Outcomes and Cost-Effectiveness of Two Nicotine Replacement Treatment Delivery Models for a Tobacco Quitline

Many tobacco cessation quitlines provide nicotine replacement therapy (NRT) in the U.S. but consensus is lacking regarding the best shipping protocol or NRT amounts. We evaluated the impact of the Minnesota QUITPLAN® Helpline’s shift from distributing NRT using a single eight-week shipment to a two-shipment protocol. For this observational study, the eight week single-shipment cohort (n = 247) received eight weeks of NRT (patches or gum) at once, while the split-shipment cohort (n = 160) received five weeks of NRT (n = 94), followed by an additional three weeks of NRT if callers continued with counseling (n = 66). Patient satisfaction, retention, quit rates, and cost associated with the three groups were compared. A higher proportion of those receiving eight weeks of NRT, whether in one or two shipments, reported that the helpline was “very helpful” (77.2% of the single-shipment group; 81.1% of the two-shipment group) than those receiving five weeks of NRT (57.8% of the one-shipment group) (p = 0.004). Callers in the eight week two-shipment group completed significantly more calls (3.0) than callers in the five week one-shipment group (2.4) or eight week single-shipment group (1.7) (p < 0.001). Using both responder and intent-to-treat calculations, there were no significant differences in 30-day point prevalence abstinence at seven months among the three protocol groups even when controlling for demographic and tobacco use characteristics, and treatment group protocol. The mean cost per caller was greater for the single-shipment phase than the split-shipment phase ($350 vs.$326) due to the savings associated with not sending a second shipment to some participants. Assuming no difference in abstinence rates resulting from the protocol change, cost-per-quit was lowest for the five week one-shipment group ($1,155), and lower for the combined split-shipment cohort ($1,242) than for the single-shipment cohort ($1,350). Results of this evaluation indicate that while satisfaction rates increase among those receiving more counseling and NRT, quit rates do not, even when controlling for demographic and tobacco use characteristics

A Giant Planet Candidate Transiting a White Dwarf

Astronomers have discovered thousands of planets outside the solar system, most of which orbit stars that will eventually evolve into red giants and then into white dwarfs. During the red giant phase, any close-orbiting planets will be engulfed by the star, but more distant planets can survive this phase and remain in orbit around the white dwarf. Some white dwarfs show evidence for rocky material floating in their atmospheres, in warm debris disks, or orbiting very closely, which has been interpreted as the debris of rocky planets that were scattered inward and tidally disrupted. Recently, the discovery of a gaseous debris disk with a composition similar to ice giant planets demonstrated that massive planets might also find their way into tight orbits around white dwarfs, but it is unclear whether the planets can survive the journey. So far, the detection of intact planets in close orbits around white dwarfs has remained elusive. Here, we report the discovery of a giant planet candidate transiting the white dwarf WD 1856+534 (TIC 267574918) every 1.4 days. The planet candidate is roughly the same size as Jupiter and is no more than 14 times as massive (with 95% confidence). Other cases of white dwarfs with close brown dwarf or stellar companions are explained as the consequence of common-envelope evolution, wherein the original orbit is enveloped during the red-giant phase and shrinks due to friction. In this case, though, the low mass and relatively long orbital period of the planet candidate make common-envelope evolution less likely. Instead, the WD 1856+534 system seems to demonstrate that giant planets can be scattered into tight orbits without being tidally disrupted, and motivates searches for smaller transiting planets around white dwarfs.Comment: 50 pages, 12 figures, 2 tables. Published in Nature on Sept. 17, 2020. The final authenticated version is available online at: https://www.nature.com/articles/s41586-020-2713-

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

A time-responsive tool for informing policy making: rapid realist review

Background: A realist synthesis attempts to provide policy makers with a transferable theory that suggests a certain program is more or less likely to work in certain respects, for particular subjects, in specific kinds of situations. Yet realist reviews can require considerable and sustained investment over time, which does not always suit the time-sensitive demands of many policy decisions. ‘Rapid Realist Review’ methodology (RRR) has been developed as a tool for applying a realist approach to a knowledge synthesis process in order to produce a product that is useful to policy makers in responding to time-sensitive and/or emerging issues, while preserving the core elements of realist methodology. Methods Using examples from completed RRRs, we describe key features of the RRR methodology, the resources required, and the strengths and limitations of the process. All aspects of an RRR are guided by both a local reference group, and a group of content experts. Involvement of knowledge users and external experts ensures both the usability of the review products, as well as their links to current practice. Results RRRs have proven useful in providing evidence for and making explicit what is known on a given topic, as well as articulating where knowledge gaps may exist. From the RRRs completed to date, findings broadly adhere to four (often overlapping) classifications: guiding rules for policy-making; knowledge quantification (i.e., the amount of literature available that identifies context, mechanisms, and outcomes for a given topic); understanding tensions/paradoxes in the evidence base; and, reinforcing or refuting beliefs and decisions taken. Conclusions ‘Traditional’ realist reviews and RRRs have some key differences, which allow policy makers to apply each type of methodology strategically to maximize its utility within a particular local constellation of history, goals, resources, politics and environment. In particular, the RRR methodology is explicitly designed to engage knowledge users and review stakeholders to define the research questions, and to streamline the review process. In addition, results are presented with a focus on context-specific explanations for what works within a particular set of parameters rather than producing explanations that are potentially transferrable across contexts and populations. For policy makers faced with making difficult decisions in short time frames for which there is sufficient (if limited) published/research and practice-based evidence available, RRR provides a practical, outcomes-focused knowledge synthesis method.Population and Public Health (SPPH), School ofNon UBCMedicine, Faculty ofReviewedFacult

