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Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."
Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011
Dr. Shankar P.R.
"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."
Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011 Anuradha
Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.
Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020
Original article / research
Full Version
Role of Nebulised Heparin as an Adjunct in Critically-ill COVID-19 Patients: A Randomised Controlled Trial
Correspondence Address :
Dr. SP Raghu,
Associate Professor, Department of Anaesthesia, Basaveshwara Medical College and Hospital, Chitradurga-577502, Karnataka, India.
E-mail: drraghusp@gmail.com
Introduction: Coronavirus Disease 2019 (COVID-19) is associated with an increased risk of Venous Thromboembolism (VTE) and coagulopathy. The available studies have shown the anticoagulant and mucolytic effects of nebulised heparin in non COVID-19 patients. Hence it was decided to conducted to study the efficacy of nebulised heparin in patients suffering from COVID-19 pneumonia requiring mechanical ventilation.
Aim: To evaluate the safety and efficacy of nebulised heparin administered to patients with COVID-19.
Materials and Methods: A double-blinded randomised controlled trial was conducted at Basaveshwara Medical College and Hospital in Chitradurga, Karnataka, India among 100 patients with COVID-19 who required mechanical ventilation from February 2021 to May 2021. They were randomly assigned to two equal groups of 50 patients each. One group received nebulised heparin, and the other group received a placebo. The patients were compared for baseline characteristics, coagulation characteristics, and Oxygen Saturation (SpO2). Data were analysed using Statistical Package for Social Sciences (SPSS) version 22.0, expressed as frequency and percentages, and displayed in tables and figures. The association between two variables was determined using the Chi-square test and paired t-test.
Results: The two groups did not differ significantly in terms of age, sex, respiratory failure, vasopressin use, and severity score. Respiratory failure was present in 54% of the heparin group and 38% of the placebo group. Vasopressin was used in 64% of the heparin group and 56% of the placebo group. The severity score was 4.44 in the heparin group and 4.42 in the placebo group. Activated Partial Thromboplastin Time (APTT) levels did not differ significantly between the groups. None of these parameters showed significant differences between the heparin and placebo groups. However, both groups showed a significant difference in Thrombin Antithrombin (TAT) complex levels from baseline to follow-up (p<0.05). D-Dimer levels decreased during follow-up, and SpO2 improved significantly in the nebulised heparin group compared to the placebo group.
Conclusion: Nebulised heparin used as an adjunct in critically ill COVID-19 patients was shown to decrease TAT and D-Dimer levels. Nebulised heparin also significantly improved oxygenation levels. Importantly, heparin nebulisation was not associated with any adverse events, even when administered with systemic heparin.
Anticoagulants, Coronavirus disease-2019, D-dimer, Placebo, Thrombin antithrombin complex, Viral pneumonia
A new coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) developed in the Chinese city of Wuhan in December 2019 (1) and was the source of an atypical viral pneumonia that resulted in cases of Acute Respiratory Distress Syndrome (ARDS) (2). Some probable clinical manifestations of COVID-19 include asymptomatic or mild respiratory symptoms, pneumonia with respiratory failure, and mortality (3). COVID-19 is associated with an increased risk of VTE and coagulopathy, especially in patients who are very sick. Endothelial injury caused by SARS-CoV-2 is now understood to be a major pathogenetic mechanism for the development of issues during the acute stage of the illness, as well as for a number of postdischarge sequelae (4).
Additionally, a large number of patients displayed coagulation abnormalities: elevated D-dimer concentration upon hospital admission, a decrease in platelet count, and an extension of the prothrombin time, all suggesting that COVID-19 was hypercoagulable, which could increase the risk of thromboembolic complications (5),(6). In fact, VTE has become a frequent consequence, especially in critically unwell patients (7). A recent study in antemortem and postmortem cohorts of critically ill COVID-19 patients revealed an increased occurrence of VTE and an improvement in prognosis following a change in anticoagulant treatment (8).
