Everyday Evaluation of Herb/Dietary Supplement-Drug Interaction: A Pilot Study.

A lack of reliable information hinders the clinician evaluation of suspected herb-drug interactions. This pilot study was a survey-based study conceived as a descriptive analysis of real-life experiences with herb-drug interaction from the perspective of herbalists, licensed health-care providers, and lay persons. Reported dietary supplement-drug interactions were evaluated against the resources most commonly cited for the evaluation of potential supplement-drug interactions. Disproportionality analyses were performed using tools available to most clinicians using data from the U.S. Federal Adverse Event Reporting System (FAERS) and the US Center for Food Safety and Applied Nutrition (CFSAN) Adverse Event Reporting System (CAERS). Secondary aims of the study included exploration of the reasons for respondent use of dietary supplements and qualitative analysis of respondent's perceptions of dietary supplement-drug interaction. While agreement among reported supplement-drug interactions with commonly cited resources for supplement-drug interaction evaluation and via disproportionality analyses through FAERS was low, agreement using data from CAERS was high.

Randomized Double-Blind, Placebo-Controlled Feasibility Study, Evaluating the Efficacy of Homeopathic Medicines in the Prevention of COVID-19 in a Quarantined Population.

INTRODUCTION: Exploring preventive therapeutic measures has been among the biggest challenges during the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We explored the feasibility and methods of recruitment, retention, and potential signal of efficacy, of selected homeopathic medicines as preventive measure for developing COVID-19 in a multi-group study. METHODS: A six-group, randomized, double-blind, placebo-controlled prophylaxis study was conducted in a COVID-19 exposed population in a quarantine facility in Mumbai, India. Each group received one of the following: Arsenicum album 30c, Bryonia alba 30c, a combination (Arsenicum album 30c, Bryonia alba 30c, Gelsemium sempervirens 30c, and Influenzinum 30c), coronavirus nosode CVN01 30c, Camphora 1M, or placebo. Six pills twice a day were administered for 3 days. The primary outcome measure used was testing recruitment and retention in this quarantined setting. Secondary outcomes were numbers testing positive for COVID-19 after developing symptoms of illness, number of subjects hospitalized, and days to recovery. RESULTS: Good rates of recruitment and retention were achieved. Of 4,497 quarantined individuals, 2,343 sought enrollment, with 2,294 enrolled and 2,233 completing the trial (49.7% recruitment, 97.3% retention). Subjects who were randomized to either Bryonia alba or to the CVN01 nosode signaled (p <0.10) a lower incidence of laboratory-confirmed COVID-19 and a shorter period of illness, with evidence of fewer hospitalizations, than those taking placebo. The three other groups did not show signals of efficacy. CONCLUSION: This pilot study supports the feasibility of a larger randomized, double-blind, placebo-controlled trial. Bryonia alba 30c and CVN01 30c should both be explored in disease prevention or shortening the course of disease symptomatology in a COVID-19-exposed population.

Safety and Evaluation of the Immune Response of Coronavirus Nosode (BiosimCovex) in Healthy Volunteers: A Preliminary Study Extending the Homeopathic Pathogenetic Trial.

Objectives: Regulatory clinical Phase I studies are aimed at establishing the human safety of an active pharmaceutical agent to be later marketed as a drug. Since homeopathic medicines are prepared by a potentizing method using alcohol, past a certain dilution, their toxicity/infectivity is assumed to be unlikely. We aimed to develop a bridge study between homeopathic pathogenetic trials and clinical trials. The primary purpose was to evaluate the safety of a nosode, developed from clinical samples of a COVID-19 patient. The secondary objectives were to explore whether a nosode developed for a specific clinical purpose, such as use during an epidemic, may elicit laboratory signals worthy of further exploration. Methods: An open-label study was designed to evaluate the safety and immune response of the Coronavirus nosode BiosimCovex, given orally on three consecutive days to ten healthy volunteers. Clinical examinations, laboratory safety and immune parameters were established. Interferon-gamma, Interleukin-6, and CD 4 were measured. (CTRI registration number: CTRI/2020/05/025496). Results: No serious/fatal adverse events were reported. Laboratory tests to measure safety were unchanged. Three subjects showed elevated Interleukin-6 (IL-6) on day 17 in comparison to the baseline, and ten subjects showed elevated IL-6 on day 34. A significant difference between IL-6 observations, calculated by repeated measures ANOVA, was found to be highly significant. On day 60, the IL-6 values of nine subjects were found to return to normal. Corresponding CD4 cell elevation was observed on day 60, when compared to day 34. Conclusions: HPT may potentially extend into physiological changes with regards to immune response and should encourage future studies.

