Estimation of the Likelihood Ratio of Different Symptoms for Six Homeopathic Medicines: Prognostic Factor Research.

BACKGROUND: Arsenicum album, Causticum, Nux vomica, Pulsatilla nigricans, Rhus toxicodendron and Sulphur are frequently prescribed homeopathic medicines; however, their symptoms, as mentioned in different homeopathic literature works, have rarely been investigated systematically. Likelihood ratio (LR), based on Bayesian statistics, may reflect a better estimation of the strengths of symptoms than the existing entries in the homeopathic literature. METHODS: A prospective, longitudinal, analytical patient outcome study was conducted in the outpatient departments of D. N. De Homeopathic Medical College and Hospital, Kolkata, on 1,954 patients over 21 months. The outcomes were recorded at each follow-up using the Outcome Related to Impact on Daily Living (ORIDL) +4 to -4 scale. The average period of treatment for each participant was 3 months. The LRs of four symptoms for each of the six selected medicines were calculated. RESULTS: One hundred and two different remedies were prescribed. The prevalence, LR + , and LR - , with respective 95% confidence intervals, of different symptoms were reported. The study found that the following symptoms had particularly high LR+ scores: "intense sympathy for the suffering of others" (Causticum, LR+ = 12.0); "dyspepsia from business anxiety" (Nux vomica, LR+ = 27.4); "burning pain relieved by heat" (Arsenicum album, LR+ = 29.6); "envy" (Pulsatilla nigricans, LR+ = 13.2); "desire for milk" (Rhus toxicodendron, LR+ = 7.5); "very selfish, no regard for others" (Sulphur, LR+ = 20.6). The findings corroborated well with the presentation of the symptoms in different homeopathic materia medica and repertories. ORIDL scores of +2 or greater were identified most prominently for Pulsatilla nigricans (n = 138) and Sulphur (n = 119). CONCLUSION: There was adequate evidence to attribute all the assessed symptoms to the medicines investigated. Further studies with a larger population are warranted to tackle the possible confirmation bias.

Homeopathic Medicines in Third (Omicron) Wave of COVID-19: Prognostic Factor Research.

BACKGROUND: With the emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, such as the Omicron variant, during the third wave of the coronavirus disease 2019 (COVID-19) pandemic, there was a need to identify useful homeopathic medicines. This study aimed to identify such medicines and their indications using prognostic factor research (PFR). METHODS: This was an open-label, multi-centred observational study conducted in January 2022, on confirmed COVID-19 cases. The data were collected from integrated COVID Care Centres in Delhi, India, where homeopathic medicines were prescribed along with conventional treatment. Only those cases that met a set of selection criteria were considered for analysis. The likelihood ratio (LR) was calculated for the frequently occurring symptoms of the frequently prescribed medicines. An LR of 1.3 or greater was considered meaningful. RESULTS: Out of the 362 COVID-19 cases, 263 cases were selected for analysis after applying selection criteria. Common symptoms included fatigue, cough, sore throat, myalgia and headache. Twenty-one medicines were prescribed, of which nine medicines - Gelsemium sempervirens, Bryonia alba, Hepar sulphuris, Rhus toxicodendron, Pulsatilla nigricans, Arsenicum album, Belladonna, Nux vomica and Phosphorus - were frequently used. By calculating LRs, the study identified meaningful indications for these medicines. CONCLUSION: Homeopathic medicines have shown promising results in the third wave of COVID-19 as an adjunct therapy. The medicines that were used in the first and second waves were found useful in the third wave also, and their indications were analogous to those found in the earlier waves. Certain new indications of some medicines were elicited in this wave, which warrant further research. However, it is important not to restrict to these medicines only and to continue data collection on COVID-19 in future waves for the improvement of the COVID-19 mini-repertory.

Homeopathic Medicines in Second Wave of COVID-19: Prognostic Factor Research.

