Prevalence and correlates of multimorbidity among patients attending AYUSH primary care settings in Delhi-National Capital Region, India.

INTRODUCTION: India has a multifaceted healthcare system and recognizes complementary and alternative systems of medicine (AYUSH) that cater to the healthcare needs of people. Multimorbidity requires frequent visits to physicians and long-term use of medications, due to which people tend to prefer AYUSH systems as they provide holistic patient-centered treatment. Hence, we aimed to estimate the prevalence of multimorbidity and assess its correlates among patients attending AYUSH primary care clinics in Delhi. METHODS: A cross-sectional study was conducted among 943 patients aged ≥ 18 years attending various AYUSH primary care clinics in Delhi from September 2021 to February 2022, employing a stratified random sampling technique. Descriptive statistics such as frequency and proportion were used to report the prevalence of multimorbidity (two or more chronic conditions in an individual out of the 33 conditions listed as per the Multimorbidity Assessment Questionnaire for Primary Care). A multivariable logistic regression assessed the association between various socio-demographic characteristics and multimorbidity, presented as an adjusted odds ratio (AOR) with a 95% confidence interval (CI). RESULTS: The prevalence of diabetes (14.7%) was found to be the highest (out of all included chronic conditions) among the patients attending various AYUSH primary care settings. The overall prevalence of multimorbidity was observed to be around 39.4%. We observed a higher likelihood of having multimorbidity among participants aged ≥ 70 years [AOR: 9.19 (95% CI: 3.75-22.54)], females [AOR: 1.57 (95% CI: 1.04-2.37)], and middle class [AOR: 2.23 (95% CI: 1.45-3.43)]. CONCLUSION: Multimorbidity was evidently prevalent across AYUSH primary care settings, which cannot be overlooked. The results suggest behavioral change communication may be aimed at older individuals, females, and the middle class.

Antiviral and anti-inflammatory activity of novel belladonna formulation against Japanese encephalitis virus via inhibition of p65 nuclear translocation and TNF-α mediated NF-kB signaling.

Japanese encephalitis (JE) is a mosquito-borne flavivirus infection, a major cause of viral encephalitis in South-East Asia with a CFR of ~30% and no specific treatment. Therefore, a novel belladonna formulation (BCT) was prepared and its antiviral and anti-inflammatory activity was elucidated during Japanese encephalitis virus (JEV) infection. Anti-JEV role of BCT was investigated aiming to prevent the infection in the peripheral immune cells. Antiviral activity of BCT was evaluated by plaque reduction assay, cell survival and apoptosis assay. BCT-mediated reduction in JEV-envelope expression was measured by indirect immunofluorescence, RT-PCR and Western blot assays. NF-κB expression and p65 nuclear translocation assays were determined to explore the mechanism of the action of BCT. TNF-α level was measured to evaluate the anti-inflammatory role of BCT during JEV infection. Consequently, molecular docking was performed with the TRAF2-TRADD complex. Our data suggested that BCT treatment reduces the JEV-plaque formation, JEV-induced cytopathic effects and increases cell survival. The antiviral effect of BCT was confirmed by reduction in the JEV-envelope protein expression. Moreover, BCT treatment and prevents the NF-κB activation via preventing the nuclear translocation of p65 and reduces the TNF-α levels. Our molecular docking analysis suggested that belladonna alkaloids interfere with the TRAF2-TRADD complex that results in inhibition of TNF-induced NF-κB signaling. For the first time, our data suggested that BCT reduces JEV expression and interferes with TNF-induced NF-κB signaling, thereby increasing cell survival via preventing the p65 nuclear translocation and may be used for the treatment and prevention of JE.Abbreviation: CFR: Case fatality rate; CAM: Complementary and alternative medicines; COX-2: Cyclooxygenase-2; IκB: Inhibitor kappa B; JE: Japanese encephalitis; JEV: Japanese encephalitis virus; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells; ORF: Open reading frame; TNFR: Tumor necrosis factor receptor; TNF-α: Tumor necrosis factor-α; TRADD: TNFR1-associated death domain protein; TRAF2: TNF Receptor Associated Factor 2.

