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking a FIASMA medication at the time of their hospital admission. The primary endpoint was a composite of intubation and/or death. We compared this endpoint between patients taking vs. not taking a FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD=12.5), the primary endpoint occurred in 104 patients (37.5%) who were taking a FIASMA medication, and 1,060 patients (41.4%) who were not. Taking a FIASMA medication was associated with reduced likelihood of intubation or death in both crude (HR=0.71; 95%CI=0.58-0.87; p<0.001) and the primary IPW (HR=0.58; 95%CI=0.46-0.72; p<0.001) analyses. This association remained significant in multiple sensitivity analyses and was not specific to one FIASMA class or medication. These results show the potential importance of the ASM/ceramide system as a treatment target in COVID-19. Double-blind controlled randomized clinical trials of these medications for COVID-19 are needed.

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Clinical significance of Q waves in ischemic cardiomyopathy

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.340 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

E Rodenas Alesina ◽

P Jordan ◽

L Herrador ◽

C Espinet-Coll ◽

N Pizzi ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Primary Endpoint ◽

Ischemic Cardiomyopathy ◽

Cox Regression ◽

Cox Model ◽

Cardiovascular Death ◽

P Value ◽

Heart Failure Hospitalization ◽

Total Cohort

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): CIBER-CV AIMS The scintigraphic translation of Q waves in patients with ischemic cardiomyopathy and LVEF < 40% has not yet been assessed. The aim of this study was to explore the relationship between Q waves and necrotic tissue and to analyze their impact in prognosis. METHODS AND RESULTS A retrospective study enrolling 487 consecutive patients (67,0 [57,4 – 75,4] years), with ischemic cardiomyopathy, LVEF <40% and narrow QRS who underwent stress-rest SPECT was conducted. Patients with Q waves (320 patients [65,7%]) had less comorbidity and ischemia, but more necrosis. Q waves correlated poorly with lack of viability (AUC = 0,63) and were independently associated with the subendocardial extent of the necrosis. After a follow-up of 5,07 years, the primary outcome (cardiovascular death, heart failure hospitalization or myocardial infarction) occurred in 192 (39,4%) patients, without differences between groups in multivariate analysis. After accounting for non-cardiovascular death as a competitive risk, the interaction between >10% of ischemia and revascularization remained in Cox model both in the total cohort (aHR= 0,46 [0,24 – 0,86]), and in patients with Q waves (aHR = 0,27 [0,11–0,69]). CONCLUSION Patients with ischemic cardiomyopathy with Q waves have larger subendocardial scarring and more transmural necrosis, although correlation between Q waves and transmural scarring is poor. Revascularization if >10% ischemia is present is associated with a better prognosis. Ischemia burden should be assessed and accordingly treated in these patients, and no differences in management should be made in the presence of Q waves. Table 1. Cox proportional hazards model Total cohort (N = 471) Patients with Q waves (N = 315) aHR p-value 95% CI aHR p-value 95% CI Age (per year) 1,02 0,007 1,01 - 1,04 n.s. Diabetes mellitus 1,35 0,047 1,00 - 1,81 1,54 0,016 1,09 - 2,20 eGFR < 60 ml/min 1,59 0,005 1,15 - 2,21 1,96 <0,001 1,36 - 2,82 Previous HF hospitalization 1,71 0,002 1,23 - 2,38 1,76 0,007 1,17 - 2,64 Previous PCI 1,32 0,069 0,98 - 1,78 n.s. Previous CABG n.s. 1,77 0,009 1,15 - 2,72 Angina or dyspnea 1,68 0,001 1,24 - 2,28 1,71 0,004 1,19 - 2,46 Indexed TDV (per quartile) 1,16 0,047 1,02 - 1,33 n.s. Revascularization*ischemia > 10% 0,46 0,015 0,24 - 0,86 0,27 0,006 0,11 - 0,69 Cox regression for the primary endpoint (cardiovascular death, heart failure hospitalization or myocardial infarction), accounting for non-cardiovascular death as a competitive risk. Abstract Figure. Survival for the primary endpoint

