Effect of fecal immunochemical test cut-off levels on adenoma detection rate: a systematic review and meta-analysis.

BACKGROUND: Adenoma detection rate (ADR) is higher after a positive fecal immunochemical test (FIT) compared to direct screening colonoscopy. OBJECTIVE: This meta-analysis evaluated how ADR, the rates of advanced adenoma detection (AADR), colorectal cancer detection (CDR), and sessile serrated lesion detection (SSLDR) are affected by different FIT positivity thresholds. METHODS: We searched MEDLINE, EMBASE, CINAHL, and EBM Reviews databases for studies reporting ADR, AADR, CDR, and SSLDR according to different FIT cut-off values in asymptomatic average-risk individuals aged 50-74 years old. Data were stratified according to sex, age, time to colonoscopy, publication year, continent, and FIT kit type. Study quality, heterogeneity, and publication bias were assessed. RESULTS: Overall, 4280 articles were retrieved and fifty-eight studies were included (277,661 FIT-positive colonoscopies; mean cecal intubation 96.3%; mean age 60.8 years; male 52.1%). Mean ADR was 56.1% (95% CI 53.4 - 58.7%), while mean AADR, CDR, and SSLDR were 27.2% (95% CI 24.4 - 30.1%), 5.3% (95% CI 4.7 - 6.0%), and 3.0% (95% CI 1.7 - 4.6%), respectively. For each 20 µg Hb/g increase in FIT cut-off level, ADR increased by 1.54% (95% CI 0.52 - 2.56%, p < 0.01), AADR by 3.90% (95% CI 2.76 - 5.05%, p < 0.01) and CDR by 1.46% (95% CI 0.66 - 2.24%, p < 0.01). Many detection rates were greater amongst males and Europeans. CONCLUSIONS: ADRs in FIT-positive colonoscopies are influenced by the adopted FIT positivity threshold, and identified targets, importantly, proved to be higher than most current societal recommendations.

The use and abuse of survival analysis and Kaplan-Meier curves in surgical trials.

BACKGROUND: Survival analysis based on Cox regression and Kaplan-Meier curves, initially devised for oncology trials, have frequently been used in other contexts where fundamental statistical assumptions (such as a constant hazard ratio) are not satisfied. This is almost always the case in trials that compare surgery with medical management. METHODS: We review a trial that compared extracranial-intracranial bypass surgery (EC-IC bypass) with medical management (MM) of patients with symptomatic occlusion of the carotid or middle cerebral artery, where it was claimed that surgery was of no benefit. We discuss a hypothetical study and review other neurovascular trials which have also used survival analysis to compare results. RESULTS: The trial comparing EC-IC bypass and MM did not satisfy the fundamental proportional hazard assumption necessary for valid analyses. This was also the case for two prior EC-IC bypass trials, as well as for other landmark neurovascular studies, such as the trials comparing endarterectomy with MM for carotid stenoses, or for the trial that compared intervention and MM for unruptured brain arteriovenous malformations. While minor deviations may have little effect on large trials, it may be impossible to show the benefits of surgery when trial size is small and deviations large. CONCLUSION: Survival analyses are inappropriate in RCTs comparing surgery with conservative management, unless survival is calculated after the postoperative period. Alternative ways to compare final clinical outcomes, using for example a fixed follow-up period, should be planned for preventive surgical trials that compare intervention with conservative management.

Promotion of Physical Activity by Québec Primary Care Physicians: What Has Changed in the Last Decade?

