Background: Opioid use disorder (OUD) has been an increasing concern in Canada as mortality rates continue to rise. Though OUD treatments, such as methadone maintenance treatment (MMT), reduce its burden, they could potentially cause harm due to OUD’s variance in severity and presentation across individuals. It is hypothesized that genetic variants such as single nucleotide polymorphisms (SNPs) could predispose patients to respond differently to MMT. In addition, sex differences have been observed in opioid use patterns, treatment outcomes, and genetic make-up. As such, this thesis aims to identify significant SNPs associated with treatment outcomes in genome-wide association studies, and test biologically relevant SNPs with MMT outcomes of interest, while highlighting sex differences. This is achieved through a systematic review protocol, a systematic review, and a candidate gene study. Methods: A protocol was prepared for the planning of the first ever systematic review of genome-wide significant findings of medication-assisted treatment outcomes for OUD patients. The systematic review assessed the literature findings and study qualities, narratively summarizing significant associations. Next, a candidate gene study analyzed the association between SNPs in OPRM1 and CYP2B6 genes, and continued opioid use, relapse, and methadone dose within an ancestrally European sample (n=1226). Sex-stratified and sex-interaction analyses were also conducted. Results: The systematic review included 5 studies and qualitatively assessed 43 unique genetic variants. The candidate gene study showed no significant associations between the selected OPRM1 and CYP2B6 SNPs and outcomes of interest. While no significant differences between the sexes were observed, rs73568641 and rs3745274 showed near significance associations in only one sex, females, and males, respectively. Discussion: Through the study of genetic variants associated with treatment outcomes in the literature and our sample of ancestrally European individuals on MMT, we were able to highlight gaps in pharmacogenetics research and identify areas of focus for future studies. / Thesis / Master of Science (MSc) / Recently, opioid use disorder (OUD) has been declared a national crisis in Canada. OUD treatments are helpful in reducing opioid use and adverse events. However, their dosing and metabolism in patients can impact continued opioid use, relapse, or treatment dose changes. Due to the variability in response between individuals, there might be a genetic basis to treatment outcomes. This thesis explores which genetic variants reported in previous studies are involved in OUD treatment outcomes. Then, it tests select genetic variants in OPRM1 and CYP2B6 genes to see if they are linked to specific outcomes in an Ontario population and tries to identify if these associations differ by sex. No significant associations were found, though associations in males and females had near-significant results in one sex but not the other. Despite suggesting sex’s possible involvement in treatment outcomes, more research is necessary to confirm these findings.

Anxiety is one of the most common mental health disorders in the U.S. and is becoming increasingly common and problematic for college students across the country. Building on research conducted at single universities, we used a large national data set from the Center for Collegiate Mental Health (CCMH) and compared self-reported levels of anxiety amongst various groups of college students across the U.S., as well as the prevalence of comorbidity between anxiety reported on the generalized anxiety subscale of the Counseling Center Assessment of Psychological Symptoms (CCAPS) and other mental health concerns. We found that a number of self-reported variables (e.g., considered attempting suicide, experienced traumatic event, non- suicidal self-injury, etc.) on the CCAPS had a positive correlation with anxiety levels at intake. Interestingly, we found that those who participated in organized college athletics and those who are international students were found to have lower anxiety at intake than others. We further found that participants from certain demographic backgrounds had higher levels of anxiety than others. Notably, participants who reported they were born female had higher levels of anxiety than those born male. Similarly, women and transgender individuals had higher anxiety levels than men, and those who self-identified their gender identity had higher anxiety scores than women, men, and transgender individuals. Our results also indicate that, at intake, those who self-identified in their sexuality and identified as bisexual reported the highest levels of anxiety compared to those who identified as lesbian, questioning, gay, or heterosexual. Our model, which contained the variables sexual orientation, gender identity, marijuana use, experienced traumatic event, considered attempting suicide, non-suicidal self-injury, current financial situation, prescribed medication for mental health concerns, and emotional support from social network, was the best fit that most parsimoniously described which variables had the greatest impact on anxiety levels at intake. Finally, our results indicate that there is a relationship between generalized anxiety symptoms and other presenting concerns (distress, depression, social anxiety, hostility, eating concerns, substance use). Given our study's large sample size, we provide more generalizable data than single university studies and provide clinical and research recommendations.

