SAMMANFATTNING  Bakgrund: Muskuloskeletal smärta är en av de främsta orsakerna till både sjukskrivning och hälso- och sjukvårdskonsumtion i de flesta västerländska samhällen. Muskuloskeletal smärta definieras som smärta i rörelseorgan såsom muskler, leder, skelettdelar eller tillhörande mjukdelar. I behandling av muskuloskeletal smärta ingår ofta fysisk aktivitet. Fysisk aktivitet definieras, som all kroppsrörelse som ökar energiförbrukningen utöver den energiförbrukning som vi har i vila. För att fysisk aktivitet skall ha önskad effekt krävs följsamhet till den fysiska aktiviteten.  Syfte: Syftet är att med hjälp av andra studiers resultat sammanställa effekt av interventioner vars syfte är att öka följsamhet till behandling med fysisk aktivitet hos patienter med muskuloskeletal smärta.  Metod: Systematisk litteraturstudie. Sökning genomfördes i databaserna PUB Med, CINAHL, AMED och PEDRO. Artiklarna granskades med mall för kvalitetsgranskning av randomiserade studier samt att en GRADE bedömning utfördes med bedömningsunderlag från Statens beredning för medicinsk och social utvärdering (SBU).  Resultat: Vid litteratursökning återfanns 514 artiklar som motsvarade syfte och frågeställningar. Efter genomgång av titel samt abstract fanns 38 artiklar kvar, efter genomläsning av hela studien fanns 10 artiklar kvar som inkluderades i litteraturstudien.De 10 artiklarna hade varierande grad av kvalitet. Ingen av studierna hade fullgod kvalitet på samtliga delar som ingår vid kvalitetsgranskningen. Evidensgradering enligt GRADE visar måttligt underlag för beteendemedicinska interventioner för att öka följsamheten till fysisk aktivitet för vuxna patienter med muskuloskeletal smärta.  Konklusion: Denna litteraturstudie visar ett svagt sambandavseende om beteendemedicinska interventioner kan öka följsamhet till fysisk aktivitet hos vuxna med muskuloskeletal smärta. Vid stödjande aktiviteter fann man inte någon positiv effekt på följsamhet till fysisk aktivitet hos vuxna patienter med muskuloskeletal smärta. / ABSTRACT  Background: Musculoskeletal pain is one of the leading causes of both sick leave and health care consumption in most western societies. Musculoskeletal pain is defined as pain in organs such as muscles, joints, skeletal parts or associated soft tissues. Treatment of musculoskeletal pain often includes physical activity. Physical activity is defined as all body movement that increases energy consumption in addition to the energy consumption we have at rest. In order for physical activity to have the desired effect, compliance with the physical activity is required.  Objective: The aim is to use the results of other studies to compile the effect of interventions whose purpose is to increase adherence to treatment with physical activity in patients with musculoskeletal pain. Methods: Systematic review. The search was conducted in the databases PubMed, CINAHL, AMED and PEDRO. The studies were assessed according to template for quality review of randomized studies and GRADE from Statens beredning för medicinsk och social utvärdering.  Results: A literature search found 514 articles that corresponded to purpose and issues. After reviewing the title and abstract, there were 38 articles left, after reading the entire study, there were 10 articles left that were included in the literature study. The 10 articles had varying degrees of quality. None of the studies had full quality on all parts included in the quality review. Evidence grading according to GRADE shows a moderate basis for behavioral medicine interventions to increase adherence to physical activity for adult patients with musculoskeletal pain.  Conclusion: This literature study shows a weak correlation regarding whether behavioral drug interventions can increase adherence can increase adherence to physical activity in adults with musculoskeletal pain. In supportive activities, no positive effect was found on compliance with physical activity in adult patients with musculoskeletal pain.

