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Hui Yee Yeo,1,2 Jacqueline Hui Yi Wong,3 Suz Jack Chan,1 Anna Tiatia Fa’atoese Latu,1 Catherine H Han,4,5 Mudassir Anwar,1 Carlo A Marra1 1School of Pharmacy, University of Otago, Dunedin, New Zealand; 2Clinical Research Center, Hospital Seberang Jaya, Seberang Jaya, Penang, Malaysia; 3Pharmacy Department, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia; 4Auckland Oncology, Auckland, New Zealand; 5Faculty of Medical and Health Sciences, University of Auckland, Auckland, New ZealandCorrespondence: Carlo A Marra, School of Pharmacy, University of Otago, PO Box 56, Dunedin, 9054, New Zealand, Tel +64-34797275, Fax +64-34797034, Email carlo.marra@otago.ac.nzPurpose: Despite the importance of acknowledging patient preferences in treatment decision-making, little is known about the treatment preferences and the factors underlying those preferences of breast cancer patients. This study aims explore patient experience and perspective regarding treatment preferences and identify the important determinants that shape these preferences in the context of New Zealand.Patients and Methods: Semi-structured online interviews comprised of six focus group discussions and five individual interviews were performed with 26 breast cancer patients. The interviews were recorded, transcribed, and analyzed using the reflexive thematic analysis approach.Results: Four main themes were derived: (1) positive treatment outcomes; (2) the negative impact of treatment-related side effects on quality of life; (3) treatment accessibility, availability, and timeliness; (4) cost of treatment. Patients revealed a strong preference towards treatments that yield longer survival, achieve remission, and prevent cancer recurrence. Additionally, patients favored treatments with minimal side effects that had minimal impact on their quality of life. There was a notable preference for treatments that were easily accessible and available in a timely manner. However, patients faced challenging decisions in balancing the costs of treatments with their benefits, leading to a consistent preference for treatments supported by government funding or medical insurance to alleviate financial burdens.Conclusion: Our study reveals that breast cancer patients in New Zealand have different perceptions and preferences regarding cancer treatment. Patients frequently find themselves making trade-offs among various attributes of a treatment, aligning these decisions with their personal values and beliefs. By considering these preferences and trade-offs in future studies that measure patient preferences, healthcare professionals can enhance their support for patients in making informed choices that align with their values and priorities. Additionally, healthcare policymakers can develop patient-centered policies that cater to the unique needs and preferences of breast cancer patients.Plain Language Summary: Breast cancer is a significant health concern in New Zealand, affecting both the well-being of patients and their families. Despite advancements in treatment, patient preferences regarding treatment risks and benefits are often neglected. This study aims to bridge this knowledge gap by qualitatively exploring the unique experiences and preferences of breast cancer patients in New Zealand, shedding light on the factors influencing their treatment decisions. The study involved a series of interviews with a group of 26 women living with breast cancer. The interview revealed four main themes that shape patients’ preferences for breast cancer treatment: 1. Positive outcomes: Patients revealed a strong preference towards treatments that yield longer survival, achieve remission, and prevent cancer recurrence. 2. Quality of life: Treatment-related side effects negatively impacted patients’ quality of life, affecting them physically, mentally, emotionally, spiritually, and psychosocially. Patients preferred a treatment that entailed few side effects with minimal impact on their quality of life. 3. Treatment accessibility and timeliness: Patients expressed concerns about administrative complexities, long distances to healthcare facilities, timely treatment, and restricted access to treatment options in the country. There was a notable preference for treatments that were easily accessible and available in a timely manner. 4. Cost of treatment: Balancing the cost of treatments with their benefits posed challenging decisions for patients, who consistently voiced a preference for treatments supported by government funding or medical insurance.The study highlights diverse perspectives and preferences among breast cancer patients in New Zealand about treatment preference. Patients frequently find themselves making trade-offs concerning various attributes of a treatment that align with their individual values and beliefs. Integrating these preferences and trade-offs into future studies and healthcare policies can help healthcare professionals and policymakers better support patients in making informed choices aligned with their values, fostering a more patient-centered healthcare system.Keywords: qualitative research, patient preference, breast cancer, reflexive thematic analysis, treatment preference, treatment decision-making