Engagement and attrition in Internet smoking cessation interventions: Insights from a cross-sectional survey of “one-hit-wonders”

Introduction: Internet interventions can reach large numbers of individuals. However, low levels of engagement and high rates of follow-up attrition are common, presenting major challenges to evaluation. This study investigated why registrants of an Internet smoking cessation intervention did not return after joining (“one hit wonders”), and explored the impact of graduated incentives on survey response rates and responder characteristics. Methods: A sample of “one hit wonders” that registered on a free smoking cessation website between 2014 and 2015 were surveyed. The initial invitation contained no incentive. Subsequent invitations were sent to random subsamples of non-responders from each previous wave offering $25 and$50 respectively. Descriptive statistics characterized respondents on demographic characteristics, reasons for not returning, and length of time since last visit. Differences were investigated with Fisher's Exact tests, Kruskal-Wallis, and logistic regression. Results: Of 8779 users who received the initial invitation, 132 completed the survey (1.5%). Among those subsequently offered a $25 incentive, 127 (3.7$50 incentive, 97 responded (5.7%). The most common reasons endorsed for not returning were being unable to quit (51%), not having enough time (33%), having forgotten about the website (28%), and not being ready to quit (21%). Notably, however, 23% reported not returning because they had successfully quit smoking. Paid incentives yielded a higher proportion of individuals who were still smoking than the $0 incentive (72$0 and $25 responders, likelihood of survey response decreased with time since registration; the$50 incentive removed the negative effect of time-since-registration on probability of response. Conclusions: One third of participants that had disengaged from an Internet intervention reported abstinence at follow-up, suggesting that low levels of engagement are not synonymous with treatment failure in all cases. Paid incentives above $25 may be needed to elicit survey responses, especially among those with longer intervals of disengagement from an intervention

Large-System Transformation in Health Care: A Realist Review

Context: An evidence base that addresses issues of complexity and context is urgently needed for large-system transformation (LST) and health care reform. Fundamental conceptual and methodological challenges also must be addressed. The Saskatchewan Ministry of Health in Canada requested a six-month synthesis project to guide four major policy development and strategy initiatives focused on patient- and family-centered care, primary health care renewal, quality improvement, and surgical wait lists. The aims of the review were to analyze examples of successful and less successful transformation initiatives, to synthesize knowledge of the underlying mechanisms, to clarify the role of government, and to outline options for evaluation. Methods: We used realist review, whose working assumption is that a particular intervention triggers particular mechanisms of change. Mechanisms may be more or less effective in producing their intended outcomes, depending on their interaction with various contextual factors. We explain the variations in outcome as the interplay between context and mechanisms. We nested this analytic approach in a macro framing of complex adaptive systems (CAS). Findings: Our rapid realist review identified five “simple rules” of LST that were likely to enhance the success of the target initiatives: (1) blend designated leadership with distributed leadership; (2) establish feedback loops; (3) attend to history; (4) engage physicians; and (5) include patients and families. These principles play out differently in different contexts affecting human behavior (and thereby contributing to change) through a wide range of different mechanisms. Conclusions: Realist review methodology can be applied in combination with a complex system lens on published literature to produce a knowledge synthesis that informs a prospective change effort in large-system transformation. A collaborative process engaging both research producers and research users contributes to local applications of universal principles and mid-range theories, as well as to a more robust knowledge base for applied research. We conclude with suggestions for the future development of synthesis and evaluation methods

Large-System Transformation in Health Care: A Realist Review

Context: An evidence base that addresses issues of complexity and context is urgently needed for large-system transformation (LST) and health care reform. Fundamental conceptual and methodological challenges also must be addressed. The Saskatchewan Ministry of Health in Canada requested a six-month synthesis project to guide four major policy development and strategy initiatives focused on patient- and family-centered care, primary health care renewal, quality improvement, and surgical wait lists. The aims of the review were to analyze examples of successful and less successful transformation initiatives, to synthesize knowledge of the underlying mechanisms, to clarify the role of government, and to outline options for evaluation. Methods: We used realist review, whose working assumption is that a particular intervention triggers particular mechanisms of change. Mechanisms may be more or less effective in producing their intended outcomes, depending on their interaction with various contextual factors. We explain the variations in outcome as the interplay between context and mechanisms. We nested this analytic approach in a macro framing of complex adaptive systems (CAS). Findings: Our rapid realist review identified five “simple rules” of LST that were likely to enhance the success of the target initiatives: (1) blend designated leadership with distributed leadership; (2) establish feedback loops; (3) attend to history; (4) engage physicians; and (5) include patients and families. These principles play out differently in different contexts affecting human behavior (and thereby contributing to change) through a wide range of different mechanisms. Conclusions: Realist review methodology can be applied in combination with a complex system lens on published literature to produce a knowledge synthesis that informs a prospective change effort in large-system transformation. A collaborative process engaging both research producers and research users contributes to local applications of universal principles and mid-range theories, as well as to a more robust knowledge base for applied research. We conclude with suggestions for the future development of synthesis and evaluation methods