MSc (Microbiology) / Department of Microbiology / Background: Patients on antiretroviral (ART) are expected to be at least 95% adherent to their treatment, as this will increase their chances of achieving treatment success (maximum and durable suppression of HIV-1 viral load); non-adherence may lead to the development of HIV drug resistance, which may lead to virologic failure and treatment failure. Therapeutic drug monitoring (TDM) has been reported to be the most efficient method to assess treatment adherence in HIV individuals, since it quantifies the concentration of ARTs in biological matrices. This is very effective when using a robust technique such as liquid chromatography tandem mass spectrometry (LCMS/MS), which has played a significant role in the evaluation and interpretation of bioavailability, bioequivalence and pharmacokinetic data. Even with patient adherence, various intra-individual factors have an influence on the expression and function of the genes responsible for the transport (MDR1) and metabolism (CYP2B6) of Efavirenz (EFV). This may lead to single nucleotide polymorphisms (SNPs) in these genes, and this may affect the way antiretrovirals (ARVs) are metabolized. The aim of this study was to evaluate the EFV concentration in plasma to assess patient adherence to treatment and correlate this with genomic occurrences in human and viral genes. Hypothesis: The concentration of ARVs in patient plasma can be used to estimate adherence to treatment; while ARVs’ transport and metabolism can affect bioavailability in a patient’s system. Research Question: Can EFV concentration in plasma be used to estimate patient adherence to treatment? Can transport and metabolism of EFV affect their bioavailability in the patient’s system? Objectives: To determine EFV concentration in plasma to assess patient adherence to treatment and correlate this with genomic occurrences in human genes and viral genes. Methodology: Twenty blood samples were collected from HIV positive individuals before treatment initiation (baseline) and between six to twelve months following treatment initiation (follow-up). The concentration of EFV in patient plasma was measured by LC-MS/MS technique. To infer other factors influencing patient pharmacokinetics output, drug resistance and human genetic characteristics were analyzed. A 1.65kb fragment of the HIV-1 Pol gene was amplified and sequenced to determine drug resistant mutations; while 363bp and 289bp of the MDR-1 and CYP2B6 human genes respectively, were also amplified and sequenced to determine polymorphisms in the transport and metabolism genes. Obtained sequences were manually edited and analyzed using Geneious Version 11.1.5 software. The Stanford HIV Drug Resistance database was used for drug resistant mutation (DRMs) analysis and MDR1 and CYP2B6 test sequences were compared with variant reference sequences to detect the presence of any SNPs. Results: The plasma EFV concentration at baseline and follow-up range was as follows: 0 – 1183ng/ml and below limits of quantification (BLQ) to 15,670ng/ml, respectively. At baseline, 0ng/ml is the expected plasma EFV concentration for patients about to commence treatment; however, two out of twenty patients had 769.9 and 1,183ng/ml drug levels in their system. Post treatment, plasma EFV levels in patients are expected to range from 1,000 – 4,000ng/ml, however, of the twenty patients, two had <1,000ng/ml, and three patients had >4,000ng/ml in their plasma. For Pol amplification, 35% (7/20) were positively amplified at baseline and 25% (5/20) were positively amplified from the follow-ups; 100% (20/20) samples were amplified for both CYP2B6 and MDR1 genes. Detection of drug resistance in the baseline Pol sequences revealed the absence of major mutations in both NRTI and NNRTI drug classes. The G516T polymorphism was present in 15% of the study participants while the homozygous GG and heterozygous GT genotype was present in 25% and 40% of the study participants, respectively. Allele determination was impossible in 20% of the samples, due to the poor nature of the sequence. The homozygous TT variant polymorphism at position 3435 was absent in the entire population, however, the CC and CT genotype was present in 15% and 85% of the study participants respectively. Analysis of EFV concentration in close proximity with the human genetic characteristics reveals that the presence of a Single Nucleotide Polymorphism affects the pharmacokinetic output observed. Discussion and Conclusion: Post treatment, 90% of the study participants indicate adherence to treatment, with only 10% of them having lower than expected EFV concentrations, implying they were non-adherent to their treatment. However, because plasma drug concentrations only reflect a patient’s adherence pattern for a few hours to at most two days, the adherence patterns of these individuals cannot be concluded with certainty. Using plasma EFV as a biomarker to evaluate adherence to treatment in HIV seropositive individuals is a feasible technique, however, its application in non-research settings is still a drawback due to the cost of the method. Characterizing patient inter-individual differences should be taken into consideration, especially since any polymorphism in their transporter and metabolizing genes may influence their overall treatment success. / NRF

