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On Sep 2018




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On Sep 2018




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"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Lucknow
On Sep 2018




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On Aug 2018




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"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
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Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


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.
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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

Important Notice

Original article / research
Year : 2023 | Month : February | Volume : 17 | Issue : 2 | Page : SC01 - SC03 Full Version

Effect of Growth Hormone Therapy in Indian Children with Short Stature- A Retrospective Study


Published: February 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/60560.17417
Ruchi Mishra, Smriti Rohatgi, Jyoti Bagla, Rajeev Kumar Malhotra

1. Associate Professor, Department of Paediatrics, ESI PGIMSR, Basaidarapur, New Delhi, India. 2. Assistant Professor, Department of Paediatrics, ESI PGIMSR, Basaidarapur, New Delhi, India. 3. Professor and Head, Department of Paediatrics, ESI PGIMSR, Basaidarapur, New Delhi, India. 4. Statistician, Department of Statistics, AIIMS, New Delhi, India.

Correspondence Address :

Smriti Rohatgi,
D-72, Ground Floor, Hauz Khas, Delhi, India.
E-mail: rohatgi.smriti@gmail.com

Abstract

Introduction: The causes for short stature are multifactorial. The recombinant Growth Hormone (rGH) is used worldwide for its treatment, however, there is paucity of data on use of growth hormone in Indian Children.

Aim: To study the effect of rGH in Indian children with short stature, who were enrolled under ESIC scheme.

Materials and Methods: This was a retrospective observational study. Subjects, who had short stature and diagnosed to have Growth Hormone Deficiency (GHD) by stimulation test and other causes for which growth hormone was indicated were enrolled. All subjects received treatment at ESI PGIMSR Basaidarapur, New Delhi, India, from July 2016 to July 2020, without discontinuation for more than one week. The data regarding gain in height was collected at the end of first year and then, at the end of second year. Height velocity and change in Height SD were calculated (Mean±Standard Deviation). The associations and correlations were calculated by Spearman’s correlation test.

Results: The present study included data of 27 children (19 males and eight females) with short stature. The mean age at treatment initiation was 9.85 years±3.04. The most common aetiology for which growth hormone was started was Idiopathic GHD (IGHD) seen in (15/27) 55.5% followed by Multiple Pituitary Hormone Deficiency (MPHD) 18.5% (5/27). The mean height and height SD at baseline was 111.76 cm±17.40 and -3.85±1.19 (-6.0 to -1.5), respectively. The mean bone age delay (chronological age bone age difference) was 40.96±25.58 months. The height velocity response was maximum during the first year of treatment (8.74±2.59 cm), declining to 8.13±2.30 cm in the second year. Correlation of the treatment response with age at treatment initiation, bone age delay and MPH was not significant.

Conclusion: It was found that the growth velocity was significantly increased after one year of treatment. The study provides long term follow-up and response to rGH Treatment (rGHT) in Indian children enrolled under ESIC scheme, however, prospective studies with large sample size and longer follow up duration, which can report final height outcomes are needed.

Keywords

Height, Idiopathic, Mid parental height, Pituitary hormone deficiency

Short stature is defined as height less than 2 Standard Deviation (SD) for that age and sex. Short stature is one of the most common cause for referral to a paediatric endocrinologist. Short stature affects approximately 2-3% children in a given population (1),(2). Physiological causes like familial short stature and constitutional delay of growth and puberty are the two main causes of short stature, while GHD is relatively less common, but important, as it is a treatable cause of short stature. The prevalence of Growth Hormone Deficiency (GHD) among children with short stature is estimated to vary between 2.8% and 69%, and is predicted to be much higher in children postneurosurgical interventions (3).

The rGHT has shown to improve auxological outcomes in children with GHD (4),(5). Various Indian studies on growth hormone therapy have shown significant improvement in height velocity in the first year of treatment (8-10 cm), however the data is limited by small sample size, short follow-up duration and inclusion of heterogenous patient population (6),(7),(8),(9),(10). In a developing country like ours, there is also lack of awareness and delay in diagnosis due to unavailability of hormonal tests and proper follow-up. There is also frequent discontinuation of treatment due to the high cost and need for prolonged therapy to measure the final outcome, in terms of difference in predicted adult height and final height.

