Cancer is a generic term for a large group of diseases where cells of the body lose their normal mechanisms for growth so that they grow in an uncontrolled way. One of the most common treatments of cancer is chemotherapy that aims to kill abnormal proliferating cells; however normal cells and other organs of the patients are also adversely affected. In practice, it's often difficult to maintain optimum chemotherapy doses that can maximise the abnormal cell killing as well as reducing side effects. The most chemotherapy drugs used in cancer treatment are toxic agents and usually have narrow therapeutic indices, dose levels in which these drugs significantly kill the cancerous cells are close to the levels which sometime cause harmful toxic side effects. To make the chemotherapeutic treatment effective, optimum drug scheduling is required to balance between the beneficial and toxic side effects of the cancer drugs. Conventional clinical methods very often fail to find drug doses that balance between these two due to their inherent conflicting nature. In this investigation, mathematical models for cancer chemotherapy are used to predict the number of tumour cells and control the tumour growth during treatment. A feedback control method is used so as to maintain certain level of drug concentrations at the tumour sites. Multi-objective Genetic Algorithm (MOGA) is then employed to find suitable solutions where drug resistances and drug concentrations are incorporated with cancer cell killing and toxic effects as design objectives. Several constraints and specific goal values were set for different design objectives in the optimisation process and a wide range of acceptable solutions were obtained trading off among different conflicting objectives. Abstract v In order to develop a multi-objective optimal control model, this study used proportional, integral and derivative (PID) and I-PD (modified PID with Integrator used as series) controllers based on Martin's growth model for optimum drug concentration to treat cancer. To the best of our knowledge, this is the first PID/I-PD based optimal chemotherapy control model used to investigate the cancer treatment. It has been observed that some solutions can reduce the cancer cells up to nearly 100% with much lower side effects and drug resistance during the whole period of treatment. The proposed strategy has been extended for more drugs and more design constraints and objectives.

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M.Phil.(Optometry) / The concept of contact lenses was conceived over 500 years ago and has now evolved into a fundamental component of optometric practice. Soft contact lenses have become a convenient, aesthetically pleasing and comfortable alternative to spectacles that are becoming increasingly popular. The use of rigid contact lenses is imperative in the management of conditions such as keratoconus due to spectacles being insufficient in providing adequate vision. Placing a contact lens onto the cornea is an invasive procedure. The contact lens is a foreign body to the eye hence it is expected that the eye would react to that foreign body. Literature has revealed that the general reactions of the eye to contact lens wear are initial tearing, alteration of the tear layer and oedema due to reduced oxygen transmission but these are just a few of the known consequences amongst the multitude of the unknown consequences. What exactly goes on under a contact lens remains an enigma which contact lens researchers have strived to uncover over the past century. The consequence of contact lens wear is a vast area of research and can best be investigated by focusing on one aspect at a time. The aim of this study was to use dioptric power matrices and multivariate statistics to explore the effects of both gas permeable and gas non-permeable rigid contact lenses on corneal curvature. This study involves auto-keratometric measurements of the corneal curvature before and after lens wear to establish if there are any curvature changes induced by the contact lens. Keratometric data was collected with an automated keratometer (Nidek ARK-700) and was analysed correctly and completely using multivariate statistics. This thesis presents the findings of a study done in an effort to establish the short-term effects of rigid contact lens wear on keratometric behaviour by using complete methods of multivariate statistical analysis. Twenty four subjects were equally divided into three groups. One group wore polymethyl methacrylate (PMMA) rigid lenses, another group wore rigid gas permeable (RGP) contact lenses and the third group served as the control. The control group was included in the study to establish a reference for normal diurnal changes in keratometric behaviour. Fifty autoii keratometric measurements were taken before and immediately after three hours of rigid contact lens wear for the experimental groups and 50 auto-keratometric measurements were taken before and immediately after three hours of no lens wear for the control group. Data collected was analysed using multivariate statistical methods that in the past have been used infrequently in this area of research.

