Thesis entitled "The issue of institutional care for the elderly with Alzheimer's disease" includes information about different types of dementia, charts the current situation in the Czech Republic and in the world, characterized fundamental questions of social policy and presents some methods of non-pharmacological treatment. The research analyzes the conditions of life of seniors with Alzheimer's disease who live in different types of institutions. It also focuses on family members. For compact view on the topic contribute opinions of experts from relevant institutions. Aim of this study is to describe and compare the system of care in individual and institutional facilities using statistical information to point to the timeliness issue.

Les néoplasmes myéloprolifératifs (NMP) sont des maladies acquises touchant la cellule souche hématopoïétique et qui aboutissent à une hyperproduction de cellules sanguines dont le phénotype dépend du type du NMP. La mutation la plus proéminente des NMP est JAK2V617F. Elle peut être associée à différents NMP sporadiques et familiaux.Une des problématiques, non résolue, des NMP est de comprendre comment une même mutation JAK2V617F peut donner plusieurs maladies. Notre hypothèse est que le phénotype observé pourrait dépendre du nombre de copies de JAK2V617F. Une autre inconnue concerne la cause génétique des formes familiales.Pour ces raisons, nous avons modélisé des NMP sporadiques et un cas familial par les iPS. Cette approche devrait nous permettre d’une part, de comparer les effets de JAK2V617F à l’état hétérozygote et homozygote sur l’hématopoïèse et d’autre part, d’avancer dans la compréhension des effets d’une duplication de 5 gènes que nous avons identifiée, par une approche de génétique, comme un facteur de susceptibilité chez 2 familles.Dans la première partie du travail, concernant la modélisation des NMP sporadiques, nous avons montré que JAK2V617F augmente la prolifération des cellules myéloïdes obtenues à partir des iPS. D’autre part, nous avons pu mettre en évidence une différence marquée dans l’hypersensibilité à la TPO et à l’EPO entre les lignées hétérozygotes et homozygotes pour JAK2V617F permettant d’expliquer le phénotype des PV et des TE. Dans la deuxième partie concernant les NMP familiaux, nous avons pu mettre en évidence un phénotype spécifique attribuable à la seule duplication. Grace à ce modèle, nous allons pouvoir identifier le(s) gène(s) responsable(s) du phénotype. Ce travail apporte la preuve de concept que les iPS sont un bon outil pour modéliser les NMP sporadiques et familiaux et qu’elles peuvent servir comme outils de criblage de petites molécules développées à des fins thérapeutiques. / Myeloproliferative neoplasms (MPN) are clonal hematologic diseases which lead to an overproduction of blood cells. The affected myeloid lineage depends on the type of MPN. JAK2V617F is the most predominant mutation in MPN and can be associated with various sporadic and familial cases.One main issue to address in MPN is to understand how a single mutation JAK2V617F can give rise to several diseases. Our hypothesis is that this phenotypic heterogeneity might be due to the JAK2V617F gene dosage. Another goal is to identify the genetic cause of familial MPN.For these reasons, we modeled sporadic and familial MPN cases with iPS technology. This approach allowed us i) to compare the impact of heterozygous and homozygous JAK2V617F mutation on hematopoiesis and ii) to get insight into the effects of a 5 genes duplication that we identified as a susceptibility locus uncovered by a genetic approach in 2 families.In the first part of the work concerning sporadic MPN modeling, we showed that JAK2V617F increases iPS myeloid potential. Furthermore, we showed a marked difference in the TPO and EPO hypersensitivity between heterozygous and homozygous JAK2V617F iPS cell lines that could be linked to the difference between PV and ET. In the second part of the work, we demonstrated a specific phenotype due to the sole duplication. This model will allow us to identify the gene(s) responsible of the phenotype. This study brings the proof of concept that iPS can be used for sporadic and familial MPN modeling and drug screening.

