Evaluation of two multi-component interventions for integrating smoking cessation treatments into routine primary care practice: a cluster randomized trial

Background and Rationale: There is a well-documented practice gap in the rates at which evidence-based smoking cessation treatments are delivered to patients in primary care settings. Multi-component intervention that combine practice, provider, and patient-level supports have been shown to increase the rates at which primary care providers deliver smoking cessation treatments to patients and increase rates of smoking abstinence amongst patients. The incremental value of adjunct telephone-based smoking cessation counselling when delivered as part of a multi-component intervention has not been examined. Aim: The primary objective of this study was to determine whether adjunct telephone-based smoking cessation follow-up counselling (FC), when delivered as part of a multi-component intervention program within primary care clinics is associated with increases in (a) the delivery of evidence-based smoking cessation treatments, (b) patient quit attempts, and (c) patient smoking abstinence when compared to the provision of practice and provider supports (PS) alone. The secondary objective of this study was to determine whether the introduction of a multi-component smoking cessation program is associated with increased delivery of evidence-based smoking cessation treatments by primary care providers and patient smoking outcomes, compared to pre-intervention rates. The study also sought to examine the association between patient, provider, clinic and implementation factors, and study outcomes. Methods: A two-group, pre-post cluster randomized controlled trial was conducted. Eligible clinics were randomly assigned to the PS group or FC group. Both groups were supported with implementing a multi-component intervention program that involved outreach facilitation visits, provider training, real time provider prompts and patient tools, and performance feedback. Clinics assigned to the FC group were also able to refer patients who smoke to a telephone-based follow-up support program for supplemental counselling support. An exit survey was completed with a cross-sectional sample of patients who smoked daily at each study clinic before and after the introduction of the intervention program, and all patients were contacted 4 months later to complete a brief telephone-based interview. Outcome measures included the rate at which evidence-based smoking cessation treatments (5As: ask, advise, assess, assist, arrange) were delivered to patients, the number of patients who made a quit attempt, and patient smoking abstinence at the 4-month follow-up. All data was analyzed using multi-level hierarchical modelling. Results: Seven family medicine clinics and 115 providers were enrolled in the study. A total of 12,585 patients were screened, and 835 eligible patients (mean age 45.8 SD± 14.6, 41% male) who smoke participated in the study. Contrary to the study hypothesis, a higher and statistically significant 7-day point prevalence abstinence (OR 6.8, 95% CI 2.1-21.7; p=<0.01) and continuous abstinence (OR 13.7, 95% CI 2.1-128.3; p=<0.05) rate was observed in the PS group compared to the FC group at the post-assessment after controlling for differences in smoking cessation rates between intervention groups during the baseline period. The introduction of the multi-component intervention program was associated with higher rates of provider 5As delivery and patient quit attempts compared to baseline, with no differences between groups documented. The odds ratios (OR) and 95% confidence intervals (CI) for 5As delivery between the pre- and post-intervention assessments for both intervention groups combined were: “ask” (OR 1.5; 95% CI 1.1, 2.0); “advise” (OR 2.0; 95% CI 1.5, 2.7); “assess” (OR 2.1; 95% CI 1.6, 2.9); “assist” with cessation (OR 2.30; 95% CI 1.70, 3.12); “arrange” (OR 1.9; 95% CI 1.2, 3.0); and “patient quit attempts” (OR 1.4; 95% CI 1.04, 1.94). Differences in 7-day point prevalence abstinence were not statistically significant between the pre- and post-intervention assessments (OR 1.5; 95% CI 0.94, 2.5). The study documented intra-provider variability in the rates at which evidence-based smoking cessation treatments are delivered to patients. Patient characteristics (readiness to quit, time to first cigarette, previous quit attempt in the last year), and the purpose of the clinic visit being for an annual health exam were associated with higher rates of 5As delivery. Conclusion: This is the first study to evaluate a multi-component smoking cessation intervention within the primary health care setting in Canada. The study findings demonstrate that the introduction of a multi-component intervention program in primary care settings was associated with significant improvements in the rates at which providers deliver evidence-based smoking cessation treatments, and increase patient quit attempts. The added value of adjunct telephone counselling was not evident at the 4-month follow-up. The conclusions that can be drawn from the present study are limited by the study design and sample size. A larger trial is required to conclusively determine the impact of the program on long-term smoking abstinence and examine the importance of clinic-level variables in explaining observed differences between study clinics