Hui Yee Yeo,1,2 Ai Ch’i Liew,2 Suz Jack Chan,1 Mudassir Anwar,1 Catherine Hye-Won Han,3 Carlo A Marra1 1School of Pharmacy, University of Otago, Dunedin, New Zealand; 2Clinical Research Center, Hospital Seberang Jaya, Penang, Malaysia; 3Faculty of Medical and Health Sciences, University of Auckland, Auckland, New ZealandCorrespondence: Carlo A Marra, School of Pharmacy, University of Otago, PO Box 56, Dunedin, 9054, New Zealand, Tel +64-34797275, Fax +64-34797034, Email carlo.marra@otago.ac.nzObjective: Conventionally, optimal treatment strategies for breast cancer have been largely determined by physicians, with a scant understanding of patients’ treatment values and preferences. Incorporating patient preferences in the decision-making process for breast cancer treatment is gaining recognition and can potentially improve treatment outcomes and compliance. This scoping review aims to synthesize evidence on the key determinants that are most valued by breast cancer patients when deciding on their treatment options.Methods: We searched three electronic databases (PubMed/MEDLINE, SCOPUS, and CINAHL Plus) utilizing a systematic scoping review method. Two reviewers independently screened, applied inclusion criteria, reviewed, and synthesized findings. A mixed-method narrative approach combining the inductive thematic analysis and content analysis methodologies was used to synthesize and summarize the findings.Results: The review included 22 studies, leading to the conceptualization of 5 overarching themes and 17 sub-themes. Among these, the most frequently cited theme was treatment benefits, followed by treatment-related process, treatment-related risk, quality of life, and cost of treatment. Women with breast cancer highly value treatments that offer good effectiveness, prolong survival, prevent recurrence, and maintain quality of life. Patient concerns include treatment-related side effects, safety, the risk of secondary cancer, and direct or indirect out-of-pocket costs. Additionally, patients also consider treatment duration, mode of administration, physician recommendation, and treatment availability and accessibility when deciding on their preferred treatment.Conclusion: The evidence synthesized in this review offers insights into refining breast cancer treatment strategies to align more closely with patient values. Recognizing and integrating patient perspectives in breast cancer care could potentially lead to improved treatment outcomes, enhanced patient compliance, and more personalized care. Healthcare professionals are encouraged to incorporate these key determinants in their treatment decision-making processes, aiming to deliver a patient-centered care that aligns with the unique preferences and values of each patient.Plain Language Summary: Breast cancer is a significant health concern, and treatment decisions have traditionally driven by physicians, often without due consideration for patients’ preferences in their treatment choices. This scoping review aimed to explore and summarize what matters most to breast cancer patients when deciding on their treatment options. We found five main themes that were important to patients:Effectiveness: Patients highly value treatments that are effective in fighting cancer, prolonging survival, and preventing recurrence.Treatment-related process: The length of treatment and availability of different therapies influenced patients’ choices. Patients trust their doctors’ expertise but also value being involved in the decision-making process to have their preferences considered.Side Effects and Safety: Concerns about treatment-related side effects and the risk of secondary cancer were critical factors in decision-making.Quality of Life: Maintaining a good quality of life during treatment is crucial for patients.Financial Burden: The additional direct and indirect out-of-pocket costs of treatment were important considerations for patients.Understanding patients’ preferences is vital in developing personalized treatments that align with their values. Healthcare professionals need to communicate effectively with patients and involve them in the decision-making process. Patient decision aids and tailored financial assistance programs could also be helpful. Further research is needed to identify effective strategies to tailor treatments to meet patients’ preferences. Overall, this review sheds light on what matters most to breast cancer patients, empowering them to be more active participants in their treatment decisions and potentially improving treatment outcomes and overall well-being.Keywords: breast cancer, patient preference, treatment decision making, narrative scoping review

Amir Khakban,1 Tima Mohammadi,2 Larry D Lynd,1 Don J Mabbott,3,4 Eric Bouffet,5,6 Louise Gastonguay,1 Zafar Zafari,7 David Malkin,5,6 Michael D Taylor,8,9 Carlo A Marra10 1Collaboration for Outcomes Research and Evaluation, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada; 2Centre for Health Evaluation and Outcome Sciences, University of British Columbia, St Paul’s Hospital, Vancouver, BC, Canada; 3Department of Psychology, University of Toronto, Toronto, ON, Canada; 4Department of Psychology, The Hospital for Sick Children, Toronto, ON, Canada; 5Department of Pediatrics, University of Toronto, Toronto, ON, Canada; 6Department of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; 7Health Policy and Management, Mailman School of Public Health, Columbia University, New York, NY, USA; 8Departments of Surgery, Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; 9Department of Neurosurgery, The Hospital for Sick Children, Toronto, ON, Canada; 10School of Pharmacy, University of Otago, Dunedin, New Zealand Objective: The aim of this study was to determine the preferences of parents with children with medulloblastoma and clinicians who manage this condition and their trade-offs between survival and disability using a best–worst scaling (BWS) choice experiment. Methods: Mixed methods were used to develop a BWS tool. Health professionals involved in the care of medulloblastoma patients were contacted through oncology networks in Canada. Parents of children diagnosed with brain tumors were recruited via two clinics in Vancouver and Toronto. The profile case BWS was used with each participant completing 12 choice profiles with the respondent indicating the best and worst features of each profile. Surveys were stratified into good, moderate, and poor prognosis based on the probability of survival presented. Paired model conditional logit analysis was used to generate quantitative preferences. Results: Fifty-four parents (80% female) and 176 providers (36% female, 79% oncologists) participated in this study. There were many similarities in the parents’ and providers’ preferences for treatment although the parents tended to value survival higher than disability while providers seemed to value the opposite. Specifically, providers were willing to take more risk of recurrence in a child with good prognosis compared to intermediate and poor prognosis. Also, parents were less willing to take more survival risks than providers when they had to trade-off between mild disability and survival rate. Conclusion: This study provides useful insights into the preferences of parents and health care providers, the stakeholders of a collaborative decision for the treatment of pediatric medulloblastoma, and compares their values and trade-offs between different levels of survival and disability. Keywords: best–worst scaling, BWS, preference, medulloblastoma, trade-off, cancer