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Survival analysis

Epidemiology with R ◽

10.1093/oso/9780198841326.003.0009 ◽

2020 ◽

pp. 181-218

Author(s):

Bendix Carstensen

Keyword(s):

Survival Analysis ◽

Competing Risks ◽

Cox Model ◽

Survival Function ◽

Event Analysis ◽

Time To Event ◽

Poisson Models ◽

Kaplan Meier ◽

Analysis Survival ◽

Event Rates

This chapter describes survival analysis. Survival analysis concerns data where the outcome is a length of time, namely the time from inclusion in the study (such as diagnosis of some disease) till death or some other event — hence the term 'time to event analysis', which is also used. There are two primary targets normally addressed in survival analysis: survival probabilities and event rates. The chapter then looks at the life table estimator of survival function and the Kaplan–Meier estimator of survival. It also considers the Cox model and its relationship with Poisson models, as well as the Fine–Gray approach to competing risks.

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A Multicenter Randomized Placebo Controlled Trial of Compression Stockings to Prevent the Post-Thrombotic Syndrome After Proximal Deep Venous Thrombosis: The S.O.X. Trial

Blood ◽

10.1182/blood.v120.21.393.393 ◽

2012 ◽

Vol 120 (21) ◽

pp. 393-393 ◽

Cited By ~ 3

Author(s):

Susan R. Kahn ◽

Stan Shapiro ◽

Phil S Wells ◽

Marc A. Rodger ◽

Michael J. Kovacs ◽

...

Keyword(s):

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Cumulative Incidence ◽

Research Funding ◽

Primary Outcome ◽

Controlled Trial ◽

Event Analysis ◽

Time To Event ◽

Compression Stockings

Abstract Abstract 393 Background: The post-thrombotic syndrome (PTS) is a burdensome, costly complication of deep venous thrombosis (DVT). Investigating strategies to prevent PTS is important, as treatments for PTS are limited. To date, randomized trials of elastic compression stockings (ECS) to prevent PTS were small, single-center, none used a placebo control and results are conflicting. Objective: To determine whether ECS, compared with inactive (placebo) stockings, are effective to prevent PTS in patients with proximal DVT. Methods: We conducted a multicenter (24 centres, Canada and U.S.) randomized placebo controlled trial of active ECS (A-ECS) vs. placebo ECS (P-ECS) to prevent PTS after a first, symptomatic proximal DVT. A-ECS were knee length 30–40 mm Hg (Class II) graduated ECS. P-ECS were manufactured to look identical to A-ECS but lacked therapeutic compression. Stockings were mailed directly to patients and worn on the DVT-affected leg daily for up to 2 years. Patients did not wear their stockings at study follow-up visits (1, 6, 12, 18 and 24 months) to maintain study personnel blinding. The primary study outcome, PTS, was diagnosed at or after the 6 month visit using the Ginsberg measure (leg pain and swelling of 3 1 month duration and typical in character: worse end of day or after prolonged sitting/standing and improved after rest/leg elevation). All PTS diagnoses were confirmed by the local study physicians. Secondary outcomes were incidence and severity of PTS using the Villalta scale, venous ulcers, VTE recurrence and death from VTE. A sample size of 800 patients was targeted based on a hypothesized cumulative incidence of the primary outcome of 30% in P-ECS vs. 20% in A-ECS, 2-tailed a of 0.05 and 80% power, and anticipated 25% rate of death/withdrawal/lost-to-follow-up. Using a modified intent to treat approach, we performed a time-to-event analysis using a Cox proportional hazards model adjusted for center to calculate hazard ratios (HR) and 95% confidence intervals (CI) to compare rates of the primary outcome in A-ECS vs. P-ECS. A similar time-to-event analysis was performed for Villalta PTS (Villalta score ≥ 5 at or after the 6 month visit). Results: From 2004–2010, 398 patients were randomized to A-ECS and 408 to P-ECS. 3 patients found to be ineligible soon after randomization were excluded from the analysis. Median time from DVT diagnosis to randomization was 4 days. Baseline features were similar in the 2 groups; overall, 60% were male, mean age was 55 years, and most proximal extent of DVT was iliac or femoral vein in 70% and popliteal vein in 30% of patients. The cumulative incidence of PTS (primary outcome) by 750 days was 14.8% in A-ECS vs. 12.3% in P-ECS (Figure) (HRadj 1.17; 95% CI 0.75–1.81; p=0.49). The cumulative incidence of Villalta PTS (secondary outcome) was 52.1% in A-ECS vs. 52.2% in P-ECS (HRadj 0.96; 95% CI 0.78–1.19; p=0.69). Additional outcomes were also similar in the two intervention groups (Table). Rates of loss to follow-up (5.5% vs. 5.4%) and withdrawal (8.3% vs. 9.1%) were similar in A-ECS and P-ECS. Overall, ∼70% of patients in both groups continued the intervention throughout study follow-up, and of these, >80% of patients in both groups reported use for ≥ 3 days per week. Conclusions: In a large randomized placebo-controlled trial, ECS did not prevent the occurrence of PTS after a first proximal DVT and did not influence the severity of PTS or rate of recurrent VTE. The reported benefits of ECS to prevent PTS in some prior studies could be due, at least in part, to bias from open-label design. Whether ECS may be of benefit to manage symptoms of established PTS should be evaluated in future studies. Disclosures: Kahn: NIH: Research Funding; Canadian Institutes for Health Research: Research Funding; Sigvaris: Research Funding.