Wound Healing Activity of a Novel Formulation SKRIN via Induction of Cell Cycle Progression and Inhibition of PCNA-p21 Complex Interaction Leading to Cell Survival and Proliferation.

The process of wound healing is a dynamic event that starts with inflammation, proliferation, and cell migration of various types of fibroblast cells. Therefore, identification of potential molecules which may increase the wound healing capacity of fibroblast cells is crucial. A novel hydroalcoholic formulation of belladonna (SKRIN), was developed and characterized by GC-MS/MS, DLS, TEM, and AFM and was found to contain atropine and scopolamine exhibit in aggregated nanosized particles. SKRIN-mediated fibroblast cell survival was elucidated in the presence of H2O2 by MTT and flow cytometry based assays. With an EC50 of 4.41 µg/mL, SKRIN treatment showed significant increase in cell survival that was evident from a 1.11-fold increase (p < 0.0122) in the live cell population and 4.21-fold (p < 0.0001) and 2.59-fold (p < 0.0001) reductions in the early and late apoptotic cell populations, respectively. SKRIN-mediated wound healing was measured by cell scratch assay and cell cycle analysis. During the wound closure phenomenon, SKRIN increases repairing fibroblast cell proliferation by 1.24-fold (p = 0.0481) and increases the count of G2/M phase cells by 1.76-fold (p = 0.0002) which was confirmed by increased PCNA and reduced p21 protein expressions probably mediated by molecular interactions of PCNA-p21 complex with alkaloids present in SKRIN. Relative gene expression analysis further showed that SKRIN increases the PI3K, Akt, and NF-κB expression. Our data suggests that SKRIN exhibits wound healing property by increasing cell survival and repairing fibroblast proliferation via activation of the PI3K-Akt-NF-κB pathway probably mediated by inhibition of PCNA-p21 complex interaction.

Prakriti Analysis of COVID 19 Patients: An Observational Study.

RATIONALE & OBJECTIVE: The concept of Prakriti is unique to Ayurveda, which is used for deciding the preventive and curative strategy to be adopted in the treatment of patients. It is the total of anatomical, physiological, and psychological domains of an individual. The diseases often manifest by susceptibility that depends upon Prakriti of individuals. COVID 19 is a new disease, where the status of the susceptibility of its victim in terms of Prakriti is not known. This study has been undertaken to determine the Prakriti of COVID 19 positive patients. METHOD: The validated instrument CCRAS Prakriti assessment scale has been applied to the COVID 19 positive patients admitted between 16 May 2020 to 10 June 2020 at COVID hospital. RESULT: Data of 117 patients aged 10 to 80 years have been analyzed. The ratio of male-female patients was 1.8:1. Most patients belonged to Vata-KaphaPrakriti (27%).Individuals with their Prakriti found in order of frequency were Pitta-Kapha (21%), Kapha (20%), Vata (13%), Vata-Pitta (11%), Sama (4%) and Pitta (3%). CONCLUSION: Patients with Vata-Kapha, Pitta-Kapha, and Kapha dominant Prakriti have been found more in COVID19. The treatment strategies can be accordingly decided in respect of each patient.

Efficacy of homoeopathic treatment for diabetic distal symmetric polyneuropathy: A multicentric randomised double-blind placebo-controlled clinical trial.