OBJECTIVE: This study aimed to assess the changes in the frequency of physical activity (PA) counseling and in the predictors of primary care PA promotion in Québec primary care physicians (PCPs) between 2010 and 2020. METHODS: In 2010, we conducted a survey among Québec PCPs. Questions included: frequency of promoting PA to patients, perceived barriers, needs to improve PA promotion practice, frequency of PCPs' PA practice, and sociodemographic information. In 2020, we took over the 2010 questionnaire to document the evolution of the PA promotion practice. RESULTS: The proportion of PCPs discussing PA with their patients significantly increased (P < .05) in 2020 for the following health conditions: depression, low back pain, chronic obstructive pulmonary disease, and cancer; it declined (P < .05) for overweight patients, those with metabolic syndrome, and in primary prevention. Collaboration with PA professionals was the major need identified, and it increased in 2020. PCPs' own practice of PA was a predictor of PA promotion in 2010 (odds ratio = 6.679; P < .001) and in 2020 (odds ratio = 6.679; P < .001). In both 2010 and in 2020, older or more experienced PCPs were more likely to discuss PA with their patients without diagnosed diseases than younger ones or those with less experience. CONCLUSIONS: Over the last 10 years, there has been a significant increase in PCPs promoting PA in Québec; however, it has been mainly oriented toward secondary prevention. It is concerning that PA counseling in primary prevention has declined, notably among younger PCPs. The stronger claim for closer collaboration with kinesiologists suggests that PCPs are in favor of an interprofessional strategy, namely collaboration with PA specialists.

The small trial problem.

BACKGROUND: Many randomized trials that aim to assess new or commonly used medical or surgical interventions have been so small that the validity of conclusions becomes questionable. METHODS: We illustrate the small trial problem using the power calculation of five Cochrane-reviewed studies that compared vertebroplasty versus placebo interventions. We discuss some of the reasons why the statistical admonition not to dichotomize continuous variables may not apply to the calculation of the number of patients required for trials to be meaningful. RESULTS: Placebo-controlled vertebroplasty trials planned to recruit between 23 and 71 patients per group. Four of five studies used the standardized mean difference of a continuous pain variable (centimeters on the visual analog scale (VAS)) to plan implausibly small trials. What is needed is not a mean effect at the population level but a measure of efficacy at the patient level. Clinical practice concerns the care of individual patients that vary in many more respects than the variation around the mean of a single selected variable. The inference from trial to practice concerns the frequency of success of the experimental intervention performed one patient at a time. A comparison of the proportions of patients reaching a certain threshold is a more meaningful method that appropriately requires larger trials. CONCLUSION: Most placebo-controlled vertebroplasty trials used comparisons of means of a continuous variable and were consequently very small. Randomized trials should instead be large enough to account for the diversity of future patients and practices. They should offer an evaluation of a clinically meaningful number of interventions performed in various contexts. Implications of this principle are not specific to placebo-controlled surgical trials. Trials designed to inform practice require a per-patient comparison of outcomes and the size of the trial should be planned accordingly.

Pharmacologic Interventions to Minimize Fluid Absorption at the Time of Hysteroscopy: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess which interventions are effective in reducing fluid absorption at the time of hysteroscopy. DATA SOURCE: Ovid MEDLINE, Ovid EMBASE, PubMed (non-MEDLINE records only), EBM Reviews-Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov , and Web of Science were searched from inception to February 2022 without restriction on language or geographic origin. METHODS OF STUDY SELECTION: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, all English-language, full-text articles reporting fluid balance, with an intervention and comparator arm, were included. Title and abstract screening and full-text review were completed independently by two authors. Conflicts were resolved through discussion and consensus. Studies' risk of bias was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale for observational studies. TABULATION, INTEGRATION, AND RESULTS: The search identified 906 studies, 28 of which were eligible for inclusion, examining the following interventions: gonadotropin-releasing hormone (GnRH) agonist; ulipristal acetate; vasopressin; danazol; oxytocin; and local, general, and regional anesthesia. A significant reduction in mean fluid absorption was seen in patients preoperatively treated with danazol (-175.7 mL, 95% CI -325.4 to -26.0) and a GnRH agonist (-139.68 mL, 95% CI -203.2, -76.2) compared with patients in a control group. Ulipristal acetate and type of anesthesia showed no difference. Data on type of anesthesia and vasopressin use were not amenable to meta-analysis; however, four studies favored vasopressin over control regarding fluid absorption. Mean operative time was reduced after preoperative treatment with ulipristal acetate (-7.1 min, 95% CI -11.31 to -2.9), danazol (-7.5 min, 95% CI -8.7 to -6.3), and a GnRH agonist (-3.3 min, 95% CI -5.6 to -0.98). CONCLUSION: Preoperative treatment with a GnRH agonist and danazol were both found to be effective in reducing fluid absorption and operative time across a range of hysteroscopic procedures. High-quality research aimed at evaluating other interventions, such as combined hormonal contraception, progestin therapy, and vasopressin, are still lacking in the literature. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021233804.

