scholarly journals A Bayesian reanalysis of the effects of hydroxychloroquine and azithromycin on viral carriage in patients with COVID-19

2020 ◽  
Author(s):  
Oliver James Hulme ◽  
Eric-Jan Wagenmakers ◽  
Per Damkier ◽  
Christopher Fugl Madelung ◽  
Hartwig Roman Siebner ◽  
...  
Keyword(s):  
Viral Load ◽  
Clinical Decision Making ◽  
Safety Information ◽  
Original Data ◽  
Statistical Evidence ◽  
Product Safety ◽  
Upper Respiratory Tract ◽  
Effect Model ◽  
Positive Effect ◽  
Veterinary Product

Gautret and colleagues reported results of a non-randomised open-label case series which examined the effects of hydroxychloroquine and azithromycin on viral load in the upper respiratory tract of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients. The authors report that hydroxychloroquine (HCQ) had significant virus reducing effects, and that dual treatment of both HCQ and azithromycin further enhanced virus reduction. These data have triggered speculation whether these drugs should be considered as candidates for the treatment of severe COVID-19. However, questions have been raised regarding the study’s data integrity, statistical analyses, and experimental design. We therefore reanalysed the original data to interrogate the main claims of the paper. Here we apply Bayesian statistics to assess the robustness of the original paper’s claims by testing four variants of the data: 1) The original data; 2) Data including patients who deteriorated; 3) Data including patients who deteriorated with exclusion of untested patients in the comparison group; 4) Data that includes patients who deteriorated with the assumption that untested patients were negative. To ask if HCQ monotherapy is effective, we performed an A/B test for a model which assumes a positive effect, compared to a model of no effect. We find that the statistical evidence is highly sensitive to these data variants. Statistical evidence for the positive effect model ranged from strong for the original data (BF+0 ∼11), to moderate when including patients who deteriorated (BF+0 ∼4.35), to anecdotal when excluding untested patients (BF+0 ∼2), and to anecdotal negative evidence if untested patients were assumed positive (BF+0 ∼0.6). To assess whether HCQ is more effective when combined with AZ, we performed the same tests, and found only anecdotal evidence for the positive effect model for the original data (BF+0 ∼2.8), and moderate evidence for all other variants of the data (BF+0 ∼5.6). Our analyses only explore the effects of different assumptions about excluded and untested patients. These assumptions are not adequately reported, nor are they justified in the original paper, and we find that varying them causes substantive changes to the evidential support for the main claims of the original paper. This statistical uncertainty is exacerbated by the fact that the treatments were not randomised, and subject to several confounding variables including the patients consent to treatment, different care centres, and clinical decision-making. Furthermore, while the viral load measurements were noisy, showing multiple reversals between test outcomes, there is greater certainty around other clinical outcomes such as the 4 patients who seriously deteriorated. The fact that all of these belonged to the HCQ group should be assigned greater weight when evaluating the potential clinical efficacy of HCQ. Randomised controlled trials are currently underway, and will be critical in resolving this uncertainty as to whether HCQ and AZ are effective as a treatment for COVID-19.WarningThere have been reports of people self-administering chloroquine phosphate (intended for treatment of disease in aquarium fish), which has led to at least one death and one serious illness. We state that under no circumstances should people self-administer hydroxychloroquine, chloroquine phosphate, azithromycin, or anything similar-sounding, or indeed any other drug, unless approved by a medical doctor. The FDA has issued a specific warning: https://www.fda.gov/animal-veterinary/product-safety-information/fda-letter-stakeholders-do-not-use-chloroquine-phosphate-intended-fish-treatment-covid-19-humans

scholarly journals A Bayesian reanalysis of the effects of hydroxychloroquine and azithromycin on viral carriage in patients with COVID-19

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245048
Author(s):  
Oliver James Hulme ◽  
Eric-Jan Wagenmakers ◽  
Per Damkier ◽  
Christopher Fugl Madelung ◽  
Hartwig Roman Siebner ◽  
...  
Keyword(s):  
Case Series ◽  
Original Data ◽  
Statistical Evidence ◽  
Negative Evidence ◽  
Upper Respiratory Tract ◽  
Group 4 ◽  
Effect Model ◽  
Highly Sensitive ◽  
B Test ◽  
Positive Effect

