This thesis considers an approach to evaluate the effectiveness of risk communications for prescription drugs by performing interrupted time series analysis of prescription drug volumes prior to and after the risk communication date. The paper presents methods for detecting change in the presence of autocorrelation and techniques to reduce bias in estimation. Statistical results and data plots are presented for 63 data series. Size and power of the statistical techniques are considered, and a correspondence analysis between these statistical techniques and a small group of physicians is performed. The methods considered in this thesis correspond weakly with physician sentiment, and exhibit inflated type I errors in the presence of significant autocorrelation.

This thesis considers an approach to evaluate the effectiveness of risk communications for prescription drugs by performing interrupted time series analysis of prescription drug volumes prior to and after the risk communication date. The paper presents methods for detecting change in the presence of autocorrelation and techniques to reduce bias in estimation. Statistical results and data plots are presented for 63 data series. Size and power of the statistical techniques are considered, and a correspondence analysis between these statistical techniques and a small group of physicians is performed. The methods considered in this thesis correspond weakly with physician sentiment, and exhibit inflated type I errors in the presence of significant autocorrelation.

Osteoporosis is a common health problem and it is increasing in prevalence due to the increase in the aging population. The interest to treat osteoporosis has increased in recent years, due to availability of screening modalities, advances in medications that may prevent osteoporotic fractures. Many studies have showed the high medical and economic burden of the disease on the patients, their caregivers and on the health system. Clinical practice guidelines for management of osteoporosis varied nationally and internationally, and the adherence of physicians to guidelines were always reported as suboptimal, though most studies were for after fragility fracture care gap and vert few looked at the primary screening to identify patients at risk before the occurrence of fractures. This thesis is composed of two manuscripts research project assessing the development and impact of screening for osteoporosis guidelines. The first chapter is an overview of osteoporosis, definition, risk factors, diagnosis and treatment. A follow up discussion of the literature on adherence of physicians to the osteoporosis guidelines, which ends up with the rational for this thesis. The first paper is a systematic review to identify guidelines for screening for osteoporosis from 2002-2016 (Chapter 2). We assessed the quality of these guidelines using the AGREE II and IOM standards, compared between the two tools, and assessed if the quality has changed over time. We extracted recommendations in key areas with summary of the systems that were used to assign the level of evidence and strength of recommendations. We found that the quality of guidelines has varied greatly between different countries with no significant change over time. The recommendations and systems for level of evidence were variable and all this may create confusion to clinicians. In the second paper, we used an interrupted time series design to assess the effect of three clinical practice guidelines for screening for osteoporosis in Ontario on the baseline bone mineral density (BMD) testing for older adults 65 years of age and above using administrative data by ICES from 1998-2006. All three guidelines recommend baseline BMD testing for this age population. In addition, we analyzed the pattern of repeated testing in accordance with the latest guideline. We have found low rates of baseline BMD testing with a decreasing pattern of testing. The last guideline in 2010 had gradually increased the trend of BMD testing, though it was a very small change. Stratified analyses by sex showed that the decrease in the total BMD testing is due to decrease in the testing for female population while there is an increasing trend of BMD testing in male population. CPG by Osteoporosis Canada in 2010 caused an immediate reduction in the BMD testing for female, yet, over a period of time, the guideline increased the BMD testing. For male population; the 2002 CPG had immediately increased the BMD testing, while over time this trend has decreased. Despite the low baseline BMD testing by physicians, there is an over use of repeated BMD testing in the low risk population, especially the annual and the 2 yearly BMD repeats. In conclusion: This research project found a varied quality of guideline development and reporting of guidelines for osteoporosis screening, and no improvement in the quality over time (2002-2016). Several systems were used to assign the level of evidence and strength of recommendations with conflicting recommendations between different health organizations in the same country such as in Canada. Many tools are available to appraise the quality of guidelines, however, comparing between two tools (AGREE II & IOM standards) showed that they may give conflicting results for guidelines quality. There is no effect of guidelines for screening for osteoporosis on the ordering of BMD testing to screen adults 65 years and above living in Ontario between 1998- 2016. A small increase the rate of baseline BMD testing followed the release of the 2010 guideline. For male population the 2002 guideline showed an evident immediate and gradual effect over time on the rate of baseline BMD testing ordering for male population. Despite the low baseline BMD testing rates for adults 65 years and above, there is an unnecessary repeated BMD testing for low risk population in Ontario between 2011-2016 which is not in compliance to the latest guideline for screening for osteoporosis.