Sharan K Rai,1 Alyssa Howren,1,2 Elizabeth S Wilcox,3 Anne F Townsend,1,4 Carlo A Marra,1,5 J Antonio Aviña-Zubieta,1,6 Mary A De Vera1,2 1Arthritis Research Canada, Vancouver, BC, Canada; 2Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; 3School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; 4University of Exeter Medical School, Exeter, UK; 5School of Pharmacy, Otago University, Dunedin, New Zealand; 6Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada Objective: Medication non-adherence is a substantial problem among patients with inflammatory arthritis (IA). Our aim was to explore IA patients’ perspectives on strategies to support medication adherence.Methods: We collaborated with a leading arthritis patient group and conducted a qualitative study on individuals with IA who were taking at least one medication for their IA. An experienced facilitator led participants through a focus group exercise where participants were asked to design, and then discuss, strategies and/or tools supporting medication use. We applied thematic analysis using an iterative, constant comparative approach.Results: We studied six focus groups with 27 participants diagnosed with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and comparatively under-represented conditions in this research area such as Sjögren’s syndrome. Five themes emerged throughout the analysis. Two themes – 1) adapting to life with IA and 2) the complexities and dynamic nature of taking medications – describe learning to live with a chronic condition and the challenges encountered when using long-term medications. Three themes – 3) developing lifestyle strategies for medication use (eg, having physical reminders and prompts), 4) becoming informed about medications (eg, information at time of diagnosis, means of receiving information) and 5) receiving support (eg, from health care team members, from family) – offer perspectives on facilitators to medication use. From the relationship between the latter themes, a framework was developed that encompasses means of receiving information and support as actionable targets for patient-oriented adherence interventions for IA.Conclusion: This patient-oriented study highlights the importance of developing timely adherence interventions for IA. Our findings also led to a framework describing means of receiving information, such as through digital media and support, including from health care team members and family, as actionable targets for patient-oriented adherence interventions for IA. Keywords: inflammatory arthritis, medication adherence, concordance, facilitators, barriers, qualitative research, synthetic DMARDs, biologic DMARDs

IntroductionBehavioral and Psychological Symptoms of Dementia (BPSD) are a heterogeneous set of psychological reactions and abnormal behaviors in people with dementia (PwD). Current assessment tools, like the Neuropsychiatric Inventory (NPI), only rely on caregiver assessment of BPSD and are therefore prone to bias.Materials and methodsA multidisciplinary team developed the BPSD-SINDEM scale as a three-part instrument, with two questionnaires administered to the caregiver (evaluating BPSD extent and caregiver distress) and a clinician-rated observational scale. This first instrument was tested on a sample of 33 dyads of PwD and their caregivers, and the results were qualitatively appraised in order to revise the tool through a modified Delphi method. During this phase, the wording of the questions was slightly changed, and the distress scale was changed into a coping scale based on the high correlation between extent and distress (r = 0.94). The final version consisted of three 17-item subscales, evaluating BPSD extent and caregiver coping, and the unchanged clinician-rated observational scale.ResultsThis tool was quantitatively validated in a sample of 208 dyads. It demonstrated good concurrent validity, with the extent subscale correlating positively with NPI scores (r = 0.64, p

We investigated the effect of copper (Cu) overload (20–160 µM/24 h) in two cell lines of human hepatic (HepG2) and pulmonary (A-549) origin by determining lipid and protein damage and the response of the antioxidant defence system. A-549 cells were more sensitive to Cu overload than HepG2 cells. A marked increase was observed in both the cell lines in the nitrate plus nitrite concentration, protein carbonyls and thiobarbituric acid reactive substances (TBARS). The TBARS increase was consistent with an increment in saturated fatty acids at the expense of polyunsaturated acids in a Cu concentration-dependent fashion. Antioxidant enzymes were stimulated by Cu overload. Superoxide dismutase activity increased significantly in both the cell lines, with greater increases in HepG2 than in A-549 cells. A marked increase in ceruloplasmin and metallothionein content in both the cell types was also observed. Dose-dependent decreases in α-tocopherol and ferric reducing ability were observed. Total glutathione content was lower in A-549 cells and higher in HepG2. Calpain and caspase-3 were differentially activated in a dose-dependent manner under copper-induced reactive oxygen species production. We conclude that Cu exposure of human lung- and liver-derived cells should be considered a reliable experimental system for detailed study of mechanism/mechanisms by which Cu overload exerts its deleterious effects. [ABSTRACT FROM AUTHOR]

