Supporting Machine Learning Model in the Treatment of Chronic Pain.

Conventional therapy options for chronic pain are still insufficient and patients most frequently request alternative medical treatments, such as medical cannabis. Although clinical evidence supports the use of cannabis for pain, very little is known about the efficacy, dosage, administration methods, or side effects of widely used and accessible cannabis products. A possible solution could be given by pharmacogenetics, with the identification of several polymorphic genes that may play a role in the pharmacodynamics and pharmacokinetics of cannabis. Based on these findings, data from patients treated with cannabis and genotyped for several candidate polymorphic genes (single-nucleotide polymorphism: SNP) were collected, integrated, and analyzed through a machine learning (ML) model to demonstrate that the reduction in pain intensity is closely related to gene polymorphisms. Starting from the patient's data collected, the method supports the therapeutic process, avoiding ineffective results or the occurrence of side effects. Our findings suggest that ML prediction has the potential to positively influence clinical pharmacogenomics and facilitate the translation of a patient's genomic profile into useful therapeutic knowledge.

The Pharmacogenetics of Cannabis in the Treatment of Chronic Pain.

BACKGROUND: The increase in the medical use of cannabis has revealed a number of beneficial effects, a variety of adverse side effects and great inter-individual variability. Association studies connecting consumption, addiction and side effects related to recreational cannabis use have led to the identification of several polymorphic genes that may play a role in the pharmacodynamics and pharmacokinetics of cannabis. METHOD: In total, 600 patients treated with cannabis were genotyped for several candidate polymorphic genes (single-nucleotide polymorphism; SNP), encoding receptors CNR1 and TRPV1; for the ABCB1 transporter; for biotransformation, bioactivation and biosynthesis; and CYP3A4, COMT and UGT2B7 conjugation. RESULTS: Three polymorphic genes (ABCB1, TRPV1 and UGT2B7) were identified as being significantly associated with decline in pain after treatment with cannabis. Patients simultaneously carrying the most favourable allele combinations showed a greater reduction (polygenic effect) in pain compared to those with a less favourable combination. Considering genotype combinations, we could group patients into good responders, intermediate responders and poor or non-responders. Results suggest that genetic makeup is, at the moment, a significant predictive factor of the variability in response to cannabis. CONCLUSIONS: This study proves, for the first time, that certain polymorphic candidate genes may be associated with cannabis effects, both in terms of pain management and side effects, including therapy dropout. SIGNIFICANCE: Our attention to pharmacogenetics began in 2008, with the publication of a first study on the association between genetic polymorphisms and morphine action in pain relief. The study we are presenting is the first observational study conducted on a large number of patients involving several polymorphic candidate genes. The data obtained suggest that genetic makeup can be a predictive factor in the response to cannabis therapy and that more extensive and planned studies are needed for the opening of new scenarios for the personalization of cannabis therapy.

Promising Health Benefits of Adjuvant Acmella and Zingiber Extracts Combined with Coenzyme Q10 Phytosomes, Supplementation in Chronic Pain Treated with Medical Cannabis: A Prospective and Open-Label Clinical Study.

Background: Chronic pain is a condition where pain persists for months or even years. Nowadays, several drugs comprising of medical cannabis are utilized for chronic pain relief. Even if there are some associated side effects, the use of supplements can widen the reliable tools available for improving an individual's quality of life. Objective: The aim of the present study was to evaluate the efficacy in terms of pain intensity, psychological well-being, and quality of life of a new dietary supplement in chronic pain subjects under current treatment with medical cannabis. Methods: In this pilot study, 48 medical cannabis-treated subjects were supplemented with a dietary supplement containing a combination of standardized Zingiber officinalis and Acmella oleracea extracts in phytosome (Mitidol), coenzyme Q10 phytosome (Ubiqsome), and group B vitamins (B1, B6, and B12), twice daily for 90 days. In order to explore the benefits of the product as an adjuvant supplementation for pain relief, the pain intensity, measured by the visual analogue scale (VAS), the pain type, and quality, evaluated by the Italian Pain Questionnaire (QUID) and the possible reduction of therapeutic and/or painkiller doses were recorded. Results: After 90 days, significant pain relief was detected in almost 70% of the subjects receiving the new dietary supplement, with sensory, emotional, and pain amelioration in one-third of them. A reduction in both tetrahydrocannabinol (THC) and cannabidiol (CBD) doses was also observed after 3 months of supplementation. These findings demonstrate new perspectives for the use of an innovative dietary supplement that combines Acmella and Zingiber extracts, Coenzyme Q10, and group B vitamins resulting in a beneficial long-term adjuvant in cannabis-treated pain subjects.

Experimental investigation on the mechanical behavior of polyurethane PICCs after long-term conservation in in vivo-like conditions.

INTRODUCTION: In a previous paper, the authors investigated the mechanical behavior of several commercial polyurethane peripherally inserted central venous catheters (PICCs) in their 'brand new' condition. The present study represents a second step of the research activity and aims to investigate possible modifications of the PICC mechanical response, induced by long-term conservation in in vivo-like conditions, particularly when used to introduce oncologic drugs. METHODS: Eight 5 Fr single-lumen catheters from as many different vendors, were examined. Several specimens were cut from each of them and kept in a bath at 37°C for 1, 2, 3 and 6 months. Two fluids were used to simulate in vivo-like conditions, i.e. ethanol and Ringer-lactate solutions, the first being chosen in order to reproduce a typical chemical environment of oncologic drugs. The test plan included swelling analyses, uniaxial tensile tests and dynamic mechanical thermal analysis (DMTA). RESULTS AND CONCLUSIONS: All tested samples were chemically and mechanically stable in the studied conditions, as no significant weight variation was observed even after six months of immersion in ethanol solution. Uniaxial tensile tests confirmed such a response. For each PICC, very similar curves were obtained from samples tested after different immersion durations in the two fluid solutions, particularly for strains lower than 10%.

A comparative study on the mechanical behavior of polyurethane PICCs.

PURPOSE: This study describes a comparative analysis of eight commercial polyurethane, single-lumen peripherally inserted central venous catheters (PICCs) from different vendors. The aim was to investigate the mechanical response of the catheters providing objective and quantitative data to support a comparison among them. Such data could help nurses and physicians to select a central venous catheter (CVC) not only on the basis of the expected dwell duration or of the assessment of the vessels at the desired insertion site but also of the chemical and mechanical properties of the CVC and of the projected response of the body to these properties. METHODS: An experimental procedure was defined and tests were performed to assess some main characteristics of the PICC lines, including macro and microgeometric features, chemical and physical properties, and mechanical response. Preliminary measurements were performed to accurately define all geometric characteristics, including length, inner and outer diameters, and any inherent initial curvature of the catheter. Micro-geometric features were investigated using surface roughness analysis, optical microscopy, and scanning electron microscopy. Mechanical properties were studied by means of dynamic mechanical thermal analysis, simple uniaxial tensile tests, and kinking tests. RESULTS: Results are discussed in order to compare the different PICC lines. In particular, they show that polyurethane catheters can have a different mechanical behavior, which might play a role in the onset of pathologic processes and result in an increased risk and incidence of catheter-related complications. CONCLUSIONS: This study provides useful information that can help identifying and facilitate the choice of a PICC.