Cancer risk, disease-modifying therapy, and age in multiple sclerosis: A retrospective population-based cohort study.

BACKGROUND: Long-term population-based safety studies are needed to investigate cancer outcomes in people with multiple sclerosis (MS) treated with modern disease-modifying therapy (DMT). OBJECTIVES: To investigate if exposure to DMT increases the risk of invasive cancer in MS. METHODS: We used population-based administrative health data from Alberta, Canada between 2008 and 2018. DMT exposure was defined in two ways: first as exposure to any DMT, and second by DMT type (modulating, sequestering, depleting). Study outcome was time to first diagnosis of invasive cancer. Cancer risk was compared to the general population using standardized incidence ratios (SIRs) and to the unexposed MS cases using hazard ratios (HRs). RESULTS: The analysis included 14,313 MS cases: 5,801 (40.5 %) were exposed to DMT. Median (interquartile range) follow-up was 8.4 (4.3, 10.4) years. Compared to the general population, there was no difference in cancer risk for the overall MS population (SIR: 0.94, 95 % confidence interval [CI]: 0.87, 1.02) or the DMT-exposed MS cases (SIR: 0.89; 95 % CI: 0.75, 1.05). Compared to unexposed MS cases, we found an interaction with age for exposure to any DMT (p = 0.001) and modulating DMT (p = 0.001), indicating that a difference in the risk of cancer associated with DMT depends on age. Cancer risk was not associated with exposure to sequestering DMT (HR: 1.28, 95 % CI: 0.78, 2.08) or depleting DMT (HR: 2.29, 95 % CI: 0.86, 6.14). CONCLUSIONS: Cancer risk for MS patients was similar to the general population. In the MS population, the age-dependent effect of DMT for cancer risk suggests a higher risk of cancer with age 62 or older and a protective effect at younger age. Further investigation is required to clarify whether the interaction between DMT exposure and age is a causal effect.

Employment status, productivity loss, and associated factors among people with multiple sclerosis.

BACKGROUND: Multiple Sclerosis (MS) affects people in their most productive years of life. Consequently, MS can substantially affect employment and work-related outcomes. OBJECTIVES: This study characterizes productivity loss and employment status of people with multiple sclerosis (pwMS) and investigates associated factors. METHODS: We used baseline data collected as part of the Canadian Prospective Cohort Study to Understand Progression in Multiple Sclerosis (CanProCo). Using the Valuation of Lost Productivity questionnaire, we measured MS-related paid work productivity loss for those employed, productivity losses incurred by those unemployed (i.e. lost employment time), and unpaid work productivity losses for all. A set of sociodemographic, disease, and performance-related factors were investigated using a two-part regression model for productivity loss and a multinomial logistic model for employment status. RESULTS: From the cohort of 888 pwMS enrolled at baseline (mostly showing mild to moderate disability), 75% were employed, and of those unemployed, 69% attributed their unemployment to health-related issues. Total productivity loss over a 3-month period averaged 64 and 395 hours for those employed and unemployed, respectively. Some factors that affected productivity loss and employment status included use of disease-modifying therapies, fatigue, and performance indicators such as cognitive processing speed. CONCLUSION: Productivity loss experienced by employed and unemployed pwMS is substantial. Targeting the identified modifiable factors is likely to improve work productivity and permanence of MS patients in the workforce.

Direct Health Care Costs Associated With Multiple Sclerosis: A Population-Based Cohort Study in British Columbia, Canada, 2001-2020.