With this background and due to the lack of availability of data from an Indian setting, the study was planned to evaluate the effect of rGH in children with short stature, who were enrolled under ESI Scheme. Under this scheme, they are eligible for free investigations and hormonal treatment, which ensures better compliance and follow-up.

Material and Methods

This is a retrospective observational study in which children, who received rGHT from July 2016 to July 2020 in Pediatric Endocrine Clinic of ESI PGIMSR Basaidarapur, New Delhi, India, were enrolled. As per protocol, all the children coming to Paediatric Endocrine Clinic for short stature evaluation were initially investigated, to rule out systemic causes and other normal variants of short stature and were followed for a minimum of one year for growth velocity. They were then subjected to Growth Hormone Stimulation Test (GHST) after ensuring normal thyroid levels and ruling out systemic causes of short stature. Ethical clearance was taken from the Institutional Ethical Committee (ESIPGIMSR-IEC/20180052).

Inclusion criteria: Subjects diagnosed to have GHD and other causes for which growth hormone was indicated were enrolled, if they received treatment for two years, without discontinuation for more than one week.

Exclusion criteria: All those subjects whose follow-up was not adequate (3-4 monthly) or had discontinued treatment for more than one week, were excluded from the study.

Study Variables

Auxological parameters: Height was measured to the nearest 0.1 cm by Harpenden stadiometer, at the start of GH treatment and then every three monthly, till continuation of treatment. Height was expressed as SD according to the formula: Height SD= (Measured height-Mean height for age)/SD for age. All measurements were made by skilled staff with participants dressed in minimal light clothing and without footwear. The stadiometer was calibrated using standard height. The Indian Academy of Paediatricians (IAP) growth charts and standards were used across all ages for the above auxological parameters. Mid-Parental Height (MPH) was computed based on height of the parents (father’s height+mother’s height)/2, +6.5 cm for boys and -6.5 cm for girls). Pubertal assessment was done by Tanner Staging. Bone age was calculated using Greulich WW and Pyle SI Atlas at the start of treatment and in follow-up (11).

Diagnosis of Growth Hormone Deficiency (GHD): The GHD was diagnosed by GHST with either clonidine or glucagon. A peak serum GH level >10 ng/mL on GHST was considered as normal, excluding GHD. A peak serum GH level <5 ng/mL was taken as confirmatory for GHD, whereas for values between 5-10 ng/mL, a repeat GHST was done with injection glucagon/oral clonidine. A peak serum GH level <10 ng/mL in second GHST was taken as GHD (12).

All subjects underwent evaluation for other pituitary axis using appropriate hormone assays (serum T4, TSH, 8:00 am serum cortisol, plasma ACTH). Subjects with involvement of other pituitary axis were defined as having Multiple Pituitary Hormone Deficiency (MPHD), while those without any such involvement were defined as having IGHD. In defining idiopathic short stature for the indication of recombinant human Growth Hormone (rhGH) treatment, the US Food and Drug Administration approved criterion of height -2.25 SD below the mean was taken (13).

Hormone assay: Growth hormone assay was done using chemiluminescent tracer-based immunometric assay (sandwich assay) using auto-analyser, in which a chemiluminescent molecule is used as an indicator label to detect and quantify immunological reactions.

Treatment with growth hormone: rGH (Norditorpin or genotropin) was initiated at a dose of 0.20-0.30 mg/kg/week (13). Subjects were followed at 3-4 months interval for assessment of anthropometric and pubertal parameters, and for monitoring of adverse effects. Dose was adjusted on the basis of insulin-like Growth Factor-1 (IGF-1) levels and auxological parameters. If the growth velocity was below the normal range after starting GH (atleast three months) or if the IGF-1 levels were below 1SD for that age then the dose was increased, and IGF maintained between 1-2 SD. The gain in height and height SDs was measured, at the end of first year and subsequently in the second year.

Statistical Analysis

Statistical analysis was carried out using Statistical Package for Social Sciences (SPSS) version 21.0. Data were presented as number (%), mean (±SD) or median Interquartile Range (IQR) if the data was skewed. Quantitative variables following normal distribution were compared using Student’s t-test and those that did not follow normal distribution were compared using Wilcoxon’s rank-sum test. A p-value of <0.05 was considered statistically significant.

