Depot medroxyprogesterone acetate (DMPA) is a long acting progesterone only contraceptive agent. Side effects such as irregular bleeding patterns and weight gain are attributed to discontinuation. The purpose of this study was to describe depot medroxyprogesterone acetate discontinuation after weight gain in 17 to 19 year-old adolescent girls.

Les dérivés de platine (cisplatine, oxaliplatine et carboplatine) et les taxanes (paclitaxel et docétaxel) font partie des grandes familles d’agents anticancéreux couramment utilisés en chimiothérapie. Ils permettent de traiter les tumeurs solides telles que les cancers de l’ovaire, du poumon, de la prostate, du sein, tête et cou. Cependant, ils sont à l’origine d’importantes neuropathies périphériques qui peuvent devenir irréversibles et laisser les patients avec des séquelles importantes. Il s'agit de vertiges, acouphènes, engourdissements, pertes de sensibilité, allodynies au toucher ou aux variations de température. Ces effets secondaires sont fortement contraignants et réduisent considérablement la qualité de vie de 30 à 50% des patients. L'importance clinique est considérable, puisque cela conduit environ 1/3 des patients atteints à l’arrêt et/ou au changement des traitements, bien que ceux-ci soient efficaces sur les tumeurs.Les dérivés de platine sont des agents pontants : leurs interactions avec les bases purines de l’ADN forment des adduits, qui vont être reconnus par des protéines de dommage à l’ADN, conduisant à la mort cellulaire. Les taxanes bloquent la dépolymérisation des microtubules, ce qui induit la mort des cellules en divisions. Le fait que deux mécanismes d’action antitumorale très différents provoquent, à court ou à moyen terme, les mêmes neuropathies périphériques, est paradoxal et n’a pas d’explication.Le but de mon projet de thèse était d’étudier le ou les mécanismes à l’origine de ces neuropathies et de développer une formulation visant à les réduire. Pour cela, j’ai étudié les effets des taxanes et dérivés de platine sur les canaux ioniques, impliqués dans la nociception. Ces canaux ioniques, appelés nocicepteurs, sont transcrits dans les corps cellulaires des ganglions spinaux (DRG), avant d’être principalement adressés à l’extrémité des nerfs périphériques. Ils détectent les stimuli mécaniques, thermiques et chimiques et génèrent ou transmettent les potentiels d’action correspondants. Le fait de perturber l’expression génique et/ou l’activité de ces nocicepteurs, aura donc pour conséquence de modifier les seuils de sensibilité et la transmission de différents stimuli.Mes résultats ont permis de quantifier dans des cultures primaires de DRG et in vivo chez la souris, le remodelage génique de nocicepteurs induit par les traitements de chimiothérapie, en corrélation avec l’apparition de neuropathies périphériques que j'ai mesurées par des tests comportementaux. Cela nous a permis d'identifier une famille de molécules candidates, qui pourraient potentiellement contrer le mécanisme identifié dans ces travaux. L'une de ces molécules permet de rétablir l’expression génique de nocicepteurs et aussi de supprimer les neuropathies périphériques chez la souris. Ce travail devrait se poursuivre dans le cadre d'un processus de valorisation, ayant pour objectif d'aboutir à un traitement préventif et/ou curatif, de ces neuropathies chez les patients. / Platinum-based drugs (cisplatin, oxaliplatin and carboplatin) and taxanes (paclitaxel and docetaxel) are among the most common drugs families used in chemotherapy. They are used for treatment of numerous human cancers including bladder, breast, head and neck, lung, ovarian, prostate and testicular cancers. However, these anticancer drugs cause significant peripheral neuropathies, that can become irreversible and leave serious clinical sequelae in patients. These include tinnitus, dizziness, tingling, numbness, loss of sensitivity, allodynia to touch or temperature changes and hyperalgesia. These side effects are highly restrictive and significantly reduce the quality of life of 30-50% of patients. The clinical significance is considerable, since it leads to about one-third of patients with stopping and/or changing treatments, although these are effective on tumors.Platinum-based drugs are DNA binding agents: they generate DNA lesions on the purine bases of DNA, that will be recognized by DNA damage response proteins, leading to cell death. Taxanes block the cell cycle in mitosis, by stabilizing the microtubule cytoskeleton against depolymerization. The fact that these two completely different antitumor mechanisms of action, induce the same peripheral neuropathies in the short to medium term, is paradoxical and has no explanation.The aim of my PhD research project was to study the mechanism(s) behind these neuropathies and to develop a new formulation to prevent and/or reduce them. Therefore, I studied the effects of taxanes and platinum-based drugs on several ion channels, involved in nociception. These ion channels, called nociceptors, are transcribed into the cell bodies of dorsal root ganglia (DRGs) and located to the peripheral nerve endings. They detect mechanical, thermal and chemical stimuli and generate or transmit the corresponding action potentials. Changes in gene expression and/or activity of nociceptors, will therefore modify the nociceptive thresholds and the transmission of different stimuli.My results allowed me to quantify, in primary cell culture of mouse DRGs and in vivo, the remodeling of ion channel expression induced by chemotherapy, in correlation with the development of peripheral neuropathies, that I measured by behavioral assessment. These results allowed us to identify a family of candidate molecules, that could potentially counteract the mechanism identified in this work. I showed that one of these molecules, can restore the gene expression of nociceptors and suppress peripheral neuropathies in mice. This work should continue as part of a valorization process, aiming to lead to a preventive and/or curative treatment, of these neuropathies in patients.