Sedan år 1998 har det i Nollvisionens fotspår startats ett utvecklingsprogram i Sverige som syftar till att omvandla gamla 13 meters landsvägar och motortrafikleder till mötesfria. Implementeringen var tänkt att påtagligt reducera antalet mötes- och omkörningsolyckor samt singelolyckor med svåra konsekvenser i form av svårt skadade och dödade utan att försämra trafiksäkerheten i övrigt. Syftet med denna studie är att göra en effektmätning av de mötesfria vägarnas införande i Karlstadsregionen samt att göra en sammanställning av de olycksrisker mötesfria vägar omfattas av. Frågeställningarna som används i studien är: - Har det blivit säkrare på vägarna sedan implementeringen av mötesfria vägar i Karlstadsregionen? - Hur sker olyckor på mötesfria vägar inom Karlstadsregionen?  För att beskriva hur olyckor sker på mötesfria vägar inom Karlstadsregionen har en deskriptiv analys tillämpats som grundats på de beskrivningar av händelseförlopp som dokumenterats i STRADA och CORE, mellan åren 2010-2013. För att avgöra huruvida vägarna blivit säkrare sedan implementering tillämpades en segmenterad linjär regressionsanalys där antalet personskadeolyckor studerats, tre år innan och tre år efter ombyggnad för respektive vägavsnitt. Singel- och upphinnandeolyckor var de dominerande olyckstyperna på mötesfria vägar i Karlstadsregionen mellan åren 2010-2013 då de sammanlagt stod för 72,3% av samtliga olyckor som medfört skada. Vid kategoriseringen av huvudorsak till olycka framgick det att 42% av alla olyckor kan spåras till brister i samspel mellan trafikanter och väderförhållanden bedömdes i 24,1% av fallen vara huvudorsak till olycka. Den statistiska analysen var inte signifikant, men gav indikation på att vägarna blivit säkrare sedan implementering då trenden för samtliga skadade minskat. / In the footsteps of Vision Zero, a development program in Sweden was initiated in 1998. The program aimed to increase road safety on existing 13-meter roads and express roads by implementing median barriers. The purpose of this study is to measure the impact of the transformed roadways in the Karlstad region and to examine the different types of accident risks the roadways are covered by. The research questions used are: - Has the implementation of median barriers in the Karlstad region contributed to safer roads? - How do accidents occur on roads with median barriers? To describe how accidents occur on roads with median barriers in Karlstad region a descriptive analysis was made by the description of event that is documented in STRADA and CORE, between the years 2010-2013. To determine whether the roads became safer after implementation a segmented linear regression analysis was applied. Accidents resulting in injury were examined, three years before and three years after reconstruction for each road section. Single-vehicle accidents and rear-end collisions were the dominating accident types on roadways with median barriers in the Karlstad region between the years 2010-2013. They together accounted for 72,3% of all accidents that resulted in injury. When the main cause of accident was examined, it emerged that 42% of all accidents could be traced to deficiencies in the interaction between road users. Weather conditions were estimated to be the main cause of accident in 24,1% of all the studied cases. The statistical analysis was not significant, but indicated that the roads became safer after the implementation since the observed trend for all types of injured decreased.

Konsumtionsbeteende är idag en viktig undersökningspunkt för att med säkerhet kunna genomföra implementeringar av nya policys inom konsumentpolitiken. Både klassiska nationalekonomiska teorier och beteendeekonomiska teorier används för att beskriva och förutsäga dessa beteenden, men det saknas undersökningar på deras faktiska kopplingar till olika typer av prissättning. Denna uppsats har gjort ett försök till att undersöka vilken påverkan en förändring i pris genom en förändring i paketstorlek har på efterfrågan. Den har även försökt ge en analys till om de förändringar som noteras är kopplade till beteendeekonomi eller klassisk nationalekonomisk teori. Med hjälp av en vanlig tidstrendsanalys tillsammans med en interrupted-time-series-analysis har försäljningstrenderna för försäljning i KG för två substituerande produkter skapats och jämförts. Dessa fastställer att förändringens påverkan framförallt stämmer överens med teorier gällande beteendeekonomi men att sambandet mellan en förändring i försäljningsnivå och en förändring i paketstorlek inte är säkerställt. Analyserna gjorda i denna studie blir därför inte fastställda och möjligtvis otillräckliga för att besvara den fråga som ställts. Jag som författare vill därför uppmana till att flera utvecklande studier inom ämnet bör utföras för att säkerställa möjliga resultat. / Consumer behaviour is today an important aspect of making quality decisions regarding policies on the consumer market. Both classical economical models and behavioural economical models are used to describe and predict these kinds of behaviours. Although todays studies on their connections to different methods of pricing are lacking. This paper tries to investigate what kind of impact a change in price by changing the size of the good has on demand. It also tries to produce an analysis on if this impact is connected with bevioural or classical economic theories. Based on a classical time-trend analysis together with an interrupted-time-series-analysis different trends for sales in KG regarding two substitutional products have been created. These determine that the effects on demand are most likely connected to behavioural economics but that the effects aren’t statistically significant. The analysis done in this paper therefore cannot be statistically determined and indicates that further studies on the subject need to be done to answer these questions with more certainty.

