AUCTORES
Globalize your Research
Research Article
*Corresponding Author: Nawab Qizilbash, MD, PhD, OXON Epidemiology, Madrid, Spain; London School of Hygiene & Tropical Medicine, London, UK.
Citation: Bélène Podmore, Nawab Qizilbash, Alessandra Lacetera, Itziar Ubillos, Kirsty Andresen, Ana Roncero Martín, Jara Majuelos-Melguizo, Ana Cuñado Moral, Marina Hinojosa Campos, Jeffrey K Aronson and Stuart Pocock (2021) Tocilizumab and Mortality in Hospitalised Patients with Covid-19. A Systematic Review Comparing Randomised Trials with Observational Studies J, Pharmaceutics and Pharmacology Research. 4(4); DOI: 10.31579/2693-7247/051
Copyright: © 2021, Nawab Qizilbash, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 08 October 2021 | Accepted: 19 October 2021 | Published: 29 October 2021
Keywords: monoclonal antibodies; epidemiology; randomised clinical trials; covid-19
Background: Early observational studies suggested that tocilizumab might produce clinical improvement in covid-19 patients leading to the use of tocilizumab. Early underpowered randomised controlled trials (RCTs) however did not show benefit until the most recent largest trial. RECOVERY trial. We aimed to compare the evidence from RCTs and observational studies of the effect of tocilizumab on in-hospital mortality in patients with covid-19.
Materials and Methods: Embase and PubMed were searched from July 2020 until 1 March 2021. Observational studies and RCTs assessing in-hospital mortality in patients receiving tocilizumab compared with standard care or placebo were included. The primary outcome was in-hospital mortality closest to 30 days. The risk of bias in observational studies was assessed using the ROBINS-I tool. A fixed effect meta-analysis was used to combine relative risks, with random effects and risk of bias as a sensitivity analysis.
Results: Of 5,792 publications screened for inclusion, eight RCTs and 33 observational studies were identified. The RCTs showed an overall relative risk reduction in in-hospital mortality at 30 days of 0.86 (95% confidence interval (CI) 0.78 to 0.96) with no statistically significant heterogeneity. 23 of the observational studies had a severe risk of bias, 10 of which did not adjust for potential confounders. The 10 observational studies with moderate risk of bias reported a larger reduction in mortality at 30-days (relative risk 0.72, 95% CI 0.64 to 0.81) but with significant heterogeneity (P<0.01).
Conclusion: This meta-analysis provides strong evidence from RCTs that tocilizumab reduces the risk of mortality in hospitalised covid-19 patients. Observational studies with moderate risk of bias exaggerated the benefits on mortality two-fold and showed heterogeneity. Collectively observational studies provide a less reliable evidence base for evaluating treatments for covid-19.
CI Confidence interval
FE Fixed effect
ICU Intensive care unit
IL-6 Interleukin-6
IPW Inverse probability weighting
RCT Randomised controlled trial
RE Random effect
TCZ Tocilizumab
Introduction
Tocilizumab, currently licensed for treatment of rheumatoid arthritis, is a monoclonal antibody that inhibits the interleukin-6 (IL-6) receptor and is being used to treat patients with severe covid-19 [1].
IL-6 is a cytokine that is released by macrophages as part of the immune response to infection. Circulating IL-6 concentrations correlate with covid-19 severity [2]. However, in severe covid-19 there is vascular inflammation and dysfunction, and IL-6 promotes endothelial dysfunction and impairs vascular permeability [3]. Tocilizumab inhibits this inflammatory process. Treatments are needed that improve survival in severely ill covid-19 patients. Severely ill patients with covid-19 have high short-term mortality rates ranging from 35% [26] to 61% [54].
At the start of the covid-19 pandemic, early case reports suggested that tocilizumab might produce clinical and biochemical improvement in covid-19 [4-6]. This was followed by reports of observational studies using retrospective data, largely supporting clinicians’ impressions of benefit in severe covid-19. This led to the use of tocilizumab, despite failure to show benefit on all-cause mortality from early underpowered randomised controlled trials (RCTs) in severe covid-19 [7]. The RECOVERY trial, the largest RCT of tocilizumab, has recently shown clear overall benefit in hospitalised patients with covid-19 of all degrees of severity, in addition to the benefit achieved with systematic corticosteroids [8].
We therefore conducted a systematic review and meta-analysis comparing both randomised trials and observational studies in the effect of tocilizumab on in-hospital mortality.
Search Strategy
A search of PubMed and Embase was conducted monthly from July 2020 until 1 March 2021, written in English, Spanish, French, and German, of treatment comparisons in hospitalised covid-19 patients and clinical outcomes. Search terms for treatment comparisons including tocilizumab and clinical outcomes were combined with search terms for study design (randomised controlled trials and observational studies separately). Where possible MeSH or index terms were used. We also searched the references in the retrieved papers for any additional relevant publications.