Background: Canada continues to face an opioid epidemic with 5,368 opioid apparent related deaths occurring between January and September of 2021. Methadone Maintenance Treatment (MMT), a form of Medication Assisted Treatment used to treat Opioid Use Disorder (OUD), has been reported to decrease opioid cravings and opioid use, however, individual differences exist in the effective dose of methadone. Further, individuals living with an OUD have higher rates of substance use including cannabis. A genetic component has been suggested to exist for both cannabis use and MMT outcomes, however inconsistent findings have been reported. Methods: Knowledge synthesis and primary genetic association studies were conducted. A protocol was prepared for the planning of a systematic review for Genome-Wide Association Studies (GWASs) of cannabis use. The full systematic review was then conducted, providing an assessment of the literature and a description of studies quality. A GWAS and Polygenic Risk Score (PRS) was then conducted for cannabis use and MMT outcomes, separately, in Europeans only. The top Single Nucleotide Polymorphisms (SNPs) were then analyzed separately by sex and sex interactions were conducted. Results: The systematic review included 6 studies, identifying 96 genetic variants associated with cannabis use. The GWASs for both cannabis use and MMT outcomes did not identify any significant results. A significant PRS was found for regular cannabis use and methadone dose. No sex-specific results were identified. Discussion: This thesis summarised the evidence on the genetics of cannabis use as well as employed GWASs and PRSs to investigate cannabis use and MMT outcomes within a European population. We were able to highlight gaps within the genetic literature of cannabis and MMT outcomes as well as identify areas of interest for future research. / Dissertation / Doctor of Philosophy (PhD) / Cannabis use rates in Canada are increasing, with Opioid Use Disorder (OUD) patients having high rates of cannabis use despite inconsistent findings on the impacts. To combat the opioid crisis, Methadone Maintenance Treatment (MMT) is utilized to reduce opioid cravings and use. However, individuals on MMT are likely to use other substances, including cannabis. This thesis explores the genetic literature on cannabis use and conducts a Genome-Wide Association Study (GWAS) and a Polygenetic Risk Score (PRS). The GWAS investigates genetic variants throughout the whole genome associated with a trait, while the PRS creates a genetic weight risk score. GWAS and PRS methods were used to investigate cannabis use and MMT outcomes within Europeans with OUD. While no significant GWAS results were found, a statistically significant PRS was found for regular cannabis use and methadone dose, suggesting each respective score can estimate an individual’s risk of that trait.

The impact of climate change on drinking water is one of the fastest-growing challenges within the water sector. Microbial contamination of drinking water has been a serious issue for decades now and will exacerbate in the coming future. Until recently the impact of climate change was only evaluated qualitatively and there has been a growing need for a quantitative risk assessment. This review covers different ways of incorporating the effects of climate change into the risk assessment framework. A comprehensive search through two databases was conducted resulting in 596 citations being screened for relevance, of which 23 were confirmed as relevant. Ten risk assessment frameworks and 3 tools obtained from this review were used for the comparative study with the Swedish QMRA tool. Data from multiple frameworks and tools were extracted to identify potential additions required for the improvement of the Swedish tool. Two approaches, i.e. data-driven and process-based, were identified and the foundation for a new framework was set up. Two pathways to implement these approaches were laid out with the first being the addition of new modules to the existing tool and the second being the use of hydrodynamic and water quality models to predict the impact of climate change on infection risks.

<p><strong> Objective:</strong> The purpose of this systematic review is to identify the effectiveness of KT strategies used to promote evidence-informed decision making (EIDM) among public health decision makers.</p> <p><strong> Methods: </strong>A search strategy was developed to identify primary studies published between 2000-2010.<strong> </strong>Studies were obtained from multiple electronic databases, supplemented by checking the reference lists of included articles and background papers. Two independent reviewers screened studies for relevance, assessed methodological quality and extracted data from relevant studies using standardized tools. Disagreements were resolved through consensus.</p> <p><strong> Results: </strong>The search identified 92, 548 titles related to KT interventions. After duplicate articles were removed 64, 391 were imported into Distiller SR of which 345 articles were deemed potentially relevant on double title and abstract review. Of the 345 articles, 30 met all relevance criteria on full text screen and after revisions to the inclusion criteria, 6 studies of moderate quality were included in this review.</p> <p>KT interventions tested in the systematic review included organization change, provider reminders, education, financial incentives and feedback. Interventions tested in the five primary studies ranged from; educational sessions; dissemination channels including print, CD-ROM and Internet; technical assistance and staff training; and web-based services such as databases, information services, registries of pre-processed research evidence and tailored targeted messaging.</p> <p>KT strategies shown to be less effective included access to registries of pre-processed research evidence or print materials. Simple or single KT interventions were shown in some circumstances to be as effective as multifaceted ones including organizational change, provider reminders and tailored targeted messaging. While knowledge brokering did not have a significant effect generally, results suggest that it did have a positive effect on organizations with low research culture.</p> <p><strong> Conclusion:</strong> KT research in public health is in early stages. Single interventions can be effective. Researchers and practitioners must pay attention to contextual factors.</p> / Master of Science in Nursing (MSN)

