Application of Multi-Criteria Decision Analysis (MCDA) to Prioritize Real-World Evidence Studies for Health Technology Management: Outcomes and Lessons Learned by the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration.

Multi-criteria decision analysis (MCDA) is a value assessment tool designed to help support complex decision-making by incorporating multiple factors and perspectives in a transparent, structured approach. We developed an MCDA rating tool, consisting of seven criteria evaluating the importance and feasibility of conducting potential real-world evidence (RWE) studies aimed at addressing uncertainties stemming from initial cancer drug funding recommendations. In collaboration with the Canadian Agency for Drugs and Technologies in Health's Provincial Advisory Group, a validation exercise was conducted to further evaluate the application of the rating tool using RWE proposals varying in complexity. Through this exercise, we aimed to gain insight into consensus building and deliberation processes and to identify efficiencies in the application of the rating tool. An experienced facilitator led a multidisciplinary committee, consisting of 11 Canadian experts, through consensus building, deliberation, and prioritization. A total of nine RWE proposals were evaluated and prioritized as low (n = 4), medium (n = 3), or high (n = 2) priority. Through an iterative process, efficiencies and recommendations to improve the rating tool and associated procedures were identified. The refined MCDA rating tool can help decision-makers prioritize important and feasible RWE studies for research and can enable the use of RWE for the life-cycle evaluation of cancer drugs.

Patients' attitudes and preferences toward delayed disease progression in the absence of improved survival.

BACKGROUND: Cancer patients' attitudes toward progression-free survival (PFS) gains offered by treatment are not well understood, particularly in the absence of overall survival (OS) gains. The objectives were to describe patients' willingness to accept treatment that offers PFS gains without OS gains, to compare these findings with treatments offering OS gains, and to qualitatively summarize patients' reasons for their preferences. METHODS: A multicenter, cross-sectional, convergent mixed-methods study design recruited patients who had received at least 3 months of systemic therapy for incurable solid tumors. A treatment trade-off exercise determined the gains in imaging PFS that patients require to prefer additional systemic treatment for a scenario of a newly diagnosed, asymptomatic, incurable abdominal tumor. A qualitative, descriptive, thematic analysis explored factors influencing patients' decisions, and a narrative method integrated the quantitative and qualitative findings. RESULTS: In total, 100 patients participated (63% were older than 60 years of age). If additional treatment with added toxicity offered no OS advantage, 17% would prefer it for no PFS benefit; 26% for some PFS benefit (range, 3-9 months), whereas 51% would decline it regardless of PFS benefit. Similarly, 71% preferred additional treatment offering a 6-month OS advantage dependent on described toxicity levels (P = .03). A spectrum of reasons for these preferences reflected the complexity of participants' attitudes and values. CONCLUSIONS: Prolongation of time to progression was not universally valued. Most patients did not prefer treatments that negatively affect quality of life for PFS gains alone. Implications for individual decision making, policy, and trials research are discussed.

Development of a Multi-Criteria Decision Analysis Rating Tool to Prioritize Real-World Evidence Questions for the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration.

The Canadian Real-world Evidence for Value of Cancer Drugs (CanREValue) collaboration developed an MCDA rating tool to assess and prioritize potential post-market real-world evidence (RWE) questions/uncertainties emerging from public drug funding decisions in Canada. In collaboration with a group of multidisciplinary stakeholders from across Canada, the rating tool was developed following a three-step process: (1) selection of criteria to assess the importance and feasibility of an RWE question; (2) development of rating scales, application of weights and calculating aggregate scores; and (3) validation testing. An initial MCDA rating tool was developed, composed of seven criteria, divided into two groups. Group A criteria assess the importance of an RWE question by examining the (1) drug's perceived clinical benefit, (2) magnitude of uncertainty identified, and (3) relevance of the uncertainty to decision-makers. Group B criteria assess the feasibility of conducting an RWE analysis including the (1) feasibility of identifying a comparator, (2) ability to identify cases, (3) availability of comprehensive data, and (4) availability of necessary expertise and methodology. Future directions include partnering with the Canadian Agency for Drugs and Technology in Health's Provincial Advisory Group for further tool refinement and to gain insight into incorporating the tool into drug funding deliberations.

