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Objectives: Care for JIA patients has been transformed in the biologics era; however, biologics carry important (although rare) risks and are costly. Flares after biological withdrawal are seen frequently, yet there is little clinical guidance to identify which patients in clinical remission can safely have their biologic discontinued (by stopping or tapering). We examined what characteristics of the child or their context are important to pediatric rheumatologists when making the decision to discuss withdrawal of biologics. Methods: We conducted a survey including a best-worst scaling (BWS) exercise in pediatric rheumatologists who are part of the UCAN CAN-DU network to assess the relative importance of 14 previously identified characteristics. A balanced incomplete block design was used to generate choice tasks. Respondents evaluated 14 choice sets of 5 characteristics of a child with JIA and identified for each set which was the most and least important in the decision to offer withdrawal. Results were analyzed using conditional logit regression. Results: Fifty-one (out of 79) pediatric rheumatologists participated (response rate 65%). The three most important characteristics were how challenging it was to achieve remission, history of established joint damage, and time spent in remission. The three least important characteristics were history of temporomandibular joint involvement, accessibility of biologics, and the patient's age. Conclusions: These findings give quantitative insight about factors important to pediatric rheumatologists' decision-making about biologic withdrawal. In addition to high quality clinical evidence, further research is needed to understand the perspective of patients and families to inform shared decision-making about biologic withdrawal for JIA patients with clinically inactive disease. Key Points ● What is already known on this topic—there is limited clinical guidance for pediatric rheumatologists in making decisions about biologic withdrawal for patients with juvenile idiopathic arthritis who are in clinical remission. ● What this study adds—this study quantitatively examined what characteristic of the child in clinical remission, or of their context, are most important to pediatric rheumatologists in deciding whether to offer withdrawal of biologics. ● How this study might affect research, practice or policy—understanding of these characteristics can provide useful information to other pediatric rheumatologists in making their decisions, and may guide areas to focus on for future research. [ABSTRACT FROM AUTHOR]

Background and Objective: Rare diseases place a significant burden on patients, families, the healthcare system, and society. Evidence on the socioeconomic burden of rare disease is limited and mostly reflects diseases where treatments are available. We developed a framework encompassing recommended cost elements for studies of the socioeconomic burden of rare diseases. Methods: A scoping review, conducted in five databases (Cochrane Library, EconLit, Embase, MEDLINE, and APA PsycINFO), identified English language publications from 2000 to 2021 presenting frameworks developed for determining, measuring or valuing costs for rare or chronic diseases. Cost elements were extracted and used to develop a literature-informed framework. Structured feedback was gathered from experts in rare diseases, health economics/health services, and policy research to revise the framework. Results: Of 2990 records identified, eight papers were included and informed our preliminary framework; three focused on rare disease and five on chronic disease. Following expert input, we developed a framework consisting of nine cost categories (inpatient, outpatient, community, healthcare products/goods, productivity/education, travel/accommodation, government benefits, family impacts, and other), with several cost elements within each category. Our framework includes unique costs, added from the expert feedback, including genetic testing to inform treatment, use of private laboratories or out-of-country testing, family involvement in foundations and organizations, and advocacy costs for special access programs. Conclusions: Our work is the first to identify a comprehensive list of cost elements for rare disease for use by researchers and policy makers to fully capture socioeconomic burden. Use of the framework will increase the quality and comparability of future studies. Future work should focus on measuring and valuing these costs through onset, diagnosis, and post-diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To determine whether and how often the information to measure a set of key performance indicators (KPIs) in juvenile idiopathic arthritis (JIA) is found in data collected routinely in a Pediatric Rheumatology Clinic. Methods: A retrospective electronic chart review and administrative data analysis was conducted for a cohort of 140 patients with JIA at a tertiary Pediatric Rheumatology Clinic between 2016–2020. The set of KPIs include measuring patient outcomes (joint assessment, physician's global assessment of disease activity, assessment of functional ability, composite disease activity measurement), access to care (waiting time between referral and first visit, visit with the rheumatologist within the first year of diagnosis, annual follow-up visits with the rheumatologist), and safety (tuberculosis screening, and laboratory monitoring). Documentation was assessed as a binary variable indicating whether the required information was ever found. Documentation frequency for each KPI was assessed with counts and percentages of the number of times the required information was documented for each clinic visit. Compliance with the safety KPI definitions was assessed using administrative databases. Results: Data for each KPI were found at least once in the cohort and documentation varied in frequency and consistency. Access to care and safety KPIs were documented more frequently than patient outcome KPIs. A joint assessment was documented at every visit for 95% of patients, 46% for an assessment of pain, and none for a physician's global assessment of disease activity, an assessment of functional ability, or a composite disease activity measurement. Conclusion: Although feasible to measure, there is an opportunity for improving the consistency of documentation. Having an active system of monitoring KPIs and tools to simplify measurement is a key step in the process toward improved patient care outcomes. Streamlining the collection of KPI data can increase the likelihood of compliance. Next steps should involve replicating this study in various centres. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis management aims to reduce pain and improve function. Many factors affect whether patients follow recommended strategies. Locus of control refers to individual beliefs around who and what influences health. Locus of control is related to the treatment strategies patients prefer. Currently, no studies explore locus of control in non‐surgical management of osteoarthritis. Objectives: To explore patients' beliefs about the influences on their osteoarthritis symptoms and disease progression. Methods: Semi‐structured interviews were conducted with individuals experiencing self‐reported hip and/or knee osteoarthritis who had at least one joint that had not undergone replacement surgery. We used a qualitative description approach and the Braun and Clarke method for thematic analysis. Participants' locus of control classifications—internal, chance, doctors, or other people—were based on the Multidimensional Health Locus of Control (MHLC) Scales Form C score. Results: Locus of control was discussed in relation to aetiology, progression, and symptoms. Participants' opinions varied on whether their osteoarthritis progression could be influenced. 46% of participants attributed control to other people. Most participants believed that a previous injury had caused their osteoarthritis and that both themselves and others had some influence over their osteoarthritis symptoms, regardless of their locus of control classification. Conclusion: This research highlights the need for education about: the aetiology of osteoarthritis, the link between management and progression, and patient management of osteoarthritis. Further research is required to discern why expected patterns were not observed between participants' beliefs and locus of control classifications. [ABSTRACT FROM AUTHOR]