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS), a leading cause of nontraumatic neurologic disability in young adults, exerts a substantial economic burden on the health care system. The objective of this study was to quantify the excess health care costs of MS in British Columbia, Canada. METHODS: A retrospective-matched cohort study of patients with MS was conducted using population-based administrative health data from 2001 to 2020. Patients with MS who satisfied a validated case definition were matched to 5 unique controls without MS on sex, age, and cohort entry date. Patients and controls were followed to the end of 2020 or to their last health care resource use, whichever came first. We calculated the direct medical costs for each individual, including outpatient services use, hospital admissions, and dispensed medications. We used generalized linear models with an identity link and normal distribution to estimate the excess cost of MS as the mean cost difference between patients with MS and controls. All costs were reported in 2020 Canadian dollars. RESULTS: A total of 17,071 patients with MS were matched to 85,355 controls. Overall, 72.4% were female, and the mean age at cohort entry date was 46.1 years. The excess cost of MS was $6,881 (95% CI: $6,713, $7,049) per patient-year. Inpatient, outpatient, and medication costs accounted for 25%, 10%, and 65% of excess costs, respectively. Excess costs were higher in patients with MS with at least one disease-modifying therapy (DMT) prescription ($13,267; 95% CI: $12,992-$13,542) compared with non-DMT users ($3,469; 95% CI: $3,297-$3,641) and even higher among frequent DMT users ($24,835; 95% CI: $24,528-$25,141). Patients with MS with a history of at least one relapse requiring hospitalization had higher excess costs ($10,543; 95% CI: $10,136-$10,950) compared with patients with MS without a relapse; hospitalizations accounted for 51% of the costs in this group. The excess cost of hospitalizations was $1,391 lower among frequent DMT users than non-DMT users. DISCUSSION: The economic burden of MS is considerable, with medications, particularly DMTs, being the largest cost driver. Future studies should investigate how disease management strategies, including early diagnosis and timely use of DMTs, could offset future and ongoing costs while improving patients' quality of life.

Productivity loss among people with early multiple sclerosis: A Canadian study.

OBJECTIVES: To analyze work productivity loss and costs, including absenteeism (time missed from work), presenteeism (reduced productivity while working), and unpaid work loss, among a sample of employed people with multiple sclerosis (pwMS) in Canada, as well as its association with clinical, sociodemographic, and work-related factors. METHODS: We used cross-sectional data collected as part of the Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo) and information from the Valuation of Lost Productivity questionnaire. RESULTS: Among 512 pwMS who were employed, 97% showed no or mild disability and 55% experienced productivity loss due to MS in the prior 3 months. Total productivity time loss over a 3-month period averaged 60 hours (SD = 107; 23 from presenteeism, 19 from absenteeism, and 18 from unpaid work), leading to a mean cost of lost productivity of CAD$2480 (SD = 4282) per patient, with an hourly paid productivity loss greater than the wage loss. Fatigue retained significant associations with all productivity loss outcomes. CONCLUSION: Unpaid work loss and productivity losses exceeding those of the employee alone (due to teamwork and associated factors) are key additional contributors of the high economic burden of MS. Workplace accommodations and treatments targeted at fatigue could lessen the economic impact of MS.

Trends in oral corticosteroids use in severe asthma: a 14-year population-based study.

BACKGROUND: Oral corticosteroids are important components of pharmacotherapy in severe asthma. Our objective was to describe the extent, trends, and factors associated with exposure to oral corticosteroids (OCS) in a severe asthma cohort. METHODS: We used administrative health databases of British Columbia, Canada (2000-2014) and validated algorithms to retrospectively create a cohort of severe asthma patients. Exposure to OCS within each year of follow-up was measured in two ways: maintenance use as receiving on average ≥ 2.5 mg/day (prednisone-equivalent) OCS, and episodic use as the number of distinct episodes of OCS exposure for up to 14 days. Trends and factors associated with exposure on three time axes (calendar year, age, and time since diagnosis) were evaluated using Poisson regression. RESULTS: 21,144 patients (55.4% female; mean entry age 28.7) contributed 40,803 follow-up years, in 8.2% of which OCS was used as maintenance therapy. Maintenance OCS use declined by 3.8%/calendar year (p < 0.001). The average number of episodes of OCS use was 0.89/year, which increased by 1.1%/calendar year (p < 0.001). Trends remained significant for both exposure types in adjusted analyses. Both maintenance and episodic use increased by age and time since diagnosis. CONCLUSIONS: This population-based study documented a secular downward trend in maintenance OCS use in a period before widespread use of biologics. This might have been responsible for a higher rate of exacerbations that required episodic OCS therapy. Such trends in OCS use might be due to changes in the epidemiology of severe asthma, or changes in patient and provider preferences over time.