Fulminant Aeromonas hydrophila infection during acute lymphoblastic leukemia treatment

Aeromonas hydrophila septicemia has a fulminant course and it has been usually reported in immunocompromised hosts and rarely among children with leukemia. High morbidity and mortality is associated with A hydrophila infections. We describe the case of a child with acute lymphoblastic leukemia who presented with septicemia due to A hydrophila. The patient presented with fever and skin discoloration during a febrile neutropenia episode, which rapidly evolved into bacteremia and extensive thigh suppuration, fasciitis, and myonecrosis. Apart from antibiotic treatment, surgical debridement to relieve compartment pressure and prevent further lower extremity compromise was promptly performed. Despite long delays in chemotherapy and an extensive tissue gap, primary closure of the involved area was possible with full cosmetic and functional limb recovery, and the patient has remained in clinical remission for more than 7 years

The Hellenic type of nondeletional hereditary persistence of fetal hemoglobin results from a novel mutation (g.-109G>T) in the HBG2 gene promoter

Nondeletional hereditary persistence of fetal hemoglobin (nd-HPFH), a rare hereditary condition resulting in elevated levels of fetal hemoglobin (Hb F) in adults, is associated with promoter mutations in the human fetal globin (HBG1 and HBG2) genes. In this paper, we report a novel type of nd-HPFH due to a HBG2 gene promoter mutation (HBG2:g.-109G>T). This mutation, located at the 3′ end of the HBG2 distal CCAAT box, was initially identified in an adult female subject of Central Greek origin and results in elevated Hb F levels (4.1%) and significantly increased Gγ-globin chain production (79.2%). Family studies and DNA analysis revealed that the HBG2:g.-109G>T mutation is also found in the family members in compound heterozygosity with the HBG2:g.-158C>T single nucleotide polymorphism or the silent HBB:g.-101C>T β-thalassemia mutation, resulting in the latter case in significantly elevated Hb F levels (14.3%). Electrophoretic mobility shift analysis revealed that the HBG2:g.-109G>T mutation abolishes a transcription factor binding site, consistent with previous observations using DNA footprinting analysis, suggesting that guanine at position HBG2/1:g.-109 is critical for NF-E3 binding. These data suggest that the HBG2:g-109G>T mutation has a functional role in increasing HBG2 transcription and is responsible for the HPFH phenotype observed in our index cases

Perceptions, Predictors of and Motivation for Quitting among Smokers from Six European Countries from 2016 to 2018: Findings from EUREST-PLUS ITC Europe Surveys

The European Tobacco Products Directive (TPD) was introduced in 2016 in an effort to decrease prevalence of smoking and increase cessation in the European Union (EU). This study aimed to explore quitting behaviours, motivation, reasons and perceptions about quitting, as well as predictors (reported before the TPD implementation) associated with post-TPD quit status. A cohort study was conducted involving adult smokers from six EU countries (n= 3195). Data collection occurred pre-(Wave 1; 2016) and post-(Wave 2; 2018) TPD implementation. Bivariate and logistic regression analyses of weighted data were conducted. Within this cohort sample, 415 (13.0%) respondents reported quitting at Wave 2. Predictors of quitting were moderate or high education, fewer cigarettes smoked per day at baseline, a past quit attempt, lower level of perceived addiction, plans for quitting and the presence of a smoking-related comorbidity. Health concerns, price of cigarettes and being a good example for children were among the most important reasons that predicted being a quitter at Wave 2. Our findings show that the factors influencing decisions about quitting may be shared among European countries. European policy and the revised version of TPD could emphasise these factors through health warnings and/or campaigns and other policies