BACKGROUND: The clinical profile and course of COVID-19 evolved perilously in a second wave, leading to the use of various treatment modalities that included homeopathy. This prognostic factor research (PFR) study aimed to identify clinically useful homeopathic medicines in this second wave. METHODS: This was a retrospective, multi-centred observational study performed from March 2021 to May 2021 on confirmed COVID-19 cases who were either in home isolation or at COVID Care Centres in Delhi, India. The data were collected from integrated COVID Care Centres where homeopathic medicines were prescribed along with conventional treatment. Only those cases that met a set of selection criteria were considered for analysis. The likelihood ratio (LR) was calculated for the frequently occurring symptoms of the prescribed medicines. An LR of 1.3 or greater was considered meaningful. RESULTS: Out of 769 confirmed COVID-19 cases reported, 514 cases were selected for analysis, including 467 in home isolation. The most common complaints were cough, fever, myalgia, sore throat, loss of taste and/or smell, and anxiety. Most cases improved and there was no adverse reaction. Certain new symptoms, e.g., headache, dryness of mouth and conjunctivitis, were also seen. Thirty-nine medicines were prescribed, the most frequent being Bryonia alba followed by Arsenicum album, Pulsatilla nigricans, Belladonna, Gelsemium sempervirens, Hepar sulphuris, Phosphorus, Rhus toxicodendron and Mercurius solubilis. By calculating LR, the prescribing indications of these nine medicines were ascertained. CONCLUSION: Add-on use of homeopathic medicines has shown encouraging results in the second wave of COVID-19 in integrated care facilities. Further COVID-related research is required to be undertaken on the most commonly prescribed medicines.

Test of a Homeopathic Algorithm for COVID-19: the Importance of a Broad Perspective.

BACKGROUND: Most of the symptoms of coronavirus disease 2019 (COVID-19) are covered by large repertory rubrics and hence many remedies have been proposed as "genus epidemicus". The aim of this study was to combine the information from various data collections to prepare a COVID-19 Bayesian mini-repertory/an algorithm-based application (app) and test it. METHODS: In July 2021, 1,161 COVID-19 cases from 100 practitioners globally were combined. These data were used to calculate "condition-confined" likelihood ratios (LRs) for 59 symptoms of COVID-19. Out of these, 35 symptoms of the 11 medicines that had at least 20 cases each were considered. The information was entered in a spreadsheet (algorithm) to calculate combined LRs of specific combinations of symptoms. The algorithm contained the medicines Arsenicum album, Belladonna, Bryonia alba, Camphora, Gelsemium sempervirens, Hepar sulphuris, Mercurius solubilis, Nux vomica, Phosphorus, Pulsatilla and Rhus toxicodendron. To test concordance, the doctors were then invited to re-enter the symptoms of their cases into this algorithm. RESULTS: The algorithm was re-tested on 358 cases, and concordance was seen in 288 cases. On analysis of the data, bias was noticed in the Merc group, which was therefore excluded from the algorithm. The remaining 10 medicines, representing 81.8% of all cases, were included in the preparation of the next version of the homeopathic mini-repertory and app. CONCLUSION: The Bayesian mini-repertory and app is based on qualitative clinical experiences of various doctors in COVID-19 and gives indications for specific medicines for common COVID-19 symptoms. It is freely available [English: https://hpra.co.uk/; Spanish: https://hpra.co.uk/es ] for further testing and utilization by the profession.

Generalizability of Homeopathic Prognostic Factor Research Outcome in COVID-19 Treatment: Comparison of Data.

BACKGROUND/OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, several homeopathic prognostic factor research (PFR) projects have been undertaken. We found two projects with comparable outcomes to assess consistency and possible flaws. METHODS: Two comparisons were made. (1) Outcome of a PFR data collection from the Liga Medicorum Homoeopathica Internationalis (LMHI) by about 100 doctors with 541 cases was compared with a previous analysis of 161 cases in the same database. (2) The updated LMHI database was also compared with a data collection carried out in India by four doctors with a total of 1,445 cases. Differences that resulted in conflicting outcomes (indication in one, contraindication in the other) were examined for possible causes. RESULTS: There was only a single outcome in the updated LMHI database that conflicted with the previous dataset, and this could have been due to statistical variation. The Indian data contained many cases, from few doctors, while the LMHI database had few cases per doctor, but many doctors. The overlap between the projects (individual cases entered in both) was between zero and 22%. In 72 comparisons we found six (8.3%) conflicting outcomes. Possible causes were statistical error due to small numbers of cases and/or observers, confirmation bias, and keynote prescribing if this resulted in symptoms being inadequately checked. CONCLUSION: There was little conflict between the outcomes of the two versions of one project and between the two different PFR projects. Differences could mostly be explained by causes that can be managed. This consistency should primarily be interpreted as showing a strong overall consensus between homeopathic practitioners worldwide, but with variation of consensus between small groups of practitioners.