Objective: This study investigates the relationship of child, caregiver, and caring context measurements with the care-related quality of life (CRQoL) and health-related quality of life (HRQoL) of caregivers of children with juvenile idiopathic arthritis (JIA). Methods: We performed a cross-sectional analysis of baseline data on caregivers of children with JIA from Canada and the Netherlands collected for the "Canada-Netherlands Personalized Medicine Network in Childhood Arthritis and Rheumatic Diseases" study from June 2019 to September 2021. We used the CRQoL questionnaire (CarerQoL), adult EQ-5D-5L, and proxy-reported Youth 5-Level version of EuroQoL (EQ-5D-5L-Y) to assess caregiver CRQoL, caregiver HRQoL, and child HRQoL, respectively. We used a multivariate analysis to assess the relationship between both caregiver CRQoL and HRQoL and patient, caregiver, and caring context measurements. Results: A total of 250 caregivers were included in this study. Most of the caregivers were from the Netherlands (n = 178, 71%) and 77% were females (n = 193). The mean CarerQoL scores was 82.7 (standard deviation (SD) 11.4) and the mean EQ-5D-5L utility score was 0.87 (SD 0.16). Child HRQoL and employment had a positive relationship with both caregiver CarerQoL and EQ-5D-5L utility scores (p < 0.05), while receiving paid or unpaid help had a negative relationship with both scores (p < 0.05). Conclusion: Our findings indicated that to understand the impact of JIA on families, we need to consider socio-economic factors, such as employment and support to carry caregiving tasks, in addition to child HRQoL. [ABSTRACT FROM AUTHOR]

Objective: Pharmacological treatment is a cornerstone of care for children with juvenile idiopathic arthritis (JIA). The objective of this study is to evaluate prescription patterns of conventional and biologic disease modifying anti-rheumatic drugs (c-DMARDs and b-DMARDs) for patients with JIA. Methods: We conducted a retrospective cohort study of children diagnosed with JIA at a rheumatology pediatric clinic. Eligibility criteria were defined as children and youth newly diagnosed with enthesis-related arthritis, polyarticular, or oligoarticular JIA between 2011 and 2019, with at least one year of observation. Data on c-DMARDs and b-DMARDs prescriptions were obtained from electronic medical charts. We used descriptive statistics, Kaplan–Meier survival methods, and Sankey diagrams to describe treatment prescription patterns. Results: A total of 325 patients with JIA were included, with a median observation time of 3.7 years. The most frequently prescribed c-DMARD and b-DMARD were methotrexate and etanercept, respectively. Within the first year of rheumatology care, 62% and 21% of patients had a c-DMARD and a b-DMARD prescribed, respectively. These proportions varied greatly by JIA subtype. Among the 147 (147/325, 45%) patients that had at least one b-DMARD prescribed, 24% were prescribed a second, and 7% a third-line of b-DMARD. A total of 112 unique treatment sequences were observed, with c-DMARD monotherapy followed by the addition of either a b-DMARD (56%) or another c-DMARD (30%) being the two most prevalent patterns in this cohort. Conclusion: We observed a variety of treatment trajectories, with many patients experiencing multiple treatment lines, illustrating the complexity of the overall JIA treatment path. [ABSTRACT FROM AUTHOR]

Introduction: Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease, whose multifaceted care path can lead to significant expenditure for the healthcare system. We aim to assess the real-world healthcare resource use (HCRU) and associated cost for children with JIA in a single center in Canada. Methods: A single-center consecutive cohort of newly diagnosed patients with JIA attending the pediatric rheumatology clinic from 2011 to 2019 was identified using an administrative data algorithm and electronic medical charts. HCRU was estimated from six administrative health databases that included hospital admissions, emergency, outpatient care, practitioners' visits, medication, and laboratory and imaging tests. Costs were assigned using appropriate sources. We reported the yearly overall and JIA-associated HCRU and costs 5 years prior to and 6 years after the first visit to the pediatric rheumatologist. The Zhao and Tian estimator was used to calculate cumulative mean costs over a 6-year timeframe. Results were stratified by disease subtype. Results: A total of 389 patients were identified. The yearly total overall mean costs per patient ranged between $804 and $4460 during the 5 years prior to the first visit to the pediatric rheumatologist and $8529 and $10,651 for the 6 years after. Medication cost, driven by use of biologic therapies, and outpatient visits were the greatest contributor to the total cost. The overall cumulative mean cost for 6 years of care was $48,649 per patient, while the JIA-associated cumulative mean cost was $26,820 per patient. During the first year of rheumatology care, systemic onset JIA had the highest cumulative mean overall cost, while oligoarticular JIA had the lowest cumulative mean cost. Conclusion: The care pathway for children with JIA can be expensive, and complex—and varies by JIA subtype. Although the yearly total mean cost per patient was constant, the distribution of costs changes over time with the introduction of biologic therapies later in the care pathway. This study provides a better understanding of the JIA costs profile and can help inform future economic studies. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this systematic review were to identify health state utility values (HSUV) of children and adults with juvenile idiopathic arthritis in the literature and to assess whether HSUV were appropriately reported and could be used to inform parameter inputs for a model-based cost-utility analysis to inform decision making. Methods: MEDLINE, EMBASE, PsycINFO, EconLit and CINAHL databases were searched in July 2019. Inclusion criteria were studies using preference-based instruments, targeting children or adults with juvenile idiopathic arthritis, and in the English language. The quality of studies was assessed using a modified checklist that included relevant sources of bias and assessment of quality of HSUV valuation and measurement. A descriptive analysis was conducted, including assessment on reporting of population characteristics and stratification of HSUV by potential health states or population subgroup. Results: From 620 identified articles, ten reported HSUV. Seven studies reported HSUV of children with juvenile idiopathic arthritis, and three of adults with a history of juvenile idiopathic arthritis. Population disease activity status and drug treatment were reported in less than half of the studies. Six (out of ten) studies stratified HSUV results for at least one of the potential health state categories, but they represent very specific situations or interventions (e.g. patients receiving different types of physiotherapy or treated with etanercept over time). Conclusions: We have identified critical gaps in the literature reporting HSUV in patients with juvenile idiopathic arthritis including a lack of HSUV measures for distinct health states, particularly in adults with a history of juvenile idiopathic arthritis. The current reported HSUV data in juvenile idiopathic arthritis are insufficient for a full cost-utility analysis with a short or lifetime horizon. [ABSTRACT FROM AUTHOR]

