Meta-Analysis of Normal Reference Values for Right and Left Ventricular Quantification by Cardiovascular Magnetic Resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) reference values are relied upon to accurately diagnose left ventricular (LV) and right ventricular (RV) pathologies. To date, reference values have been derived from modest sample sizes with limited patient diversity and attention to 1 but not both commonly used tracing techniques for papillary muscles and trabeculations. We sought to overcome these limitations by meta-analyzing normal reference values for CMR parameters stemming from multiple countries, vendors, analysts, and patient populations. METHODS: We comprehensively extracted published and unpublished data from studies reporting CMR parameters in healthy adults. A steady-state free-precession short-axis stack at 1.5T or 3T was used to trace either counting the papillary muscles and trabeculations in the LV volume or mass. We used a novel Bayesian hierarchical meta-analysis model to derive the pooled lower and upper reference values for each CMR parameter. Our model accounted for the expected differences between tracing techniques by including informative prior distributions from a large external data set. RESULTS: A total of 254 studies from 25 different countries were systematically reviewed, representing 12 812 healthy adults, of which 52 were meta-analyzed. For LV parameters counting papillary muscles and trabeculations in the LV volume, pooled normative reference ranges in men and women, respectively, were as follows: LV ejection fraction of 52% to 73% and 54% to 75%, LV end-diastolic volume index of 60 to 109 and 56 to 96 mL/m2, LV end-systolic volume index of 18 to 45 and 16 to 38 mL/m2, and LV mass index of 41 to 76 and 33 to 57 g/m2. For LV parameters counting papillary muscles and trabeculations in the LV mass, pooled normative reference ranges in men and women, respectively, were as follows: LV ejection fraction of 57% to 74% and 57% to 75%, LV end-diastolic volume index of 60 to 97 and 55 to 88 mL/m2, LV end-systolic volume index of 18 to 37 and 15 to 34 mL/m2, and LV mass index of 50 to 83 and 38 to 65 g/m2. For RV parameters, pooled normative reference ranges in men and women, respectively, were as follows: RV ejection fraction of 47% to 68% and 49% to 71%, RV end-diastolic volume index of 64 to 115 and 57 to 99 mL/m2, RV end-systolic volume index of 23 to 52 and 18 to 42 mL/m2, and RV mass index of 14 to 29 and 13 to 25 g/m2. CONCLUSIONS: Our Bayesian hierarchical meta-analysis provides normative reference values for CMR parameters of LV and RV size, systolic function, and mass, encompassing both tracing techniques across a diverse multinational sample of healthy men and women.

Weight of Evidence: Participatory Methods and Bayesian Updating to Contextualize Evidence Synthesis in Stakeholders' Knowledge.

Mixed methods research is well-suited to grapple with questions of what counts as valid knowledge across different contexts and perspectives. This article introduces Weight of Evidence as a transformative procedure for stakeholders to interpret, expand on and prioritize evidence from evidence syntheses, with a focus on engaging populations historically excluded from planning and decision making. This article presents the procedure's five steps using pilot data on perinatal care of immigrant women in Canada, engaging family physicians and birth companions. Fuzzy cognitive mapping offers an accessible and systematic way to generate priors to update published literature with stakeholder priorities. Weight of Evidence is a transparent procedure to broaden what counts as expertise, contributing to a more comprehensive, context-specific, and actionable understanding.

Life Course Tobacco Smoking and Risk of HPV-Negative Squamous Cell Carcinomas of Oral Cavity in Two Countries.

