Future Intentions Regarding Quitting and Reducing Cigarette Use in a Representative Sample of Canadian Daily Smokers: Implications for Public Health Initiatives

Pre-cessation reduction is associated with quitting smoking. However, many smokers reduce the amount consumed but may not quit altogether. Using a representative sample of adult current daily smokers, this project explored future intentions of smokers regarding cigarette consumption. This information is important because it can provide a framework within which to plan tobacco cessation initiatives. A random digit dialing telephone survey was conducted of 889 Canadian current daily smokers, 18 years and older. The response rate was 65% (of households with a smoker in residence, 65% agreed to participate). Analyses focused on the 825 respondents who smoked at least 10 cigarettes per day at some point in their lives. As part of this survey, respondents were asked their future plans about their smoking (maintain, increase, reduce, quit). Of these 825 respondents, the majority of respondents had plans to change their cigarette use, with 55% planning to quit, 18.8% to reduce and 22.5% to maintain the amount they smoked (3.4% did not know and 2 respondents planned to increase). Most smokers who planned to reduce their smoking saw it as a step towards quitting smoking completely. These results present a picture of smokers, the majority of whom appear to be in some form of transition. Many smokers planned to reduce, of which the overwhelming majority saw their reduction as a step towards quitting. Opportunities exist to capitalize on these intentions to change in efforts to promote tobacco cessation

The Effects of Malignant Transformation on Susceptibility of Human Urothelial Cells to CD40-Mediated Apoptosis

Background: The tumor necrosis factor (TNF) superfamily of ligands and receptors mediates immune cell survival. Some members possess a death domain, a protein motif that functions to transmit apoptotic signals, whereas others, such as CD40, do not. CD40 is expressed by both normal and malignant epithelial cells. To investigate the functional significance of this expression, we studied the effects of ligation of CD40, Fas, and TNF receptors (TNFRs) on the proliferation and survival of normal and malignant human urothelial cells and urothelial cells with disabled p53 function. Methods: Normal and malignant human urothelial cells were cultured with soluble TNF family agonists (CD40 ligand [CD40L], TNF-α, anti-Fas antibody, or cocultured with mouse fibroblasts stably transfected with plasmids that caused the cells to constitutively express CD40L or CD32; cell proliferation was estimated by an [3H]thymidine incorporation assay, and apoptosis was determined by Annexin V staining and by a DNA fragmentation assay. Messenger RNA levels for CD40 and potential downstream effector molecules were quantified by polymerase chain reaction-based and ribonuclease protection assays, respectively, and nuclear factor (NF) κB nuclear translocation was detected by immunofluorescence. All statistical tests were two-sided. Results: Soluble trimeric CD40L inhibited the growth of normal and malignant urothelial cells but did not induce apoptosis. Cell surface-presented CD40L induced massive apoptosis in CD40-positive transitional cell carcinoma cells but not in normal urothelial cells. Normal cells underwent CD40L-mediated apoptosis only in the presence of other TNFR agonists. An agonistic anti-CD40 antibody presented on the surface of CD32-transfected fibroblasts also induced apoptosis in transitional cell carcinoma cells and in normal urothelial cells. Apoptotic responses of tumor (but not normal) cells to soluble agonists were enhanced by blocking protein synthesis. Karyotypically normal urothelial cells with disabled p53 function underwent apoptosis during coculture with CD40L-expressing fibroblasts alone but were not additionally sensitive to additional TNFR agonists. Conclusions: Susceptibility to CD40 ligation-induced apoptosis may be a novel mechanism for eliminating neoplastically transformed urothelial cells. Loss of CD40 expression may be an important adaptive mechanism for transitional cell carcinoma development and progressio