Eligibility
All titles, abstracts, and selected full-text articles were reviewed for eligibility by five reviewers (KA, AC, AR, MH, JM). We included observational studies (either prospective or retrospective) and RCTs that reported the effect of tocilizumab on in-hospital mortality closest to 30 days in-patients with covid-19. Observational studies were eligible if they compared tocilizumab with standard care. Earlier publications that used the same data source over the same study period as a later publication were excluded as duplicates. RCTs were eligible if they compared tocilizumab against standard care or placebo. Studies that reported only mortality at 14 days or less were excluded.
Data Extraction and Risk of bias assessment
For each RCT, data were extracted on study design (randomisation and blinding), comparator (placebo or standard care), the relative risk estimate, 95% confidence intervals (CI), p values and analytic method. For each eligible observational study, information on study design, data source, population characteristics, outcome, analytical methods and covariate adjustments were extracted. A single measure was extracted from each study with adjusted measures in preference to unadjusted measures, where available. Where no measure of association was reported, the numbers of events were extracted. Data extraction was conducted by six reviewers (KA, JM, AC, AR, AL, MH) and any discrepancies were resolved by three separate senior reviewers (BP, SP, NQ).
The risk of bias was appraised using the Cochrane ROBINS-I (‘Risk Of Bias In Non-randomised Studies of Interventions’) tool for observational studies [9]. Three reviewers (NQ, BP, IU) rated studies as being of low, moderate, serious or critical risk in each of the seven domains (see supplementary file 3). Immortal time bias was assessed in the Bias due to Selection domain of the ROBINS-I tool. Any discrepancies in the assessment of the risk of bias were resolved with two senior reviewers (SP, NQ).
Data synthesis and analysis
The first stage of data synthesis involved ensuring that a measure of association was available from each study. For studies in which no relative risk measure was reported, an unadjusted odds ratio was calculated. Owing to heterogeneity in the reporting of relative risks (rate ratio, hazard ratio, odds ratio), and the inclusion of both adjusted and unadjusted estimates from observational studies, the risk estimation methods could not be homogenised, and the reported relative risk estimates, were used as reported in each study.
The relative risk estimates from RCTs and observational studies were combined using both the inverse variance-weighted method for a fixed effect model and the Der Simonian-Laird random effect model. Heterogeneity was assessed using the I2 statistic and an interaction test p value, and corresponding forest plots were constructed. A sensitivity analysis to assess the effect of the risk of bias on the reported relative risk estimates was conducted. All analyses were conducted using R software [10].
The full search results are presented in the flow chart (see Figure 1). We have included 41 published comparative studies that evaluated the effect of tocilizumab on mortality in patients hospitalised with covid-19. These comprised eight randomised controlled trials (RCTs) (1-8) and 33 observational studies (9-42) (see supplementary file 2). Study sizes ranged from 123 to 4,116 patients in RCTs and 33 to 3,924 patients in observational studies. The 41 studies came from 10 countries; the highest number (14 (34%)) came from the USA.
The Randomised Evidence
Figure 2 presents a meta-analysis of the eight RCTs regarding the estimated relative risk effect of tocilizumab compared with standard care on 30-day mortality. In all cases, the dosage regimen was 8 mg/kg intravenously given once or twice (see supplementary file 2: Table 1). Using a fixed effect model, the combined estimate is a relative risk of 0.86 (95% CI 0.78 to 0.96, P=0.15).
The RECOVERY trial is the largest, contributing 83.7% of the total weight. Hence, the meta-analysis produces a very similar treatment effect estimate to that in RECOVERY: relative risk 0.86 (95% CI 0.77 to 0.96). The next largest trial REMAP-CAP, weighted 7.8% and produced large treatment effect, relative risk 0.61 (95% CI 0.43 to 0.88). The other six smaller trials all had non-significant effect estimates, in the opposite direction.
The test for heterogeneity of effect sizes across trials was non-significant (interaction P=0.15). Nevertheless, this hint of apparent heterogeneity is sufficient to generate somewhat different results for a random-effects meta-analysis: the combined relative risk estimate of 0.92 comes nearer the null, with a wider 95% CI (0.73 to 1.17) and is non-significant. This arises because the random effect model gives increased weight to the six smaller studies (combined weight 37% compared with 8.8% in the fixed-effects model), and this pulls the overall estimate away from the highly positive RECOVERY result and increases the uncertainty.
While the absolute treatment benefit; the percentage reduction in mortality is of interest, it is hard to summarise. Since the mortality risk depends on the severity of the disease at the time of randomisation, it is plausible that the absolute treatment benefit will be more marked in patients with more severe disease. This could be explored in future subgroup analyses.