A pediatric intensivist in the University of Iowa Hospitals and Clinic's (UIHC) Pediatric Intensive Care Unit (PICU) was concerned about antimicrobial use in the unit. However, no one had quantified antimicrobial use in the UIHC's PICU or described the patterns of antimicrobial use in this unit. To address the intensivist's concern, the principal investigator (PI) conducted a retrospective study to determine the percentage of patients who received antimicrobial treatments, to determine the indications for antimicrobial use, and to identify antimicrobial agents used most frequently in the unit. On basis of our data, we hypothesized that empiric antimicrobial use, particularly the duration of therapy, could be decreased. We implemented a six-month intervention during which we asked the pediatric intensivists to complete an antimicrobial assessment form (AA) to document their rationale for starting antimicrobial treatments. We postulated that this documentation process might remind physicians to review antimicrobial therapies, especially empiric therapies, when the microbiologic data became available. In addition, we utilized the AA form to identify factors pediatric intensivists considered when deciding to prescribe empiric antimicrobial treatments. Data from the AA forms suggested that pediatric intensivists in the UIHC's PICU often considered elevated C-reactive protein, elevated white blood cell counts, and elevated temperatures when deciding to start empiric antimicrobial therapy. Data from the three nested periods showed that the median duration of empiric and targeted treatments decreased during the intervention and remained stable during the post-intervention period. The PI estimated that 193 days of empiric antimicrobial therapy and 59 days of targeted antimicrobial therapy, respectively, may have been saved by the decreased durations of therapy. Time series analysis assessing the trend in use of piperacillin-tazobactam, cefepime, and ceftriaxone (measured in mg/wk) did not reveal a significant change over time. On the basis of our results, an intervention strategy using an AA form alone may not be an effective strategy for antimicrobial stewardship in PICUs. Additional measures such as automatic stop orders and computer decision support may be useful for reducing the duration of empiric therapy in PICUs.

Background: This thesis is composed of three studies testing the effect of the Colon Cancer Check (CCC) program, the organized screening program for colorectal cancer in Ontario, on screening participation. In the first paper, we described the trends of participation to Fecal Occult Blood Test (FOBT) and endoscopy, and the trend of ‘up-to-date’ consistent with guidelines, overall and stratified by demographic characteristics between 2005 and 2011. In the second paper, we tested the effect of physician’s recommendation on FOBT participation and disparities in participation. In the third paper, we measured the effect of the CCC program on FOBT participation using an interrupted time series. Methods: We identified six annual cohorts of individuals eligible for CRC screening in Ontario between 2005 and 2011 by linking the Registered Persons Database to Ontario Health Insurance Plan and 2006 Census from Statistics Canada. We used descriptive statistics to describe the trends of participation. The effect of physician’s recommendation on screening participation was tested using multiple logistic regression analysis. The effect of the CCC program on FOBT participation was tested using segmented regression analysis. Results: An increasing trend in FOBT participation and ‘up-to-date’ status was observed across all demographic characteristics. The disparity gaps persisted over time by gender, income, recent registrant and age. The rural/urban gap was removed. Physician’s recommendation tripled the likelihood of FOBT participation (prevalence rate ratio=3.23, CI= 3.22-3.24) and mitigated disparities. The CCC led to a temporary increase in level (8.2‰ person-month) in FOBT participation followed by a decline in trend and then a plateau. The increase in level was significant across all population sub-groups. Conclusions: We found that CRC screening has increased in Ontario across all subgroups of the population but remained suboptimal. Disparities in screening participation were identified. Proposed strategies to improve performance include interventions to increase the rate of physician’s recommendation at the practice level, tailored interventions to motivate under-users and public media campaigns.