Background Animal models can be used to mimic human conditions of psychopathology, and also as pre-clinical models to evaluate candidate drugs. With hormonal treatment it is possible to produce behavior in the rat which corresponds to the mental symptoms of pre-menstrual syndrome (PMS), and pre-menstrual dysphoric disorder (PMDD). PMS affects 25-30 % of all women in fertile age and 3-8% are diagnosed with the more severe condition PMDD. The cardinal mental symptoms are; irritability, mood-swings, depression, anxiety, fatigue, insomnia, difficulties with concentration and memory and learning difficulties. The symptoms of PMS/PMDD occur in the luteal phase in conjunction with increasing concentrations of progesterone (P4) and P4-metabolites. In anovulatory cycles the symptoms are absent. The hormones which produce the monthly reoccurring negative symptoms on mood are foremost the neuroactive metabolites; allopregnanolone (ALLO) and tetrahydro-deoxycorticosterone (THDOC). ALLO is produced by the corpus luteum, but can also be synthesized in the brain, both ALLO and THDOC can also be released from the adrenal cortex during stress. These steroids are active on the inhibitory GABA neurotransmitter system through the GABAA receptor, and the effects are similar to that of alcohol and benzodiazepines. These steroids have strong sedative and hypnotic effects. A paradox is that some individuals seem to react with negative mood on sex steroids while all fertile women have the cyclical steroid changes during the menstrual cycle. Some individuals are more sensitive to neuroactive steroids with influences of personality, heritability and stress factors. Aims The thesis aims were to develop pre-clinical animal models of PMS/PMDD and to investigate induction of ALLO tolerance, individual sensitivity to neurosteroids and the interactions between chronic social stress and neurosteroids. Methods In these studies male and female Wistar rats were used to test steroid hormone effects on learning and memory and behaviors analogous to negative mood symptoms. This was accomplished through hormonal treatment and a subsequent withdrawal period from P4 (P4) + estradiol (E2) (PEWD), or ALLO. To assess tolerance, memory and learning in the Morris water maze (MWM) was studied. Anxiety-like behaviors were tested with the elevated plus maze (EPM), open field test (OFT), and the intruder test (IT). The EPM or OFT was used to classify the rats as high or low responders on risk-taking and explorative behavior (HR/LR). For social ranking order assessment the tube test (TT) and food competition test (FCT) were used. Chronic social stress was accomplished through co-habituation with two older rats (chronic subordination stress). In female rats the estrous cycle followed using staining of vaginal smears. Concentration of corticosterone (CORT) was measured by radio-immuno-assay (RIA). Results In the MWM ALLO pre-treatment produced tolerance to the acute negative ALLO effects. Both male and female rats showed behavioral correlations between the EPM and OFT tests, and correlations were also seen in CORT levels. Individuals with the stable trait of high risk-taking and explorative behavior (HR) were more sensitive to PEWD induction of anxiety-like behavior. These animals also showed decreased CORT levels during withdrawal. Chronic subordination stress enhanced the response to PEWD on measures of locomotor activity and social anxiety-like behavior. Conclusions It is possible to induce tolerance to the negative ALLO effects on learning and memory. The animal models of anxiety-like behavior show an individual PEWD response profile where HR rats are more sensitive. Exposure to chronic social stress enhanced the PEWD response. Hence there are both inherent and environmental factors behind the behavioral response to steroid hormones in rats. / Stress- och könshormoners verkningar på centrala nervsystemet

SYFTE: Syftet är att belysa patienternas upplevelse av läkemedelsfri smärtlindring med stöd av grindteorin. DESIGN: Litteraturstudie BAKGRUND: Kunskap om hur patienterna upplever läkemedelsfri smärtbehandling baserad på grindteorin, kan göra det lättare för den enskilda sjuksköterskan att fatta beslut om användande av dessa metoder. URVAL: Vetenskapliga artiklar med empiriska studier på vuxna publicerade mellan åren 2000-2012. METOD: Databassökningar och manuella sökningar RESULTAT: 14 studier med sammanlagt 1771 deltagarevisar att smärtlindringsmetoderna med stöd av grindteorin hade avsedd effekt på smärta. De gav även patienterna lindring vad avser oro och rädsla. Några av studierna tar även upp att patienterna fick en känsla av att själv kunna påverka smärtan. Metoderna som användes var såväl hudstimulerande, som kognitiva. SLUTSATS: Smärtlindring baserad på grindteorin, såväl hudstimulering som kognitiva metoder, är något som sjuksköterskan bör ha kunskap om och använda för att lindra smärta och oro/rädsla. Metoderna är även ett sätt att låta patienten känna sig delaktig, då speciellt de kognitiva metoderna. / PURPOSE: The aim is to illuminate the patients experience of non-pharmacological pain relief with support of the gate-control theory. DESIGN: Literature review/over-view BACKGROUND: Knowledge of how the patients experience non-pharmacological pain treatment based on the gate-control theory can make it easier for the individual nurse to make decisions on the use of these methods. SAMPLE: Scientific studies with empirical studies on adults, published in articles between 2000-2012 METHOD: Database- and manual searches FINDINGS: 14 studies with in total 1771 participants show that the pain relief methods with support of the gate-control theory had the intended effect on pain. They also gave the patients relief with regard to anxiety. Some of the studies also mention that the patients got a feeling of being able to affect the pain themselves. The methods used were skin-stimulating as well as cognitive. CONCLUSIONS: Pain relief based on the gate-control theory, skin-stimulating as well as cognitive methods, is something that the nurse should have knowledge about and use to relieve pain and anxiety. The methods are also a way of letting the patient feel involved, especially the cognitive methods.

