From statin efficacy to everyday effectiveness: Studying the gap in between.

Statins are indicated for preventing cardiovascular disease events. Patients with diabetes have a risk of major cardiovascular events double the risk of their peers without diabetes. Thus, clinical treatment guidelines recommend statins for the management of diabetic dyslipidemia. The evidence base for statin use in cardiovascular disease derives from the randomized controlled statin trials designed to prove statin efficacy under ideal conditions, among a homogenous study population meeting strict trial eligibility criteria. This thesis was implemented as four pharmacoepidemiological statin studies using register data on realworld statin users. The overall purpose was to evaluate the trends, patterns and effectiveness of statin use in everyday life. More specifically, nationwide secular trends in statin use in Finland were analysed, especially among patient groups which had been underrepresented in the statin trials. Furthermore, the benchmarking statin trials in diabetes, the Heart Protection Study and the Collaborative Atorvastatin Diabetes Study, were evaluated for their representativeness for real-world diabetes care with the emphasis placed on adherence to statin use. The association between good adherence and the incidence of major cardiovascular events in the real-world was further investigated in diabetes. These studies demonstrate that statin initiations increased from 1995 to 2005 in Finland. The increase was most pronounced among those aged at least 75 years and was observed already before the publication of rigorous trial data conducted in elderly subjects. Thus, statins seem to have been initiated in clinical practice also going beyond the strict trial eligibility criteria. Nonetheless, low adherence to statin use among the real-world patients with diabetes was found not only to limit the representativeness of the trials for clinical care but also to attenuate in all likelihood their benefits in the real-world. In fact, good adherence to statin use was found to associate with a decreased risk for major cardiovascular events in patients with diabetes. In conclusion, these studies highlight the importance of good adherence to statin use in clinical practice in order to obtain the full therapeutic value demonstrated in the statin trials. Simply increasing the number of statin users will not alone suffice in sharing our common resources appropriately.

High incidence of adverse reactions to initial antiretroviral therapy in Brazil

A concurrent prospective study was conducted from 2001 to 2003 to assess factors associated with adverse reactions among individuals initiating antiretroviral therapy at two public referral HIV/AIDS centers in Belo Horizonte, MG, Brazil. Adverse reactions were obtained from medical charts reviewed up to 12 months after the first antiretroviral prescription. Cox proportional hazard model was used to perform univariate and multivariate analyses. Relative hazards (RH) were estimated with 95% confidence intervals (CI). Among 397 charts reviewed, 377 (95.0%) had precise information on adverse reactions and initial antiretroviral treatment. Most patients received triple combination regimens including nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. At least one adverse reaction was recorded on 34.5% (N = 130) of the medical charts (0.17 adverse reactions/100 person-day), while nausea (14.5%) and vomiting (13.1%) were the most common ones. Variables independently associated with adverse reactions were: regimens with nevirapine (RH = 1.78; 95% CI = 1.07-2.96), indinavir or indinavir/ritonavir combinations (RH = 2.05; 95% CI = 1.15-3.64), female patients (RH = 1.93; 95% CI = 1.31-2.83), 5 or more outpatient visits (RH = 1.94; 95% CI = 1.25-3.01), non-adherence to antiretroviral therapy (RH = 2.38; 95% CI = 1.62-3.51), and a CD4+ count of 200 to 500 cells/mm³ (RH = 2.66; 95% CI = 1.19-5.90). An independent and negative association was also found for alcohol use (RH = 0.55; 95% CI = 0.33-0.90). Adverse reactions were substantial among participants initiating antiretroviral therapy. Specially elaborated protocols in HIV/AIDS referral centers may improve the diagnosis, management and prevention of adverse reactions, thus contributing to improving adherence to antiretroviral therapy among HIV-infected patients.