Differentiation of focal nodular hyperplasia and hepatocellular adenoma using qualitative and quantitative imaging features and classification and regression tree analysis.

PURPOSE: To assess qualitative and quantitative analysis of gadoxetate disodium-enhanced hepatobiliary phase MR imaging (MRI) and assess the performance of classification and regression tree analysis for the differentiation of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). MATERIALS AND METHODS: This retrospective study was approved by our local ethics committee. One hundred seventy patients suspected of having FNH or HCA underwent gadoxetate disodium-enhanced MRI. The reference standard was either pathology or follow-up imaging. Two readers reviewed images to identify qualitative imaging features and measure signal intensity on unenhanced, dynamic, and hepatobiliary phase images. For quantitative analysis, contrast enhancement ratio (CER), lesion-to-liver contrast (LLC), signal intensity ratio (SIR), and relative signal enhancement ratio (RSER) were calculated. A classification and regression tree (CART) analysis was developed. RESULTS: Eighty-five patients met the inclusion criteria, with a total of 97 FNHs and 43 HCAs. For qualitative analysis, the T1 signal intensity on the hepatobiliary phase provided the highest overall classification performance (91.9% sensitivity, 90.1% specificity, and 90.9% accuracy). For quantitative analysis, RSER in the hepatobiliary phase with a threshold of 0.723 provided the highest classification performance (92.6% sensitivity and 89.4% specificity) to differentiate FNHs from HCAs. A CART model based on five qualitative imaging features provided an accuracy of 94.4% (95% confidence interval 90.0-98.9%). CONCLUSION: Gadoxetate disodium-enhanced hepatobiliary phase provides high diagnostic performance as demonstrated in quantitative and qualitative analysis in differentiation of FNH and HCA, supported by a CART decision model.

Impact of Implementing a Bendamustine-Based Conditioning Regimen on Outcomes of Autologous Stem Cell Transplantation in Lymphoma while Novel Cellular Therapies Emerge.

With the advent of new cellular and targeted therapies, treatment options for relapsed and refractory (r/R) lymphomas have multiplied, and the optimal approach offering the best outcomes remains a matter of passionate debate. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is still considered a treatment option for patients with chemosensitive lymphoma when cure is the expected goal. The myeloablative conditioning regimen preceding the stem cell infusion is considered the effective component of this approach. Carmustine (BCNU)-based preparative regimens, such as BEAM and BEAC, are considered the standard of care and have shown efficacy and low nonrelapse mortality (NRM). Comparative studies between conditioning regimens have failed to identify a better option. After a BCNU drug shortage in Canada followed by a steep increase in price, we elected to substitute BCNU for bendamustine (benda) in the preparative regimen. The purpose of this substitution was to improve response while preserving safety and controlling costs. From May 2015 to May 2018, a total of 131 consecutive lymphoma patients received benda-EAM conditioning. These patients were compared with 96 consecutive patients who received BCNU-based conditioning from January 2012 to May 2015. Apart from conditioning, supportive care measures were the same in the 2 groups. Patients receiving benda were older (55.7 years versus 51.1 years; P = .002). The development of grade ≥3 mucositis was more frequent with benda conditioning (39.5% versus 7.8%; P < .001) leading to a greater requirement for parenteral nutrition (48.9% versus 21.9%; P < .001). A transient creatinine increase >1.5 times the upper limit of normal (15.3% versus 4.2%; P < .008) and intensive care unit admission (6.9% versus 1.1%; P < .029) were more frequent with benda; however, there were no between-group differences in cardiac, pulmonary, or liver toxicity and NRM. With a median follow-up of 48 months for the benda group and 60 months for the BCNU group, benda was associated with significantly better progression-free survival (71% versus 61%; P = .040; hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.0 to 2.7) and overall survival (86% vs 71%; P = .0066; HR, 2.6; 95% CI, 1.3 to 5.4) compared with BCNU-based conditioning regimens. While novel therapies emerge, our study demonstrates that benda-EAM is safe and effective and should be considered a valid alternative to BCNU conditioning to improve outcomes of patients with chemosensitive r/R lymphomas undergoing ASCT.

