|Year : 2017 | Volume
| Issue : 3 | Page : 184-195
Symptom prevalence in a cohort of 65 patients improved with the homoeopathic medicine Mangifera indica: A multicentric open observational clinical verification study
Raj K Manchanda1, Partha Sarathi Chakraborty2, Pramodji Singh3, MK Rai4, Ojit Singh5, DK Singh6, Souradipta Paul7, Chaturbhuja Nayak8
1 Central Council for Research in Homoeopathy, New Delhi, India
2 Dr. Anjali Chatterjee Regional Research Institute Homoeopathy, Kolkata, West Bengal, India
3 Clinical Verification Unit (Homoeopathy), Vrindaban, Uttar Pradesh, India
4 Retired, Dr. D. P. Rastogi Central Research Institute (Homoeopathy), Noida, Uttar Pradesh, India
5 Regional Research Institute (Homoeopathy), Imphal, Manipur, India
6 Retired, Homoeopathic Drug Research Institute, Lucknow, Uttar Pradesh, India
7 Independent Researcher, Homoeopathy University, Jaipur, Rajasthan, India
8 President, Homoeopathy University, Jaipur, Rajasthan, India
|Date of Web Publication||15-Sep-2017|
Partha Sarathi Chakraborty
Dr. Anjali Chatterjee Regional Research Institute for Homoeopathy, Kolkata, West Bengal
Source of Support: None, Conflict of Interest: None
Introduction: Clinical verification is an ongoing research program of the Council that verified many rare homoeopathic drugs. Aim: To clinically verify the ‘symptomatology’ of Mangifera indica by ascertaining the symptoms improved during verification. Materials and Methods: The study was a multicentric open label observational trial. Total 114 patients were enrolled after matching with the available symptom compendium and eligibility criteria in five centres of the Council. The medicine was prescribed in 6C, 30C, 200C and 1M potencies, as per need of the patient following the homoeopathic principles and protocol developed by the Council. The collected data were presented in terms of descriptive statistics. Prevalence of symptoms in the responding and non-responding population has been compared using Chi-square test. Results: Among the total 114 patients enrolled in the study, 77 patients who completed the follow up were analysed, as there were 37 drop out cases. The demographic analysis shows, male/female: 41/36, mean age 28.61 years. There was “clinical success” in 65 cases (84.41%) and failures in 12 cases (15.59%), judged subjectively by the physicians. A minimum of two prescriptions were considered for pick listing each symptom as a rule of thumb. Conclusions: Total 16 CCRH proving symptoms were verified, 4 symptoms from other literatures were also verified. 51 new clinical symptoms/symptom components were identified. Further replication and estimation of likelihood ratio in general practice setting is crucial for confirmation and inclusion of such symptoms in homoeopathic literatures.
Keywords: Cohort, Clinical verification, Homoeopathy, Mangifera indica, Observational study
|How to cite this article:|
Manchanda RK, Chakraborty PS, Singh P, Rai M K, Singh O, Singh D K, Paul S, Nayak C. Symptom prevalence in a cohort of 65 patients improved with the homoeopathic medicine Mangifera indica: A multicentric open observational clinical verification study. Indian J Res Homoeopathy 2017;11:184-95
|How to cite this URL:|
Manchanda RK, Chakraborty PS, Singh P, Rai M K, Singh O, Singh D K, Paul S, Nayak C. Symptom prevalence in a cohort of 65 patients improved with the homoeopathic medicine Mangifera indica: A multicentric open observational clinical verification study. Indian J Res Homoeopathy [serial online] 2017 [cited 2017 Oct 21];11:184-95. Available from: http://www.ijrh.org/text.asp?2017/11/3/184/214841
| Introduction|| |
Traditional medicinal plants are used in different health problems due to their important therapeutic potentials and comparatively less side effects than the conventional drugs. Mangifera indica, also known as mango, aam, is an important herb in indigenous medical systems for over 4000 years.
Mangifera indica L. is an evergreen tree in the anacardiaceae family that grows to a height of 10-45 metres, dome shaped with dense foliage, typically heavy branched from a stout trunk. It is native tropical Asia and has been cultivated in the Indian subcontinent for over 4000 years and is now found naturalized in most tropical countries.
The bark of the tree is used for the homoeopathic preparation of Mangifera indica.