BACKGROUND: In course of diabetes, some 20-90% of individuals eventually develop diabetic neuropathy. Looking at the disease burden research studies in Homoeopathy were conducted and have shown positive results. These studies were not robust enough to prove the efficacy of individualized homoeopathy. OBJECTIVE: To assess efficacy of individualized homoeopathic medicines in management of DDSP. METHODS: A multi-centric double-blind, placebo controlled, randomised clinical trial was conducted by the Central Council for Research in Homoeopathy at six centres with a sample size of 84. Based on earlier observational studies and repertorial anamnesis of DDSP symptoms 15 homoeopathic medicines were shortlisted and validated scales were used for evaluating the outcomes post-intervention. Primary outcome measure was change in Neuropathy Total Symptom Score-6 (NTSS-6) from baseline to 12 months. Secondary outcomes included changes in peripheral nerve conduction study (NCS), World Health Organization Quality of Life BREF (WHOQOL-BREF) and Diabetic Neuropathy Examination (DNE) Score at 12 months. RESULTS: Data of 68 enrolled cases was considered for data analysis. Statistically significant difference (p<0.014) was found in NTSS-6 post intervention in the Verum group. Positive trend was noted for Verum group as per the graph plotted for DNE score and assessment done for NCS. No significant difference was found between the groups for WHOQOL-Bref. Out of 15 pre-identified homoeopathic medicines 11 medicines were prescribed in potencies in ascending order from 6C to 1M. CONCLUSION: Further studies must be taken up with larger sample size and defined parameters for NCS to assess the effectiveness of homoeopathy.

Homeopathic Treatment as an Add-On Therapy May Improve Quality of Life and Prolong Survival in Patients with Non-Small Cell Lung Cancer: A Prospective, Randomized, Placebo-Controlled, Double-Blind, Three-Arm, Multicenter Study.

LESSONS LEARNED: Conventional medicine and homeopathy work well together. Quality of life improves with additive homeopathy in patients with non-small cell lung cancer (NSCLC). Survival improves with additive homeopathy in patients with NSCLC. BACKGROUND: Patients with advanced non-small cell lung cancer (NSCLC) have limited treatment options. Alongside conventional anticancer treatment, additive homeopathy might help to alleviate side effects of conventional therapy. The aim of the present study was to investigate whether additive homeopathy might influence quality of life (QoL) and survival in patients with NSCLC. METHODS: In this prospective, randomized, placebo-controlled, double-blind, three-arm, multicenter, phase III study, we evaluated the possible effects of additive homeopathic treatment compared with placebo in patients with stage IV NSCLC, with respect to QoL in the two randomized groups and survival time in all three groups. Treated patients visited the outpatients' centers every 9 weeks: 150 patients with stage IV NSCLC were included in the study; 98 received either individualized homeopathic remedies (n = 51) or placebo (n = 47) in a double-blinded fashion; and 52 control patients without any homeopathic treatment were observed for survival only. The constituents of the different homeopathic remedies were mainly of plant, mineral, or animal origin. The remedies were manufactured by stepwise dilution and succussion, thereby preparing stable Good Manufacturing Practice grade formulations. RESULTS: QoL as well as functional and symptom scales showed significant improvement in the homeopathy group when compared with placebo after 9 and 18 weeks of homeopathic treatment (p < .001). Median survival time was significantly longer in the homeopathy group (435 days) versus placebo (257 days; p = .010) as well as versus control (228 days; p < .001). Survival rate in the homeopathy group differed significantly from placebo (p = .020) and from control (p < .001). CONCLUSION: QoL improved significantly in the homeopathy group compared with placebo. In addition, survival was significantly longer in the homeopathy group versus placebo and control. A higher QoL might have contributed to the prolonged survival. The study suggests that homeopathy positively influences not only QoL but also survival. Further studies including other tumor entities are warranted.

Antiviral Activity of Belladonna During Japanese Encephalitis Virus Infection via Inhibition of Microglia Activation and Inflammation Leading to Neuronal Cell Survival.

