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

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Dr Mohan Z Mani

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Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"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."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"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.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
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.
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

Important Notice

Original article / research
Year : 2022 | Month : November | Volume : 16 | Issue : 11 | Page : OC31 - OC35 Full Version

Quantitative Definition of Fever Needs a Change: A Longitudinal Study from the Hospital Workers and their Family Members


Published: November 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/57583.17169
Nitin Kumar, Mayank Kapoor, Prasan Kumar Panda, Yogesh Singh, Ajeet Singh Bhadoria, Minakshi Dhar

1. Junior Resident, Department of Internal Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India. 2. Junior Resident, Department of Internal Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India. 3. Associate Professor, Department of Internal Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India. 4. Associate Professor, Department of Physiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India. 5. Associate Professor, Department of Community and Family Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India. 6. Additional Professor, Department of Internal Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.

Correspondence Address :
Dr. Prasan Kumar Panda,
Sixth Floor, College Block, All India Institute of Medical Sciences (AIIMS), Rishikesh-249203, Uttarakhand, India.
E-mail: motherprasanna@rediffmail.com

Abstract

Introduction: The age-old definition of fever was derived using cross-sectional population surveying utilising old techniques without considering symptomatology. However, the diagnosis of fever must be made only in the presence of associated symptoms that can distinguish it, from the mere asymptomatic physiologic rise of temperature.

Aim: Analysis of symptoms to redefine the cut-off of fever based on symptomatology.

Materials and Methods: A longitudinal study on the healthy population of Uttarakhand, India was conducted and the population was followed-up from July 2019 to September 2020. Healthy staff and students of All India Institute of Medical Sciences (AIIMS), and their family members between 4-100 years of age were chosen. Participants were advised to self-monitor oral temperature with a standard digital thermometer in either left or right sublingual pocket and record it in the thermometry diary. The study was considered complete, if the participant had all the three phases of the study (i.e., prefebrile, febrile, and postfebrile phases) or completed the duration of the study. The febrile phase was defined when the participants subjectively ‘felt feverish’. Associated symptoms like fatigue, warmth, headache, and feeling malaise were also recorded.

Results: Mean age of the participants was 24.24±5.92 years, and 52.1% (75) were males. Per protocol analysis was done for febrile participants (n=144, temperature recordings=6544). The mean febrile phase temperature was 100.25±1.44°F. A temperature of 99.1°F had maximum diagnostic accuracy for feeling feverish (98.2%), along with 1 (98.3%) or 2 (99%) associated symptoms. Summer and spring months showed higher temperatures (100.38±1.44 vs 99.80±1.49, p-value <0.001), whereas no significant temperature difference could be noted amongst the genders.

Conclusion: Based on the findings of the present study, the revised temperature cut-off to define fever should be 99.1°F along with one or two associated symptoms.

Keywords

Pyrexia, Symptomatology, Temperature variability, Thermometry

“Humanity has but three great enemies: fever, famine, and war, and of these by far the greatest, by far the most terrible, is fever.” This statement by William Osler describes the paramount importance of fever since ancient medicine. The temperature has been one of the most important vital signs and recordings; it has been a critical component of good patient management. The core human body temperature depends on the appropriate functioning of the body (1). Maintaining it within an optimal range, is necessary for human life. It undergoes a regular circadian fluctuation of 0.5-0.7°C, with the lowest in the early morning and highest in the evening. Similar temperature variation is also seen in the females during their menstrual cycle. The temperature may rise 0.6°C or more through the menstrual cycle (2). Furthermore, the balance between heat production and heat loss determines the body temperature. Once this balance is lost, the temperature is raised in the body, known as fever. Hence, technically fever is a sign of some underlying pathology.