The chromatography and mass spectrometry study reveals that the bark contains many important constituents, viz., protocatechic acid, catechin, mangiferin, alanine etc. which exhibited anti-inflammatory, antioxidative, biosynthesis of proteins, antihelminthic, and other pharmacological properties.,,
In a folkloric use in Cuba it is reported that the aqueous extract of the bark of the plant is recommended as antispasmodic, antipyretic and as an anti-inflammatory agent. The bark extract (Vimang®) was found to be useful as supplement in treatment of various pathologies such as gastric and dermatological disorders, AIDS, cancer and asthma, after conducting both in vitro and in vivo studies in experimental models.,,,,,,
Another in vitro study conducted on Herpes simplex virus with mangiferin showed that it has the capacity to inhibit the replication of HSV-1 and HSV-2 viruses within the cells and even to antagonize the cytopathic effects of HIV.,, Many other in-vitro studies conducted in various cancer cell lines exhibited it's anticancerous activity in inhibiting the proliferation and inducing apoptosis of cancer cell lines, suggesting the potentiality of mangiferin as a chemo preventive agent.,,, The stem bark extract of MI has also found to possess antiplasmodial and antipyretic activity.,
The regulatory standard of this drug has been mentioned as monograph in the 7th volume of Homoeopathic Pharmacopoeia of India (HPI), 1999. The proving of the drug Mangifera indica Linn, was conducted by the CCRH in 1995–1996 using double blind method. The drug was proved in 6CH and 30CH potencies in ascending order. The proving was carried out at (i) Regional Research Institute, New Delhi, (ii) Drug Proving Research Unit, Ghaziabad (Uttar Pradesh). Seventeen (17) provers in the age group of 18–49 years had taken part in the proving including three females. This paper presents the symptom compendium of Mangifera indica Linnverified clinically under the councils Clinical Verification Programme.
| Materials and Methods|| |
The study was conducted between 2005-2010 in 5 centres of CCRH: Homoeopathic Drug Research Institute, Lucknow; Regional Research Institute(H), Shimla; Regional Research Institute(H), Imphal; Dr. D. P. Rastogi Central Research Institute(H), Noida and Clinical Verification Unit(H), Vrindaban.
As per the inclusion criteria, the patients from all age groups, both sexes, having symptomatic similarity with Mangifera indica, and persons willing to participate were included in the study. If patient was taking any acute medicine, he/she was included in the study after a wash-out period of one week. Patients unwilling to participate, having a clinical presentation not corresponding with the study medicine, patients on regular medication for any systemic diseases and patients under chronic medicinal treatment were excluded from the study.
The study medicine was procured from a Good Manufacturing Practice (GMP) compliant homoeopathic pharmacy of India in various potencies, viz. 6C, 30C, 200C and 1M and was distributed to above mentioned institutes/units. After recording the presenting signs and symptoms of the patients in case recording proforma, the symptoms were repertorized using a repertory prepared for clinical verification by CCRH and then a specially developed Materia Medica was consulted for final selection of the remedy. If the presenting symptoms of the case corresponded with the symptomatolgy of Mangifera indica, then the medicine was prescribed in 6C potency and was repeated three times a day, till improvement/aggravation occurred when the drug was stopped; otherwise it was continued for 5/7 days allowing the drug to act. Then the subsequent potencies like 30C, 200C, 1M were prescribed following the guidelines defined in the protocol. In cases of improvement under action of any of the above mentioned potencies, Placebo was prescribed so far the improvement continued. If the improvement stopped, i.e., if the case relapsed or became standstill, then the prescription was repeated in same potency. In no case the same potency was repeated for more than two times. In cases where aggravation of the presenting symptoms resulted under trial without any relief, then change of medicine was considered. When new symptoms appeared after administration of the medicine, and if these new symptoms were mild and did not cause much concern to the patient, placebo was prescribed for one week. But if no improvement followed or worsening occurred after one week, then change of medicine was considered. If the new symptoms were severe and cause considerable discomfort to the patient from the beginning, then change of medicine/therapy was considered at once.
In cases where no perceptible improvement occurred after adequate repetition of medicine in different potencies, then it was searched for any obstacle(s) to cure and steps were taken to remove it (when identified) as far as possible. In cases where no response was achieved even after removal of probable obstacle(s), the case was referred for appropriate medical care.
The cases were followed up and assessed once a week or even earlier, if required.
Each and every case has been evaluated in depth to find out any known causative factors to find out the etiological factors and also any obstacle to recovery whether present or not which may hinder the action of the drug and once found, efforts were made to remove/minimize them. A nutritious, well balanced, healthy diet was recommended, as it can help in balancing of immune system.