Japanese encephalitis virus (JEV) is the main cause of viral encephalitis resulting in more than 68 000 clinical cases every year with case fatality rate as high as 30-40% for which no specific treatments are available. We have recently exhibited belladonna may be widely applicable for the treatment of various neurological disorders. Therefore, we developed a hydroalcoholic formulation of belladonna (B200) consisting of atropine and scopolamine and showed its antiviral efficacy against JEV infection. B200 treatment increases neuronal cell survival by reducing JEV induced cytopathic effects which were evident from significant reduction in necrotic cell population by flow-cytometry analysis and caspase 3 and 8 enzymatic activities. B200 treatment was found to reduce the intracellular JEV level observed by significant reduction in JEV-fluorescein isothiocyanate (FITC) expression in both neurons and microglia. Because microglia plays a crucial role in JEV pathogenesis, we further investigated the anti-JEV effects of B200 on human microglia cells and elucidated the mechanism of action by performing whole-transcriptome sequencing. Gene expression analysis revealed that B200 reduces the pro-apoptotic and inflammatory gene expression observed by significant reduction in BAD, BAX, CASP3, CASP8, IL1B, and CXCL10 and increase in IL10 responsive gene expression. Interestingly, our molecular docking analysis revealed that atropine and scopolamine interact with the His288 residue of NS3 protein, a crucial residue for RNA unwinding and ATPase activity that was further confirmed by degradation of NS3 protein. Drug likeness, ADME (absorption, distribution, metabolism, and excretion), and toxicity analysis further suggests that atropine and scopolamine both cross the blood-brain barrier, which is crucial for effective treatment of Japanese encephalitis (JE).

Calcarea carbonica treatment rescues lipopolysaccharide-induced inflammatory response in human mononuclear cells via downregulation of inducible cyclooxygenase pathway.

OBJECTIVE: Prolonged use of nonsteroidal anti-inflammatory drugs is associated with severe side effects and toxicity. Therefore, we studied the anti-inflammatory role of Calcarea carbonica which had minimal toxicity at the low doses. METHODS: THP-1 human mononuclear cells were treated with C. carbonica to evaluate the 50% cytotoxicity concentration (CC50) and 50% effective concentration (EC50). Cell survival was evaluated in lipopolysaccharide-stimulated C. carbonica-treated cells. Nitric oxide (NO) and tumor necrosis factor-α (TNF-α) were measured to evaluate the anti-inflammatory activity of C. carbonica. Cyclooxygenase-2 (COX-2) protein expression was determined by Western blotting analysis, and the interaction of C. carbonica with the COX-2 protein was evaluated using molecular docking simulation. RESULTS: The CC50 and EC50 of C. carbonica were found to be 43.26 and 11.99 µg/mL, respectively. The cell survival assay showed a 1.192-fold (P = 0.0129), 1.443-fold (P = 0.0009) and 1.605-fold (P = 0.0004) increase in cell survival at 24, 48 and 72 h after initiating C. carbonica treatment, respectively. C. carbonica-treated cells showed a reduction in NO levels by 2.355 folds (P = 0.0001), 2.181 folds (P = 0.0001) and 2.071 folds (P = 0.0001) at 24, 48 and 72 h, respectively. The treated cells also showed a reduction in TNF-α levels by 1.395 folds (P = 0.0013), 1.541 folds (P = 0.0005) and 1.550 folds (P = 0.0005) at 24, 48 and 72 h, respectively. In addition, a 1.193-fold reduction (P = 0.0126) in COX-2 protein expression was found in C. carbonica-treated cells. The molecular docking showed interaction of C. carbonica with the phenylalanine 367 residue present in active site of Cox-2. CONCLUSION: C. carbonica exhibited anti-inflammatory properties in lipopolysaccharide-stimulated cells by significantly reducing NO production and TNF-α level through downregulation of the COX-2 protein. This effect is probably mediated through interaction of C. carbonica with the phenylalanine 367 residue present in active site of Cox-2.

Dark Classics in Chemical Neuroscience: An Evidence-Based Systematic Review of Belladonna.

Belladonna has diverse pharmacotherapeutic properties with a shadowy history of beauty, life, and death. Alkaloids present in belladonna have anti-inflammatory, anticholinergic, antispasmodic, mydriatic, analgesic, anticonvulsant, and antimicrobial activities, which makes it widely applicable for the treatment of various diseases. However, because of its associated toxicity, the medicinal use of belladonna is debatable. Therefore, an evidence-based systematic review was planned to elucidate the pharmacotherapeutic potential of belladonna. A comprehensive literature search was performed in PubMed, MEDLINE, the Cochrane database, Embase, and ClinicalTrials.gov using the keywords "belladonna", "belladonna and clinical trials", and "safety and efficacy of belladonna". Articles published from 1965 to 2020 showing the efficacy of belladonna in diverse clinical conditions are included. The quality of evidence was generated using the GRADE approach, and 20 studies involving 2302 patients were included for the systematic review. Our analyses suggest that belladonna treatment appears to be safe and effective in various disease conditions, including acute encephalitis syndrome, urethral stent pain, myocardial ischemia injury, airway obstructions during sleep in infants, climacteric complaints, irritable bowel syndrome, and throbbing headache. However, better understanding of the dosage and the toxicity of tropane alkaloids of belladonna could make it an efficient remedy for treating diverse medical conditions.