Clinical Uncertainty and Equipoise in the Management of Recurrent Glioblastoma.

BACKGROUND: A significant proportion of glioblastoma (GBM) patients are considered for repeat resection, but evidence regarding best management remains elusive. Our aim was to measure the degree of clinical uncertainty regarding reoperation for patients with recurrent GBM. METHODS: We first performed a systematic review of agreement studies examining the question of repeat resection for recurrent GBM. An electronic portfolio of 37 pathologically confirmed recurrent GBM patients including pertinent magnetic resonance images and clinical information was assembled. To measure clinical uncertainty, 26 neurosurgeons from various countries, training backgrounds, and years' experience were asked to select best management (repeat surgery, other nonsurgical management, or conservative), confidence in recommended management, and whether they would include the patient in a randomized trial comparing surgery with nonsurgical options. Agreement was evaluated using κ statistics. RESULTS: The literature review did not reveal previous agreement studies examining the question. In our study, agreement regarding best management of recurrent GBM was slight, even when management options were dichotomized (repeat surgery vs. other options; κ=0.198 [95% confidence interval: 0.133-0.276]). Country of practice, years' experience, and training background did not change results. Disagreement and clinical uncertainty were more pronounced within clinicians with (κ=0.167 [0.055-0.314]) than clinicians without neuro-oncology fellowship training (κ=0.601 [0.556-0.646]). A majority (51%) of responders were willing to include the patient in a randomized trial comparing repeat surgery with nonsurgical alternatives in 26/37 (69%) of cases. CONCLUSION: There is sufficient uncertainty and equipoise regarding the question of reoperation for patients with recurrent glioblastoma to support the need for a randomized controlled trial.

Surgical or Endovascular Management of Middle Cerebral Artery Aneurysms: A Randomized Comparison.

OBJECTIVE: There are few randomized data comparing clipping and coiling for middle cerebral artery (MCA) aneurysms. We analyzed results from patients with MCA aneurysms enrolled in the CURES (Collaborative UnRuptured Endovascular vs. Surgery) and ISAT-2 (International Subarachnoid Aneurysm Trial II) randomized trials. METHODS: Both trials are investigator-led parallel-group 1:1 randomized studies. CURES includes patients with 3-mm to 25-mm unruptured intracranial aneurysms (UIAs), and ISAT-2 includes patients with ruptured aneurysms (RA) for whom uncertainty remains after ISAT. The primary outcome measure of CURES is treatment failure: 1) failure to treat the aneurysm, 2) intracranial hemorrhage during follow-up, or 3) residual aneurysm at 1 year. The primary outcome of ISAT-2 is death or dependency (modified Rankin Scale score >2) at 1 year. One-year angiographic outcomes are systematically recorded. RESULTS: There were 100 unruptured and 71 ruptured MCA aneurysms. In CURES, 90 patients with UIA have been treated and 10 await treatment. Surgical and endovascular management of unruptured MCA aneurysms led to treatment failure in 3/42 (7%; 95% confidence interval [CI], 0.02-0.19) for clipping and 13/48 (27%; 95% CI, 0.17-0.41) for coiling (P = 0.025). All 71 patients with RA have been treated. In ISAT-2, patients with ruptured MCA aneurysms managed surgically had died or were dependent (modified Rankin Scale score >2) in 7/38 (18%; 95% CI, 0.09-0.33) cases, and 8/33 (24%; 95% CI, 0.13-0.41) for endovascular. One-year imaging results were available in 80 patients with UIA and 62 with RA. Complete aneurysm occlusion was found in 30/40 (75%; 95% CI, 0.60-0.86) patients with UIA allocated clipping, and 14/40 (35%; 95% CI, 0.22-0.50) patients with UIA allocated coiling. Complete aneurysm occlusion was found in 24/34 (71%; 95% CI, 0.54-0.83) patients with RA allocated clipping, and 15/28 (54%; 95% CI, 0.36-0.70) patients with RA allocated coiling. CONCLUSIONS: Randomized data from 2 trials show that better efficacy may be obtained with surgical management of patients with MCA aneurysms.

Abnormal glucose tolerance in a pediatric cystic fibrosis cohort: Trends in clinical outcomes and associated factors in the preceding years.

