L'évolution des soins médicaux en milieu hospitalier se caractérise par une intensité accrue des soins et de l'utilisation des médicaments, ces derniers étant de plus en plus nombreux et souvent onéreux. De plus, les personnes âgées, en nombre croissant dans notre société, souffrent fréquemment de pathologies concomitantes et nécessitent donc une polythérapie. Il devient dès lors de plus en plus complexe d'assurer un usage optimal (efficace, non toxique, et économique) des médicaments, et également d'assurer un suivi adéquat du traitement lorsque ces patients sont transférés entre milieux de soins aigus et chroniques. De nombreuses publications ont mis en évidence, à l'étranger, une prévalence élevée d'utilisation inappropriée des médicaments en gériatrie (sous forme d'overuse, de misuse, et d'underuse). Les facteurs explicatifs d'une utilisation inappropriée n'ont cependant jamais été étudiés dans cette population. Or, cette étape d'identification est indispensable pour le développement d'interventions appropriées. Elle a donc constitué la première partie du travail de recherche (1). Ensuite, certaines études ont tenté d'évaluer l'impact de diverses approches permettant d'améliorer la prescription (y compris la pharmacie clinique), mais peu ont utilisé une méthodologie robuste. De plus, l'intérêt de cette approche de pharmacie clinique n'a jamais été évaluée en Belgique, alors qu'il existe un potentiel certain pour la développer. C'est dans ce cadre que s'est effectuée la deuxième partie du travail (2). (1) Pour répondre au premier objectif, une étude qualitative combinant des données issues d'entretiens et d'observations avec des professionnels et patients au sein de services de gériatrie a été réalisée. Trois grandes catégories de facteurs sous-jacents à une utilisation inappropriée des médicaments ont été identifiés : référence au modèle de soins de santé aigus pour des adultes en général ; attitude d'apprentissage passive; prise de décisions paternaliste. A l'inverse la prise en charge par un gériatre et la communication multidisciplinaire permettent une meilleure utilisation des médicaments. Les mesures d'optimisation potentielles devraient donc entre autres concerner les compétences individuelles, les relations médecin-patient et médecin-médecin, et les systèmes de transfert d'informations entre milieux de soins. (2) Afin de quantifier la qualité de prescription, et l'impact d'une collaboration avec un pharmacien clinicien, une étude randomisée contrôlée a été réalisé, et a inclus 200 patients hospitalisés au sein d'un service de gériatrie. Les résultats montrent que l'intervention d'un pharmacien clinicien permet de réduire de façon significative l'overuse, l'underuse et le misuse des médicaments. L'acceptation des interventions est excellente, et leur pertinence clinique élevée.Enfin, l'intervention s'accompagne d'une tendance à une diminution de la mortalité et de la morbidité des patients, un an après leur sortie de l'hôpital. Ce travail démontre donc l'intérêt de la pharmacie clinique dans le contexte belge, et ouvre plusieurs perspectives, dont une évaluation de la généralisation à d'autres services cliniques, et une évaluation de son rapport coût-efficacité.

Läkemedels relaterade problem är en stor orsak till återinläggningar på sjukhus. Problemen orsakar både fysiska, psykiska och ekonomiska konsekvenser för patienten och samhället. Tidigare studier visar att många patienter har dålig kunskap om sin läkemedelsbehandling. Syftet med denna studie är att undersöka patienters upplevelser av läkemedelshantering såväl inneliggande som i den vana hemmiljön, samt att inhämta underlag för förbättringar i läkemedelshanteringen. Metoden är kvalitativ med fenomenologisk ansats och elva intervjuer har utförts. Analysen utfördes enligt kvalitativ innehållsanalys. Resultatet visar att patienter känner att de måste lita på det vårdpersonalen säger och gör och ser inget annat val. Bristande information leder till att patienten ifrågasätter om det verkligen är rätt medicin han eller hon får. Resultatet visar på vissa faktorer som är viktiga för att få en väl fungerande läkemedelshantering och det latenta innehållet i resultatet sammanfattas som att en väl fungerande läkemedelshantering bygger på goda kunskaper, kommunikation och delaktighet. / Drug related problems (DRP) are a major concern for hospital readmissions. These problems have physical, physiological and economical implications for the patients and for society. Research has shown that many patients´ have a lack of knowledge about their drug therapy. The aim of this study was to investigate patients´ perceptions of the medication use process in hospitals as well as in their own home environment, and in addition to establish foundations to provide a better medication use process. The research was based on eleven interviews using a qualitative method with a phenomenological approach. A qualitative content analysis was applied. The study shows that patients´ have a feeling that they have to trust their caregivers for what they say and what they do and there is no other choice. Lack of information leads to questioning if its´ the right medication he or she received. The results show that certain main factors are important for a functional medication use process. The main factor being that a good medication use process is based on good knowledge, communication and involvement. / " En säker läkemedelsprocess"