Associations Between Physical Activity Vital Sign in Patients and Health Care Utilization in a Health Care System, 2018-2020.

BACKGROUND: Physical inactivity is a risk factor for many chronic conditions. This retrospective cohort study examined associations between physical activity (PA) with health care utilization (HU). METHODS: A PA vital sign was recorded in clinics from January 2018 to December 2020. Patients were categorized as inactive, insufficiently active, or sufficiently active by US PA aerobic guidelines. Associations between PA vital sign and visits (inpatient admissions, emergency department, urgent care, and primary care) were estimated using population average regression by visit type. RESULTS: 23,721 patients had at least one PA vital sign recorded, with a mean age of 47.3 years and mean body mass index (BMI) of 28; 52% were female and 63% were White. Sufficiently active patients were younger, male, White, and had lower BMI than insufficiently active patients. Achieving 150 minutes per week of moderate to vigorous PA per 1000 patient years was associated with 34 fewer emergency department visits (P < .001), 19 fewer inpatient admissions (P < .001), and 38 fewer primary care visits (P < .001) compared with inactive patients. Stronger associations between lower PA and higher HU were present among those who were older or had a higher comorbidity. BMI, sex, ethnicity, and race did not modify the association between PA and HU. CONCLUSIONS: Meeting aerobic guidelines was associated with reduced HU for inpatient, primary care, and emergency department visits.

Gambling Associated Risk-taking Behaviors Correlate with Emotional Regulation and the Iowa Gambling Task but not Wisconsin Card Sorting.

It is not known why some novice gamblers eventually develop Gambling Disorder while most do not. This study tested predictions from two competing models of Gambling Disorder etiology: the Pathways Model of Problem and Pathological Gambling (Blaszczynski & Nower, 2002) and the Allostatic Model of addictions (Koob & Schulkin, 2019) applied to Gambling Disorder. Participants were drawn from introductory psychology courses and screened as non-gamblers (N = 91). They completed computerized versions of the Iowa Gambling Task (IGT-2), Wisconsin Sorting Task (WCST-64), and a Difficulties with Emotional Regulation Scale (DERS). Risk-taking tendencies were observed by having participants play a typical electronic slots game for up to 15 min. Higher betting on the slots game was correlated with the frequency of Deck A selections on the IGT-2 and lower total DERS scores. There were no significant correlations involving slots betting and the WCST-64. Greater risk-taking on the slots game was correlated with more frequent wins, partial losses that were disguised as wins, bonus game features, and the largest nominal amount won on a single spin. However, there were no significant correlations between betting behaviors and the 'payback percentage', defined as total winnings as a proportion of total wagers made throughout the session. Post-game ratings were positively correlated with frequency of reinforcing outcomes. These findings suggest that novice gamblers' likelihood of further gambling participation may be elevated by high sensitivity to immediate rewards and low difficulty self-regulating negative emotions. These findings are consistent with the Allostatic Model; they are not consistent with Pathways Model.

Engaging Patients in the Canadian Real-World Evidence for Value in Cancer Drugs (CanREValue) Initiative: Processes and Lessons Learned.

The Canadian Real-world Evidence for Value in Cancer Drugs (CanREValue) Collaboration established the Engagement Working Group (WG) to ensure that all key stakeholders had an opportunity to provide input into the development and implementation of the CanREValue Real-World Evidence (RWE) Framework. Two consultations were held in 2021 to solicit patient perspectives on key policy and data access issues identified in the interim policy and data WG reports. Over 30 individuals, representing patients, caregivers, advocacy leaders, and individuals engaged in patient research were invited to participate. The consultations provided important feedback and valuable lessons in patient engagement. Patient leaders actively shaped the process and content of the consultation. Breakout groups facilitated by patient advocacy leaders gave the opportunity for open and thoughtful contributions from all participants. Important recommendations were made: the RWE framework should not impede access to new drugs; it should be used to support conditional approvals; patient relevant endpoints should be captured in provincial datasets; access to data to conduct RWE should be improved; and privacy issues must be considered. The manuscript documents the CanREValue experience of engaging patients in a consultative process and the useful contributions that can be achieved when the processes to engage are guided by patients themselves.

