Investigating the Statistical and Policy Frameworks Used to Gauge Potential Pharmacotherapy Recalls: A Scoping Review

Paramount attention is often afforded to pharmacotherapies being brought to market. The anticipation from companies, their shareholders, and the patients poised to benefit are met with stiff statistical and methodological requirements set forth by Health Canada’s Health Products and Food Branch (HPFB). Once a pharmacotherapy has been approved by the HPFB, however, the onus to monitor these drugs falls largely on the shoulders of Health Canada, the manufacturers, and to a lesser degree, the Drug Safety and Effectiveness Network (DSEN). This scoping review identified existing pharmacovigilance frameworks recommendations from SCOPUS, PubMed and EMBASE and compared the guidelines employed by Health Canada, the US FDA, and the European Union Medicines Agency. The review found that the current system disproportionately relies on manufacturers to “self-regulate” and passively report adverse reactions, posing an obvious conflict of interest as to the safety of pharmacotherapies. As well, there remains a lack of clarity from Health Canada regarding their statistical methods and vision for improving risk mitigation strategies for post-market surveillance. This lack of centralization and standardization in the recall process lends itself to a suboptimal piecemeal solution meant to protect Canadians

Regulatory Implications of Inadequately Designed Pimavanserin Drug Trials Published with Risk of Bias on Expedited Regulatory Approval Processes

The objective of this retrospective critical appraisal study was to determine if the trials submitted to the Food and Drug Administration for the expedited approval of pimavanserin was of sufficient methodological quality to ascertain its safety and efficacy. After the general metrics of the trials were assessed, the Risk of Bias 2 tool and the PRagmatic Explanatory Continuum Indicator Summary tool were employed to evaluate the risk of bias and the design suitability of the trials. This study suggests that the decision to approve pimavanserin for the treatment of Parkinson’s Disease Psychosis failed to meet the threshold of evidence normally required for FDA drug applications. It also revealed serious risks of bias with the pivotal trial that was foundational to pimavanserin’s delineation as a breakthrough drug, and that the safety studies were also questionably designed. These findings highlight the need to continue monitoring pimavanserin and re-examine expedited drug approval processes

Interdisciplinary Health Care Evaluation Instruments: A Review of Psychometric Evidence.

Teamwork among health care professionals has been found to improve patient outcomes and reduce burnout. Surveys from individual team members are often used to measure the effectiveness of teamwork performance, as they provide an efficient way to capture various constructs of teamwork. This allows evaluators to better understand team functioning, areas of strength, and to identify potential areas for improvement. However, the majority of published surveys are yet to be validated. We conducted a review of psychometric evidence to identify instruments frequently used in practice and identified in the literature. The databases searched included MEDLINE, EMBASE, CINAHL, and PsycINFO. After excluding duplicates and irrelevant articles, 15 articles met the inclusion criteria for full assessment. Seven surveys were validated and most frequently identified in the literature. This review aims to facilitate the selection of instruments that are most appropriate for research and clinical practice. More research is required to develop surveys that better reflect the current reality of teamwork in our evolving health system, including a greater consideration for patient as team members. Additionally, more research is needed to encompass an increasing development of team assessment tools

Lessons learned from inadequate implementation planning of team-based chronic disease management: implementation evaluation.

BACKGROUND: This study was a retrospective evaluation of an unsuccessfully implemented team-based, chronic disease management program, with an aim to understand more about implementation barriers. The program, the Chronic Disease Management Initiative (CDMI) was a new collaborative model of care for patients with COPD. It utilized customized health information and interactive tools, mainly smartphones, for ongoing disease management. The program\u27s goal was to demonstrate that integrated team-based models of care could improve patient care, as well as reduce readmission rates and emergency department visits. The program planning for CDMI began in 2017, followed by the implementation and evaluation period in 2018. After a 10-month implementation period, the program was unable to enroll a sufficient number of patients to examine if there was an improvement in patient outcomes. METHODS: A retrospective case-study design using multiple data sources was used to gather feedback from participants involved in CDMI. Data collection occurred throughout planning and implementation and continued into early 2019. Semi-structured interviews were conducted, and transcripts were analyzed using NVivo 10 software. This was followed by content analysis. RESULTS: Analysis revealed four key themes as barriers to CDMI\u27s implementation: 1) lack of a needs assessment with key stakeholders; 2) lack of buy-in from medical staff; 3) inadequate patient engagement and; 4) contextual barriers. Planners did not conduct a proper needs assessment, nor include patients in the study design. In addition, there was insufficient consideration for how CDMI should be integrated into the usual COPD care plan, leading to confusion in roles and responsibilities. Poor communication between the implementation team and healthcare providers implementing the program, led to a lack of buy-in and engagement. CONCLUSION: The key themes resonate with what is already known in the literature. This study supports the importance of using a theoretically grounded plan for implementation. Using a model only in the planning stages is insufficient even when an intervention is based on evidence to support higher quality care. It is imperative to consider practical and contextual factors of program implementation and their interactions. By detailing the \u27failed implementation\u27 of this intervention, we hope to share important lessons about the need to plan implementation processes early in program planning

Using Visual Methods to Capture Patient Perspectives in Interprofessional Team-Based Care for Chronic Disease Management

