Use of oxygen-ozone therapy to improve the effectiveness of antibiotic treatment on infected arthroplasty: protocol for a superiority, open-label, multicentre, randomised, parallel trial.

INTRODUCTION: Surgical site infections still remain a major public health challenge and have become an increasing universal risk, especially for the implantation of orthopaedic devices.Unfortunately, the discovery and increasingly widespread use (especially the misuse) of antibiotics have led to the rapid appearance of antibiotic-resistant strains today; more and more infections are caused by microorganisms that fail to respond to conventional treatments.Oxygen-ozone therapy has been extensively used and studied for decades across various potential medical applications and has provided consistent effects with minimal side effects.This study aims to determine the superiority of oxygen-ozone therapy in combination with oral antibiotic therapy in patients with wound infections after an orthopaedic device implantation when compared with antibiotic therapy alone. METHODS AND ANALYSIS: This is an open-label, multicentre, randomised, parallel-group study that aims to assess the efficacy and safety of oxygen-ozone therapy in combination with oral antibiotic therapy to treat infections in patients (male or female aged ≥18 years) having undergone surgery for the implant of an orthopaedic device. Patients must have at least one (but no more than three) postoperative wounds in the site of surgery (ulcers, eschars and sores) and at least one symptom (pain, burning, redness and malodour) and at least one sign (erythema, local warmth, swelling and purulent secretion) of infection of at least moderate intensity (score ≥2) in the target lesion at the screening visit (patients with wounds without signs of localised infection or with undermining wounds will be excluded).Patients (n=186) will be recruited from five Italian hospitals and studied for 7 weeks. All will be assigned to one of the two treatment groups according to a web-based, centralised randomisation procedure and placed into either the (1) intervention: oxygen-ozone therapy 2-3 times a week for 6 weeks (for a maximum of 15 sessions) simultaneously with an appropriate oral antibiotic therapy prescribed at baseline or (2) control: oral antibiotic therapy prescribed at baseline.The primary outcome is the efficacy and superiority of the treatment (ozone and oral antibiotic therapies); secondary outcomes include the resolution of signs and symptoms, modifications in lesion size and the treatment's safety and tolerability. ETHICS AND DISSEMINATION: This study has been reviewed and approved by the responsible Independent Ethics Committee (IEC) of COMITATO ETICO CAMPANIA NORD, located at 'Azienda Ospedaliera San Giuseppe Moscati di Avellino'.After completion of the study, the project coordinator will prepare a draft manuscript containing the final results of the study on the basis of the statistical analysis. The manuscript will be derived by the co-authors for comments, and after revision, it will be sent to a major scientific journal. Findings will be disseminated via online and print media, events and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04787575.

Increasing delta-9-tetrahydrocannabinol (Δ-9-THC) content in herbal cannabis over time: systematic review and meta-analysis.

AIM: The objective of this meta-analysis is to assess the data regarding changes in herbal cannabis potency over time (from 1970 to 2009). METHODS: Systematic searches of 17 electronic scientific databases identified studies on this topic, within which 21 case series studies satisfied our inclusion criteria of reporting the mean tetrahydrocannabinol (THC) value per number of samples per year. No language, publication date, publication type or status restrictions were imposed. The study selection and data extraction processes were performed independently but uniformly by two authors, included screening, determination of eligibility and inclusion of the eligible studies in the systematic review, and a meta-analysis of the results on THC content in herbal cannabis samples. We considered papers and not monographic scientific publications, rejecting all studies that were not focused on the subject of this review. RESULTS: Meta-analysis by year was performed on 21 studies containing 75 total mean THC observations from 1979 to 2009 using the random effects model. The results revealed much variability between studies. Further, there was a significant correlation between year and mean THC in herbal cannabis. The combined data indicated the correlation between year and mean THC in herbal cannabis, revealing a temporal trend of increasing potency (5% above the mean THC value in the Poisson regression analysis). CONCLUSIONS: The results of the analysis suggest that there has been a recent and consistent increase in cannabis potency worldwide.

A real-time PCR assay for the relative quantification of the tetrahydrocannabinolic acid (THCA) synthase gene in herbal Cannabis samples.

In this study, we wanted to investigate whether or not the tetrahydrocannabinolic acid (THCA) synthase gene, which codes for the enzyme involved in the biosynthesis of THCA, influences the production and storage of tetrahydrocannabinol (THC) in a dose-dependent manner. THCA is actually decarboxylated to produce THC, the main psychoactive component in the Cannabis plant. Assuming as the research hypothesis a correlation between the gene copy number and the production of THC, gene quantification could be useful in forensics in order to complement or replace chemical analysis for the identification and classification of seized Cannabis samples, thus distinguishing the drug-type from the fibre-type varieties. A real-time PCR assay for the relative quantification of the THCA synthase gene was then validated on Cannabis samples; some were seized from the illegal drug market and others were derived from experimental cultivation. In order to determine the gene copy number to compare high vs. low potency plants, we chose the ΔΔCt method for TaqMan reactions. The assay enabled single plants with zero, one, and two copies of the gene to be distinguished. As a result of this first part of the research on the THCA synthase gene (the second part will cover a study of gene expression), we found no correlation between THCA synthase gene copy number and the content of THC in the herbal Cannabis samples tested.