Background: Tobacco smoking remains one of the major risk factors for oral cavity cancers (OCC), a subgroup of head and neck cancer (HNC) less attributed to human papillomavirus (HPV) infection. Although a strong dose-dependent association between tobacco smoking and OCC exists, several important questions on the age-dependent effects of this habit remain unanswered. We investigated which life course hypothesis best describes the association between tobacco smoking and HPV-negative (HPV-ve ) OCC in Canada and India. Methods: We used data from the HeNCe Life study, a hospital-based case-control study conducted in Canada and India, using similar protocols. Cases were newly diagnosed subjects with primary squamous cell carcinomas of the head and neck region. Control subjects were patients with non-cancer selected from various outpatient clinics in a hospital located in the same catchment area as the cases and frequency-matched to cases according to age and sex. We collected information on an array of life course exposures using a structured questionnaire with the help of a life grid. Tobacco exposure (pack-years) during three life periods (≤ 30, 31-50, and >50 years of age) was calculated from the entire life course history of smoking. We used CDx brushes to collect oral exfoliated cells. Alpha HPV DNA detection and genotyping were performed for 36 HPV genotypes using the linear array. Participants who tested positive for HPV were excluded from the analysis. We used the Bayesian relevant life course exposure model (BRLM) to identify the life course hypothesis that best described the relationship between tobacco smoking and HPV-ve OCC. Results: We show evidence for a late-life sensitive period (>50 years of age) for tobacco smoking in relation to the risk of HPV-ve OCC in both Canada and India. An increase of 1 pack-year of tobacco smoking increased the risk of OCC by ~3% in both countries. Conclusion: Our findings from the Canadian and Indian data suggest that smoking tobacco after 50 years of age may carry a higher risk of developing oral cancer than earlier in life. Further studies are warranted to confirm the results.

Look Around Me: Environmental and Socio-Economic Factors Related to Community Participation for Children with Cerebral Palsy in Québec.

Aims: This study aimed at gaining a deeper understanding of the environmental and socio-economic factors affecting participation outcomes in community and leisure activities for children with disabilities, as well as the trajectories of participation for these children to promote their health and guarantee their rights are respected.Methods: A participatory action research (PAR) approach and linear regression analysis were employed to identify contextual factors associated with the community participation of children with cerebral palsy (CP) living in Quebec, Canada. Stakeholders engaged through the entire research process supported the development of questionnaires, data collection, analysis and interpretation of results.Results: Neighborhood outings were ranked among the most practiced activities by children with CP. Only in a few cases (9%) did children participate in more than two types of activities outside of school. Factors limiting children's participation were predominantly extrinsic in origin, including financial burden and lack of information about existing opportunities.Conclusions: There is a serious need for communities and local governments to inform parents about available resources, programs and policies that can support their child's participation. Rehabilitation professionals could partner with stakeholders to inform the development of public policies that target the identified barriers and promote children's integration and fulfillment.

A novel method to interpret early phase trials shows how the narrowing of the coronary sinus concordantly improves symptoms, functional status and quality of life in refractory angina.

BACKGROUND: Reduction of the coronary sinus was shown to improve angina in patients unsuitable for revascularisation. We assessed whether a percutaneous device that reduces the diameter of the coronary sinus improved outcomes across multiple endpoints in a phase II trial. METHODS: We conducted a novel analysis performed as a post hoc efficacy analysis of the COSIRA (Coronary Sinus Reducer for Treatment of Refractory Angina) trial, which enrolled patients with Canadian Cardiovascular Society (CCS) class 3-4 refractory angina. We used four domains: symptoms (CCS Angina Scale), functionality (total exercise duration), ischaemia (imaging) and health-related quality of life. For all domains, we specified a meaningful threshold for change. The primary endpoint was defined as a probability of ≥80% that the reducer exceeded the meaningful threshold on two or more domains (group-level analysis) or that the average efficacy score in the reducer group exceeded the sham control group by at least two points (patient-level analysis). RESULTS: We randomised 104 participants to either a device that narrows to coronary sinus (n=52) or a sham implantation (n=52). The reducer group met the prespecified criteria for concordance at the group level and demonstrated improvement in symptoms (0.59 CCS grade, 95% credible interval (CrI)=0.22 to 0.95), total exercise duration (+27.9%, 95% CrI=2.8% to 59.8%) and quality of life (stability +11.2 points, 95% CrI=3.3 to 19.1; perception +11.0, 95% CrI=3.3 to 18.7). CONCLUSIONS: The reducer concordantly improved symptoms, functionality and quality of life compared with a sham intervention in patients with angina unsuitable for coronary revascularisation. Concordant analysis such as this one can help interpret early phase trials and guide the decision to pursue a clinical programme into a larger confirmatory trial. TRAIL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT01205893.