Recommendations for Designing, Conducting and Reporting Observational Studies in Homeopathy.

BACKGROUND: Randomized placebo-controlled trials are considered to be the gold standard in clinical research and have the highest importance in the hierarchical system of evidence-based medicine. However, from the viewpoint of decision makers, due to lower external validity, practical results of efficacy research are often not in line with the huge investments made over decades. METHOD: We conducted a narrative review. With a special focus on homeopathy, we give an overview on cohort, comparative cohort, case-control and cross-sectional study designs and explain guidelines and tools that help to improve the quality of observational studies, such as the STROBE Statement, RECORD, GRACE and ENCePP Guide. RESULTS: Within the conventional medical research field, two types of arguments have been employed in favor of observational studies. First, observational studies allow for a more generalizable and robust estimation of effects in clinical practice, and if cohorts are large enough, there is no over-estimation of effect sizes, as is often feared. We argue that observational research is needed to balance the current over-emphasis on internal validity at the expense of external validity. Thus, observational research can be considered an important research tool to describe "real-world" care settings and can assist with the design and inform the results of randomised controlled trails. CONCLUSIONS: We present recommendations for designing, conducting and reporting observational studies in homeopathy and provide recommendations to complement the STROBE Statement for homeopathic observational studies.

Efectos del tratamiento homeopático individualizado en la hipertensión esencial de estadio I: ensayo aleatorizado, simple ciego, controlado con placebo / Effects of Homeopathic Treatment Individualized in Hypertension Stage I Essential: Randomized Trial, Single Blind, Placebo controlled

Fundamentos: la hipertensión arterial es el cuarto principal factor de riesgo de muerte e incapacidad, así como el responsable de más de 1.6 millones de fallecimientos en la India. Los informes de casos clínicos, los estudios observacionales y los ECA evidencian los efectos de los medicamentos homeopáticos en la hipertensión. Objetivos: los resultados de este estudio se añaden a la evidencia de la eficacia del uso de los medicamentos homeopáticos individualizados en la hipertensión de estadio I. Materiales y métodos: Se ha realizado un ensayo aleatorizado, simple ciego y controlado por placebo entre octubre de 2013 y marzo de 2018. El parámetro primario fue evaluar los cambios en la presión sistólica (PS) y la presión diastólica (PD) mensualmente durante tres meses. 217 pacientes de los 2,127 pacientes examinados cumplieron los criterios de selección y fueron aleatorizados para recibir un medicamento en potencias Q (o potencias LM) más indicaciones para la modificación del estilo de vida (MEV) (116 pacientes) o bien placebo + MEV (101 pacientes). La modificación del estilo de vida incluyó actividad física y dieta como parte de la pauta terapéutica. El análisis fue de intención de tratamiento. Resultados: Las mediciones ANOVA repetidas entre los grupos mostraron una diferencia estadística significativa (Lambda de Wilks 0.85, F=12.12, dF=213, P=0.0001) tanto en la PS como en la PD a favor de la Homeopatía individualizada. La prueba t independiente post hoc mostró una reducción media significativa de la PS [diferencia media 7.12 mmHg, IC del 95%; CI 4.72 a 9.53, P=0.0001] y un descenso medio de la PD [diferencia media 5.76 mmHg, IC del 95%: 4.18 a 7.23, P=0.0001] a favor del grupo con Homeopatía más MEV. Los medicamentos más utilizados fueron: Sulphur (n=24), Natrium muriaticum (n=21), Lycopodium (n=16), Nux vomica (n=12) y Phosphorus (n=10). Conclusiones: Se ha constatado que la Homeopatía individualizada junto con la MEV fue más eficaz que el placebo junto con la MEV en los pacientes que sufren hipertensión en estadio I. Se precisan más ensayos en un marco estricto. (AU)