Case Reporting in Homeopathy-An Overview of Guidelines and Scientific Tools.

Case reports have been of central importance to the development of homeopathy over the past 200 years. With a special focus on homeopathy, we give an overview on guidelines and tools that may help to improve the quality of case reports. Reporting guidelines such as CARE (Case Report), HOM-CASE (Homeopathic Clinical Case Reports), and the WissHom Documentation Standard help to improve the quality of reporting and strengthen the scientific value of a case report. Additional scientific tools such as prospective outcome assessment, prognostic factor research, cognition-based medicine, and the Modified Naranjo Criteria for Homeopathy (MONARCH) score may be helpful in improving case documentation and evaluation.

Impact of Bias in Data Collection of COVID-19 Cases.

BACKGROUND: Prognostic factor research (PFR), prevalence of symptoms and likelihood ratio (LR) play an important role in identifying prescribing indications of useful homeopathic remedies. It involves meticulous unbiased collection and analysis of data collected during clinical practice. This paper is an attempt to identify causes of bias and suggests ways to mitigate them for improving the accuracy in prescribing for better clinical outcomes and execution of randomized controlled studies. METHODS: A prospective, open label, observational study was performed from April 2020 to December 2020 at two COVID Health Centers. A custom-made Excel spreadsheet containing 71 fields covering a spectrum of COVID-19 symptoms was shared with doctors for regular reporting. Cases suitable for PFR were selected. LR was calculated for commonly occurring symptoms. Outlier values with LR ≥5 were identified and variance of LRs was calculated. RESULTS: Out of 1,889 treated cases of confirmed COVID-19, 1,445 cases were selected for pre-specified reasons. Nine medicines, Arsenicum album, Bryonia alba, Gelsemium sempervirens, Pulsatilla nigricans, Hepar sulphuricus, Magnesia muriaticum, Phosphorus, Nux vomica and Belladonna, were most frequently prescribed. Outlier values and large variance for Hepar sulphuricus and Magnesia muriaticum were noticed as indication of bias. Confirmation bias leading to lowering of symptom threshold, keynote prescribing, and deficiency in checking of all symptoms in each case were identified as the most important sources of bias. CONCLUSION: Careful identification of biases and remedial steps such as training of doctors, regular monitoring of data, checking of all pre-defined symptoms, and multicenter data collection are important steps to mitigate biases.

Psychometric validation of the modified Naranjo algorithm used in homeopathy for chronic cases.

OBJECTIVES: The modified Naranjo algorithm assesses the physician assigned cause-effect relationship for homeopathic medicines. It is being adopted in homeopathy researches, but not yet validated systematically. We intended to validate the modified Naranjo algorithm by examining its psychometric properties. METHODS: An online survey sought agreement of 25 experts on the 10 items of the tool on 5-point agreement scale. Next, 285 responses from collected prospectively from chronic cases enrolled under the clinical verification program of the council in 2018 were subjected to testing of construct validity using exploratory principal component analysis (PCA). Confirmatory factor analysis (CFA; n=150) was performed to verify the goodness-of-fit of the model. Reliability was tested using internal consistency, test-retest reliability, and inter-rater reliability by kappa statistics. RESULTS: Experts' responses mean values were 4 or higher (i.e. responses were relevant) and standard deviations were less than 1 (i.e. less heterogeneous). In PCA using varimax, all the items loaded above the pre-specified value of 0.4 and identified 4 components explaining 64.1% of variation. The goodness-of -fit of the 4-component CFA model was acceptable (chi-square 89.253, p<0.001). Internal consistency (Cronbach's alpha 0.7) was borderline; test-retest reliability was acceptable. Kappa statistics was moderate to fair, but poor for few of the items. CONCLUSIONS: Statistical evaluations indicate that the modified Naranjo algorithm is useful, but needs improvement.