Latency of tobacco smoking for head and neck cancer among HPV-positive and HPV-negative individuals.

Human papillomavirus (HPV) infection and tobacco smoking are well-known risk factors for head and neck cancers (HNC). Although an effect modification between oral HPV infection and tobacco smoking may exist, evidence is lacking on how they interact temporally. We investigated the latency and life course effects of tobacco smoking on risk of HNC among HPV-positive (HPV+ve ) and negative (HPV-ve ) individuals. We used data from 631 ever-smoker participants of a hospital-based case-control study conducted in four major hospitals in Montréal, Canada. Cases (n = 320), incident, histologically confirmed, primary squamous cell carcinomas, were frequency-matched to controls (n = 311) by age and sex. Sociodemographic and behavioral factors (e.g., tobacco and alcohol use and sexual history) were collected using a structured interview applying a life grid technique. Oral exfoliated cells were used for HPV DNA detection and genotyping. Latency effects were estimated flexibly using a Bayesian relevant exposure model and further extended with a life course approach. Retrospective smoking trajectories for HPV+ve cases and controls had similar shapes. Exposure to tobacco smoking even 40 years before diagnosis was associated with an increased HNC risk among both HPV+ve and HPV-ve participants. The effect of smoking before the start of sexual activity compared to afterwards was higher among HPV+ve individuals. This pattern of association was less profound among HPV-ve participants. Temporal interactions may exists between oral HPV infection and life course smoking trajectories in relation to HNC risk.

Bayesian consensus-based sample size criteria for binomial proportions.

Many sample size criteria exist. These include power calculations and methods based on confidence interval widths from a frequentist viewpoint, and Bayesian methods based on credible interval widths or decision theory. Bayesian methods account for the inherent uncertainty of inputs to sample size calculations through the use of prior information rather than the point estimates typically used by frequentist methods. However, the choice of prior density can be problematic because there will almost always be different appreciations of the past evidence. Such differences can be accommodated a priori by robust methods for Bayesian design, for example, using mixtures or ϵ-contaminated priors. This would then ensure that the prior class includes divergent opinions. However, one may prefer to report several posterior densities arising from a "community of priors," which cover the range of plausible prior densities, rather than forming a single class of priors. To date, however, there are no corresponding sample size methods that specifically account for a community of prior densities in the sense of ensuring a large-enough sample size for the data to sufficiently overwhelm the priors to ensure consensus across widely divergent prior views. In this paper, we develop methods that account for the variability in prior opinions by providing the sample size required to induce posterior agreement to a prespecified degree. Prototypic examples to one- and two-sample binomial outcomes are included. We compare sample sizes from criteria that consider a family of priors to those that would result from previous interval-based Bayesian criteria.

Bayesian Methods for Exposure Misclassification Adjustment in a Mediation Analysis: Hemoglobin and Malnutrition in the Association Between Ascaris and IQ.