Herb-Drug Interactions: Worlds Intersect with the Patient at the Center.

This review examines three bodies of literature related to herb-drug interactions: case reports, clinical studies, evaluations found in six drug interaction checking resources. The aim of the study is to examine the congruity of resources and to assess the degree to which case reports signal for further study. A qualitative review of case reports seeks to determine needs and perspectives of case report authors. Methods: Systematic search of Medline identified clinical studies and case reports of interacting herb-drug combinations. Interacting herb-drug pairs were searched in six drug interaction resources. Case reports were analyzed qualitatively for completeness and to identify underlying themes. Results: Ninety-nine case-report documents detailed 107 cases. Sixty-five clinical studies evaluated 93 mechanisms of interaction relevant to herbs reported in case studies, involving 30 different herbal products; 52.7% of these investigations offered evidence supporting reported reactions. Cohen's kappa found no agreement between any interaction checker and case report corpus. Case reports often lacked full information. Need for further information, attitudes about herbs and herb use, and strategies to reduce risk from interaction were three primary themes in the case report corpus. Conclusions: Reliable herb-drug information is needed, including open and respectful discussion with patients.

The SOFIA Study: Negative Multi-center Study of Low Dose Fluoxetine on Repetitive Behaviors in Children and Adolescents with Autistic Disorder.

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that reduces obsessive-compulsive symptoms. There is limited evidence supporting its efficacy for repetitive behaviors (RRBs) in autistic spectrum disorder (ASD). We conducted a randomized controlled trial (RCT) of fluoxetine in 158 individuals with ASD (5-17 years). Following 14 treatment weeks (mean dose 11.8 mg/day), no significant differences were noted on the Children's Yale-Brown Obsessive Compulsive Scale; the proportion of responders was similar (fluoxetine: 36%; placebo: 41%). There were similar rates of AEs (e.g., insomnia, diarrhea, vomiting); high rates of activation were reported in both groups (fluoxetine: 42%; placebo: 45%). Overly cautious dosing/duration may have prevented attainment of a therapeutic level. Results are consistent with other SSRI RCTs treating RRBs in ASD.Trial Registration: clinicaltrials.gov Identifier: NCT00515320.

C1-esterase inhibitor infusion increases survival rates for patients with sepsis*.

OBJECTIVES: Systemic inflammatory response variability displays differing degrees of organ damage and differing outcomes of sepsis. C1-esterase inhibitor, an endogenous acute-phase protein, regulates various inflammatory and anti-inflammatory pathways, including the kallikrein-kinin system and leukocyte activity. This study assesses the influence of high-dose C1-esterase inhibitor administration on systemic inflammatory response and survival in patients with sepsis. DESIGN: Open-label randomized controlled study. SETTING: Surgical and medical intensive care units of nine university and city hospitals. PATIENTS: : Sixty-one patients with sepsis. INTERVENTIONS: Patients were randomized to receive either 12,000 U of C1-esterase inhibitor infusions in addition to conventional treatment or conventional treatment only (n = 41 C1-esterase inhibitor, 20 controls). Blood samples for measurement of C1-esterase inhibitor, complement components C3 and C4, and C-reactive protein concentrations were drawn on days 1, 3, 5, 7, 10, and 28. MEASUREMENTS AND MAIN RESULTS: Quartile analysis of C1-esterase inhibitor activity in sepsis subjects revealed that the lowest quartile subgroup had similar activity levels (0.7-1.2 U/L), when compared to healthy volunteers (p > .05). These normal-level C1-esterase inhibitor sepsis patients nevertheless displayed increased C-reactive protein (p = .04) production and higher likelihoods of a more severe sepsis (p = .001). Overall, infusion of C1-esterase inhibitor increased C1-esterase inhibitor (p < .005 vs. control on days 2, 3, and 5) functional activity, resulted in higher C3 levels (p < .05 vs. control on days 2 and 3), followed by decreased C-reactive protein (p < .05 vs. control on days 3 and 10). Simultaneously, C1-esterase inhibitor infusion in sepsis patients was associated with reduced all-cause mortality (12% vs. 45% in control, p = .008) as well as sepsis-related mortality (8% vs. 45% in control, p = .001) assessed over 28 days. The highest absolute reduction risk of 70% was achieved in sepsis patients with Simplified Acute Physiology Score II scores >27. CONCLUSION: In the present study, patients in the lowest quartile of C1-esterase inhibitor activity in combination with high C-reactive protein demonstrated a higher risk of developing severe sepsis. In general, high-dose C1-esterase inhibitor infusion down-regulated the systemic inflammatory response and was associated with improved survival rates in sepsis patients, which could have important treatment and survival implications for individuals with C1-esterase inhibitor functional deficiency.

