Background Lung cancer mortality decreases as a result of low-dose computed tomography (LDCT) screening, but suffers from low uptake and high false-positive rates. The impact of integrating genetic risk using a polygenic risk score (PRS) to optimize lung cancer screening remains underexplored. Methods We developed a genome-wide PRS and evaluated its performance in pre- and post-screening contexts. Screening eligibility was assessed using two UK Biobank (UKB) subsets: UKBPLCO (n = 8957; PLCOm2012norace risk ≥2%) and UKBScreeningCriteria (n = 74,024 meeting screening eligibility criteria). To evaluate nodule management, we used a cohort of 669 ever-smokers with PLCO ≥2% and Lung-RADS score ≥3, referred to as SYNERGIQCPLCO_LungRADS. Multivariable Cox models, time-dependent area under the curve (AUC), and decision curve analyses (DCA) evaluated association, discrimination, and clinical net benefit. Results In UKBPLCO, the PRS was associated with a hazard ratio (HR) of 1.18 per standard deviation. In UKBScreeningCriteria, PRS showed HR of 1.34. Adding PRS to the PLCOm2012 model improved discrimination (AUC: 0.707 vs 0.696; P = 6.85e−27[likelihood ratio test]) and correctly reclassified 9.2% of incident lung cancer cases. Six-year absolute risks stratified by PRS deciles indicate 3.1-fold increase in the top compared to the bottom decile. In SYNERGIQCPLCO_LungRADS, HRPRS was 1.22. In this context, DCA indicated a modest net benefit for decision thresholds between 10% and 30%. Conclusion PRS in lung cancer reveals context-dependent net benefit across studied populations. Although PRS adds limited value for determining screening eligibility, it may help reclassify borderline individuals and inform decisions regarding closer follow-up or invasive diagnostic procedures for high-risk screened groups.

BACKGROUND:The routine use of CT imaging and lung cancer screening has increased the identification of peripheral pulmonary lesions (PPLs). Sampling may be needed for some nodules. Many new technologies are available to improve the diagnostic performance of bronchoscopy for the sampling of PPLs, but few comparative trials exist. The objective of this study was to compare the diagnostic performance of bronchoscopy with radial endobronchial ultrasound (rEBUS) using an ultrathin bronchoscope (BF-MP190F; Olympus) with a non-ultrathin bronchoscope and to compare the diagnostic performance of bronchoscopy with and without rapid on-site evaluation (ROSE). RESEARCH QUESTION:Does diagnostic performance differ between ultrathin and non-ultrathin bronchoscopes with rEBUS, and what impact does ROSE have on diagnostic performance of rEBUS? STUDY DESIGN AND METHODS:This pragmatic, multicenter, 2 × 2 factorial, randomized controlled trial involved adult patients with PPLs (mean diameter < 5 cm) and radiographic stage N0 disease referred for bronchoscopy. The study was powered to detect a 20% improvement in the primary outcome of difference in diagnostic yield (DY) between ultrathin and non-ultrathin bronchoscopes and between procedures with and without ROSE. Secondary outcomes included sensitivity for malignancy, complications, and procedure duration. RESULTS:Of 215 patients assessed, 186 patients were randomized and 181 patients were analyzed. Malignancy prevalence was 84%. No significant differences in DY or sensitivity for malignancy were found between non-ultrathin and ultrathin bronchoscopes: 65.6% vs 58.2% (difference, -7.3%; P = .36) and 84.3% vs 74.3% (difference, -10.0%; P = .21), respectively. Similarly, no significant differences were observed with or without ROSE: 60.4% vs 63.5% (difference, -3.1%; P = .76) and 80.3% vs 78.3% (difference, 2.0%; P = .83), respectively. INTERPRETATION:We could not identify a difference in DY or sensitivity for malignancy for the diagnosis of PPLs between an ultrathin bronchoscope and a non-ultrathin bronchoscope and between ROSE and no ROSE. The study was underpowered to detect smaller but potentially clinically meaningful differences. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov; No.: NCT03809169; URL: www. CLINICALTRIALS:gov.