La 3,4-metilendioximetamfetamina (MDMA, èxtasi) és una droga de síntesi que es consumeix entre els joves de forma recreativa. S'ha postulat que la 3,4-dihidroximetamfetamina (HHMA), metabòlit que es forma a partir de l'O-demetilenació de la MDMA a través majoritàriament de l'isoenzim CYP2D6, podria tenir un paper important en el desenvolupament de la neurotoxicitat atribuïda a la MDMA. Així, un dels objectius de la tesi ha estat establir quin paper juga i quina importància té, des d'un punt de vista quantitatiu, aquest metabòlit HHMA en el metabolisme global de la MDMA in vivo. Per altra banda, el CYP2D6 és un enzim polimòrfic, i potencialment els subjectes metabolitzadors lents per aquesta acitivitat enzimàtica podrien tenir un risc més alt de patir toxicitat aguda. La MDMA es consumeix sovint concomitantment amb inhibidors selectius de la recaptació de serotonina (SSRI). Alguns SSRI, com la paroxetina i la fluoxetina, són inhibidors del CYP2D6 i es pot preveure una interacció metabòlica entre aquests tipus de substàncies. Mitjançant un assaig clínic (aleatori, doble cec, creuat i controlat amb placebo) en humans, s'ha estudiat la rellevància de la inhibició de l'activitat del CYP2D6, la seva contribució en el metabolisme de la MDMA i els efectes farmacològics que resulten de la co-administració de la MDMA i la paroxetina.Han estat determinades les concentracions plasmàtiques i urinàries de la MDMA i dels metabòlits més importants de la MDMA, així com les concentracions plasmàtiques de paroxetina juntament amb el seu metabòlit principal.Dels resultats obtinguts, la tesi conclou que l'HHMA és un metabòlit rellevant en la disposició metabòlica de la MDMA. L'estudi d'interacció mostra que la MDMA veu reduït el seu metabolisme oxidatiu al voltant d'un 30% i que ambdós compostos mostren una interacció metabòlica. El CYP2D6 podria contribuir in vivo en l'O-demetilenació de la MDMA en un 30%. / 3,4-methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine derivative misused among youths for recreational purposes. It has been postulated that 3,4-dihydroxymethamphetamine (HHMA), a metabolite resulting from the O-demethylenation of MDMA through CYP2D6 may play a role in the development of the neurotoxicity. Thus, one of the major aims of the thesis was to establish HHMA relevance, from a quantitative point of view, in MDMA metabolism. Moreover, CYP2D6 is a polymorphic enzyme and the participation of CYP2D6 in the oxidative metabolism of MDMA may suggest an increased risk for acute toxicity in poor metabolizers for this enzymatic activity. MDMA is sometimes consumed concomitantly with selective serotonin reuptake inhibitors (SSRI). Some SSRI are potent CYP2D6 inhibitors such as paroxetine or fluoxetine and a metabolic interaction between these drugs and MDMA could be expected. Thus, interaction studies of MDMA with SSRI may be an in vivo approach to evaluate the contribution of CYP2D6 on MDMA disposition and the effects of the co-administration of both compounds. The major objective was to assess the contribution of CYP2D6 to MDMA disposition using paroxetine as a metabolic probe inhibitor. It was carried out a clinical trial in humans. The study was randomized, double blind, crossover, and controlled with placebo. Plasma concentration-time profiles and urinary recoveries of MDMA and main metabolites including HHMA were obtained. Paroxetine and its main metabolite (hydroxy-methoxy-paroxetine) plasma concentrations were also determined. From the results obtained, it is conclude that HHMA is a relevant metabolite on MDMA disposition in humans. The interaction study shows a 30% reduction of MDMA metabolic disposition and both MDMA and paroxetine show a pharmacodynamic interaction. It is estimated that CYP2D6 may accounts for a 30% of MDMA O-demethylenation in humans.