Implementation of a standardized pregnancy screening process to address gender disparities in radiology turn-around-time and ED length of stay.

OBJECTIVE: The objective of this initiative was to quantify and intervene upon suspected gender disparities in CT turn-around-time and emergency department (ED) length of stay. METHODS: This was a single-site before-after quality improvement initiative including patients aged 12-50 who underwent CT chest and/or abdomen/pelvis. The intervention included protocolization of the pregnancy screening process in triage. Primary outcomes included the difference between women of childbearing age and similarly aged men in regards to CT turn-around-time and ED length of stay. Pre- and post-intervention data were analyzed, including an "intensive intervention period" subanalysis. RESULTS: CT turn-around-time for women of childbearing age was 19 min longer than for similarly aged men at baseline and did not change significantly post-intervention. ED length of stay was 27 min longer for women of childbearing age compared to similarly aged men at baseline and 7 min longer post-intervention, although this was still a significant difference. During the intensive intervention period, CT turn-around-time for women of childbearing age was 15 min longer than similarly aged men but the difference in ED length of stay of 10 min was no longer significant. CONCLUSIONS: There is gender disparity in CT turn-around-time and ED length of stay in our ED, highlighting an important area for improvement to promote equitable care. A quality improvement initiative that aimed to protocolize pregnancy testing in triage did not show sustainable improvement in these outcomes but did result in increased pregnancy testing.

RéSUMé: OBJECTIF: L'objectif de cette initiative était de quantifier et d'intervenir sur les disparités présumées entre les sexes dans le délai d'exécution du scanner et la durée du séjour au service des urgences. MéTHODES: Il s'agissait d'une initiative d'amélioration de la qualité à un seul site avant-après, incluant les patients âgés de 12 à 50 ans qui ont subi une TDM thoracique et/ou abdominale/bassin. L'intervention comprenait la protocolisation du processus de dépistage de la grossesse lors du triage. Les résultats primaires comprenaient la différence entre les femmes en âge de procréer et les hommes du même âge en ce qui concerne le délai d'exécution du scanner et la durée du séjour aux urgences. Les données avant et après l'intervention ont été analysées, y compris une sous-analyse de la "période d'intervention intensive". RéSULTATS: Le temps d'exécution de la TDM chez les femmes en âge de procréer était 19 minutes de plus que chez les hommes de même âge au départ et n'a pas changé de façon significative après l'intervention. La durée de séjour aux urgences était de 27 minutes de plus pour les femmes en âge de procréer par rapport aux hommes du même âge au départ et de 7 minutes de plus après l'intervention, bien que cette différence reste significative. Au cours de la période d'intervention intensive, le temps de passage au scanner des femmes en âge de procréer était de 15 minutes plus long que celui des hommes du même âge, mais la différence de 10 minutes dans la durée de séjour aux urgences n'était plus significative. CONCLUSIONS: Il existe une disparité entre les sexes en ce qui concerne le délai d'exécution du scanner et la durée de séjour dans nos urgences, ce qui met en évidence un domaine important à améliorer pour promouvoir des soins équitables. Une initiative d'amélioration de la qualité visant à protocoliser le test de grossesse au triage n'a pas montré d'amélioration durable de ces résultats mais a entraîné une augmentation des tests de grossesse.

Altered toxicological endpoints in humans from common quaternary ammonium compound disinfectant exposure.