Major depressive disorder (MDD) is rapidly growing among the population. A widely believed neurobiological explanation is that the symptoms arise due to an imbalance of the neurotransmitter serotonin. Therefore, the most provided antidepressant is currently selective serotonin reuptake inhibitors (SSRI), which increase the serotonin in the synaptic cleft by inhibit the reuptake of serotonin. There are medications which challenge the serotonin hypothesis such as tianeptine. Tianeptine increases the reuptake of serotonin in the synaptic cleft and thus decreasing the serotonin levels. The thesis has three aims: First, to investigate what mechanisms tianeptine and SSRI work upon. Second, compare the efficiency of SSRI and tianeptine. Third, if the two agents display any differences in adverse side effects. A systematic review and search through relevant databases were made to obtain results. The main findings of this thesis were the two agents act differently of many aspects of the brain mechanisms and neurochemistry such as the cannabinoid system, expression of different cell types and their dependence of protein kinase. Even so, the results show that both agents are equally efficient in treating the depressive symptoms in the larger context, although some interesting findings are seen when zooming in. Anxiety is often comorbid with depression and even though both tianeptine and SSRI are shown to reduce these symptoms during chronic administration, SSRI can produce an anxiogenic effect in the beginning. Another noteworthy finding was that tianeptine showed to be clinically significant, but so did placebo. The third aim investigated the differences in side-effects between these two agents, and both agents were equally safe in number of adverse side-effects. Though tianeptine showed to have some slight advantages in manners of sexual dysfunction and the item 3 on the CGI scale.

3,4-methlenedioxymethamphetamine (MDMA), the main constituent of Ecstasy, is a ring-substituted amphetamine commonly abused in recreational users. High doses of MDMA determined by allometric scaling produce serotonin (5-HT) axon deneveration. Studies suggest that this interspecies scaling does not reflect human use. An 'effects' scale comparing similar behavioral and physiological effects between species has been postulated as more accurate for translational studies. Experiment 1 examined the effects of MDMA on serotonergic forebrain innervation using immunohistochemical labeling targeting the serotonin transporter protein (SERT). Experiments 2 and 3 examined low and high doses of MDMA on spatial memory, prefrontal functioning, and serotonergic neurotoxicity using 'effects' scaling. Long Evans rats were given MDMA regimens of: chronic low dose (daily injections of 1.5 mg/kg for 10 days); binge low dose (2 days of 4 x 1.5 mg/kg spaced 2 hours apart), binge high dose (2 x 7.5 mg/kg sp aced 2 hours apart). Acquisition, retention, and spatial reversal (SR) were measured in a water maze task. A 2.0 mg/kg MDMA drug challenge was then given prior to a serial spatial reversal (SSR) task to assess performance while under the effect of the drug. Attentional set shifting and behavioral flexibility were assessed in an intradimensional extradimensionl (IED) task using odor/texture discriminations. MDMA chronic and binge low doses did not impair water maze or IED performance and produced no reductions in SERT expression. MDMA binge high dose resulted in significant reductions of SERT density in the prefrontal cortex, striatum, cortical mantle, hippocampus, amygdala, and many thalamic nuclei. Despite prominent 5-HT denervation, water maze performance was unaffected. Selective impairment in behavioral flexibility on the IED test was found. / This suggests that low doses of MDMA do not produce long-term deleterious effects. But, high doses of MDMA taken in 'binges' produces widespread loss of forebrain SERT fiber innervation and significant impairments in reversal learning, while leaving attentional set shifting and spatial navigation unscathed. / by Stephanie Brooke Linley. / Thesis (Ph.D.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.

Bakgrund: Cancer är en ledande dödsorsak och är en av de största hotande faktorerna för människors hälsa över hela världen. En av de vanligaste behandlingarna för cancer är cytostatika, cellhämmande läkemedel, som ger svåra biverkningar, vilka påverkar patientens dagliga liv. Syfte: Syftet var att beskriva upplevelser av cytostatikabehandling hos patienter med cancer. Metod: Metoden som användes var en allmän litteraturstudie baserat på tio vetenskapliga artiklar av kvalitativa data vilket analyserades med innehållsanalys. Resultat: I resultatet framkom det tre teman och åtta kategorier. De tre teman var: upplevelsen av fysiska biverkningar, upplevelsen av psykiska biverkningar och delaktighet. Slutsats: Resultaten visade att cytostatikabehandling och dess biverkningar påverkade patientens liv både fysiskt, psykiskt och socialt. Att få tillräcklig information från vårdpersonal hade en stor betydelse för patienten. Patienter med cancer upplevde många gånger svårigheter att hantera information och osäkerhet i samband med prognosen samt vid typen av tillgängliga behandlingar. Det förekom även att patientens livskvalitet påverkades negativt i samband med cytostatikabehandling. Förslag på fortsatt forskning: Biverkningar till följd av cytostatikabehandling upplevs som ett stort problem för de flesta patienterna med cancer, då är det viktigt att vidare forskning kring dessa område görs. / Background: Cancer is a leading cause of death and is one of the biggest threatening factors for human health worldwide. One of the most common treatments for cancer is chemotherapy, cytostatic agents, which cause severe side effects, which affect the patient's daily life. Aim: The aim was to describe experiences of chemotherapy in patients with cancer. Method: The method used was a general literature study based on ten scientific articles of qualitative data which was analyzed with content analysis. Result: In the result, three theme and eight categories emerged. The three themes were: the experience of physical side effects, the experience of psychological side effects and participation. Conclusion: The results showed that chemotherapy and its side effects affected the patient's life, both physically, mentally and socially. Obtaining sufficient information from healthcare staff had a great impact on the patient. Patients with cancer often experienced difficulties in managing information and uncertainty in connection with the prognosis as well as the type of treatments available. It also occurred that the patient's quality of life was adversely affected in connection with chemotherapy. Suggestions for continued research: Side effects due to chemotherapy are perceived as a major problem for most patients with cancer, then it is important that further research on these areas be done.

