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 Table of Contents  
GUEST EDITORIAL
Year : 2021  |  Volume : 4  |  Issue : 1  |  Page : 3-5

Case reports bridge physicians, scientists, and therapeutics


Consultant Dermatologists, Institute of Applied Dermatology, Kasaragod, Kerala, India

Date of Submission16-May-2021
Date of Acceptance22-May-2021
Date of Web Publication17-Jun-2021

Correspondence Address:
Dr. S R Narahari
Institute of Applied Dermatology, Kasaragod - 671 124, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jacr.jacr_36_21

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How to cite this article:
Narahari S R, Prasanna K S. Case reports bridge physicians, scientists, and therapeutics. J Ayurveda Case Rep 2021;4:3-5

How to cite this URL:
Narahari S R, Prasanna K S. Case reports bridge physicians, scientists, and therapeutics. J Ayurveda Case Rep [serial online] 2021 [cited 2021 Dec 4];4:3-5. Available from: http://www.ayucare.org/text.asp?2021/4/1/3/318660



Case reports by practitioners of Indian Systems of Medicine can contribute to integrative medicine when factual and based on truths recognizable as scientific writing. In recent years, the most approved scientific writing has required a large number of participants, analyzed as randomized, controlled, and double-blinded. There is a contemporary hierarchy called evidence-based medicine, which places systematic reviews of trials of this kind at the top and case reports well below this, especially if they are also labeled alternative or complementary. However, medicine developed over the last 400 years from, for example, Transactions of the Royal Society in London which mainly were case reports. The Principles and Practice of Medicine (1892) of Sir William Osler, also known as the father of change as clinical biomedicine, were based on the examinations of sometimes only one or two patients in life, often followed by post mortems and hardly depended on large numbers nor systematic reviews.

Below we are arguing in favor of the use of case histories/case reports by Ayurveda practitioners. We illustrate some examples that may encourage writers to be scientific, and when done with utmost dedication, how would it change the medical practice as happened in the past till the recent times.

Sir Archibald Garrod (1899) described in his book “The Inborn Errors of Metabolism,” an illness that ran in a few families with children who passed dark-colored urine (Alcaptonuria), and he initiated a belief that some hereditary material is responsible for it.[1] In 1952, it was just one photograph that changed our perception of the scientific basis of medicine. In King's College, London, Rosalind Franklin clicked the X-Ray diffraction photograph (No 51) of the DNA fiber, demonstrating intertwined helical chains. James Watson from Cambridge visited her biophysics laboratory and examined just that one clear photograph and completed the DNA crystal model. It was enough for James Watson, Francis Crick, and Maurice Wilkins (Franklin's colleague) to win the Nobel Prize in 1962.[2]

In 2010, French scientist Barrangou stumbled on one case of bacterial defence in her cheese and yoghurt producing research lab. She and her team identified a bacterial protein Cas9 that cut the enemy viral genome after matching it precisely, heralding the era of genomic surgery and gene therapy.[3] These are only a few examples of famous single experiments and case reports that changed the direction of science and clinical practice. There are many others.

Riley DS is passionate about case reports. He led the development of reporting guidelines for case reports (2013) and later revised them in 2017.[4] More elaborate ways of writing and publishing case reports are debated in https://www.care-statement.org/and Equator network https://www.equator-network.org/. While case reports are important sources of new ideas and information in medicine and come at the bottom of the evidence hierarchy, we will argue that for Indian Systems of Medicine, this should no longer be so.