Many people - especially during their elderly - consume multiple drugs for the treatment of complex or co-existing diseases. Identifying side effects caused by polypharmacy is crucial for reducing mortality and morbidity of the patients which will lead to improvement in their quality of life. Since there is immense space for possible drug combinations, it is infeasible to examine them entirely in the lab. In silico models can offer a convenient solution, however, due to the lack of a sufficient amount of homogenous data it is difficult to develop both reliable and scalable models in its ability to accurately predict Polypharmacy Side Effect. Recent advancement in the field of representational learning has utilized the power of graph networks to harmonize information from the heterogeneous biological databases and interactomes. This thesis takes advantage of those techniques and incorporates them with the state-of-the-art Graph Neural Network algorithms to implement a Deep learning pipeline capable of predicting the Adverse Drug Reaction of any given paired drug combinations.

Thesis (MPH.) -- University of Limpopo, 2019 / Virological failure occurs when the viral load fails to supress to undetectable limit and immunological failure is when the immune system fails to improve with the CD4 count remaining low on clients on antiretroviral drugs. These being markers of poor adherence to antiretroviral drugs or treatment failure. Upon routine blood-monitoring of students on antiretroviral drugs, the researcher noticed that some students’ viralload levels were not suppressing and their immune system was not improving. The purpose of the study was to identify the experiences of those students whose viral load is not suppressing and their immune system not improving. The objective was to identify and describe the experiences of students with immunological and virological failure on antiretroviral drugs at the University of Limpopo. A qualitative, explorative and descriptive study design was used. Convenience purposive sampling method was adopted. Using a semi-structured interview guide, face-toface interviews were conducted on 10 students on antiretroviral drugs at the Student Health and Wellness Centre, University of Limpopo. Techs’ method was used to analyse data. Guba’s model for establishing trustworthiness was used. The study yielded the following themes: Disclosure, stigma, antiretroviral drugs packaging, side effects of antiretroviral drugs and service delivery. The study concluded that students are afraid to take their treatment for fear of stigmatisation and disclosure is still a problem. Students tend to forfeit taking drugs when studying for examinations due to side effects of the drugs. It is recommended that service delivery and antiretroviral drugs packaging be user friendly. Key words: Disclosure, stigma, side effects, antiretroviral drugs packaging and antiretroviral drugs.