Gautret and colleagues reported the results of a non-randomised case series which examined the effects of hydroxychloroquine and azithromycin on viral load in the upper respiratory tract of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients. The authors reported that hydroxychloroquine (HCQ) had significant virus reducing effects, and that dual treatment of both HCQ and azithromycin further enhanced virus reduction. In light of criticisms regarding how patients were excluded from analyses, we reanalysed the original data to interrogate the main claims of the paper. We applied Bayesian statistics to assess the robustness of the original paper’s claims by testing four variants of the data: 1) The original data; 2) Data including patients who deteriorated; 3) Data including patients who deteriorated with exclusion of untested patients in the comparison group; 4) Data that includes patients who deteriorated with the assumption that untested patients were negative. To ask if HCQ monotherapy was effective, we performed an A/B test for a model which assumes a positive effect, compared to a model of no effect. We found that the statistical evidence was highly sensitive to these data variants. Statistical evidence for the positive effect model ranged from strong for the original data (BF+0 ~11), to moderate when including patients who deteriorated (BF+0 ~4.35), to anecdotal when excluding untested patients (BF+0 ~2), and to anecdotal negative evidence if untested patients were assumed positive (BF+0 ~0.6). The fact that the patient inclusions and exclusions are not well justified nor adequately reported raises substantial uncertainty about the interpretation of the evidence obtained from the original paper.

Analisis Pengaruh Kepemilikan Blockholder, Kepemilikan Manajerial, Kepemilikan Institusional, dan Komite Audit terhadap Nilai Perusahaan

2018 ◽  
Vol 2 (1) ◽  
pp. 96-121
Author(s):  
Iwan Wirawardhana ◽  
Meco Sitardja
Keyword(s):  
Firm Value ◽  
Audit Committee ◽  
Stock Exchange ◽  
Random Effect ◽  
Random Effect Model ◽  
Institutional Ownership ◽  
Managerial Ownership ◽  
Estimation Model ◽  
Effect Model ◽  
Positive Effect

The aim of this study is to analyse the effect of Blockholder Ownership, Managerial Ownership,Institutional Ownership, and Audit Committee towards Firm Value. The background of this research isthe agency theory and ownership theory. The population in this study are 46 property companies listedon the Indonesia Stock Exchange (IDX) for the period 2012-2016. By using purposive samplingtechnique, 35 companies are qualified as data samples. This research uses the random effect model asthe estimation model and multiple regression as the method of analysis. The results of this study showsthat Institutional Ownership has a positive effect on Firm Value. Meanwhile, Blockholder Ownership,Managerial Ownership, and Audit Committee have no effect on Firm Value. Moreover, the F-testimplies that the variables, blockholder ownership, managerial ownership, institutional ownership, andaudit committee, simultaneously influence firm value.

scholarly journals Pengaruh Kualitas Pengungkapan Keuangan dan Struktur Kepemilikan Terhadap Asimetri Informasi

2021 ◽  
Vol 8 (1) ◽  
pp. 44-50
Author(s):  
Farma Andiansyah ◽  
Slamet Haryono
Keyword(s):  
Information Asymmetry ◽  
Panel Data Analysis ◽  
Fixed Effect Model ◽  
Accounting Disclosure ◽  
Effect Model ◽  
Statistical Effect ◽  
The Board Of Directors ◽  
Mobilizing Information ◽  
Positive Effect

Abstract -The presence of information asymmetry increases transaction costs and reduces liquidity, and reduces the quality of investment decisions taken by investors. So that in turn it weakens the overall function of the market. Accounting disclosure plays a role in mobilizing information from management and investors so as to reduce information asymmetry. In addition, it is hoped that the presence of a concentration of investor ownership can carry out internal monitoring of the company so as to reduce information asymmetry. On the other hand, institutional investors have many incentives to access company information for their trading purposes due to the conflict of interest between outside investors and the board of directors. This study aims to determine the effect of disclosure quality and ownership structure on information asymmetry in companies listed on the Jakrta Islamic Index (JII) during the 2015-2019 period. Based on the results of panel data analysis of the Fixed Effect Model (FEM), it was found that institutional ownership had a significant positive effect on information asymmetry, while the quality of disclosure and ownership concentration did not have a statistical effect on information asymmetry.

scholarly journals Rapid Diagnosis of SARS-CoV-2 Pneumonia on Lower Respiratory Tract Specimens

2021 ◽  
Author(s):  
Vanessa De Pace ◽  
Patrizia Caligiuri ◽  
Valentina Ricucci ◽  
Nicola Nigro ◽  
Barbara Galano ◽  
...  
Keyword(s):  
Intensive Care ◽  
Viral Load ◽  
Respiratory Tract ◽  
Intensive Care Units ◽  
Lower Respiratory Tract ◽  
Clinical Decision Making ◽  
High Viral Load ◽  
Rt Pcr ◽  
Predictive Values ◽  
Rapid Pcr