From genotype to phenotype : diversity and population structure of Flavobacterium psychrophilum

Flavobacterium psychrophilum is the etiological agent of bacterial cold-water disease (BCWD) causing high fish mortalities and significant economic losses to the freshwater salmonid aquaculture industry around the world. Today BCWD outbreaks are mainly treated with environmentally hazardous antimicrobial agents and alternative preventative measures are urgently needed in order to ensure the well-being of animals and the sustainability of aquaculture. The diversity of pathogenic bacteria challenges the development of universal control strategies and in many cases the pathogen population structure, i.e. the total genetic diversity of the species must be taken into account. This work integrates the tools of modern molecular biology and conventional phenotypic microbiology to gain knowledge about the diversity and population structure of F. psychrophilum. The present work includes genetic characterization of a large collection of isolates collected from diverse origins and years, from aquaculture in a whole region including different countries, and provides the first international validation of a universal multilocus sequence typing (MLST) approach for unambiguous genetic typing of F. psychrophilum. Population structure analyses showed that the global F. psychrophilum population is subdivided into pathogenic species-specific clones, of which one particular genetic lineage, clonal complex CC-ST2, has been responsible for the majority of BCWD outbreaks in rainbow trout (Oncorhynchus mykiss) in European aquaculture facilities over several decades. Genotypic and phenotypic population heterogeneity affecting antimicrobial resistance in F. psychrophilum within BCWD outbreaks was discovered. Specific genotypes were associated with severe infections in farmed rainbow trout and Atlantic salmon (Salmo salar), and in addition to high adherence, antimicrobial resistance was strongly associated with outbreak strains. The study brought additional support for the hypothesis of an epidemic F. psychrophilum population structure, where recombination is an important force for the generation and maintenance of genetic diversity, and a significant contribution towards mapping the genetic diversity of this important fish pathogen. Evidence indicating dissemination of virulent strains with commercial movement of fish and fish products was strengthened.

Psykoosipotilaille tarkoitetun sähköisen potilasopetusmentelmän levitys ja mielenterveystyön ammattilaisten kokemuksia käytöstä

Tämän laadullisen tutkimuksen tarkoituksena oli kuvata psykoosipotilaille tarkoitetun sähköisen potilasopetusmentelmän (MieliNet) levitystä sekä sosiaali- ja terveydenhuollon psykiatristen toimintayksiköiden mielenterveystyön ammattilaisten kokemuksia sähköisen potilasopetusmenetelmän käytöstä. Tutkimuksen tavoitteena on saatavan tiedon avulla kehittää edelleen MieliNet-ohjelman hyödynnettävyyttä psykiatrisessa hoitotyössä. Tutkimusaineisto kerättiin kolmessa vaiheessa. Ensimmäisessä vaiheessa selvitettiin sosiaali- ja terveydenhuollon psykiatristen toimintayksiköiden (n = 125) kiinnostusta tutustua sähköiseen potilasopetukseen. Potilasopetuksesta kiinnostuneiden organisaatioiden (n = 16) taustatiedot kuvattiin sekä selvitettiin mielenterveystyön ammattilaisten (n = 41) halukkutta tutustua MieliNet-sivustoon ja osallistua sähköisen potilasopetuksen verkkokurssille. Toisessa ja kolmannessa vaiheessa aineisto kerättiin sähköiselle moodle-alustalle sähköisen potilasopetusmenetelmän koekäyttäjiltä (n=7). Aineisto analysoitiin induktiivista ja deduktiivista sisällön analyysiä käyttäen. Tutkimustulosten mukaan sähköisestä potilasopetusmenetelmästä kiinnostuneiden organisaatioiden osuus oli 4% niistä organisaatioista, joille tiedon levitys tapahtui. Sähköisen potilasopetusmenetelmän koekäyttäjistä valtaosa työskenteli erikoissairaanhoidossa toimivissa aikuispsykiatrian avohoidon yksiköissä. Sähköisen potilasopetusmenetelmän käytön vahvuuksina koettiin potilasopetuksen tehostuminen, omahoitajasuhteen kehittyminen ja potilaiden lisääntynyt hoitoon sitoutuminen. Heikkouksina koettiin ongelmat sähköisen potilasopetusohjelman käytössä ja ennakkoluulot sähköisen potilasopetusohjelman käytöstä sekä potilaiden psyykkisen voinnin heikentyminen. Mahdollisuuksina koettiin potilasopetuksen tehostuminen ja potilasopetusohjelman uudet käyttömahdollisuudet. Uhkina koettiin sähköisen potilasopetusmenetelmän riittämätön arvostus sekä ongelmat ja ennakkoluulot potilasopetusohjelman käytössä. Potilaiden yksilöllisyys huomioitiin hyvin potilasopetustilanteissa. Sähköinen potilasopetusmenetelmä synnytti keskustelua potilaille tärkeistä asioista. Potilasopetustilanteiden sujuminen, potilaiden asenne ja oma osaaminen aiheuttivat huolta. Potilasopetustilanteisiin valmistautumiseen halutaan jatkossa kiinnittää enemmän huomiota.

