Authenticating medicines with dual laser handheld Raman spectroscopy

The World Health Organisation (WHO) defines counterfeit medicines as those that have been "deliberately and fraudulently mislabelled according to identity or source'"1. Such illegitimate drugs can have defects in their active pharmaceutical ingredients (APIs), excipients or coating, or their packaging might have been tampered with. The harm resulting from them is unpredictable and can range from treatment ineffectiveness to drug resistance and even death. Additionally, drug counterfeiting is not limited to a class or formulation type and can be encountered anywhere in the wholesale supply chain. In this respect, rapid and mobile techniques that can authenticate medicines where they are encountered are favourable

Evaluating handheld spectroscopic techniques for identifying counterfeit branded and generic medicines worldwide

Counterfeit medicines represent a global public health problem which accounts for 10% of the world market including 50% in some countries. Medicine counterfeiting can occur to any class of medicines, any type of formulation and can be encountered anywhere in the world. Consequently, rapid methods are needed to identify counterfeit medicines at their site of origin. Handheld spectroscopic techniques offer this advantage. This work features the use of nearinfrared (NIR) and Raman spectroscopic methods for identification of counterfeit medicines obtained worldwide. A total of 300 branded and generic medicines were measured using five spectroscopic instruments; being two NIR and three Raman (of different laser wavelength). Spectra obtained from these instruments were exported into a multiparadigm numerical computing environment where multivariate classification and regression algorithms were applied. The results showed that the selection of the technique depended on the type of medicine used. Thus, NIR was more successful in authenticating branded medicines where the physicochemical properties were of interest. On the other hand, Raman was ideal for authenticating generic medicines where the chemical signature of the API and/or excipient(s) were the subject of analyses. Furthermore, where adequate number of batches were available, the application of multivariate algorithms offered more accurate classification of the medicines. In summary, both techniques alongside multivariate algorithms proposed rapid methods for identifying counterfeit branded and generic medicines worldwide

Design of a Statistics Lecture for Multidisciplinary Postgraduate Students Using a Range of Tools and Techniques

Teaching statistics is a critical and challenging issue especially to students from multidisciplinary and diverse postgraduate backgrounds. Postgraduate research students require statistics not only for the design of experiments; but also for data analysis. Students often perceive statistics as a complex and technical subject; thus, they leave data analysis to the last moment. The lecture needs to be simple and inclusive at the same time to make it comprehendible and address the learning needs of each student. Therefore, the aim of this work was to design a simple and comprehendible statistics lecture to postgraduate research students regarding ‘Research plan, design and data collection’. The lecture adopted the constructive alignment learning theory which facilitated the learning environments for the students. The learning environment utilized a student-centered approach and used interactive learning environment with in-class discussion, handouts and electronic voting system handsets. For evaluation of the lecture, formative assessment was made with in-class discussions and poll questions which were introduced during and after the lecture. The whole approach showed to be effective in creating a learning environment to the students who were able to apply the concepts addressed to their individual research projects

From "Special K" to "Special M" : The Evolution of the Recreational use of Ketamine and Methoxetamine

Objective: To review the recreational use of ketamine (‘Special K’; KET) and explore the recent diffusion of its new derivative methoxetamine (‘Special M’; MXE). Methods: The literature search on the non-clinical/recreational use of KET and MXE was carried out in a range of medical databases. Considering the limitations of peer-reviewed information, data were integrated with a qualitative assessment of a range of websites, drug fora and other online resources including. Results: The recreational use of KET has started since its discovery in 1962. This was due to its rapid onset, short duration of action, and peculiar psychotropic effects (‘K-hole’). The latter effect ranges from confusion to dissociation and depersonalization (near-death experience). However, KET abuse is often associated with physical and psychological side effects of which the worst is urological/bladder toxicity. Recently, MXE has emerged as a legal and ‘bladder friendly’ KET alternative. MXE presents with the same dissociative effect of KET but with slower onset and longer duration of action. However, MXE seems to be associated with worse side effects than KET, ranging from mood disturbances/suicidal attempts to acute cerebellar toxicity. Conclusions: After 50 years of its discovery, KET has led to the emergence of MXE. However, this latter derivative does not appear to be a safer alternative to KET itself.Peer reviewe

The effects and toxicity of cathinones from the users' perspectives: A qualitative study.