<p>Low back pain (LBP) is a common musculoskeletal condition that can lead to pain, functional limitations and disability. Due to the prevalence of LBP, multiple self-reported outcome measures have been developed, which have resulted in redundancy in the literature. Two frequently used outcome measures are the Roland Morris Questionnaire (RMQ) and the Oswestry Disability Index (ODI). Few authors have performed head-to-head comparison studies to determine which of these outcome measures are the most successful at measuring sensitivity to change. The purpose of this thesis was to answer the question: Is there a difference in the sensitivity to change between the RMQ and the ODI in their ability to measure pain-related functional status in persons with low back pain?</p> <p>The first part of this thesis involves a systematic review of head-to-head comparison studies to determine the difference in the sensitivity to change of the RMQ and the ODI. Five databases were searched and nine articles were located. The second part of this thesis entails the development of a quality criteria form to evaluate head-to-head comparison studies.</p> <p>The third aspect of this research was to perform a head-to-head comparison study of the RMQ and the ODI using data from the nine studies. A small but significant difference was noted in favour of the RMQ in terms of the Spearman rank correlation coefficient between its change scores and the reference standard (Z = 2.36, p = 0.018; Z = 3.28, p = 0.001) and also in the Receiver Operating Characteristic curve area (<em>X</em>²₁ = 8.58, p = 0.003).</p> / Master of Science Rehabilitation Science (MSc)

<p><strong>Background:</strong> Major adverse cardiac events, MACE – a composite endpoint of cardiac death and nonfatal myocardial infarction (MI) – are severe harmful outcomes that commonly arise after elective vascular surgeries. As current pre-operative risk prediction models are not as effective in predicting post-operative outcomes, this thesis will discuss the key results of an individual patient data meta-analysis that is based on data from six cohort studies of patients undergoing vascular surgery.</p> <p><strong>Objectives:</strong> The purpose of this thesis is to determine optimal thresholds of continuous covariates and create a prediction model for major adverse cardiac events (MACE), within 30 days after a vascular surgery. The goals include exploring the minimum p-value method to dichotomize cutpoints for continuous variables; employing logistic regression analysis to determine a prediction model for MACE; evaluating its validity against other samples; and assessing its sensitivity to clustering effects. The secondary objectives are to determine individual models for predicting all-cause mortality, cardiac death, and nonfatal MI within 30 days of a vascular surgery, using the final covariates assessed for MACE.<strong></strong></p> <p><strong>Methods: </strong>Both B-type naturietic peptide (BNP) and its N-terminal fragment (NTproBNP) are independently associated with cardiovascular complications after noncardiac surgeries, and particularly frequent after noncardiac vascular surgeries. In a previous study, these covariates were dichotomized using the receiver operating characteristic (ROC) curve approach and a simple logistic regression (SLR) model was created for MACE [1]. The first part of this thesis applies the minimum p-value method to determine a threshold for each natriuretic peptide (NP), BNP and NTproBNP. SLR is then used to model the prediction of MACE within 30 days after a patient’s vascular surgery. Comparisons were made with the ROC curve approach to determine the optimal thresholds and create a prediction model. The validity of this model was tested using bootstrap samples and its robustness was assessed using a mixed effects logistic regression (MELR) model and a generalized estimating equation (GEE). Finally, MELR was performed on each of the secondary outcomes.</p> <p><strong>Results:</strong>A variable, ROC_thrshld, was created to represent the cutpoints of Rodseth’s ROC curve approach, which identified 116pg/mL and 277.5pg/mL to be the optimal thresholds for BNP and NTproBNP, respectively [1]. The minimum p-value method dichotomized these NP thresholds as BNP: 115.57pg/mL (p</p> <p><strong>Discussion:</strong> One key limitation to this thesis is the small sample size received for NTproBNP. Also, determining only one cutpoint for each NP concentration may not be sufficient, since dichotomizing continuous factors can lead to loss of information along with other issues. Further research should be performed to explore other possible cutpoints along with performing reclassification to observe improvements in risk stratification. After validating our final model against other samples, we can conclude that MINP_thrshld, the type of surgery, and diabetes are significant covariates for the prediction of MACE. With the simplicity in only requiring a blood test to measure NP concentration levels and easily learning the status of the other two factors, minimal effort is needed in calculating the points and risk estimates for each patient. Further research should also be performed on the secondary outcomes to examine other factors that may be useful in prediction.</p> <p><strong>Conclusions: </strong>The minimum p-value method produced similar results to the ROC curve method in dichotomizing the NP concentration levels. The cutpoints for BNP and NTproBNP were 115.57pg/mL and 241.7 pg/mL, respectively. Further research needs to be performed to determine the optimality of the final prediction model of MACE, with covariates MINP_thrshld, type of surgery, and diabetes mellitus. <strong></strong></p> <p><strong><br /></strong></p> / Master of Science (MSc)

