Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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On Sep 2018




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Chairman, Research Group, Charutar Arogya Mandal, Karamsad
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Ex-Member, Governing Body, National Neonatology Forum, New Delhi
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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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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.
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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.


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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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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 : 2010 | Month : December | Volume : 4 | Issue : 6 | Page : 3331 - 3336 Full Version

The Performance Of Haematological Screening Parameters And CRP In Early Onset Neonatal Infections


Published: December 1, 2010 | DOI: https://doi.org/10.7860/JCDR/2010/.1054
RAMESH BHAT Y* AND AMITHA RAO**

MD (Paed), Associate Professor; **MD (Paed), Associate Professor, Department Of Pediatrics, Kasturba Medical College, Manipal. 576104, Udupi District, Karnataka, India

Correspondence Address :
Ramesh Bhat. Y. MD (Paed)
Associate Professor
Department of Paediatrics
Kasturba Medical College,
Manipal-576104
Manipal University
Udupi District, Karnataka, INDIA
E-mail: docrameshbhat@yahoo.co.in
Tel: (91) 9448296564
Fax: (91) 820 2571934

Abstract

Background: In neonates with early onset sepsis (EOS), the haematological screening parameters and C-reactive protein (CRP) have wide variations in performance.
Objective: To evaluate the performance of haematological screening parameters and CRP in blood culture positive neonatal EOS.
Methods: We retrospectively studied the neonates who were suspected to have bacterial infections within the first 48 hours of life, based on the risk factors and/or the clinical features in whom haematological screening parameters, CRP and blood cultures were obtained. The screening parameters included total leukocyte count (TLC), the ratio of immature to mature neutrophil count (B: N), micro-ESR, platelet count (PLT), toxic granules (TG) and cytoplasmic vaccuolations (CV) in peripheral smear, and CRP. The screening parameters were assessed for individual performance and in combination in culture positive neonates.
Results: Of the 1291 neonates who were screened for EOS, 212 (16.4%) had positive blood cultures. The male to female ratio was 1.08:1. Preterm, small for gestational age and symptomatic newborns constituted 33.9%, 17.9% and 39.2% of the total number of neonates respectively. Coagulase negative Staphylococcus, Klebsiella and Pseudomonas were the predominant culture isolates. Among the haematological parameters, the positivity was best with micro-ESR (44.8%) and the least with TG/CV (2.8%). Any 2 or more parameters were positive in one third of the subjects. TLC and micro-ESR had significantly more positivity among the symptomatic than the asymptomatic neonates (P<0.01). Odds of any 2 or more parameters which were positive for symptomatic relatives to the asymptomatic neonates was 3.89 (95% CI: 2.14 - 7.06; P <0.001)
Conclusion: The sensitivities of the traditional haematological screening parameters and CRP were not satisfactory in identifying the neonates with EOS. A relatively better performance is expected in the symptomatic than in the asymptomatic neonates.

Keywords

, early-onset sepsis, screening, haematological parameters, CRP ____________________________

The successful treatment and good treatment outcome of bacterial infections in neonates depend on the early initiation of appropriate antibiotic therapy. Hence, clinicians are always compelled to make an early diagnosis. However, the early diagnosis of bacterial infections is a difficult task. (1) (2) (3) The positive blood culture report which is a gold standard for the diagnosis of neonatal sepsis, requires 48-72 hours of time. (2) (3) Further, the yield of the blood culture is also low (2) (3) (4) (5) (6) and in some hospitals, the facilities may not be available. Hence, for early identification, several screening tests and their usefulness, either individually or in combinations, have been reported. The published haematological screening parameters and C-reactive protein (CRP) have wide variations in performance. (2) (3) (6) (7) (8) (9) (10) Few authors have reported a poor prediction of sepsis by the individual parameters (11) (12), but a sensitivity of above 90% by a combination of parameters has been reported by others.(6) (9) Recently, few researchers suggested the need for the reassessment of the complete blood count. (13) They did not use CRP as a screening tool and reported a higher sensitivity of the physical examination. In this context, the present study was undertaken to evaluate the performance of various haematological screening parameters and CRP in neonates with blood culture proven early-onset sepsis (EOS) over a period of five years.