Oxford-based clinical pharmacologist Aronson argued in an article in the BMJ that deserves complete analysis that case reports have functions different from randomized control trials or systematic reviews.[5] They include describing a newly recognized adverse reaction or interaction, generating hypotheses, testing hypotheses and diagnostic techniques, elucidating mechanisms, management methods, education, and descriptions of new diseases.[6],[7] Sometimes, case reports on adverse effects lead to removing drugs from the market[8] or re-purpose those drugs to new treatments.[9]

At the Institute of Applied Dermatology in Kerala, we have learned to believe that Indian Systems of Medicine have an excellent potential for demonstrating the value of case reports. In 2004, we presented and published the first case report on integrative medicine for the morbidity management of the swollen legs of Lymphatic Filariasis (lymphedema).[10] It evolved into a more extensive case series and then a community-based clinical trial. The government of India (through the Central Council for Research in Ayurvedic Science) supported a large-scale clinical trial at the primary health center level in the endemic districts.[11] Later studies differentiated lymphedema biochemically,[12] influencing patient management globally. Today experts recommend its massive scale up to benefit patients worldwide,[13] and it is also under the active consideration of the public health administrators in India.[14] However, behind the successful lymphedema treatment, there exists a lifetime experience of Terence Ryan, Emeritus Professor of Dermatology at Oxford, UK.[15] His deep understanding of the lymphatic system and previous studies on lymphedema.

We believe that one illuminating observation may take too long to become a case report in the same way. As stated by Martini, the effect of limes and other Vitamin C sources on scurvy may have taken too long to be fully appreciated and still longer to become a widely read publication.[6] Physicians spend years in clinics, with considerable enduring experience, to get that intuition of how a drug could be re-purposed or to recognize a rare case study taking the road less traveled.

Why should case reports be in a different platform in evidence-based medicine? “Evidence-based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients.” The practise of evidence-based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research.[16] Inherent in this definition is a suggestion for a significant role of judgment and, as Prof Sackett wrote, “individual clinical experience” in the selection and interpretation of evidence. Evidence groups are beginning to argue that the “narrative reviews” serve different purposes than “systematic review” and should be viewed as complementary to each other. There is a view that systematic reviews currently sitting at the top of the evidence pyramid have a narrow and unexciting research agenda and contributing to research waste.[17] There is a growing demand in the evidence-based world that intervention studies should reduce uncertainties in the generalizability of research outcome by recognizing the minor changes observed in practice through non-randomized study designs of diverse types of evidence.[18]

Ayurveda case reports have the potential to lift them from the bottom of the evidence pyramid and take up space for themselves in clinic to laboratory research, also known as reverse pharmacology. The origin of life, according to Ayurveda, is through a combination of five elements; air, water, fire, earth, and other elements in the environment. It is known as Panchamahabootha theory. The origin of life has been intriguing to many scientists. These fundamental theories of Ayurveda could be linked to the physician-scientist research paradigm embracing modern scientific advances with ancient wisdom.[19] Stanley Miller at the University of Chicago used an aspirator that injected steam into the electric discharge chamber, simulating a volcanic eruption to understand the origin of the gene (life). He created a “primordial environment” (as believed by the geologists at that time) in a sealed glass flask with water, air, brimstone and blew methane, carbon dioxide, and ammonia.[20] Miller later heated and cooled the flask repeatedly. Three weeks later, he found traces of amino acids (building units of protein) and trace amounts of sugars, lipids, fats, and building blocks of RNA and DNA. Decades later, Zhou et al.,[21] Harvard and Parker et al.,[22] California, carried out similar and more sophisticated experiments and inferred that micelles formed from such combinations could self-assemble to form RNA chains. Especially in integrative medicine, where Ayurveda is a major component, combining concepts to critical technology is the much-needed paradigm shift. The Ministry of Ayush, Government of India, giving a push to traditional Indian medicine's expansion, will probably be delighted to fund intersectoral ayurvedic research from well-thought-out case studies.

Do Ayurveda case reports have the ability to disrupt the clinical practice? If so, how to identify such game-changers? In the history of science and technology, breakthroughs came in two sectors:

  1. Scale shifts where the advance emerges by the alteration in the size or scale alone (“the moon rocket as a massive jet plane pointed vertically at the moon”)[2] and
  2. Conceptual shifts in which advance arises due to a radical new idea (linear to circular motion: the wheel).