Individualized Homeopathic Medicines in the Treatment of Generalized Anxiety Disorder: A Double-Blind, Randomized, Placebo-Controlled, Pilot Trial.

INTRODUCTION: Evidence favoring homeopathy in generalized anxiety disorder (GAD) remains scarce. The objective of this pilot trial was to test feasibility of a definitive trial in future. We also experimented whether individualized homeopathic medicines (IH) plus psychological counseling (PC) can produce significantly different effects beyond placebo plus PC in the treatment of GAD. METHODS: A double-blind, randomized, placebo-controlled, parallel arm, pilot trial was conducted on 62 GAD patients at the National Institute of Homoeopathy, India. GAD-7 questionnaire and Hamilton Anxiety Scale (HAM-A) were used as the primary and secondary outcomes, respectively, measured at baseline and 3 months. Patients received either IH plus PC (n = 31) or identical-looking placebo plus PC (n = 31). Intention-to-treat sample was analyzed to detect group differences using unpaired t tests. RESULTS: Recruitment and retention rates were 56 and 90%, respectively. Mean age was 31.5 years; 56.5% were male. GAD-7 reductions were non-significantly higher in IH than placebo (p = 0.122). Group differences on HAM-A favored IH significantly (p = 0.018). Effect sizes were small to medium. Calcarea carbonica was the most frequently indicated medicine. No serious adverse events happened. CONCLUSIONS: A small but positive direction of anxiolytic effect was observed favoring homeopathy over placebo. A definitive trial appeared feasible in future.

Data Collection during the COVID-19 Pandemic: Learning from Experience, Resulting in a Bayesian Repertory.

BACKGROUND: A novel pandemic disease offered the opportunity to create new, disease-specific, symptom rubrics for the homeopathic repertory. OBJECTIVE: The aim of this study was to discover the relationship between specific symptoms and specific medicines, especially of symptoms occurring frequently in this disease. MATERIALS AND METHODS: Worldwide collection of data in all possible formats by various parties was coordinated by the Liga Medicorum Homeopathica Internationalis. As the data came in, more symptoms were assessed prospectively. Frequent analysis and feedback by electronic newsletters were used to improve the quality of the data. Likelihood ratios (LRs) of symptoms were calculated. An algorithm for combining symptom LRs was programmed and published in the form of an app. The app was tested against 18 well-described successful cases from Hong Kong. RESULTS: LRs of common symptoms such as 'Fatigue' and 'Headache' provided better differentiation between medicines than did existing repertory entries, which are based only on the narrow presence or absence of symptoms. A mini-repertory for COVID-19 symptoms was published and supported by a web-based algorithm. With a choice of 20 common symptoms, this algorithm produced the same outcome as a full homeopathic analysis based upon a larger number of symptoms, including some that are traditionally considered more specific to particular medicines. CONCLUSION: A repertory based on clinical data and LRs can differentiate between homeopathic medicines using a limited number of frequently occurring epidemic symptoms. A Bayesian computer algorithm to combine symptoms can complement a full homeopathic analysis of cases.

Prevalence and Likelihood Ratio of Six Objective Signs among Good Responders to Natrum muriaticum: Multi-centre Observational Assessment.

BACKGROUND: The reliability of homeopathic prescriptions may increase through resource to objective signs and guiding symptoms with significant positive likelihood ratio (LR). We estimated LR for six objective signs attributed to the homeopathic medicine Natrum muriaticum (Nat-m). METHODS: In this multi-centre observational assessment, we investigated the prevalence of six signs in the general patient population and among good responders to Nat-m in daily homeopathic practice. Next, we calculated LR for these six signs. RESULTS: Data from 36 good responders to Nat-m and 836 general population patients were compared. We found statistically significant positive LR (95% confidence interval) for signs such as lip cracks (1.94; 1.15 to 3.24), recurrent herpes (2.29; 1.20 to 4.37), hairline eruptions (2.07; 1.03 to 4.18), and dry hands (2.13; 1.23 to 3.69). CONCLUSIONS: Objective signs with significant positive LR might increase the reliability of homeopathic prescriptions. Further studies are warranted to confirm the validity of this approach.