BACKGROUND AND AIMS: Deterioration of anthropometric and lung function parameters was shown to precede the onset of cystic fibrosis-related diabetes (CFRD) in adults. In children, studies have been conducted in small cohorts with relatively short observation period. Study objectives were to document the longitudinal trends of anthropometric, pulmonary, nutritional and metabolic parameters from cystic fibrosis (CF) diagnosis to the ascertainment of abnormal glucose tolerance and identify parameters associated with the incidence of such abnormalities in a pediatric CF cohort. METHODS AND RESULTS: Retrospective cohort study of 281 children with CF. Longitudinal trends of anthropometric, lung function, nutritional and metabolic data were generated from CF diagnosis to the ascertainment of abnormal glucose tolerance defined as the presence of either impaired glucose tolerance (IGT), unconfirmed CFRD or CFRD. Cox models and Kaplan-Meier curves were used to identify factors associated with developing abnormal glucose tolerance. Forty-five percent of cohort had normal glucose tolerance (NGT), 27% IGT, 10% unconfirmed CFRD and 18% CFRD. Children who developed CFRD displayed lower height z-scores from a very early age. Conversely, HbA1c levels began to rise closer to CFRD ascertainment. Height z-scores (HR: 0.45; CI 95% [0.29-0.69]) and HbA1c (HR: 2.43; CI 95% [1.86-3.18]) in years preceding ascertainment were associated with the risk of developing CFRD. CONCLUSION: Children who developed CFRD display distinctive trends for height z-scores from a very early age, whereas HbA1c appears as a marker of established glucose metabolism derangements.

Effect of mannitol on acute kidney injury induced by cisplatin.

PURPOSE: Acute kidney injury (AKI) is a frequent dose-limiting toxicity induced by cisplatin. Mannitol has been used in hydration protocols to mitigate this adverse event but its role remains controversial. The aim of this study is to define the impact of mannitol on AKI in patients receiving cisplatin. METHODS: This retrospective observational study was conducted in cancer patients who received at least one dose of cisplatin between September 2010 and December 2016 at the Centre hospitalier de l'Université de Montréal. The primary outcome of this study was the comparison of all grade cisplatin-associated AKI between hydration protocols with or without mannitol. RESULTS: A total of 1821 patients were included of which 658 received mannitol whilst 1163 received hydration alone. The risk of all grade cisplatin-associated AKI was significantly lower for the mannitol group (Hazard Ratio (HR) = 0.62; 95% CI [0.42, 0.89]). This result was mainly driven by gynecologic (HR = 0.50), upper gastrointestinal (HR = 0.32), urinary tract malignancies (HR = 0.29) and lymphoma (HR = 0.33). No significant difference was seen for head and neck (HN), lung, germ cells and other cancers. However, HN cancers patients receiving mannitol had fewer grade 2 and 3 AKI. Significantly fewer AKI events were observed in HN, lung, upper gastrointestinal and urinary tract cancer when mannitol was added for cisplatin dose <75 mg/m2. CONCLUSION: Although the results were generally driven by a decrease of grade 1 AKI for most cancers, the greatest benefit of mannitol was seen with cisplatin doses lower than 75 mg/m2 and should probably be reinstated in this setting.

Systemic Inflammatory Markers Are Predictive of the Response to Brachytherapy in the Prostate.

We analyzed the influence of the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) on the biochemical recurrence (BCR) in low-intermediate risk prostate cancer (PCa). A total of 604 patients treated with exclusive brachytherapy for low- and intermediate-risk cancers were included in this study. No patient received either androgen deprivation or brachytherapy as a boost. BCR was defined according to the Phoenix definition (nadir prostatic specific antigen (PSA) +2). The median follow-up was 60 months (IQR 44-48 months). An NLR > 3 was more frequent in statin users (p = 0.025), but not in diabetics (p = 0.079). In univariate analysis (UVA) and multivariate analysis (MVA), a NLR > 3 (MVA p = 0.03), as well as Cancer of the Prostate Risk Assessment (CAPRA) low- vs. intermediate-risk (MVA p = 0.04), were predictive of BCR. When combining the NLR score with the CAPRA risk group, CAPRA intermediate risk patients with an NLR ≤ 3 (n = 157) had the worst (p = 0.0276) BCR rates, with a 5-year recurrence-free survival (p = 0.004, Bonferroni correction for six comparisons p = 0.024). We were able to identify a subgroup of PCa patients with CAPRA intermediate-risk and an NLR ≤ 3 who had worse BCR. This is in contrast to most other cancers, which have a worse prognosis when the NLR is high.