Humans are frequently exposed to Quaternary Ammonium Compounds (QACs). QACs are ubiquitously used in medical settings, restaurants, and homes as cleaners and disinfectants. Despite their prevalence, nothing is known about the health effects associated with chronic low-level exposure. Chronic QAC toxicity, only recently identified in mice, resulted in developmental, reproductive, and immune dysfunction. Cell based studies indicate increased inflammation, decreased mitochondrial function, and disruption of cholesterol synthesis. If these findings translate to human toxicity, multiple physiological processes could be affected. This study tested whether QAC concentrations could be detected in the blood of 43 human volunteers, and whether QAC concentrations influenced markers of inflammation, mitochondrial function, and cholesterol synthesis. QAC concentrations were detected in 80 % of study participants. Blood QACs were associated with increase in inflammatory cytokines, decreased mitochondrial function, and disruption of cholesterol homeostasis in a dose dependent manner. This is the first study to measure QACs in human blood, and also the first to demonstrate statistically significant relationships between blood QAC and meaningful health related biomarkers. Additionally, the results are timely in light of the increased QAC disinfectant exposure occurring due to the SARS-CoV-2 pandemic. MAIN FINDINGS: This study found that 80 % of study participants contained QACs in their blood; and that markers of inflammation, mitochondrial function, and sterol homeostasis varied with blood QAC concentration.

Difficult intravenous access in the emergency department: Performance and impact of ultrasound-guided IV insertion performed by nurses.

BACKGROUND: Difficult intravenous access (DIVA) is a common problem in Emergency Departments (EDs), yet the prevalence and clinical impact of this condition is poorly understood. Ultrasound-guided peripheral intravenous catheter (USGPIV) insertion is a successful modality for obtaining intravenous (IV) access in patients with DIVA. OBJECTIVES: We aimed to describe the prevalence of DIVA, explore how DIVA affects delivery of care, and determine if nurse insertion of USGPIV improves care delays among patients with DIVA. METHODS: We retrospectively queried the electronic medical record for all ED patients who had a peripheral IV (PIV) inserted at a tertiary academic medical center from 2015 to 2017. We categorized patients as having DIVA if they required ≥3 PIV attempts or an USGPIV. We compared metrics for care delivery including time-to-IV-access, time-to-laboratory-results, time-to-IV-analgesia, and ED length of stay (LOS) between patients with and without DIVA. We also compared these metrics in patients with DIVA with a physician-inserted USGPIV versus those with a nurse-inserted USGPIV. RESULTS: A total of 147,260 patients were evaluated during the study period. Of these, 13,192 (8.9%) met criteria for DIVA. Patients with DIVA encountered statistically significant delays in time-to-IV-access, time-to-laboratory-results, time-to-IV-analgesia, and ED LOS compared to patients without DIVA (all p < 0.001). Patients with nurse-inserted USGPIVs also had statistically significant improvements in time-to-IV-access, time-to-laboratory-results, time-to-IV-analgesia, and ED LOS compared to patients with physician-inserted USGPIVs (all p < 0.001). CONCLUSION: DIVA affects many ED patients and leads to delays in PIV access-related care. Nurse insertion of USGPIVs improves care in patients with DIVA.

Are We Making a Difference? A Qualitative Study of Patient Engagement at the pan-Canadian Oncology Drug Review: Perspectives of Patient Groups.

OBJECTIVES: Despite wide support for patient involvement in health technology assessments (HTA), determining meaningful engagement is complex. This article explores experiences and perceptions among patient groups participating in the Canadian Agency for Drugs and Technologies in Health (CADTH)'s pan-Canadian Oncology Drug Review (pCODR) process. METHODS: We created a qualitative interview study comprising 22 semi-structured telephone interviews with individuals representing 21 different patient groups registered with the pCODR process. The analysis used a qualitative descriptive approach employing techniques from grounded theory. RESULTS: Patient groups view the ability to make submissions to the pCODR process as a meaningful activity closely aligned with organizational priorities. Concurrently, they face substantial resource challenges to prepare submissions, including high opportunity costs and difficulty accessing needed literature and finding relevant patients. Although patient groups felt that CADTH is committed to transparency, they expressed considerable uncertainty around the direct impact of their submissions and desired additional avenues for engagement. CONCLUSIONS: This study suggests a strong commitment by patient groups to participate in the pCODR process despite uncertainty about how their submissions are used to inform HTA recommendations. Identifying opportunities to provide both financial and nonfinancial resources to patient groups is crucial to encouraging and supporting their meaningful participation in HTA processes.

