This thesis applied a novel interdisciplinary approach for pharmacovigilance to examine the use of complementary and integrative medicine (CIM), focusing on herbal remedies, to manage pediatric attention-deficit hyperactivity disorder (ADHD). The safety and potential risk of herb-drug interactions in ADHD management were first evaluated through an assessment of available information on the safety and efficacy of natural health products (NHPs) commonly used by ADHD patients as a means of identifying knowledge gaps. A clinical questionnaire was administered to caregivers of pediatric patients with ADHD to determine the factors and related outcomes of CIM use, including adverse events. A systematic search was conducted to further identify clinical adverse events involving herbal remedies and ADHD drugs to determine causal links to herb-drug interactions. In vitro analysis of identified herbal remedies was conducted to determine their potential for pharmacokinetic interactions, specifically on carboxylesterase-1 (CES1) mediated metabolism. The presented research builds on otherwise scarce evidence of the safety of herbal remedies for ADHD, particularly with respect to herb-drug interactions and adverse events (AEs) associated with concurrent use of NHPs and ADHD prescription drugs. Beyond studies conducted on the pharmacokinetic safety of herbal remedies through the cytochrome P450 pathways that metabolize some ADHD drugs, including amphetamine, atomoxetine and guanfacine, few data were available for CES1, which metabolizes methylphenidate, the first line of drug used to manage ADHD. The clinical questionnaire revealed that 40% of patients had used CIM and confirmed the use of a variety of CIM. Moreover, the majority of CIM users were also concurrently taking ADHD medication, and eight mild adverse events were self-reported. The systematic search on the adverse event reporting system highlighted a potential NHP-drug interaction between methylphenidate and St. John’s wort, and the overall poor quality of NHP-related adverse event reports. As a follow-up from the adverse event results, various commercial St. John’s wort products showed variable inhibition of recombinant human CES1 in vitro. Although the concentration of marker phytochemicals was not correlated to inhibition, hyperforin showed stronger activity than hypericin and quercetin. The preliminary in vitro investigation revealed that the herbal remedies used by ADHD patients have the potential to interact with CES1 mediated metabolism, with Rhodiola rosea identified as the most potent inhibitor. Further investigation on various commercial products of Rhodiola rosea revealed both reversible and irreversible inhibition of recombinant CES1. However, the inhibition was not dependent on the concentration of marker phytochemicals, and rosarin, rosavin, rosin, and salidroside were not potent inhibitors of recombinant CES1. Moreover, a commercial Rhodiola rosea extract showed concentration-dependent inhibition of human liver microsome meditated metabolism of methylphenidate. Overall, results from this thesis suggest potential risk from use of NHPs concurrently with conventional medicine used to manage ADHD. Improved evidence and pharmacovigilance for the use of NHPs in a pediatric population is warranted.

The Sanitary Dignity Framework (2019) is a policy that aims to preserve and maintain indigent girls' and women's dignity during menstruation. In South Africa, the term “sanitary dignity”, can be equated to what the rest of the world recognizes as menstrual hygiene management (MHM). Sanitary dignity or MHM is centred around the provision of menstrual health hygiene products (MHPs) such as tampons and sanitary pads to anyone who menstruates and cannot afford to purchase MHPs for themselves. Limited of access to MHPs, water and sanitation facilities, and privacy make it impossible for vulnerable menstruators to achieve sanitary dignity. This policy excludes street-based homeless menstruators as it only makes provisions for those who have access to state-funded institutions such as; quintile 1, 2, and 3 schools, mental institutions, hostels, places of care, and prisons. Street-based homeless menstruators are marginalized twofold; they reside on the streets and they menstruate. This dissertation discusses how the social exclusion of street-based homeless menstruators within the Sanitary Dignity Framework strips them of their fundamental right to dignity by denying them access to the sanitary dignity they are entitled to.

The thesis is comprised of three separate studies that each relate to one of the aforementioned therapy types: complementary, alternative, and integrative medicine (CAIM), natural health products (NHPs), and medical cannabis. Parallels can be drawn across these therapy types in general including patient preference and prevalence of use, quality of patient health information, and safety and effectiveness concerns. Knowledge of these parallels both informed the development of these three studies and emerged across findings. Chapter 1 provides a comprehensive introduction to these parallels in the context of CAIM, NHPs, and medical cannabis. Chapter 2 comprises a cross-sectional survey determining NHP use disclosure to primary care physicians among patients attending a Canadian naturopathic clinic. Chapter 3 comprises a qualitative interview study identifying attitudes towards medical cannabis among family physicians practicing in Ontario, Canada. Chapter 4 comprises a sentiment analysis of Twitter data to understand how CAIM is mentioned during the COVID-19 pandemic. Lastly, chapter 5 serves as the conclusion of this thesis, and summarizes the most important findings, addresses study strengths and limitations, and discusses future directions from this work. / Thesis / Doctor of Philosophy (PhD)