Wen Er Ya Jane. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 130-134). / Table of contents --- p.ii / List of tables --- p.iv / List of figures --- p.vi / Abstract --- p.vii / Glossary of abbreviations --- p.ix / Acknowledgments --- p.x / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- DEFINITIONS AND CLASSIFICATIONS...............................Error! Bookmark not defined / Chapter 1.1.1 --- Classification of drug-related problems --- p.2 / Chapter 1.1.2 --- Adverse drug reactions (ADRs) --- p.2 / Chapter 1.1.3 --- Drug interactions (DI) --- p.7 / Chapter 1.1.4 --- Therapeutic failures (TF) --- p.8 / Chapter 1.1.5 --- Non-compliance --- p.10 / Chapter 1.1.6 --- Drug overdoses (DO) or drug poisonings --- p.11 / Chapter 1.1.7 --- Drug-related hospitalizations (DRH) --- p.12 / Chapter 1.1.8 --- Other relevant definitions --- p.13 / Chapter 1.2 --- LITERATURE REVIEW --- p.16 / Chapter 1.2.1 --- Adverse drug reactions --- p.16 / Chapter 1.2.2 --- Hospital admission due to ADRs --- p.18 / Chapter 1.2.3 --- Drug-related hospitalizations (DRH) --- p.22 / Chapter 1.2.4 --- Discussion --- p.24 / Chapter 1.3 --- PURPOSE OF THIS STUDY --- p.27 / Chapter CHAPTER 2 --- METHODS --- p.30 / Chapter 2.1 --- BACKGROUND --- p.30 / Chapter 2.2 --- DATA COLLECTION --- p.31 / Chapter 2.2.1 --- The patients --- p.31 / Chapter 2.2.2 --- The drug history --- p.31 / Chapter 2.2.3 --- Patients knowledge of drugs they were taking --- p.33 / Chapter 2.2.4 --- Compliance --- p.33 / Chapter 2.2.5 --- Previous episodes of adverse drug reactions --- p.34 / Chapter 2.2.6 --- Diagnosis and outcome --- p.34 / Chapter 2.2.7 --- Laboratory Results --- p.34 / Chapter 2.2.8 --- Demographic characteristics of the patients --- p.35 / Chapter 2.2.9 --- The data sheet --- p.36 / Chapter 2.3. --- CASE REVIEW (REASSESSMENT) --- p.41 / Chapter 2.4 --- CODING OF DATA --- p.41 / Chapter 2.4.1 --- Coding of general data except diagnoses and drugs --- p.41 / Chapter 2.4.2 --- Coding of diagnoses --- p.42 / Chapter 2.4.3 --- Coding of drugs --- p.42 / Chapter 2.5 --- STATISTICAL ANALYSIS --- p.42 / Chapter CHAPTER 3 --- RESULTS --- p.43 / Chapter 3.1 --- THE PATIENTS --- p.43 / Chapter 3.1.1 --- Age and sex distributions --- p.43 / Chapter 3.1.2 --- Patients' ADL and living environments --- p.47 / Chapter 3.1.3 --- Baseline liver and renal function tests --- p.50 / Chapter 3.1.4 --- Diagnoses --- p.52 / Chapter 3.2 --- DRUG USE PRIOR TO ADMISSION --- p.54 / Chapter 3.2.1 --- Overview --- p.54 / Chapter 3.2.2 --- Consumption patterns for the prescribed drugs --- p.61 / Chapter 3.2.3 --- Sources and durations for the prescribed drugs --- p.69 / Chapter 3.2.4 --- Consumption patterns for self-medications --- p.71 / Chapter 3.2.5 --- Source and duration of the self-medications --- p.73 / Chapter 3.2.6 --- Drug overdose patterns --- p.75 / Chapter 3.3 --- PATIENTS' KNOWLEDGE OF THE EFFECTS AND SIDE-EFFECTS OF DRUGS --- p.74 / Chapter 3.3.1 --- Overview --- p.74 / Chapter 3.3.2 --- Patients' knowledge of the effects of their prescribed drugs --- p.74 / Chapter 3.3.3 --- Patients' knowledge of the side-effects of their prescribed