We report a systematic review and meta-analysis of research using animal models of chemotherapy-induced peripheral neuropathy (CIPN). We systematically searched 5 online databases in September 2012 and updated the search in November 2015 using machine learning and text mining to reduce the screening for inclusion workload and improve accuracy. For each comparison, we calculated a standardised mean difference (SMD) effect size, and then combined effects in a random-effects meta-analysis. We assessed the impact of study design factors and reporting of measures to reduce risks of bias. We present power analyses for the most frequently reported behavioural tests; 337 publications were included. Most studies (84%) used male animals only. The most frequently reported outcome measure was evoked limb withdrawal in response to mechanical monofilaments. There was modest reporting of measures to reduce risks of bias. The number of animals required to obtain 80% power with a significance level of 0.05 varied substantially across behavioural tests. In this comprehensive summary of the use of animal models of CIPN, we have identified areas in which the value of preclinical CIPN studies might be increased. Using both sexes of animals in the modelling of CIPN, ensuring that outcome measures align with those most relevant in the clinic, and the animal’s pain contextualised ethology will likely improve external validity. Measures to reduce risk of bias should be employed to increase the internal validity of studies. Different outcome measures have different statistical power, and this can refine our approaches in the modelling of CIPN. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling pain condition resulting from chemotherapy for cancer. Severe acute CIPN may require chemotherapy dose reduction or cessation. There is no effective CIPN prevention strategy; treatment of established chronic CIPN is limited, and the prevalence of CIPN is not known. Here we used a systematic review to identify studies reporting the prevalence of CIPN. We searched Embase, Medline, CAB Abstracts, CINAHL, PubMed central, Cochrane Library, and Web of Knowledge for relevant references and used random-effects meta-regression to estimate overall prevalence. We assessed study quality using the CONSORT and STROBE guidelines, and we report findings according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance. We provide a qualitative summary of factors reported to alter the risk of CIPN. We included 31 studies with data from 4179 patients in our analysis. CIPN prevalence was 68.1% (57.7–78.4) when measured in the first month after chemotherapy, 60.0% (36.4–81.6) at 3 months and 30.0% (6.4–53.5) at 6 months or more. Different chemotherapy drugs were associated with differences in CIPN prevalence, and there was some evidence of publication bias. Genetic risk factors were reported in 4 studies. Clinical risk factors, identified in 4 of 31 studies, included neuropathy at baseline, smoking, abnormal creatinine clearance, and specific sensory changes during chemotherapy. Although CIPN prevalence decreases with time, at 6 months 30% of patients continue to suffer from CIPN. Routine CIPN surveillance during post-chemotherapy follow-up is needed. A number of genetic and clinical risk factors were identified that require further study. [ABSTRACT FROM AUTHOR]

Objective To investigate medication prescription patterns among children with JIA, including duration, sequence and reasons for medication discontinuation. Methods This study is a single-centre, retrospective analysis of prospective data from the electronic medical records of JIA patients receiving systemic therapy aged 0–18 years between 1 April 2011 and 31 March 2019. Patient characteristics (age, gender, JIA subtype) and medication prescriptions were extracted and analysed using descriptive statistics, Sankey diagrams and Kaplan–Meier survival methods. Results Over a median of 4.2 years follow-up, the 20 different medicines analysed were prescribed as monotherapy (n  = 15) or combination therapy (n  = 48 unique combinations) among 236 patients. In non-systemic JIA, synthetic DMARDs were prescribed to almost all patients (99.5%), and always included MTX. In contrast, 43.9% of non-systemic JIA patients received a biologic DMARD (mostly adalimumab or etanercept), ranging from 30.9% for oligoarticular persistent ANA-positive JIA, to 90.9% for polyarticular RF-positive JIA. Among systemic JIA, 91.7% received a biologic DMARD (always including anakinra). When analysing medication prescriptions according to their class, 32.6% involved combination therapy. In 56.8% of patients, subsequent treatment lines were initiated after unsuccessful first-line treatment, resulting in 68 unique sequences. Remission was the most common reason for DMARD discontinuation (44.7%), followed by adverse events (28.9%) and ineffectiveness (22.1%). Conclusion This paper reveals the complexity of pharmacological treatment in JIA, as indicated by: the variety of mono- and combination therapies prescribed, substantial variation in medication prescriptions between subtypes, most patients receiving two or more treatment lines, and the large number of unique treatment sequences. [ABSTRACT FROM AUTHOR]

The use of systematic review and meta-analysis of preclinical studies has become more common, including those of studies describing the modeling of cerebrovascular diseases. Empirical evidence suggests that too many preclinical experiments lack methodological rigor, and this leads to inflated treatment effects. The aim of this review is to describe the concepts of systematic review and meta-analysis and consider how these tools may be used to provide empirical evidence to spur the field to improve the rigor of the conduct and reporting of preclinical research akin to their use in improving the conduct and reporting of randomized controlled trials in clinical research. As with other research domains, systematic reviews are subject to bias. Therefore, we have also suggested guidance for their conduct, reporting, and critical appraisal. [ABSTRACT FROM AUTHOR]

Abstract: Background: The specification of the utility function has received limited attention within the discrete choice experiment (DCE) literature. This lack of investigation is surprising given that evidence from the contingent valuation literature suggests that welfare estimates are sensitive to different specifications of the utility function. Objective: This study investigates the effect of different specifications of the utility function on results within a DCE. Methods: The DCE elicited the public’s preferences for waiting time for hip and knee replacement and estimated willingness to wait (WTW). Results: The results showed that the WTW for the different patient profiles varied considerably across the three different specifications of the utility function. Assuming a linear utility function led to much higher estimates of marginal rates of substitution (WTWs) than with nonlinear specifications. The goodness-of-fit measures indicated that nonlinear specifications were superior. [Copyright &y& Elsevier]