Objectives To investigate the value for money of strategies to prevent falls in older adults living in the community. Design Systematic review of peer reviewed journal articles reporting an economic evaluation of a falls prevention intervention as part of a randomised controlled trial or a controlled trial, or using an analytical model. MEDLINE, PUBMED, EMBASE and NHS EED databases were searched to identify cost-effectiveness, cost-utility and cost-benefit studies from 1945 through July 2008. Main outcome measures The primary outcome measure was incremental cost-effectiveness, cost-utility and cost-benefit ratios in the reported currency and in pounds sterling at 2008 prices. The quality of the studies was assessed using two instruments: (1) an economic evaluation checklist developed by Drummond and colleagues and (2) the Quality of Health Economic Studies instrument. Results Nine studies meeting our inclusion criteria included eight cost-effectiveness analyses, one cost-utility and one cost-benefit analysis. Three effective falls prevention strategies were cost saving in a subgroup of PARTICIPANTS: (1) an individually customised multifactorial programme in those with four or more of the eight targeted fall risk factors, (2) the home-based Otago Exercise Programme in people >/=80 years and (3) a home safety programme in the subgroup with a previous fall. These three findings were from six studies that scored >/=75% on the Quality of Health Economic Studies instrument. Conclusions Best value for money came from effective single factor interventions such as the Otago Exercise Programme which was cost saving in adults 80 years and older. This programme has broad applicability thus warranting warrants health policy decision-makers' close scrutiny. [ABSTRACT FROM AUTHOR]

Background: Long-term control or remission of rheumatoid arthritis (RA) may be possible with very early treatment. However, no optimal first therapeutic strategy has been determined. Objective: To assess the potential cost-effectiveness of major therapeutic strategies for very early RA. Design: Decision analytic model with probabilistic sensitivity analyses. Data Sources: Published data, the National Data Bank for Rheumatic Diseases, and actual 2007 hospital costs. Target Population: U.S. adults with very early RA (symptom duration Time Horizon: Lifetime. Perspective: Health care provider and societal. Intervention: 3 management strategies were compared: a symptomatic or "pyramid" strategy with initial nonsteroidal anti-inflammatory drugs, patient education, pain management, and low-dose glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs) at 1 year for nonresponders; early DMARD therapy with methotrexate; and early therapy with biologics and methotrexate. Outcome Measures: Cost per quality-adjusted life-year (QALY) gained. Results Of Base-case Analysis: By reducing the progression of joint erosions and subsequent functional disability, both early intervention strategies increase quality-adjusted life more than the pyramid strategy and save long-term costs. When the cost of very early intervention is factored in, the cost-effectiveness ratio of the early DMARD strategy is $4849 per QALY (95% CI, $0 to $16 354 per QALY) compared with the pyramid strategy, whereas the benefits gained through the early biologic strategy come at a substantial incremental cost. The early DMARD strategy maximizes the effectiveness of early DMARDs and reserves the use of biologics for patients with more treatment-resistant disease of longer duration, for which the incremental benefit of biologics is greater. Results Of Sensitivity Analysis: The early biologic strategy becomes more cost-effective if drug prices are reduced, risk for death is permanently lowered through biologic therapy, patients experience drug-free remission, responders can be selected before therapy initiation, or effective alternative antirheumatic agents are available for patients for whom several biologics have failed. Limitations: Data on the long-term effect of very early therapeutic interventions on the natural progression in disability and joint erosions are limited. The study considered only tumor necrosis factor inhibitors and not the newer biologics. Conclusion: According to the most objective measures of RA progression, very early intervention with conventional DMARDs is cost-effective. The cost-effectiveness of very early intervention with biologics remains uncertain. [ABSTRACT FROM AUTHOR]