Measurement of annexin V uptake and lactadherin labeling for the quantification of apoptosis in adherent Tca8113 and ACC-2 cells

Phosphatidylserine (PS) exposure occurs during the cell death program and fluorescein-labeled lactadherin permits the detection of PS exposure earlier than annexin V in suspended cell lines. Adherent cell lines were studied for this apoptosis-associated phenomenon to determine if PS probing methods are reliable because specific membrane damage may occur during harvesting. Apoptosis was induced in the human tongue squamous carcinoma cell line (Tca8113) and the adenoid cystic carcinoma cell line (ACC-2) by arsenic trioxide. Cells were harvested with a modified procedure and labeled with lactadherin and/or annexin V. PS exposure was localized by confocal microscopy and apoptosis was quantified by flow cytometry. The detachment procedure without trypsinization did not induce cell damage. In competition binding experiments, phospholipid vesicles competed for more than 95 and 90% of lactadherin but only about 75 and 70% of annexin V binding to Tca8113 and ACC-2 cells. These data indicate that PS exposure occurs in three stages during the cell death program and that fluorescein-labeled lactadherin permitted the detection of early PS exposure. A similar pattern of PS exposure has been observed in two malignant cell lines with different adherence, suggesting that this pattern of PS exposure is common in adherent cells. Both lactadherin and annexin V could be used in adherent Tca8113 and ACC-2 cell lines when an appropriate harvesting procedure was used. Lactadherin is more sensitive than annexin V for the detection of PS exposure as the physical structure of PS in these blebs and condensed apoptotic cell surface may be more conducive to binding lactadherin than annexin V.

Potential pathogenic role of aggregative- adhering Corynebacterium diphtheriae of different clonal groups in endocarditis

Invasive diseases caused by Corynebacterium diphtheriae have been described increasingly. Several reports indicate the destructive feature of endocarditis attributable to nontoxigenic strains. However, few reports have dealt with the pathogenicity of invasive strains. The present investigation demonstrates a phenotypic trait that may be used to identify potentially invasive strains. The study also draws attention to clinical and microbiological aspects observed in 5 cases of endocarditis due to C. diphtheriae that occurred outside Europe. Four cases occurred in female school-age children (7-14 years) treated at different hospitals in Rio de Janeiro, Brazil. All patients developed other complications including septicemia, renal failure and/or arthritis. Surgical treatment was performed on 2 patients for valve replacement. Lethality was observed in 40% of the cases. Microorganisms isolated from 5 blood samples and identified as C. diphtheriae subsp mitis (N = 4) and C. diphtheriae subsp gravis (N = 1) displayed an aggregative adherence pattern to HEp-2 cells and identical one-dimensional SDS-PAGE protein profiles. Aggregative-adhering invasive strains of C. diphtheriae showed 5 distinct RAPD profiles. Despite the clonal diversity, all 5 C. diphtheriae invasive isolates seemed to display special bacterial adhesive properties that may favor blood-barrier disruption and systemic dissemination of bacteria. In conclusion, blood isolates from patients with endocarditis exhibited a unique adhering pattern, suggesting a pathogenic role of aggregative-adhering C. diphtheriae of different clones in endocarditis. Accordingly, the aggregative-adherence pattern may be used as an indication of some invasive potential of C. diphtheriae strains.