Epidermolysis bullosa simplex (EBS) and epidermolytic ichthyosis (EI) are rare skin fragility diseases characterized by intra-epidermal blistering due to autosomal dominant-negative mutations in basal (KRT5 or KRT14) and suprabasal (KRT1 or KRT10) keratin genes,  respectively. Despite vast knowledge in the disease pathogenesis, the pathomechanisms are not fully understood, and no effective remedies exist. The purpose of this work was to search for keratin gene mutations in EBS patients, to develop in vitro models for studying EBS and EI, and to investigate novel pharmacological approaches for both diseases. We identified both novel and recurrent KRT5 mutations in all studied EBS patients but one which did not show any pathogenic keratin mutations. Using cultured primary keratinocytes from EBS patients, we reproduced a correlation between clinical severity and cytoskeletal instability in vitro. Immortalized keratinocyte cell lines were established from three EBS and three EI patients with different phenotypes using HPV16-E6E7. Only cell lines derived from severely affected patients exhibited spontaneous keratin aggregates under normal culture conditions. However, heat stress significantly induced keratin aggregates in all patient cell lines. This effect was more dramatic in cells from patients with a severe phenotype. In organotypic cultures, the immortalized cells were able to differentiate and form a multilayered epidermis reminiscent of those observed in vivo. Addition of two molecular chaperones, trimethylamine N-oxide dihydrate (TMAO) and sodium 4-phenylbutyrate (4-PBA), reduced the keratin aggregates in both stressed and unstressed EBS and EI keratinocytes, respectively. The mechanism of action of TMAO and 4-PBA was shown to involve the endogenous chaperone system (Heat shock proteins e.g. Hsp70). Besides, MAPK signaling pathways also seemed to be incriminated in the pathogenesis of EBS. Furthermore, depending on which type of keratin is mutated, 4-PBA up-regulated Hsp70 and KRT4 (possibly compensating for mutated KRT1/5), and down-regulated KRT1 and KRT10, which could further assist in protecting EBS and EI cells against stress. In conclusion, novel and recurrent pathogenic keratin mutations have been identified in EBS. Immortalized EBS and EI cell lines that functionally reflect the disease phenotype were established. Two pharmacologic agents, TMAO and 4-PBA, were shown to be promising candidates as novel treatment of heritable keratinopathies in this in vitro model.

La douleur articulaire associée à l’arthrose est un problème clinique majeur, spécialement chez les personnes âgées. L’intensité de la douleur est souvent amplifiée lors de mouvement de l’articulation et principalement lors du soutien de la charge corporelle sur le membre lésé. Malheureusement, les traitements pharmacologiques proposés sont trop souvent associés à des effets secondaires néfastes et à une inefficacité pour le soulagement de la douleur à long terme. Divers modèles murins sont utilisés en laboratoire de recherche pour des études précliniques de molécules aux propriétés analgésiques. Une évaluation comparative de la réponse comportementale douloureuse des animaux d’un modèle d’instabilité articulaire induit par le sectionnement du ligament croisé antérieur accompagné d’une méniscectomie partielle (le modèle ACLT+pMMx) et d’un modèle de dégénérescence articulaire induite par le monoiodoacetate (le modèle MIA) a permis de sélectionner un modèle approprié pour la continuité du projet. Les deux modèles ont démontré des lésions tissulaires, mais le modèle MIA a démontré une réponse douloureuse plus prononcée que le modèle ACLT+pMMx. Par l’analyse de la démarche, le modèle MIA a démontré une boiterie claire dans le patron de la démarche des animaux qui est associée à une lésion unilatérale. Le modèle MIA a donc été choisi pour la suite du projet. La problématique principale dans la recherche sur la douleur associée à l’arthrose est une compréhension incomplète des mécanismes de douleur responsables de l’induction et du maintien de l’état de douleur. Il devient donc nécessaire d’améliorer nos connaissances de ces mécanismes en effectuant une caractérisation plus approfondie des modèles animaux employés pour l’évaluation de stratégies pharmacologiques analgésiantes. Afin de bien comprendre le modèle MIA, une caractérisation des événements moléculaires centraux lors de la progression du processus dégénératif des structures articulaires de ce modèle s’est effectuée aux jours 3, 7, 14, 21 et 28 post injection. Des mécanismes hétérogènes qui modulent l’information nociceptive en fonction de la progression temporelle de la pathologie ont été observés. Les changements du contenu i spinal des neuropeptides sélectionnés (substance P, CGRP, dynorphine A et