Background The most near-term clinical application of genome-wide association studies in lung cancer is a polygenic risk score (PRS). Methods A case-control dataset was generated consisting of 4002 lung cancer cases from the LORD project and 20,010 ethnically matched controls from CARTaGENE. A genome-wide PRS including >1.1 million genetic variants was derived and validated in UK Biobank (n = 5419 lung cancer cases). The predictive ability and diagnostic discrimination performance of the PRS was tested in LORD/CARTaGENE and benchmarked against previous PRSs from the literature. Stratified analyses were performed by smoking status and genetic risk groups defined as low (<20th percentile), intermediate (20-80th percentile) and high (>80th percentile) PRS. Findings The phenotypic variance explained and the effect size of the genome-wide PRS numerically outperformed previous PRSs. Individuals with high genetic risk had a 2-fold odds of lung cancer compared to low genetic risk. The PRS was an independent predictor of lung cancer beyond conventional clinical risk factors, but its diagnostic discrimination performance was incremental in an integrated risk model. Smoking increased the odds of lung cancer by 7.7-fold in low genetic risk and by 11.3-fold in high genetic risk. Smoking with high genetic risk was associated with a 17-fold increase in the odds of lung cancer compared to individuals who never smoked and with low genetic risk. Interpretation Individuals at low genetic risk are not protected against the smoking-related risk of lung cancer. The joint multiplicative effect of PRS and smoking increases the odds of lung cancer by nearly 20-fold. Copyright (c) 2024 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Purpose:Chronic bronchitis (CB), a chronic obstructive pulmonary disease (COPD) phenotype defined by persistent mucus hypersecretion and cough, is associated with poor quality of life, exacerbations, and lung function impairment. Bronchial Rheoplasty (BR) delivers non-thermal pulsed electric fields to airway epithelium and submucosa. Preliminary studies demonstrated reduced airway goblet cell hyperplasia and symptom improvement in response to BR. This study aimed to further assess the safety and clinical feasibility of BR in the setting of CB. Patients and Methods:This 3-center, single-arm study evaluated the safety and feasibility of BR in Canadian patients. The major inclusion criteria were the sum of CAT first 2 questions (cough and mucus) ≥ 7 out of 10 and FEV1 ≥ 30% predicted. Right-sided airways were treated first; left, 1 month later. Serious adverse events (SAEs) were tabulated through 12 months. Outcomes were evaluated using the SGRQ and CAT. Results:Ten patients with CB were enrolled and followed for 12 months. The BR procedure was successful in all patients (mean age 69 ± 5.8 years, post-BD FEV1 77.1 ± 28.3, SGRQ 56.2 ± 8.8, CAT 25.4 ± 4.7). Only one SAE, a COPD exacerbation 13 days following the BR procedure, was considered device related. No additional SAEs occurred through 12 months, and 90% of the patients were CAT responders (≥ 2-point improvement) at 3 and 6 months. Similar results were observed in SGRQ. Conclusion:BR was safe and well-tolerated. Meaningful symptom improvement was observed through 12 months, suggesting BR may be a viable treatment option for patients with CB.

Rationale: Transbronchial cryobiopsy (TBCB) for the diagnosis of interstitial lung disease (ILD) has shown promising results, but prospective studies with matched surgical lung biopsy (SLB) have yielded conflicting results. Objectives: We aimed to assess within- and between-center diagnostic agreement between TBCB and SLB at both the histopathologic and multidisciplinary discussion (MDD) levels in patients with diffuse ILD. Methods: In a multicenter prospective study, we performed matched TBCB and SLB in patients referred for SLB. After a blinded review by three pulmonary pathologists, all cases were reviewed by three independent ILD teams in an MDD. MDD was performed first with TBCB, then with SLB in a second session. Within-center and between-center diagnostic agreement was evaluated using percentages and correlation coefficients. Measurements and Main Results: Twenty patients were recruited and underwent contemporaneous TBCB and SLB.Within-center diagnostic agreement between TBCB-MDD and SLB-MDD was reached in 37 of the 60 (61.7%) paired observations, resulting in a Cohen's k value of 0.46 (95% confidence interval [CI], 0.29-0.63). Diagnostic agreement increased among high-confidence or definitive diagnoses on TBCB-MDD (21 of 29 [72.4%]), but not significantly, and was more likely among cases with SLB-MDD diagnoses of idiopathic pulmonary fibrosis than fibrotic hypersensitivity pneumonitis (13 of 16 [81.2%] vs. 16 of 31 [51.6%]; P = 0.047). Between-center agreement for cases wasmarkedly higher for SLB-MDD (k = 0.71 [95% CI, 0.52-0.89]) than TBCB-MDD (k = 0.29 [95% CI, 0.09-0.49]). Conclusions: This study demonstrated moderate TBCB-MDD and SLB-MDD diagnostic agreement for ILD, while between-center agreement was fair for TBCB-MDD and substantial for SLB-MDD.

