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Hypothetical bias continues to be a primary challenge for stated preference methods. The source of hypothetical bias might be approached from the conceptual framework of \"psychological distance.\" By comparing the two samples of pregnant and non-pregnant women, this study aimed to investigate the impact of psychological distance from real-life choice on prenatal screening and diagnostic strategies preferences. A discrete choice experiment was conducted among a sample of pregnant women and a sample of the general Canadian population. The attributes included: timing of the results, false-negative rate, false-positive rate, risk of miscarriage, and out-of-pocket cost. The dual response design, including forced and unforced choices, was used. Hierarchical Bayes modelling was employed to estimate part-worth utilities at the individual level. The relative importance scores of the attributes and willingness to pay for improvement in attributes were compared between pregnant and non-pregnant women. Using the individual-level preference weights, we also estimated the uptake rates for various scenarios and compared the two samples. We quantified hypothetical bias by comparing the real-world decision and predicted choices for different strategies for the pregnant and non-pregnant women samples. A sample of 426 pregnant women was matched to 426 non-pregnant women from the general public sample. For pregnant women, the ability to detect chromosomal abnormalities was the most important attribute. For the matched sample of non-pregnant women, false-negative rate and risk of miscarriage were the most important attributes. In addition, pregnant women were willing to pay more for improvement in test characteristics and less sensitive to changes in strategy cost than non-pregnant women. The findings also showed a more significant difference between the actual and predicted choice among non-pregnant women. Our findings showed that although both groups valued safer and more accurate screening strategies, there was a difference in willingness to pay, sensitivity to cost, and predictive power of discrete choice experiment estimates between pregnant and non-pregnant women. This difference can be explained by their psychological distance from the decision. In conclusion, psychological distance impacts decision-making and can be identified as a source of hypothetical bias in measuring prenatal screening and diagnosis preferences.

Background Overweight and obese persons are at risk of a number of medical conditions which can lead to further morbidity and mortality. The primary objective of this study is to provide an estimate of the incidence of each co-morbidity related to obesity and overweight using a meta-analysis. Methods A literature search for the twenty co-morbidities identified in a preliminary search was conducted in Medline and Embase (Jan 2007). Studies meeting the inclusion criteria (prospective cohort studies of sufficient size reporting risk estimate based on the incidence of disease) were extracted. Study-specific unadjusted relative risks (RRs) on the log scale comparing overweight with normal and obese with normal were weighted by the inverse of their corresponding variances to obtain a pooled RR with 95% confidence intervals (CI). Results A total of 89 relevant studies were identified. The review found evidence for 18 co-morbidities which met the inclusion criteria. The meta-analysis determined statistically significant associations for overweight with the incidence of type II diabetes, all cancers except esophageal (female), pancreatic and prostate cancer, all cardiovascular diseases (except congestive heart failure), asthma, gallbladder disease, osteoarthritis and chronic back pain. We noted the strongest association between overweight defined by body mass index (BMI) and the incidence of type II diabetes in females (RR = 3.92 (95% CI: 3.10–4.97)). Statistically significant associations with obesity were found with the incidence of type II diabetes, all cancers except esophageal and prostate cancer, all cardiovascular diseases, asthma, gallbladder disease, osteoarthritis and chronic back pain. Obesity defined by BMI was also most strongly associated with the incidence of type II diabetes in females (12.41 (9.03–17.06)). Conclusion Both overweight and obesity are associated with the incidence of multiple co-morbidities including type II diabetes, cancer and cardiovascular diseases. Maintenance of a healthy weight could be important in the prevention of the large disease burden in the future. Further studies are needed to explore the biological mechanisms that link overweight and obesity with these co-morbidities.