Both are reinforcing. Scale shifts enable conceptual shifts, and new concepts, in turn, demand expansion. Identifying the exact clinical features of the disease by integrating objective outcomes of biomedicine will lead to selecting herbal formulations as re-purposed drugs. This holistic clinical view might bring out promising studies but should include adequate controls, sound methodology, and experimental design with definite conclusions to throw light on its practical usefulness. Government or philanthropic agencies could support such concepts to scale up through reverse pharmacology. In the case of lymphedema, parameters for analysis (scaling) could be determined by known mechanisms. These must include estimating pro-inflammatory Th2 cytokines (interleukin [IL]-4, IL-6, and IL-10) and pro-fibrotic cytokines (IL-5, IL-13, and transforming growth factor-beta), the ratio of MMP1/TIMP4 and MMP8/TIMP4, angiogenesis, and collagen regulation. It is sure to achieve the greater impact of Ayurveda case reports at lesser cost and time, contributing to global health.

More information does not make us more informed,[23] wrote John Chambers, who, as the CEO of Cisco Systems, showed that conceptual shift could be combined with scale shifts, and new ideas have their own space in science and technology. In the context of Ayurveda, they are currently positioned globally as a substitute for biomedicine hence, grouped under complementary and alternative medicine. Despite its millennia of existence, Ayurveda is fighting the odds of losing its base.[24] Conceptual shifts through transitions across its boundaries, such as re-purposing drugs through reverse pharmacology as therapeutic integration and thereby absorbing technological advances, seems the right way forward.[25] Clinical medicine made significant progress based on unexpected discoveries in single cases/experiments from penicillin[26] to sildenafil.[27] Case studies are bridging physicians, scientists and therapeutics, re-emerging and persuading for the recognition it deserves within the evidence-based paradigm. Its acceptance reflected in the rapid increase of new case report journals.[28]



 
  References Top

1.
Piro A, Tagarelli G, Lagonia P, Quattrone A, Tagarelli A. Archibald Edward Garrod and alcaptonuria: “Inborn errors of metabolism” revisited. Genet Med 2010;12:475-6.  Back to cited text no. 1
    
2.
Mukherjee S. The Gene: An Intimate History. New Delhi: Allen Lane (Penguin Books); 2016.  Back to cited text no. 2
    
3.
Gasiunas G, Barrangou R, Horvath P, Siksnys V. Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc Natl Acad Sci U S A 2012;109:E2579-86.  Back to cited text no. 3
    
4.
Riley DS, Barber MS, Kienle GS, Aronson JK, von Schoen-Angerer T, Tugwell P, et al. CARE guidelines for case reports: Explanation and elaboration document. J Clin Epidemiol 2017;89:218-35.  Back to cited text no. 4
    
5.
Aronson JK. Anecdotes as evidence. BMJ 2003;326:1346.  Back to cited text no. 5
    
6.
Martini E. Treatment for scurvy not discovered by Lind. Lancet 2004;364:2180.  Back to cited text no. 6
    
7.
Centers for Disease Control (CDC). Pneumocystis pneumonia – Los Angeles. MMWR Morb Mortal Wkly Rep 1981;30:250-2.  Back to cited text no. 7
    
8.
Narahari SR. Terfenadine precipitating exfoliative dermatitis in Psoriasis. Ind J Dermatol Venereol Leprol 1996;62:408-12.  Back to cited text no. 8
    
9.
Burton JL, Marshall A. Hypertrichosis due to minoxidil. Br J Dermatol 1979;101:593-5.  Back to cited text no. 9
    
10.
Narahari SR. Role of Indian system of medicine in the management of filarial lymphoedema. Lymphology 2004;37 (Suppl):673-77.  Back to cited text no. 10
    