Introduction: Bronchial thermoplasty (BT), an endobronchial procedure consisting in radiofrenquency delivery of thermal energy in the airways, is a non-pharmacological alternative offered to uncontrolled severe asthmatics. This approach has been associated with better asthma control and reduced exacerbations. However, biological mechanisms explaining asthma control improvement following BT are still not well understood. Our group performed transcriptomic analysis on bronchial epithelial cells (BEC) obtained from severe asthmatic subjects before and one-year after BT treatment. We found a significant gene expression decrease in S100 family of alarmins. Objective: validation of S100A7/A8/A9 expression in bronchial biopsies obtained from severe patients before and one-year post BT and evaluation of S100A7/A8/A9 in BEC from these patients. Method: BEC and biopsies were collected from severe asthmatics before as well as one year after BT. These were compared to BEC isolated from participants without asthma and allergy. S100A7/A8/A9 gene expression was evaluated by qPCR and proteins by Western blot and immunohistochemistry. Results: S100A7/A8/A9 are highly expressed in BEC and bronchial biopsies obtained from severe asthma compared to healthy controls. BT treatment of severe asthmatics showed a significant decrease in S100A7/A8/A9 at gene and protein level in epithelial cells and in bronchial biopsies. This decrease was observed one-year post BT. Conclusion: BT induces a significant decrease in alarmine expression in severe asthmatics which could contribute to better asthma control.

Lung cancer is the leading cause of cancer death worldwide, with a five-year survival of 22% in Canada. Guidelines recommend rapid evaluation of patients with suspected lung cancer, but the impact on survival remains unclear. We reviewed medical records of all patients with newly diagnosed lung cancer in four hospital networks across the province of Quebec, Canada, between 1 February and 30 April 2017. Patients were followed for 3 years. Wait times for diagnosis and treatment were collected, and survival analysis using a Cox regression model was conducted. We included 1309 patients, of whom 39% had stage IV non-small cell lung cancer (NSCLC). Median wait times were, in general, significantly shorter in patients with stage III–IV NSCLC or SCLC. Surgery was associated with delays compared to other types of treatments. Median survival was 12.9 (11.1–15.7) months. The multivariate survival model included age, female sex, performance status, histology and stage, treatment, and the time interval between diagnosis and treatment. Longer wait times had a slightly protective to neutral effect on survival, but this was not significant in the stage I–II NSCLC subgroup. Wait times for the diagnosis and treatment of lung cancer were generally within targets. The shorter wait times observed for advanced NSCLC and SCLC might indicate a tendency for clinicians to act quicker on sicker patients. This study did not demonstrate the detrimental effect of longer wait times on survival.

"Lobe-Specific Mediastinal Staging in cN0/N1 Non-Small Cell Lung Cancer.." Annals of the American Thoracic Society, 0(ja), pp. –

BACKGROUND:Surgical lung biopsy (SLB) is considered in the investigation of interstitial lung diseases (ILDs) when a complete clinical evaluation and a multidisciplinary discussion (MDD) do not allow the clinician to make a confident diagnosis. Owing to the risk of the procedure, an appropriate assessment of the risk/benefit ratio prior to the intervention is recommended. We aimed to assess the postoperative outcomes and diagnostic yield of SLB for the investigation of ILD in a tertiary care institution.METHODS:We conducted a retrospective cohort study of consecutive subjects who underwent a SLB for the investigation of ILD in our center from 2009 to 2020. The postoperative mortality and complications rates as well as the diagnostic yield of the procedure were assessed.RESULTS:Of the 1,805 patients newly investigated for ILD in our center from 2009 to 2020, 71 (3.93%) underwent a SLB. At days 30 and 90, the mortality rates were 0 and 2.8%, whereas 4.3 and 7.6% patients experienced an acute ILD exacerbation, respectively. In addition, 4 (5.8%) patients experienced infectious complications and 5 (7.0%) presented prolonged air leaks (all within 30 days). A definite pathological diagnosis was made in 47 (66.2%) patients. Following postoperative MDD, a confident diagnosis was made in 61 patients (85.9%) and resulted in a change of therapy in 49 (69.0%) patients.CONCLUSION:SLB for the diagnosis of unclassifiable ILDs is associated with low mortality but significant morbidity. However, it results in a confident diagnosis and a change in therapy in the majority of patients.