Wunderlich (1868) had defined the normal body temperature as 37°C (98.6°F). However, his methods were outdated. Mackowiak PA et al., set out to question this time-honoured Wunderlich’s dictum. They did a cross-sectional study on young adults (younger than 40 years) using a standardised thermometer and concluded that, 36.8°C (98.2°F) rather than 37.0°C (98.6°F) was the mean oral temperature of their participants; 37.7°C (99.9°F) rather than 38.0°C (100.4°F) was the upper limit of the normal temperature range (3). Protsiv M et al., hypothesised that the normal oral temperature of adults is lower than the established 37°C of the 19th century and concluded that body temperature has decreased over time in the United States of America (USA) using measurements (4). Recent studies suggest that normal temperature has invariably decreased by 0.03°C per birth decade, probably due to lowered metabolic rate and infections, henceforth drifting down the normal morning body temperature to less than <98.6°F over the last two centuries (4),(5),(6),(7),(8). The influence of age, time of day, gender, and economic development preclude an updated definition of fever (9).

All studies till now, were cross-sectional resulting in a complete bias of the measured temperature whether in prefebrile, febrile, or postfebrile phase. Temperature rise above normal (known as fever) is a sign that should be studied longitudinally. The change over time provides important physiologic clues to alterations in human health. Considering 98.6oF as normal body temperature in the light of newly available evidence would have untoward consequences, and it has been riddling since the inception of modern medicine and needs to be relooked into a new dimension preferably through a developing society. This can be done by prospectively studying body temperature of a healthy population when they are afebrile, have fever, and in the postfebrile phase.

Thereby, a longitudinal study was done on healthy participants using a standardised electronic thermometer in the left or right posterior sublingual pocket and analysing the associated symptomatology, to derive a new symptom-associated definition of fever.

Material and Methods

The longitudinal study was conducted at All India Institute of Medical Sciences Rishikesh (AIIMS), a tertiary healthcare centre in Uttarakhand, India. It was conducted from July 2019 to September 2020, after approval from Institute Ethical Committee (IEC) (No. 235/IEC/PGM/2019).
Lists of employees and students of AIIMS Rishikesh were obtained from the Human Resource Department and Registrar’s office. Information of participating family members was obtained from consenting employees and students. Participants were selected via a simple random sampling method using the computer. If the participant did not consent to the study, then the next person on the list was selected. Taking the standard deviation according to a study done by Mackowiak PA et al., as 0.7 and employing T-distribution to estimate sample size, a sample size of 192 with 95% confidence and a precision of 0.1 was estimated (3).

The participants were recruited based on the following inclusion and exclusion criteria, after taking informed consent.

Inclusion criteria: Healthy staff and students of AIIMS and their accompanying family members between 4-100 years working/studying at AIIMS during the study duration.

Exclusion criteria: Any individuals with any diagnosed or suspected disease (any acute infectious or non infectious illness (including trauma) within last one month and postpartum period upto eight weeks; any known case of or past history of chronic illness-infective (e.g. tuberculosis, Kala azar, brucellosis, infective endocarditis, Human Immunodeficiency Virus (HIV), hepatitis B/C/D etc.), rheumatological (e.g. rheumatoid arthritis, systemic lupus erythematosus, vasculitis etc.), chronic liver disease, chronic kidney disease, cardiovascular disease (e.g. systemic hypertension, coronary artery disease, valvular heart disease, pulmonary arterial hypertension, peripheral vascular disease etc.), chronic lung disease (e.g. any obstructive or restrictive airway diseases), endocrinopathy (e.g. diabetes mellitus, diabetes insipidus, hypo/hyperthyroidism etc.), gastrointestinal disease (e.g. dyspepsia, inflammatory bowel disease, malabsorption syndromes etc.), neurologic disorders (e.g. epilepsy, stroke, dementia, movement disorder, degenerative disorder, cerebral palsy etc.), psychiatric disorder (e.g. mood disorders, psychosis, dependence syndrome (s) etc.), dermatological diseases (e.g. bullous disorders, psoriasis, tinea etc.), any malignancy (treated or otherwise), recent history of vaccination in last six months, and ankyloglossia were all excluded from the study.

Study Procedure

Detailed clinical evaluation (history and examination) was done. Basic investigations (which were done within the last one year; as per Institute recruitment policy): ECG, chest X-ray, viral markers (anti-HIV-1 and 2, HBsAg, anti-HCV), urine routine, complete blood count, fasting blood glucose, liver and kidney function tests were collected from medical record section. If any abnormality was detected, they were excluded without sharing details.