Dynamic contrast-enhanced MRI to assess hepatocellular carcinoma response to Transarterial chemoembolization using LI-RADS criteria: A pilot study.

PURPOSE: To identify quantitative dynamic contrast-enhanced (DCE)-MRI perfusion parameters indicating tumor response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE). MATERIALS AND METHODS: This prospective pilot study was approved by our institutional review board; written and informed consent was obtained for each participant. Patients underwent DCE-MRI examinations before and after TACE. A variable flip-angle unenhanced 3D mDixon sequence was performed for T1 mapping. A dynamic 4D mDixon sequence was performed after contrast injection for assessing dynamic signal enhancement. Nonparametric analysis was conducted on the time-intensity curves. Parametric analysis was performed on the time-concentration curves using a dual-input single-compartment model. Treatment response according to Liver Reporting and Data System (LI-RADS) v2018 was used as the reference standard. The comparisons within groups (before vs. after treatment) and between groups (nonviable vs. equivocal or viable tumor) were performed using nonparametric bootstrap taking into account the clustering effect of lesions in patients. RESULTS: Twenty-eight patients with 52 HCCs (size: 10-104 mm) were evaluated. For nonviable tumors (n = 27), time to peak increased from 62.5 ±â€¯18.2 s before to 83.3 ±â€¯12.8 s after treatment (P< 0.01). For equivocal or viable tumors (n = 25), time to peak and mean transit time significantly increased (from 54.4 ±â€¯24.1 s to 69.5 ±â€¯18.9 s, P < 0.01 and from 14.2 ±â€¯11.8 s to 33.9 ±â€¯36.8 s, P= 0.01, respectively) and the transfer constant from the extracellular and extravascular space to the central vein significantly decreased from 14.8 ±â€¯14.1 to 8.1 ±â€¯9.1 s-1 after treatment (P= 0.01). CONCLUSION: This prospective pilot DCE-MRI study showed that time to peak significantly changed after TACE treatment for both groups (nonviable tumors and equivocal or viable tumors). In our cohort, several perfusion parameters may provide an objective marker for differentiation of treatment response after TACE in HCC patients.

LI-RADS for MR Imaging Diagnosis of Hepatocellular Carcinoma: Performance of Major and Ancillary Features.

Purpose To evaluate the performance of major features, ancillary features, and categories of Liver Imaging Reporting and Data System (LI-RADS) version 2014 at magnetic resonance (MR) imaging for the diagnosis of hepatocellular carcinoma (HCC). Materials and Methods This retrospective institutional review board-approved study included patients with liver MR imaging and at least one pathologically proved lesion. Between 2004 and 2016, 102 patients (275 observations including 113 HCCs) met inclusion criteria. Two radiologists independently assessed major and ancillary imaging features for each liver observation and assigned a LI-RADS category. Per-lesion estimates of diagnostic performance of major features, ancillary features, and LI-RADS categories were assessed by using generalized estimating equation models. Results Major features (arterial phase hyperenhancement, washout, capsule, and threshold growth) had a sensitivity of 88.5%, 60.6%, 32.9%, and 41.6%, and a specificity of 18.6%, 84.8%, 98.8%, and 83.2% for HCC, respectively. Ancillary features (mild-moderate T2 hyperintensity, restricted diffusion, mosaic architecture, intralesional fat, lesional fat sparing, blood products, and subthreshold growth) had a sensitivity of 62.2%, 54.8%, 9.9%, 30.9%, 23.1%, 2.8%, and 48.3%, and a specificity of 79.4%, 90.6%, 99.4%, 94.2%, 83.1%, 99.3%, and 91.4% for HCC, respectively. The LR-5 or LR-5 V categories had a per-lesion sensitivity of 50.8% and a specificity of 95.8% for HCC, respectively. The LR-4, LR-5, or LR-5 V categories (determined by using major features only vs combination of major and ancillary features) had a per-lesion sensitivity of 75.9% and 87.9% and a per-lesion specificity of 87.5% and 86.2%, respectively. Conclusion The use of ancillary features in combination with major features increases the sensitivity while preserving a high specificity for the diagnosis of HCC.