Abstract: Pain can significantly decrease the quality of life of patients with advanced cancer. Current treatment strategies often provide inadequate analgesia and unacceptable side effects. Animal models of bone cancer pain are used in the development of novel pharmacological approaches. Here we conducted a systematic review and meta-analysis of publications describing in vivo modelling of bone cancer pain in which behavioural, general health, macroscopic, histological, biochemical, or electrophysiological outcomes were reported and compared to appropriate controls. In all, 150 publications met our inclusion criteria, describing 38 different models of bone cancer pain. Reported methodological quality was low; only 31% of publications reported blinded assessment of outcome, and 11% reported random allocation to group. No publication reported a sample size calculation. Studies that reported measures to reduce bias reported smaller differences in behavioural outcomes between tumour-bearing and control animals, and studies that presented a statement regarding a conflict of interest reported larger differences in behavioural outcomes. Larger differences in behavioural outcomes were reported in female animals, when cancer cells were injected into either the tibia or femur, and when MatLyLu prostate or Lewis Lung cancer cells were used. Mechanical-evoked pain behaviours were most commonly reported; however, the largest difference was observed in spontaneous pain behaviours. In the spinal cord astrocyte activation and increased levels of Substance P receptor internalisation, c-Fos, dynorphin, tumor necrosis factor-α and interleukin-1β have been reported in bone cancer pain models, suggesting several potential therapeutic targets. However, the translational impact of animal models on clinical pain research could be enhanced by improving methodological quality. [Copyright &y& Elsevier]

Adult brain connectivity is shaped by the balance of sensory inputs in early life. In the case of pain pathways, it is less clear whether nociceptive inputs in infancy can have a lasting influence upon central pain processing and adult pain sensitivity. Here, we show that adult pain responses in the rat are ‘primed’ by tissue injury in the neonatal period. Rats that experience hind-paw incision injury at 3 days of age, display an increased magnitude and duration of hyperalgesia following incision in adulthood when compared with those with no early life pain experience. This priming of spinal reflex sensitivity was measured by both reductions in behavioural withdrawal thresholds and increased flexor muscle electromyographic responses to graded suprathreshold hind-paw stimuli in the 4 weeks following adult incision. Prior neonatal injury also ‘primed’ the spinal microglial response to adult injury, resulting in an increased intensity, spatial distribution and duration of ionized calcium-binding adaptor molecule-1-positive microglial reactivity in the dorsal horn. Intrathecal minocycline at the time of adult injury selectively prevented both the hyperalgesia and early microglial reactivity associated with prior neonatal injury. The enhanced neuroimmune response seen in neonatally primed animals could also be demonstrated in the absence of peripheral tissue injury by direct electrical stimulation of tibial nerve fibres, confirming that centrally mediated mechanisms contribute to these long-term effects. These data suggest that early life injury may predispose individuals to enhanced sensitivity to painful events. [ABSTRACT FROM PUBLISHER]

This paper explores the relevance of the literature on for-profit versus not-for-profit hospital care to the Alberta government's Health Care Protection Act and to contracting-out of health services more generally. Thirty-four studies were identified and most found no difference between for-profit and not-for-profit full-service hospitals with respect to relative costs, quality of care or efficiency — a conclusion that is contrary to more selective reviews of this literature. Further assessment of the content and context of this literature leads us to argue that this "evidence" is irrelevant to Canadian health care and, therefore, the debate on contracting-out. [ABSTRACT FROM AUTHOR]

Discusses economic evaluation of health-care intervention. Topic of incremental cost effectiveness ratios, which imply a need for more resources and raise questions about resource allocation; Suggestion that more attention be paid to the type of efficiency question being considered and its implications for opportunity cost; Revision of guidelines for economic evaluations.

The article offers the authors' perspectives on several factors affecting preclinical studies such as those on rheumatological disease. According to the authors, the purpose of research is to improve human health, and that promising findings from preclinical studies most often fail to translate to the clinic. The authors are critical to the data about high drug attrition rate, citing a larger percentage of anticancer drugs fail at Phase I clinical trials.

Background: This study aims to describe current practice in identifying and measuring health care resource use and unit costs in economic evaluations or costing studies of juvenile idiopathic arthritis (JIA). Methods: A scoping review was conducted (in July 2018) in PubMed and Embase to identify economic evaluations, costing studies, or resource utilization studies focusing on patients with JIA. Only English language peer-reviewed articles reporting primary research were included. Data from all included full-text articles were extracted and analysed to identify the reported health care resource use items. In addition, the data sources used to obtain these resource use and unit costs were identified for all included articles. Results: Of 1176 unique citations identified by the search, 20 full-text articles were included. These involved 4 full economic evaluations, 5 cost-outcome descriptions, 8 cost descriptions, and 3 articles reporting only resource use. The most commonly reported health care resource use items involved medication (80%), outpatient and inpatient hospital visits (80%), laboratory tests (70%), medical professional visits (70%) and other medical visits (65%). Productivity losses of caregivers were much more often incorporated than (future) productivity losses of patients (i.e. 55% vs. 15%). Family borne costs were not commonly captured (ranging from 15% for school costs to 50% for transportation costs). Resource use was mostly obtained from family self-reported questionnaires. Estimates of unit costs were mostly based on reimbursement claims, administrative data, or literature. Conclusions: Despite some consistency in commonly included health care resource use items, variability remains in including productivity losses, missed school days and family borne costs. As these items likely substantially influence the full cost impact of JIA, the heterogeneity found between the items reported in the included studies limits the comparability of the results. Therefore, standardization of resource use items and unit costs to be collected is required. This standardization will provide guidance to future research and thereby improve the quality and comparability of economic evaluations or costing studies in JIA and potentially other childhood diseases. This would allow better understanding of the burden of JIA, and to estimate how it varies across health care systems. [ABSTRACT FROM AUTHOR]