BACKGROUND: Soil-transmitted helminth infections have been found to be associated with child development. The objective was to investigate hemoglobin levels and malnutrition as mediators of the association between Ascaris infection and intelligence quotient (IQ) scores in children. METHODS: We conducted a longitudinal cohort study in Iquitos, Peru, between September 2011 and July 2016. A total of 1760 children were recruited at 1 year of age and followed up annually to 5 years. We measured Ascaris infection and malnutrition at each study visit, and hemoglobin levels were measured as of age 3. The exposure was defined as the number of detected Ascaris infections between age 1 and 5. We measured IQ scores at age 5 and used Bayesian models to correct exposure misclassification. RESULTS: We included a sample of 781 children in the analysis. In results adjusted for Ascaris misclassification, mean hemoglobin levels mediated the association between Ascaris infection and IQ scores. The natural direct effects (not mediated by hemoglobin) (95% CrI) and natural indirect effects (mediated by hemoglobin) (95% CrI) were compared with no or one infection: -0.9 (-4.6, 2.8) and -4.3 (-6.9, -1.6) for the effect of two infections; -1.4 (-3.8, 1.0) and -1.2 (-2.0, -0.4) for three infections; and -0.4 (-3.2, 2.4) and -2.7 (-4.3, -1.0) for four or five infections. CONCLUSION: Our results are consistent with the hypothesis that hemoglobin levels mediate the association between Ascaris infection and IQ scores. Additional research investigating the effect of including iron supplements in STH control programs is warranted.

Pneumococcal pneumonia prevalence among adults with severe acute respiratory illness in Thailand - comparison of Bayesian latent class modeling and conventional analysis.

BACKGROUND: Determining the etiology of pneumonia is essential to guide public health interventions. Diagnostic test results, including from polymerase chain reaction (PCR) assays of upper respiratory tract specimens, have been used to estimate prevalence of pneumococcal pneumonia. However limitations in test sensitivity and specificity and the specimen types available make establishing a definitive diagnosis challenging. Prevalence estimates for pneumococcal pneumonia could be biased in the absence of a true gold standard reference test for detecting Streptococcus pneumoniae. METHODS: We conducted a case control study to identify etiologies of community acquired pneumonia (CAP) from April 2014 through August 2015 in Thailand. We estimated the prevalence of pneumococcal pneumonia among adults hospitalized for CAP using Bayesian latent class models (BLCMs) incorporating results of real-time polymerase chain reaction (qPCR) testing of upper respiratory tract specimens and a urine antigen test (UAT) from cases and controls. We compared the prevalence estimate to conventional analyses using only UAT as a reference test. RESULTS: The estimated prevalence of pneumococcal pneumonia was 8% (95% CI: 5-11%) by conventional analyses. By BLCM, we estimated the prevalence to be 10% (95% CrI: 7-16%) using binary qPCR and UAT results, and 11% (95% CrI: 7-17%) using binary UAT results and qPCR cycle threshold (Ct) values. CONCLUSIONS: BLCM suggests a > 25% higher prevalence of pneumococcal pneumonia than estimated by a conventional approach assuming UAT as a gold standard reference test. Higher quantities of pneumococcal DNA in the upper respiratory tract were associated with pneumococcal pneumonia in adults but the addition of a second specific pneumococcal test was required to accurately estimate disease status and prevalence. By incorporating the inherent uncertainty of diagnostic tests, BLCM can obtain more reliable estimates of disease status and improve understanding of underlying etiology.

The Sustainability of a Workplace Wellness Program That Incorporates Gamification Principles: Participant Engagement and Health Benefits After 2 Years.

PURPOSE: To evaluate the results of a workplace wellness program that incorporates gamification principles. DESIGN: In this prospective cohort study, the participation rate and observed health outcomes were evaluated after approximately 2 years. SETTING AND PARTICIPANTS: All permanent employees (n = 775) of a national company located in Canada were eligible to participate. INTERVENTION: The wellness program included web-based challenges (team or individual) incorporating gamification strategies to improve exercise, nutrition, weight reduction, and mental health management behaviors. MEASURES AND ANALYSIS: The primary outcomes were employee participation rates. The secondary pre-specified outcomes were the sustained benefits of the program on physical and mental health measures. RESULTS: Participation rates in the health screenings were 78% (baseline), 54% (year 1), and 56% (year 2). Participation in the 4 team web-based challenges ranged from 33% to 68% with 76% to 86% of participants tracking their activity on at least half of the days. After 2 years, there were significant clinical improvements in systolic blood pressure (-1.3mm Hg), total cholesterol/high-density lipoprotein (HDL) ratio (-0.14), glycated haemoglobin (HbA1c; -0.1%), weekly physical activity (+264 Metabolic Equivalents [METs]), perceived stress score (-17%), insomnia severity index (-16%), general fatigue (-10%), and reductions in the cardiovascular age gap (-0.3 years). Greater benefits occurred among employees at higher risk. CONCLUSIONS: Workplace wellness programs that evolve over time and focus primarily on fun and competitive challenges may support long-term participation, behavior change, and sustained improvements in clinical outcomes.