Critical international relations and the impact agenda

How should critical International Relations (IR) scholars approach the ‘impact agenda’? While most have been quite resistant to it, I argue in this essay that critical IR should instead embrace the challenge of impact – and that both IR as a field and the impact agenda more broadly would gain greatly from it doing so. I make this case through three steps. I show, firstly, that critical IR has till now been very much at the impact agenda’s margins, and that this situation contrasts strikingly with its well-established importance within IR teaching and research. I argue, secondly, that critical IR scholars both could and should do more impact work – that the current political conjuncture demands it, that many of the standard objections to doing so are misplaced, and indeed that ‘critical’ modes of research are in some regards better suited than ‘problem-solving’ ones to generating meaningful change – and offer a series of recommended principles for undertaking critically-oriented impact and engagement work. But I also argue, thirdly, that critical social science holds important lessons for the impact agenda, and that future impact assessments need to take these lessons on board – especially if critical IR scholarship is to embrace impact more fully. Critical IR, I submit, should embrace impact; but at the same time, research councils and assessments could do with modifying their approach to it, including by embracing a more critical and political understanding of what impact is and how it is achieved

Engagement with consumer smartwatches for tracking symptoms of individuals living with multiple long-term conditions (multimorbidity)::A longitudinal observational study

INTRODUCTION: People living with multiple long-term conditions (multimorbidity) (MLTC-M) experience an accumulating combination of different symptoms. It has been suggested that these symptoms can be tracked longitudinally using consumer technology, such as smartphones and wearable devices. AIM: The aim of this study was to investigate longitudinal user engagement with a smartwatch application, collecting survey questions and active tasks over 90 days, in people living with MLTC-M. METHODS: ‘Watch Your Steps’ was a prospective observational study, administering multiple questions and active tasks over 90 days. Adults with more than one clinician-diagnosed long-term conditions were loaned Fossil® Sport smartwatches, pre-loaded with the study app. Around 20 questions were prompted per day. Daily completion rates were calculated to describe engagement patterns over time, and to explore how these varied by patient characteristics and question type. RESULTS: Fifty three people with MLTC-M took part in the study. Around half were male ( = 26; 49%) and the majority had a white ethnic background (n = 45; 85%). About a third of participants engaged with the smartwatch app nearly every day. The overall completion rate of symptom questions was 45% inter-quartile range (IQR 23–67%) across all study participants. Older patients and those with greater MLTC-M were more engaged, although engagement was not significantly different between genders. CONCLUSION: It was feasible for people living with MLTC-M to report multiple symptoms per day over 3 months. User engagement appeared as good as other mobile health studies that recruited people with single health conditions, despite the higher daily data entry burden

Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.

BackgroundHIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.MethodsWe measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.ResultsAmong 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.ConclusionsHigher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH

Antiangiogenic cancer therapy combined with oncolytic virotherapy leads to regression of established tumors in mice

Clinical trials of oncolytic virotherapy have shown low toxicity and encouraging signs of efficacy. However, it remains critically important to develop methods for systemic viral delivery if such therapies are to be clinically implemented to treat established tumors. In this respect, much effort is being focused on combining oncolytic viruses with standard treatment modalities such as inhibitors of VEGF165 (an alternatively spliced isoform of VEGF-A) signaling, which are widely used to treat several different cancers. Here, we have demonstrated that combining VEGF165 inhibitors with systemic delivery of oncolytic viruses leads to substantial regression and cure of established tumors in immunocompetent mice. We have shown that manipulating VEGF165-mediated signaling by administering VEGF165 to mice harboring mouse melanoma cells that do not express VEGF165 and by administering a VEGF inhibitor and then withdrawing treatment to allow VEGF levels to rebound in mice harboring mouse melanoma cells expressing VEGF165 allows tumor-associated endothelial cells transiently to support viral replication. This approach led to direct tumor cell lysis and triggered innate immune–mediated attack on the tumor vasculature. It also resulted in long-term antitumor effects, even against tumors in which viral replication is poorly supported. Since this combinatorial approach targets the tumor endothelium, we believe these data have direct, wide-ranging, and immediate clinical applicability across a broad range of tumor types

Randomized controlled trial of mailed Nicotine Replacement Therapy to Canadian smokers: study protocol