Counting Polar Symptoms: How to Represent Results?

BACKGROUND: Polar symptoms (PS)-symptoms with opposite values-are frequently used in homeopathy, but have many misleading entries in the repertory. This is caused by using absolute occurrence of symptoms, causing the same medicine to appear in both (opposite) symptom rubrics, and by lack of comparison with other medicines. Some PS, like 'aversion/desire for sweets' have a frequency distribution that is not evenly distributed around the neutral value: a desire for sweets is much more common than aversion. A desire for sweets is an indication for a specific medicine only if this desire occurs more frequently in this specific medicine population than in the remainder of the population. We need to find the best way to represent this difference. METHODS: A multi-centre, explorative, prospective, observational study was conducted by nine centres of the Central Council for Research in Homoeopathy. Two-hundred and sixteen patients were enrolled with chronic cough lasting more than 8 weeks, and received usual homeopathic care. During intake, 30 general PS, 27 polar cough symptoms and 3 non-polar cough symptoms were checked. Different ways of representing results were explored, including two quantities borrowed from mechanics: Centre of Mass (CoM) and Leverage. RESULTS: At the fourth follow-up, three medicines with more than 10 cases with good results were identified: 20 Phosphorus, 19 Pulsatilla and 13 Sulphur. The mean value of the frequency distribution of some symptoms in the whole sample was considerably different from the neutral value. Comparing a medicine population with the remainder of the respective population can give results that differ from polarity analysis. For some symptoms, the 'distance' (Leverage) between the CoMs of the medicine population and the remainder of the population was clearer than the likelihood ratio (LR). CONCLUSION: If the LR value is not clear about the prognostic value in PS, notions from mechanics such as CoM and Leverage can clarify how to interpret a polar symptom.

Evaluation of the Modified Naranjo Criteria for Assessing Causal Attribution of Clinical Outcome to Homeopathic Intervention as Presented in Case Reports.

OBJECTIVES: The objective of this study was to establish the reliability and content validity of the "Modified Naranjo Criteria for Homeopathy-Causal Attribution Inventory" as a tool for attributing a causal relationship between the homeopathic intervention and outcome in clinical case reports. METHODS: Purposive sampling was adopted for the selection of information-rich case reports using pre-defined criteria. Eligible case reports had to fulfil a minimum of nine items of the CARE Clinical Case Reporting Guideline checklist and a minimum of three of the homeopathic HOM-CASE CARE extension items. The Modified Naranjo Criteria for Homeopathy Inventory consists of 10 domains. Inter-rater agreement in the scoring of these domains was determined by calculating the percentage agreement and kappa (κ) values. A κ greater than 0.4, indicating fair agreement between raters, in conjunction with the absence of concerns regarding the face validity, was taken to indicate the validity of a given domain. Each domain was assessed by four raters for the selected case reports. RESULTS: Sixty case reports met the inclusion criteria. Inter-rater agreement/concordance per domain was "perfect" for domains 1 (100%, κ = 1.00) and 2 (100%, κ = 1.00); "almost perfect" for domain 8 (97.5%, κ = 0.86); "substantial" for domains 3 (96.7%, κ = 0.80) and 5 (91.1%, κ = 0.70); "moderate" for domains 4 (83.3%, κ = 0.60), 7 (67.8%, κ = 0.46) and 9 (99.2%, κ = 0.50); and "fair" for domain 10 (56.1%, κ = 0.38). For domains 6A (46.7%, κ = 0.03) and 6B (50.3%, κ = 0.18), there was "slight agreement" only. Thus, the validity of the Modified Naranjo Criteria for Homeopathy tool was established for each of its domains, except for the two that pertain to direction of cure (domains 6A and 6B). CONCLUSION: The MO: dified NAR: anjo C: riteria for H: omeopathy-Causal Attribution Inventory was identified as a valid tool for assessing the likelihood of a causal relationship between a homeopathic intervention and clinical outcome. Improved wordings for several criteria have been proposed for the assessment tool, under the new acronym "MONARCH". Further assessment of two MONARCH domains is required.