Background: COPD impairs the physiological and structural function of the lungs and negatively impacts physical performance. Patients with emphysema typically have significant impairments in daily activities and a reduced quality of life. Objective: We assessed health-related quality of life at the 24-month followup in patients with severe heterogeneous emphysema treated with the Spiration Valve System (SVS) versus optimal medical managment (Control) in EMPROVE. Methods: EMPROVE was a prospective, mulitcenter, randomized controlled trial. Patients were randomized in a 2:1 allocation to SVS treatment (n=97) or Control (n=44). Disease-targeted measures of health-related quality of life were determined using the St. George9s Respiratory Questionnaire (SGRQ), the modified Medical Research Council dyspnea scale (mMRC) and the COPD Assessment Test (CAT) at 1, 3, 6,12 and 24 months. Results: The SVS-treated group demosntrated significant improvements in SGRQ (p=0.037) at 24 months with a mean change of -6.5 points, with a similar improvement in CAT (−2.6 points for the SVS treatment and Control groups, respectively, p=0.048). Dyspena also improved post SVS treament compared to the Control group with a mean reduction of -0.6 points in the mMRC Dyspena Scale, yielding a significant difference between groups (p=0.0012). Conclusion: Our results from the EMPROVE trial demonstrate that SVS treatment provides a sustained clinically significant benefit in health-related quality of life in patients with severe heterogeneous emphysema.

IntroductionIn 2019, the Québec provincial health technology assessment body (INESSS) recommended that lung cancer screening with low-dose computed tomography (LDCT) be accessible in Québec only within the context of an evaluation in the ‘real-world’ care setting. Based on this recommendation, the ministry of health (MSSS) decided, in 2020, to implement a screening pilot project and to conduct a formal evaluation, partnering with a clinical leader (principal investigator), participating hospitals, the provincial public health agency (INSPQ) and INESSS. The goal of this evaluation is to facilitate decision-making regarding the implementation of a province-wide screening program.MethodsTo support the implementation of the pilot project, algorithms and recommendations were developed to guide management of screening program participants. This material, based on Lung-RADS (Lung Computed Tomography Screening Reporting and Data System of the American College of Radiology), was developed by reviewing the literature and by consulting clinical experts. The evaluation plan proposes various indicators, focusing on six main topics: (i) costs, (ii) screening and investigation processes, (iii) clinical effectiveness and other effects on health, (iv) effects on smoking cessation, (v) organizational impact and (vi) implementation issues.ResultsINESSS has developed 12 algorithms and close to 50 recommendations for lung cancer screening and investigation, a tool for assessing lung cancer risk and a benefits/risks table. For the evaluation of the pilot project, MSSS, INSPQ and INESSS developed more than 100 indicators; short-term indicators are currently being measured and others will follow in the longer term. Since starting in June 2021, the pilot project is progressing well (as of November 28, 2021): 2,365 people have been referred, 1,272 were eligible for screening, 678 have had their first LDCT and 19 were Lung-RADS 4B or 4X. Results on indicators will help the ministry decide on the feasibility of scaling up screening to the provincial level and will highlight aspects to be improved.ConclusionsThis project shows how health technology assessment products can elicit changes in the health system, and how multi-stakeholder collaboration can actively support practice implementation and inform decision-making.