Current practices and perceived barriers to tobacco-treatment delivery among healthcare professionals from 15 European countries. The EPACTT Plus project

Introduction: The latest evidence-based Guidelines for Treating Tobacco Dependence highlight the significant role of healthcare professionals in supporting smokers interested to quit. This study aimed to identify the current practices of healthcare professionals in Europe and perceived barriers in delivering tobacco treatment to their patients who smoke. Methods: In the context of EPACTT-Plus, collaborating institutions from 15 countries (Albania, Armenia, Belgium, Italy, France, Georgia, Greece, Kosovo, Romania, North Macedonia, Russia, Serbia, Slovenia, Spain, Ukraine) worked for the development of an accredited eLearning course on Tobacco Treatment Delivery available at http://elearning-ensp.eu/. In total, 444 healthcare professionals from the wider European region successfully completed the course from December 2018 to July 2019. Cross-sectional data were collected online on healthcare professionals' current practices and perceived barriers in introducing tobacco-dependence treatment into their daily clinical life. Results: At registration, 41.2% of the participants reported having asked their patients if they smoked. Advise to quit smoking was offered by 47.1% of the participants, while 29.5% reported offering assistance to their patients who smoked in order to quit. From the total number of participants, 39.9% regarded the lack of patient compliance as a significant barrier. Other key barriers were lack of: interest from the patients (37.4%), healthcare professionals training (33.1%), community resources to refer patients (31.5%), and adequate time during their everyday clinical life (29.7%). Conclusions: The identification of current practices and significant barriers is important to build evidence-based guidelines and training programs (online and/or live) that will improve the performance of healthcare professionals in offering tobacco-dependence treatment for their patients who smoke

Knowledge of the health risks of smoking and impact of cigarette warning labels among tobacco users in six European countries: Findings from the EUREST-PLUS ITC Europe Surveys

INTRODUCTION The aim of this study was to examine knowledge of health effects of smoking and the impact of cigarette package warnings among tobacco users from six European Union (EU) Member States (MS) immediately prior to the introduction of the EU Tobacco Products Directive (TPD) in 2016 and to explore the interrelationship between these two factors. METHODS Cross-sectional data were collected via face-to-face interviews with adult smokers (n=6011) from six EU MS (Germany, Greece, Hungary, Poland, Romania, Spain) between June-September 2016. Sociodemographic variables and knowledge of health risks of smoking (KHR) were assessed. Warning salience, thoughts of harm, thoughts of quitting and foregoing of cigarettes as a result of health warnings were assessed. The Label Impact Index (LII) was used as a composite measure of warning effects. Linear and logistic regression analyses were used to examine sociodemographic predictors of KHR and LII and the inter-relationship between knowledge and LII scores. RESULTS The KHR index was highest in Romania and Greece and lowest in Hungary and Germany. While the majority of smokers knew that smoking increases the risk for heart diseases, lung and throat cancer, there was lower awareness that tobacco use caused mouth cancer, pulmonary diseases, stroke, and there were very low levels of knowledge that it was also associated with impotence and blindness, in all six countries. Knowledge regarding the health risks of passive smoking was moderate in most countries. The LII was highest in Romania and Poland, followed by Spain and Greece, and lowest in Germany and Hungary. In almost all countries, there was a positive association between LII scores and higher KHR scores after controlling for sociodemographic variables. Several sociodemographic factors were associated with KHR and LII, with differences in these associations documented across countries. CONCLUSIONS These data provide evidence to support the need for stronger educational efforts and policies that can enhance the effectiveness of health warnings in communicating health risks and promoting quit attempts. Data will serve as a baseline for examining the impact of the TPD

Current practices and perceived barriers to tobacco treatment delivery among healthcare professionals from 15 European countries. The EPACTT Plus project