In RECOVERY, the percentage mortality reduction was 3.6% (95% CI 0.8 to 6.3) (3), while in REMAP-CAP (1) it was 7.3% (95% CI 0.95 to 13.2) (see supplementary file 4). Although the latter recruited more high-risk patients from intensive care units, the mortality rates in the control groups were similar (33% versus 35% respectively). We note that the five smallest RCTs all had much lower mortality rates (collectively 7.2%); it is, therefore, likely that they lacked the power to show a survival benefit of tocilizumab.
Evidence from Observational Studies
The 33 observational studies comparing patients receiving tocilizumab against standard care are summarised in Figure 3. In all studies the dosage regimen was 4-8 mg/kg, to a maximum of 800 mg intravenously, given once or twice (see supplementary file 2: Table 2). We concentrate on the 23 studies that adjusted for potential confounders, separating the 10 other unadjusted studies as providing intrinsically unreliable evidence (see supplementary file 3). Overall, the 23 adjusted observational studies produce a larger effect of tocilizumab on mortality than the RCTs. There is also significant heterogeneity among them (interaction P<0>
Observational studies vary in their methodological quality. Of the 23 adjusted studies, 10 studies have a moderate risk of bias and 13 studies a severe or critical risk of bias. In Figure 4, we compared the treatment effect estimates for the RCTs with those for observational studies, split according to their risk of bias (moderate or severe). For the 10 observational studies with a moderate risk of bias the overall mortality relative risk from a fixed-effects model is 0.72 (95% CI 0.64 to 0.81), an apparently larger treatment effect than for the meta-analysis of RCTs (about twice as large a relative risk reduction).
Four of the 10 studies dominate this overall estimate, with a combined weight of 66% in the fixed-effects meta-analysis. It is therefore worth exploring their methods. The largest cohort study (17) in patients admitted to 68 US intensive care units compared 433 patients who received tocilizumab within 2 days of admission, of whom 125 (29%) died with 3,491 patients who did not, of whom 1,419 (41%) died. Adjustment for over 20 potential confounders, using a propensity score with inverse probability weighting (IPW), resulted in a mortality hazard ratio of 0.71 (95% CI 0.56 to 0.92).
The second largest study (9), in patients admitted to 13 US intensive care units, included 210 patients who received tocilizumab, of whom 102 (49%) died. Of the 554 patients who did not receive tocilizumab, 420 were matched for propensity scores and 256 (61%) died. This involved adjustment for 13 potential confounders and correction for immortal time bias. The primary analysis yielded a mortality hazard ratio of 0.64 (95% CI 0.47 to 0.87).
The third study [51] was a retrospective cohort study of all patients with covid-19 in 17 Spanish hospitals. The 440 patients treated with tocilizumab had markedly higher unadjusted 28-day mortality than the other 2,107 patients (hazard ratio 2.35) but also had a poorer risk profile. After covariate adjustment for 22 factors (including corticosteroids) of which 13 were time-updated covariates, the hazard ratio became 1.20 (95% CI 0.87 to 1.64, P=0.26).
The fourth study [42] was in patients admitted to 18 tertiary hospitals in Spain with severe covid-19; 254 patients who received tocilizumab, of whom 45 (18%) died in hospital were compared with 235 patients who did not, of whom 75 (32%) died in hospital. Adjustment for over 20 potential confounders, using a propensity score with inverse probability weighting, resulted in a mortality hazard ratio of 0.74 (95% CI 0.62 to 0.89). It is puzzling that this study produces a substantially more precise treatment effect estimate (i.e., a narrower CI) than that of Gupta et al [26], even though it was around one-third the size. We suspect that this contradiction arises because the latter study correctly used a robust variance estimator to account for potential replication of patients induced by inverse probability, whereas the former did not.
It is generally recognised that RCTs provide the highest quality of evidence on which to base therapeutic recommendations, while evidence from observational studies requires much more cautious interpretation. Hence, in interpreting this systematic review of the effect of tocilizumab on survival of patients with covid-19, it is appropriate that we first concentrate on the randomised evidence.
Overall, based on a fixed effect meta-analysis of eight RCTs, we see a 14% relative risk reduction in mortality with tocilizumab (95% CI 4-22%). This is very similar to the findings in the RECOVERY trial, which dominates the analysis, owing to its size.
We have also presented a random effect meta-analysis, since it is conventional to do so. It provides a weaker overall effect estimate, an 8% relative risk reduction with a wider 95% CI that includes no effect on mortality. However, this is likely to be a misleading analysis. There is no significant heterogeneity of effect across randomised trials (interaction P=0.15), yet the random effect model increases the weight given to the six smaller trials, none of which point in the direction of treatment benefit. This undue influence of small studies appears to dilute a treatment effect and generate increased uncertainty. There is a long-standing debate on the relative merits of fixed effect and random effect meta-analyses. In this case, we think that a random effect model is less trustworthy.