The study was done in three phases:

• The first phase (non febrile phase)
• The second phase (febrile phase)
• The third phase (postfebrile phase).

The participant’s subjective sensation of feeling ‘feverish’ was taken to define the febrile phase’s onset with change in baseline temperature. One clinical thermometry diary, a ball pen, and a standard electronic thermometer [Dr. Morepen Digiflexi Flexi Tip Thermometer® (MT222) with error 0.05oF] were provided to all the participants. They washed their hands and ensured no physical exertion in the preceding 30 minutes. The thermometer was placed in the oral left or right posterior sublingual pocket. The participants recorded the temperature on the Fahrenheit scale and the time in the thermometry diary. Three readings were taken, once after waking up (AM), once in the afternoon (AN; 12-3 PM), and once before sleeping (PM). They also recorded any symptoms from the checklist simultaneously. There were three days of more frequent temperature charting (every 2nd hour, except sleeping time) during the non febrile phase and two days of frequent 32temperature charting during postfebrile phase, and for all the days during the febrile phase.

The investigator verified the first reading. Participants were followed-up fortnightly physically and reminded weekly telephonically for recording temperatures. Self-recording of data was done in the provided clinical thermometry diary, and the same was assessed fortnightly by the investigator (s) for troubleshooting and to see the status of the recording.

There was no comparator except among three phases of temperature recordings. Participants with the febrile phase were further divided into four subgroups based on seasonal months: November-January (represented coldest months of the year); February-April (representing spring months); May-July (representing hottest months); August-October (representing autumn months). A maximum of 45 days of data was taken immediately before the febrile phase, during the non febrile phase of per protocol analysis. A maximum of 10 days of data was taken immediately after the febrile phase during the postfebrile phase, and complete data of the febrile phase was taken for analysis. The frequent temperature readings (i.e. two hourly temperature records) were taken for analysis for all three phases, especially to see variations.

Statistical Analysis

The data was entered in the excel sheet, and primary outcomes were analysed as per protocol analysis (for those participants who had all the three phases in the study) using Statistical Package for Social Sciences (SPSS) version 23.0. Categorical variables were presented as number and percentage (%) and continuous variables as mean±Standard Deviation (SD). The Kolmogorov-Smirnov test tested the normality of data, and if rejected, a non parametric test was used. Quantitative variables were compared using the independent t-test/Wilcoxon’s Mann Whitney test (when the data sets were not normally distributed) between two groups and the Kruskal’s Wallis test between three and more groups. The continuous variables, those that were not normally distributed, were analysed using Shapiro-Wilk Test. To define fever cut-offs with respect to symptoms, Receiver Operating Characteristic (ROC) curve analysis was done, and the cut-off was taken as the point with maximum diagnostic accuracy. Taking confidence level as 95%, a p-value <0.05 was taken as statistically significant.

Results

Three hundred fifty (350) participants were screened, 250 consented to be a part of the study, and 215 were found to be clinically healthy, 144 were included in the per protocol analysis (Table/Fig 1). The participants included healthy subjects with a mean age of 24.24±5.92 years (8-58 years); 72.2% (104) belonged to the age group 20-40 years; 52.1% (75) were males (Table/Fig 2). The normal temperature variation was measured (Table/Fig 3) along with associated symptoms. According to the per protocol analysis for the 144 participants, 6544 readings were taken for analysis.

The temperature cut-offs for feeling feverish were determined based on ROC analysis with diurnal, seasonal, and gender variations (Table/Fig 4),(Table/Fig 5)a,b. The temperature values were highest in the months of spring (100.38±1.44°F) and summer (100.26±1.40°F) months as compared to winter (100.13±1.42°F) and autumn (99.80±1.49°F) (p-value <0.001).