Down syndrome (DS) is the most frequently occurring fetal chromosomal abnormality and different prenatal screening strategies are used for determining risk of DS worldwide. New non-invasive prenatal testing (NIPT), which uses cell-free fetal DNA in maternal blood can provide benefits due to its higher sensitivity and specificity in comparison to conventional screening tests. This study aimed to assess the cost-effectiveness of using population-level NIPT in fetal aneuploidy screening for DS. We developed a microsimulation decision-analytic model to perform a probabilistic cost-effectiveness analysis (CEA) of prenatal screening and diagnostic strategies for DS. The model followed individual simulated pregnant women through the pregnancy pathway. The comparators were serum-only screening, contingent NIPT (i.e., NIPT as a second-tier screening test) and universal NIPT (i.e., NIPT as a first-tier screening test). To address uncertainty around the model parameters, the expected values of costs and quality-adjusted life-years (QALYs) in the base case and all scenario analyses were obtained through probabilistic analysis from a Monte Carlo simulation. Base case and scenario analyses were conducted by repeating the micro-simulation 1,000 times for a sample of 45,605 pregnant women per the population of British Columbia, Canada (N = 4.8 million). Preliminary results of the sequential CEAs showed that contingent NIPT was a dominant strategy compared to serum-only screening. Compared with contingent NIPT, universal NIPT at the current test price was not cost-effective with an incremental cost-effectiveness ratio over $100,000/QALY. Contingent NIPT also had the lowest cost per DS case detected among these three strategies. Including NIPT in existing prenatal screening for DS is shown to be beneficial over conventional testing. However, at current prices, implementation of NIPT as a second-tier screening test is more cost-effective than deploying it as a universal test.

In a 48-week trial in patients with active rheumatoid arthritis despite treatment with methotrexate, adding sulfasalazine and hydroxychloroquine to methotrexate was not inferior to adding etanercept. The prognosis for patients with rheumatoid arthritis has improved dramatically over the past two decades. 1 , 2 The reasons for the improved prognosis include earlier diagnosis, treatment targeted to low disease activity or remission, the use of disease-modifying antirheumatic drugs (DMARDs) in combinations, and the availability of biologic therapies. 1 – 4 A substantial portion of patients who are diagnosed today will have a clinical remission with therapy. 1 , 2 , 5 , 6 Unfortunately, the cost of treating rheumatoid arthritis has also risen dramatically, and this disease is now more expensive to treat than diabetes, 7 largely as a consequence of the biologic therapies. Most clinicians . . .

ABSTRACTBackgroundThe Patented Medicine Prices Review Board (PMPRB), the agency that regulates the prices of patented medicines in Canada, published proposed amendments to the regulatory framework in December 2017. Because of a series of changes and delays, the revised policy has not yet been finalized. We sought to evaluate the potential early impact of the uncertainty about the PMPRB policy on patented-medicine launches. MethodsWe developed a retrospective cohort of patented medicines (molecules) sold in Canada and the 13 countries that the PMPRB currently uses or has proposed to use as price comparators, from sales data from the IQVIA MIDAS database for 2012–2021. The outcome was whether a molecule was launched (i.e., sold) in a specific country within 2 years of its global first launch (2-yr launch). We compared the change of 2-year launch before (2012–2017) and after the proposed amendments were published (“uncertain period,” 2018–2021) in Canada with the change in the United States and the other 12 countries as a group (“other-countries group”), using interrupted time series and logistic regressions, respectively. We further conducted analyses for each individual country and subgroups by molecule characteristics, such as therapeutic benefit, separately. ResultsWe included 242 and 107 new molecules launched before publication of the proposed amendments and during the uncertain period, respectively. The corresponding 2-year launch proportions were 45.0% and 30.8% in Canada, 81.4% and 82.2% in the US, and 83.9% and 70.1% in the other-countries group. All analyses showed changes in 2-year launch during the uncertain period in the US and in the other-countries group that were similar to the changes in Canada. Greater decreases were observed in Norway and Sweden than in Canada. The 2-year launch proportion for molecules with major therapeutic benefit decreased from 45.8% to 31.3% in Canada during the uncertain period and from 87.5% to 62.5% in the other-countries group, but increased from 91.7% to 100% in the US. InterpretationNo negative impact of the PMPRB-policy uncertainty on molecule launches was observed when comparing Canada with price-comparator countries, except for molecules with major therapeutic benefit. The reduction in launches of medicines with major therapeutic benefit in Canada requires continuing investigation.