Abstract Background: An evaluation of patients' preferences is necessary to understand the demand for different insulin delivery systems. The aim of this study was to investigate the association between socioeconomic status (SES) and patients' preferences and willingness to pay (WTP) for various attributes of insulin administration for diabetes management. Methods: We conducted a discrete choice experiment (DCE) to determine patients; preferences and their WTP for hypothetical insulin treatments. Both self-reported annual household income and education completed were used to explore differences in treatment preferences and WTP for different attributes of treatment across different levels of SES. Results: The DCE questionnaire was successfully completed by 274 patients. Overall, glucose control was the most valued attribute by all socioeconomic groups, while route of insulin delivery was not as important. Patients with higher incomes were willing to pay significantly more for better glucose control and to avoid adverse events compared to lower income groups. In addition, they were willing to pay more for an oral short-acting insulin ($Can 71.65 [95% confidence interval, $40.68, $102.62]) compared to the low income group ($Can 9.85 [95% confidence interval, 14.86, 34.56; P < 0.01]). Conversely, there were no differences in preferences when the sample was stratified by level of education. Conclusions: This study revealed that preferences and WTP for insulin therapy are influenced by income but not by level of education. Specifically, the higher the income, the greater desire for an oral insulin delivery system, whereas an inhaled route becomes less important for patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tuberculosis (TB) remains a public health threat with significant annual impacts on morbidity and mortality. However, few studies have examined the impact of active and latent TB infection (LTBI) on health-related quality of life (HRQL). METHODS: Patients with recently diagnosed active TB or LTBI patients were administered the Short Form-36 (SF-36) and the Beck depression inventory (DI) at baseline, 3 months, and 6 months. Mixed-effect linear regression was used to compare the trajectory of HRQL over time in the two patient groups after adjusting for potential confounders. Ordinal logistic regression was used to determine the relationship between changes in HRQL of at least the minimal important difference. RESULTS: One hundred four active TB and 102 LTBI patients participated. At baseline, participants with active TB had significantly lower SF-36 mean domain and component scores (4 to 12 points lower, p < 0.03) and higher mean Beck DI scores (4 points higher, p < 0.0001) when compared to LBTI participants. In the responder analysis, those with active TB were associated with reporting improved scores at 6 months of at least the minimal important difference in vitality (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.3 to 5.6), role physical (OR, 3.1; 95% CI, 1.4 to 6.5), mental component score (OR, 3.2; 95% CI, 1.5 to 6.9), social functioning (OR, 11.1; 95% CI, 3.8 to 33), and role emotional (OR, 2.7; 95% CI, 1.2 to 6.0). CONCLUSIONS: Active TB patients had large improvements in most HRQL domains by 6 months. However, when compared to LTBI participants and US norms, HRQL was still low at completion of therapy. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a common, chronic disease where health-related quality of life (HRQL) is one of the main goals of therapy. As such, instruments used to measure HRQL in RA must be able to discriminate across RA severity. The two basic categories of instruments used to measure HRQL are generic instruments and disease-specific instruments. Generic instruments can be further subdivided into preference-based measures which yield both single and multi-attribute utility values anchored at zero (death) and 1.00 (perfect health) as a measure of HRQL. The scores from these types of instruments can be integrated into cost-utility analyses as the weightings for quality adjusted life years. We assessed the construct validity of utility scores from four generic preference-based measures (the Health Utilities Index 2 and 3 (HUI2, HUI3), the EuroQol 5D (EQ-5D), and the Short Form 6-D (SF-6D) and disease specific measures (the Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) and the Health Assessment Questionnaire (HAQ)) in a sample of 313 RA patients in British Columbia, Canada. We also estimated the minimally important differences (MID) for each of the measures. Generally, as anticipated, the disease-specific measures were better able to discriminate across groups with higher RA severity; however, utility scores from each of the scales also appeared to discriminate well across RA severity categories. The MID values agreed with those previously reported in the literature for the HUI2, SF-6D and the HAQ and provided new information for the HUI3, EQ-5D and the RAQoL. We conclude that the all of the preference-based utility measures that were evaluated appear to adequately discriminate across levels of RA severity. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory disease that affects approximately 0.5-1% of the adult population. The introduction of new disease-modifying antirheumatic drugs (DMARDs) such as leflunomide, anakinra and the tumour necrosis factor (TNF)-alpha antagonists (infliximab, etanercept and adalimumab) have transformed the management of RA. In particular, the last class of agents has generated substantial controversy. Costing between 16,000 US dollars and 20,000 US dollars per patient-year (2001 values), the potential greater efficacy of treatment with TNFalpha antagonists comes at much higher drug costs, making these agents natural candidates for cost-effectiveness analyses (CEAs).A MEDLINE search (until 31 January 2004) identified six original CEAs evaluating TNFalpha antagonists in RA. The aim of a CEA is to facilitate the allocation of scarce health resources and to inform policy decisions. However, to enhance the reliability and relevance of these analyses to policy makers, there must be similarity between the methodologies used. Recently, the OMERACT (Outcome Measures in Rheumatoid Arthritis Clinical Trials) group produced a document to define such a reference case; the OMERACT document was used as a foundation to structure comparisons and highlight discrepancies.The methodologies employed in each analysis differed; in particular, disparate time horizons, comparators, quantities of drug and treatment sequences prohibit the comparison of cost effectiveness between studies. Outcomes also differed between the analyses. Most reported health-related quality of life (HR-QOL) in quality-adjusted life-years (QALYs). The QALYs metric was based on preference scores that were typically derived from linear regressions using the Health Assessment Questionnaire (HAQ). However, models also used American College of Rheumatology (ACR) criteria, as well as the disease activity score (DAS). Common to all studies was the lack of data from long-term randomised studies where efficacy and resource consumption in comparison with standard care has been investigated. As such, investigators combined short-term randomised control trial data with that of a long-term observational cohort, and modelled cost effectiveness over an appropriate time horizon. In addition, most analyses lacked rigorous sensitivity analysis to examine the impact of uncertainty in the parameters.Those analyses that examined time horizons of 6 months and 1 year published incremental cost-effectiveness ratios (ICERs) of 34,800 US dollars per ACR 70% response criteria (ACR70) weighted response (duration 6 months, 1999 values) and 96,166 US dollars (duration 1 year, 2002 values). Analyses that modelled costs and health outcomes beyond the first year reported ICER estimates ranging between 26,800 US dollars (patients' lifetime, 1998 values) and 40,308 US dollars (10 years, 2002 values). In terms of HR-QOL, the analyses reported incremental QALYs that ranged from 0.116 (over 19 years) to 1.6 (over 10 years). Discounted costs of therapy ranged from 30,362 US dollars (10 years, 2002 values) to 93,000 US dollars (22 years, 1998 values), and comparator costs ranged from 22,593 US dollars (10 years, 2002 values) to 84,000 US dollars (22 years, 1998 values). [ABSTRACT FROM AUTHOR]