Discussion

Analysis of 6544 temperature readings of the 144 healthy participants was done longitudinally over one year. This longitudinal study of a healthy population, mainly in the adult age group, demonstrated that a temperature of 99.1°F had the highest diagnostic accuracy in predicting fever (98.2%), which increased further when associated with 1 (98.3%) or 2 (99%) additional symptoms. The diagnostic accuracy of temperature measurement and the associated symptomatology for fever prediction was highest in the morning compared to the afternoon or evening. The predictive ability was maximum in the summer months (May-July) compared with spring, winter, and autumn (Table/Fig 4)a,b,c,(Table/Fig 5)a,b. The criteria demonstrated, higher sensitivity amongst the females than the males. Accuracy increased with the increase in the number of associated symptoms.

An AM temperature of >37.2°C (>98.9°F) or a PM temperature of >37.7°C (>99.9°F) defines fever (10). American College of Critical Care Medicine, the International Statistical Classification of Diseases, and the Infectious Diseases Society of America define fever as a core temperature of 38.3°C (100.9°F) or higher, just above the upper limit of normal human temperature, irrespective of the cause (11). This quantitative diagnostic study considers the associated symptomatology to determine the temperature cut-off for fever and is the first to be reported. As mentioned before, all previous studies on the definition of fever were cross-sectional, and no study took into account the symptomatology along with the quantification of fever. The present study defines fever accurately, because of the longitudinal instead of cross-sectional design. Accordingly, when the person has the associated symptoms, fever sets in as mere temperature rise can be physiological also. Usually, the body temperature rises as the day passes (12). This formed the basis of the old fever definition having a lower threshold for the morning temperature than the evening.

Renbourn ET and Bonsall FF in British India found out that oral temperatures higher than those accepted as usual for temperate climates were recorded during the summer months in North India (13). This again demonstrates that, the temperature per se is just a quantitative variable that can also undergo fluctuations with the outside seasonal variation, further strengthening present study’s importance. A mere rise of temperature value should not be called fever, but this should be termed fever when combined with the associated symptoms. In present study also, the temperature values were highest in the spring (100.38±1.44°F) and summer (100.26±1.40°F) months as compared to winter (100.13±1.42°F) and autumn (99.80±1.49°F) (p-value <0.001). No previous studies have observed these changes. Females are considered to have higher baseline temperatures, although present study could not find any significant temperature difference between the two sexes in present study.

Limitation(s)

The sample was unicentric and difficult to generalise; thus, a more extensive multicentric study is required. The vulnerable group of the population, elderly and children, could not be included in the study desirably. The participants were defined healthy, based on history and predefined biochemical and laboratory parameters; therefore, indolent chronic infections and subclinical non infectious illnesses could not be ruled out. No physical way of checking the adherence to the advised procedure for the temperature measurement was there. The participants were reviewed and followed-up fortnightly. So, strategies to measure directly observed temperature may be required. The oral temperature in the left or right sublingual pocket is close representative of core body temperature but not precisely the core body temperature. The ongoing Coronavirus Disease-2019 (COVID-19) pandemic might have influenced the results. The participants constituted were a high-risk populace for infectious agents and stress. As mentioned, patients were allowed to take antipyretics; hence the temperature values could be lower with drug use. Another major limitation was that the febrile phase’s categorisation was solely based on the subject’s subjective sensation of feeling feverish. As it is a subjective sensation, it can vary from person to person. Nevertheless, this in itself forms the basis of the present study that fever is a sign that varies from person to person, and it is not merely a numerical cut-off that can be generalised to the whole population.

Conclusion

Authors propose an oral temperature cut-off of 99.1°F, along with one or more associated symptoms, to accurately predict fever with a sensitivity of 88% and specificity of 99%. This finding calls for a universal change in the definition of the same in Indians. There is lower value of the evening temperatures in the febrile phase, may be due to more antipyretics intakes at day times. The temperature values were highest in the spring and summer months as compared to winter and autumn.

Declaration

There is a preprint online version of the present manuscript available with URL: https://doi.org/10.1101/2021.06.13.21258846.

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DOI and Others

DOI: 10.7860/JCDR/2022/57583.17169

Date of Submission: May 05, 2022
Date of Peer Review: Jun 11, 2022
Date of Acceptance: Sep 20, 2022
Date of Publishing: Nov 01, 2022

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

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