<p><strong>Objective: </strong>To provide an overview of the state of trial methodology concerning measurement of patient adherence and patient recruitment, and explore how the quality of these methods impact the adherence results found in trials.</p> <p><strong>Data sources: </strong>Major bibliographic sources, reference lists, and clinicaltrials.gov were searched for relevant trials up to January 2013.</p> <p><strong>Study selection: </strong>Approximately 150 trials were included in the full systematic review, from which 50 trials were selected to represent several methods of measuring adherence.</p> <p><strong>Results: </strong>There were a variety of different measures of adherence with qualities ranging from valid and unobtrusive, to unreliable and subjective. The median overall quality of adherence measures was 5 (IQR 3, maximum score 9, higher is better). The overall correlation of the quality of the measures of adherence and the coefficient of variation (CV) or proportion adherence suggested that adherence measures rated as higher quality were associated with a higher CV but not associated with a lower proportion adherence. The median overall quality of patient recruitment methods was 2 (IQR 1, maximum score 6, higher is better). The correlation of the power of a trial and the quality of the patient recruitment methods, was slightly positively correlated for both binary and continuous data.</p> <p><strong>Conclusions: </strong>The quality of methods employed in adherence trials varies considerably and affects at least some findings of these trials. The importance of these differences in quality merits further study, but it is clear that better standards of adherence measurement are needed to support adherence research.</p> / Master of Science (MSc)

<p><em>Background:</em> There is a shifting culture toward evidence-based plastic surgery. The use of high-quality evidence in patient decision-making is essential. To help achieve this goal the best evidence in the field needs to be identified, and the validity of this evidence verified.</p> <p><em>Objective:</em> This systematic review was designed to evaluate the plastic surgery literature by focusing on the prevalence of, and examining key components of quality of, Randomized Controlled Trials (RCTs) comparing surgical interventions.</p> <p><em>Methods: </em>An electronic search of the pertinent plastic surgery literature identified all RCTs published from 2000 to 2013 that compared one surgical intervention to another surgical intervention. Working in teams of two investigators independently, and in duplicate, assessed each manuscript for potential relevance and performed data extraction. Descriptive statistics, theory-driven multinomial regression, and independent samples t-test were used for data analysis.</p> <p><em>Results:</em> Of the 1664 hits obtained, 173 RCTs were included. These RCTs demonstrated the following data: 35% of RCTs performed and reported randomization properly, and 12% of RCTs reported proper allocation concealment methods. Outcome assessors were blinded in 48 (34%) RCTs, and patients blinded in 45 (26%) RCTs. Multinomial regression demonstrated that trials reporting an a <em>priori</em> sample size are significantly more likely to have a low risk of bias. One-third of trials did not state a primary outcome. The mean and median sample sizes were 73 and 43 patients respectively. Funding and conflict of interest reporting improved over time.</p> <p><em>Conclusions:</em> This systematic review establishes a baseline of the quality of evidence that currently guides practice for surgical interventions in plastic and reconstructive surgery. For the readers of plastic surgery literature to have confidence in the literature, risks of bias should be minimized and transparently reported. This will encourage plastic surgeons to apply the results and findings from published RCTs in their practice, providing patients them with the best possible treatments.</p> / Master of Science (MSc)