Material and Methods

The study was conducted retrospectively in the neonatal unit of a teaching hospital between January 2000 and December 2004. Neonates who were clinically suspected to have bacterial infections within the first 48 hours of life, based on the risk factors and/or clinical features, were subjected to various haematological screening parameters and blood cultures. Neonates developing symptoms after 48 hours of life and blood cultures which grew fungi were excluded. The haematological screening parameters included total leukocyte count (TLC), platelet count (PLT), micro- erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), band to mature neutrophil ratio (B: N) and the presence of cytoplasmic vaccuolations (CV) and/or toxic granulations (TG) in peripheral smear examinations. The semi quantitative measurement of CRP by the slide agglutination technique was done between the first 24- 36 hours of life. The blood culture samples included a single sample from a peripheral vein/artery which was taken under aseptic conditions before commencing antibiotics. Chest X-ray and other investigations were performed whenever indicated.
For the study, a TLC of <5000 or >20000/mm3 (7) (8) (9), a PLT of <150000/mm3 (9), a CRP of >6mg/L, B: N ratios of ≥0.2 (8) (12) and the presence of CV or TG in the peripheral smears (2) (10) were considered to be abnormal. Micro-ESR (14) was considered to be positive if the readings were more than >97th percentile/1st hour. These haematological parameters were assessed for the performance individually and in combination in neonates having positive blood cultures. We also compared the positivity of the parameters in symptomatic and asymptomatic neonates. A neonate was considered to be symptomatic if he/she had lethargy, fever, hypothermia, poor feeding and/ or manifestations which were pertaining to the respiratory, gastrointestinal, cardiovascular, central nervous (CN) or the haematological systems. Other neonates with no abnormalities were considered to be asymptomatic.
Statistical analyses were performed by using the Statistical Package for Social Sciences for Windows version 11.5 software. Chi square (χ2) tests were used to compare the categorical variables. A p-value of <0.05 was considered to be significant.

Results

The study was conducted retrospectively in the neonatal unit of a teaching hospital between January 2000 and December 2004. Neonates who were clinically suspected to have bacterial infections within the first 48 hours of life, based on the risk factors and/or clinical features, were subjected to various haematological screening parameters and blood cultures. Neonates developing symptoms after 48 hours of life and blood cultures which grew fungi were excluded. The haematological screening parameters included total leukocyte count (TLC), platelet count (PLT), micro- erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), band to mature neutrophil ratio (B: N) and the presence of cytoplasmic vaccuolations (CV) and/or toxic granulations (TG) in peripheral smear examinations. The semi quantitative measurement of CRP by the slide agglutination technique was done between the first 24- 36 hours of life. The blood culture samples included a single sample from a peripheral vein/artery which was taken under aseptic conditions before commencing antibiotics (Table/Fig 1). Chest X-ray and other investigations were performed whenever indicated.
For the study, a TLC of <5000 or >20000/mm3 (7) (8) (9), a PLT of <150000/mm3 (9), a CRP of >6mg/L, B: N ratios of ≥0.2 (8) (12) and the presence of CV or TG in the peripheral smears (2) (10) were considered to be abnormal. Micro-ESR (14) was considered to be positive if the readings were more than >97th percentile/1st hour. These haematological parameters were assessed for the performance individually and in combination in neonates having positive blood cultures. We also compared the positivity of the parameters in symptomatic and asymptomatic neonates. A neonate was considered to be symptomatic if he/she had lethargy, fever, hypothermia, poor feeding and/ or manifestations which were pertaining to the respiratory, gastrointestinal, cardiovascular, central nervous (CN) or the haematological systems. Other neonates with no abnormalities were considered to be asymptomatic.
Statistical analyses were performed by using the Statistical Package for Social Sciences for Windows version 11.5 software. Chi square (χ2) tests were used to compare the categorical variables. A p-value of <0.05 was considered to be significant.newborns

ESR, erythrocyte sedimentation rate; CRP, C-reactive protein, B: N ratio, band to mature neutrophil ratio; OR, odds ratio; CI, confidence interval.
A, two or more parameters positivity was seen in a higher percentage of symptomatic (53%) than asymptomatic (22.5%) neonates, with blood culture positivity (Odds ratio: 3.89; 95% CI: 2.14 - 7.06; P <0.001).