Objective To synthesize and determine the relative effectiveness of diverse opioid agonist treatment (OAT) medications, including injectables, for opioid use disorder (OUD). Methods We searched EMBASE, PubMed, and CENTRAL for Randomised Controlled Trials (RCTs) (CRD42018109469) and previously published systematic reviews of head-to-head trials of OAT medications. The primary outcome was treatment retention, and secondary outcomes included days of opioid use, days of cocaine use, and proportion of participants involved in criminalized activities. We calculated odds ratios (ORs) and mean differences (MDs) and corresponding 95% credible intervals (CrI) using Bayesian network meta-analyses (NMAs) to indirectly compare treatments at varying lengths of follow-up (3 to 12 months). Sensitivity analyses examined influence of follow-up duration and other trial factors. Results Twenty-four RCTs were included. Diacetylmorphine plus oral methadone and injectable hydromorphone plus oral methadone had similar retention compared to one another (OR: 1.05; 95%CrI: 0.27, 4.10). Diacetylmorphine plus oral methadone had similar or statistically favourable retention versus low, medium, and high doses of conventional OATs: buprenorphine (OR: 13.55; 95%CrI: 4.51, 42.52; OR: 5.07; 95%CrI: 2.03, 12.47; OR: 2.21; 95%CrI: 0.18, 21.54) and methadone (OR: 5.88; 95%CrI: 2.34, 16.33; OR: 3.66; 95%CrI: 1.57, 8.82; OR: 3.67; 95%CrI: 1.83, 8.35). Similarly, injectable hydromorphone plus oral methadone also showed favourable or similar retention relative to conventional OATs. Limiting analyses to trials that included only OAT-experienced patients, that offered no extra participation incentive, and/or with 6 months (± 0.5) of follow-up generally did not change the direction of the findings. Injectable hydromorphone plus oral methadone was also statistically favoured in terms of reduced days of opioid use relative to methadone, but mean differences in days of cocaine use were similar. Diacetylmorphine plus oral methadone was associated with a smaller proportion of participation in criminalized activities relative to methadone alone. Conclusion Both diacetylmorphine and injectable hydromorphone supplemented with methadone showed favourable retention compared to methadone and buprenorphine, depending on the strength of the OAT being co-prescribed or being compared to. These results provide further support for alternatives to conventional OATs such as diacetylmorphine or injectable hydromorphone for treatment retention.

Background The 2018 World Health Organization HIV guidelines were based on the results of a network meta-analysis (NMA) of published trials. This study employed individual patient-level data (IPD) and aggregate data (AgD) and meta-regression methods to assess the evidence supporting the WHO recommendations and whether they needed any refinements. Methods Access to IPD from three trials was granted through ClinicalStudyDataRequest.com (CSDR). Seven modelling approaches were applied and compared: 1) Unadjusted AgD network meta-analysis (NMA) – the original analysis; 2) AgD-NMA with meta-regression; 3) Two-stage IPD-AgD NMA; 4) Unadjusted one-stage IPD-AgD NMA; 5) One-stage IPD-AgD NMA with meta-regression (one-stage approach); 6) Two-stage IPD-AgD NMA with empirical-priors (empirical-priors approach); 7) Hierarchical meta-regression IPD-AgD NMA (HMR approach). The first two were the models used previously. Models were compared with respect to effect estimates, changes in the effect estimates, coefficient estimates, DIC and model fit, rankings and between-study heterogeneity. Results IPD were available for 2160 patients, representing 6.5% of the evidence base and 3 of 24 edges. The aspect of the model affected by the choice of modeling appeared to differ across outcomes. HMR consistently generated larger intervals, often with credible intervals (CrI) containing the null value. Discontinuations due to adverse events and viral suppression at 96 weeks were the only two outcomes for which the unadjusted AgD NMA would not be selected. For the first, the selected model shifted the principal comparison of interest from an odds ratio of 0.28 (95% CrI: 10.17, 0.44) to 0.37 (95% CrI: 0.23, 0.58). Throughout all outcomes, the regression estimates differed substantially between AgD and IPD methods, with the latter being more often larger in magnitude and statistically significant. Conclusions Overall, the use of IPD often impacted the coefficient estimates, but not sufficiently as to necessitate altering the final recommendations of the 2018 WHO Guidelines. Future work should examine the features of a network where adjustments will have an impact, such as how much IPD is required in a given size of network.