The purpose of this study was twofold: to critically review existing systematic reviews and meta-analyses on the topic of music and pain; and to systematically review and conduct a meta-analysis of clinical trials investigating the effect of music on pain encompassing a wide range of medical diagnoses, settings, age groups, and types of pain. For the review of systematic reviews, the author conducted a comprehensive search and identified 14 systematic reviews and meta-analyses. These studies were critically analyzed to present a comprehensive overview of findings, to evaluate methodological quality of the reviews, to determine issues or gaps in the literature, and to generate research questions for the following meta-analysis. For the meta-analysis, the author conducted electronic searches of 12 databases and a handsearch of related journals and reference lists of relevant systematic reviews, with partial restrictions on design (i.e., randomized controlled trials); language (i.e., English, German, Korean, and Japanese); year of publication (i.e., 1995 to 2014) and intervention (i.e., music therapy and music medicine). Analyzed studies included 87 music medicine (MM) and 10 music therapy (MT) trials; eighty-nine of the included studies involved adults and eight trials focused on children. In terms of the types of pain, there were 51 trials on acute, 34 on procedural, and 12 on cancer or chronic pain; the trials were conducted in over 20 different medical specialty areas. For the assessment of study quality, I used the risk of bias tool developed by the Cochrane collaboration, and pooled data from the included studies were analyzed using the Revman 5.3 software according to the effects of music on levels of pain intensity, amount of analgesic use, and changes in vital signs. The results indicated that music interventions resulted in a significant reduction of 1.13 units on 0-10 scales and a small to moderate pain reducing effect on other scales (SMD = -0.39). Participants in the music group experienced a significantly lower level of emotional distress from pain (MD = -10.8), and required significantly fewer anesthetics (SMD = -0.56), opioids (SMD = -0.24), and non-opioid medications (SMD = -0.54). Moreover, the music group showed statistically significant decreases in heart rate of 4.25 bpm, systolic blood pressure of 3.34 mmHg, diastolic blood pressure of 1.18 mmHg, and respiration rate of 1.46 breaths per minute. Findings from several analyses of moderator variables suggest: MT has a stronger effect in reducing self-rated pain intensity than MM; MT is more effective in reducing chronic/cancer pain than other types of pain, but MM seems to be more effective in managing procedural pain; children benefit more from music interventions than do adults, and more from MT than MM; providing different levels of choices in the selection of music yields different outcomes for MM; having a rationale for selection of music greatly improves the treatment outcome for MM; and an active MT approach is more effective in relieving perceived levels of pain than a passive MT approach. The results from the current meta-analysis demonstrate that music interventions may have beneficial effects on pain, emotional distress from pain, use of anesthetics and pain killers, and vital signs including heart rate, systolic blood pressure, diastolic blood pressure and respiration rate. However, these results need to be interpreted with caution due to highly heterogeneous outcomes among the included studies. Considering all the possible benefits, music interventions may provide an effective complimentary approach for the relief of acute, procedural and cancer/chronic pain in the medical setting. / Music Therapy

Background and objectives: Incorporating patient values and preferences as an essential input for decision-making has its potential merits in respecting the autonomy of patients, improving adherence and clinical outcomes. The Grading of Recommendations Assessment, Development and Evaluation (short GRADE) working group conceptualizes patient values and preferences as “the relative importance patient place on the main outcomes”. The objectives of this thesis include: 1) to provide an overview of a process for systematically incorporating values and preferences in guideline development; 2) to conduct a systematic review on outcome importance studies, using chronic obstructive pulmonary disease (COPD) as an example; 3) to provide guidance on how to assess certainty of evidence describing outcome importance using the GRADE criteria. Methods: We performed systematic reviews, asked clinical experts to provide feedback according to their clinical experience, and consulted patient representatives to obtain information about relative importance of outcomes in a new national guideline program. We conducted a systematic review to summarize the COPD related relative importance of outcome studies. We used a multi-pronged approach to develop the guidance for assessing certainty of evidence about relative importance of outcome and values and preferences. We applied the developed GRADE approach to relative importance of outcome systematic review examples and consulted the stakeholders in the GRADE working group for feedback. Results and conclusion: We provided an empirical strategy to find and incorporate values and preferences in guidelines by performing systematic reviews and eliciting information from guideline panel members and patient representatives. However, we identified the need for researches on how to assess the certainty of this evidence, and best summarize and present the findings. In our comprehensive systematic review project on COPD patient values and preferences we demonstrated the utility of rating evidence in systematic reviews of outcome importance. We describe the rationale for considering GRADE domains for the evidence about the importance of outcomes. We propose the assessment of the body of evidence starts at “high certainty”, and rate down for serious problems in GRADE domains including risk of bias, indirectness, inconsistency, imprecision and publication bias. Specific to risk of bias domain, we propose a preliminary consideration for risk of bias. The sources of indirectness for relative importance of outcome evidence include indirectness from PICO (population, intervention, comparison, and outcome) elements, and methodological indirectness. As meta-analyses are uncommon when summarizing the evidence about relative importance of outcome, inconsistency and imprecision assessments are challenging. Inconsistency arises from PICO and methodological elements that should be explored. The width of the confidence interval and sample size should inform judgments about imprecision. We also provide suggestions on how to detect publication bias based on empirical information. Finally, we also discuss the applicability of domains to rate up the certainty. We develop the GRADE approach for rating risk of bias, indirectness, inconsistency, imprecision and other domains when evaluating a body of evidence describing the relative importance of outcomes. Our examples should guide users and provide a basis for discussion and further development of the GRADE system. / Thesis / Doctor of Philosophy (PhD)