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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
Metabolic Derangements with Anticonvulsants in Children with Generalised Tonic-clonic Epilepsy: A Cross-sectional Study
Correspondence Address :
Himani Deswal,
Sector-4, Rohtak, Haryana, India.
E-mail: des.himani8014@gmail.com
Introduction: Epilepsy is one of the most prevalent non-communicable neurologic conditions, accounting for significant disability and mortality. The effects of Antiepileptic Drugs (AEDs) on total cholesterol, triglycerides, High-Density Lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and apolipoprotein levels have been demonstrated in many studies, mainly conducted with adults. However, there have been very few studies in children. Derangement of lipid profile and other metabolic abnormalities could lead to the development of metabolic syndrome in children. The adverse metabolic effects of anti-epileptics are underestimated, as only a few studies have been done in this area, which is a legitimate concern.
Aim: To assess the impact of AEDs on metabolic parameters in children with epilepsy.
Materials and Methods: This was a descriptive, cross-sectional study conducted in the Department of Paediatrics and Pharmacology at Pt. B.D. Sharma PGIMS, Rohtak, Haryana, India. The study included 100 children with epilepsy from May 2022 to October 2022. A predefined case record form, including demographic and clinical characteristics, was filled for each participant. The parameters recorded were age, gender, outpatient number, type of epilepsy, history of duration of epilepsy, current AED history, and seizure frequency over the preceding six months, as per the case record form. Guidelines from the International Diabetes Federation were used for diagnosing metabolic syndrome in children. The data was entered into Microsoft excel and presented using descriptive statistics. The chi-square test was used to differentiate between categorical variables.
Results: The mean age of the study participants was 10.2±2.97 years. There were more males (62%) than females (38%). A 48% of the patients received monotherapy, while 52% received polytherapy. A total of 24% of the patients had derangement in lipid profile (increased triglycerides and decreased HDL), with 14% of patients on monotherapy and 10% on polytherapy. The difference in metabolic derangements between monotherapy and polytherapy was not statistically significant (p=0.25). Out of 100 participants, 3% fulfilled the criteria for metabolic syndrome, with a predominance in males.
Conclusion: Metabolic derangements are known with 1st generation AEDs, but 2nd generation AEDs can also lead to significant metabolic abnormalities.
Child, Combination drug therapy, Metabolic syndrome
Epilepsy is one of the most prevalent non-communicable neurological conditions, accounting for significant disability and mortality in adults as well as children (1). The high incidence of epilepsy in children, coupled with the need for long-term antiepileptic treatment, could lead to the development of metabolic complications at an early age. The effect of AEDs on total cholesterol, triglycerides, HDL cholesterol, low-density lipoprotein cholesterol, and apolipoprotein levels has been demonstrated in many studies, mainly performed with adults, but very few in children (2). Derangement of lipid profile and other metabolic abnormalities could lead to the development of metabolic syndrome in children. Paediatric Metabolic Syndrome (PMS) in childhood can lead to the early onset of diabetes mellitus and cardiovascular diseases in adulthood (3). Metabolic syndrome also has a negative impact on mental health and overall cognitive performance in children and adolescents (4).
Despite the development and implementation of multiple treatment strategies, the prevalence of metabolic syndrome remained high in the majority of high-income countries (5), with significant variations across countries (6). Primary studies supported this finding by demonstrating that the prevalence in the general population ranges from (7) (0.4%) to (8) (24%), and in the obese population ranges from (9) (6%) to (10) (55.8%). Moreover, there are no standard guidelines or criteria for metabolic syndrome, with significant variation in the diagnostic methods in children (11). Various studies (12),(13) found in the literature show metabolic side effects with first-generation anticonvulsants in children. Now-a-days, with the increasing use of second-generation anticonvulsants due to their better pharmacological profile, the metabolic adverse effect profile with these drugs in children is still unexplored. Since clinicians are following treatment with combination therapy of both generation drugs due to resistance with a single agent, their combination side effects are still not documented. The present study is being undertaken to assess the impact of AEDs on metabolic parameters in children with epilepsy. The objective of the study was to compare the effect of monotherapy and polytherapy in children with epilepsy.
This was a descriptive and cross-sectional study conducted in the Department of Paediatrics and Pharmacology, Pt. B.D. Sharma PGIMS, Rohtak, Haryana, India, on 100 children with epilepsy between May 2022 and October 2022. Written informed consent was obtained from the parents before enrollment, and assent was obtained from children above seven years of age. Approval was obtained from the Institutional Ethics Committee (IEC/19/71) before the study commenced.
A total of 130 patients between 5 and 18 years of age with a history of epilepsy, presenting at the paediatric outpatient clinic, were screened using a simple random sampling technique.
Sample size calculation: was done using the formula:
N=4pq/d2
N=sample size, p=prevalence, q=1-p, d=precision
A sample size of 104 patients was required to achieve 5% precision at a 95% confidence level, assuming a prevalence rate of metabolic syndrome with AEDs to be 7% (14).