Antenatal depression (depression under graviditeten) drabbar 10–20% av gravida och innebär risker för både den gravida och barnet. Forskning visar att internetbaserad kognitiv beteendeterapi (IKBT) tycks vara effektivt jämfört med sedvanlig mödravård. Uppsatsen var en sambands- och prediktionsstudie som genomfördes inom den randomiserade DANA-studien för IKBT vid antenatal depression. En inomgruppsdesign med upprepade mätningar tillämpades där 40 kvinnor med antenatal depression deltog. Syftet var att undersöka (a) patientnöjdhet med bedömningssamtalet i relation till behandlingsföljsamhet, avhopp och minskning av depressionssymtom under IKBTbehandlingen, samt (b) jämföra förändring i depressionssymtom mot två tidigare studier. Resultatet visade att en högre patientnöjdhet med bedömningssamtalet signifikant predicerade en mindre minskning av depressionssymtom mellan screening och förmätning. Inga signifikanta samband hittades mellan patientnöjdhet med bedömningssamtalet och behandlingsföljsamhet eller avhopp. Slutsatser bör dras med stor försiktighet utifrån metodologiska begränsningar. Resultatet visade även att depressionssymtom jämfört med förmätningen signifikant minskade från andra veckomätningen i behandlingen till och med eftermätningen vecka tio. Detta bekräftade tidigare studiers resultat. Framtida randomiserade prövningar kan ge underlag till utvecklingen av bedömningssamtal och IKBT mot antenatal depression. / Antenatal depression (depression during pregnancy) affects 10–20% of pregnant women and involves risks for both the pregnant woman and the child. Research shows that internet-based cognitive behavioral therapy (ICBT) seems to be effective compared to conventional maternity care. The thesis was a correlational predictive study that was conducted within the randomized DANAstudy for ICBT during antenatal depression. An in-group design with repeated measurements was applied in which 40 women with antenatal depression participated. The purpose was to examine (a) patient-satisfaction with the assessment interview in relation to adherence, dropouts and remissionof depressive symptoms during ICBT treatment, and (b) compare changes in depressive symptoms against two previous studies. The result showed that a higher patient-satisfaction with the assessment interview significantly predicted a lesser reduction of depressive symptoms between screening and pre-measurement. No significant correlations were found between patient-satisfaction with the assessment interview and treatment adherence or dropouts. Conclusions should be drawn with great caution based on methodological limitations. The result also showed that depressive symptoms compared with the pre-measurement decreased significantly from the second weekly measurement in the treatment until the post-measurement week ten. This confirmed the results of previous studies. Future randomized trials may provide a basis for the development of assessment interviews and ICBT for antenatal depression.

Few studies have assessed the optimum second line highly active anti-retroviral therapy (HAART) regimen in patients who had failed on the first-line HAART in resource-limited settings. This study aimed to compare the Protease inhibitor (PI)-based second line HAART regimens used in one clinic in Trinidad by comparing immunological, virological and clinical outcomes of patients on the different second line HAART regimens. The records of 35 treatment-experienced patients, over 21years of age and on PI-based regimens for at least six months, were analysed using SPSS version 20. The regimen containing TDF/FTC/AZT/LPV/r proved to produce superior outcomes compared to the other second line regimens. Due the small number of usable patients’ records, the findings cannot be generalised but indicate directions for future studies attempting to compare the treatment outcomes of different second line HAART regimens / Health Studies / M. A. (Public Health)