Expostats: A Bayesian Toolkit to Aid the Interpretation of Occupational Exposure Measurements.

INTRODUCTION: Interpretation of exposure measurements has evolved into a framework based on the lognormal distribution. Most available practical tools are based on traditional frequentist statistical procedures that do not satisfactorily account for censored data and are not amenable to simple probabilistic risk statements. Bayesian methods offer promising solutions to these challenges. Such methods have been proposed in the literature but are not widely and freely available to practitioners. METHODS: A set of computer applications were developed aimed at answering typical inferential questions that are important to occupational health practitioners: Is a group of workers compliant with an occupational exposure limit? Are some individuals within this group likely to experience substantially higher exposure than its average member? How does an intervention influence the distribution of exposures? These questions were addressed using Bayesian models, simultaneously accounting for left, right, and interval-censored data with multiple censoring points. The models are estimated using the JAGS Gibbs sampler called through the R statistical package. RESULTS: The Expostats toolkit is freely available from www.expostats.ca as four tools accessible through a Web application, an offline standalone application or algorithms. The tools include a variety of calculations and graphical outputs useful according to current practices in analysis and interpretation of exposure measurements collected by occupational hygienists. Tool1 and its simplified version Tool1 Express focus on inferences from data from a similarly exposed group. Tool2 evaluates within- and between-worker components of variability, as well as the probability that an individual worker might be overexposed. Tool3 compares exposure data across groups, e.g. evaluates the effect of an intervention. Uncertainty management includes the calculation of credible intervals and produces probabilistic statements about the exposure metrics (e.g. probability that over 5% of exposures are above a limit). DISCUSSION: Expostats is the first freely available toolkit that leverages the flexibility of Bayesian analysis to perform an extensive list of calculations recommended in several international guidelines on the practice of occupational hygiene.

An Unsupervised Smart App-Optimized HIV Self-Testing Program in Montreal, Canada: Cross-Sectional Study.

BACKGROUND: Although HIV self-testing strategies have been recommended by the World Health Organization, HIV self-tests are not yet approved in Canada. Currently approved HIV self-tests offer toll-free lines that are insufficient for initiating expedited linkages to counseling and care, accurate interpretation, and support during HIV self-testing. We developed an innovative, multilingual software app called HIVSmart! to plug these gaps. OBJECTIVE: This study aimed to test our app-optimized oral HIV self-testing strategy for feasibility in men who have sex with men (MSM) who presented to test at a large sexual health clinic (Clinique Médicale L'Actuel) in Montreal. METHODS: Between July 2016 and February 2017, we offered a strategy consisting of the OraQuick In-Home HIV Test (an investigational device) and a tablet installed with the HIVSmart! app to study participants, who presented at a private office in the clinic, mimicking an unsupervised home environment. We evaluated the strategy for its feasibility, acceptability, and preference. Using the HIVSmart! app, participants were guided through the self-testing process. We determined feasibility with a metric defined as the completion rate, which consisted of the following 3 steps: (1) self-test conduct; (2) self-test interpretation; and (3) linkages to care. Participants independently performed, interpreted, recorded their self-test and result, engaged in pre- and posttest counseling, and sought linkages to care. Laboratory tests (p24, Western Blot, and RNA), as per country algorithms, were expedited, and linkages based on the rapid test status were arranged. RESULTS: Mean age of the 451 participants enrolled was 34 (range, 18-73) years. Of all participants, 97.1% (438/451) completed and submitted the survey through the HIVSmart! app. In total, 84.7% (371/438) of the participants were well educated (beyond high school) and 52.5% (230/438) had been tested within the past 6 months. Of the 451, 11.5% (52/451) were on pre-exposure prophylaxis. Feasibility (completion rate), an average proportion of the 3 steps, was computed to be 96.6% (419/451). The acceptability of the strategy was high at 98.5% (451/458). A majority of the participants (448/451, 99.3%) were found to be self-tested and lab-confirmed negative and were counseled after self- and rapid tests. In total, 0.7% (3/451) of the participants who self-tested positive and were lab-confirmed positive were linked to a physician within the same day. Furthermore, 98.8% (417/422) of the participants found the app to be useful and 94.0% (424/451) were willing to recommend it to a friend or partner. CONCLUSIONS: The HIVSmart! app-optimized strategy was feasible, accepted, and preferred by an educated, urban MSM population of Montreal. With the app, participants were able to perform, interpret, store results, and get rapidly linked to care. The HIVSmart!-optimized, self-testing strategy could be adapted and contextualized to many at-risk populations within Canada and worldwide, thereby maximizing its public health impact.