The goal of the present study was to examine the relationships between college students with prior therapy and psychotropic drug experience and total number of therapy sessions. This study also investigated specific types of medications students were taking and total number of therapy sessions attended. The first hypothesis under investigation was that students who have received therapy prior to beginning treatment would remain in therapy significantly longer than participants who have received no prior therapy. It was also hypothesized that students who were prescribed psychotropic medications prior to beginning therapy will remain in therapy significantly longer than students who were taking no psychotropic medications. Lastly, it was hypothesized that students who reported taking anti-anxiety or anti-depressant medications would stay in therapy longer than students taking other types of psychotropic medications will. Participants (n = 279) were collected from a pre-existing database and included students who received therapeutic services from a Southern university whose population comprised 18,485 students. The first two hypotheses were evaluated using a 2 (Prior Therapy: Yes vs. No) x 2 (Prior Medication: Yes vs. No) Analysis of Variance (ANOVA). The third hypothesis was analyzed using a 2 (Antidepressant Medication: Yes vs. No) x 2 (Anxiolytic Medication: Yes vs. No) x 2 (Other Psychotropic Medications: Yes vs. No) ANOVA. Results supported hypothesis 1: students who have previously attended therapy will stay in therapy significantly longer than students with no prior therapy experience F (1, 275) = 6.65, p = .01). However, findings did not support either hypotheses 2 or 3: students who were taking psychotropic medications prior to entering therapy did not stay in therapy significantly longer than students who were not taking psychotropic medications prior to therapy, regardless of type of medication. Results of the present study are important, as they provide a basis for future research examining prior college student therapy and psychotropic medication experience and duration of treatment at campus counseling centers. Additionally, results suggest that students with prior exposure to therapy stay in therapy longer than students with no prior exposure to therapy. One explanation for this finding is that students with prior therapy experience are likely more familiar, and more comfortable, with the therapy process than those with no prior experience. In turn, they stay in treatment longer. Universities and campus counseling centers may consider providing students with information about mental health and therapy, as this finding and research suggests that students with personal experience or prior knowledge of mental illness or therapy have more favorable attitudes about therapy than those with no prior knowledge or experience. It is also feasible that students who continue therapy while attending college have more severe mental health problems or disorders and require further treatment. This finding is significant for universities and campus counseling centers, also, as many counseling centers use a brief model of therapy, which may not prove beneficial for students with more severe problems. However, definitive information is not available, as the current data set lacks important information, such as the previous duration of treatment, student diagnoses, time of semester that the students entered therapy, and improvement in symptoms following current therapy. Thus, results should be interpreted with caution. Other limitations and suggestions for further research are also discussed.

Older patients suffer from a greater number of medical morbidities, consume a greater number of prescribed medications, and report lower levels of quality of life than their younger counterparts. The objectives of this study were to determine whether there is 1) an association between medical morbidity and symptom burden or 2) an association between medication use and symptom burden. This was a cross-sectional study of the symptoms, medical morbidities, and medications reported by 159 community-dwelling male patients 65 years of age or older. Correlations were drawn using linear regression analysis. On average, the participants in this study suffered from 2.56 +/- 1.36 medical morbidities, were prescribed 7.91+/- 2.83 medications, and reported 3.17 symptoms at any severity. The results of this study demonstrated a direct correlation between number of medical morbidities and symptom burden (R2 = 0.94). Our study did not find a significant correlation between medication use and symptom burden (R2 = 0.20). The findings of this study suggest that the number of medical morbidities has a stronger negative impact on symptom burden than the number of medications used. Thus, when attempting to improve quality of life for older patients, physicians should focus on the treatment and alleviations of symptoms associated with medical morbidity.