‘Clinical success’ was defined a priori as cases showing clinical improvement, objective or subjective, of present complaint(s) as judged by the investigating physician(s) and/or as reported by the patient(s). ‘Clinical failures’ were such cases showing no change and/or worsening or deterioration of the condition, or cases requiring change of medicines/therapy. All the data were collected and compiled in specially designed excel spreadsheet for analysis. Data were presented using descriptive statistics – mean, standard deviations (SD), absolute values, percentages and 95% confidence intervals (CI). As a rule of thumb, a minimum of two prescriptions for each symptom have been considered for pick-listing. Prevalence of the symptoms in the responding and non-responding population was compared using Chi Square test, keeping P value less than 0.05 (two tailed) as statistically significant.
| Results|| |
A total of 114 patients were enrolled in the study having similar ‘symptomatology’ of Mangifera indica, and meeting the pre-specified eligibility criteria. Of these, 37 cases were dropped out and 77 complete cases were analysed [Figure 1]. The socio demographic information of these patients is given in [Table 1]. Clinical success and failure was judged subjectively by the treating physicians. “Clinical success” in 65 cases (84.41%), and “Clinical failure” was observed in 12 cases (15.59%).
|Table 1: List of verified symptoms (Central Council for Research in Homoeopathy proving) of Mangifera indica|
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The clinically verified symptoms were enlisted along with the outcomes on the basis of existing proving records and the symptoms available in other literature, and also the new clinically observed symptoms or traits, those are not mentioned elsewhere. Among the completed cases, 41 cases (53.25%) were male, 36 cases (46.75%) were females. The mean age of the patients was 28.61 years (SD = 19.05). The patients enrolled were from all age groups but majority were from 16-30 years (n = 31, 40.26%). 74 patients (96.10%) were Hindu, 42 were single (54.55%) and 26 patients (33.77%) were married. No. of student patients were more than of other category (n = 30, 38.96%) [Table 5]. The mean height and weight of the patients were 145.09 cm (n = 64; SD = 26.08) and 48.01 kg (n = 65; SD = 14.02) respectively. The mean SBP and DBP were 118.06 (n = 62, SD = 11.51) and 75.89 (n = 62, SD = 6.42) respectively [Table 6]. Majority of patients have had normal BMI (n = 35, 54.69%) [Table 7]. Among the 65 cases who responded well to Mangifera indica, a total of 10 clinical conditions or diagnosis were obtained; with “Acute upper respiratory tract infection” being the commonest (n = 20, 30.77%) [Table 8].
Among the proving symptoms of CCRH, the followings were most frequently observing symptoms with prevalence rate higher in responding population than in the non-responding population.
- Coryza with watery nasal discharge (prevalence in responding population: n = 35 (53.85%); 95% CI = 0.42, 0.65)
- Coryza with heaviness of head (prevalence in responding population: n = 11 (16.92%); 95% CI = 0.09, 0.28)
- Appetite diminished (prevalence in responding population: n = 11 (16.92%); 95% CI = 0.09, 0.28)
- Pain in joints, better from pressure (prevalence in responding population: n = 5 (7.69%); 95% CI = 0.03, 0.17)
- Fever with chill and body-ache (prevalence in responding population: n = 5 (7.69%); 95% CI = 0.03, 0.17).
Among the existing symptoms from other literatures, the most frequently observed symptom were:
- Skin of face dark as if sunburn and swollen (Prevalence in responding population: n=16 (24.7); 95% CI=0.16-0.36)
- White spots on skin (Prevalence in responding population: n=2 (3.1%); 95% CI=0.008-0.1)
But the prevalence of these symptom were found higher in non responding population [ n=5 (41.7%), 95% CI= 0.19-0.68 & n=2(16.7), 95% CI= 0.05-0.45]
Among the new clinical symptoms observed during verification, the most frequently observed symptoms with prevalence rate higher in responding population than in the non-responding population were:
- Dry cough, agg. at night (prevalence in responding population: n = 4 (6.15%); 95% CI = 0.02, 0.15)
- Pain in throat while talking (prevalence in responding population: n = 3 (4.62%); 95% CI = 0.01, 0.13).
During Clinical verification of Mangifera indica, it has been observed that patients with some distinct character have responded well to the prescribed drug. These distinct features though have not been modified under the action of the drug in trial (hence cannot be classified under Clinical Symptoms) in the present study, but may come out as important personal characteristics in future studies. These distinct features are given below along with their prevalence in responding population which have been found higher than the non-responding population.