Results

The present study included data of 27 children (19 males and eight females) with short stature, being treated for minimum of 2 years with rGH. The mean age at treatment initiation was 9.85±3.04 years, with 20 of them being in peripubertal or pubertal age group (more than eight years). The most common aetiology for which the hormone therapy was started was IGHD (15/27, 55.5%), while the second most common indication was MPHD (18.5%, 5/27). (Table/Fig 1) illustrates the mean age of diagnosis for the various aetiology and change in height with growth hormone treatment. The mean height and height SD at baseline was 111.76±17.40 cm and -3.85±1.19 (-6.0 to -1.5), respectively. The mean bone age delay (chronological age-bone age difference) was 40.96±25.58 months.

The baseline height velocity was significantly lower, as compared to first and second year of treatment. The height velocity response was maximum during the first year of treatment (8.74±2.59 cm), declining to 8.13±2.30 cm in the second year, however, the difference in height velocity between the two years was not statistically significant. One factor repeated measures Analysis of Variance (ANOVA) revealed a significant change in velocity over the time. Mean height SDs also showed a significant change from baseline to first and second year of treatment. Pair-wise Bonferroni adjusted p-value are presented in (Table/Fig 2).

Height velocity in first year was negatively associated with age at initiation of treatment (p=0.042; ρ=-0.395) (Table/Fig 3). However, multiple linear regressions did not find significant association between height velocity at first and second year with bone age delay and MPH.

Discussion

The present study presents the data of 27 children, who got growth hormone treatment without interruption for atleast two years. Data on such therapy is sparse in Indian literature due to the high cost and lack of easy availability. However, this was possible as all patients were ESI beneficiary and thus, entitled for free investigations and treatment.

In the present study, there was significant improvement in mean height SDs from -3.85±1.1 to -3.17±0.98 after one year treatment and -3.17±0.98 to -2.51±0.90 in the second year. The height velocity was maximum (8.74±2.59) in the first year of treatment. This is in accordance with most of the studies, which also showed that the height velocity response was maximum during the first three years after treatment initiation, followed by a graded decline over the subsequent years (6),(7),(8),(9),(10) [Table/Fig 4]. Mean height at presentation in the present study was 115.7±17.5 cm, which is similar to other Indian studies (7),(8).

The most common indication for GHT in the present study was primary IGHD. This is in accordance with most of the studies on growth hormone, where most common indication for growth hormone therapy is IGHD [6,14]. Mean age of treatment initiation was 9.85±3.04 years, as seen in most of the studies in India [6,12], due to lack of awareness and late presentation. However, the mean age at presentation was lower in patients with systemic diseases, as compared to IGHD, though not statistically significant, as they were brought to medical attention, earlier due to their primary illness. Bone age deficit in this study was 40.96±25.58 months, which is also comparable to another study (9).

The present study shows significant correlation between first year change in height velocity and age at initiation of treatment, however, there was no correlation between MPH or bone age delay. Whereas, Gahlot M et al., showed significant negative correlation between first year change in height SDs and age at initiation of treatment, baseline height SDs, baseline serum IGF 1 and peak serum GH level while a significant positive correlation was seen with bone age delay (12). The difference is probably due to the small sample size in the present study. Thus, in clinical practice, these could serve as important predictors of first year response, to growth hormone treatment. The strength of the present study is that, there was no discontinuation of treatment and better compliance, since the treatment was given free of cost and the dose could be increased according to the needs without any financial constraints.

Limitation(s)

The study was retrospective in nature with a small sample size and follow-up data was there for two years only.

Conclusion

The present study provided data to reflect the response to rGHT among Indian children. There was a significant improvement in the height velocity in the first two years. There is also significant negative correlation between age of initiation and first year height velocity after initiating treatment. However, prospective studies with large sample size and longer follow-up duration, which can report final height outcomes are needed in the near future.

References

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Kannan V, Usharani K. Human growth hormone therapy: Long term responses in 30 children with growth hormone deficiency. Indian J Paediatr (Suppl). 1991;58:65-69. Doi: 10.1007/BF02750986. [crossref] [PubMed]
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DOI and Others

DOI: 10.7860/JCDR/2022/60560.17417

Date of Submission: Oct 03, 2022
Date of Peer Review: Oct 27, 2022
Date of Acceptance: Dec 06, 2022
Date of Publishing: Feb 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: Oct 04, 2022
• Manual Googling: Dec 01, 2022
• iThenticate Software: Dec 05, 2022 (12%)

ETYMOLOGY: Author Origin

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