A longitudinal cohort study of soil-transmitted helminth infections during the second year of life and associations with reduced long-term cognitive and verbal abilities.

BACKGROUND: Soil-transmitted helminth (STH) infection leads to malnutrition and anemia, and has been linked to impaired child development. Previous research on this topic is limited and mostly conducted in school-age children. The goal of this study was to determine the effect of the number of detected STH infections between one and two years of age on subsequent cognitive and verbal abilities, in a cohort of preschool children. METHODOLOGY/PRINCIPAL FINDINGS: A longitudinal cohort study was conducted in 880 children in Iquitos, Peru between September 2011 and July 2016. Children were recruited at one year of age and followed up at 18 months and then annually between two and five years of age. STH infection was measured with the Kato-Katz technique or the direct smear technique. Child development was measured with the Bayley Scales of Infant and Toddler Development-III at the one to three-year visits and with the Wechsler Preschool and Primary Scale of Intelligence-III at the four and five-year visits. Hierarchical multivariable linear regression models were used to account for the repeated outcome measures for each child and Bayesian latent class analysis was used to adjust for STH misclassification. Children found infected with any STH infection between one and two years of age had lower cognitive scores between two and five years of age (between group score differences (95% credible intervals) for infected once, and infected two or three times, compared to never infected: -4.31 (-10.64, -0.14) and -3.70 (-10.11, -0.11), respectively). Similar results were found for Ascaris infection and for verbal scores. CONCLUSIONS/SIGNIFICANCE: An association was found between having been infected with Ascaris or any STH between one and two years of age and lower cognitive and verbal abilities later in childhood. These results suggest that targeting children for STH control as of one year of age is particularly important.

The effect of cumulative soil-transmitted helminth infections over time on child development: a 4-year longitudinal cohort study in preschool children using Bayesian methods to adjust for exposure misclassification.

Background: Limited research has documented an association between soil-transmitted helminth (STH) infections and child development. This has recently been identified as an important knowledge gap. Methods: A longitudinal cohort study was conducted in Iquitos, Peru, between September 2011 and July 2016. A cohort of 880 children, recruited at 1 year of age, was followed up to 5 years. STH infection was measured annually and child development was measured with the Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III) at 5 years. Linear-regression models were used to investigate the effect of the number of detected STH infections between 1 and 5 years of age on WPPSI-III scores at 5 years of age. Bayesian latent class analysis was used to adjust for exposure misclassification. Results: A total of 781 (88.8%) children were included in the analysis. In multivariable analysis, adjusted for STH misclassification, increasing numbers of Ascaris, Trichuris, hookworm and any STH infections were associated with lower WPPSI-III scores. Among the largest observed effects were those for the effect of Ascaris infection on verbal IQ scores [difference in IQ (95% CrI) for two, three, and four or five detected infections compared with zero or one infection: -8.27 (-13.85, -3.10), -6.69 (-12.05, -2.05) and -5.06 (-10.75, 0.05), respectively]. Misclassification of STH infection generally led to a bias towards the null. Conclusions: These results document an association between STH infection and child development. The results highlight the importance of adjusting for STH misclassification; however, future research is needed to accurately determine the sensitivity of STH diagnostic techniques. STH control in preschool children may contribute to lowering the disease burden associated with poor child development.