Using Best-Worst Choice Methodology in a Survey of Pharmacists Regarding Pharmacy Practice Skills Teaching.

Objective. To conduct a survey of practicing pharmacists in which best-worst choice methodology was used to prioritize pharmacy practice skills for inclusion in a pharmacy curriculum in New Zealand.Methods. A literature search and review of pharmacy curricula were conducted, and the findings were used to develop a best-worst choice survey instrument regarding inclusion of pharmacy practice skills in the pharmacy curriculum. The survey was sent to registered pharmacists and intern pharmacists in New Zealand. Participants were asked to prioritize 16 skills in terms of their importance and relevance to pharmacy practice.Results. Of the 3836 pharmacists invited to participate in the survey, 388 completed the questionnaire. Comprehensive chronic disease management, specialty medications, and medicines use review were the top three prioritized skills. Injections, independent prescribing, and specialty compounding were the skills ranked as having the lowest priority. The pharmacists' gender, age, practice setting, and ethnicity all influenced their skill prioritization. The pharmacists emphasized skills required in their current practice but deemphasized some skills that were emerging professional responsibilities.Conclusion. If curricular reform is to include new skills that are largely unfamiliar to or deemed unimportant by practicing pharmacists, quality assurance of students' experiential education will be needed. Furthermore, preceptor education about changing expectations for pharmacy graduates' skill sets must be adequately developed and implemented to ensure that preceptors provide students with opportunities to practice the full range of skills they will need in practice and provide them with accurate assessment and helpful feedback.

Healthcare system encounters before COPD diagnosis: a registry-based longitudinal cohort study.

BACKGROUND: There is high interest in strategies for improving early detection of chronic obstructive pulmonary disease (COPD). These strategies often rely on opportunistic encounters between patients with undiagnosed COPD and the healthcare system; however, the frequency of these encounters is currently unknown. METHODS: We used administrative health data for the province of British Columbia, Canada, from 1996 to 2015. We identified patients with COPD using a validated case definition, and assessed their visits to pharmacists, primary care and specialist physicians in the 5 years prior to the initial diagnosis of COPD. We used generalised linear models to compare the rate of outpatient visits between COPD and non-COPD comparator subjects matched on age, sex and socioeconomic status. RESULTS: We assessed 112 635 COPD and non-COPD pairs (mean 68.6 years, 51.0% male). Patients with COPD interacted with pharmacists most frequently in the 5 years before diagnosis (mean 14.09, IQR 4-17 visits/year), followed by primary care (10.29, IQR 4-13 visits/year) and specialist (8.11, IQR 2-11 visits/year) physicians. In the 2 years prior to diagnosis, 72.1% of patients with COPD had a respiratory-related primary care visit that did not result in a COPD diagnosis. Compared with non-COPD subjects, patients with COPD had higher rates of primary care (rate ratio (RR) 1.40, 95% CI 1.39 to 1.41), specialist (RR 1.35, 95% CI 1.34 to 1.37) and pharmacist (RR 1.62, 95% CI 1.60 to 1.63) encounters. CONCLUSIONS: Patients with COPD used higher rates of outpatient services before diagnosis than non-COPD subjects. Case detection technologies implemented in pharmacy or primary care settings have opportunities to diagnose COPD earlier.

Extent, trends, and determinants of controller/reliever balance in mild asthma: a 14-year population-based study.