Heparin’s biological effects, known as its pleiotropic effects, include anti-inflammatory, antiapoptotic, and anticancer properties, in addition to its primary function of preventing clotting (9),(10),(11). Despite previous anticoagulant failures in critical illness, the high incidence of VTE in COVID-19 and strong evidence of coagulopathy suggest that heparin may improve patient outcomes. A retrospective report of 449 COVID-19 patients from Wuhan, China, where prophylaxis in medical patients is comparatively uncommon due to a low incidence of VTE, first suggested the usefulness of heparin as an anticoagulant in COVID-19 (12). In this cohort, 99 patients received low-dose prophylactic heparin doses, while 350 patients received no heparin therapy (neither low-dose prophylactic nor high-dose therapeutic). Receiving prophylactic heparin reduced mortality in patients with elevated D-dimer (>6-fold over the upper limit of normal) or raised sepsis-induced coagulopathy scores by almost 20% (13). Another finding that supports the clinical importance of thrombosis in severe disease is that intravenous tissue plasminogen activator, a strong thrombolytic, can momentarily enhance oxygenation in acute respiratory distress syndrome linked to COVID-19 (14).
The present study was conducted to study the efficacy of nebulised heparin in patients suffering from COVID-19 pneumonia requiring mechanical ventilation.
A double-blinded randomised controlled study was conducted among patients admitted with COVID-19 aged over 18 years at Basaveshwara Medical College and Hospital in Chitradurga, Karnataka, India. The study took place for a period of three months, from February 2021 to May 2021. IEC clearance (BMCH/IEC/2020-2021/97) was obtained before initiating the study.
Sample size calculation: The sample size was determined in consultation with a statistician and based on initial pilot observations. For a difference of 1 in TAT levels between the two groups (d), the Standard Deviation (SD) was calculated as 1.7, indicating that approximately 46 patients should be included in each group. Considering a 5% dropout rate, the authors fixed 50 patients for each group.
Sample size calculation:
Sample size=(SD)2/(d)2
=(1.7)2/(1)2
=46.24
Inclusion criteria:
1. Patients aged over 18 years.
2. Reverse Transcription Polymerase Chain Reaction (RT-PCR) positive within the last 21 days.
3. Computed Tomography (CT) severity score greater than 15 (15).
Exclusion criteria:
1. Patients with heparin allergy.
2. Patients with an Activated Partial Thromboplastin Time (APTT) exceeding 120 seconds.
3. Platelet count less than 20,000.
4. Pregnant patients.
5. Patients with brain injury and myopathy.
Study Procedure
Informed written consent was obtained from the patients. Those admitted to the intensive care unit due to ARDS were randomly divided into two groups using computer-generated random numbers (Table/Fig 1). The intervention group consisted of 50 patients suffering from ARDS due to COVID-19, who were administered nebulised Heparin (25,000 IU). The control group, also consisting of 50 patients, received treatment with other drugs, including parenteral heparin. The heparin and placebo were presented in identical 5 mL plastic ampules: heparin sodium (porcine mucous) 25,000 U/5 mL and placebo (0.9% sodium chloride) (16). Double-blinding (both investigator and patient) was implemented. Patients received 5 mL of the study medication every four hours, or if they were less than 165 cm in height, every six hours. Heparin and placebo were nebulised using a standard nebuliser for 30 minutes.
The nebuliser was placed in the inspiratory limb just before the Y piece. An active humidification system was used.
A mechanical ventilation system with pressure control was utilised. The target tidal volume was set at no more than mL/kg of estimated body weight, following standard procedures during the study period. Demographic information was collected upon study admission, including breathing parameters, clinical data, sputum characteristics, medication usage, and adverse events such as red cell transfusions and blood-stained sputum, including frank blood. TAT levels (normal <3.0 ng/mL) and D-dimer levels (normal <1.0 mcg/mL) were assessed at baseline and followed-up daily until day 4 as the primary outcome of the study (17). Spo2 levels were also recorded at baseline and monitored for four days as a secondary outcome of the study. The data was collected using a proforma specifically designed for the study. CT severity scores were employed for the study (Table/Fig 2) (15).
Statistical Analysis
The data was analysed using SPSS version 22. It was entered into an Excel sheet for further analysis. The outcomes were presented in tables and figures, accompanied by frequency and percentage explanations. To assess the relationship between two variables, the paired t-test and the chi-square test were employed.
In the present study, the two groups did not show significant differences in terms of age, sex, respiratory failure, vasopressin use, and CT severity score (Table/Fig 3).
The thrombin antithrombin complex exhibited significant differences at baseline and follow-up, with notable changes observed in both groups. D-Dimer levels decreased on follow-up compared to baseline in both groups, with a more pronounced decrease in the heparin group. Mean SPO2 levels also improved during the four-day follow-up period (Table/Fig 4).