Background and Objectives: Rare diseases have a significant impact on patients, families, the health system, and society. Measuring the socioeconomic burden is crucial to valuing interventions for rare diseases. Healthcare system costs are significant, but so are costs to other government sectors, patients, families, and society. To understand the breadth of costs captured in rare disease studies, we examined the cost categories and elements of socioeconomic burden captured in published studies. Methods: A scoping review was conducted using five electronic databases to identify English language economic evaluations and cost-of-illness studies of interventions for rare diseases (2011–21). We mapped costs using a previously developed evidence-informed framework of socioeconomic burden costs for rare disease. Results: Of 4890 studies identified, 48 economic evaluations and 22 cost-of-illness studies were included. While 18/22 cost-of-illness studies utilized a societal perspective, only 7/48 economic evaluations incorporated societal costs. Most reported cost categories related to medical costs, with medication and hospitalizations being the most common elements for both study designs. Costs borne by patients, families, and society were reported less among economic evaluations than cost-of-illness studies. These included: productivity (10% vs 77%), travel/accommodation (6% vs 68%), government benefits (4% vs 18%), and family impacts (0% vs 50%). Conclusions: Contrary to cost-of-illness analyses, most of the included economic evaluations did not account for the hidden burden of rare diseases, that is, costs borne by patients, families, and societies. Including these types of costs in future studies would provide a more comprehensive picture of the burden of disease, providing empirical data to inform how we value and make decisions regarding rare disease interventions, health policy, and resource allocation. [ABSTRACT FROM AUTHOR]

Background: As Canada and other high-income countries continue to welcome newcomers, we aimed to 1) understand newcomer parents' attitudes towards routine-childhood vaccinations (RCVs), and 2) identify barriers newcomer parents face when accessing RCVs in Alberta, Canada. Methods: Between July 6th—August 31st, 2022, we recruited participants from Alberta, Canada to participate in moderated focus group discussions. Inclusion criteria included parents who had lived in Canada for < 5 years with children < 18 years old. Focus groups were transcribed verbatim and analyzed using content and deductive thematic analysis. The capability opportunity motivation behaviour model was used as our conceptual framework. Results: Four virtual and three in-person focus groups were conducted with 47 participants. Overall, parents were motivated and willing to vaccinate their children but experienced several barriers related to their capability and opportunity to access RCVs. Five main themes emerged: 1) lack of reputable information about RCVs, 2) language barriers when looking for information and asking questions about RCVs, 3) lack of access to a primary care provider (PCP), 4) lack of affordable and convenient transportation options, and 5) due to the COVID-19 pandemic, lack of available vaccine appointments. Several minor themes were also identified and included barriers such as lack of 1) childcare, vaccine record sharing, PCP follow-up. Conclusions: Our findings highlight that several barriers faced by newcomer families ultimately stem from issues related to accessing information about RCVs and the challenges families face once at vaccination clinics, highlighting opportunities for health systems to better support newcomers in accessing RCVs. [ABSTRACT FROM AUTHOR]

Objective: Approximately one third of children with JIA receive biologic therapy, but evidence on biologic therapy withdrawal is lacking. This study aims to increase our understanding of whether and when pediatric rheumatologists postpone a decision to withdraw biologic therapy in children with clinically inactive non-systemic JIA. Methods: A survey containing questions about background characteristics, treatment patterns, minimum treatment time with biologic therapy, and 16 different patient vignettes, was distributed among 83 pediatric rheumatologists in Canada and the Netherlands. For each vignette, respondents were asked whether they would withdraw biologic therapy at their minimum treatment time, and if not, how long they would continue biologic therapy. Statistical analysis included descriptive statistics, logistic and interval regression analysis. Results: Thirty-three pediatric rheumatologists completed the survey (40% response rate). Pediatric rheumatologists are most likely to postpone the decision to withdraw biologic therapy when the child and/or parents express a preference for continuation (OR 6.3; p < 0.001), in case of a flare in the current treatment period (OR 3.9; p = 0.001), and in case of uveitis in the current treatment period (OR 3.9; p < 0.001). On average, biologic therapy withdrawal is initiated 6.7 months later when the child or parent prefer to continue treatment. Conclusion: Patient's and parents' preferences were the strongest driver of a decision to postpone biologic therapy withdrawal in children with clinically inactive non-systemic JIA and prolongs treatment duration. These findings highlight the potential benefit of a tool to support pediatric rheumatologists, patients and parents in decision making, and can help inform its design. [ABSTRACT FROM AUTHOR]

In biomedicine and many other fields, there are growing concerns around the reproducibility of research findings, with many researchers bein g unable to replicate their own or others' results. This raises important questions as to the validity and usefulness of much published research. In this review, we aim to engage researchers in the issue of research reproducibility and equip them with the necessary tools to increase the reproducibility of their research. We first high light the causes and potential impact of non-reproducible research and emphasise the benefits of working reproducibly for the researcher and broader research community. We address specific targets for improvement and steps that individual researchers can take to increase the reproducibility of their work. We next provide recommendations for improving the design and conduct of experiments, focusing on in vivo animal experiments. We describe common sources of poor internal validity of experiments and offer practical guidance for limiting these potential sources of bias at different experi mental stages, as well as discussing other important considerations during experimental design. We provide a list of key resources available to researchers to improve experimental design, conduct, and reporting. We then discuss the importance of open research practices such as study preregistration and the use of preprints and describe recommendations around data management and sharing. Our review emphasises the importance of reproducible work and aims to empower every individual researcher to contribute to the reproducibility of research in their field. [ABSTRACT FROM AUTHOR]