Lactobacillus rescues postnatal neurobehavioral and microglial dysfunction in a model of maternal microbiome dysbiosis.

Increasing reports of pregnancy events leading to maternal microbiome dysbiosis (MMD) show strong correlates with atypical neurodevelopmental outcomes. However, the mechanism(s) driving microbiome-mediated behavioral dysfunction in offspring remain understudied. Here, we demonstrate the presence of a novel gut commensal bacterium strain, Lactobacillus murinus HU-1, was sufficient to rescue behavioral deficits and brain region-specific microglial activationobserved in MMD-reared murine offspring. We furtheridentified a postnatal window of susceptibility that could prevent social impairments with timed maternal administration of the symbiotic bacterium. Moreover, MMD increased expression of microglial senescence genes, Trp53 and Il1ß, and Cx3cr1 protein in the prefrontal cortex, which correlated with dysfunctional modeling of synapses and accompanied dysbiosis-induced microglial activation. MMD male offspring harboring Lactobacillus murinus HU-1 or lacking Cx3cr1 showed amelioration of these effects. The current study describes a new avenue of influence by which maternally transferred Lactobacillus drives proper development of social behavior in the offspring through microglia-specific regulation of Cx3cr1 signaling.

Networks underlying trait impulsivity: Evidence from voxel-based lesion-symptom mapping.

Impulsivity is considered a multidimensional construct that encompasses a range of behaviors, including poor impulse control, premature decision-making, and the inability to delay gratification. In order to determine the extent to which impulsivity and its components share a common network, a voxel-based lesion-symptom mapping (VLSM) analysis was performed in a large sample of patients (N = 131) with focal, penetrating traumatic brain injuries (pTBI). Impulsivity was assessed using the Barratt Impulsiveness Scale (BIS-11), a standard self-report measure that allows for unique estimates of global impulsivity and its factor analysis-derived components (e.g., "motor impulsivity"). Heightened global impulsivity was associated with damage to multiple areas in bilateral prefrontal cortex (PFC), left superior, middle and inferior temporal gyrus, and left hippocampus. Moreover, a cluster was identified within the left PFC associated specifically with motor impulsivity (defined as "acting without thinking"). The results were consistent with the existing literature on bilateral prefrontal cortical involvement in behavioral impulsivity, but also provided new evidence for a more complex neuroanatomical representation of this construct, characterized by left-lateralized temporal and hippocampal involvement, as well as a left-lateralized prefrontal network specifically associated with motor impulsivity. Hum Brain Mapp 38:656-665, 2017. © 2016 Wiley Periodicals, Inc.

Patient safety in a pediatric centre: partnering with families.

Patient Centred Care (PCC) is a recognized pillar of quality healthcare. According to the Institute of Medicine (Kohn et al. 2000), PCC respects and is responsive to individual patient preferences, needs and values, and ensures they guide all clinical decisions. In a pediatric setting, both the child and family's preferences and values are critical; as a result, the concept of PCC is broadened to include the entire family, and is termed Family Centred Care (FCC). True FCC requires transparent and ongoing collaboration between the child, family, and all members of the healthcare team. An institution's commitment to Family Centred Care must be explicit and permeate all aspects of healthcare provisions. At Toronto's Hospital for Sick Children (SickKids), the Families as Partners in Patient Safety Committee has proven to be a successful initiative based on Family Centred Care principles. This interdisciplinary committee includes healthcare providers, parents and representatives from our hospital's Children's Council. The mandate of the group is to: (1) identify patient safety (PS) issues, (2) make recommendations to improve PS and (3) increase awareness and promote the partnership between parents and staff in PS. Key initiatives to date include developing PS information for families, a combined hand hygiene campaign and a campaign to make the hospital 100% smoke-free. A task-oriented partnership between families and healthcare workers has proven to be a productive model for advancing pediatric patient safety.