11.
Narahari SR, Bose KS, Aggithaya MG, Swamy GK, Ryan TJ, Unnikrishnan B, et al. Community level morbidity control of lymphoedema using self care and integrative treatment in two lymphatic filariasis endemic districts of South India: A non randomized interventional study. Trans R Soc Trop Med Hyg 2013;107:566-77.  Back to cited text no. 11
    
12.
Karayi AK, Basavaraj V, Narahari SR, Aggithaya MG, Ryan TJ, Pilankatta R. Human skin fibrosis: Up-regulation of collagen type III gene transcription in the fibrotic skin nodules of lower limb lymphoedema. Trop Med Int Health 2020;25:319-27.  Back to cited text no. 12
    
13.
Narahari SR, Ryan TJ. Morbidity management and disability prevention: An agenda for developing nations initiated in India. Lymphology 2020;53:157-61.  Back to cited text no. 13
    
14.
Narahari SR, Ryan TJ. Mainstreaming of an integrative medicine protocol for morbidity management and disability prevention of lymphatic filariasis: An opportunity for establishing AYUSH based national health programme. AAM 2020;9:108-15.  Back to cited text no. 14
    
15.
Vaqas B, Ryan TJ. Lymphoedema: Pathophysiology and management in resource-poor settings – Relevance for lymphatic filariasis control programmes. Filaria J 2003;2:4.  Back to cited text no. 15
    
16.
Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: What it is and what it isn't. BMJ 1996;312:71-2.  Back to cited text no. 16
    
17.
Greenhalgh T, Thorne S, Malterud K. Time to challenge the spurious hierarchy of systematic over narrative reviews? Eur J Clin Invest 2018;48:e12931.  Back to cited text no. 17
    
18.
Ogilvie D, Adams J, Bauman A, Gregg EW, Panter J, Siegel KR, et al. Using natural experimental studies to guide public health action: Turning the evidence-based medicine paradigm on its head. J Epidemiol Community Health 2020;74:203-8.  Back to cited text no. 18
    
19.
Goldstein JL, Brown MS. The clinical investigator: Bewitched, bothered, and bewildered But still beloved. J Clin Invest 1997;99:2803-12.  Back to cited text no. 19
    
20.
Miller SL. A production of amino acids under possible primitive earth conditions. Science 1953;117:528-9.  Back to cited text no. 20
    
21.
Zhou L, Ding D, Szostak JW. The virtual circular genome model for primordial RNA replication. RNA 2021;27:1-11.  Back to cited text no. 21
    
22.
Parker ET, Cleaves HJ, Callahan MP, Dworkin JP, Glavin DP, Lazcano A, et al. Enhanced synthesis of alkyl amino acids in Miller's 1958 H2S experiment. Orig Life Evol Biosph 2011;41:569-74.  Back to cited text no. 22
    
23.
Chambers J, Brady D. Connecting the Dots: Lessons for Leadership in a Start up World. London: Harper Collins Publishers; 2018.  Back to cited text no. 23
    
24.
Singh RH. Declining popularity of AYUSH, the recent report of national sample survey organization. Ann Ayurvedic Med 2015;4:1-2.  Back to cited text no. 24
    
25.
Narahari SR. Integrative Medicine is 'one small step' for allopathy and 'one giant leap' for Ayurveda. Ann Ayurvedic Med 2016;5:60-4.  Back to cited text no. 25
    
26.
Foletti A, Fais S. Unexpected discoveries should be reconsidered in science A look to the past? Int J Mol Sci 2019;20:3973.  Back to cited text no. 26
    
27.
Goldstein I, Burnett AL, Rosen RC, Park PW, Stecher VJ. The Serendipitous story of sildenafil: An unexpected oral therapy for erectile dysfunction. Sex Med Rev 2019;7:115-28.  Back to cited text no. 27
    
28.
Akers KG. New journals for publishing medical case reports. J Med Libr Assoc 2016;104:146-9.  Back to cited text no. 28
    




 

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