L'arthrose (OA) est l’atteinte la plus répandue chez les animaux de compagnie et se manifeste par l'apparition de douleurs chroniques et d'incapacités fonctionnelles. En l’absence de remède, des composés comme les produits de santé naturels (PSN) ont gagné en popularité. Cette revue systématique, enregistrée sur PROSPERO (CRD42021279368), avait pour objectif d'examiner les preuves d’efficacité analgésique des PSN et de diffuser correctement les conclusions sur leur potentiel thérapeutique. Quatre bases de données bibliographiques ont été consultées pour identifier les études testant leur efficacité sur l'OA canine et féline, naturelle ou induite. Après sélection des résultats de recherche, les données de qualité et d’efficacité ont été extraites à l’aide d’une grille d’évaluation originale basée sur les directives ARRIVE, CONSORT et l’outil d’évaluation CAMARADES. Ces grilles ont été préalablement validées : validation apparente, de contenu (interne / externe) et de construit (reproductibilité, répétabilité, sensibilité). Un consensus de 3 évaluateurs, de niveau d’expertise différent, était obligatoire pour chaque score attribué aux données extraites. La méta-analyse montre des preuves solides d’efficacité des suppléments et des diètes thérapeutiques enrichies d’acides gras en oméga-3 dans le traitement de l’OA, et le cannabidiol présente des preuves prometteuses. Les formulations de sulfate de glucosamine/chondroïtine ne présentent toutefois aucun intérêt et ne doivent plus être recommandées dans la prise en charge thérapeutique de cette maladie articulaire dégénérative des animaux de compagnie. Les résultats obtenus soulignent un manque évident de preuves pour supporter la recommandation d’utilisation de nombreux nutraceutiques et dénotent la nécessité de mettre en place des procédures normalisées de bonne pratique clinique pour de futurs essais. / Osteoarthritis (OA) is the most common disease in pets and manifests itself as chronic pain and functional disability. In the absence of a cure, compounds such as natural health products (NHPs) have gained popularity. This systematic review, registered on PROSPERO (CRD42021279368), aimed to examine the evidence for analgesic efficacy of NHPs and to properly disseminate findings on their therapeutic potential. Four bibliographic databases were searched to identify studies testing their efficacy in natural and induced canine and feline osteoarthritis. After selection of the search results, quality and efficacy data were extracted using an original evaluation grid based on the ARRIVE and CONSORT guidelines and the CAMARADES evaluation tool. The grids were previously validated: face, content (internal/external) and construct (reproducibility, repeatability, sensitivity) validation. A consensus of three evaluators, with different levels of expertise, was required for each score assigned to the extracted data. The meta-analysis shows strong evidence of efficacy in OA for omega-3 enriched supplements and therapeutic diets, while cannabidiol shows promising evidence. Glucosamine/chondroitin sulphate formulations are of no value and should no longer be recommended for the therapeutic management of OA in pets. The results highlight a clear lack of evidence to support the recommendation for use of many nutraceuticals and indicate the need for standardised good clinical practice procedures for future trials.

Marketing aimed towards children under the age of 12 is prohibited in Sweden. Packaging design has a crucial role from a marketing perspective as it might be the only way to reach this target group. The purpose of this study is to analyze how graphic design and visual communication differs when it is aimed to children and adults. This essay also examines how media characters are used in marketing of health products targeted towards children and adults to create synergies. The use of media characters in packaging design results in two different types of synergies. The first type is the synergy between two brands when the collaboration benefits them by mutually increasing their legitimacy. The other type of synergy occurs when marketing of a product is designed to simultaneously reach two different target groups: children and adults.