- Desire for Salty food (prevalence in responding population: n = 15 (23.08%); 95% CI = 0.14, 0.34)
- Thermal reaction - Chilly (prevalence in responding population: n = 22 (33.85%); 95% CI = 0.24, 0.46)
- Thermal reaction - Ambithermal (prevalence in responding population: n = 23 (35.38%); 95% CI = 0.25, 0.48)
- Tongue-clean & moist (prevalence in responding population: n = 51 (78.46%); 95% CI = 0.67, 0.87)
- Memory weak, forgetfulness (prevalence in responding population: n = 9 (13.85%); 95% CI = 0.07, 0.24).
There were altogether 57 symptoms, where the prevalence rate in responding population was found higher than the prevalence rate in non-responding population. But the prevalence of these symptoms in the responding population was not found to be statistically significant (P > 0.05).
| Discussion|| |
A total of 71 symptoms were verified which includes CCRH proving symptoms, symptoms from other existing literatures and symptoms identified as new clinical symptoms. Among these 71 symptoms, 54 symptoms were identified where the symptom prevalence was higher in the responding population than the symptom prevalence in non-responding population. But the prevalence of none of these symptoms was found statistically significant. 16 symptoms were verified from CCRH proving symptoms of Mangifera indica; 10 new symptom components of the proving symptoms were also identified and are presented in italics under the respective proving symptoms [Table 1]. Only 4 symptoms were verified from other existing homoeopathic literature [Table 2]. During the study, 41 entire new symptoms (Clinical symptoms) were identified [Table 3]. Some distinct clinical patterns/features were also identified during the study among the responding population due to their higher prevalence [Table 4]; though these features were not modified under the action of the drug and hence cannot be classed with Clinical symptoms, but they may come out as important personal characteristics in future studies when their prevalence in general population and Likelihood ratio will be estimated.
|Table 2: List of verified symptoms (from other literatures - Boericke Materia Medica and Lotus Materia Medica) of Mangifera indica|
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|Table 4: List of new clinical patterns/features (other than clinical symptoms) identified on the basis of their prevalence in the responding population|
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The “Acute upper respiratory tract infection” was found to be the most commonly responded clinical condition followed by “Vitiligo”.
At this point of time, Bayesian probability and likelihood ratios (LR) seem to be the mainstay of future homoeopathic research for confirming/validating the accuracy of the symptoms listed under any drug., Retrospective assessment of prevalence and LR of symptoms in good responders could be a mean for better selection of symptoms for prospective research; but feasibility of conducting such retrospective analysis deserves further discussion. Though the prevalence of symptoms of Mangifera indica, can be identified in the good response group of study population through retrospective analysis of available case records, but finding out the prevalence of these symptoms in remainder of the general population treated during the study period in those institutes/units of CCRH where the study had been conducted, is not feasible. Hence, formulation of 2 × 2 contingency table for calculation of LR does not seem possible at this point of time. All these results should be considered as provisory and need confirmation through prospective research. The causal association can be tested prospectively and systematically in all cases using modified Naranjo criteria in future studies.
The overall results generated were contributed by different study sites/units of the Council, indicating enhanced generalizability of the study findings. However, being an observational trial, this study cannot address the threats to various internal validity issues, e. g., absence of matching, randomization and blinding, the placebo effect, spontaneous recovery of symptoms under question, the therapeutic relationship with the clinician (empathy, compassion, social desirability, etc.), the regression effect toward the mean, and use of undisclosed adjuvant treatments, if any.
In this study, we compared responding and not-responding patients for one medicine. This way, we can only get some idea of symptoms that can be further investigated. These could be of great value when compared with similar data of other medicines. However, the prevalence of symptoms should preferably be compared with the whole population. If possible, this can be estimated or derived from literature. The symptom prevalence should necessarily be higher in the responding population than in the whole population to be considered as an indication for the given medicine. The prevalence of any symptom under investigation can probably be best assessed in multi-center drug validation or clinical verification programs that can produce more reliable and generalizable nation-wide data. Some data are already available but still in a nascent state and how far they can be extrapolated to the remaining nations remains a matter subjected to future research.
| Conclusions|| |
This study exhibited a list of clinically verified symptoms of Mangifera indica and warrants further evaluation using enhanced methodological rigor. On many occasions, limited number of prescriptions were generated for specific symptoms making interpretation difficult. Calculation of LR will enable more accurate and quantitative description of strength of the probable or claimed characteristic symptoms of the drug, based on empirical evidence instead of assumption. So, further confirmation of the symptoms in larger sample size, analysis of polarity, and prospective estimation of LR of the symptoms using Bayesian statistical methods in routine practice is necessary prior to inclusion of the symptoms in Homoeopathic Materia Medica and Repertory.
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Conflicts of interest
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]