Objectives: Medical management based on palliative chemotherapy is currently the standard of care in malignant pleural mesothelioma (MPM). Median survival of 12-16 months has been reported with modern chemotherapy regimens with or without anti-angiogenic agents. Multimodality therapy incorporating cytoreductive surgery, systemic chemotherapy and radiotherapy has been offered for years to fit patients with early-stage disease, but its role remains debated. Our objective was to compare overall survival in patients offered multimodality therapy in a specialized clinic setting in London, UK to that of patients offered exclusively medical treatment at another academic institution in Quebec, Canada. Materials and Methods: We retrospectively compared the survival rates of 2 separate cohorts of patients treated consecutively: Cohort 1 (n = 106) received multimodality therapy including systemic chemotherapy, extended pleurectomy/decortication (P/D) and prophylactic radiotherapy in London (United Kingdom) between 2009 and 2016, while Cohort 2 (n = 98) received medical treatment at the Quebec Heart and Lung Institute (Canada) during the same period. Results: In Cohort 1, all patients but two completed trimodality therapy. In cohort 2, 51 % received palliative care only and 40 % received systemic chemotherapy. Median survival was 32 months vs 10 months in Cohort 1 and Cohort 2, respectively (hazard ratio with age, gender, pathology and TNM staging as covariates: 3.81; 95 % CI: 2.67-5.45; p < 0.0001). Similar results were obtained in sensitivity analyses, after excluding those who received best supportive care only and in a propensity score-matched analysis. Conclusion: Aggressive therapy of MPM using cancer-directed surgery, systemic chemotherapy and prophylactic radiotherapy may provide a significant survival benefit in selected patients.

Background: The emergence of covid-19 has the potential to change the way in which the health care system can accommodate various patient populations and might affect patients with non–covid-19 problems. The Quebec Lung Cancer Network, which oversees thoracic oncology services in the province of Quebec under the direction of the Ministère de la Santé et des Services sociaux, convened to develop recommendations to deal with the potential disruption of services in thoracic oncology in the province of Quebec. The summary provided here has been adapted from the original document posted on the Programme québécois du cancer Web site at: https://www.msss.gouv.qc.ca/professionnels/documents/coronavirus-2019-ncov/PJ1_Recommandations_oncologie-thoracique-200415.pdf. Methods: Plans to optimize the health care system and potentially to prioritize services were discussed with respect to various levels of activity. For each level-of-activity scenario, suggestions were made for the services and treatments to prioritize and for those that might have to be postponed, as well as for potential alternatives to care. Results: The principal recommendation is that the cancer centre executive committee and the multidisciplinary tumour board always try to find a solution to maintain standard-of-care therapy for all patients with thoracic tumours, using novel approaches to treatment and the adoption of a network approach to care, as needed. Conclusions: The effect of the covid-19 pandemic on the health care system remains unpredictable and requires that cancer teams unite and offer the most efficient and innovative therapies to all patients under the various conditions that might be forced upon them.

Dans le cancer du poumon non à petites cellules (CPNPC) avec médiastin radiologiquement normal (cN0/N1), plusieurs études ont rapporté une faible sensibilité de l’échographie endobronchique (EBUS) pour diagnostiquer une atteinte ganglionnaire médiastinale occulte [1]. La sensibilité de l’EBUS peut cependant varier en excluant les ganglions non accessibles comme ceux de la station subaortique (5), qui est l’atteinte médiastinale la plus fréquente dans les tumeurs du lobe supérieur gauche. L’objectif de cette étude est d’analyser les performances diagnostiques de l’EBUS pour détecter une atteinte médiastinale occulte dans le CPNPC de stade clinique N0 et N1, et d’évaluer si ces performances peuvent être améliorées après exclusion des tumeurs du LSG. Les données des patients avec un CPNPC de stade cN0/N1 ayant eu un staging médiastinal par EBUS ont été rétrospectivement collectés à l’institut cardiopulmonaire de Québec (Canada) de 01/2014 à 12/2017. En l’absence d’atteinte médiastinale diagnostiquée en EBUS, tous les patients ont bénéficié d’une résection chirurgicale avec dissection ganglionnaire. Cent soixante patients présentant un CPNPC de stade cN0/N1 ont été inclus. La prévalence d’atteinte pN2 occulte était de 12,5 % (cN0 = 8,5 %, cN1 = 20,4 %). Huit atteintes N2 ont été diagnostiquées en EBUS (cN0 = 2 ; cN1 = 6) et 12 en chirurgie (cN0 = 7 ; cN1 = 5). Parmi les 12 faux négatifs de l’EBUS, 5 concernaient des ganglions qui avaient été correctement échantillonnés durant la stadification, et 7 concernaient la station 5, non accessible en EBUS. La Se et VPN de l’EBUS pour diagnostiquer une atteinte médiastinale occulte étaient respectivement de 40 % (cN0 = 22 % ; cN1 = 55 %) et 92 % (cN0 = 93 % ; cN1 = 90 %). Après exclusion des tumeurs du LSG, la Se et VPN de l’EBUS augmentaient à 58 % (cN0 = 40 % ; cN1 = 71 %) et 95 % (cN0 = 96 % ; cN1 = 94 %). La Se de l’EBUS pour diagnostiquer une atteinte médiastinale occulte est faible chez les cN0, de même que sa prévalence, remettant en question l’utilité de cet examen dans ce sous-groupe. Dans le stade cN1, la Se de l’EBUS est plus importante et augmente davantage après exclusion des tumeurs du LSG. Il est nécessaire de considérer les stades cN0 et cN1 différemment dans l’évaluation préopératoire du cancer pulmonaire et d’adapter la stadification médiastinale en fonction des caractéristiques du patient.