Background: Hypertension (HTN) is a leading risk factor for death and disability and responsible for over 1.6 million deaths in India. Clinical case reports, observational studies and randomised controlled trials show the effects of homoeopathic medicine in HTN. Objectives: The results of this study will add to the evidence of effectiveness of individualised homoeopathic medicine in Stage I HTN. Methods: A single-blind, randomised, placebocontrolled trial was undertaken from October 2013 to March 2018. The primary outcome measure was to evaluate the change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) every month for 3 months. Of 2,127 patients screened, 217 patients who fitted the inclusion criteria were randomised to receive either homoeopathic Q potencies (or LM potencies) plus lifestyle modification (LSM)=116 or placebo + LSM=101. LSM included physical activity and diet as part of the treatment regimen. Analysis was by intention to treat. Results: Repeated-measure ANOVA between the groups showed statistically significant difference (Wilk lambda 0.85, F=12.12, df=213, P=0.0001), in both SBP and DBP favouring Individualised Homoeopathy (IH) along with LSM. Post hoc independent t-test showed a significant mean reduction in SBP (mean difference 7.12 mmHg, 95% confidence interval [CI] 4.72-9.53, P=0.0001) and DBP (mean difference 5.76 mmHg, 95% CI: 4.18-7.23, P=0.0001) favouring Homoeopathy plus LSM group. Sulphur (n=24), Natrum muriaticum (n=21), Lycopodium (n=16), Nux vomica (n=12) and Phosphorus (n=10) were the most useful medicines. Conclusion: IH in LM potency along with LSM was found effective over placebo along with LSM in the patients suffering from Stage I HTN. Further trials in rigorous setting are warranted. (AU)

Effect of Adjuvant Homeopathy with Usual Care in Management of Thrombocytopenia Due to Dengue: A Comparative Cohort Study.

BACKGROUND: Dengue is an emerging threat to public health. At present, no clear modalities are available for the prevention and management of thrombocytopenia due to dengue. This article reports the clinical outcomes of integrative homeopathic care in a hospital setting during a severe outbreak of dengue in New Delhi, India, during the period September to December 2015. METHODS: Based on preference, 138 patients received a homeopathic medicine along with usual care (H+UC), and 145 patients received usual care (UC) alone. Assessment of thrombocytopenia (platelet count < 100,000/mm3) was the main outcome measure. Kaplan-Meier analysis enabled comparison of the time taken to reach a platelet count of 100,000/mm3. RESULTS: There was a statistically significantly greater rise in platelet count on day 1 of follow-up in the H+UC group compared with UC alone (mean difference = 12,337; 95% confidence interval [CI], 5,421 to 19,252; p = 0.001). This trend persisted until day 5 (mean difference = 14,809; 95% CI, 1,615 to 28,004; p = 0.02). The time taken to reach a platelet count of 100,000/mm3 was nearly 2 days earlier in the H+UC group compared with UC alone (H+UC: 3.44 days ± standard error of the mean [SEM] 0.18; 95% CI, 3.08 to 3.80; UC: 5.28 days ± SEM 0.29; 95% CI, 4.71 to 5.86; p < 0.001). CONCLUSION: These results suggest a positive role of adjuvant homeopathy in thrombocytopenia due to dengue. Randomized controlled trials may be conducted to obtain more insight into the comparative effectiveness of this integrative approach.

Homeopathy in Public Health in India.