The present studies attempted to clarify the constructs of self-efficacy and outcome expectancies in relation to college student drinking. In study 1, heavy-drinking college students were asked for efficacy judgments for limiting their heavy-drinking for increasing periods of time (e.g. 1 day, 1 week, 1 month, etc.). Students were also asked for efficacy judgments for throwing a basketball into a hoop from increasing distances (e.g. 5 feet, 10 feet, 15 feet). Hypothetical incentives were offered to change efficacy ratings for the first tasks on each hierarchy (limiting drinking and basketball) to which the participant had responded with a negative efficacy judgments. Hypothetical incentives were also offered for the most difficult task on each hierarchy. As predicted, students changed efficacy ratings for limiting drinking much more frequently. Additionally, heavy-drinking college students indicated that money persuaded them to alter their efficacy judgments for limiting drinking, but lack of ability predominated as the reason for not altering basketball task efficacy. In study 2, the relationship between ability judgments, willingness, and outcome expectancies was explored by manipulating the wording of questionnaires presented to heavy-drinking college students. Results indicated that ability judgments were higher than willingness judgments for limiting drinking. Willingness appeared to be related to expected positive and negative effects of consuming alcohol. Principle components analysis indicated that ability and willingness were distinct constructs. Results of both studies are discussed in terms of the ongoing debate between Albert Bandura and Irving Kirsch and the need for a more clarity regarding efficacy and its measurement. / Master of Science

Self-efficacy for avoiding alcohol use predicts alcohol use after treatment. However, self-efficacy predicts outcome differentially depending on whether ratings are made before or after treatment. In order to increase the predictive validity of self-efficacy judgments, the hypothesized sources of self-efficacy were examined in the current study utilizing a college student population. Self-efficacy ratings for avoiding heavy drinking before and after self-monitoring of drinking behavior were examined in order to understand whether careful examination of current behavior would result in more informed self-efficacy judgments. Participants (N = 135) completed questionnaires that assessed self-efficacy, drinking behaviors, alcohol expectancies, and perceived normative alcohol use. Participants were assigned to either the control or self-monitoring condition. Self-monitors recorded drinking behaviors during the four weeks after the baseline assessment. All participants returned for a follow-up assessment four weeks later. Consistent with predictions based on social cognitive theory, heavy drinking, positive alcohol expectancies, and perceived norms of use were inversely related to self-efficacy. Hierarchical multiple regression analyses indicated that self-monitoring did not lead to stronger relationships between source variables and self-efficacy. Individuals who appeared to be overconfident in their self-efficacy judgments at baseline did not make more accurate ratings as a result of self-monitoring. Results from this study highlight potential sources of information individuals use in making self-efficacy judgments. / Master of Science