Injection drug users (IDUs) account for an estimated 44% of people living with HIV/AIDS in China and are the major driving force behind the expanding epidemic. Developing effective antiretroviral therapy (ART) adherence interventions in the Chinese IDU population is a major challenge. In conjunction with ART scale-up in Yunnan province, our goal was to gather patient perspectives on ART and ideas for feasible adherence support. Between December 2005 and March 2006, eight focus groups with a total of 55 HIV positive IDUs were conducted at three sites in Yunnan to ascertain ART knowledge, barriers to adherence, and acceptable adherence support methods. Focus groups included ART experienced and naïve participants, and HIV positive IDUs in methadone maintenance clinics. Discussions were audiotaped, notes were transcribed and coded for analyses. All participants were former or current IDUs and 31 were from the rural countryside (59.6%), and 19 (36.5%) resided in a small city. ART was viewed positively but the principal barriers for urban IDUs were stigma and discrimination, while geography was the main problem for rural IDUs. Major themes were stratified between four components: knowledge, motivation, cues to action, and access to care. Adherence tools that were spontaneously endorsed included watches, pill boxes, and diaries. Directly observed therapy (DOT) within methadone programs was acceptable but community-based DOT would need to address stigma issues in urban areas. Two separate HIV epidemics exist within IDUs in China, stratified between small-city urban and rural populations. No single model for adherence will work and interventions must be broad-based. This study provides an expanded conceptual framework for ART adherence in the HIV positive IDU population, which includes the unique barriers posed by the ecological context surrounding this doubly-discriminated population.

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Osteoporosis is a common condition characterized by bone fragility and fractures. Hip fracture, leads to disability, morbidity, excess mortality and growing costs to health care systems. / Antiresorptive agents are used to treat osteoporosis and fractures; it is unknown if these agents are effective in preventing recurrent fractures in individuals who have sustained a hip fracture. / Using health services administrative databases, we ascertained the incidence of hip fractures and associated-mortality rates in the elderly population in Quebec, from 1996 to 2002 and, evaluated the effectiveness of antiresorptive agents for the prevention of recurrent hip fractures. / We identified 33,243 hip fractures. Age-adjusted annual rates of hip fractures decreased in women by 11% from 1996 to 2002 while they did not change in men. Overall one-year mortality rates were higher in men than in women (37% versus 24%), and remained stable over time. Patients exposed to antiresorptives had a 26% reduction in the rate of recurrent fractures (95% CI, 0.64--0.86) compared to patients who were not exposed to these agents. / Hip fractures remain a prevalent disease with serious complications. Further research is essential to confirm our results and, to clarify the association between increasing use of antiresorptive agents and the trend reversal in the incidence of hip fractures.

Glial-derived lipoparticles facilitate the transport of cholesterol and lipids between cells within the CNS and have been shown to support neuronal growth and synaptogenesis. Partial deafferentation of the hippocampus by unilateral entorhinal cortex lesioning (uECL) induces well-described cytoarchitectural reorganisation and reactive sprouting in the dentate gyrus (DG). Previous studies have demonstrated a dynamic regulation of cholesterol homeostasis in the hippocampus following deafferentation, and suggest that mechanisms facilitating cholesterol transport are important during reinnervation. Furthermore, there is growing evidence that statins, a family of cholesterol-lowering drugs which inhibit the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA-R), may confer neuroprotection following trauma. / The ATP binding cassette transporters (ABC) A1 and G1 assist the generation of lipoparticles by mediating cholesterol and phospholipid efflux to extracellular apolipoprotein E (APOE), the brain's primary lipoprotein. To examine a role for these transporters in the regulation of cholesterol efflux during synaptic remodelling, and the effects of low-dose pravastatin (a potent HMGCoA-R inhibitor) on such intercellular transport mechanisms, we measured the expression of ABCA1, ABCG1, APOE, apoE(LDL)R and HMGCoA-R in the hippocampus of saline and pravastatin treated mice over time following uECL. It is shown here that ABCA1 and not ABCG1 is up-regulated at the level of mRNA and protein expression, along with APOE, in the hippocampus during active regeneration (14DPL) as determined by histochemical analysis of acetylcholinesterase staining density in the DG. While pravastatin treatment was observed to differentially influence the expression of ABCA1 mRNA and protein over time, no effects on APOE or ABCG1 mRNA expression were observed following uECL. Additionally, HMGCoA-R mRNA expression was significantly down-regulated at 21 DPL in the deafferented hippocampus in pravastatin-treated animals. While the low-dose pravastatin treatment applied here was sufficient to inhibit HMGCoA-R activity in the liver, enzymatic activity was unaffected in the cortex. / These findings suggest that ABCA1 and not ABCG1 may be important in the APOE-mediated cholesterol recycling observed during the active phase of neural reinnervation in response to uECL. In addition, the results presented here suggest that the administration of clinically-relevant statin therapy may be sufficient to influence the regulation of cerebral cholesterol homeostasis following trauma in the adult mouse brain.