OBJECTIVE: The objective of this study is to explore the users' perspectives regarding the effects and toxicity of cathinones. METHODS: A systematic search of Internet discussion forums yielded 303 threads relevant to the research objectives. The threads were analysed by conventional content analysis where concepts were developed from codes and themes. RESULTS: The study identified 3 main themes in relation to cathinone use, effects, and toxicity. The first theme considered the modalities of intake of cathinones in relation to the derivative taken (mainly mephedrone, 3-methylmethcathinone, and methylenedioxypyrovalerone), route of administration (eyeballing, insufflation, smoking, intravenous, oral, rectal, and sublingual), multidrug use, and purity of the cathinone derivative. The second theme characterised the main effects of cathinones, that is, increased energy, euphoria, and empathogenic. Toxic effects were reported regarding the nervous system (anxiety, hallucinations, nervousness, and paranoia), cardiovascular system (angina, myocardial infarction, and tachycardia), skin (discolouration, itching, and allergy), and renal system (difficulty in urination). Drug-drug interactions were also reported including multiple drug use between cathinones, stimulants, depressants, and hallucinogens. CONCLUSIONS: The Internet discussion forums provide useful sources of information regarding the effects and toxicity of cathinones, which can be taken into account when assessing the safety of drugs

Evaluation of portable near-infrared spectroscopy for authentication of mRNA based COVID-19 vaccines

Since its identification in 2019, Covid-19 has spread to become a global pandemic. Until now, vaccination in its different forms proves to be the most effective measure to control the outbreak and lower the burden of the disease on healthcare systems. This arena has become a prime target to criminal networks that spread counterfeit Covid-19 vaccines across the supply chain mainly for profit. Counterfeit vaccines provide false sense of security to individuals, heightens the risk of exposure and outbreak of the virus, and increase the risk of harm linked to Covid-19 infection. Moreover, the increase in counterfeit vaccines feeds hesitancy towards vaccination and erodes the trust in mass immunisation programmes. It is therefore of paramount importance to work on rapid and reliable methods for vaccine authentication. Subsequently this work utilised a portable and non-destructive near infrared (NIR) spectroscopic method for authentication of Covid-19 vaccines. A total of 405 Covid-19 vaccines samples, alongside their main constituents, were measured as received through glass vials. Spectral quality and bands were inspected by considering the raw spectra of the vaccines. Authentication was explored by applying principal component analysis (PCA) to the multiplicative scatter correction-first derivative spectra. The results showed that NIR spectra of the vaccine featured mainly bands corresponding to the mRNA active ingredient. Fewer bands corresponded to the excipients and protein spectra. The vaccines NIR spectra were strongly absorbing with maximum absorbances up to 2.7 absorbance units and that differentiated them from samples containing normal saline only (constituent reported for counterfeit Covid-19 vaccines). Clustering based on PCA offered optimal authentication of Covid-19 vaccines when applied over the range of 9000-4000 cm-1These findings shed light on the potential of using NIR for analysing Covid-19 vaccines and presents a rapid and effective initial technique for Covid-19 vaccine authentication

Evaluation of portable near-infrared spectroscopy for authentication of mRNA based COVID-19 vaccines