Effect of incorporation of amaranth on the physical properties and nutritional value of cheese bread

At the present celiac disease has no known cure, and its only treatment is a strict lifelong adherence to a gluten-free diet. Cheese bread is a traditional Brazilian product and a safe option for celiacs. However, like other gluten-free breads, it has inherent low levels of fibers and minerals. The objective of this study was to evaluate the effect of incorporation of whole amaranth flour on the physical properties and nutritional value of cheese bread. Amaranth flour was incorporated at 10, 15, and 20% proportions in different formulations. The increasing amaranth levels darkened the product, reduced specific volume, and increased compression force. Ten percent amaranth-content cheese breads exhibited slight differences in physical properties compared with the controls. These results demonstrated the possibility of incorporating 10% of whole amaranth flour in the formulation of cheese bread resulting in a product with higher dietary fiber and iron contents and the same level of acceptance as that of the conventional formulation. The aim of this approach is to increase the availability of gluten-free bakery products with added nutritional value contributing to increase the variety of the diet of celiac patients.

Purple urine bag syndrome in end-stage chronic kidney disease

Introduction: When faced with violet, purple or purplish-blue urine, clinicians should consider urinary tract infection in their differential diagnosis. Case report: A 60-year-old woman with end-stage kidney disease and non-adherence to renal replacement therapy was admitted to our hospital for placement of hemodialysis catheter. During her hospitalization she had purple urine, and purple urine bag syndrome (PUBS) was diagnosed. She was effectively treated with antibiotics and her urine returned to a dark yellow color. Discussion: Although this condition is often easily treated, diagnosing PUBS in chronic renal patients probably means an increased serum concentration of indoxyl sulfate, metabolite that is involved in the progression of both CKD and cardiovascular disease. Conclusion: Hence, in the context of our renal patients, perhaps PUBS is not as benign as supposed.

Cholesterol, cardiovascular disease and statin use in older persons

Older age increases the risk of developing a chronic atherosclerotic cardiovascular disease (CVD), such as coronary heart disease. Complications of CVDs, myocardial infarction or stroke often lead to loss of functional capacity or premature death. Dyslipidemia, high serum levels of total or low-density lipoprotein cholesterol (LDL-c) and low levels of high-density lipoprotein cholesterol (HDL-c), is among the most important modifiable risk factors for CVDs; it can be treated with lifestyle modifications, and with lipid-lowering drugs, primarily statins. In older persons, however, the association of cholesterol levels with cardiovascular and all-cause mortality has been inconsistent in previous studies. Furthermore, the beneficial effects of statins in older persons without previous CVD are still somewhat unclear, and older persons are more prone to adverse effects from statins. This thesis presents a prospective cohort study (TUVA), exploring associations of cholesterol levels with mortality and the changes in cholesterol levels of a 70-year-old population in long-term follow-up. Further, prevalence of CVDs, risk factors and preventive medication use in the TUVA cohort is compared with respective prevalences in another age-matched cohort (UTUVA) 20 years later in order to examine the changes in cardiovascular risk over time. Additionally, to evaluate statin use patterns among older persons, an observational register study was conducted covering the total Finnish population aged 70 and older during 2000-2008. Based on individual-level data retrieved from national health registries, the population was classified into low, moderate and high risk groups according to estimated CVD risk. The prevalence, incidence and persistence of statin use among the risk groups was then evaluated based upon yearly statin purchases tracked from the Prescription Register. The prospective cohort study demonstrated that low total cholesterol, LDL-c and HDL-c were associated with higher mortality in a cohort of home-dwelling 70-year-olds. However, after adjusting for traditional cardiovascular risk factors and cancer this association disappeared. Further, low total cholesterol seemed to be protective, whereas low HDL-c strongly predicted increased risk of CVD death. Cholesterol levels of those elderly who remained available for follow-up and were still home-dwelling at the age of 85 seemed to improve with advancing age. Compared to the TUVA cohort, the later born UTUVA cohort had less CVDs and their risk factors were better controlled, which was reflected in the higher use of preventive medications such as statins and antihypertensives. The register studies confirmed that statin use has increased significantly during 2000-2008 among older persons, especially among the oldest (80+) age groups and among those at high risk for cardiovascular events. Two-thirds of new statin users persisted with their use during the four years of follow-up; the most discontinuations were made during the first year of use. In conclusion, statins are commonly used among older age groups in Finland. Most of the older statin users had a high cardiovascular event risk, indicating that the treatment is well directed towards those who are likely to benefit from it the most. No age-limits should be put on the screening and treatment of dyslipidemia in older persons, but the benefits and adverse effects of statin treatment should be carefully weighed based on an individual assessment of the person’s general health status and functional capacity. Physicians should pay more attention to medication adherence, especially when prescribing preventive medications.