Introduction : La scoliose idiopathique de l’adolescent (SIA) est une déformation du tronc chez 4 % des 10-18 ans. Le corset est le seul traitement conservateur ayant démontré son efficacité pour limiter sa progression. On note un problème d’adhésion au traitement avec un temps de port moyen de 13 heures/jour (prescription de 22 heures), dont les causes ont été peu étudiées. Objectif et hypothèse : Développer et valider un questionnaire des facteurs liés à l’adhésion au corset. Nos hypothèses sont les suivantes : IMCO aura de bonnes validités de contenu et fiabilité, une validité de construit satisfaisante et pourra discerner les patients adhérents/non-adhérents. Ses scores varieront selon l’âge, l’indice de masse corporelle (IMC) et la sévérité de la courbe. Méthodologie : Un cadre conceptuel intégrateur a été défini. Les items candidats ont été élaborés puis sélectionnés avec les experts. IMCO a été validé avec des jeunes patients traités par corset (n=159) pour tester : la stabilité temporelle (ICC), cohérence interne (alpha Cronbach), validité convergente/divergente (Rho de Spearman) avec deux questionnaires de qualité de vie SF-12 et SRS-22, et capacité discriminante (ANOVA/régression). Résultat/discussion : IMCO comprend 34 items selon 4 barrières à l’adhésion : liées aux facteurs sociaux et émotionnels, au traitement, au patient, et au système de santé. La cohérence interne est excellente (0,89). Les scores IMCO sont associés au temps de port du corset, et varient selon la sévérité de la courbe, l’IMC et l’âge. Les scores sont corrélés avec le domaine satisfaction envers le traitement du SRS-22. Conclusion : IMCO rencontre les critères COSMIN, sauf pour la stabilité temporelle (échantillon inadéquat). Il constitue un instrument approprié pour la recherche. Une analyse factorielle est recommandée pour poursuivre sa validation. / Introduction: Adolescent idiopathic scoliosis (AIS) is a trunk deformity that affects 4% of 10– 18-year olds. The brace is the only effective conservative treatment that has been proven to limit its progression. A treatment adherence problem has been reported with an average wearing time of 13 hours/day (full time bracing prescription of 22 hours), for which underlying causes have been insufficiently studied. Objectives and hypotheses: our goal is to develop and to validate a questionnaire to measure the factors related to brace adherence. Our hypotheses are: The IMCO will display good content validity and reliability, acceptable construct validity, and will be able to discriminate adherent from non-adherent patients. Its scores will vary according to age, body mass index (BMI) and severity of the curve. Methodology: An integrative conceptual framework was defined. Candidate items were developed and selected with experts. The IMCO was validated with young AIS patients (n=159) to test: temporal stability (ICC), internal consistency (alpha Cronbach), convergent/divergent validity (Spearman's Rho) with two quality of life questionnaires SF-12 and SRS-22, and discriminant capacity (ANOVA/regression). Result/discussion: IMCO includes 34 items according to 4 barriers to adherence: related to social and emotional factors, to the treatment, to the patient, and to the health system. Internal consistency is excellent: 0.89. IMCO scores are associated with adherence to treatment, severity of the curve, BMI and age. Scores correlated with the SRS-22 satisfaction with treatment domain. Conclusion: IMCO meets the COSMIN criteria except for temporal stability (inadequate sample). It is an appropriate instrument for research. A factorial analysis is recommended for further validation.