BACKGROUND: The majority of patients with asthma have the mild form of the disease. Whether mild asthma patients receive appropriate asthma medications has not received much attention in the literature. We examined the trends in indicators of controller/reliever balance. METHODS: Using administrative health databases of British Columbia, Canada (2000 to 2013), we created a population-based cohort of adolescents/adults with mild asthma using validated case definition algorithms. Each patient-year of follow-up was assessed based on two markers of inappropriate medication prescription: whether the ratio of controller medications (inhaled corticosteroids [ICS] and leukotriene receptor antagonists [LTRA]) to total asthma-related prescriptions was low (cut-off 0.5 according to previous validation studies), and whether short-acting beta agonists (SABA) were prescribed inappropriately according to previously published criteria that considers SABA in relation to ICS prescriptions. Generalized linear models were used to evaluate trends and to examine the association between patient-, disease-, and healthcare-related factors and medication use. RESULTS: The final cohort consisted of 195,941 mild asthma patients (59.5% female; mean age at entry 29.6 years) contributing 1.83 million patient-years. In 48.8% of patient-years, controller medications were suboptimally prescribed, while in 7.2%, SABAs were inappropriately prescribed. There was a modest year-over-year decline in inappropriate SABA prescription (relative change - 1.3%/year, P < 0.001) and controller-to-total-medications (relative change - 0.5%/year, P < 0.001). Among the studied factors, the indices of type and quality of healthcare (namely respirologist consultation and receiving pulmonary function test) had the strongest associations with improvement in controller/reliever balance. CONCLUSIONS: Large number of mild asthma patients continue to be exposed to suboptimal combinations of asthma medications, and it appears there are modifiable factors associated with such phenomenon.

How do parents and providers trade-off between disability and survival? Preferences in the treatment of pediatric medulloblastoma.

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 medullo-blastoma, and compares their values and trade-offs between different levels of survival and disability.

Testing the External Validity of a Discrete Choice Experiment Method: An Application to Latent Tuberculosis Infection Treatment.

OBJECTIVES: To explore the external validity and predictive power of stated preferences obtained from a discrete choice experiment (DCE) by comparing the predicted behavior of respondents to their actual choices at an individual level. METHODS: A DCE was performed in patients before being offered treatment for latent tuberculosis infection. A mixed logit model was estimated using hierarchical Bayes. The individual-specific preference coefficients were used to calculate the expected probability of choosing the treatment by each patient. The predicted choice using this probability was compared with their actual decision. We used a receiver-operating characteristic curve and different thresholds to convert probabilities into the predicted choices. The comparability of different distributions for the random parameters was also examined. RESULTS: Our results identified significant heterogeneity in preferences for all attributes among respondents. The best model correctly predicted actual treatment decisions for 83% of the participants. The results from using different thresholds and a receiver-operating characteristic curve also confirmed the compatibility between predicted and actual choices. We showed that individual-specific coefficients reflected respondents' actual choices more closely compared with the aggregate-level estimates. CONCLUSIONS: The results of this study provided support for the external validity of DCEs on the basis of their power to predict actual behavior in this setting. Future investigations are, however, required to establish the external validity of DCEs in different settings.

Opinions and preferences of British Columbia pharmacists and physicians on medication management services.

BACKGROUND: Medication management (MM) services are being provided by pharmacists across Canada in various forms, but pharmacist-physician collaboration is still not a routine practice in most jurisdictions. This survey aimed to gather pharmacists' and physicians' opinions and preferences for MM provision. METHODS: Two parallel, cross-sectional online surveys, including best-worst scaling tasks, were designed for pharmacists and physicians in British Columbia to capture and compare their preferences for a number of attributes of MM. RESULTS: Surveys were completed by 119 pharmacists and 146 physicians. Results indicate that pharmacists and physicians had similar opinions on many aspects of MM. Ninety-five percent of pharmacists and 69% of physicians believed that additional health services are needed to help patients optimize the use of their medications. However, the majority of each group felt that they were the most important health care professional in providing this service. Most pharmacists (79%) and some physicians (25%) thought that optimizing use of medications would result in both decreased costs and utilization to the health care system. Both pharmacists and physicians felt that the best attribute of an MM service would be if the services resulted in improved health and medication use for patients. Both groups were motivated by increased remuneration for MM; however, the relative strength of preference for this was higher among physicians. Interestingly, physicians valued improved medication adherence as a result of MM more highly than pharmacists did. DISCUSSION AND CONCLUSION: Most pharmacists and physicians agreed that improving patients' health and medication use would be the best attribute of MM and that there is a need for such services. However, physicians also had strong preferences for being remunerated for participating in MM provision.