Objectives: Utility scores can be assessed indirectly using preference-based instruments and used as weightings for quality-adjusted life years in economic analyses. It is not clear whether available instruments yield similar results or what domains of health are contributing to the overall score in a sample of patients with rheumatoid arthritis (RA).Subjects: Our study included 313 individuals with rheumatologist-confirmed RA.Measures: A self-completed survey that permitted scoring of 4 indirect utility instruments (the Health Utilities Index Mark 2 and 3 (HUI-2 and HUI-3), the EuroQoL (EQ-5D), and the Short Form 6D (SF-6D) was the basis of our study.Results: Mean (standard deviation) global utility scores were 0.63 (0.24) for the SF-6D, 0.66 (0.13) for the EQ-5D, 0.71 (0.19) for the HUI-2, and 0.53 (0.29) for the HUI-3 (P = 0.02 by repeated-measures analysis of variance). The intraclass correlation across all the indices was 0.67 (95% confidence interval 0.62-0.71). Bland-Altman plots revealed that agreement among instruments was poor at lower utility values. In this elderly RA sample, all of the global utilities mostly measured functional ability and pain.Conclusions: There are significant differences in utilities obtained from different indirect methods. Agreement among the instruments was moderate but poorer at lower utilities. It is unlikely that these utility values, if used as the weightings for quality-adjusted life years, would result in comparable estimates. [ABSTRACT FROM AUTHOR]

Objective: To examine the risk of breast cancer in pre- and postmenopausal women with type 2 diabetes (T2D).Research Design and Methods: This was a population-based retrospective cohort study. Cox regression, stratified by pre- (<55 years) and postmenopausal (≥55 years) status, was used to estimate hazard ratios (HRs) for breast cancer, during earlier (0-3 months) and later (3 months to 10 years) time windows after diabetes index date.Results: Compared with women without T2D, HRs for breast cancer were 0.95 (95% CI 0.48-1.86; P = 0.88) and 1.31 (0.92-1.86; P = 0.14) in pre- and postmenopausal women with T2D, respectively, in the early time window, and 0.92 (0.75-1.13; P = 0.45) and 1.00 (0.90-1.11; P = 0.93) in pre- and postmenopausal women with T2D, respectively, in the later time window.Conclusions: We observed a trend toward an increased risk of breast cancer in postmenopausal women with T2D, but only in the time period immediately after diabetes index date. [ABSTRACT FROM AUTHOR]

Objectives Physical inactivity has been associated with significant increases in disease morbidity and mortality. This study assessed the association between physical activity and (1) health resource use and (2) health resource use costs. Design and Participants The responses from 24 281 respondents >65 years to the Canadian Community Health Survey Cycle 1.1 were used to find activity levels and determine health resource use and costs. Logistic regression models were used to assess risks of hospitalisation. Results Physical inactivity was associated with statistically significant increases to hospitalisations, lengths of stay and healthcare visits (p<0.01). Average healthcare costs (based on the 2007 value of the Canadian dollar) for the physically inactive were $C1214.15 higher than the healthcare costs of the physically active ($C2005.27 vs $C791.12, p<0.01). Conclusion Among those >65 years, physical activity is strongly associated with reduced health resource use and costs. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Asthma is difficult to diagnose in children and at times misdiagnosis of an infection can occur. However, little is known about the magnitude and patterns of antibiotic consumption in children with asthma relative to those without asthma. Methods Using population-based data, 128,872 children were identified with at least 6 years of follow-up. The adjusted rate-ratio (RR) of antibiotics dispensed to asthmatic as compared to non-asthmatic children was determined. Results At age six, the RR of antibiotic consumption for asthmatics compared to non-asthmatics varied between, 1.66 to 2.32, depending on the year of asthma diagnosis. Of the 18,864 children with asthma at ages 2-8, 52% (n = 9,841) had antibiotics dispensed in the 6 months prior to their index date of asthma diagnosis. The RR of antibiotic consumption in the 1 month prior to asthma diagnosis compared to 5 months prior was 1.66 (95% CI 1.60-1.71). The RR was lower in males compared to females (1.58 vs 1.77), and lower in those who received antibiotics in the first year of life relative to those that did not (1.60 vs. 1.76). Conclusions There is higher antibiotic consumption in children with asthma compared to those without asthma. The pattern of antibiotic use suggests that diagnosis guidelines are difficult to follow in young children leading to misdiagnosis and over treatment with antibiotics.