INTRODUCTION The latest evidence-based Guidelines for Treating Tobacco Dependence highlight the significant role of healthcare professionals in supporting smokers interested to quit. This study aimed to identify the current practices of healthcare professionals in Europe and perceived barriers in delivering tobacco treatment to their patients who smoke. METHODS In the context of EPACTT-Plus, collaborating institutions from 15 countries (Albania, Armenia, Belgium, Italy, France, Georgia, Greece, Kosovo, Romania, North Macedonia, Russia, Serbia, Slovenia, Spain, Ukraine) worked for the development of an accredited eLearning course on Tobacco Treatment Delivery available at http:// elearning-ensp.eu/. In total, 444 healthcare professionals from the wider European region successfully completed the course from December 2018 to July 2019. Cross-sectional data were collected online on healthcare professionals’ current practices and perceived barriers in introducing tobacco-dependence treatment into their daily clinical life. RESULTS At registration, 41.2% of the participants reported having asked their patients if they smoked. Advise to quit smoking was offered by 47.1% of the participants, while 29.5% reported offering assistance to their patients who smoked in order to quit. From the total number of participants, 39.9% regarded the lack of patient compliance as a significant barrier. Other key barriers were lack of: interest from the patients (37.4%), healthcare professionals training (33.1%), community resources to refer patients (31.5%), and adequate time during their everyday clinical life (29.7%). CONCLUSIONS The identification of current practices and significant barriers is important to build evidence-based guidelines and training programs (online and/or live) that will improve the performance of healthcare professionals in offering tobacco-dependence treatment for their patients who smoke

Impact of the ENSP eLearning platform on improving knowledge, attitudes and self-efficacy for treating tobacco dependence. An assessment across 15 European countries

INTRODUCTION In 2018, the European Network for Smoking Cessation and Prevention (ENSP) released an update to its Tobacco Treatment Guidelines for healthcare professionals, which was the scientific base for the development of an accredited eLearning curriculum to train healthcare professionals, available in 14 languages. The aim of this study was to evaluate the effectiveness of ENSP eLearning curriculum in increasing healthcare professionals’ knowledge, attitudes, self-efficacy (perceived behavioral control) and intentions in delivering tobacco treatment interventions in their daily clinical routines. METHODS We conducted a quasi-experimental pre-post design study with 444 healthcare professionals, invited by 20 collaborating institutions from 15 countries (Albania, Armenia, Belgium, Italy, France, Georgia, Greece, Kosovo, Romania, North Macedonia, Russia, Serbia, Slovenia, Spain, Ukraine), which completed the eLearning course between December 2018 and July 2019. RESULTS Healthcare professionals’ self-reported knowledge improved after the completion of each module of the eLearning program. Increases in healthcare professionals’ self-efficacy in delivering tobacco treatment interventions (p&lt;0.001) were also documented. Significant improvements were documented in intentions to address tobacco use as a priority, document tobacco use, offer support, provide brief counselling, give written material, discuss available medication, prescribe medication, schedule dedicated appointment to develop a quit plan, and be persistent in addressing tobacco use with the patients (all p&lt;0.001). CONCLUSIONS An evidence-based digital intervention can be effective in improving knowledge, attitudes, self-efficacy and intentions on future delivery of tobacco-treatment interventions

Mutant KRAS promotes malignant pleural effusion formation

Malignant pleural effusion (MPE) is the lethal consequence of various human cancers metastatic to the pleural cavity. However, the mechanisms responsible for the development of MPE are still obscure. Here we show that mutant KRAS is important for MPE induction in mice. Pleural disseminated, mutant KRAS bearing tumour cells upregulate and systemically release chemokine ligand 2 (CCL2) into the bloodstream to mobilize myeloid cells from the host bone marrow to the pleural space via the spleen. These cells promote MPE formation, as indicated by splenectomy and splenocyte restoration experiments. In addition, KRAS mutations are frequently detected in human MPE and cell lines isolated thereof, but are often lost during automated analyses, as indicated by manual versus automated examination of Sanger sequencing traces. Finally, the novel KRAS inhibitor deltarasin and a monoclonal antibody directed against CCL2 are equally effective against an experimental mouse model of MPE, a result that holds promise for future efficient therapies against the human condition