Background/aim. The risk of injury among Pee Wee (ages 11–12 years) ice hockey players in leagues that allow body checking is threefold greater than in leagues that do not allow body checking. We estimated the cost–effectiveness of a no body checking policy versus a policy that allows body checking in Pee Wee ice hockey. Methods. Cost–effectiveness analysis alongside a prospective cohort study during the 2007–2008 season, including players in Quebec (n=1046), where policy did not allow body checking, and in Alberta (n=1108), where body checking was allowed. Injury incidence rates (injuries/1000 player-hours) and incidence proportions (injuries/100 players), adjusted for cluster using Poisson regression, allowed for standardised comparisons and meaningful translation to community stakeholders. Based on Alberta fee schedules, direct healthcare costs (physician visits, imaging, procedures) were adjusted for cluster using bootstrapping. We examined uncertainty in our estimates using cost–effectiveness planes. Results. Associated with significantly higher injury rates, healthcare costs where policy allowed body checking were over 2.5 times higher than where policy disallowed body checking ($C473/1000 player-hours (95% CI $C358 to $C603) vs $C184/1000 player-hours (95% CI $C120 to $C257)). The difference in costs between provinces was $C289/1000 player-hours (95% CI $C153 to $C432). Projecting results onto Alberta Pee Wee players registered in the 2011–2012 season, an estimated 1273 injuries and $C213 280 in healthcare costs would be avoided during just one season with the policy change. Conclusion. Our study suggests that a policy disallowing body checking in Pee Wee ice hockey is cost-saving (associated with fewer injuries and lower costs) compared to a policy allowing body checking. As we did not account for long-term outcomes, our results underestimate the economic impact of these injuries. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the effect of season on playground surface injury rates. METHODS: Injuries were identified through student incident report forms used in school districts in Calgary (Alberta) and the surrounding area. Playground surface exposure data were estimated based on school enrollment. RESULTS: A total of 539 injuries were reported during the 2007/2008 school year. Abrasions, bruises and inflammation were the most frequently reported injuries. The head, neck or face were most commonly injured. Injury rates per 1000 student days ranged between 0.018 (rubber crumb in spring) and 0.08 (poured-in-place and natural rock in the fall). Rubber crumb surfacing, compared with natural rock, had a significantly lower rate of injury in the spring, but no other season-surface comparisons were statistically significant. CONCLUSIONS: Rates of injury were similar for natural rock, poured-in-place, and crushed rock in the fall and winter. There was some evidence of a lower rate of injury on rubber crumb surfaces in the spring. [ABSTRACT FROM AUTHOR]

Background. Clinical practice, policy and research, and the ethical bases upon which they are founded, should be systematically and transparently informed by both patient and professional values. [ABSTRACT FROM PUBLISHER]

The efficacy of brief treatments for media-recruited pathological gamblers was tested in a randomized clinical trial design (N = 314). Two self-directed motivational interventions were compared with a 6-week waiting list control and a workbook only control. Brief motivational treatment involved a telephone motivational interview and a mailed self-help workbook. Brief motivational booster treatment involved a telephone motivational interview, a workbook, and 6 booster telephone calls over a 9-month period. Primary outcomes were gambling frequency and dollar losses. As hypothesized, brief and brief booster treatment participants reported less gambling at 6 weeks than those assigned to the control groups. Brief and brief booster treatment participants gambled significantly less often over the first 6 months of the follow-up than workbook only participants. However, the workbook only participants were as likely to have significantly reduced their losses over the year and to have not met criteria for pathological gambling. Contrary to the hypothesis, participants in the brief booster treatment group showed no greater improvement than brief treatment participants. These results provide further support for the value of brief motivational treatments for pathological gambling. [ABSTRACT FROM AUTHOR]

Background: Norovirus is a leading cause of acute gastroenteritis. With vaccines in development, population-based estimates of norovirus burden are needed to identify target populations, quantify potential benefits, and understand disease dynamics.Methods: We estimated the attributable fraction (AF) for norovirus infections in children, defined as the proportion of children testing positive for norovirus whose gastroenteritis was attributable to norovirus. We calculated the standardized incidence and emergency department (ED) visit rates attributable to norovirus using provincial gastroenteritis visit administrative data.Results: From 3731 gastroenteritis case patients and 2135 controls we determined that the AFs were 67.0% (95% confidence interval [CI], 31.5%-100%) and 91.6% (88.8%-94.4%) for norovirus genogroups I (GI) and II (GII), respectively. Norovirus GII AF varied by season but not age. We attributed 116 episodes (95% CI, 103-129) and 59 (51-67) ED visits per 10 000 child-years to norovirus GII across all ages, accounting for 20% and 18% of all medically attended gastroenteritis episodes and ED visits, respectively.Conclusions: In children, a large proportion of norovirus GII detections reflect causation, demonstrating significant potential for norovirus GII vaccines. Seasonal variation in the norovirus GII AF may have implications for understanding the role asymptomatic carriage plays in disease dynamics. [ABSTRACT FROM AUTHOR]

Assessment of outcome in preclinical studies of vascular cognitive impairment (VCI) is heterogenous. Through an ARUK Scottish Network supported questionnaire and workshop (mostly UK-based researchers), we aimed to determine underlying variability and what could be implemented to overcome identified challenges. Twelve UK VCI research centres were identified and invited to complete a questionnaire and attend a one-day workshop. Questionnaire responses demonstrated agreement that outcome assessments in VCI preclinical research vary by group and even those common across groups, may be performed differently. From the workshop, six themes were discussed: issues with preclinical models, reasons for choosing functional assessments, issues in interpretation of functional assessments, describing and reporting functional outcome assessments, sharing resources and expertise, and standardization of outcomes. Eight consensus points emerged demonstrating broadly that the chosen assessment should reflect the deficit being measured, and therefore that one assessment does not suit all models; guidance/standardisation on recording VCI outcome reporting is needed and that uniformity would be aided by a platform to share expertise, material, protocols and procedures thus reducing heterogeneity and so increasing potential for collaboration, comparison and replication. As a result of the workshop, UK wide consensus statements were agreed and future priorities for preclinical research identified. [ABSTRACT FROM AUTHOR]