Objective: The objective of this study was to assess the cost attributable to lost productivity from arthritis and the association between the degree of loss and demographic, disease-related, occupational, and psychosocial variables for people. Methods: In a prospective study, 383 employed individuals with arthritis were recruited from southwestern Ontario, Canada. Respondents completed structured questionnaires assessing demographic, disease-related, workplace, and psychosocial variables as well as employment-related transitions at 2 time points 18 months apart. Indirect costs resulting from arthritis-related absences, reduced performance, decreased work hours, job change, and work disability were estimated. A proportional odds model was used to assess the impact of the various variables on lost productivity. Results: The average cost attributable to arthritis was CAN $11,553 ($CAN = 0.75 $US) per person per year. The largest component of the loss was the result of reduced performance at work, which accounted for 41% ($4724) of the total loss. This was followed by wage loss resulting from stopping working or changing jobs, which comprised 37% ($4309) of the total. Another 12% ($1398) and 10% ($1121) of the loss were the result of the decrease in hours of work and absenteeism, respectively. Four variables were associated with the productivity loss: greater symptom severity (odds ratio [OR] = 1.11), low or medium control over the work schedule (OR = 0.55 and 0.60, respectively), greater workspace limitation (OR = 1.10), and higher depression (OR = 1.04). Conclusions: Indirect arthritis-related costs are substantial. Our results show that not only the disease itself, but also psychosocial and work-related factors affect the magnitude of the costs.

Objectives Our objective was to determine the relationship between osteoarthritis (OA) and heart diseases (myocardial infarction (MI), angina, congestive heart failure (CHF)) and stroke using population-based survey data. Design Cross-sectional study. Setting Canadian Community Health Survey (CCHS). Participants Adult participants in the CCHS cycles 1.1, 2.1 and 3.1 were included. CCHS provides nationally representative data on health determinants, health status and health system utilisation. We have identified 40 817 self-reported OA subjects and selected 1:1 matched non-OA respondents by age, sex and CCHS cycles. Main outcome measures Self-reported heart disease was the primary outcome and MI, angina, CHF and stroke were considered as secondary outcomes. Multivariable logistic regression models were used to estimate the ORs after adjusting for sociodemographic status, obesity, physical activity, smoking status, fruit and vegetable consumption, medication use, diabetes, hypertension and chronic obstructive pulmonary disease. Results The mean age of OA cases was 66 years and 71.6% were women. OA exhibited increased odds of prevalent heart disease, and adjusted overall OR (95% CI) was 1.45 (1.36 to 1.54), 1.35 (1.21 to 1.50) among men and 1.51 (1.39 to 1.64) among women with OA. OA showed increased ORs for angina and CHF in both men and women, and for MI in women. ORs (95% CI) for men and women, respectively, were 1.08 (0.91 to 1.28) and 1.49 (1.28 to 1.75) for MI, 1.76 (1.43 to 2.17) and 1.84 (1.59 to 2.14) for angina, 1.50 (1.13 to 1.97) and 1.81 (1.49 to 2.21) for CHF, and 1.08 (0.83 to 1.40) and 1.13 (0.93 to 1.37) for stroke. Conclusions Prevalent OA was associated with self-reported heart disease, particularly angina, and CHF in both men and women, after controlling for established risk factors for these conditions. This study provides a rationale for further investigation of the association between OA and heart disease in longitudinal studies for investigating possible biological and behavioural mechanisms.

Although diacetylmorphine has been proven to be more effective than methadone maintenance treatment for opioid dependence, its direct costs are higher. We compared the cost-effectiveness of diacetylmorphine and methadone maintenance treatment for chronic opioid dependence refractory to treatment. We constructed a semi-Markov cohort model using data from the North American Opiate Medication Initiative trial, supplemented with administrative data for the province of British Columbia and other published data, to capture the chronic, recurrent nature of opioid dependence. We calculated incremental cost-effectiveness ratios to compare diacetylmorphine and methadone over 1-, 5-, 10-year and lifetime horizons. Diacetylmorphine was found to be a dominant strategy over methadone maintenance treatment in each of the time horizons. Over a lifetime horizon, our model showed that people receiving methadone gained 7.46 discounted quality-adjusted life-years (QALYs) on average (95% credibility interval [CI] 6.91–8.01) and generated a societal cost of $1.14 million (95% CI $736 800–$1.78 million). Those who received diacetylmorphine gained 7.92 discounted QALYs on average (95% CI 7.32–8.53) and generated a societal cost of $1.10 million (95% CI $724 100–$1.71 million). Cost savings in the diacetylmorphine cohort were realized primarily because of reductions in the costs related to criminal activity. Probabilistic sensitivity analysis showed that the probability of diacetylmorphine being cost-effective at a willingness-to-pay threshold of $0 per QALY gained was 76%; the probability was 95% at a threshold of $100 000 per QALY gained. Results were confirmed over a range of sensitivity analyses. Using mathematical modelling to extrapolate results from the North American Opiate Medication Initiative, we found that diacetylmorphine may be more effective and less costly than methadone among people with chronic opioid dependence refractory to treatment.