Discussion

Newborns are uniquely susceptible to overwhelming bacterial infections. The incidence of early-onset bacterial infections range from 1-10 per 1000 live births and the related mortality ranges between 15% and 30 %.(15) (18) The morbidity among the survivors is also high.(1) (4) (15) (16) (17) (18) Further, newborns who develop sepsis often deteriorate rapidly. Because the failure or delay in treatment is likely to result in significant mortality and morbidity, early and efficient diagnosis is challenging to the clinician. The blood culture not only takes time, but is also complicated, with a low yield. In the present study, the blood culture yield was 16.4%. This was low, as compared to the 20 % yield which was obtained by many authors.(2) (4) (5) (11) A much lower yield (14%) has been reported by Varsha et al. (6) In the present study, the treatment of the mothers of at -a -risk neonates and the single blood culture samples could have contributed to the low culture yield.

The traditional sepsis work up included various haematological parameters and CRP. The predictive ability of these parameters has been found to vary widely in the literature.(7) (8) (9) (10) (12) (13) (18) (19) (20) In the present study, the sensitivity of the haematological screening parameters and CRP varied from 2.8%-44.8%. Micro ESR had the best sensitivity, but it was only 45%. None of the screening parameters individually predicted the presence of bacteraemia satisfactorily. Similar observations were made earlier too. (11) (12)

The total leukocyte count and the B: N ratios have been correlated with an increased risk of bacterial infections in neonates.(7) (8) (9) However, they had a wide range of sensitivity (17-90%).(2) (6) (7) (8) (9) (19) In our study, the sensitivity was 29.7% for TLC and 15.6% for the B: N ratio. Neutropenia was observed in 1.9% of the culture proven sepsis cases. Degenerative changes in neutrophils like cytoplasmic vacuolization and toxic granulation were reported to be a valuable adjunct in the early detection of neonatal bacterial infection. A sensitivity of 81% to CV and 67% to TG has been found by Liu and his colleagues. (10) Sharma et al (2) found a sensitivity of TG in 60% and CV of 15% among the proven sepsis cases. In contrast, we observed a sensitivity of only 2.8% in TG/CV.

The micro-ESR is an inexpensive, easy bedside screening test. Its sensitivity ranges from 30% to 73% (2) (3) (8) in proven sepsis cases. An enhanced sensitivity of revised over traditional micro-ESR has been reported earlier. (14) In the present study, the revised micro-ESR had the best sensitivity (44.8%). Thrombocytopenia as an important parameter in supporting the diagnosis of sepsis has been described, although it appears to be a late finding and to be nonspecific. (3)(18) The positivity of thrombocytopenia was 16.9% in our study. The reported sensitivity of CRP for the detection of bacterial infections varied widely from 47% to 100%.(6) (8) (12) (20) Further, Benitz (21) et al found that the sensitivity of CRP in culture proven EOS rose from 35% at the initial evaluation to 78.9% in next 24 hours. They also opined that the sensitivity of a normal CRP at the initial evaluation is not sufficient to justify withholding antibiotic therapy and they suggested serial CRP estimations. The CRP level done on day 2 of life in our study, showed a sensitivity of only 16.9%. The importance of the serial measurement of the septic screens was demonstrated by Gerdes (20) et al, who performed two separate screens (WBC, I/T, CRP, micoESR), 12 to 24 hours apart. Infants who had normal initial screens were positive on repeat testing and identified all septic neonates. Our study has been limited by a one- time evaluation of the screening parameters.