Tidigare forskning visar att det finns ett samband mellan depressionssymtom och svårigheter i partnerrelationer. Forskning visar att deltagare efter parterapi har en ökad grad av relationsnöjdhet och en lägre grad av depressionssymtom. Uppsatsen genomfördes inom DANA-projektet (IKBT vid antenatal depression) och syftet var att analysera hur relationsnöjdhet hänger ihop med behandlingsutfall, följsamhet i behandling samt vilja att arbeta med relationer i behandling. Syftet var även att analysera vilka sociodemografiska och kliniska faktorer hos gravida med depression som har ett samband med relationsnöjdhet. I resultatet framkom inget signifikant samband mellan relationsnöjdhet och behandlingsutfall, följsamhet eller val att arbeta med relationer i behandlingen. I resultatet framkom ett signifikant samband mellan högre relationsnöjdhet och högre ekonomi, högre relationsnöjdhet och högre graviditetsönskan, samt högre relationsnöjdhet och lägre grad av depressionssymtom. För att kunna dra säkrare slutsatser över hur relationsnöjdhet och större fokus på relationer påverkar behandlingsutfall vid depressionsbehandling, behövs fortsatt forskning. Fortsatt forskning behövs även för att undersöka bakomliggande faktorer och hur dessa påverkar paret och deras mående. / Previous research shows a connection between symptoms of depression and difficulties in partner-relations. It also shows that the participants relationship satisfaction increased after couples-therapy and that their symptoms of depression decreased. This thesis was conducted in the DANA-project (ICBT during antenatal depression) and the intention was to examine the effect of relationship satisfaction on treatment outcome, adherence, and motivation to work with relationships in treatment. The intention was also to analyze the connection between relationship satisfaction and sociodemographic and clinical factors during pregnancy. The result presented no significant connection between relationship satisfaction and treatment outcome, adherence, or motivation to work with relationships in treatment. Furthermore, the result presented a significant connection between higher relationship satisfaction and higher economic status, higher relationship satisfaction and higher pregnancy desire and higher relationship satisfaction and lower symptoms of depression. Further research is needed to examine how more focus on relations in treatment and relationship satisfaction effects treatment outcome. Further research is also needed to examine underlying factors and how these effect the couple and their well-being.

No description available.

This study analysed data obtained from respondents and their medical records to determine the barriers and motivators for good adherence to ART. Respondents' records were also reviewed together with their pharmacy refill records to identify any correlation between .CD4 cell counts, viral load, VL and adherence to antiretroviral drugs at extension 15 ARV clinic in Gaborone, Botswana. The study investigated whether the combination of pharmacy refills and pill counts adherence measurement methodologies could predict immunological recovery and virologic response through increased CD4 cell counts and suppressed VL. . There was a positive relationship between adherence, CD4 cell counts and VL. Pharmacy refills and pill counts adherence measurement methodologies scored high on sensitivity, specificity, and positive predictive values but low on negative predictive values. / Health Studies / M.A. (Public Health)