BACKGROUND: Based on a pluralistic approach to health care, India offers a range of medical treatment modalities to its population. In that context, the government of India aims at providing its people with wider access to homeopathy. This article provides insight into the infrastructural support put in place by the government to meet that aim. DATA AND METHODS: A literature review was carried out of recent surveys and articles to assess the morbidity trends in India and the treatment modalities being sought by patients. Extensive attempts were made to identify and access all data sources that could contribute to understanding the situation of homeopathy in public health in India. These efforts included analysis of secondary data about government wellness centres, as also a case study of one such centre. RESULTS: In India, homeopathy is well represented in public health, being a close second among the AYUSH (Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homeopathy) services. Homeopathy wellness centres comprise 31% of the total for AYUSH. Seven out of 10 diseases recognised as a national health burden are in the category of most commonly reported diseases at the homeopathy wellness centres. Academic homeopathy institutes comprise 35.8% of AYUSH colleges, the total student intakes of which are 13,658 and 32,256 respectively. Homeopathy practitioners are 37% of the AYUSH total. Homeopathy units comprise 1/19th of the number of allopathy units, yet the annual patient footfall in the former is 1/5th of the latter. CONCLUSION: Homeopathy services, wherever available, are being used fully and thus sharing the patient load in the government-run wellness centres. There is the potential for more homeopathic practitioners to contribute importantly to health care delivery in India.

An Assessment of a Public Health Initiative of Homeopathy for Primary Teething.

BACKGROUND: During primary teething, children suffer from running nose, mild fever, diarrhoea and other mild irritations and inflammations. A public health programme, 'Homoeopathy for the Healthy Child', was undertaken on a pilot basis focusing on promotion of healthy teething by provision of home-based care through six pre-identified homeopathic medicines for complaints commonly observed during primary teething. This article assesses the feasibility of this programme and reports the impact of this initiative on teething profile in children and episodes of diarrhoea and upper respiratory tract infection (URTI). MATERIALS AND METHODS: Accredited Social Health Activists (ASHAs) were trained in child care and usage of a kit comprising six medicines, namely Calcarea phosphoricum 6X (CP), Ferrum phosphoricum 3X, Magnesium phosphoricum 6X, Belladonna 30C, Chamomilla 30C and Podophyllum 30C. Calcarea phosphoricum was given regularly to each participating child from 6 months to 1 year of age. Home-based care for diarrhoea, URTI and mild fever was provided by ASHAs using the other five medicines in the kit. Dentition pattern and diarrhoea/URTI episodes were recorded over a period of the next 12 months. RESULTS: Eleven thousand four-hundred and twenty-six children were followed up regularly. Amongst those who enrolled at 6-7 months, a larger proportion of children were approaching expected teething in successive months as compared with children enrolled at 12 months, thus indicating that teething delays, if any, were overcome during this period. Incidence of diarrhoea and URTI showed decrease in the months after enrolment. Children responded favourably to the medicines given by ASHAs at the time of diarrhoea/URTI episodes, and ASHAs expressed satisfaction with the programme. CONCLUSION: An approach with regular use of CP and home-based care with homeopathy through health workers for common problems in teething children is acceptable to the community and enhances outreach of services to the public at large. Observations in terms of the healthy teething period may be further validated through studies of homeopathy with suitable comparator group.

Effectiveness of Homeopathic Medicines as Add-on to Institutional Management Protocol for Acute Encephalitis Syndrome in Children: An Open-Label Randomized Placebo-Controlled Trial.

BACKGROUND: Acute encephalitis syndrome (AES) is endemic to certain parts of India, with limited treatment options. In our initial exploratory comparative observational study of 151 patients with AES, there was significantly reduced mortality with adjunctive homeopathy compared to institutional management protocol (IMP). The present randomized placebo-controlled trial brings more statistical rigor to this research program. METHODS: This study was conducted at a pediatric unit from 2013 to 2015. Children aged > 6 months and ≤ 18 years and receiving IMP were randomized to receive adjunctive homeopathy (n = 325) or placebo as control (n = 323). The primary effectiveness analysis was based on Glasgow Outcome Scale (GOS). Morbidity was assessed using the Liverpool Outcome Score for Assessing Children at Follow-up. Analysis was by intention to treat. RESULTS: A total of 612 children were analyzed (Homeopathy [H] = 304; Control [C] = 308). The primary outcome, GOS, differed significantly between H and C groups. There was 14.8% death/neuro-vegetative state in the H group compared to 29.8% in the C group. Relative risk was 0.49 (95% confidence interval [CI]: 0.36 to 0.68), with absolute risk reduction of 15.0% (95% CI: 8.6 to 21.6%). Number needed to treat to prevent one additional death/neuro-vegetative state was 6.6 (95% CI: 4.6 to 11.6). Proportional-odds analysis also revealed a greater effect in the H group: odds ratio, 0.40 (95% CI: 0.27 to 0.60). The most frequently used medicines were Belladonna (n = 116), Stramonium (n = 33), Arsenicum album (n = 25), Sulfur (n = 18), Opium (n = 17), and Nux vomica (n = 10). CONCLUSION: Adjunctive homeopathic medicines may improve clinical outcomes associated with AES. Further randomized and controlled studies, using double-blinded trial design, are recommended to discover if the current findings may be corroborated.