Inclusion criteria: The study included children between the ages of 5-18 years, of either gender, diagnosed with generalised epilepsy and who had been stable on anti-convulsants (monotherapy or combination) for at least three months were included in the study after their parents provided written informed consent.
Exclusion criteria: Those with psychogenic/Non-Epileptic Seizures (NES), a history of focal brain pathology/lesions, co-existing diabetes mellitus, dyslipidemia already on lipid-lowering agents, taking medications known to interfere with body weight status (such as antidepressants, corticosteroids, etc.,), co-morbid neurodevelopmental conditions (mental retardation, developmental delay, cerebral palsy, autism, attention deficit hyperactivity disorder), and chronic medical conditions (asthma, hypertension, chronic renal failure, chronic lung disease, thalassaemia, hypothyroidism, etc.,) were excluded from the study.
Procedure
A pre-defined case record form was used for each participant, which included demographic and clinical characteristics. The recorded parameters were age, gender, outpatient number, type of epilepsy, history and duration of epilepsy, current Anti Epilepsy Drugs (AED) history, and seizure frequency over the preceding six months.
Anthropometric data were obtained for each child. Standing height (cm) was measured to the nearest 0.1 cm with a standard calibrated stadiometer, and body weight (kg) was noted on a standard weighing scale to the nearest 0.1 kg, with children dressed in minimal clothing. Waist circumference was measured using a constant tension flexible tape at the midpoint between the lower part of the lowest rib and the highest point of the hip on the mid-axillary line (15). Blood pressure was measured twice using a sphygmomanometer and stethoscope, and the lower reading was utilised for analysis. Fasting blood sugar, total cholesterol, High Density Lipoprotein (HDL), and triglyceride levels were recorded from laboratory data.
In the present study, guidelines from the International Diabetes Federation were used for diagnosing metabolic syndrome in children (Table/Fig 1) (3). According to these guidelines, paediatric metabolic syndrome is defined as the presence of any two of the following parameters along with abdominal obesity.
Statistical Analysis
The data was tabulated in a Microsoft excel sheet and analysed using SPSS version 23.0 software. The results of the descriptive analysis will be presented as proportions (percentages) with 95% confidence intervals. The Chi-square (χ2) test will be used to analyse differences between categorical variables. A p-value <0.05 will be considered statistically significant.
A total of 100 patients were analysed for the study. Out of these, four patients were lost to follow-up due to the COVID-19 pandemic outbreak. The mean age of the study participants was 10.2±2.97 years. Males constituted the majority (62%) while females accounted for 38%. The mean duration of treatment in years was 2.75±2.07.
To facilitate assessment, the patients were categorised based on the AEDs prescribed by the clinician. They were divided into two groups: the monotherapy group (receiving only one AED) and the polytherapy group (receiving a combination of two or more AEDs). The monotherapy group was further subcategorised into first-generation AEDs {Valproate (VPA), Phenytoin (PHT), Carbamazepine (CBZ), Ethosuximide (ESM)} and second-generation AEDs {Levetiracetam (LEV) and Oxcarbazepine (OXC)}.
Similarly, the polytherapy group was further divided into combinations of only first-generation AEDs, combinations of first and second-generation AEDs, combinations of first and third-generation AEDs, combinations of second and third-generation AEDs, and combinations of first, second, and third-generation AEDs. Out of the total patients, 48 received monotherapy, while 52 received polytherapy (Table/Fig 2). The distribution of prescribed drugs in the study population is shown in (Table/Fig 2).
The study included 33 participants (33%) who had alterations in any of the metabolic parameters while taking long-term monotherapy or polytherapy with AEDs. Among those on monotherapy, abdominal obesity was observed in six patients (6%), out of which four patients (4%) had abdominal obesity while taking the first-generation drug, VPA. Additionally, three patients (3%) were on triple therapy with VPA+LEV+CLB (p-value- 0.24). A total of 24 patients (24%) showed derangement in their lipid profiles, characterised by increased triglyceride levels and decreased HDL.
Out of these, 14 patients (14%) were on monotherapy, while 10 patients (10%) were on polytherapy (p-value-0.25). The maximum lipid derangement was observed in patients taking VPA (7%) and triple therapy with VPA+LEV+CLB (5%). An increase in Fasting Blood Glucose (FBG) was more common in patients on monotherapy compared to polytherapy. Specifically, six patients (6%) on monotherapy and three patients (3%) on polytherapy experienced derangement in FBG (p-value- 0.24). Among those on monotherapy, the highest increase in FBG was seen in patients taking valproate (4%). Raised blood pressure was observed in seven patients (7%) on monotherapy and four patients (4%) on polytherapy (p-value- 0.27). However, the difference in metabolic derangements between monotherapy and polytherapy was not statistically significant (Table/Fig 3),(Table/Fig 4).