Abstract Background: The ongoing pandemic of SARS-CoV-2 requires the availability of accurate and rapid diagnostic tests, especially in some clinical settings like emergency and intensive care units. The objective of this study was to evaluate the diagnostic performances of rapid PCR kit Vivalytic SARS-CoV-2 in lower respiratory tract (LRT) specimens.Methods: A consecutive sample of LRT specimens (bronchoalveolar lavage and bronchoaspirates) was collected from Intensive Care Units of San Martino Hospital (Genoa, Italy) between November 2020 and January 2021. All samples were tested in RT-PCR by using Allplex™ SARS-CoV-2 assay (Seegene Inc., South Korea). Based on RT-PCR results, specimens were categorized into negative, positive with high viral load [cycle threshold (Ct) ≤30] and positive with low viral load (Ct of 31–35). A quota 1:1:1 sampling was used to achieve a sample size of 75. Then, all specimens were tested in the rapid PCR assay Vivalytic SARS-CoV-2 (Bosch Healthcare Solutions GmbH, Germany). The diagnostic performance of the rapid PCR against RT-PCR was assessed through calculation of accuracy, Cohen’s κ, sensitivity, specificity and expected positive (PPV) and negative (NPV) predictive values.Results: The overall diagnostic accuracy of the Vivalytic SARS-CoV-2 was 97.3% (95% CI: 90.9–99.3%) with an excellent Cohen’s κ of 0.94 (95% CI: 0.72–1). The sensitivity and specificity were 96% (95% CI: 86.5–98.9%) and 100% (95% CI: 86.7–100%), respectively. Samples with high viral loads had a sensitivity of 100% (Table 1). The distributions of E gene Ct values were similar (Wilcoxon’s test: P=0.070) with medians of 35 (IQR: 25–36) and 35 (IQR: 25–35), respectively (Figure 1). NPV and PPV was 92.6% and 100%, respectively.Conclusions: This study shows Vivalytic SARS-CoV-2 can be used following the sample liquefaction on LRT specimens. It’s a feasible and highly accurate molecular procedure especially in high viral load samples. This assay allows having a result in about 40 min and therefore may accelerate the clinical decision making in urgent/emergency situations.

scholarly journals Modelling upper respiratory viral load dynamics of SARS-CoV-2

BMC Medicine ◽  
2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Joseph D. Challenger ◽  
Cher Y. Foo ◽  
Yue Wu ◽  
Ada W. C. Yan ◽  
Mahdi Moradi Marjaneh ◽  
...  
Keyword(s):  
Viral Load ◽  
Immune Responses ◽  
Mechanistic Model ◽  
Severity Of Illness ◽  
Upper Respiratory Tract ◽  
Neutralising Antibodies ◽  
Immune Mediated ◽  
Peak Viral Load ◽  
Upper Respiratory ◽  
Serial Measurements

AbstractRelationships between viral load, severity of illness, and transmissibility of virus are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with the control of the viral load. Neutralising antibodies correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralising antibodies. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions.

Systematic Review and Meta-analysis of Pirfenidone, Nintedanib, and Pamrevlumab for the Treatment of Idiopathic Pulmonary Fibrosis

2020 ◽  
pp. 106002802096445
Author(s):  
Enrica Di Martino ◽  
Alessio Provenzani ◽  
Patrizio Vitulo ◽  
Piera Polidori
Keyword(s):  
Systematic Review ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
World Health ◽  
Effect Model ◽  
All Cause Mortality ◽  
Positive Effect

Background: The comparative efficacy of pirfenidone, nintedanib, and pamrevlumab in slowing the rate of forced vital capacity (FVC) decline and mortality in patients with idiopathic pulmonary fibrosis (IPF) is unknown. Objective: To perform a systematic review and meta-analysis (MA) of these drugs for IPF. Methods: We searched CENTRAL, PubMed, EMBASE, ClincalTrials.gov, and the World Health Organization’s registry databases up to March 2020. Phase II/III randomized controlled trials in adults with IPF were eligible. The random-effect model was implemented calculating the effect size and respective 95% CI as Cohen’s d for change from baseline FVC (in percentage predicted and liters) and odds ratio (OR) for 10% reduction in FVC and all-cause mortality (ACM). Results: Six studies were included in the MA. For change from baseline in percentage predicted FVC, the MA indicated that the 3 drugs were more effective than placebo (pirfenidone: d=3.30%, 95% CI=2.15-4.45; nintedanib: d=3.15%, 95% CI=2.35-3.95; pamrevlumab: d=4.30%, 95% CI=0.45-8.15). These results are superimposable to those relating to change from baseline FVC in liters (pirfenidone: d=0.09L, 95% CI=0.04-0.14; nintedanib: d=0.13L, 95% CI=0.10-0.16; pamrevlumab: d=0.20L, 95% CI=0.05-0.35). Each drug had a positive effect on 10% reduction in FVC (pirfenidone: OR=0.57, 95% CI=0.45-0.74; nintedanib: OR=0.66, 95% CI=0.51-0.85; pamrevlumab: OR=0.24, 95% CI=0.08-0.73), but only pirfenidone showed an effect on ACM (OR=0.50; 95% CI=0.31-0.83). Conclusion and Relevance: This MA provided encouraging results on pamrevlumab efficacy in slowing the decline in FVC compared with pirfenidone and nintedanib. Actually, in phase 3, it could become a potential IPF treatment.