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PMH3 FOLLOW-UP OF SCHIZOPHRENIA PATIENTS DISCHARGED ON RISPERIDONE OR OLANZAPINE: A TIME-TO-EVENT ANALYSIS

Value in Health ◽

10.1016/s1098-3015(10)66073-1 ◽

2004 ◽

Vol 7 (6) ◽

pp. 776-777

Author(s):

I Adriaenssen ◽

D Rosillon ◽

A Mehnert ◽

M Price ◽

M Ingham

Keyword(s):

Event Analysis ◽

Time To Event

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From positive to negative: a time to event analysis during the first COVID 19 epidemic period

10.21203/rs.3.rs-97923/v3 ◽

2021 ◽

Author(s):

Gabriele Del Castillo ◽

Silvana Castaldi ◽

Giuseppe Marano ◽

Ambra Castrofino ◽

Francesca Grosso ◽

...

Keyword(s):

Public Health Practice ◽

Contact Tracing ◽

Event Analysis ◽

Time To Event ◽

Rna Detection ◽

Time To Death ◽

Epidemic Period ◽

Conversion Time ◽

Negative Conversion

Abstract BackgroundThe ability to identify the positive subjects is crucial for public health practice to reduce transmission and supporting contact tracing and isolation. The reliability of the criteria of the test-based criteria as the required condition for the reintroduction of the asymptomatic and positive patients of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the community was evaluated assessing the time span from positive to negative for RNA detection by Real Time – Polymerase Chain Reaction (RT-PCR). Methods. We used information concerning negative conversion time and the respective times. Cumulative probabilities of negative conversion time during the follow-up were evaluated by Crude Cumulative Incidences (CCIs). Non-parametric estimates of CCIs and respective 95% C.I.s were obtained.Results. We report the results for 52,186 individuals. 33486 subjects resulted negative or potentially negative with a CCI of 75.2% at 70 days from the first swab (95% CI: 74.8% to 75.7%). 11,000 subjects deceased before 14/05/2020 without diagnosis of negative status (CCI 21.9%; 95% CI: 21.5% to 22.3%), at 56 days from the first swab (maximum observed time to death).Conclusions. SARS-CoV-2 positivity is a condition that frequently lasts more than 30 days. More solid studies are required to determinate the significance of a prolonged state of positivity and the consequences on the policies of dismission of quarantine and isolation.