Out of 100 participants, three fulfilled the criteria for metabolic syndrome. One participant was on monotherapy with Valproate, another was on levetiracetam, and the third one was on polytherapy with valproate+ levetiracetam + clobazam. All patients had abdominal obesity above the 90th percentile, as per guidelines from IDF.
Additionally, the patient on levetiracetam had been on the therapy for the past one and a half years and experienced derangements in HDL, triglyceride cholesterol, and blood pressure. The patients on valproate and triple therapy showed derangements in FBS, TGs, HDL cholesterol, along with abdominal obesity. Both patients had been under treatment for six months (Table/Fig 5).
Epilepsy in children is one of the most common non-communicable neurological conditions, leading to morbidity and affecting their quality of life. The need for long-term antiepileptic treatment in children can result in the development of metabolic complications at an early age. Metabolic derangements have a slow onset, insidious progression, and manifest gradually. Definitions of metabolic syndrome in adults have been published by many organisations, including the World Health Organisation (WHO) (16), NCEP III (17), International Diabetes Foundation (IDF) (18), and the National Heart, Lung, and Blood Institute (NHLBI) (19). However, there are no consensus guidelines for diagnosing metabolic syndrome in the paediatric population. This study followed the guidelines provided by the International Diabetes Federation for diagnosing metabolic syndrome in children (3).
In this cross-sectional study, various metabolic parameters were found to be altered in 33% of children receiving long-term monotherapy as well as polytherapy with AEDs. There was a higher incidence of derangement in metabolic parameters such as FBG, lipid profile, and blood pressure with monotherapy, especially with the 1st generation AED, VPA. An increase in FBS was more common with valproate compared to polytherapy. Similarly, derangement in the lipid profile was more prevalent with valproate compared to 2nd generation drugs. However, a few patients were also found to have deranged lipid parameters with polytherapy involving a combination of 1st, 2nd, and 3rd generation AEDs. Changes in waist circumference, i.e., abdominal obesity, were also more pronounced in children who received a combination of 1st, 2nd, and 3rd generation AEDs, but the incidence was lower than in children who received monotherapy, especially valproate. The increase in blood pressure was also higher with monotherapy. A study conducted by Dhir A et al., also reported a higher incidence of deranged lipid profiles (24.6%) with valproate monotherapy (20).
In this study, significant derangement in lipid profile was observed in 24.3% of patients who received 2nd generation AED, levetiracetam, as monotherapy or in combination. Approximately, 72% of children receiving levetiracetam monotherapy showed overall derangement in one or more metabolic parameters. However, studies conducted by Nishiyama M et al., and Attilakos A et al., found no significant derangements in lipid parameters in epileptic children treated with levetiracetam monotherapy (21),(22).
The definition of metabolic syndrome in children is still evolving. Only a few studies have reported metabolic syndrome in children receiving antiepileptics (14),(23). Inaloo S et al., showed that the prevalence of metabolic syndrome in children with seizure disorder taking AEDs (sodium valproate and Carbamezipine) was higher than in healthy children (7.8% vs 1.1%, p-value=0.032) (14). Verrotti A et al., reported metabolic syndrome in 46.5% of obese older children on valproate monotherapy (24). In this study, 3% of children were found to have metabolic syndrome with AEDs.
This cross-sectional study clearly indicates that children with epilepsy on long-term AEDs have derangements in metabolic parameters compared to their healthy peers of the same age. The study also suggests a trend regarding the adverse effects of certain drugs, especially 2nd generation AEDs, compared to other drugs. Appropriate and careful selection of AEDs, without compromising therapeutic efficacy, supplemented by lifestyle counseling for exercise and diet, along with routine monitoring, should be practiced to avoid metabolic derangements in children taking long-term AEDs.
Limitation(s)
The main limitations of this cross-sectional study include the unavailability of baseline lipid profiles and anthropometric parameters, the lack of serial measurements, and the absence of standard definitions for paediatric metabolic syndrome. This study demonstrated derangement in metabolic parameters in children on long-term AEDs. However, various studies in the literature altered metabolic parameters with 1st generation AEDs, which is also observed in the present study. Additionally, this study found derangements in various metabolic parameters with levetiracetam when given as monotherapy or in combination therapy with other drugs. Therefore, it is necessary to confirm the results of this study with better-designed cohort studies to ascertain the metabolic abnormalities and underlying mechanisms observed in children on levetiracetam.
Long-term therapy with anticonvulsants in children can lead to metabolic derangements, which could increase their susceptibility to metabolic syndrome. Clinicians should actively monitor for metabolic side effects, particularly with 2nd generation AEDs, as observed in the present study. The definition of metabolic syndrome in children needs to be properly established, and further analytical studies are required in this direction to confirm the findings of the present study.
DOI: 10.7860/JCDR/2023/66133.18784
Date of Submission: Jun 19, 2023
Date of Peer Review: Aug 07, 2023
Date of Acceptance: Nov 09, 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 (from parents)
• For any images presented appropriate consent has been obtained from the subjects. NA
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