<p>Abstract</p> <p>Background</p> <p>Considerable public health efforts are ongoing Canada-wide to reduce the prevalence of smoking in the general population. From 1985 to 2005, smoking rates among adults decreased from 35% to 19%, however, since that time, the prevalence has plateaued at around 18-19%. To continue to reduce the number of smokers at the population level, one option has been to translate interventions that have demonstrated clinical efficacy into population level initiatives. Nicotine Replacement Therapy (NRT) has a considerable clinical research base demonstrating its efficacy and safety and thus public health initiatives in Canada and other countries are distributing NRT widely through the mail. However, one important question remains unanswered - do smoking cessation programs that involve mailed distribution of free NRT work? To answer this question, a randomized controlled trial is required.</p> <p>Methods/Design</p> <p>A single blinded, panel survey design with random assignment to an experimental and a control condition will be used in this study. A two-stage recruitment process will be employed, in the context of a general population survey with two follow-ups (8 weeks and 6 months). Random digit dialing of Canadian home telephone numbers will identify households with adult smokers (aged 18+ years) who are willing to take part in a smoking study that involves three interviews, with saliva collection for 3-HC/cotinine ratio measurement at baseline and saliva cotinine verification at 8-week and 6-month follow-ups (N = 3,000). Eligible subjects interested in free NRT will be determined at baseline (N = 1,000) and subsequently randomized into experimental and control conditions to receive versus not receive nicotine patches. The primary hypothesis is that subjects who receive nicotine patches will display significantly higher quit rates (as assessed by 30 day point prevalence of abstinence from tobacco) at 6-month follow-up as compared to subjects who do not receive nicotine patches at baseline.</p> <p>Discussion</p> <p>The findings from the proposed trial are timely and highly relevant as mailed distribution of NRT require considerable resources and there are limited public health dollars available to combat this substantial health concern. In addition, findings from this randomized controlled trial will inform the development of models to engage smokers to quit, incorporating proactive recruitment and the offer of evidence based treatment.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01429129">NCT01429129</a></p

Engagement with consumer smartwatches for tracking symptoms of individuals living with multiple long-term conditions (multimorbidity): A longitudinal observational study

From SAGE Publishing via Jisc Publications RouterHistory: received 2021-07-16, accepted 2021-11-08, epub 2021-11-30Publication status: PublishedFunder: University of Manchester/Medical Research Council; Grant(s): Confidence in Concepts funding scheme 6Introduction: People living with multiple long-term conditions (multimorbidity) (MLTC-M) experience an accumulating combination of different symptoms. It has been suggested that these symptoms can be tracked longitudinally using consumer technology, such as smartphones and wearable devices. Aim: The aim of this study was to investigate longitudinal user engagement with a smartwatch application, collecting survey questions and active tasks over 90 days, in people living with MLTC-M. Methods: ‘Watch Your Steps’ was a prospective observational study, administering multiple questions and active tasks over 90 days. Adults with more than one clinician-diagnosed long-term conditions were loaned Fossil® Sport smartwatches, pre-loaded with the study app. Around 20 questions were prompted per day. Daily completion rates were calculated to describe engagement patterns over time, and to explore how these varied by patient characteristics and question type. Results: Fifty three people with MLTC-M took part in the study. Around half were male ( = 26; 49%) and the majority had a white ethnic background (n = 45; 85%). About a third of participants engaged with the smartwatch app nearly every day. The overall completion rate of symptom questions was 45% inter-quartile range (IQR 23–67%) across all study participants. Older patients and those with greater MLTC-M were more engaged, although engagement was not significantly different between genders. Conclusion: It was feasible for people living with MLTC-M to report multiple symptoms per day over 3 months. User engagement appeared as good as other mobile health studies that recruited people with single health conditions, despite the higher daily data entry burden

An Association of Cancer Physicians' strategy for improving services and outcomes for cancer patients.

The Association of Cancer Physicians in the United Kingdom has developed a strategy to improve outcomes for cancer patients and identified the goals and commitments of the Association and its members.The ACP is very grateful to all of its members who have expressed views on the development of the strategy and to the sponsors of our workshops and publications, especially Cancer Research UK and Macmillan Cancer SupportThis is the final version of the article. It was first available from Cancer Intelligence via http://dx.doi.org/10.3332/ecancer.2016.60