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Associated Factories and Time to Occurrence of Tuberculosis Among Children on HIV/AIDS Care in Assosa and Pawe General Hospitals North West Ethiopia: A Retrospective Cohort Study 2020

10.21203/rs.3.rs-118270/v1 ◽

2020 ◽

Author(s):

Fassikaw kebede Bizuneh ◽

Tadese Tollosa Daba ◽

Belayneh Mengist Mitike ◽

Tamrat sheawno Fikretsion ◽

Belete Negese Negese

Keyword(s):

Cohort Study ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Cox Regression ◽

Cox Model ◽

Incidence Density ◽

Human Immune Deficiency Virus ◽

Cox Regression Analysis ◽

Hiv Aids

Abstract Background: Tuberculosis (TB) incidence in peadtrics and children living with human immune-deficiency virus (HIV) is an emerging global concern. Although, the incidence of TB among adult HIV patients is exhaustively studied in Ethiopia, but among children on HIV/AIDS care is overlooked. Knowledge of the time when TB develops during successive follow up could be helpful for time relevant intervention strategies.Methods: health institution based retrospective cohort study conducted among 421 children on HIV/AIDS from 2009-2018. Time to develop TB was defined as time from enrollment for ART care until development of TB among children on ART. Proportional hazard assumption was checked for each variable and no variable was found with Schoenfeld test <0.05. Variables with P-value <0.25 at bivariate Cox regression analysis were entered into multivariable Cox model. Multivariable Cox regression model with 95%CI and AHR was used to identify significant predictor variables to develop TB at P< 0.05.Result: Totally 421 children were followed for a total of 662.5 Person Years of observation (PYO). The maximum and minimum follow up time on ART was 0.37 and 4.49 years, respectively. The median age of the children on ART at enrollment was 8 years (IQR=2-15). The Overall incidence density of tuberculosis in HIV infected children was 9.6/ 100 PYOs 95%CI (8.06-10.3). Tuberculosis occurrence among HIV infected children was significantly associated within TB history of contact AHR=3.7, 95%CI (2.89-7.2), not started on cotrimoxazole(CPT) AHR=2.4: 95%CI (1.84-4.74), incomplete vaccination AHR=2.4, 95%CI (1.32-4.5), sever stunting AHR =2.99:95%CI (1.2-7.81), having hemoglobin (Hgb) ≤10 mg/dl AHR = 4.02, 95%CI (2.01-8.1).Conclusion: More than 80% of TB incidences occurred during two years of follow up after ART started. So intensified screening of CPT& therapeutic feeding is highly recommended for all children.

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Barriers to applying for medical rehabilitation: a time-to-event analysis of employees with severe back pain in Germany

Journal of Rehabilitation Medicine ◽

10.2340/jrm.v53.1408 ◽

2022 ◽

Author(s):

Julia-Marie Zimmer ◽

David Fauser ◽

André Golla ◽

Andreas Wienke ◽

Nadine Schmitt ◽

...

Keyword(s):

Back Pain ◽

Cox Regression ◽

Medical Rehabilitation ◽

Event Analysis ◽

Pension Insurance ◽

Randomized Sampling ◽

Severe Back Pain ◽

Physician Support ◽

Age Range

Objective: Longitudinal studies on barriers to applying for rehabilitation in Germany are lacking in light of the suspected underutilization of rehabilitation services. The aim of this study was to examine application behaviour in persons with disabling back pain and to identify relevant predictors for making an application. Design: A prospective cohort study with randomized sampling of insurants in the German Pension Insurance, using a questionnaire at baseline and follow-up with linked administrative data for 1.5 years. Subjects/patients: Employed persons (age range 45–59 years) with a high degree of limitations due to back pain and a self-reported risk of permanent work disability (not applied for disability pension, no medical rehabilitation within the last 4 years). Methods: Multivariable Cox regression was used to examine the influence of pre-selected variables on making an application in the follow-up period. Results: Of 690 persons, only 12% applied for rehabilitation. Predictors for making an application were: support from physicians (hazard ratio (HR)=2.24; 95% confidence interval (95% CI) 1.32–3.80), family, and friends (HR=1.67; 95% CI 1.02–2.73), more pain-related disability days (HR=1.02; 95% CI 1.01–1.03), and worse work ability (HR=0.86; 95% CI 0.75–0.97). An intention to apply at baseline mediated the effect of family and physician support on the application. Conclusion: The low number of applications for rehabilitation despite disabling back pain indicates access barriers to, and underuse of, medical rehabilitation.

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