Objectives: Guideline compliant CPR is associated with improved survival for patients with cardiac arrest. Conventional Basic Life Support (BLS) training results in suboptimal CPR competency and skill retention. We aimed to compare the effectiveness of distributed CPR training with real-time feedback to conventional BLS training for CPR skills in pediatric healthcare providers.Methods: Healthcare providers were randomized into receiving annual BLS training (control) or distributed training with real-time feedback (intervention). The intervention group was asked to practice CPR for 2 min on mannequins while receiving real-time CPR feedback, at least once per month. Control group participants were not asked to practice CPR during the study period. Excellent CPR was defined as 90% guideline-compliance for depth, rate and recoil of chest compressions. CPR performance of participants was assessed (on infant and adult-sized mannequins) every 3 months for a duration of 12 months. CPR performance was compared between the 2 groups.Results: A total of 87 healthcare providers were included in the analyses (control n = 41, intervention n = 46). Baseline assessment showed no significant difference in CPR performance across the 2 groups. The intervention group has a significantly greater proportion of participants with excellent CPR compared with the control group on an adult sized mannequin (14.6% vs. 54.3%, p < 0.001) and infant-sized mannequin (19.5% vs. 71.7%, p < 0.001) at the end of the study. In the intervention group, all CPR metrics except infant depth were improved and retained over the course of the study.Conclusion: Distributed CPR training with real-time feedback improves the compliance of AHA guidelines of quality of CPR. [ABSTRACT FROM AUTHOR]

Context: Simulation‐based medical education (SBME) is now ubiquitous at all levels of medical training. Given the substantial resources needed for SBME, economic evaluation of simulation‐based programmes or curricula is required to demonstrate whether improvement in trainee performance (knowledge, skills and attitudes) and health outcomes justifies the cost of investment. Current literature evaluating SBME fails to provide consistent and interpretable information on the relative costs and benefits of alternatives. Content: Economic evaluation is widely applied in health care, but is relatively scarce in medical education. Therefore, in this paper, using a focus on SBME, we define economic evaluation, describe the key components, and discuss the challenges associated with conducting an economic evaluation of medical education interventions. As a way forward to the rigorous and state of the art application of economic evaluation in medical education, we outline the steps to gather the necessary information to conduct an economic evaluation of simulation‐based education programmes and curricula, and describe the main approaches to conducting an economic evaluation. Conclusion: A properly conducted economic evaluation can help stakeholders (i.e., programme directors, policy makers and curriculum designers) to determine the optimal use of resources in selecting the modality or method of assessment in simulation. It also helps inform broader decision making about allocation of scarce resources within an educational programme, as well as between education and clinical care. Economic evaluation in medical education research is still in its infancy, and there is significant potential for state‐of‐the‐art application of these methods in this area. [ABSTRACT FROM AUTHOR]

There is growing concern about lack of scientific rigor and transparent reporting across many preclinical fields of biological research. Poor experimental design and lack of transparent reporting can result in conscious or unconscious experimental bias, producing results that are not replicable. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration sponsored a consensus meeting of the Preclinical Pain Research Consortium for Investigating Safety and Efficacy (PPRECISE) Working Group. International participants from universities, funding agencies, government agencies, industry, and a patient advocacy organization attended. Reduction of publication bias, increasing the ability of others to faithfully repeat experimental methods, and increased transparency of data reporting were specifically discussed. Parameters deemed essential to increase confidence in the published literature were clear, specific reporting of an a priori hypothesis and definition of primary outcome measure. Power calculations and whether measurement of minimal meaningful effect size to determine these should be a core component of the preclinical research effort provoked considerable discussion, with many but not all agreeing. Greater transparency of reporting should be driven by scientists, journal editors, reviewers, and grant funders. The conduct of high-quality science that is fully reported should not preclude novelty and innovation in preclinical pain research, and indeed, any efforts that curtail such innovation would be misguided. We believe that to achieve the goal of finding effective new treatments for patients with pain, the pain field needs to deal with these challenging issues. [ABSTRACT FROM AUTHOR]

The reliability of experimental findings depends on the rigour of experimental design. Here we show limited reporting of measures to reduce the risk of bias in a random sample of life sciences publications, significantly lower reporting of randomisation in work published in journals of high impact, and very limited reporting of measures to reduce the risk of bias in publications from leading United Kingdom institutions. Ascertainment of differences between institutions might serve both as a measure of research quality and as a tool for institutional efforts to improve research quality. [ABSTRACT FROM AUTHOR]

Purpose: Preference-weighted HRQoL (utility) ratings are increasingly used to guide clinical and resource allocation decisions, but their performance has not always been adequately explored. We sought to examine patterns of health utility ratings in community populations with depressive disorders and painful conditions. Methods: We used two Canadian cross-sectional health surveys that obtained Comprehensive Health Status Measurement System/Health Utilities Index Mark 3 (HUI3) ratings and identified people with painful conditions and major depression. We estimated the frequency of item endorsements and mean utility ratings in these groups. Results: Interesting differences between health state ratings and diagnostic categories were noted. For example, 71 % of those professionally diagnosed with migraine reported that they usually have 'no pain.' Despite this, utility ratings were lower in those respondents with depressive episodes and in those with painful conditions. Greater than additive reductions in HUI3 scores were noted in most instances where both depressive disorders and painful conditions were present. Conclusions: Health utility ratings confirm the clinical impression that painful conditions and depressive disorders magnify each other's impact. Despite weak alignment between the health state definitions incorporated into utility ratings and the diagnostic concepts examined, the HUI3 appeared to capture HRQoL decrements and negative synergies associated with the co-occurrence of depressive episodes and painful conditions. [ABSTRACT FROM AUTHOR]

Purpose: Birth cohorts are a common tool used in epidemiological studies about pregnancy; yet these datasets systematically miss pregnancies that are spontaneously lost or terminated. This study examined the feasibility of linking administrative and clinical datasets from Alberta Canada to identify a pregnancy cohort that includes spontaneous and medical pregnancy losses. Methods: Deterministic linkage was used to link data from twelve clinical and administrative datasets for women who conceived between November 2007 and February 2008. Descriptive statistics were used to characterize the relative contribution of each dataset to the overall dataset. Results: Overall, 6,477 unique pregnancies were eligible for inclusion, resulting in a live birth rate of 94.1%, a stillbirth rate of 0.5%, a fetal death rate of 4.1%, and an estimated 1.3% of the cohort moving out of the study area. No single dataset could identify all pregnancies. Individual databases identified 2.0-99.1% of the cohort. Fetal deaths were most frequently identified in outpatient physician claims, emergency room visits, ultrasound data, or from the cytogenetic laboratory. Conclusions: Linkage of clinical and administrative databases to identify pregnancy is feasible and can overcome many limitations associated with the use of a single dataset; however, fetal deaths continue to be under-ascertained. [ABSTRACT FROM AUTHOR]