Contexte : Les enfants atteints de maladies chroniques utilisent souvent des médecines complémentaires. Plusieurs études traitent de l’utilisation de ces traitements et des facteurs qui y sont associés chez les enfants atteints d’arthrite juvénile mais aucune étude n’est longitudinale. De plus, aucune n’a documenté l’utilisation de ces traitements chez les enfants ayant des incapacités physiques en attente de services publics de réadaptation. Objectifs : Les objectifs de cette étude étaient de déterminer la fréquence d’utilisation des médecines complémentaires chez les enfants atteints d’arthrite juvénile et d’incapacités physiques, d’évaluer leur efficacité telle que perçue par les parents et d’explorer les facteurs associés à leur utilisation. Méthodes : Une cohorte d’enfants atteints d’arthrite juvénile idiopathique (n=182, âge moyen : 10,2 ans) qui fréquentent des cliniques d’arthrite et une cohorte d’enfants ayant des incapacités physiques en attente de services de réadaptation publics (n=224, âge moyen : 2,6 ans) ont été suivis durant une période d’un an. L’utilisation des médecines complémentaires et la perception de leur efficacité d’après les parents ont été évaluées à l’aide de statistiques descriptives à chaque trois mois pour la cohorte d’enfants atteints d’arthrite et au début de l’étude pour la cohorte d’enfants ayant des incapacités physiques. Les facteurs associés à l’utilisation de ces traitements ont été explorés par des analyses de type GEE (« Generalized estimating equations ») et des régressions polytomique et logistique. Résultats : L’utilisation antérieure de ces médecines était de 51,1% pour les enfants atteints d’arthrite et de 15% pour les enfants ayant des incapacités physiques. Les médecines complémentaires étaient considérées comme étant efficaces dans 72% des cas par les parents d’enfants atteints d’arthrite et dans 83% des cas par les parents d’enfants ayant des incapacités physiques. Les facteurs associés à l’utilisation des médecines complémentaires chez les enfants atteints d’arthrite étaient l’utilisation antérieure des médecines complémentaires par les parents et la perception des parents que les médicaments prescrits ne sont pas utiles pour leur enfant. Chez les enfants ayant des incapacités physiques, les facteurs associés à l’utilisation des médecines complémentaires étaient l’origine culturelle canadienne, un niveau de scolarité plus élevé que le diplôme d’études secondaires et une moins bonne qualité de vie reliée à la santé. Finalement, l’utilisation des médecines complémentaires semblait associée à de moins bons résultats chez les enfants atteints d’arthrite. Conclusion: Une proportion non-négligeable des enfants participant à la présente étude ont utilisé des médecines complémentaires. Leur utilisation était plus fréquente chez les enfants atteints d’arthrite juvénile idiopathique, surtout chez ceux dont les parents avaient déjà utilisé les médecines complémentaires par le passé et chez ceux qui trouvaient la médication peu efficace. Chez les enfants ayant des incapacités physiques, l’utilisation des médecines complémentaires était associée à des facteurs socio-démographiques et à des besoins plus élevés en matière de santé. Les médecines complémentaires étaient considérées comme étant efficaces dans les deux cohortes mais leur utilisation était associée à de faibles résultats chez les enfants atteints d’arthrite. Ces résultats démontrent l’importance d’évaluer l’utilisation des médecines complémentaires afin de mieux renseigner les parents et de les aider à prendre les meilleures décisions possibles concernant le traitement de leur enfant. / Background: Children with chronic diseases often use complementary and alternative health care (CAHC). Several studies described the use of these treatments and the factors associated with it. However, no longitudinal studies were conducted to determine the use of these treatments over time. Furthermore, no study has evaluated CAHC use in children who were waiting for public rehabilitation services. Objective: The aim was to determine the frequency of CAHC use in children with juvenile idiopathic arthritis (JIA) and children with various physical disabilities (PD), to evaluate its effectiveness from the parents’ points of view and to explore the factors associated with their utilization. Methods: A cohort of children with JIA (n=182, mean age: 10.2 years) who attended arthritis clinics and a cohort of children with physical disabilities (n=224, mean age: 2.6 years) waiting for public rehabilitation services were followed for one year. We evaluated the use of CAHC and its effectiveness from the parents’ points of view at three month intervals for children with JIA and at the beginning of the study for children with PD, using descriptive statistics. We explored factors associated with their utilization, using GEE (“Generalized estimating equations »), polytomous and logistic regression. Results : Previous use of CAHC was 51.1% for children with JIA and 15% for children with PD. CAHC was considered beneficial in 72% of the cases by parents of children with JIA and in 83% of the cases by parents of children with PD. Factors associated with higher use of CAHC in children with JIA were previous use of CAHC by parents and lower perceived helpfulness of prescribed medications (p<0.05). In children with PD, factors associated with higher use of CAHC were Canadian cultural background, mother’s level of education higher than high school and lower health-related quality of life. Finally, in children with JIA, CAHC use was associated with worse outcomes. Conclusions: Many children in our study used CAHC. Its use was more common in children with JIA, particularly among those whose parents used it previously and found medications to be less helpful. For children with PD, use of CAHC was associated with socio-demographic factors as well as higher children’s health needs. CAHC were perceived to be beneficial in both cohorts but its use was associated with worse outcomes for children with JIA. This underlines the importance for health professionals to evaluate CAHC use in order to better inform parents, which may help them make the best decisions regarding their child’s treatment.

This study analysed data obtained from respondents and their medical records to determine the barriers and motivators for good adherence to ART. Respondents' records were also reviewed together with their pharmacy refill records to identify any correlation between .CD4 cell counts, viral load, VL and adherence to antiretroviral drugs at extension 15 ARV clinic in Gaborone, Botswana. The study investigated whether the combination of pharmacy refills and pill counts adherence measurement methodologies could predict immunological recovery and virologic response through increased CD4 cell counts and suppressed VL. . There was a positive relationship between adherence, CD4 cell counts and VL. Pharmacy refills and pill counts adherence measurement methodologies scored high on sensitivity, specificity, and positive predictive values but low on negative predictive values. / Health Studies / M.A. (Public Health)

No description available.