scholarly journals Effects of hydrokinesitherapy on balance and walking ability in stroke survivors: a systematic review and meta-analysis of randomized controlled studies

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Guanli Xie ◽  
Tao Wang ◽  
Bo Jiang ◽  
Yan Su ◽  
Xiaoxia Tang ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Fixed Effect Model ◽  
Fixed Effect ◽  
Sufficient Evidence ◽  
Cochrane Library ◽  
Stroke Survivors ◽  
Walking Ability ◽  
Balance Function ◽  
Effect Model ◽  
Positive Effect

Abstract Background Balance and walking impairment are common dysfunctions after stroke. Emerging data has demonstrated that hydrokinesitherapy may have a positive influence on improvement of balance and walking ability. However, there is no firm evidence to support these results. Therefore, the aim of this review is to evaluate the effects of hydrokinesitherapy in stroke survivors systematically. Methods Medline, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, CINAHL and SPORTDiscus were systemic searched from their inception to Septemter 30, 2018. RevMan 5.3 software was used to perform data synthesis. The fixed-effect model or random-effect model was employed according to the results of heterogeneity test. The mean differences (MD) or standardized mean difference (SMD) was used to evaluate the pooled effect of hydrokinesitherapy on balance function, walking ability and activty of daily life (ADL). Results A total of 13 studies were included involving 381 stroke survivors. Meta-analysis results indicated that hydrokinesitherapy could improve balance ability based on three test: Berg balance scale (BBS: MD = 3.84, 95% confidence interval (95% CI) 2.84 to 4.86, P < 0.001), Time Up To Go Test (TUGT: MD = − 1.22, 95% CI − 2.25 to − 0.18, P = 0.02, fixed-effect model), Functional Reach Test (FRT: MD = 2.41, 95% CI 1.49 to 3.33, P < 0.001). Additionally, we found a weakly positive effect on walking speed (SMD = 0.75, 95% CI 0.26 to 1.25, P = 0.003) and walking ability test (SMD = 0.36, 95% CI 0.04 to 0.68, P = 0.03). There was no significant difference between experimental group and control group in terms of ADL. Short conclusion Hydrokinesitherapy can improve balance function and had a weakly positive effect on walking ability in stroke survivors. We did not find sufficient evidence to indicate that hydrokinesitherapy could improve the ADL of stroke survivors. However, due to the methodological shortcoming and small number of included studies, caution is needed when interpreting these results. Due to imprecision and publication bias, the quality of the evidence was downgraded to “low-quality” for the primary outcomes of balance and walking ability. Trial registration CRD42018110787.

scholarly journals Recommendations on the Use of Mobile Applications for the Collection and Communication of Pharmaceutical Product Safety Information: Lessons from IMI WEB-RADR

Drug Safety ◽  
2019 ◽  
Vol 42 (4) ◽  
pp. 477-489 ◽  
Author(s):  
Carrie E. Pierce ◽  
Sieta T. de Vries ◽  
Stephanie Bodin-Parssinen ◽  
Linda Härmark ◽  
Phil Tregunno ◽  
...  
Keyword(s):  
Mobile Applications ◽  
Safety Information ◽  
Pharmaceutical Product ◽  
Product Safety

scholarly journals Can the Famous University Experience of Top Managers Improve Corporate Performance? Evidence from China

2019 ◽  
Vol 11 (24) ◽  
pp. 6975
Author(s):  
Weifeng Xu ◽  
Qingsong Ruan ◽  
Chang Liu
Keyword(s):  
Corporate Performance ◽  
Top Management Team ◽  
Listed Companies ◽  
Fixed Effect Model ◽  
Top Managers ◽  
Effect Model ◽  
University Experience ◽  
The Impact ◽  
Business Complexity ◽  
Positive Effect

With the continuous improvement of China’s overall education level, the number of top managers with famous university experience in listed companies has been increasing. The question then becomes whether the performance of the listed companies is better if there are more top managers with famous university experience in the top management team (TMT). Based on the sample of listed companies in China from 2008 to 2018, we adopted the two-way fixed effect model and panel propensity score matching (Panel-PSM) methodology to examine the impact of top managers with famous university experience on corporate performance and its mechanism. We found that the higher the proportion of top managers with famous university experience in the TMT, the better the corporate performance will be, and this positive effect is larger in companies with high business complexity. We also found that this effect is mediated by overconfidence of the TMT. The proportion of top managers with famous university experience in the TMT will inhibit the overconfidence of the TMT, which will ultimately benefit corporate performance.

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