Abstract Background The association between lower socioeconomic status and poorer health outcomes has been observed using both individual-level and aggregate-level measures of income and education. While both are predictive of health outcomes, previous research indicates poor agreement between individual-level and aggregate-level measures. The purpose of this study was to determine the level of agreement between aggregate-level and individual-level measures of income and education among three distinct patient groups, specifically asthma, diabetes, and rheumatoid patients. Methods Individual-level measures of annual household income and education were derived from three separate surveys conducted among patients with asthma (n = 359), diabetes (n = 281) and rheumatoid arthritis (n = 275). Aggregate-level measures of income and education were derived from the 2001 Canadian census, including both census tract-and dissemination area-level measures. Cross-tabulations of individual-level income by aggregate-level income were used to determine the percentage of income classifications in agreement. The kappa statistic (simple and weighted), Spearman's rank correlations, and intra-class correlation coefficient (ICC) were also calculated. Individual-level and aggregate-level education was compared using Chi-Square tests within patient groups. Point biserial correlation coefficients between individual-level and aggregate-level education were computed. Results Individual-level income was poorly correlated with aggregate-level measures, which provided the worst estimations of income among patients in the lowest income category at the individual-level. Both aggregate-level measures were best at approximating individual-level income in patients with diabetes, in whom aggregate-level estimates were only significantly different from individual-level measures for patients in the lowest income category. Among asthma patients, the proportion of patients classified by aggregate-level measures as having a university degree was significantly lower than that classified by individual-level measures. Among diabetes and rheumatoid arthritis patients, differences between aggregate and individual-level measures of education were not significant. Conclusions Agreement between individual-level and aggregate-level measures of socioeconomic status may depend on the patient group as well as patient income. Research is needed to characterize differences between patient groups and help guide the choice of measures of socioeconomic status.

Abstract Background Granting dispensing pharmacists the authority to prescribe has significant implications for pharmaceutical and health human resources policy, and quality of care. Despite the growing number of jurisdictions that have given pharmacists such privileges, there are few rigorous evaluations of these policy changes. This study will examine a January 2009 policy change in British Columbia (BC), Canada that allowed pharmacists to independently adapt and renew prescriptions. We hypothesize this policy increased drug utilization and drug costs, increased patient adherence to medication, and reduced total healthcare resource use. Methods/Design We will study a population-based cohort of approximately 4 million BC residents from 2004 through 2010. We will use data from BC PharmaNet on all of the prescriptions obtained by this cohort during the study period, and link it to administrative billings from physicians and hospital discharges. Using interrupted time series analysis, we will study longitudinal changes in drug utilization and costs, medication adherence, and short-term health care use. Further, using hierarchical modelling, we will examine the factors at the regional, pharmacy, patient, and prescription levels that are associated with prescription adaptations and renewals. Discussion In a recent survey of Canadian policymakers, many respondents ranked the issue of prescribing privileges as one of their most pressing policy questions. No matter the results of our study, they will be important for policymakers, as our data will make policy decisions surrounding pharmacist prescribing more evidence-based.

Abstract Aim To test the early effect of fructose-induced changes in fatty acid composition and oxidative stress markers in perivascular adipose tissue (PVAT) upon vascular contractility. Methods Adult male Wistar rats were fed a commercial diet without (CD) or with 10% fructose (FRD) in the drinking water for 3 weeks. We measured plasma metabolic parameters, lipid composition and oxidative stress markers in aortic PVAT. Vascular contractility was measured in aortic rings sequentially, stimulated with serotonin (5-HT) and high K+-induced depolarization using intact and thereafter PVAT-deprived rings. Results Comparable body weights were recorded in both groups. FRD rats had increased plasma triglyceride and fructosamine levels. Their PVAT had an increased saturated to mono- or poly-unsaturated fatty acid ratio, a significant decrease in total superoxide dismutase and glutathione peroxidase activities and in the total content of glutathione. Conversely, lipid peroxidation (TBARS), nitric oxide content, and gluthathione reductase activity were significantly higher, indicating an increase in oxidative stress. In aortic rings, removal of PVAT increased serotonin-induced contractions, but the effect was significantly lower in rings from FRD rats. This effect was no longer observed when the two contractions were performed in PVAT-deprived rings. PVAT did not affect the contractions triggered by high K+-induced depolarization either in CD or FRD rats. Conclusions FRD induces multiple metabolic and endocrine systemic alterations which also alter PVAT and the vascular relaxant properties of this tissue. The changes in PVAT would affect its paracrine modulation of vascular function.