Sex Differences in Attaining Cigarette Smoking and Nicotine Dependence Milestones Among Novice Smokers.

There may be sex differences in the response to nicotine, according to findings of studies in animals; however, sex differences in the natural course of cigarette smoking and nicotine dependence are documented in few studies. Prevalent (n = 240 girls; n = 184 boys) and incident (n = 231 girls; n = 184 boys) cigarette smokers from the Nicotine Dependence in Teens Study were followed up to 5 years after first puff, from age 12 to 18 years (1999-2005). We used Cox proportional hazards models to compare time to development of 3 cigarette-use (i.e., whole cigarette; 100 cigarettes lifetime; regular smoking), and 3 nicotine-dependence symptom (i.e., "really need a cigarette"; mentally addicted; physically addicted) milestones across sex. Girls were at higher risk than boys of attaining all milestones; hazard ratios (95% confidence intervals) ranged from 1.35 (1.06, 1.72) for 100 cigarettes lifetime to 1.74 (1.44, 2.10) for "really need a cigarette." Among nonregular smokers, 26% (8%; 43%) and 25% (6%; 44%) more girls than boys reported "really need a cigarette" 1 and 2 years, respectively, after first puff. Preventive interventions may need adjustment to incorporate these findings. Additional research should clarify the relative contribution of biological and social underpinnings of these sex differences.

Efficacy of a Web-Based Tailored Intervention to Reduce Cannabis Use Among Young People Attending Adult Education Centers in Quebec.

BACKGROUND: Cannabis use is common among young adults. Web-based interventions are an increasingly popular way to reach this population. The aim of this study was to evaluate the efficacy of a Web-based tailored intervention, developed on theoretical and empirical grounds, to reduce cannabis use among young people by promoting a more positive intention to abstain. METHODS: An experimental design was employed to evaluate the efficacy of the intervention in reducing cannabis use (primary outcome) by bolstering intention (secondary outcome) to abstain from use. Participants were randomly assigned either to an experimental group that received the Web-based tailored intervention or to a control group that did not. RESULTS: Of 588 young adults (18-24 years of age) recruited, 295 were randomly assigned to the experimental group and 293 to the control group. At baseline, 343 reported using cannabis at least once in the past year. An intention-to-treat analysis showed that, at postintervention, a higher proportion of participants in the experimental group had reduced their cannabis use compared with the control group [10.8% vs. 5.1%, χ2(2) = 9.89, p = 0.007]. A mixed model for repeated measures revealed a statistically significant difference in terms of change in intention to abstain from cannabis use in the coming month [Group × Time interaction, F(1,474) = 8.03, p = 0.005]: intention increased for the experimental group (5.07 ± 2.07 to 5.45 ± 1.88; p < 0.001), but stayed stable for the control group (5.32 ± 2.03 to 5.36 ± 1.99; p = 0.779). CONCLUSION: This study shows that the intervention can be efficacious in reducing cannabis use among young people attending adult education centers.

Predictors of Cigarette Smoking Initiation in Early, Middle, and Late Adolescence.

PURPOSE: Little is known about age-related differences in risk factors for cigarette smoking initiation. We identified predictors of initiation in early, middle, and late adolescence from among sociodemographic factors, indicators of smoking in the social environment, psychological characteristics, lifestyle indicators, and perceived need for cigarettes. METHODS: Data were drawn from a longitudinal study of 1,801 children recruited at age 10-11 years from 29 elementary schools in Montreal, Canada. Multivariable logistic regression within a generalized estimating equations framework was used to identify predictors among never smokers across three 2-year windows: age 11-13 years (n = 1,221); age 13-15 years (n = 737); and age 15-17 years (n = 690). RESULTS: Among the 18 risk factors investigated, two differed across age. Friends' smoking, a strong risk factor in early adolescence (odds ratio [95% confidence interval] = 5.78 [3.90-8.58]), lost potency in late adolescence (1.83 [1.31-2.57]). Depressive symptoms, a risk factor in early and middle adolescence (1.60 [1.26-2.02] and 1.92 [1.45-2.54], respectively), were inversely associated in late adolescence (.76 [.58-1.00]). Sex, TV viewing, and weight-related goals were not associated with initiation at any age. All other factors were significant in two or three age groups. CONCLUSIONS: Most risk factors for smoking initiation were stable across age. Tobacco control interventions may be robust for risk factors across age groups and may not need adjustment. At all ages, interventions should focus on eliminating smoking in the social environment and on reducing the availability of tobacco products.