Contexte. Les produits de santé naturels (PSN) suscitent de plus en plus d’intérêt au sein de la population. Les professionnels de la santé, dont les nutritionnistes, doivent être à l’affût de cette tendance afin de conseiller les utilisateurs et de limiter les risques liés à leur utilisation. Objectif. Explorer l’expérience, les perceptions et les besoins de formation des nutritionnistes du Québec à l’égard des PSN. Méthodes. Un sondage électronique a été envoyé à tous les membres de l’Ordre professionnel des diététistes du Québec via Fluid Survey. Les questions visaient à identifier les expériences, les attitudes à l’égard des PSN et de leur clientèle qui en consomme, les sources d’informations utilisées dans leurs consultations et d’identifier les besoins de formations en relation avec les PSN. Résultats. Au total, 295 nutritionnistes ont complété le questionnaire. Parmi ceux-ci, 93 % ont déjà reçu des questions portant sur les PSN. Environ 91 % ont déclaré consommer ou avoir déjà consommé un PSN et, au moins 94 % ont affirmé avoir recommandé un PSN. Aussi, 95 % de l’échantillon désiraient davantage d’informations sur les PSN. Enfin, ils ont une perception positive quant à leur rôle dans ce dossier, puisque 77 % de l’échantillon ont indiqué que le nutritionniste devrait être une source d’informations sur les PSN. Conclusion. Les grands constats de notre étude révèlent que le rôle des nutritionnistes du Québec en relation avec les PSN n’est pas clairement défini. Ils ont besoin de formation sur les PSN afin d’être outillés pour conseiller la population et, ainsi, leur ouvrir un nouveau champ d’expertise. / Background. Natural Health Products (NHPs) are becoming an increasing interest within the population. Health professionals, including nutritionists, must keep up to date with this trend in order to properly advise users and limit the risks associated with their use. Objective. Explore Quebec’s nutritionist’s experiences, perceptions and their training needs about NHPs. Methods. An electronic survey was administered to members of the Professional Order of Dietitians of Quebec through Fluid Survey. The 21 questions were designed to identify personal experiences, attitudes towards NHPs and towards their clientele that consume them, identify which sources of information they rely on and their training needs. Results. A total of 295 nutritionists completed the questionnaire. Among these, 93 % have already received questions on NHPs. Approximately 91 % of nutritionists admitted using or having used NHPs and at least 94 % said they recommended them. Also, 95 % of the sample would like to receive more information on NHPs. Finally, they have a positive perception as to their role regarding this subject, since 77 % indicated that the nutritionist should be a reliable source of information for NHPs. Conclusion. The major findings of our study are that Quebec’s nutritionists’ roles related to NHPs are not clearly defined. They need training on NHPs in order to be able to advise the population and, thus, form a new field of expertise for nutritionists.

Le médicament est un produit de consommation particulier ayant une multiple vocation.Biens spécifiques porteurs de risques par essence, sa répartition ne peut être laissée au seul jeudu marché. Ils doivent être évalués aussi bien à priori qu’à postéri et durant toute leur viecommerciale. Produit actif nécessaire à la santé, ils comportent de nombreux risques. Latotalité du cycle (production, dispensation, récupération) de tout produit de santé doit être trèsétroitement encadrée et confiée à la responsabilité de professionnels. Leur prise en chargerequiert donc l’attention de toute la collectivité, et doit faire l’objet d’une réglementationrigoureuse en raison des problèmes de santé publique résultant d’une mauvaise utilisation.Ces particularités du médicament entraînent un certain nombre de codification. Descontraintes réglementaires régissent la mise sur le marché et l’utilisation de ces biens, afind’assurer leur qualité, leur efficacité et leur innocuité. Les événements indésirables graves nesont pas toujours bien encadrés dans les pays, milieux médical et hospitalier africain. Et encas de dommages à la santé résultant d’une mauvaise utilisation, il importe de s’interroger surles droits et les responsabilités des différents acteurs (professionnels de santé, patient, Etat).On ne peut espérer prévenir les erreurs médicamenteuses si on n’implante pas dans les espritsla culture du risque et de la responsabilité, préalable indispensable à la réorganisation ducircuit des produits de santé. / Drugs are a particular consumer product having a multiple purposes. Specific goods carryrisks in themselves, and shouldn’t be distributed solely to the mainstream market. Rather, theymust be evaluated before, during and after their commercial life. Active products arenecessary for healthcare, but contain numerous risks. The entire cycle (production, delivery,recovery) of all health products must be very strictly supervised and entrusted to aprofessional’s responsibility. Their supervision therefore requires the attention of the wholehealth care community, and must be strictly regulated because health problems can resultfrom misuse. These features of the drug involve a certain codification system. Regulatoryrequirements govern the place on the market and use of these assets to ensure their quality,effectiveness and safety. Medical malpractice is not always well supervised in the medicaland hospital atmosphere of Africa. And in case of damage to health resulting from misuse, itis important to consider the rights and responsibilities of the various people involved(healthcare professionals, patients, government). Medical errors cannot be prevented if theculture of risk and responsibility is not instilled in the minds of the public. This is aprerequisite for the reorganisation of the distribution of health products.