Abstract Background Cognition is a multidimensional construct and to our knowledge, no previous studies have examined the independent contribution of specific domains of cognition to health related quality of life. To determine whether executive functions are independently associated with health related quality of life assessed using Quality Adjusted Life Years (QALYs) calculated from the EuroQol EQ-5D (EQ-5D) in older women after adjusting for known covariates, including global cognition. Therefore, we conducted a secondary analysis of community-dwelling older women aged 65-75 years who participated in a 12-month randomized controlled trial of resistance training. We assessed global cognition using the Mini-Mental State Examination (MMSE) and executive functions using the: 1) Stroop Test; 2) Trail Making Test (Part B) and 3) Digits Verbal Span Backwards Test. We calculated QALYs from the EQ-5D administered at baseline, 6 months and 12 months. Results Our multivariate linear regression model demonstrated the specific executive processes of set shifting and working memory, as measured by Trail Making Test (Part B) and Digits Verbal Span Backward Test (p < 0.01) respectively, were independently associated with QALYs after accounting for age, comorbidities, general mobility, and global cognition. The final model explained 50% of the variation in QALYs. Conclusions Our study highlights the specific executive processes of set shifting and working memory were independently associated with QALYs -- a measure of health related quality of life. Given that executive functions explain variability in QALYs, clinicians may need to consider assessing executive functions when measuring health related quality of life. Further, the EQ-5D may be used to track changes in health status over time and serve as a screening tool for clinicians. Trial Registration ClinicalTrials.gov Identifier: NCT00426881.

Abstract A response to Weis and Pasipanodya 'Measuring health-related quality of life in tuberculosis: a systemic review - Response'.

Abstract Background Asthma is associated with enormous healthcare expenditures that include both direct and indirect costs. It is also associated with the loss of future potential earnings related to both morbidity and mortality. The objective of the study is to determine the burden of disease costs associated with asthma. Methods We performed a systematic search of MEDLINE, EMBASE, CINAHL, CDSR, OHE-HEED, and Web of Science Databases between 1966 and 2008. Results Sixty-eight studies met the inclusion criteria. Hospitalization and medications were found to be the most important cost driver of direct costs. Work and school loss accounted for the greatest percentage of indirect costs. The cost of asthma was correlated with comorbidities, age, and disease severity. Conclusion Despite the availability of effective preventive therapy, costs associated with asthma are increasing. Strategies including education of patients and physicians, and regular follow-up are required to reduce the economic burden of asthma.

Abstract Introduction Tuberculosis remains a major public health problem worldwide. In recent years, increasing efforts have been dedicated to assessing the health-related quality of life experienced by people infected with tuberculosis. The objectives of this study were to better understand the impact of tuberculosis and its treatment on people's quality of life, and to review quality of life instruments used in current tuberculosis research. Methods A systematic literature search from 1981 to 2008 was performed through a number of electronic databases as well as a manual search. Eligible studies assessed multi-dimensional quality of life in people with tuberculosis disease or infection using standardized instruments. Results of the included studies were summarized qualitatively. Results Twelve original studies met our criteria for inclusion. A wide range of quality of life instruments were involved, and the Short-Form 36 was most commonly used. A validated tuberculosis-specific quality of life instrument was not located. The findings showed that tuberculosis had a substantial and encompassing impact on patients' quality of life. Overall, the anti-tuberculosis treatment had a positive effect of improving patients' quality of life; their physical health tended to recover more quickly than the mental well-being. However, after the patients successfully completed treatment and were microbiologically 'cured', their quality of life remained significantly worse than the general population. Conclusion Tuberculosis has substantially adverse impacts on patients' quality of life, which persist after microbiological 'cure'. A variety of instruments were used to assess quality of life in tuberculosis and there has been no well-established tuberculosis-specific instrument, making it difficult to fully understand the impact of the illness.

Abstract Background Chronic conditions could negatively affect the quality of life of older adults. This may be partially due to a relative lack of physical activity. We examined whether physical activity mediates the relationship between different chronic conditions and several health outcomes that are important to the quality of life of older adults. Methods The data were taken from the Canadian Community Health Survey (cycle 1.1), a cross-section survey completed in 2001. Only respondents who were 65 years or older were included in our study (N = 22,432). The Health Utilities Index Mark 3 (HUI3) was used to measure overall quality of life, and to measure selected health outcomes (dexterity, mobility, pain, cognition, and emotional wellbeing) that are considered to be of importance to the quality of life of older adults. Leisure-time physical activity was assessed by determining weekly energy expenditure (Kcal per week) based on the metabolic equivalents of self-reported leisure activities. Linear and logistic regression models were used to determine the mediating effect of leisure-time physical activity while controlling for demographic variables (age and sex), substance use (tobacco use and alcohol consumption), and obesity. Results Having a chronic condition was associated with a relative decrease in health utility scores and a relative increase in mobility limitations, dexterity problems, pain, emotional problems (i.e., decreased happiness), and cognitive limitations. These negative consequences could be partially attributed to a relative lack of physical activity in older adults with a chronic condition (14% mediation for the HUI3 score). The corresponding degree of mediation was 18% for mobility limitations, 5% for pain, and 13% for emotional wellbeing (statistically significant mediation was not observed for the other health attributes). These values varied with respect to the different chronic conditions examined in our study. Conclusion Older adults with chronic conditions are less likely to engage in leisure-time physical activities of at least 1,000 Kcal per week, and this association partially accounts for some negative consequences of chronic conditions, including mobility limitations, pain, and emotional problems. These findings provide support for health promotion programs that facilitate or encourage increased leisure-time physical activity in older people with chronic conditions.