A Bayesian approach to investigate life course hypotheses involving continuous exposures.

Background: Different hypotheses have been proposed in life course epidemiology on how a time-varying exposure can affect health or disease later in life. Researchers are often interested in investigating the probability of these hypotheses based on observed life course data. However, current techniques based on model/variable selection do not provide a direct estimate of this probability. We propose an alternative technique for a continuous exposure, using a Bayesian approach that has specific advantages, to investigate which life course hypotheses are supported by the observed data. Methods: We demonstrate the technique, the relevant life course exposure model (RLM), using simulations. We also analyse data from a case-control study on risk factors of oral cancer, with repeated measurements of betel quid chewing across life. We investigate the relative importance of chewing one quid of betel per day, at three life periods: ≤20 years, 21-40 years and above 40 years of age, on the risk of developing oral cancer. Results: RLM was able to correctly identify the life course hypothesis under which the data were simulated. Results from the case-control study showed that there was 74.3% probability that betel quid exposure earlier in life, compared with later, results in higher odds of developing oral cancer later in life. Conclusions: RLM is a useful option to identify the life course hypothesis supported by the observed data prior to the estimation of a causal effect.

A two-stage model in a Bayesian framework to estimate a survival endpoint in the presence of confounding by indication.

Background Biomarker series can indicate disease progression and predict clinical endpoints. When a treatment is prescribed depending on the biomarker, confounding by indication might be introduced if the treatment modifies the marker profile and risk of failure. Objective Our aim was to highlight the flexibility of a two-stage model fitted within a Bayesian Markov Chain Monte Carlo framework. For this purpose, we monitored the prostate-specific antigens in prostate cancer patients treated with external beam radiation therapy. In the presence of rising prostate-specific antigens after external beam radiation therapy, salvage hormone therapy can be prescribed to reduce both the prostate-specific antigens concentration and the risk of clinical failure, an illustration of confounding by indication. We focused on the assessment of the prognostic value of hormone therapy and prostate-specific antigens trajectory on the risk of failure. Methods We used a two-stage model within a Bayesian framework to assess the role of the prostate-specific antigens profile on clinical failure while accounting for a secondary treatment prescribed by indication. We modeled prostate-specific antigens using a hierarchical piecewise linear trajectory with a random changepoint. Residual prostate-specific antigens variability was expressed as a function of prostate-specific antigens concentration. Covariates in the survival model included hormone therapy, baseline characteristics, and individual predictions of the prostate-specific antigens nadir and timing and prostate-specific antigens slopes before and after the nadir as provided by the longitudinal process. Results We showed positive associations between an increased prostate-specific antigens nadir, an earlier changepoint and a steeper post-nadir slope with an increased risk of failure. Importantly, we highlighted a significant benefit of hormone therapy, an effect that was not observed when the prostate-specific antigens trajectory was not accounted for in the survival model. Conclusion Our modeling strategy was particularly flexible and accounted for multiple complex features of longitudinal and survival data, including the presence of a random changepoint and a time-dependent covariate.

Defining the "Critical Elements" for the Most Common Procedures in Spine Surgery: A Consensus of Orthopedic and Neurosurgical Surgeons.