Model validity of randomised placebo-controlled trials of non-individualised homeopathic treatment.

BACKGROUND: The comprehensive systematic review of randomised placebo-controlled trials (RCTs) in homeopathy requires examination of a study's model validity of homeopathic treatment (MVHT) as well as its risk of bias (extent of reliable evidence). OBJECTIVE: To appraise MVHT in those RCTs of non-individualised homeopathy that an associated investigation had judged as 'not at high risk of bias'. DESIGN: Systematic review. METHODS: An assessment of MVHT was ascribed to each of 26 eligible RCTs. Another 49 RCTs were ineligible due to their high risk of bias. MAIN OUTCOME MEASURES: MVHT and the prior risk of bias rating per trial were merged to obtain a single overall quality designation ('high', 'moderate', 'low'), based on the GRADE principle of downgrading. RESULTS: The trials were rated as 'acceptable MVHT' (N = 9), 'uncertain MVHT' (N = 10) and 'inadequate MVHT' (N = 7); and, previously, as 'reliable evidence' (N = 3) and 'non-reliable evidence' (N = 23). The 26 trials were designated overall as: 'high quality' (N = 1); 'moderate quality' (N = 18); 'low quality' (N = 7). CONCLUSION: Of the 26 RCTs of non-individualised homeopathy that were judged 'not at high risk of bias', nine have been rated 'acceptable MVHT'. One of those nine studies was designated 'high quality' overall ('acceptable MVHT' and 'reliable evidence'), and is thus currently the only reported RCT that represents best therapeutic practice as well as unbiased evidence in non-individualised homeopathy. As well as minimising risk of bias, new RCTs in this area must aim to maximise MVHT and clarity of reporting.

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.

Model validity and risk of bias in randomised placebo-controlled trials of individualised homeopathic treatment.

BACKGROUND: To date, our programme of systematic reviews has assessed randomised controlled trials (RCTs) of individualised homeopathy separately for risk of bias (RoB) and for model validity of homeopathic treatment (MVHT). OBJECTIVES: The purpose of the present paper was to bring together our published RoB and MVHT findings and, using an approach based on GRADE methods, to merge the quality appraisals of these same RCTs, examining the impact on meta-analysis results. DESIGN: Systematic review with meta-analysis. METHODS: As previously, 31 papers (reporting a total of 32 RCTs) were eligible for systematic review and were the subject of study. MAIN OUTCOME MEASURES: For each trial, the separate ratings for RoB and MVHT were merged to obtain a single overall quality designation ('high', 'moderate, "low", 'very low'), based on the GRADE principle of 'downgrading'. RESULTS: Merging the assessment of MVHT and RoB identified three trials of 'high quality', eight of 'moderate quality', 18 of 'low quality' and three of 'very low quality'. There was no association between a trial's MVHT and its RoB or its direction of treatment effect (P>0.05). The three 'high quality' trials were those already labelled 'reliable evidence' based on RoB, and so no change was found in meta-analysis based on best-quality evidence: a small, statistically significant, effect favouring homeopathy. CONCLUSION: Accommodating MVHT in overall quality designation of RCTs has not modified our pre-existing conclusion that the medicines prescribed in individualised homeopathy may have small, specific, treatment effects.