drugs --- p.77 / Chapter 3.4 --- COMPLIANCE --- p.79 / Chapter 3.5 --- DRUG-RELATED HOSPITALIZATIONS (DRH) --- p.82 / Chapter 3.5.1 --- Overview --- p.82 / Chapter 3.5.2 --- Adverse drug reactions (ADRs) --- p.84 / Chapter 3.5.3 --- Outcome of ADRs --- p.98 / Chapter 3.5.4 --- "Therapeutic failures (Non-compliance, Inappropriate dose reduction)" --- p.100 / Chapter 3.5.5 --- Drug overdoses --- p.104 / Chapter CHAPTER 4 --- DISCUSSION --- p.106 / Chapter 4.1 --- ABOUT THE PATIENTS --- p.106 / Chapter 4.2 --- DISEASE PATTERNS AND DRUG CONSUMPTION PATTERNS --- p.107 / Chapter 4.2.1 --- Diagnoses on admission --- p.107 / Chapter 4.2.2 --- Drug consumption patterns --- p.109 / Chapter 4.2.3 --- About the sources and durations of the prescribed drugs --- p.112 / Chapter 4.2.4 --- About the self-medications --- p.113 / Chapter 4.3 --- ABOUT PATIENTS' KNOWLEDGE OF THE DRUGS --- p.114 / Chapter 4.4 --- ABOUT COMPLIANCE --- p.116 / Chapter 4.5 --- ABOUT ADRS AND DRUGS INTERACTIONS --- p.118 / Chapter 4.5.1 --- The incidence of ADRs --- p.118 / Chapter 4.5.2 --- The patterns of ADRs --- p.119 / Chapter 4.5.3 --- The drugs and ADRs --- p.119 / Chapter 4.5.4 --- Self-medications and ADRs --- p.121 / Chapter 4.5.5 --- The risk factors for ADRs --- p.122 / Chapter 4.5.6 --- Drug interactions --- p.125 / Chapter 4.6 --- ABOUT THERAPEUTIC FAILURES --- p.126 / Chapter 4.7 --- ABOUT DRUG OVERDOSES --- p.127 / Chapter 4.8 --- CONCLUSIONS --- p.128 / BIBLIOGRAPHY --- p.130

Abstract BACKGROUND: Psychotic disorders are associated with symptoms such as delusions and hallucinations as well as impaired functioning. Second generation antipsychotic medications are the first line treatment for psychotic disorders, however a proportion of individuals will not respond to the medication. Clozapine is the most effective second generation anti-psychotics, however it is only used as a third line treatment because of serious side-effects. It is associated with metabolic side-effects, which increase the risk of obesity and diabetes mellitus. AIM: Determine the changes in the weight, waist circumference and blood pressure as well as triglycerides, fasting glucose and cholesterol in young people commenced on clozapine after 18 weeks and 6 months of commencement. METHOD: This is a cohort study, including participants aged 15-24 commenced on clozapine between the time period 1st of April 2016 and 30th of September 2017. Data concerning measured outcomes was gathered from patient journals. RESULTS: A total of 36 young people were commenced on clozapine during the study period and the mean age was 19.8 (SD±3.1). At the time of commencing clozapine, the mean weight of the cohort was 86.30kg (±17.08) and after 18 weeks it was 88.90kg (±16.71), and this difference was statistically significant (n=27,df=26,p=0.02) and this weight gain was present for males (n=17,df=16,p=0.038) but not females (n=10,df=9,p=0.214). CONCLUSION: Clozapine may be associated with weight gain in the early stages of commencement and it appears that males are more susceptible to this side-effect. More interventions aimed at attenuating this weight gain is needed.