Assessment of Likelihood Ratio for Four Contact Dermatitis Symptoms of Vinca Minor.

BACKGROUND: Contact dermatitis (CD) is a frequently occurring medical condition, for which Vinca minor (VM) is one of the recommended homeopathic medicines. However, the symptoms indicating this medicine have not yet been assessed systematically. Likelihood ratio (LR), based on Bayesian statistics, may yield better estimation of a medicine's indication than the existing method of entry of symptoms into materia medica and repertories. METHODS: We investigated LRs of four CD symptoms of VM: (1) great sensitiveness of skin, with redness and soreness from slightest rubbing; (2) weeping eczema with foul, thick crusts; (3) itching amelioration in open air; and (4) CD of scalp. An observational, prospective, patient-outcome study was conducted in five different practice settings on 390 CD patients over 18 months using three outcomes-Glasgow Homeopathic Hospital Outcome Scale (GHHOS), Scoring Atopic Dermatitis (SCORAD), and Dermatology Life Quality Index (DLQI), assessed at baseline, after 3 and 6 months. The LR of each of the four symptoms was estimated as per the patient-rated outcomes on GHHOS. RESULTS: Seventy-four VM and 316 non-VM cases were analyzed. Estimated LRs were as follows: symptom 1, 1.29 (95% confidence interval [CI]: 0.65 to 2.60); symptom 2, 1.48 (95% CI: 0.80 to 2.74); symptom 3, 1.70 (95% CI: 0.94 to 3.07); symptom 4, 1.36 (95% CI: 0.74 to 2.51). There were statistically significant reductions in SCORAD and DLQI scores over 3 and 6 months. CONCLUSION: There was insufficient evidence to attribute any of the four assessed symptoms clearly to VM. Though non-significant, a high LR was observed for "itching amelioration in open air" (symptom 3). Symptoms in the homeopathic materia medica for VM are perhaps over-represented. More research of this nature is warranted.

Flawed statistics and science confirming existing paradigms.

BACKGROUND: Part of the scientific community states that implausible methods cannot have a true effect and that epidemiological proof can only lead to false positives. DISCUSSION: Homeopathy is regarded as an example of an implausible method with false positive evidence. However, epidemiological proof is necessary to falsify the placebo hypothesis. Implausibility is now supposed to rectify selection of a part of all trials, but the applied selection criteria are diverse and not common in conventional medicine. Applying Bayes' theorem only once to demonstrate that a low prior chance does not lead to reasonable probability is flawed application of this theorem. CONCLUSION: Demanding scientific evidence and then rejecting the same with post-hoc selection of trials and flawed statistics shows unwillingness to falsify the completeness of existing paradigms.

Generalisability of prognostic factor research: further analysis of data from the IIPCOS2 study.

Prognostic factor research is important as it helps in refining diagnosis, taking clinical and therapeutic decisions, enhances the design and analysis of intervention trials and helps to identify targets for new interventions that aim to modify the course of a disease. Prognostic factor research in homeopathy can be done by applying Bayes' theorem. This paper considers Bayes' theorem; Likelihood Ratio, conditional probability and research in subpopulations of a condition with examples. We analysed the likelihood ratios for 11 homeopathic medicines for the symptom 'cough' and other upper respiratory tract symptoms, based on data from the IIPCOS2 study. This yielded useful information since several medicines, including Belladonna, had LR >1 for cough, indicating that cough is not an indication for this medicine. The implications for improving homeopathic prescribing are discussed.

Data collection: Treat every variable as a treasure.

UNLABELLED: Collection of data concerning case histories is not yet common in homeopathy despite its great importance for this method. Computer program development progresses slowly and discussion about requirements is scarce. Two Dutch projects assessed Materia Medica of some homeopathic medicines and six homeopathic symptoms. Especially the second project relied heavily on data collection. In both projects much effort was spent on consensus between participating doctors. There was much variance between doctors despite our consensus efforts. Assessing causality seems the most important source of bias, there is also much variance in assessing symptoms. CONCLUSION: Data collection software should be developed step-by-step, guided by close monitoring and feedback of participating practitioners.