Background: Understanding how patients perceive their role in the healthcare team can improve overall satisfaction of care and health outcomes. However, it has been challenging to capture the diversity of patient experiences using traditional research approaches. The goal of this study was to explore the perspectives of patients involved in an interprofessional team-based chronic disease management program for chronic obstructive pulmonary disease using visual research techniques. Methods: Our visual approach began with patients autonomously drawing (or mapping) experiences with their healthcare team. The maps were explored with the patients through focus group discussions. Maps were inductively coded to identify similarities and differences between participants’ perceptions. Focus group transcripts were first analyzed independently, then compared to and integrated into the map analysis. Findings: Overall, participants (n = 13) were satisfied as patients of team-based care. Participants drew multiple healthcare providers, sources of information, and themselves to represent their teams. Relationships and significance were represented using arrows, the size of each team member, facial expressions, and symbols. Four key elements of effective team-based models of care emerged: 1) effective information sharing, 2) diversity of providers’ roles, 3) empowerment through self-management, and 4) enhanced access to care. Conclusion: This study used visualization methodology to obtain patient feedback on the program’s performance, elicit patients’ experiences, and attempt to mitigate some of the limitations of isolated survey and focus group methodology, subsequently obtaining rich data on team-based care. Our research also informs ongoing quality improvement of the team nbased model for chronic disease management

On the Emergence of Unstable Modes in an Expanding Domain for Energy-Conserving Wave Equations

Motivated by recent work on instabilities in expanding domains in reaction-diffusion settings, we propose an analog of such mechanisms in energy-conserving wave equations. In particular, we consider a nonlinear Schr{\"o}dinger equation in a finite domain and show how the expansion or contraction of the domain, under appropriate conditions, can destabilize its originally stable solutions through the modulational instability mechanism. Using both real and Fourier spacediagnostics, we monitor and control the crossing of the instability threshold and, hence, the activation of the instability. We also consider how the manifestation of this mechanism is modified in a spatially inhomogeneous setting, namely in the presence of an external parabolic potential, which is relevant to trapped Bose-Einstein condensates

A Comparative Study of the Formation of Aromatics in Rich Methane Flames Doped by Unsaturated Compounds

For a better modeling of the importance of the different channels leading to the first aromatic ring, we have compared the structures of laminar rich premixed methane flames doped with several unsaturated hydrocarbons: allene and propyne, because they are precursors of propargyl radicals which are well known as having an important role in forming benzene, 1,3-butadiene to put in evidence a possible production of benzene due to reactions of C4 compounds, and, finally, cyclopentene which is a source of cyclopentadienylmethylene radicals which in turn are expected to easily isomerizes to give benzene. These flames have been stabilized on a burner at a pressure of 6.7 kPa (50 Torr) using argon as dilutant, for equivalence ratios (?) from 1.55 to 1.79. A unique mechanism, including the formation and decomposition of benzene and toluene, has been used to model the oxidation of allene, propyne, 1,3 butadiene and cyclopentene. The main reaction pathways of aromatics formation have been derived from reaction rate and sensitivity analyses and have been compared for the three types of additives. These combined analyses and comparisons can only been performed when a unique mechanism is available for all the studied additives

Galaxy Formation Theory

We review the current theory of how galaxies form within the cosmological framework provided by the cold dark matter paradigm for structure formation. Beginning with the pre-galactic evolution of baryonic material we describe the analytical and numerical understanding of how baryons condense into galaxies, what determines the structure of those galaxies and how internal and external processes (including star formation, merging, active galactic nuclei etc.) determine their gross properties and evolution. Throughout, we highlight successes and failings of current galaxy formation theory. We include a review of computational implementations of galaxy formation theory and assess their ability to provide reliable modelling of this complex phenomenon. We finish with a discussion of several "hot topics" in contemporary galaxy formation theory and assess future directions for this field.Comment: 58 pages, to appear in Physics Reports. This version includes minor corrections and a handful of additional reference

Modeling Heterogeneous Statistical Patterns in High-dimensional Data by Adversarial Distributions: An Unsupervised Generative Framework

Since the label collecting is prohibitive and time-consuming, unsupervised methods are preferred in applications such as fraud detection. Meanwhile, such applications usually require modeling the intrinsic clusters in high-dimensional data, which usually displays heterogeneous statistical patterns as the patterns of different clusters may appear in different dimensions. Existing methods propose to model the data clusters on selected dimensions, yet globally omitting any dimension may damage the pattern of certain clusters. To address the above issues, we propose a novel unsupervised generative framework called FIRD, which utilizes adversarial distributions to fit and disentangle the heterogeneous statistical patterns. When applying to discrete spaces, FIRD effectively distinguishes the synchronized fraudsters from normal users. Besides, FIRD also provides superior performance on anomaly detection datasets compared with SOTA anomaly detection methods (over 5% average AUC improvement). The significant experiment results on various datasets verify that the proposed method can better model the heterogeneous statistical patterns in high-dimensional data and benefit downstream applications

Identification of a Fundamental Transition in a Turbulently-Supported Interstellar Medium

The interstellar medium in star-forming galaxies is a multiphase gas in which turbulent support is at least as important as thermal pressure. Sustaining this configuration requires continuous radiative cooling, such that the overall average cooling rate matches the decay rate of turbulent energy into the medium. Here we carry out a set of numerical simulations of a stratified, turbulently stirred, radiatively cooled medium, which uncover a fundamental transition at a critical one-dimensional turbulent velocity of ~ 35 km/s. At turbulent velocities below ~35 km/s, corresponding to temperatures below 300,000 K, the medium is stable, as the time for gas to cool is roughly constant as a function of temperature. On the other hand, at turbulent velocities above the critical value, the gas is shocked into an unstable regime in which the cooling time increases strongly with temperature, meaning that a substantial fraction of the interstellar medium is unable to cool on a turbulent dissipation timescale. This naturally leads to runaway heating and ejection of gas from any stratified medium with a one-dimensional turbulent velocity above ~35 km/s, a result that has implications for galaxy evolution at all redshifts.Comment: 16 Pages, 11 figures, ApJ, in pres