A physical activity intervention in a workplace setting

Physical inactivity poses a huge burden on Canada's health care system and is detrimental to the health of Canadians (Katzmarzyk & Janssen, 2004). Walking is a viable option for individuals to become physically active on a daily basis and is in fact the most commonly reported leisure time physical activity. It has been associated with many health benefits including weight loss/weight control, reduced risk of coronary artery disease and diabetes, lowered blood pressure, and improved psychological wellbeing (Brisson & Tudor-Locke, 2004). Specifically, individuals' stage of change, selfefficacy and health related quality of life (HRQL) are three psychological constructs that can be greatly improved with increased physical activity (Dishman, 1991; Penedo & Dahn, 2005; Poag & McAuley, 1992). Public health physical activity recommendations exist but many individuals find these difficult to meet due to overly busy lifestyles (Public Health Agency of Canada, 2003). Pedometers are inexpensive devices that can monitor individual bouts of walking so that the incorporation of physical activity into one's daily life is more plausible. They are also excellent tools for motivation, goalsetting, and immediate feedback (Brisson & Tudor-Locke, 2004). Since many people spend a large proportion of their time at their places of employment, workplaces have begun to be a common site for the development of physical activity interventions. These programs have been growing in popUlarity and have shown numerous benefits for both employees and employers (Voit, 2001). The purpose of the current study was to implement and evaluate the use of a pedometer-based physical activity intervention incorporating goal-setting and physical activity logs in a workplace setting, and to examine the relationship between different types of self-efficacy (task, barrier, and scheduling) and different phases of the intervention. Twenty male participants from a local steel manufacturing plant who exhibited health risk factors (e.g. hypertension, diabetes, etc.) were assigned to one of two groups (group A or group B). All participants were asked to wear pedometers on their waists, record their daily steps, set goals that were outlined on a step-tracking sheet (detennined by their baseline number of steps), and keep track of their work days, wakelbed time, sedentary time, and time spent doing other physical activity. Group A began the intervention immediately following the baseline measures, whereas group B continued with their regular routine for 4 weeks before beginning. Physiological measures (height, weight, blood pressure, relative body fat, waist and hip circumference, and body mass index) were taken and a battery of questionnaires that assessed barrier, task and scheduling self-efficacy, HRQL, and stage of change administered at baseline, week 5 (end of intervention for group A), week 9 (end of intervention for group B; follow-up for group A) and week 13 (follow-up for both groups). Results showed that this workplace physical activity intervention was successful at increasing the participants' daily steps, that task self-efficacy is a significant predictor of participants' exercise adherence during the initial stages of participation (intervention phase), and that the participants felt that this intervention was effective. Finally, further exploratory analyses showed that this intervention was effective for all participants, but most valuable for participants most in need of improvement - that is, those who were most sedentary prior to the intervention. This intervention is an inexpensive use of simple and effective tools (e.g. pedometers), has the potential to attract a wide variety of participants and become a pennanent part of any health promotion initiative.

Overcoming victim behaviour through physical education

This study presents infonnation gathered during personal interviews in which participants were asked how they, as physical educators, might possibly assist the victim of bullying through their programs. The research is a qualitative study, using an inductive approach. Five participants were chosen, based on convenience sampling, with semi-structured interviews which were audio recorded. The theoretical research found that the most stable characteristics of victimized boys were lack of strength and lack of physical fitness. This suggested that Physical Education class might be the best place in which to empower victimized students to reduce their own victimization by addressing these areas of strength and fitness. From the interviews it became clear that, while these educators showed a willingness to help bullying victims through their programs, their adherence to a Physical Education model based primarily on elitism, as opposed to individual fitness, would make it difficult for them to do so effectively.