Since its identification in 2019, Covid-19 has spread to become a global pandemic. Until now, vaccination in its different forms proves to be the most effective measure to control the outbreak and lower the burden of the disease on healthcare systems. This arena has become a prime target to criminal networks that spread counterfeit Covid-19 vaccines across the supply chain mainly for profit. Counterfeit vaccines provide false sense of security to individuals, heightens the risk of exposure and outbreak of the virus, and increase the risk of harm linked to Covid-19 infection. Moreover, the increase in counterfeit vaccines feeds hesitancy towards vaccination and erodes the trust in mass immunisation programmes. It is therefore of paramount importance to work on rapid and reliable methods for vaccine authentication. Subsequently this work utilised a portable and non-destructive near infrared (NIR) spectroscopic method for authentication of Covid-19 vaccines. A total of 405 Covid-19 vaccines samples, alongside their main constituents, were measured as received through glass vials. Spectral quality and bands were inspected by considering the raw spectra of the vaccines. Authentication was explored by applying principal component analysis (PCA) to the multiplicative scatter correction-first derivative spectra. The results showed that NIR spectra of the vaccine featured mainly bands corresponding to the mRNA active ingredient. Fewer bands corresponded to the excipients and protein spectra. The vaccines NIR spectra were strongly absorbing with maximum absorbances up to 2.7 absorbance units and that differentiated them from samples containing normal saline only (constituent reported for counterfeit Covid-19 vaccines). Clustering based on PCA offered optimal authentication of Covid-19 vaccines when applied over the range of 9000–4000 cm-1These findings shed light on the potential of using NIR for analysing Covid-19 vaccines and presents a rapid and effective initial technique for Covid-19 vaccine authentication

Gender Bias in Diagnosis, Prevention, and Treatment of Cardiovascular Diseases:A Systematic Review

Cardiovascular disease (CVDs) has been perceived as a ‘man’s disease’, and this impacted women’s referral to CVD diagnosis and treatment. This study systematically reviewed the evidence regarding gender bias in the diagnosis, prevention, and treatment of CVDs. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. We searched CINAHL, PubMed, Medline, Web of Science, British Nursing Index, Scopus, and Google Scholar. The included studies were assessed for quality using risk bias tools. Data extracted from the included studies were exported into Statistical Product and Service Solutions (SPSS, v26; IBM SPSS Statistics for Windows, Armonk, NY), where descriptive statistics were applied. A total of 19 studies were analysed. CVDs were less reported among women who either showed milder symptoms than men or had their symptoms misdiagnosed as gastrointestinal or anxiety-related symptoms. Hence, women had their risk factors under-considered by physicians (especially by male physicians). Subsequently, women were offered fewer diagnostic tests, such as coronary angiography, ergometry, electrocardiogram (ECG), and cardiac enzymes, and were referred to less to cardiologists and/or hospitalisation. Furthermore, if hospitalised, women were less likely to receive a coronary intervention. Similarly, women were prescribed cardiovascular medicines than men, with the exception of antihypertensive and anti-anginal medicines. When it comes to the perception of CVD, women considered themselves at lower risk of CVDs than men. This systematic review showed that women were offered fewer diagnostic tests for CVDs and medicines than men and that in turn influenced their disease outcomes. This could be attributed to the inadequate knowledge regarding the differences in manifestations among both genders

Authentication of Antibiotics Using Portable Near-Infrared Spectroscopy and Multivariate Data Analysis

Counterfeit medicines represent a global public health threat warranting the development of accurate, rapid, and nondestructive methods for their identification. Portable near-infrared (NIR) spectroscopy offers this advantage. This work sheds light on the potential of combining NIR spectroscopy with principal component analysis (PCA) and soft independent modelling of class analogy (SIMCA) for authenticating branded and generic antibiotics. A total of 23 antibiotics were measured “nondestructively” using a portable NIR spectrometer. The antibiotics corresponded to six different active pharmaceutical ingredients being: amoxicillin trihydrate and clavulanic acid, azithromycin dihydrate, ciprofloxacin hydrochloride, doxycycline hydrochloride, and ofloxacin. NIR spectra were exported into Matlab R2018b where data analysis was applied. The results showed that the NIR spectra of the medicines showed characteristic features that corresponded to the main excipient(s). When combined with PCA, NIR spectroscopy could distinguish between branded and generic medicines and could classify medicines according to their manufacturing sources. The PCA scores showed the distinct clusters corresponding to each group of antibiotics, whereas the loadings indicated which spectral features were significant. SIMCA provided more accurate classification over PCA for all antibiotics except ciprofloxacin which products shared many overlapping excipients. In summary, the findings of the study demonstrated the feasibility of portable NIR as an initial method for screening antibiotics