Optimal Pancreatic Phase Delay with 64-Detector CT Scanner and Bolus-tracking Technique.

RATIONALE AND OBJECTIVES: To assess the optimal pancreatic phase delay in terms of parenchymal enhancement and tumor-to-pancreas contrast with a bolus-tracking method. MATERIALS AND METHODS: Patients referred for suspicion of pancreatic tumor and undergoing 64-detector computed tomography scanner were randomized to an individualized scan delay of 10, 20, or 30 seconds of nonionic contrast material (370 mg I/mL) after aortic enhancement above 150 Hounsfield units. The volume of contrast was adjusted to patient weight. Pancreatic and tumor enhancements were measured. Statistical analysis included analysis of variance and post hoc Tukey tests. RESULTS: One hundred and fifty patients were randomized to individualized scan delays of 10, 20, or 30 seconds. Pancreatic parenchymal enhancement in all patients (n = 150) was significantly higher with a delay of 20 or 30 seconds than that with 10 seconds (P < .001 for both). Tumor-to-pancreas contrast for solid tumors (n = 59) was significantly higher with a delay of 30 seconds than that with 10 seconds (P = .015). Adenocarcinoma-to-pancreas contrast during pancreatic phase was significantly higher for a 20- or 30-second delay than for a 10-second delay (P = .027 and .011, respectively) for one reader. CONCLUSIONS: With a flow rate of 4 mL/s and weight-adjusted contrast volume, an individualized scan delay of 30 seconds after aortic transit time revealed higher pancreatic enhancement and tumor-to-pancreas contrast than that with a delay of 10 seconds.

Uncertainty and agreement in the management of unruptured intracranial aneurysms.

OBJECT: The management of unruptured intracranial aneurysms remains controversial. The goal of this study was to evaluate the clinical community agreement in decision making regarding unruptured intracranial aneurysms. METHODS: A portfolio of 41 cases of unruptured intracranial aneurysms with angiographic images, along with a short description of the patient presentation, was sent to 28 clinicians (16 radiologists and 12 surgeons) with varying years of experience in the management of unruptured intracranial aneurysms. Five senior clinicians responded twice at least 3 months apart. Nineteen cases (46%) were selected from patients recruited in the Canadian UnRuptured Endovascular versus Surgery trial, an ongoing randomized comparison of coil embolization and clip placement. For each case, the responder was to first choose between 3 treatment options (observation, surgical clip placement, or endovascular coil embolization) and then indicate their level of certainty on a quantitative 0-10 scale. Agreement in decision making was studied using κ statistics. RESULTS: Decisions to coil were more frequent (n = 612, 53%) than decisions to clip (n = 289, 25%) or to observe (n = 259, 22%). Interjudge agreement was only fair (κ = 0.31 ± 0.02) for all cases and all judges, despite substantial intrajudge agreement (range 0.44-0.83 ± 0.10), with high mean individual certainty levels for each case (range 6.5-9.4 ± 2.0 on a scale of 0-10). Agreement was no better within specialties (surgeons or radiologists), within capability groups (those able to perform endovascular coiling alone, surgical clipping alone, or both), or with more experience. There was no correlation between certainty levels and years of experience. Agreement was lower when the cases were taken from the randomized trial (κ = 0.19 ± 0.2) compared with nontrial cases (κ = 0.35 ± 0.2). CONCLUSIONS: Individuals do not agree regarding the management of unruptured intracranial aneurysms, even when they share a background in the same specialty, similar capabilities in aneurysm management, or years of practice. If community equipoise is a necessary precondition for trial participation, this study has found sufficient uncertainty and disagreement among clinicians to justify randomized trials.