Searching for the Genus Epidemicus in Chinese Patients: Findings from the Clificol COVID-19 Clinical Case Registry.

BACKGROUND: The Clificol COVID-19 Support Project is an innovative international data collection project aimed at tackling some of the core questions in homeopathy. This paper reports on the further investigation of the genus epidemicus concept during the first wave of the pandemic in the Chinese population. METHODS: The design is an observational clinical case registry study of Chinese patients with confirmed or suspected coronavirus disease 2019 (COVID-19). The symptoms were prospectively collected via a 150-item questionnaire. The concept of genus epidemicus, including the role of treatment individualization, was investigated by analyzing whether presenting symptoms clustered into distinct groups. Two standard statistical analysis techniques were utilized: principal component analysis for extracting the most meaningful symptoms of the dataset; the k-means clustering algorithm for automatically assigning groups based on similarity between presenting symptoms. RESULTS: 20 Chinese practitioners collected 359 cases in the first half of 2020 (766 consultations, 363 prescriptions). The cluster analysis found two to be the optimum number of clusters. These two symptomatic clusters had a high overlap with the two most commonly prescribed remedies in these sub-populations: in cluster 1 there were 297 prescriptions, 95.6% of which were Gelsemium sempervirens; in cluster 2 there were 61 prescriptions, 95.1% of which were Bryonia alba. CONCLUSION: This is the first study to investigate the notion of genus epidemicus by using modern statistical techniques. These analyses identified at least two distinct symptom pictures. The notion of a single COVID-19 genus epidemicus did not apply in the studied population.

Systematic Review and Meta-Analysis of Randomised, Other-than-Placebo Controlled, Trials of Non-Individualised Homeopathic Treatment.

INTRODUCTION: This study focuses on randomised controlled trials (RCTs) of non-individualised homeopathic treatment (NIHT) in which the control (comparator) group was other than placebo (OTP). OBJECTIVES: To determine the comparative effectiveness of NIHT on health-related outcomes in adults and children for any given condition that has been the subject of at least one OTP-controlled trial. For each study, to assess its risk of bias and to determine whether its study attitude was predominantly 'pragmatic' or 'explanatory'. METHODS: Systematic review. For each eligible trial, published in the peer-reviewed literature up to the end of 2016, we assessed its risk of bias (internal validity) using the seven-domain Cochrane tool, and its relative pragmatic or explanatory attitude (external validity) using the 10-domain PRECIS tool. We grouped RCTs by whether these examined IHT as alternative treatment (study design 1a), adjunctively with another intervention (design 1b), or compared with no intervention (design 2). RCTs were sub-categorised as superiority trials or equivalence/non-inferiority trials. For each RCT, we designated a single 'main outcome measure' to use in meta-analysis: 'effect size' was reported as odds ratio (OR; values > 1 favouring homeopathy) or standardised mean difference (SMD; values < 0 favouring homeopathy). RESULTS: Seventeen RCTs, representing 15 different medical conditions, were eligible for study. Three of the trials were more pragmatic than explanatory, two were more explanatory than pragmatic, and 12 were equally pragmatic and explanatory. Fourteen trials were rated 'high risk of bias' overall; the other three trials were rated 'uncertain risk of bias' overall. Ten trials had data that were extractable for analysis. Significant heterogeneity undermined the planned meta-analyses or their meaningful interpretation. For the three equivalence or non-inferiority trials with extractable data, the small, non-significant, pooled effect size (SMD = 0.08; p = 0.46) was consistent with a conclusion that NIHT did not differ from treatment by a comparator (Ginkgo biloba or betahistine) for vertigo or (cromolyn sodium) for seasonal allergic rhinitis. CONCLUSIONS: The current data preclude a decisive conclusion about the comparative effectiveness of NIHT. Generalisability of findings is restricted by the limited external validity identified overall. The highest intrinsic quality was observed in the equivalence and non-inferiority trials of NIHT.

Common polymorphisms in the SERPINI2 gene are associated with refractive error in the 1958 British Birth Cohort.

PURPOSE: To identify heritable genetic factors altering susceptibility to refractive error in the general population. METHODS: This was a genetic association study of refractive error investigating genetic polymorphisms in regions previously reported through linkage. Two study panels were drawn from the British 1958 Birth Cohort, composed of 2211 persons 44 years of age at the time of visit. Two main outcomes were considered: refractive error as a continuous outcome (spherical equivalent) and myopia as a diagnosis (defined as spherical equivalent equal to or worse than-1.00 diopter). Genotyping was initially performed in 1188 subjects from the outer tertiles of the population distribution, using customized arrays of single nucleotide polymorphisms (SNPs) saturating regions of previously reported highly significant linkage. In a second stage, SNPs most significantly associated were validated in 1023 more persons. Findings were investigated further through human fetal expression studies. RESULTS: Polymorphisms within the SERPINI2 gene were associated with refractive error in two different European subgroups from the 1958 British Birth Cohort (meta-analysis P = 7.4E-05 for rs9810473). Association was also significant for myopia (best association: OR = 0.80; 95% CI, 0.69-0.93; P = 0.003 for rs10936538). Expression profiling of SERPINI2 revealed that the gene is expressed in the retina and in other eye and CNS tissues. CONCLUSIONS: The novel association of SERPINI2 with refractive error and myopia is suggestive of a possible link between physiological pathways controlling eye growth and development and those controlling glucose metabolism. The findings indicate that SERPINI2 is a promising candidate for further investigations of the genetic susceptibility to myopia.

Comparison of Iroquois gene expression in limbs/fins of vertebrate embryos.

In Drosophila, Iroquois (Irx) genes have various functions including the specification of the identity of wing veins. Vertebrate Iroquois (Irx) genes have been reported to be expressed in the developing digits of mouse limbs. Here we carry out a phylogenetic analysis of vertebrate Irx genes and compare expression in developing limbs of mouse, chick and human embryos and in zebrafish pectoral fin buds. We confirm that the six Irx gene families in vertebrates are well defined and that Clusters A and B are duplicates; in contrast, Irx1 and 3, Irx2 and 5, and Irx4 and 6 are paralogs. All Irx genes in mouse and chick are expressed in developing limbs. Detailed comparison of the expression patterns in mouse and chick shows that expression patterns of genes in the same cluster are generally similar but paralogous genes have different expression patterns. Mouse and chick Irx1 are expressed in digit condensations, whereas mouse and chick Irx6 are expressed interdigitally. The timing of Irx1 expression in individual digits in mouse and chick is different. Irx1 is also expressed in digit condensations in developing human limbs, thus showing conservation of expression of this gene in higher vertebrates. In zebrafish, Irx genes of all but six of the families are expressed in early stage pectoral fin buds but not at later stages, suggesting that these genes are not involved in patterning distal structures in zebrafish fins.