A key question is whether the overall survival benefit from tocilizumab relates to all hospitalised patients with covid-19 or if there are specific subgroups in whom the benefit is greater or absent. The RECOVERY trial reports that these benefits were seen in all patient subgroups, including those requiring oxygen, and those requiring mechanical ventilation in an intensive care unit (ICU) (3). The combination of tocilizumab and a systemic corticosteroid (e.g., dexamethasone) appears to reduce mortality to a greater extent. It is also plausible that the reduction in mortality due to tocilizumab is more marked in more severe disease, in which IL-6 release may be more marked. For instance, the second largest RCT, the REMAP-CAP trial, was in critically ill patients in an ICU and reported a 39% relative reduction in in-hospital mortality, although with a wide 95% CI (12-57%) [11]. However, in the RECOVERY trial [8], patients requiring non-invasive ventilation and invasive mechanical ventilation (each subgroup having more deaths than in the REMAP-CAP trial) did not have larger relative reductions in in-hospital mortality than patients who did not require ventilatory support.
Interpretation of the evidence from observational studies presents more of a challenge. For the sake of completeness, we have included all 33 observational studies that evaluated the association between tocilizumab treatment and mortality (see Figure 3), but we feel it best to ignore the findings of most of them, owing to their unreliability. 10 studies did not adjust for confounders in their mortality analyses and a further 13 studies were classified as having a severe risk of bias. Reasons for such a poor rating include lack of adjustment for key covariates and bias in the selection of patients.
This leaves 10 observational studies classified as having a moderate risk of bias. Their combined data (2,093 patients given tocilizumab, of whom 460 died in hospital) amounted to a slightly lower mortality than in the RCTs. Overall, these 10 studies showed a stronger association between tocilizumab treatment and survival than the RCTs, with a relative reduction in mortality of 29% (95% CI 20-36%). The four largest were all retrospective cohort studies based on multiple hospitals, two in the USA and two in Spain. While the pooled 95% confidence interval in these studies at moderate risk of bias overlapped with the pooled estimate from the RCTs, it is noteworthy that only two observational studies had point estimates that fell within the 95% confidence interval of the pooled RCTs or the RECOVERY trial, the largest RCT.
The diversity of statistical methods across these studies is a challenge: propensity adjustment with IPW, propensity matching, and covariate adjustment were all used to account for potential confounders. Inevitably, one doubts whether any study has adequately corrected for the selection bias involved in the clinical decisions about who received tocilizumab and who did not. Unmeasured confounders may well play an important role. Hence, the extent to which one can trust the adjusted relative risk estimate in each observational study is open to debate, and the overall effect estimate across the 10 observational studies with moderate bias may have been overestimated two-fold (14% in RCTs versus 29% in observational studies).
Our systematic review has some limitations. We have only evaluated treatment effects on mortality, whereas other outcomes such as time to recovery and need for mechanical ventilation may have an important bearing on the overall benefit profile of tocilizumab and its cost-effectiveness by reducing the duration of illness. We believe that in-hospital mortality, as well as being the most important outcome, provides the least scope for bias in comparing RCTs and observational studies. We have concentrated on overall mortality in all patients, whereas there could be subgroups for whom the survival benefit is more (or less) marked, although subgroup analyses according to severity in the RECOVERY trial suggest that that is not the case.
The role of observational studies of treatments in covid-19, and more generally, is controversial. For tocilizumab, the pooled observational studies agree with the RCTs in the direction of benefit on mortality but exaggerated its magnitude two-fold. The large observational studies may seem to have been more informative motivation than the early underpowered RCTs which even when pooled showed no evidence of tocilizumab’s efficacy. We did not combine RCTs and observational studies with network meta-analysis, which may produce highly misleading results [52]. The results of observational studies should be used mainly to generate hypotheses and to inform the design of RCTs and not as a basis for treating patients, except when RCTs are not reliable, as recently reported for the efficacy of prophylactic anticoagulation in covid-19 patients [53].
This systematic review of all reported RCTs of tocilizumab versus standard care shows strong evidence that tocilizumab reduces mortality in severe covid-19. Observational studies of adequate methodological quality also provided evidence of efficacy, but the effect size was exaggerated two-fold. Collectively observational studies provide a less reliable evidence base for evaluating treatment for covid-19.
OXON Epidemiology is a scientific service provider of observational research, pragmatic trials and meta-analysis to the pharmaceutical industry.
The real-time systematic review process was partially funded by GSK. GSK had no involvement in the analysis of the data, writing of the manuscript or the decision or timing of its submission.
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