Economic justification for rehabilitative services has resulted in the need for outcome based research which could quantify success or failure in individual patients and formulate baseline variables which could predict outcomes. The purpose of this study is to investigate the utilization of baseline clinical, exercise test, and psychosocial variables to predict clinically relevant changes in exercise tolerance of cardiac patients who participated in early outpatient cardiac rehabilitation. Clinical records were analyzed retrospectively to obtain clinical, psychosocial and exercise test data for 94 patients referred to an early outpatient cardiac rehabilitation program at a large urban hospital in the Southeast US. All patients participated in supervised exercise training 3d/wk for 2-3 months. A standardized training outcome score STO) was devised to evaluate training effect by tabulating changes in patients predicted VO2, body weight and exercising heart rates after 8-12 weeks of exercise based cardiac rehabilitation. STO = Predicted VO2 change + BW change- HR change. The Multi-Factorial Analysis was applied to derive coefficients in the STO formula so that the STO scores reflected the independent effects of BW, HR and Predicted V02 changes on training outcome. Patients were classified into one of three possible outcome categories based on STO scores, i.e. improvement, no change, or decline. Thresholds for classifying patients were the following; STO scores greater than or equal to 3 SEM above the mean = improved, (N= 40: 41%), STO scores less than or equal to 3 SEM below the mean = decline, (N=34: 35%), STO scores within 3 SEM= no change, (N=23: 24%). Multiple logistic regression was used to identify patient attributes predictive of improvement, decline, or no change from measures routinely collected at the point of admission to rehabilitation. The model for prediction of improvement correctly classified 70% of patients as those who improved vs. those who did not (sensitivity 70%, specificity 71%). This model generated the following variables as having predictive capabilities; recent CABG, emotional status, social status, calcium channel blocker, recent angioplasty, maximum diastolic BP, maximum systolic BP and resting systolic BP. The model for predicting those who declined vs. those who did not decline demonstrated higher correct classification rate of 74% and specificity (84%). This model generated the following variables as having predictive capabilities; social status, calcium channel blocker, orthopedic limitation, role function, QOL score and Digitalis. However, these models may include certain bias because the same observations to fit the model were also used to estimate the classification errors. Therefore, cross validation was performed utilizing the single point deletion method; this method yielded somewhat lower fraction correct classification rates (66%,69%) and sensitivity rates (56%,44%) for improvement vs. no improvement and decline vs. no decline groups respectively. Conclusion A combined set of baseline clinical, psychosocial and exercise measures can demonstrate moderate success in predicting training outcome based on STO scores in hospital outpatient cardiac rehabilitation. In contrast psychosocial data seem to account for more of the variance in prediction of decline than other types of baseline variables examined in this study. Baseline blood pressure responses both at rest and during exercise were the greatest predictors of improvement. However, cross validation of these models indicates that these results could be biased eliciting overly optimistic predictive capabilities, due to the analysis of fitted data. These models need to be validated in independent sample with patients in similar settings. / Master of Science

Distal radius fracture (DRF) is the most common fracture encountered in clinical practice. Every year, more than 20000 people in Sweden suffer from this injury. It has been shown that there is a correlation between malalignment and function following distal radial fractures and malunion may cause persistent pain and disability. A problem has been in making a correct initial assessment of the fracture. Many fractures are unstable despite an acceptable position on the initial radiographic examination or following a successful closed fracture reduction. Numerous classification systems have been developed for evaluation of DRF in order to predict the outcome. However, the values of these are limited since they have not shown satisfactory reliability. Furthermore, the utility of these systems to predict radiographic or clinical outcome is not yet proven. These shortcomings may be one reason why optimal DRF management is still controversial. Requests for a new classification system of DRF, predictive of outcome and easy to use, have been made. Improvement in initial assessment of DRF will benefit a large group of patients, as well as the society, by reducing persistent symptoms and disability. Study I: In this study we evaluated the interobserver and intraobserver reliability of a new classification system (the Buttazzoni classification). Two hundred and thirty-two patients with acute DRF were blindly evaluated using the new classification by three orthopaedic surgeons twice with a 1-year interval. The new classification showed fair to substantial interobserver and intraobserver reliability, i.e., results comparable with other commonly used classification systems. Study II: This was a prospective multicenter study of fracture stability in 428 DRF. The study investigated whether cortical comminution and intra-articular involvement, as well as the new classification system, could predict displacement in DRF. Logistic regression analysis showed that initial position of the fracture and volar or dorsal comminution predicted later displacement, while intra-articular involvement did not. Volar comminution was the strongest predictor of displacement. The new classification system, which is the first to include volar comminution as a separate parameter, was highly predictive of fracture instability. Furthermore we found that it is quite common for non-operatively treated fractures to displace at a later stage than two weeks. Study IV: In study II it was found that late displacement of DRF, still in acceptable radiologic position after 10-14 days, occurred in approximately 1/3 of cases. Despite this, we have not been able to find any study focusing on evaluating the clinical outcome in patients with late displacement. Two hundred and nine unilateral DRF from study II were still in good position after 10-14 days and were included in the study. One hundred and seventy five patients had radiographs taken at a minimum of 3 months and a clinical examination 1 year after the fracture. Late displaced distal radius fractures had significantly higher loss of ROM and grip strength compared to fractures that didn’t displace. No significant differences were seen in subjective outcome. In conclusion, initial position of the fracture predicted later displacement and was the most important parameter in predicting clinical outcome. Comminution of the fracture also affected radiological stability and clinical outcome. Volar comminuted fractures are highly unstable and need surgical intervention if displacement is to be avoided. Intra-articular involvement affected clinical outcome. Late displacement is common in DRF and may result in loss of range of motion and grip strength. To detect late displacement, DRF should be followed for more than 2 weeks. The new classification system had a moderate reliability and reproducibility. The classification was found predictive of radiologic and objective clinical outcome. However, it was not predictive of subjective outcome. The classification system was also predictive of fractures at risk for late displacement.