Big dynorphine) ont débuté sept jours suivant l’injection de MIA. L’observation histologique a démontré que les dommages structuraux les plus importants surviennent entre les jours 14 et 21. C’est entre les jours 7 et 21 que les lésions démontrent le plus de similarités à la pathologie humaine. Cela suggère que lors d’une évaluation préclinique d’un traitement pharmacologique pour pallier la douleur articulaire utilisant le modèle MIA, l’étude doit tenir compte de ces événements afin de maximiser l’évaluation de son efficacité. Puisque les traitements pharmacologiques conventionnels proposés pour le soulagement de la douleur ne font pas l’unanimité en terme d’efficacité, d’effets non désirés et de coûts monétaires parfois onéreux, les molécules de dérivés de plante deviennent une alternative intéressante. L’eugénol, le principal constituant de l’huile de clou de girofle, a été administré oralement pour une période de 28 jours chez des rats ayant reçu l’injection intra-articulaire de MIA afin d’évaluer son efficacité pour le traitement de la douleur articulaire. L’eugénol à une dose de 40 mg/kg s’est révélé efficace pour l’amélioration du patron de la démarche des animaux ainsi que pour la diminution de l’allodynie mécanique secondaire. De plus, les concentrations spinales de neuropeptides pronocicepteurs ont diminué chez les animaux traités. Par une évaluation histopathologique, l’eugénol n’a démontré aucune évidence d’effets toxiques suite à une administration per os quotidienne pour une période prolongée. Ces résultats suggèrent le potentiel thérapeutique complémentaire de la molécule d’eugénol pour le traitement de la douleur articulaire. / Pain is the most predominant clinical symptom associated with osteoarthritis (OA), mostly among older people. Joint movement and weight bearing often increase the pain intensity. Unfortunately, the proposed pharmacological treatments are frequently associated with side effects and ineffective for pain alleviation for long time periods. Many murine models are used in laboratories for preclinical studies evaluating analgesic compounds. A comparative evaluation of the behavioral pain responses of animals with a joint instability model induced by the transection of the anterior cruciate ligament followed by a partial menisectomy (the ACLT+pMMx model) and of an articular degenerative model induced by an intra-articular injection of monoiodoacetate (the MIA model) was conducted to select an appropriate model for the continuation of the project. Both models demonstrated articular lésions, however the MIA model demonstrated a clearer behavioral pain response over the ACLT+pMMx model. The gait pattern of the MIA model revealed a clear limping gait similar to that observed with unilateral OA in humans. The MIA model was chosen for the subsequent studies. An unresolved issue in pain OA research is the lack of understanding of the pain mechanisms responsible for the induction and maintenance of the pain. Therefore, there is an urgent clinical need to improve the characterization of animal models to effectively discover novel pain relief pharmacological treatment stratégies for OA patients. A characterization of the spinal pain molecular events during the progression of the joint degenerative process in the MIA model was performed on days 3, 7, 14, 21 and 28 post injection. Heterogeneous nociceptive central molecular events were observed in respect to the time course of the pathology’s progression. Changes in selected spinal neuropeptide content (substance P, CGRP, dynorphin A, Big dynorphin) began 7 days following the MIA injection. Most severe joint structural damage on histology occured between days 14 and 21 post injection. These results suggest that preclinical drug evaluation employing this model should be conducted between 7 and 21 days post injection when the lesions resemble most those of human OA. iii As current pharmacological therapy for the alleviation of joint pain does not achieve the unanimity in respect to efficacy, side effects and cost, plant derivate compounds are now interesting alternatives to improve the situation. Eugenol, the main constituent of clove oil, was evaluated for its efficacy for alleviation of joint pain in rats who previously received an intra-articular injection of mono-iodoacetate to induce the MIA model. Eugenol, administered orally for 28 consecutive days at a dose of 40 mg/kg, improved gait pattern and reduced secondary mechanical allodynia. Furthermore, spinal concentrations of pronociceptive neuropeptides were also decreased in the treated animals. No toxic effects of the compoud were identified on histopathological assessment of the various tissues. These results suggest that eugenol could be a potential therapeutic option for alleviating OA joint pain.