STUDY DESIGN: Survey. OBJECTIVE: To define the critical elements of common spine surgeries. SUMMARY OF BACKGROUND DATA: Despite significant relevance to the field of spine surgery, the term "critical element" of surgery has not been clearly defined. Every surgical procedure involves numerous steps, each with its own potential for complications and harm to the patient. Despite its crucial role in surgical training, billing, and the ethicality of concurrent surgery, the term "critical element" of surgery has not been defined. METHODS: A survey was administered to surgeons associated with AO Spine North America and the Society for Minimally Invasive Spine Surgery to determine the critical elements for four common spine procedures: open lumbar laminectomy and fusion, microdiscectomy, anterior cervical discectomy and fusion (ACDF), and posterior cervical laminectomy and fusion. Respondents were asked which steps necessitated their direct supervision. Surgical subspecialty, level of experience, and practice demographics were also recorded. RESULTS: For all applicable procedures, decompression, instrumentation, and fusion were designated as critical elements. Patient positioning and fascial closure were not. Radiographic localization was considered critical for all procedures, except posterior cervical laminectomy and fusion. Exposure was not considered critical for any procedures, except ACDF. Certain substeps of decompression in ACDF and open lumbar laminectomy and fusion were not considered critical. Orthopaedic surgeons considered exposure and fusion in ACDF procedures to be critical whereas neurosurgeons did not. Surgeons operating in private practice considered every step of these common procedures to be critical elements. CONCLUSION: Decompression, instrumentation, and fusion were considered critical elements of common spine surgeries. There were significant differences in responses according to surgical specialty and practice setting. Future research is necessary to determine the implications of these findings and guide the definition of the "critical portions" of surgery. LEVEL OF EVIDENCE: 1.

The Measurable Benefits of a Workplace Wellness Program in Canada: Results After One Year.

OBJECTIVE: The aim of this study was to evaluate the impact of an employee wellness program in Canada. METHODS: A comprehensive program including web-based lifestyle challenges was evaluated with annual health screenings. RESULTS: Among 730 eligible employees, 688 (94%) registered for the program, 571 (78%) completed a health screening at baseline, and 314 (43%) at 1 year. Most (66%) employees tracked their activity for more than 6 weeks. At 1-year follow-up, there were significant clinical improvements in systolic blood pressure -3.4 mm Hg, and reductions in poor sleep quality (33% to 28%), high emotional stress (21% to 15%), and fatigue (11% to 6%). A positive dose-response was noted where the greatest improvements were observed among those who participated the most. CONCLUSION: The program had high employee engagement. After 1 year, the benefits included clinically important improvements in physical and mental health.

Disparities in rate, triggers, and management in pediatric and adult cases of suspected drug-induced anaphylaxis in Canada.

INTRODUCTION: Data is sparse on drug-induced anaphylaxis (DIA) and there have not been studies assessing the differences in clinical characteristics and management of DIA between adults and children. OBJECTIVE: We assessed the percentage, diagnosis, and management of DIA among all anaphylaxis visits in three pediatric and one adult emergency departments (ED) across Canada. METHODS: Children presenting to the Montreal Children's Hospital (MCH), British Columbia Children's Hospital (BCCH), and Children's Hospital at London Health Sciences Center and adults presenting to Hôpital du Sacré-Coeur with anaphylaxis were recruited as part of the Cross-Canada Anaphylaxis Registry. A standardized data form documenting the reaction and management was completed and patients were followed annually to determine assessment by allergist and use of confirmatory tests. RESULTS: From June 2012 to May 2016, 51 children were recruited from the pediatric centers and 64 adults from the adult center with drug-induced anaphyalxis. More than half the cases were prospectively recruited. The percentage of DIA among all cases of anaphylaxis was similar in all three pediatric centers but higher in the adult center in Montreal. Most reactions in children were triggered by non-antibiotic drugs, and in adults, by antibiotics. The majority of adults and a third of children did not see an allergist after the initial reaction. In those that did see an allergist, diagnosis was established by either a skin test or an oral challenge in less than 20% of cases. CONCLUSIONS: Our results reveal disparities in rate, culprit, and management of DIA in children versus adults. Further, most cases of suspected drug allergy are not appropriately diagnosed. Guidelines to improve assessment and diagnosis of DIA are required.