ABSTRACTThe evaluation of bone complications in chronic kidney disease (CKD) often requires a bone biopsy, the analysis of which can refine the diagnosis of bone defects. Bone histomorphometry performed on sections of the iliac crest biopsy remains the reference procedure for the quantitative assessment of bone health in CKD patients, whereas immunohistochemistry and other molecular biology analyses are indispensable tools for studying the disrupted signaling pathways. Traditionally, the whole iliac crest biopsy was included in methyl‐methacrylate (MMA) and was exclusively used for bone histomorphometry to describe static, dynamic, and structural parameters. Therefore, further molecular analysis of the bone tissue or the need for tissue banking would require a second biopsy to be made, because inclusion in MMA prevents the extraction of good‐quality nucleic acids. In this work, we describe a simple approach to divide a single iliac crest bone biopsy into multiple parts. This allows for simultaneous assessments of histology, immunohistochemistry, biomolecular analysis, and tissue banking while preserving the same bone surface area for histomorphometry. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Background: Recruitment to clinical trials is suboptimal, increasing costs, and delaying the potential implementation of clinical advances. Among other barriers, the lack of marketing experience among trialists may limit recruitment. In this observational study, in the context of the Pan-Canadian Early Detection of Lung Cancer Trial, we assessed the value of a motivational survey of study participants in planning a tailored advertising campaign and analysed the value of individual components of advertising in generating telephone calls to the study and recruited subjects. Methods: The Pan-Canadian Early Detection of Lung Cancer Trial was a single arm study assessing risk modelling for lung cancer screening by low-dose computed tomography scan and autofluorescence bronchoscopy. Individuals were recruited to eight sites across Canada without a central marketing plan. On contact with the study, individuals reported how they heard about the study according to a predefined list. One site, the Juravinski Cancer Centre, worked with a marketing expert to develop a survey to assess participant motivations, source of study awareness, and personal habits. The survey was used to develop a media campaign for recruitment. Media events were collected from all sites. The primary analysis assessed the number of telephone contacts and recruited subjects associated with various media factors. Individual print media characteristics were assessed for their effect on recruitment. Results: At all sites, 7059 individuals contacted the study, and 2537 were eligible and recruited. Among 52 individuals completing the Juravinski Cancer Centre survey, motivation included concern for personal risk of lung cancer (71%), followed by desire to contribute to a cure (67%), followed by personal knowledge of a person with lung cancer (50%). Most reported hearing of the study from the newspaper (58%) despite no print ad yet being distributed. With survey input, a newsprint campaign was executed. The number of media events varied by site (median: 13, range: 3–28). Among all recruits, 56.4% reported referral by newspaper followed by family/friend (14%). Telephone contacts and recruited subjects per event varied significantly by site, while unpaid media events appeared superior to paid events. Print media characteristics associated with increased telephone contacts and recruitment included use of a rational appeal (vs a mixed rational–emotional), less use of white space, and larger headline font. Conclusion: A survey of trial candidates provides useful information regarding personal motivation, media use, and lifestyle. Unpaid media events appear superior in generating recruitment, while print media may be superior to radio and television in selecting eligible recruits. The utility of individual print media characteristics appears to differ from the commercial advertising literature. Further research on marketing in clinical trials is encouraged to improve recruitment ( ClinicalTrials.gov registration: NCT00751660, https://clinicaltrials.gov/ct2/show/NCT00751660 ).