Abstract: Clear reporting of research is crucial to the scientific process. Poorly designed and reported studies are damaging not only to the efforts of individual researchers, but also to science as a whole. Standardised reporting methods, such as those already established for reporting randomised clinical trials, have led to improved study design and facilitated the processes of clinical systematic review and meta-analysis. Such standards were lacking in the pre-clinical field until the development of the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines. These were prompted following a survey which highlighted a widespread lack of robust and consistent reporting of pre-clinical in vivo research, with reports frequently omitting basic information required for study replication and quality assessment. The resulting twenty item checklist in ARRIVE covers all aspects of experimental design with particular emphasis on bias reduction and methodological transparency. Influential publishers and research funders have already adopted ARRIVE. Further dissemination and acknowledgement of the importance of these guidelines is vital to their widespread implementation. Conclusions and implications: Wide implementation of the ARRIVE guidelines for reporting of in vivo preclinical research, especially pain research, are essential for a much needed increased transparency and quality in publishing such research. ARRIVE will also positively influence improvements in experimental design and quality, assist the conduct of accurate replication studies of important new findings and facilitate meta-analyses of preclinical research. [Copyright &y& Elsevier]

Abstract: A key objective of discrete choice experiments is to obtain sufficient quantity of high quality choice data to estimate choice models to be used to explore various policy/clinically relevant issues. This paper focuses on a relatively new form of choice experiment, ‘Best Worst Discrete Choice Experiments’ (BWDCEs) and their relevance to health research as a new way to meet such an objective. We explain what BWDCEs are, how and when to apply them and we present several analytical approaches to model the resulting data. We demonstrate this preference elicitation approach in an empirical application exploring preferences of 898 members of the general public in Edmonton and Calgary, Canada for treatment of cardiac arrest occurring in a public place and show the gains achieved compared to traditional analysis of first best data. We suggest that BWDCEs are a valuable way to investigate preferences in the health sector and discuss implications for task design, analysis and areas for future research. [Copyright &y& Elsevier]

Forensic scientists are often asked to physically compare duct tape samples found in association with criminal activity. This study was designed to statistically evaluate the error and accuracy rates associated with duct tape physical end matching. The experimental design consisted of a blind study in which three researchers independently analyzed eight types of tape subjected to four methods of separation. The lowest mean accuracy observed was 98.15%, the highest mean false-positive rate observed was 3.33%, and the highest mean false-negative rate was 2.67%. Overall, high accuracy with low false-positive and false-negative error rates were observed. This study confirms the use of physical end matching in identifying duct tape samples as matching or nonmatching and that the differences between analysts, brands, tape grades, tape color, and methods of separation have varying contributions to misidentifications and inconclusive results. This study also demonstrates the importance of peer review in duct tape analysis. [ABSTRACT FROM AUTHOR]

Abstract: Neurotrophin-3 (NT-3) is a target-derived neurotrophic factor that regulates sensory neuronal survival and growth. Here we report that NT-3 plays a critical permissive role in cutaneous sensory nerve sprouting that contributes to pain and sensitivity following skin wounding in young animals. Sensory terminal sprouting in neonatally wounded dermis and epidermis is accompanied by increased NT-3 transcription, NT-3 protein levels, and NT-3 protein release 3-7days post skin injury in newborn rats and mice. Functional blockade of NT-3 activity with specific antibodies greatly reduces sensory neurite outgrowth induced by wounded skin, but not by naïve skin, in dorsal root ganglion/skin co-cultures. The requirement for NT-3 for sensory terminal sprouting in vivo is confirmed by the absence of wound-induced hyperinnervation in heterozygous transgenic mice (NT-3+/−lacZ). We conclude that upregulation of NT-3 in neonatally wounded skin is a critical factor mediating the sensory nerve sprouting that underlies hypersensitivity and pain following skin injury. [Copyright &y& Elsevier]

To compare the effect of a specialized care facility (SCF) on quality of life (QoL) for residents with middle- to late-stage dementia over a 1-year period with residence in traditional institutional facilities. A prospective, matched-group design with assessments of QoL every 3 months for 1 year. Twenty-four long-term care centers and four designated assisted living environments in an urban center in western Canada. One hundred eighty-five residents with Global Deterioration Scores of 5 or greater were enrolled: 62 in the intervention SCF group and 123 in the traditional institutional facilities groups. The SCF is a 60-bed purpose-built facility with 10 people living in six bungalows. The facility followed an ecologic model of care that is responsive to the unique interplay of each person and the environment. This model encompasses a vision of long-term care that is more comfortable, more like home, and offers more choice, meaningful activity, and privacy than traditional settings. QoL outcomes were assessed using the Brief Cognitive Rating Scale, Functional Assessment Staging, Cohen-Mansfield Agitation Inventory, Pleasant Events Scale—Alzheimer's disease, Multidimensional Observation Scale of Elderly Subjects, and Apparent Affect Rating Scale. The intervening SCF group demonstrated less decline in activities of daily living, more sustained interest in the environment, and less negative affect than residents in the traditional institutional facilities. There were no differences between groups in concentration, memory, orientation, depression, or social withdrawal. The present study suggests that QoL for adults with middle- to late-stage dementia is the same or better in a purpose-built and staffed SCF than in traditional institutional settings. [ABSTRACT FROM AUTHOR]

Reports on health care in Canada as of October, 2001. History of Medicare which was founded on principles of universality, accessibility, comprehensiveness, portability, and public administration; View that the system has deteriorated from an icon of Canadian values and organisational know how to an apparent state of crisis; Proposed reasons for the deterioration, including less federal funding for the system; Impact of privatization.

A correction to the article "Risk of Bias in Reports of In Vivo Research: A Focus for Improvement" that was published in the 2015 issue is presented.