Bakalauro baigiamajame darbe yra analizuojamos neigiamos nedarbo pasekmės ekonominėje ir socialinėje srityje. Darbas susideda iš dviejų dalių. Teorinėje darbo dalyje nagrinėjami Lietuvos ir užsienio šalių autorių moksliniai straipsniai apie neigiamas nedarbo pasekmes įvairiems ekonominiams ir socialiniams rodikliams. Empirinėje darbo dalyje analizuojama 1998-2009 m. laikotarpio Lietuvos statistinė informacija apie nedarbo lygį ir tam tikrus ekonominius (bendrajį vidaus produktą, vidutinę metinę infliaciją, emigrantų skaičių, vidutinį mėnesinį Bruto darbo užmokestį, biudžeto pajamas iš gyventojų pajamų mokesčio, valdžios sektoriaus išlaidas, susijusias su nedarbu) ir socialinius (apsilankymų pas gydytojus, mirusiųjų nuo kraujotakos sistemos ligų ir savižudybių skaičių, skurdo rizikos lygį bei užregistruotų nusikaltimų skaičių) rodiklius. Taip pat, bandoma nustatyti, kuriems ekonominiams ir socialiniams rodikliams nedarbas turi neigiamą poveikį ir kuriuo laikotarpiu šis poveikis didžiausias - bendruoju, nedarbo mažėjimo ar didėjimo laikotarpiu. / In Bachelor‘s final work, the negative impacts of unemployment on economic and social areas are analysed. The work consists of 2 parts – theory and practice. In theoretic part Lithuania’s and foreign countries’ science articles about negative impacts of unemployment to economic and social areas are analysed. In Empiric part there are analyses of 1998-2009 years statistic information in Lithuania about unemployment levels and certain economic and social indicators like: (gross domestic product (GDP), inflation rate, emigrants, average monthly gross wage, budget income and expenditure, visits to physicians, deaths of diseases of the circulatory system, intentional self-harms, poverty, crimes). Also, try to determine which economic and social indicators, unemployment has a negative effect on the period and the maximum impact - the aggregate, decrease or increase in unemployment during the period.

No description available.

No description available.

Adams et al. was the first to demonstrate an association between improved outcomes and provider experience in a 1973 study examining complication rates from coronary arteriograms.[1] In this study, a questionnaire was mailed to the directors of coronary arteriography laboratories throughout the US. They found that mortality was eight times higher in institutions performing fewer than 200 examinations per two-year period compared to institutions performing more than 800 examinations per two-year period. It was not until 1979, however, that efforts to systematically study outcomes in surgery were made by Luft and colleagues.[2] They demonstrated lower mortality rates at high-volume centers compared with low-volume centers for several high risk procedures, such as coronary artery bypass graft surgery (CABG) and vascular surgery. This landmark study set the stage for outcomes research in surgery. Over the past decade, additional studies have continued to show higher surgeon or hospital volumes to be associated with improved patient outcomes. [3-13] To what degree surgeon versus hospital volume each contribute to outcomes is controversial and depends on the procedure examined. Nevertheless, formal recommendations encouraging certain high-risk procedures be performed at high-volume hospitals began as early as 2000 by the Leapfrog group and other policy initiatives.[14, 15] Formal recommendations for surgeon volume, on the other hand, have been lacking. There has been mounting evidence, particularly in the last decade, that surgeon volume is associated with improved patient outcomes, independent of hospital volume. To what measure these data have influenced referral patterns from low- to high-volume surgeons is unknown.