A xerostomia é um efeito adverso comum e frequentemente irreversível decorrente da radioterapia de neoplasias malignas da região de cabeça e pescoço, afetando, sobremaneira, a qualidade de vida dos pacientes. Diferentes métodos para solucionar tal problema são propostos, de resultados, todavia questionáveis. Este estudo avaliou a eficácia clínica da acupuntura como método de tratamento preventivo e curativo de tais condições. Os pacientes foram distribuídos, aleatoriamente, em três grupos: grupo preventivo, constituído de 12 indivíduos, sem queixa de secura bucal, tratados com 12 a 16 sessões de acupuntura, antes e durante a radioterapia; grupo curativo, constituído de 12 indivíduos, diagnosticados, clinicamente, com xerostomia severa, tratados com 12 aplicações de acupuntura após concluído o tratamento oncológico, e grupo controle, formado pelos mesmos indivíduos do grupo curativo no momento da primeira consulta, precedente à terapêutica com acupuntura. O tratamento foi conduzido de acordo com os princípios da medicina tradicional chinesa e medicina ocidental ortodoxa, realizado de forma padronizada para todos os pacientes, duas vezes por semana, por um período de 20 minutos cada sessão. A avaliação da eficácia terapêutica fundamentou-se na mensuração da xerostomia, conduzida sob duas formas: objetiva, através da sialometria, com o registro quantitativo dos índices de fluxo salivar em repouso e estimulado (IFSR e IFSE), e subjetiva, por intermédio dos questionários Xerostomia Inventory (XI) modificado, Escala Visual Analógica (EVA) e Treatment Emergent Symptom Scale (TESS), mensurando o grau de severidade dos sintomas. Os resultados obtidos no grupo preventivo foram estatisticamente significativos quanto as avaliações objetivas e subjetivas, evidenciados por índices de fluxo salivar mais elevados tanto para o IFSR (P<0.001) como para o IFSE (P<0.001) e pela menor intensidade dos sintomas (P<0.001), quando comparadas ao controle. Para o grupo curativo, resultados também significativos foram constatados em ambas as avaliações, demonstrados pelo aumento dos IFSR (P<0.05) e IFSE (P<0.05) e redução da sintomatologia (P<0.05), comparados aos valores iniciais. Constatamos também que houve efeito de grupo e os pacientes que se beneficiaram do método preventivo, obtiveram médias estatisticamente mais significativas (P<0.001), para ambas as respostas clínicas, objetivas e subjetivas. É lícito concluir que a acupuntura mostrou-se um importante método de tratamento de xerostomia decorrente da radioterapia, visto ter alcançado uma confiabilidade significativa de eficácia, que nos faz indicá-la e sugerir a disponibilização do método preventivo nos centros de tratamento. / Xerostomia is a common and usually irreversible radiotherapy side effect in patients with head and neck cancer, affecting the patients’ quality of life. Many attempts have been suggested to manage this condition nevertheless of questionable results. This study evaluated the acupuncture treatment efficacy as a preventive and curative method for radiation-induced xerostomia. The patients were randomly assigned in three groups: preventive, composed of 12 individuals, without complaints of dry mouth, treated with 12-16 acupuncture sessions, before and concomitant radiotherapy; curative, composed by 12 individuals, diagnosed with severe xerostomia, treated with 12 acupuncture sessions after radiation therapy, and control, comprised of the curative’s group patients at the moment of the first visit, preceding this therapy. Acupuncture treatment, according to traditional Chinese medicine and occidental orthodox medicine concepts was performed twice a week, lasting 20 minutes each session, following standardize techniques for all patients. Acupuncture efficacy was evaluated, based upon objective and subjective methods of xerostomia measurements, performed by sialometry, measuring the resting and stimulated salivary flow rates (RSFR and SSFR), and by means of questionnaires such as Xerostomia Inventory (XI) modified, Visual Analog Scale (VAS) and Treatment Emergent Symptom Scale (TESS), which evaluated referred symptoms. Results obtained in preventive group, evidenced RSFR (P<0.001) and SSFR (P<0.001) significantly increased, and improvement of symptoms (P<0.001), compared with control. Within curative group, after acupuncture treatment, the results showed statistically significant improved for both resting and stimulated salivary flow rates (P<0.05) and reduces of referred symptoms (P<0.05). There were statistically differences between groups, being the patients in preventive group those who evidenced the most significant improved of values (P<0.001) for objective and subjective evaluations. We concluded that acupuncture plays an important role in xerostomia’s treatment, as shown by the results, reaching a significant confiability of efficacy, indicating and suggesting the preventive method at oncology centers.

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