One of the aims included in the United Nations Millennium Development Goals is to decrease the number of the world’s population without access to sanitation and water that is safe, by half by the year 2015. The use of water that is not safe for consumption leads to water–related diseases. For the purpose of this study gastro–intestinal disease was redefined as diseases of the gastro–intestinal tract caused by pathogens that spread via contaminated drinking water, poor sanitation and inadequate hygiene. Information obtained regarding the use of gastro–intestinal disease medication, may provide information about the prevalence of gastro–intestinal disease in South Africa. The general objective of this study was to determine the prescribing patterns of gastro–intestinal medication in different geographical areas in the private health care sector of South Africa. A retrospective drug utilisation review was conducted on data obtained from a medicine claims database of a pharmacy benefit management company for 2007 and 2008. A pharmacoepidemiological approach was followed in order to determine the prevalence of gastro–intestinal disease as well as the use of gastro–intestinal medication in South Africa as well as the different provinces of South Africa. The impact of water quality and sanitation on the prevalence of gastro–intestinal disease was also investigated. Gastro–intestinal medication (used in the treatment of gastro–intestinal disease) included the following pharmacological groups according to the MIMS®–classification: antivertigo and anti–emetic agents (group 1.8), antispasmodics (group 12.3), antidiarrhoeals (group 12.7), minerals and electrolytes (group 20.4, selected according to specified NAPPI–codes) and antimicrobials (group 18). Antimicrobials had to be prescribed in combination with one of the specified gastro–intestinal medication groups in order to be classified as a gastro–intestinal medication. In 2007 and 2008 respectively, 428864 and 340921 gastro–intestinal medication items were prescribed. The most frequently prescribed gastro–intestinal medication pharmacological groups in 2007 and 2008 were beta–lactam antimicrobials (with proportion percentages of 22.77% and 20.85% in 2007 and 2008 respectively), antivertigo and anti–emetic agents, antispasmodics, antidiarrhoeals and quinolone antimicrobials. Minerals and electrolytes represented only a small proportion (2.99% and 2.56% in 2007 and 2008 respectively) of the prescribed gastro–intestinal medication in South Africa. In the Free State and Western Cape antivertigo and anti–emetic agents were the most frequently prescribed gastro–intestinal medication items, while in other provinces beta–lactam antimicrobials ranked the highest. In all provinces except the Western Cape and the Northern Cape, amoxicillin/clavulanic acid was the most frequently prescribed gastro–intestinal medication active ingredient. In the Western Cape loperamide was the most frequently prescribed active ingredient, while ciprofloxacin ranked highest as active ingredient in the Northern Cape in 2008. Based on the prescribing patterns of gastro–intestinal disease medications the treatment of gastro–intestinal disease in this section of the private health care sector of South Africa, does not fully comply with the Standard Treatment Guidelines with regard to the use of antimicrobials and electrolyte replacement therapy. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

One of the aims included in the United Nations Millennium Development Goals is to decrease the number of the world’s population without access to sanitation and water that is safe, by half by the year 2015. The use of water that is not safe for consumption leads to water–related diseases. For the purpose of this study gastro–intestinal disease was redefined as diseases of the gastro–intestinal tract caused by pathogens that spread via contaminated drinking water, poor sanitation and inadequate hygiene. Information obtained regarding the use of gastro–intestinal disease medication, may provide information about the prevalence of gastro–intestinal disease in South Africa. The general objective of this study was to determine the prescribing patterns of gastro–intestinal medication in different geographical areas in the private health care sector of South Africa. A retrospective drug utilisation review was conducted on data obtained from a medicine claims database of a pharmacy benefit management company for 2007 and 2008. A pharmacoepidemiological approach was followed in order to determine the prevalence of gastro–intestinal disease as well as the use of gastro–intestinal medication in South Africa as well as the different provinces of South Africa. The impact of water quality and sanitation on the prevalence of gastro–intestinal disease was also investigated. Gastro–intestinal medication (used in the treatment of gastro–intestinal disease) included the following pharmacological groups according to the MIMS®–classification: antivertigo and anti–emetic agents (group 1.8), antispasmodics (group 12.3), antidiarrhoeals (group 