As the sensitivity and the specificity of the individual tests may not justify their individual use in newborn infants, a significant improvement of diagnostic capability when used in various combinations, has been studied. The greatest sensitivity when 2 or more of 5 tests (WBC, B:N, CRP, heptoglobin and micro-ESR) were done, was established by Philip et al.(8) To further improve the diagnostic efficacy, Rodwell(9) et al developed a seven-point haematological scoring system which had 96% sensitivity. An above 80% sensitivity by the combination of any 2 or more positive tests in culture positive EOS was also reported earlier from Indian studies.(2) (6) In contrast, we observed a sensitivity of 34.4% by the combination of any two or more parameters. This observation agrees with that of Fowlie and Schmidt (22)

An accurate and timely diagnosis of early onset neonatal sepsis remains challenging to the clinician and the laboratory. A test with a rapid turnaround time, with 100% sensitivity which allows accurate diagnosis and appropriate antimicrobial treatment, is desirable. A reasonable specificity is also required to allow the antibiotics to be safely withheld in non-infected infants. The sensitivity of individual tests or combinations varies widely. Escobar (7) et al did not use CRP in their evaluation because of a lack of the full assessment of its utility. They opined that the current recommendations were vague, that the B: N ratio was unreliable and that the risk of sepsis among asymptomatic infants was low. Further, they reported that the sensitivity of the physical examinations was much higher. They also suggested the reassessment of the complete blood count and the need for more research in the areas of clinician compliance, as well as the clinician perception of the risk of sepsis. Recently, measures of acute phase proteins, cytokines, cell surface antigens, and bacterial genomes have been used alone or in combination to improve the diagnosis of neonatal sepsis.(23)

Among the cytokines, interleukin (IL)-6 and IL-8 have been demonstrated to have good diagnostic utilities as early phase markers, while acute phase reactants such as C-reactive protein and procalcitonin have superior diagnostic properties during the later phases. Other markers, including inter-alpha-inhibitor proteins and IL-10 have been demonstrated to yield important prognostic information. The advent of flow cytometry and molecular techniques have made crucial contributions to the field and have improved the diagnostic accuracy.(24)(25) Among the promising cytokines, interleukin (IL)-6 has been most intensively studied. Its sensitivity ranges from 70-80%. Khassawneh M et al . (26) reported that the IL-6 cut-off value of 18.2 pg/ml was associated with a sensitivity and specificity of 87% and 50% respectively. Procalcitonin (PCT) is another promising marker with a sensitivity in the range of 70–80% at birth.(25) In the immediate postnatal period however, although the sensitivity of IL-6 decreases over time, the sensitivity of PCT (as well as that of CRP) increases, making the serial measurements useful for those situations in which one needs to decide how long to treat the infant. Cutoff concentrations of >6.1 ng/ml of PCT for the optimum prediction of sepsis in neonates, were reported.(27)

Hassawneh M et al (26) also studied the role of immunoglobulin M (IgM). The sensitivity of IgM as a single test at a value of ≥10 mg/dl was 91.3% for patients with ‘sepsis’ or ‘probable sepsis’. This sensitivity in identifying patients with sepsis was paralleled with a low specificity of 45%. They found that the performance of CRP was better than IgM and IL-6 in distinguishing between the neonates with sepsis and without sepsis.

Recently, attention has been directed to the leukocyte cell surface antigens as the diagnostic markers of sepsis. Neutrophil surface CD64 and CD11b expression have been studied. For culture-positive sepsis episodes, the CD64 index having the highest area under the curve (0.852) of all haematologic variables, with a sensitivity of 80% and a specificity of 79%, with a cutoff value of 4.02, was reported.(28) Dorothee et al (29) suggested that the expression levels of the Toll-like receptor (TLR)2 on monocytes by flow cytometry, is comparably more valuable than C-reactive protein, IL-8, and IL-6 as early sepsis markers. The routine availability of new tests at affordable costs is likely to enhance the rapid identification of neonatal sepsis

Conclusion

The sensitivities of the traditional haematological screening parameters and CRP are not satisfactory in neonates with blood culture positive early onset infections. The sensitivity of a combination of any two or more parameters is also not satisfactory, although a relatively better sensitivity is likely in symptomatic than in asymptomatic neonates. Because an early onset neonatal infection is a serious but treatable condition whose treatment should not be missed or delayed, a test or a combination of tests with a high sensitivity is desirable. A better understanding of the neonatal inflammatory response to sepsis and the identification of sensitive and specific markers of inflammation or rapid microbe-specific diagnostic tests are needed to assist the clinician in the early detection of neonatal sepsis.

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