In the light of the current patient-centred approach to healthcare delivery, this research investigated the effectiveness and safety of paediatric complementary and alternative medicines (CAMs) from the users' perspective in order to generate suitable data to inform healthcare policy and planning. The research was in three parts: a systematic review (SR), a database analysis and a survey. The SR of papers published on the topic from 2000 to July 2011 identified 46 eligible studies conducted predominantly in the USA (14; 30%); with only 5 UK studies (11%), of which 2 were Scottish. Generally, their findings indicated a high report of positive health outcomes by CAM users, and a low report of adverse outcomes. Critical appraisal, however, highlighted the low methodological quality of most studies; with an overall quality rating of 45%, and only 9 studies (20%) possessing up to 8 of 12 quality indices. A tendency towards selective outcome reporting bias was also observed. The database research explored the suspected adverse reactions (ADRs) associated with paediatric use of natural health products (NHPs) as reported on the Yellow Card Scheme (YCS) from its inception until July 2012. The YCS data was mined to estimate the frequency and seriousness of the ADRs reported. NHPs were found to have contributed < 1% of ADR reports within the period, with paediatric subjects contributing 8.6% of NHP reports (192 reports). These profiled 332 specific ADRs, 30% of which were described as serious. Female subjects contributed marginally more ADRs than males (51.5%). Rash and other skin and subcutaneous disorders were the most common ADRs. Herb-drug combination products were found to generate the most ADRs, with the senna-piperazine combination being the most frequently reported (89 ADRs). The product most associated with fatalities was soybean oil (5 reports). Generally, however, NHP-related ADRs reported for paediatric subjects in the YCS were found to be relatively few, and of low severity (6%) and fatality (2%); with over 75% resolution, and mostly within 3 days (68%). The survey component of the research was a bi-modal analytic cross-sectional survey of parents in Aberdeen, and aimed to determine the nature and demography of the use and user-reported outcomes of CAM among children in Aberdeen. Consenting parents recruited from the general population were invited to complete online or paper versions of a validated questionnaire. 212 parents of 391 children completed the survey, of which 143 reported CAM use in their children (67.5%). Participants were mainly mothers (73.6%); Caucasian (84.4%); aged 30-44 years (59.7%); and educated beyond secondary level (85.3%). 213 children had ever used CAM, 64.3% of which had always used CAM; while 21.1% had only used CAM within the last 12 months, and 14.6% had used it only previously. 53.1% of child CAM users were female. Parental self CAM use was found to be the strongest predictor of paediatric CAM use. 102 of the 123 parents that rated their children's CAM use (82.9%) perceived them as helpful; 76 of which said they helped 'a lot'. Finding personal CAM use helpful was the only factor found to significantly predict perceived effectiveness for paediatric CAM use. 9 parents reported adverse outcomes, mainly allergic skin reactions. In all, this research featured the first SR of user-perceived effectiveness and safety outcomes of paediatric CAMs; the first analysis of NHP-associated ADR reports on the YCS; and the first population-based Scottish study of paediatric CAM use. A triangulation of the results from these three strands validated the key finding that CAM is used widely among children, with high perceived effectiveness and safety outcomes. The implications of this finding for healthcare policy and planning were highlighted.

Seventeen Cree anti-diabetic herbal medicines and eight Traditional Chinese Medicines have been examined for their potential to cause interactions with drugs, which is considered as a major reason for adverse drug effects. Specifically, the effect of these natural health products was examined on major Phase I drug metabolism enzymes including cytochrome P450, human carboxylesterase-1 and flavin-containing monooxygenases. Several of these natural health products have the potential to cause adverse drug effect through the inhibition of major drug metabolism enzymes. The results indicated that 7 Cree medicines plant extracts inhibited CYP3A4 activity, and 3 of them have been proven to cause potent mechanism-based inactivation of CYP3A4. Seven of eight Traditional Chinese Medicines have been identified as strong CYP3A4 inhibitors; the ethanol extract of Goji has identified as a potent inhibitor for CYP2C9 and 2C19. Goji juice showed universal inhibitory effects on most of the tested enzymes except flavin-containing monooxygenases 3.

Seventeen Cree anti-diabetic herbal medicines and eight Traditional Chinese Medicines have been examined for their potential to cause interactions with drugs, which is considered as a major reason for adverse drug effects. Specifically, the effect of these natural health products was examined on major Phase I drug metabolism enzymes including cytochrome P450, human carboxylesterase-1 and flavin-containing monooxygenases. Several of these natural health products have the potential to cause adverse drug effect through the inhibition of major drug metabolism enzymes. The results indicated that 7 Cree medicines plant extracts inhibited CYP3A4 activity, and 3 of them have been proven to cause potent mechanism-based inactivation of CYP3A4. Seven of eight Traditional Chinese Medicines have been identified as strong CYP3A4 inhibitors; the ethanol extract of Goji has identified as a potent inhibitor for CYP2C9 and 2C19. Goji juice showed universal inhibitory effects on most of the tested enzymes except flavin-containing monooxygenases 3.