Societal preferences in the treatment of pediatric medulloblastoma: Balancing risk of death and quality of life.

PURPOSE: Medulloblastoma is the most prevalent childhood brain cancer. Children with medulloblastoma typically receive a combination of surgery, radiation, and chemotherapy. The survival rate is high but survivors often have sequelae from radiotherapy of the entire developing brain and spinal cord. Ongoing genetic studies have suggested that decreasing the dose of radiation might be possible among children with favorable molecular variants; however, this may result in an increased disease recurrence. As such, there is a need to investigate the nature of trade-offs that individuals are willing to make regarding the treatment of medulloblastoma. METHOD: We used best-worst scaling to estimate the importance of attributes affecting the general public's decision making around the treatment of medulloblastoma. After conducting focus groups, we selected three relevant attributes: (1) the accuracy of the genetic test; (2) the probability of serious adverse effects of the treatment(s); and (3) the survival rate. Using the paired method, we applied a conditional logit model to estimate preferences. RESULTS: In total, 3,006 respondents (51.3% female) with an average age of 43 years answered the questionnaires. All coefficients were statistically significantly different from zero and the attribute levels of adverse effects and the survival rate had the most impact on individuals' stated decision making. CONCLUSION: Overall, respondents showed high sensitivity to children experiencing disability particularly in the setting of a good prognosis. However, among children with poor prognostic molecular variants, participants showed tolerance about having a child with mild and partial disability compared to a low rate of survival.

Are patients willing to pay for total shoulder arthroplasty? Evidence from a discrete choice experiment.

BACKGROUND: Total shoulder arthroplasty (TSA) is a common treatment to decrease pain and improve shoulder function in patients with severe osteoarthritis (OA). In Canada, patients requiring this procedure often wait a year or more. Our objective was to determine patient preferences related to accessing TSA, specifically comparing out-of-pocket payments for treatment, travel time to hospital, the surgeon's level of experience and wait times. METHODS: We administered a discrete choice experiment among patients with endstage shoulder OA currently waiting for TSA. Respondents were presented with 14 different choice sets, each with 3 options, and they were asked to choose their preferred scenario. A conditional logit regression model was used to estimate the relative preference and willingness to pay for each attribute. RESULTS: Sixty-two respondents completed the questionnaire. Three of the 4 attributes significantly influenced treatment preferences. Respondents had a strong preference for an experienced surgeon (mean 0.89 ± standard error [SE] 0.11), while reductions in travel time (-0.07 ± 0.04) or wait time (-0.04 ± 0.01) were of less importance. Respondents were found to be strongly averse (-1.44 ± 0.18) to surgical treatment by a less experienced surgeon and to paying out-of-pocket for their surgical treatment (-0.56 ± 0.05). CONCLUSION: Our results suggest that patients waiting for TSA to treat severe shoulder OA have minimal willingness to pay for a reduction in wait time or travel time for surgery, yet will pay higher amounts for treatment by an experienced surgeon.