Children who have received radiation therapy for the treatment of brain tumors have been shown to experience neurocognitive deficits which appear to increase over time. The purpose of this study was to examine the memory functioning of 22 children irradiated for brain tumor and 22 healthy children of the same age who had not received irradiation. Subjects were administered a brief form of the WISC-III, to obtain an IQ, and the Wide Range Assessment of Memory and Learning (WRAML), to evaluate visual and verbal memory. Results indicated that, although there were no significant differences between the IQ scores of healthy children and children who had been irradiated, children who have received radiation therapy for brain tumor evidence memory deficits which effect visual and verbal memory abilities. Among the children who had been irradiated, as time since treatment increased, visual memory and overall memory functioning appeared to decline. Findings also suggested that children who received total tumor resection may evidence greater memory deficits than those who received only a partial resection. Visual memory was more closely related to IQ in the children irradiated for brain tumor than in the healthy children. The overall importance of research with this population lies in refining the understanding of memory deficits and strengths in order to formulate more effective remediation compensation, strategies.

Tardive dyskinesia is an insidious and debilitating extrapyramidal side effect of neuroleptic drug treatment. Recent research has suggested that lecithin has been effective in treating tardive dyskinesia. Lecithin's effects were evaluated under double-blind placebo controlled conditions. Treatment conditions included a placebo control group, a lecithin treatment group, and a no-treatment control group. Subjects in the lecithin group received 60 gms/day of lecithin (33 gms of phosphatidylcholine) . Subjects in the placebo group received a similar mixture which contained no lecithin. Subjects received mixtures for 9-11 days. Treatment effectiveness was determined by subjective, objective, and global evaluations. All subjects were evaluated 3 to 4 days prior to treatment and following 9 to 11 days of treatment.

NSAIDs depress prostaglandins synthesis through inhibition of COX-1 that is involved in maintaining cell integrity and COX-2 that, although presents particularly in the kidneys, is overexpressed in response to inflammation. Both the beneficial and side effects of NSAIDs are, therefore, through their inhibition of COX enzymes. Introduction of COX-2-selective inhibitors has improved the safety profile of the drugs with regard to their most common side effect which occurs at the gastrointestinal level but has not rendered them less cardio-nephrotoxic. Renal side effects of NSAIDs are rare, sometimes transient and often reversible upon drug withdrawal. The incident rate and the severity of the renal side effect, however, increase in patients with risk factors such as those with diabetes, heart failure, renal dysfunction and in the elderly. The side effects range from electrolyte retention and reduce glomerular filtration to nephritic syndrome and chronic renal failure. These effects are shared among NSAIDs with evidence of dose and exposure dependency. There is no known predictor for the nephrotoxicity. However, a relationship has been found between high plasma concentration and the renal adverse effect of NSAIDs. The usefulness of therapeutic drug monitoring in patients with risk factors needs to be explored.

Indiana University-Purdue University Indianapolis (IUPUI) / Oral endocrine therapy (OET) is standard therapy for millions of estrogen receptor-positive breast cancer survivors (ER+BCS). OET reduces recurrence, mortality, and metastasis. ER+BCS often do not take their OET as recommended due to adverse side effects. The purpose of this dissertation was to develop an explanatory framework of decision making by women with ER+ breast cancer who report experiencing side effects from OET. This project was comprised of two components. The first component was a systematic review with three main findings: (1) side effects negatively impact OET non-adherence, (2) there is an absence of decisional supports provided to or available for ER+BCS who are experiencing OET side effects,, and (3) ER+BCS likely have unmet decisional needs related to OET. The second component was a grounded theory study that included 31 ER+BCS reporting OET side effects. During a single semi-structured interview, participants described the experience of OET over time. This study produced two qualitatively derived projects. First, a theoretical framework was developed that depicted four stages through which the experience of OET decision making unfolded. The stages were (1) being told what I need to do to live, (2) doing what I need to do to live, (3) enduring what I need to do to live, and (4) deciding how I want to live. Second, a typology was developed that depicted six sources of external decisional supports (healthcare providers, husbands, other breast cancer survivors, friends and family, the internet and other media sources, and God) that met four types of decisional needs (information about OET and its side effects, in-depth discussions about side effects, help in managing side effects, and emotional support). Findings can be used to develop interventions, such as decision aids, to promote quality decision making in women experiencing OET side effects.