Background: Multiple factors contribute to mother-to-child transmission (MTCT) of HIV-1, including virological, obstetric and biological factors. Other possible contributory determinants for high MTCT rates include immunological factors such as host genetics and viral genetic variations. Despite several therapeutic, prophylactic and obstetric interventions to reduce the proportion of infants infected during labour and delivery, mechanisms for intrapartum HIV-1 transmission remain elusive and current interventions, could, therefore remain sub-optimal. Much controversy has surrounded the correlation of HIV-1 RNA (viral load) in the systemic and genital compartments of women. The influence of short-term antiretroviral (ARV) drugs on genital tract HIV-1 is also unclear. At the time the present study was initiated, a regimen of maternal intrapartum and neonatal postpartum single-dose Nevirapine (sdNVP) was the standard of care for the prevention of mother-to-child transmission (PMTCT). In most low and middle-income countries, including South Africa, sdNVP has been documented as effective intrapartum HIV-1 prevention based on plasma pharmacokinetic levels, decreased viral loads (HIV-1 RNA) and reduced rates of intrapartum transmission, yet operational studies continue to report high intrapartum transmission rates despite the administration of sdNVP. As a result perinatal HIV-1 transmission remains a significant public health concern in several African countries. Aim: The primary aim of this study was to describe the pharmacological dynamics of Nevirapine in association with virological and immunological risk factors for intrapartum HIV-1 transmission in a South African PMTCT programme where sdNVP was the standard of care. Methods: Following regulatory approval from the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (UKZN), one hundred and twenty pregnant HIV-infected women who received the sdNVP regimen for prevention of mother-to-child HIV-1 transmission were enrolled between April-December 2006 at King Edward VIII Hospital (KEH) in Durban. Blood and cervicovaginal lavage (CVL) samples were collected from women at pre-NVP (during pregnancy) and post-NVP dosing (during labour/delivery). In addition to infant blood sampling at birth (post-NVP), postnatal infants were assessed at four and six weeks postnatally. Pharmacological laboratory investigations involved measurement of NVP drug concentration by Tandem Mass spectrophotometry. Virological investigations comprised HIV-1 RNA (viral load) quantitation, HIV-1 drug resistance testing (HIV-1 transmitting women only) and HIV-1 DNA PCR testing (infants only). Immunological investigations were only undertaken in a selected case-control subset of HIV-1 transmitting women and their infants. In this component, laboratory investigations included the determination of CCL3 and CCL3-L1 gene copy numbers, identification of single nucleotide polymorphisms (SNP’s) and haplotype characterisation of the CCL3 gene. All women were also screened for the presence of sexually transmitted infections (STI’s) during pregnancy. Results: One hundred and twenty women were enrolled onto this study. Of these, 110 women delivered 117 live infants (103 singletons and 7 twin pairs). Twelve (10.9%) women transmitted HIV-1 to their infants, while 95 (86.0%) were classified as non-transmitters. As a result of seven twin deliveries, the infant cohort comprised of 117 infants in total. Following two separate DNA PCR tests, HIV-1 infection was identified in 14 (11.9%) of study infants while the remaining 90 (76.9%) were exposed-uninfected. HIV infection status remained unknown for 13 infants due to infant demise (1.7%), lost to follow-up (7.7%) or study withdrawal (1.7%). During active labour (sampling that was best representative of the intrapartum phase) and within 20 hours of dosing, the median NVP concentration of 1070 ng/ml in the maternal systemic compartment was almost 44 times higher than the NVP levels detected in the genital compartment [24.5 ng/ml] (p < 0.001). NVP drug levels were below the 100 ng/ml therapeutic target in seven (13.7%) of 51 plasma and in all 39 CVL samples. While no significant association was found between NVP concentration in the systemic compartment and HIV-1 transmission (p = 0.4), this association was statistically significant in the genital compartment(p = 0.02). The median plasma NVP level detected among infants at birth was 83 times above the IC50 WT (10 ng/ml) and eight times higher than the 100 ng/ml therapeutic target for NVP. More than 71.0% of the infants achieved NVP drug levels above the therapeutic target. In general, higher levels of HIV-1 RNA (viral load) were observed in maternal plasma when compared to CVL. Following intrapartum sdNVP dosing, reduction in HIV-1 RNA levels did occur, however R80.0% of the women experienced no change to their HIV-1 RNA levels in both systemic and genital compartments during active labour. These findings were further supported by the strong correlation observed when comparing pre and post-NVP HIV-1 RNA levels in both maternal systemic [r = 0.81, p < 0.0001] and genital compartments [r = 0.80, p < 0.0001] during active labour. HIV-1 transmitting women had significantly higher viral loads than their non-transmitting counterparts in systemic and genital compartments, before and after intrapartum sdNVP administration. In terms of perinatal transmission this observation was only statistically significant for plasma (p = 0.02) and not CVL (p = 0.7). Maternal viral load was inversely correlated with maternal CD4 cell counts in both systemic and genital compartments. Almost 40.0% of women in this study had at least one type of STI detected during pregnancy. Maternal STI’s were detected in four (66.6%) intrapartum transmitting women and in 38 (38.8%) of non-transmitting women. No significant association was observed between the presence of maternal STI’s and the risk for intrapartum MTCT (p = 0.2,RR: 2.90, 95% CI: 0.60-15.40). The presence of maternal STI’s was associated with higher median viral loads in both systemic and genital compartments of all women, independent of intrapartum HIV-1 transmission. Despite trial-like conditions and optimal sdNVP dosing, the overall MTCT rate in this exclusively formula-fed cohort was 11.9%, of which 50.0% were in utero and 50.0% were intrapartum HIV-1 transmissions. In utero and intrapartum MTCT rates were 5.9% and 5.9% respectively. Discussion/Conclusion: Detectable CVL HIV-1 RNA that correlated well with plasma HIV-1 RNA, in conjunction with sub-optimal NVP drug concentration in maternal CVL during active labour, suggests that intrapartum HIV-1 infected women continue to act as reservoirs for both vertical and horizontal HIV-1 transmission throughout the duration of pregnancy. These findings confirm that the role of sdNVP in PMTCT was primarily one of infant prophylaxis. This was further supported by relatively unchanged maternal HIV-1 RNA (viral load) during active labour, in both systemic and genital compartments. Early identification of women who need highly active antiretroviral therapy (HAART), and initiation of such therapy as early as possible during pregnancy, not only benefits maternal health but remains the best prophylaxis against mother-to-child HIV-1 transmission. Universal access to HAART and improving strategies to optimize coverage of the current dual ARV regimen sdNVP and Zidovudine for PMTCT remain urgent research priorities in several resource-limited settings. Ongoing STI counseling, intensive screening/testing of women and their partners together promotion of condom usage, safer sex practices and aggressive STI treatment are simple interventions with tremendous impact for PMTCT in resource-limited settings. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2009.

Following a review of treatment outcome study methodology, a comparative study of psychological versus pharmacological treatments was conducted; subsidiary studies investigated aspects of treatment outcome in more detail. 193 patients with DSM III-R panic disorder with or without agoraphobia were randomly allocated to; fluvoxamine, placebo, fluvoxamine + CBT (cognitive behaviour therapy), placebo + CBT, or CBT alone. Patients received no concurrent treatments and were treated to the same schedule, with therapist contact balanced across groups. Treatments were conducted in the primary care setting. Outcome at treatment end-point and 6 month follow-up, assessed in terms of both statistical and clinical significance, showed patients receiving active treatments improved significantly, with improvement better preserved over follow-up in the groups receiving CBT. The CBT alone and fluvoxamine + CBT groups showed the most consistent gains, the latter group showing gains earliest in treatment. Outcome was also investigated using brief global ratings of symptom severity, change in symptoms following treatment, general wellbeing and social disruption, completed by psychologist, referring GPs, and patients. Using these measures all active treatments showed statistical advantage over placebo with the groups employing CBT showing the most robust and consistent response. Overall there were no significant differences in drop-out rates between groups although the drop-out rate for patients receiving CBT alone was higher than that for placebo + CBT. Agreement with main outcome measures was demonstrated for psychologist and patient ratings, but not for GP ratings. An investigation of panic attack variables as treatment outcome measures indicated that these did not function as discriminative treatment outcome measures with all treatment groups showing significant reductions in panic attack variables over treatment with few significant differences between treatment groups on any variable throughout treatment. An investigation of prognostic indicators of treatment outcome indicated good prediction of post treatment response using pre-treatment measures of anxiety level, frequency of panic attacks, extroversion and treatment group. Predictions of outcome at 6 month follow-up were less robust. Results are discussed in terms of their relevance to wider clinical practice.