Self-Esteem and Mastery in Maintenance Cardiac Rehabilitation

Background: CVD is the second leading cause of death in Canada. Mastery and self-esteem are psychosocial factors, suggested to be emerging risk factors for CVD. Purpose: The purpose of the study was two-fold; first to establish whether mastery and self-esteem predicted adherence to maintenance CR; and second, whether mastery and self-esteem improved after a 6-month maintenance CR program. Methods: Data were collected at the Brock University Heart Institute. The study involved a sample of 98 participants. At intake to the program and 6-month follow-up, participants completed a questionnaire battery which included the Rosenberg Self-Esteem Scale and the Pearlin-Schooler Mastery Scale. Results: Mastery and self-esteem scores did not alter the likelihood of adherence to the CR program. Mastery and self-esteem did significantly improve after 6-months of CR amongst participants with the lowest exercise capacity. Conclusion: Maintenance CR does improve mastery and self-esteem amongst those with diminished exercise capacity.

Clinician-Perceived Bridges and Barriers to Parental Implementation of Picture Exchange Communication System (PECS): An evaluation.

Picture Exchange Communication System (PECS) is an augmentative and alternative communicative system that improves communication and decreases problem behaviors in children with Developmental Disabilities and Autism. The mediator model is a validated approach that clinicians use to train parents to perform evidence-based interventions. Parental non-adherence to treatment recommendations is a documented problem. This qualitative study investigated clinician-perceived factors that influence parental adherence to PECS recommendations. Three focus groups (n=8) were conducted with Speech Language Pathologists and Behavior Therapists experienced in providing parents with PECS recommendations. Constant comparison analysis was used. In general, clinicians believed that PECS was complex to implement. Thirty-one bridges were identified to overcome complexity. Twenty-two barriers and 6 other factors also impacted parental adherence. Strategies to address these factors were proposed based on a review of the literature. Future research will be performed to validate these findings using parents and a larger sample size.

Can a Manipulated Mind Alter Matter? : The Effects of Verbal Feedback on Self-Efficacy, Exercise Intention, and Exercise Behaviour among Low-Active College-Aged Women

Self-efficacy (SE), a person’s confidence in the ability to perform a task, is an important predictor of the adoption and maintenance of physical activity. The present study examined the effects of SE manipulated through verbal persuasion on exercise intentions and behaviour during a 4-week follow-up period and investigated the role of social physique anxiety (SPA) as a moderator. Female college infrequent exercisers (n = 66) were randomly assigned into one of three groups (high-efficacy [HE], low-efficacy [LE], or control) and asked to complete several questionnaires at baseline. The HE and LE groups were provided with positive and negative exercise adherence feedback, respectively. The HE group reported higher SE from pre- to post-feedback. Both the HE and LE groups reported increases in exercise behaviour at the 4-week follow-up. Pre- to post-feedback changes in SE, exercise intention, and exercise behaviour did not depend on level of SPA reported.

Bridging the Conceptualization of Youth with Intellectual Disabilities to Sentencing under the YCJA

The current study examined how disability and the concepts of risk, need and responsivity are understood by criminal justice professionals and inform their perceptions of young offenders with ID at sentencing under the ‘different but equal’ philosophy. Semi-structured interviews were conducted with 11 lawyers and 8 mental health workers across 6 major urban areas in Ontario. Participants primarily perceived ID through a medical discourse, overlooking social and structural barriers that, in some cases, may hinder adherence to sentencing dispositions. Specifically, participants discussed balancing the reduced culpability of offenders (e.g., intent) – justifying lenient sentencing – with public safety concerns (i.e., ID viewed as a barrier to rehabilitation) – justifying increasing the severity of sentences. Participants assessed clients with ID and their risks, needs and responsivity within the context of other legal factors: criminal history, severity of the offence, and YCJA objectives. Participants articulated the importance of tailored courthouse identification programs, services/funding, and education/training.