Background: This thesis is composed of three studies testing the effect of the Colon Cancer Check (CCC) program, the organized screening program for colorectal cancer in Ontario, on screening participation. In the first paper, we described the trends of participation to Fecal Occult Blood Test (FOBT) and endoscopy, and the trend of ‘up-to-date’ consistent with guidelines, overall and stratified by demographic characteristics between 2005 and 2011. In the second paper, we tested the effect of physician’s recommendation on FOBT participation and disparities in participation. In the third paper, we measured the effect of the CCC program on FOBT participation using an interrupted time series. Methods: We identified six annual cohorts of individuals eligible for CRC screening in Ontario between 2005 and 2011 by linking the Registered Persons Database to Ontario Health Insurance Plan and 2006 Census from Statistics Canada. We used descriptive statistics to describe the trends of participation. The effect of physician’s recommendation on screening participation was tested using multiple logistic regression analysis. The effect of the CCC program on FOBT participation was tested using segmented regression analysis. Results: An increasing trend in FOBT participation and ‘up-to-date’ status was observed across all demographic characteristics. The disparity gaps persisted over time by gender, income, recent registrant and age. The rural/urban gap was removed. Physician’s recommendation tripled the likelihood of FOBT participation (prevalence rate ratio=3.23, CI= 3.22-3.24) and mitigated disparities. The CCC led to a temporary increase in level (8.2‰ person-month) in FOBT participation followed by a decline in trend and then a plateau. The increase in level was significant across all population sub-groups. Conclusions: We found that CRC screening has increased in Ontario across all subgroups of the population but remained suboptimal. Disparities in screening participation were identified. Proposed strategies to improve performance include interventions to increase the rate of physician’s recommendation at the practice level, tailored interventions to motivate under-users and public media campaigns.

Approximately 20% of congestive heart failure (CHF) patients are readmitted within 30 days of hospital discharge, a rate which may be affected by in-hospital and post-discharge care. Reducing this rate is important to hospitals, both to improve outcomes and to avoid reductions in Medicare reimbursement. Assessing outcomes within a short post-discharge window best measures the impact of the care, planning, and followup of that admission; but most research on the effects of changes in CHF care has measured outcomes over periods longer than 30 days, adding the unpredictable long-term course of CHF to the factors affecting the outcome. As well, almost no studies to date have included the appreciable effects of CHF comorbidities in their analyses. This study addresses these needs by measuring rates of 30-day all-cause readmission, and by adjusting for comorbidities and demographic factors in our analysis. We hypothesize that an improved CHF care protocol including both in-hospital and post-discharge components will reduce the risk of readmission, and may alter the rate of change of that risk. We have analyzed as an interrupted time series data on 2764 discharges of CHF patients from a hospital that implemented such a change to assess the effect of the new protocol on the readmission risk and on the trend in that risk, comparing outcomes in the 22 months preceding introduction of the new protocol to those in the first 31 months of full implementation. Using multiple logistic regression, we have tested for an association between the new protocol and both the unadjusted risk of readmission, and that risk in a model including comorbidities and demographic factors as covariates. Neither model found a statistically significant association between introduction of the protocol and log-odds of readmission (unadjusted p = 0.847, adjusted p = 0.755) or between introduction of the protocol and change in risk of readmission over time (unadjusted p = 0.437, adjusted p = 0.313). These results, in comparison with other published results, can clarify what changes to care protocols have been shown to be effective. Further, post hoc power analysis of this study can inform study design for further research.

The United States Defense Industrial Base (USDIB) is an essential industry to both the economic prosperity of the US and its strategic control over many advanced military systems and technologies. The USDIB, which encompasses the industries of aerospace and defense, is a volatile industry - prone to many internal and external factors that cause demand to ebb and flow widely year over year. Among the factors that influence the volume of systems the USDIB delivers to its international customers are the arms export controls of the US. These controls impose a divergence from the historical US foreign policy of furthering an open exchange of ideas and liberalized trade. These controls, imposed by the Departments of Commerce, Defense, and State rigidly control all international presence of the Industry. The overlapping controls create an inability to conform to rapidly changing realpolitiks, leaving these controls in an archaic state. This, in turn, imposes a great deal of anxiety and expense upon managers within and outside of the USDIB. Using autoregressive integrated moving average time-series analyses, this paper confirms that the implementation of or amendment to broad arms export controls correlates to significant and near immediate declines in USDIB export volumes. In the context of the US's share of world arms exports, these controls impose up to a 20% decline in export volume.