12.7), minerals and electrolytes (group 20.4, selected according to specified NAPPI–codes) and antimicrobials (group 18). Antimicrobials had to be prescribed in combination with one of the specified gastro–intestinal medication groups in order to be classified as a gastro–intestinal medication. In 2007 and 2008 respectively, 428864 and 340921 gastro–intestinal medication items were prescribed. The most frequently prescribed gastro–intestinal medication pharmacological groups in 2007 and 2008 were beta–lactam antimicrobials (with proportion percentages of 22.77% and 20.85% in 2007 and 2008 respectively), antivertigo and anti–emetic agents, antispasmodics, antidiarrhoeals and quinolone antimicrobials. Minerals and electrolytes represented only a small proportion (2.99% and 2.56% in 2007 and 2008 respectively) of the prescribed gastro–intestinal medication in South Africa. In the Free State and Western Cape antivertigo and anti–emetic agents were the most frequently prescribed gastro–intestinal medication items, while in other provinces beta–lactam antimicrobials ranked the highest. In all provinces except the Western Cape and the Northern Cape, amoxicillin/clavulanic acid was the most frequently prescribed gastro–intestinal medication active ingredient. In the Western Cape loperamide was the most frequently prescribed active ingredient, while ciprofloxacin ranked highest as active ingredient in the Northern Cape in 2008. Based on the prescribing patterns of gastro–intestinal disease medications the treatment of gastro–intestinal disease in this section of the private health care sector of South Africa, does not fully comply with the Standard Treatment Guidelines with regard to the use of antimicrobials and electrolyte replacement therapy. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

Livslängden ökar och befolkningen blir äldre och därigenom blir demenssjukdomar allt vanligare. Psykologiska och motoriska besvär som orsakas av demenssjukdomar har samlingsnamnet, Beteendemässiga och Psykiska Symtom vid Demens (BPSD). En personcentrerad omvårdnad bygger på ett individualiserat förhållningssätt, något som är viktigt vid behandling av BPSD. Användning av läkemedel hos äldre personer med demenssjukdom ger en ökad risk för biverkningar som kardiovaskulära förändringar och ökad mortalitet. En ökad kunskap om icke-farmakologiska interventioner kan bidra till att minska onödigt användande av antipsykotiska läkemedel vid BPSD. Syftet var att sammanställa kunskap om icke-farmakologiska interventioner vid Beteendemässiga och Psykiska Symtom vid Demens (BPSD). För att besvara syftet genomfördes en kunskapsöversikt där data samlades in via en systematisk litteratursökning i databaserna, CINAHL, PubMed och PsycInfo och analyserades via en innehållsanalys. I analysen ingick 26 artiklar och samtliga var kvantitativa. Till frågeställningen, vilka icke-farmakologiska interventioner används vid BPSD symtom, framkom det sju kategorier; Aktivitet, Djur, Kognitiv, Musik, Riktlinjer, Sensorisk och Övrigt. Till frågeställningen, hur påverkar interventionerna symtom vid BPSD, framkom det sex kategorier; BPSD-, Affektiva-, Hyperaktivitets-, Apati-, Psykossymtom och Psykiskt/Psykosocialt mående. Resultatet visade för 97% av de 29 icke-farmakologiska interventionerna en positiv påverkan, med förbättring av något BPSD symtom. Därför är det viktigt att implementera icke-farmakologiska interventioner i omvårdnaden av personer drabbade av demenssjukdom. / The lifespan increases and the population grows older, thus are the numbers of dementia diseases increasing. Psychological and motor disorders caused by dementia have the collective name, Behavioral and Psychological Symptoms of Dementia (BPSD). A person-centered care is based on an individualized approach, something that is important in the treatment of BPSD. The use of drugs in elderly people with dementia presents an increased risk of side effects such as cardiovascular changes and increased mortality. Increased knowledge of non-pharmacological interventions can help reduce unnecessary use of antipsychotic drugs for BPSD. The purpose was to compile knowledge of non-pharmacological interventions for behavioral and psychological symptoms of Dementia (BPSD). To answer the purpose, a knowledge review was conducted where data was collected via a systematic literature search in the databases, CINAHL, PubMed and PsycInfo and analyzed with content analysis. The analysis included 26 articles and all were quantitative. To the question, which non-pharmacological interventions are used in BPSD symptoms, seven categories emerged; Activity, Animal, Cognitive, Music, Guidelines, Sensory and Other. To the question, how does the intervention affect symptoms of BPSD, there were six categories; BPSD, Affective, Hyperactivity, Apathy, Psychosis, and Psychological / Psychosocial Mood. The result showed a positive effect for 97% of the 29 non-pharmacological interventions, with improvement of some BPSD symptoms. Therefore, it is important to implement non-pharmacological interventions in the care of people affected by dementia.