ABSTRACT Background: Breast cancer is the most common cancer among women worldwide. There are three common treatments for breast cancer, chemotherapy, surgery and radiation. Cancer treatment has several side effects that effects women´s experience of their quality of life. Nurses play a significant role concerning health care and patients´ experience of treatment.  Aim: To describe how women with breast cancer experience the side effects of cancer treatment and how it affects their quality of life.  Method: A literature study with descriptive qualitative design based on eleven scientific articles from PudMed, Cinahl and PsycInfo. Joyce Travelbee´s nursing theory was used.   Result: The women describes several different experiences where both positive and negative aspects are addressed. The result is presented with the following five categories; the experience of cognitive changes, the experience of body changes, the experience of psychosocial changes who affects quality of life, the importance of family and friends support for women´s quality of life and the experience of changes in sexual life and the importance of the partner. Conclusion: Women with breast cancer had different experiences concerning side effects and quality of life. Several of the woman had bad experience of the side effects. Another perspective was that women saw the side effects different and did not experience worse quality of life, these women started to appreciate life and was grateful to be alive.  Keywords: Breast cancer, treatment, side effects and quality of life. / SAMMANFATTNING Bakgrund: Bröstcancer är den vanligaste cancerformen bland kvinnor i världen. Tre vanliga cancerbehandlingar vid bröstcancer är cytostatika, kirurgi och strålning. I samband med cancerbehandlingarna förekommer flertalet biverkningar som påverkar kvinnans upplevelse av livskvalitet. Sjuksköterskan har en betydande roll för kvinnornas omvårdnad och patientens upplevelse av behandling.  Syfte: Att beskriva hur kvinnor med bröstcancer upplever biverkningarna av behandlingen samt hur det påverkar livskvaliteten.  Metod: En litteraturstudie med deskriptiv kvalitativ design som baserats på elva vetenskapliga artiklar hämtade från PubMed, Cinahl och PsycInfo. Den teoretiska referensram som använts är omvårdnadsteorin av Joyce Travelbee.  Resultat: Det framkom flertalet olika upplevelser hos kvinnorna där både positiva och negativa aspekter tas upp. Fem kategorier identifierades; upplevelsen av kognitiva förändringar, upplevelsen av kroppsliga förändringar, upplevelsen av psykosociala förändringar som påverkar livskvaliteten, familj och vänners betydelse för kvinnornas livskvalitet samt upplevelsen av förändringar i sexuallivet och partnerskapets betydelse. Slutsats: Kvinnor med bröstcancer upplevde biverkningarna och dess effekt olika. Många upplevde biverkningar som svåra vilket påverkade deras livskvalitet till det sämre. Andra kvinnor har sett biverkningarna ur ett annat perspektiv och istället upplevt en tacksamhet över att vara vid liv och börjat fokusera på det viktiga i livet.  Nyckelord: Bröstcancer, behandling, biverkningar och livskvalitet.

Background: Breast cancer is the most common type of cancer among women. A range of treatments are offered, all of which have side effects. Previous research has shown that women suffer from various side effects associated with breast cancer treatment. Knowledge of the women's experiences is needed, to provide support and good care. Aim: The aim of this study was to describe women’s experiences of side effects caused by breast cancer treatment. Method: This literature-based study was based on qualitative research. Friberg's five-step model was used in the analysis of the study. Eleven articles were analysed. Results: Four themes and eleven subthemes were identified. Themes that emerged were A different body, Different everyday life, Adherence to treatment and The need for knowledge and to be seen. A different body describes bodily-, sexual-, and cognitive changes. Different everyday lifedescribes how the women´s daily lives are limited by the different side effects. Adherence to treatment highlights emotions and how the emotions affected the women´s adherence to breast cancer treatment and The need for knowledge and to be seen describes experiences of lack of information and support. Conclusion: Women experience several challenges during breast cancer treatment. By having a holistic perspective and conducting person centred care, side effects can become more manageable, and women's suffering can be alleviated.