CONTEXTE: L'arthroplastie totale de l'épaule est un traitement courant visant à atténuer la douleur et à augmenter la fonction de l'épaule chez les patients atteints d'arthrose grave. Au Canada, l'attente est souvent d'un an ou plus pour cette intervention. Notre objectif était de cerner les préférences des patients concernant l'accès à l'arthroplastie, particulièrement en ce qui a trait aux déboursés personnels pour le traitement, à la durée du trajet vers l'hôpital, à l'expérience du chirurgien et au temps d'attente. MÉTHODES: Nous avons mené une expérience avec choix discrets auprès de patients atteints d'arthrose de l'épaule au stade terminal actuellement en attente d'une arthroplastie totale. Les répondants ont reçu 14 ensembles de choix différents, comportant chacun 3 options, et devaient choisir leur scénario préféré. Nous avons utilisé un modèle de régression logit conditionnelle pour estimer la préférence relative et la disposition à payer pour chaque caractéristique. RÉSULTATS: En tout, 62 répondants ont rempli le questionnaire. Trois des 4 caractéristiques ont significativement influencé les préférences de traitement. Les répondants avaient une forte préférence pour un chirurgien expérimenté (moyenne de 0,89 ± écart-type de 0,11), alors que la réduction de la durée du trajet (­0,07 ± 0,04) ou du temps d'attente (­0,04 ± 0,01) était moins importante. Les répondants se sont révélés très réfractaires (­1,44 ± 0,18) à se faire opérer par un chirurgien peu expérimenté et à payer de leur poche leur traitement chirurgical (­0,56 ± 0,05). CONCLUSION: Nos résultats semblent indiquer que les patients en attente d'une arthroplastie totale de l'épaule pour traiter une arthrose grave sont très peu disposés à payer pour réduire le temps d'attente ou la durée du trajet, mais qu'ils sont prêts à desserrer les cordons de leur bourse pour être opérés par un chirurgien chevronné.

Perceptions of British Columbia residents and their willingness to pay for medication management services provided by pharmacists.

BACKGROUND: Across Canada, pharmacists have expanded their scope of practice by performing medication management (MM) services. However, little is currently known about the opinions and attitudes of patients and the general population toward MM services. METHODS: A cross-sectional online survey, including a best-worst scaling task, was designed to understand the general public's opinions, preferences and willingness-to-pay with respect to MM services in British Columbia. RESULTS: Of 977 individuals contacted, 819 responded to the questionnaire (84% response rate). The mean age was 45 years (standard deviation [SD] 16 years), and 37% were male. Overall, 93% of respondents felt that the medication advice from their pharmacist resulted in improvement in patient outcomes and/or medication use. This was also selected as the "best" attribute of MM, while other preferred attributes of MM included being able to obtain an appointment with the pharmacist on the same day or via walk-in, improved patient-physician relationships and MM sessions able to be completed in 15 minutes with the pharmacist. The average willingness to pay for MM was $24.55 (SD $21.44). Younger males with higher household income and those who had had MM in the past were willing to pay more for MM services out of pocket. DISCUSSION AND CONCLUSION: The accessibility of pharmacists was valued highly by respondents who, overall, were supportive of MM services and recognized the potential of pharmacists' involvement in drug therapy management to improve patient outcomes and medication use. Alternative models of funding are worth considering for the sustainability of MM service provision.

Ten-Year Trends in Direct Costs of COPD: A Population-Based Study.

BACKGROUND: Up-to-date estimates of burden of diseases are required for evidence-based decision-making. The objectives of this study were to determine the excess costs of COPD and its trend from 2001 to 2010 in British Columbia, Canada. METHODS: We used British Columbia's administrative health data to construct a cohort of patients with COPD and a matched comparison cohort of subjects without COPD. We followed each patient from the time of first COPD-related health-care event (or equivalent time for the comparison cohort). Direct medical costs (in 2010 Canadian dollars [$]) were calculated based on billing records pertaining to hospital admissions, outpatient services use, medication dispensations, and community care services. We determined the excess medical costs of COPD by calculating the difference in overall medical costs between the COPD and the comparison cohorts. RESULTS: The COPD and comparison cohorts comprised 153,570 and 246,801 people, respectively (for both cohorts, mean age at entry was 66.9 years; 47.2% female patients). The excess costs of COPD during the study period were $5,452 per patient-year. Inpatient, outpatient, medication, and community care costs were responsible for 57%, 16%, 22%, and 5% of the excess costs, respectively. Excess costs increased by $296/person-y (P < .01), with hospital costs demonstrating the largest increase over time ($258/person-y; P < .01). CONCLUSIONS: The direct economic burden of COPD is high and has increased significantly between 2001 and 2010 over and above the increase in the health-care costs of the general population. Further investigation is required to elucidate the underlying reasons for the temporal increase in COPD direct costs.