The study demonstrated that heparin nebulisation was not associated with any adverse events, even when administered alongside systemic heparin. The drug was well-tolerated by the patients. The occurrence of blood-stained sputum in the heparin group was significantly lower in the present study.
The present study focused on investigating the efficacy of nebulised heparin in COVID-19 pneumonia patients requiring mechanical ventilation. The study included 50 cases in both the Heparin group and the placebo group. The mean age of patients in the Heparin group was 46.2 years, while it was 46.0 years in the placebo group. The majority of patients in both groups were male. In a study conducted by Gupta B et al., which examined the role of nebulised heparin in reducing COVID-19-induced acute lung injury, they reported a mean age of 54.5 years, with the majority of patients being male (79.0%) (17).
The authors observed that mean SPO2 levels improved over the four-day follow-up period, with a more significant improvement in the nebulised heparin group compared to the placebo group. These findings align with Gupta B et al.’s study, where they also reported a statistically significant improvement in oxygenation (pO2/FiO2 ratio) over seven days (mean=184.96, p=0.00) (17). Additionally, they found a significant improvement in PaO2 (84.17±33.82) and SO2 (92.30±3.49). Compared to the present study, the heparin group demonstrated a notable daily change in oxygenation levels over the first three days. There was a significant clinical improvement in terms of ventilation-free days in patients receiving nebulised heparin.
Reduced fibrin deposition in the pulmonary microcirculation and alveolar sacs, known as hyaline membranes, may be the underlying mechanism (18). A study has shown that intravenous heparin significantly reduced histological signs of pulmonary microvascular thrombosis in individuals with acute inflammation following heart surgery (19). Fibrin deposition causing a barrier to gas exchange has been associated with reduced alveolar perfusion and ventilation (20). Pulmonary microvascular thrombosis may lead to ischaemic damage to alveolar tissue and strain on the right heart by increasing the right ventricular afterload (21). In addition, leukocyte infiltration of lung tissue mediated by fibrin may cause further harm (22). Nebulised heparin has been associated with fewer days of mechanical ventilation in a study by Dixon B et al., (18).
In the present study, significant differences were observed between baseline and follow-up thrombin antithrombin complexes, with notable changes in both groups. D-Dimer levels were lower on follow-up compared to baseline in both groups, with a more pronounced decrease in the heparin group. This finding is similar to a study by Gupta B et al., where D-dimer levels did not show a statistically significant change (17).
The systemic anticoagulant effect of nebulised heparin is often reflected in higher Activated Partial Thromboplastin Time (APTT) readings compared to placebo (18). The absence of a discernible difference in APTT values between the groups in this investigation may be due to delayed heparin clearance from the lungs (23).
The study demonstrated that heparin nebulisation, even after systemic heparin dosing, did not result in any adverse side-effects. The medication was well tolerated by the patients. The number of patients with blood-stained sputum in the heparin group was significantly reduced. The increased prevalence of Venous Thromboembolism (VTE) in COVID-19 patients and its impact on mortality, particularly in Intensive Care Unit (ICU) patients, has been confirmed by data from various studies. Additionally, there was an increased risk of bleeding (24),(25),(26),(27).
Limitation(s)
In the present study, the authors were unable to evaluate the duration of hospitalisation as it was fixed for 14 days of mechanical ventilation. Long-term follow-up assessments could be conducted.
The administration of nebulised heparin as an adjunct in COVID-19-induced lung injury resulted in reduced coagulant markers (TAT and D-dimer levels) and increased oxygen concentration. The present study also demonstrated that systemic heparin dosing, combined with heparin nebulisation, did not lead to any side-effects. The study further showed no noticeable difference in APTT values between the groups. Additional trials are needed to confirm these study findings with other variables.
DOI: 10.7860/JCDR/2023/66578.18808
Date of Submission: Jul 19, 2023
Date of Peer Review: Sep 12, 2023
Date of Acceptance: Nov 16, 2023
Date of Publishing: Dec 01, 2023
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA
PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Jul 19, 2023
• Manual Googling: Sep 15, 2023
• iThenticate Software: Nov 14, 2023 (9%)
ETYMOLOGY: Author Origin
EMENDATIONS: 8
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