Methodological considerations for future controlled influenza treatment trials in complementary and alternative medicine.

BACKGROUND: The continuous threat of influenza pandemic, as well as the ongoing costs to human life and health care systems from yearly epidemics, create a continual need for progress in this area of public health. The diversity of available complementary and alternative medicine (CAM) treatment options are well known to the CAM profession, but poorly understood and accepted in mainstream medicine. This situation comes as no surprise given conventional medicine's reliance on repeated, large-scale randomized controlled trials of standardized design to support evidence-based clinical use of influenza antiviral drugs. The relatively low volume of well-conducted clinical trials on the treatment of influenza with CAM therapies compared to the high availability of conventional antiviral drug trials magnifies this problem. OBJECTIVES: The aim of this article is to provide structured guidelines for future CAM influenza studies based on a thorough review of consistent and standard design elements present in the controlled-trial design of conventional antiviral influenza therapies. RESULTS: A selection of high-quality, influenza antiviral controlled trials from the published literature is reviewed, and important design elements are extracted and summarized to show both the consistency and the flexibility within study design elements. CONCLUSIONS: The standardized elements from influenza antiviral trials can be considered and mirrored in future CAM studies. In this way, CAM therapies might be looked at on similar grounds as conventional medicines in terms of potential usefulness and benefit in the treatment of influenza.

Clinical prediction rules: new opportunities for pharma.

Clinical prediction rules (CPRs) are important tools in the development of an evidence-based, personalized medical system. This article compares CPRs to other medical information tools, giving solvent examples of their clinical application and potential to increase efficacy and efficiency, as well as their utility in drug development. The primary focus is on the potential of CPRs to define the most effective level of generalization, predictably and reproducibly identifying homogenous groups of subjects (based on outcome) in heterogeneous and undifferentiated trial populations. This potential can be met if CPR construction integrates three elements: the identification of variables both within and outside the disorder that affect outcome and the mapping of relevant human physiome types based upon identifiable trait and reactionary patterns.

Angiotensin-converting enzyme inhibitor-induced angioedema in a community hospital emergency department.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACE-Is) are associated with angioedema, a potentially life-threatening adverse reaction. Although multiple studies have been conducted in tertiary care emergency departments (EDs), scarce data are available about the presentation and management of ACE-I-induced angioedema (AIIA) in the community hospital ED. OBJECTIVE: To describe the frequency, presentation, and management of AIIA in patients seen in a community hospital ED. METHODS: A 5-year medical record review of all patients seen with angioedema at a community hospital ED. Data abstraction focused on demographic factors, initial clinical characteristics, and ED management and disposition of patients with AIIA. RESULTS: We identified 166 ED visits for angioedema, including a subset of 50 visits for AIIA (30%; 95% confidence interval, 23%-38%). The AIIA was significantly more likely to be associated with an age of 65 years or older (P = .02), unilateral symptoms (P = .02), and absence of urticaria or itching (P < .001). The ED treatment choices and admission rates were similar between patients with and without AIIA. Community hospital admission rates for AIIA (14%) were significantly lower than those from a comparable tertiary care study (41%) (P = .003); ambulance transport to the ED was nearly 3-fold higher in the tertiary care center study (P = .006). Admission was most strongly related to lack of improvement (P < .001) and history of angioedema in AIIA (P = .009). CONCLUSIONS: Angioedema frequency, presentation, and management are similar in community and tertiary care EDs (30%). Urticaria or itching may help differentiate AIIA from allergic reactions, which are otherwise similar in community ED presentation and management.

New England School of Homeopathy - NESH

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